There is an essential demand for developing biocompatible grafts for knee anterior cruciate ligament reconstruction (ACLR). This study investigated cell infiltration into decellularized bovine tendon xenografts using a rat knee ACLR model. Twelve-week-old Sprague-Dawley rats were used. At weeks 1, 2, 4, 8, 16, 26, and 52 (each period, n = 6) after ACLR, rats receiving decellularized bovine tendon (group D, n = 42) or autologous tendon (group A, n = 42) as grafts underwent peritibial bone tunnel bone mineral density (BMD), histological, and immunohistological assessments. BMD increased over time in both the groups until week 16 and then remained unchanged without exhibiting significant differences between the groups. Initially, cellularity in group D was lower than that in group A; however, by weeks 4-8, both the groups were comparable to the native anterior cruciate ligament group and cellularity remained unchanged until week 52. Initially, group A had more M1 macrophages, indicating inflammation, whereas group D had more M2 macrophages, indicating tissue regeneration. Nonetheless, the M1 and M2 macrophage counts of both the groups were comparable at most times. This study revealed the excellent recellularization and tendon-bone integration abilities of decellularized tendons using a cross-species model.

The Stanford Biodesign program was first introduced in Japan in 2015 at three national universities to develop medical technology innovation and its talent. This study aimed to (1) show the outcomes of leadership talent development, (2) indicate the educational results of the program, and (3) objectively analyze the ways in which the program executed in Japan, effectively promoted entrepreneurship orientation and the origination of new businesses. The latter is especially relevant as Japan has low entrepreneurial awareness and new business entry rates compared to the United States and Europe. Herein, fellows were subjected to questionnaires, interviews, and a survey based on academic papers, extant literature, and treatises issued by the Nihon Biodesign Gakkai (Academic Society of Japan Biodesign). Overall program performance showed notable results, despite indicating a need to improve business-related programs and team learning which is greatly influenced by Japanese culture. An externship program, planned and developed in Japan, was most inspiring and served to expose participants to role models. Comparing Japan Biodesign education elements to factors of general entrepreneurship promotion in Japan, sampled and organized from relevant White Papers, proved its educational effectiveness in entrepreneurship promotion from an objective viewpoint. Within the 4-year timeframe, the results indicated that leadership talent was indeed developed. Medical device innovation should progress through the stages of establishing new ventures, followed by contriving medical devices with novel, impactful value. This study revealed that Japan Biodesign education provides a platform for achieving these goals, despite the challenging Japanese new business environment.

Left atrial appendage closure (LAAC) are emerging treatment for patients with atrial fibrillation (AF). However, data on the safety, efficacy, and medications for LAAC devices in patients with AF are lacking. We aimed to investigate the incidence of all-cause mortality, stroke, and major bleeding in AF patients with LAAC devices and DOACs. Moreover, we aimed to investigate the incidence rate of device-related thrombus (DRT) and the medications used in the management of AF patients with LAAC devices to gain insights into achieving better outcome. Based on a literature search using PubMed, EMBASE, Cochrane Library, and Web of Science databases between January 2015 and December 2020, eight LAAC device studies that used WATCHMAN and Amulet, and three DOAC studies that used rivaroxaban, with a total of 24,055 AF patients (LAAC devices, n = 2855; DOAC, n = 21,200), were included. A random-effects model was used to incorporate heterogeneity among studies. The pooled incidence of events per person-years were as follows: all-cause mortality, 0.06 (95% confidence interval [CI] 0.02-0.10) for WATCHMAN, 0.04 (95% CI 0.00-0.14) for Amulet, and 0.03 (95% CI 0.01-0.04) for rivaroxaban; stroke; 0.02 (95% CI 0.00-0.04) for WATCHMAN, 0 for Amulet, and 0.01 (95% CI 0.01-0.02) for rivaroxaban; major bleeding, 0.04 (95% CI 0.02-0.06) for WATCHMAN, 0.02 (95% CI 0.00-0.06) for Amulet, and 0.02 (95% CI 0.01-0.03) for rivaroxaban. The incidence rate of DRT was 2.3%, and complications were reported in 9%. The incidence of all-cause mortality, stroke, and major bleeding were similar between LAAC devices and DOACs. The rate of complications was acceptable, and those of DRT were lower than the average incidence reported in previous studies. However, further follow-up is needed. Concomitant anticoagulant and antiplatelet therapies should be further evaluated to find the optimal regimen for AF patients with LAAC devices.

This meta-analysis aimed to evaluate the device performance of conventional balloon catheters (POBA), drug-coated balloons (DCB), bare-metal stents (BMS), and drug-eluting stents (DES) in below-the-knee (BTK) ischemic lesions with regard to lesion characteristics. Online searches of PubMed, Web of Science, and Cochrane databases (2010-2019) were conducted for each of the test devices. Primary patency rates (pp) and major amputation rates 1 year after the use of each device were analyzed using a random-effects meta-analysis model. Meta-regression analysis was conducted to test associations between the outcomes and lesion characteristics. The analysis included 18 studies reporting on 24 separate cohorts comprising 2,438 patients. DES demonstrated the best pp among the test devices (83.6%; 95% confidence interval = 78.4-88.8%, studies = 8; I2 = 66%, P = 0.005). A negative coefficient between lesion length and pp (P = 0.002) was obtained. The ratio of critical limb ischemia (CLI) patients impacted the amputation rates (P = 0.031), whereas no statistically significant difference was found between the devices. DES showed favorable pp in BTK lesions; however, as the lesion lengths using DES were short, pp in long lesions still needs to be evaluated. Shorter lesions gained better pp. A higher ratio of CLI patients resulted in increased amputation rates.

BACKGROUND: The limited availability of balloon sizes for cryoballoon leads to anatomical limitations for pulmonary vein (PV) isolation. We conducted a comprehensive systematic analysis on procedural success rate, atrial fibrillation (AF) recurrence rate and complications of cryoballoon ablation in association with the anatomy of the left atrium and PV based on preprocedural CT to gain insights into proper treatments of patients with AF using cryoballoon. METHOD: A systematic search of literature databases, including PubMed, Web of Science and Cochrane Library, from the inception of each database through February 2021 was conducted. Search keywords included 'atrial fibrillation', 'cryoballoon ablation' and 'anatomy'. RESULTS: Overall, 243 articles were identified. After screening, 16 articles comprising 1396 patients were included (3, 5 and 8 for acute success, AF recurrence and complications, respectively). Regarding acute success and AF recurrences, thinner width of the left lateral ridge, higher PV ovality, PV ostium-bifurcation distance, shorter distance from the non-coronary cusp to inferior PVs, shallower angle of right PVs against the atrial septum and larger right superior PV (RSPV) were associated with poor outcomes. Regarding complications, shorter distance between the RSPV ostium and the right phrenic nerve, larger RSPV-left atrium angle, larger RSPV area and smaller right carina width were associated with incidences of phrenic nerve injury. CONCLUSION: This study elucidated several key anatomical features of PVs possibly affecting acute success, AF recurrence and complications in patients with AF using cryoballoon ablation. CT analysis has helped to describe benefits and anatomical limitations for cryoballoon ablation.

OBJECTIVES: Sinus plication has emerged as a promising tool that can lead to better stability in bicuspid aortic valve (BAV) repair. However, the mechanisms underlying the efficacy of this technique are unclear. We evaluated the hydrodynamic effect of sinus plication using the experimental pulsatile flow simulator and our original BAV model in vitro. METHODS: Based on the computed tomography data of a BAV patient who had undergone aortic valvuloplasty, a BAV model (group C, n = 6) was developed with bovine pericardium and vascular prosthesis (J-graft Shield Neo Valsalva 24 mm). We performed sinus plication (group SP, n = 6) in the BAV model and compared hydrodynamic data with the control model in the pulsatile flow simulator. Non-fused cusp angle, annulus diameter and effective height were measured by ultrasonography. RESULTS: The average flow was significantly increased in group SP compared to group C (4.24 ± 0.14 l/min vs 4.14 ± 0.15 l/min, respectively, P = 0.034). The mean transvalvular pressure gradient and regurgitant fraction were significantly decreased in group SP compared to group C (11.6 ± 4.3 mmHg vs 16.6 ± 5.0 mmHg, respectively, P = 0.009 and 14.1 ± 2.0% vs 17.4 ± 2.1%, respectively, P = 0.001). Ultrasound measurement indicated that non-fused cusp angle was significantly increased in group SP compared to group C (163.8° ± 9.2° vs 153.0° ± 4.6°, respectively, P = 0.012). CONCLUSIONS: Sinus plication in the BAV model significantly increased the commissural angle. It was effective in not only controlling regurgitation but also improving valve opening. These finding should be confirmed by evaluating cusp stress and/or long-term durability in the future studies.

BACKGROUND: Side branch (SB) dilation with an ultra-short balloon after main vessel (MV) stenting may minimise stent failure in coronary bifurcation lesions. AIMS: We sought to investigate the feasibility and efficacy of the Glider balloon (GB), a side branch (SB)-dedicated balloon 4 mm in length, in coronary bifurcation stenting. METHODS: In bench testing, stent configuration was examined with micro-focus computed tomography after crossover stenting followed by GB dilation or kissing balloon inflation (KBI). In the clinical study we performed GB dilatation after MV stenting for 207 lesions in 194 patients. Failure of the GB dilation and additional procedures due to inducible stent failure were investigated as well as adverse cardiac events at 1-year follow-up. RESULTS: In bench testing GB dilation maintained cross-sectional stent area without significant deformation and presented effective jailed strut removal in a high-angled bifurcation model. In the clinical study the cohort included left main, true bifurcation lesion, and two-stent treatment in 42.0%, 45.9%, and 14.0%, respectively. The proximal optimisation technique (POT) or POT-like inflation was performed in 82.1%. GB crossing failure, SB stenting due to dissection, and stent deformation requiring correction by KBI or MV dilation occurred in 8.7%, 1.4%, and 5.8%, respectively. Finally, simple GB dilation without KBI was completed in 91.8% for SB dilation. At one-year follow-up, target lesion revascularisation, cardiac death, myocardial infarction, and stent thrombosis were found in 7.2%, 2.1%, 2.1%, and 1.0%, respectively. CONCLUSIONS: Simple GB dilation after adequate expansion of the proximal MV stent provided acceptable acute and long-term results as an alternative to KBI.

Assessment of coronary artery lesions using the fractional flow reserve and instantaneous flow reserve (iFR) measurements has been found to reduce the incidence of further cardiovascular events. Here, we investigated differences in terms of coronary flow velocity and resistance within the analysis interval between the iFR and the intracoronary electrocardiogram (IC-ECG)-triggered distal/aortic pressure (Pd/Pa) ratio (ICE-T). We enrolled 23 consecutive patients (n = 33 stenoses) who required coronary flow measurements. ICE-T was defined as the average Pd/Pa ratio in the period corresponding to the isoelectric line of the IC-ECG. We compared the index value, flow velocity, and intracoronary resistance during the analysis intervals of the iFR and the ICE-T, both at rest and under hyperemia. ICE-T values and ICE-T intracoronary resistance were both found to be significantly lower, whereas flow velocity was significantly higher than those of the iFR at both rest and under hyperemia (P < 0.001), and all fluctuations in ICE-T values were also significantly smaller than those in the iFR. In conclusion, the ICE-T appears theoretically superior to pressure-dependent indices for analyzing phases with low and stable resistance, without an increase in invasiveness.

[This corrects the article DOI: 10.1253/circrep.CR-20-0099.].

The differences in aortic root geometry associated with various valve-sparing root replacement (VSRR) techniques have not fully been understood. We evaluated the root configuration of current VSRR techniques by developing in vitro test apparatus. Six fresh porcine hearts were used for each model. The aortic root remodeling control group involved replacement of the ascending aorta with diameter reduction of sino-tubular junction (STJ) (C1). The aortic valve reimplantation control group involved replacement of the ascending aorta alone (C2). VSRR included remodeling without (RM) or with annuloplasty (RM + A) and reimplantation with a tube (RI) or a handmade neo-Valsalva graft (RI + V). The root geometry of each model in response to closing hydraulic pressures of 80 and 120 mmHg was investigated using echocardiography. Among the VSRR models, RM yielded the largest aorto-ventricular junction (AVJ), which was similar to those in non-VSRR models [mean AVJ diameter (mm) at 80 mmHg; RM = 25.1 ± 1.5, RM + A = 20.9 ± 0.7, RI = 20.7 ± 0.9, RI + V = 20.8 ± 0.4]. RI + V yielded the largest Valsalva size and largest ratio of Valsalva/AVJ, which was similar to the control group [mean Valsalva diameter (mm) at 80 mmHg; RM = 28.4 ± 1.4, RM + A = 25.8 ± 1.3, RI = 23.6 ± 1.0, RI + V = 30.5 ± 0.8, ratio of Valsalva/AVJ at 80 mmHg; RM = 1.14 ± 0.06, RM + A = 1.24 ± 0.06, RI = 1.15 ± 0.06, RI + V = 1.47 ± 0.05]. The STJ diameter at 80 mmHg was numerically smaller with RM + A (22.4 ± 1.2 mm) than with RM (24.8 ± 2.3 mm, p = 0.11). There were no significant differences in AVJ, Valsalva, or STJ distensibility or ellipticity between procedures. Current modifications, including annuloplasty for remodeling or reimplantation in the setting of neo-Valsalva graft, yield near-physiological root geometries.

Further development of medical devices for children is required in Japan, but the development of such devices is delayed compared to that of medical devices for adults. Herein, we investigated policies for advancing the development of pediatric medical devices in Japan and the United States. Considering the achievements of each policy, we proposed a strategy to promote further development of pediatric medical devices in Japan. We investigated policies for supporting the development of pediatric medical devices and approved cases in Japan and the United States by searching contents of websites of regulatory bodies and other related administrations, and scientific papers. We found the main six policies in Japan and nine main policies in the United States for the development of pediatric medical devices. In the United States, various measures have initiated mainly in the 2000s, while in Japan, the main measures have been in place since 2013. Similarities were found in both countries, such as subsidies for application fees and research and development expenses, exemption of requirements for regulatory approval, and priority review and consultation by the regulatory body. Our study revealed that there are similarities in initiatives by both countries. To promote further development of pediatric medical devices in the future, improvements to expediting the review process to approval by the regulatory body, global development, and implementation of alternative measures to ensure the efficacy and safety of the device instead of large-scale clinical trials should be anticipated through cooperation among industry, government, and academia.

The characteristics of aortic valvular outflow jet affect aortopathy in the bicuspid aortic valve (BAV). This study aimed to elucidate the effects of BAV morphology on the aortic valvular outflow jets. Morphotype-specific valve-devising apparatuses were developed to create aortic valve models. A magnetic resonance imaging-compatible pulsatile flow circulation system was developed to quantify the outflow jet. The eccentricity and circulation values of the peak systolic jet were compared among tricuspid aortic valve (TAV), three asymmetric BAVs, and two symmetric BAVs. The results showed mean aortic flow and leakage did not differ among the five BAVs (six samples, each). Asymmetric BAVs demonstrated the eccentric outflow jets directed to the aortic wall facing the smaller leaflets. In the asymmetric BAV with the smaller leaflet facing the right-anterior, left-posterior, and left-anterior quadrants of the aorta, the outflow jets exclusively impinged on the outer curvature of the ascending aorta, proximal arch, and the supra-valvular aortic wall, respectively. Symmetric BAVs demonstrated mildly eccentric outflow jets that did not impinge on the aortic wall. The circulation values at peak systole increased in asymmetric BAVs. The bicuspid symmetry and the position of smaller leaflet were determinant factors of the characteristics of aortic valvular outflow jet.

Calcified artery lesions cause stent under-expansion and increase the risk of in-stent restenosis and stent thrombosis. Cutting balloons facilitate the fracturing of calcification prior to stent implantation, although vessel dissection and perforation are potential issues. In clinical practice, calcifications having maximum calcium angles ≤ 180° are rarely fractured during conventional balloon angioplasty. We hypothesize that the lesion/device diameter ratio and the number of blades facing a non-circular calcified lesion may be crucial for fracturing the calcification while avoiding vessel injury. The geometries of the cutting balloons were constructed and their finite-element models were generated by folding and wrapping the balloon model. Numerical simulations were performed for balloons with five different diameters and two types of blade directions in a 180° calcification model. The calcification expansion ability was distinctly higher when two blades faced the calcification than when one blade did. Moreover, when two blades faced the calcification model, larger maximum principal stresses were generated in the calcification even when using undersized balloons with diameters reduced by 0.25 or 0.5 mm from the reference diameter, when compared with the case where one blade faced the calcified model and a balloon of diameter equal to the reference diameter was used. When two blades faced the calcification, smaller stresses were generated in the artery adjacent to the calcification; further, the maximum stress generated in the artery model adjacent to the calcification under the rated pressure of 12 atm when employing undersized balloons was smaller than that when only one blade faced the calcification and when lesion-identical balloon diameters were used under a nominal pressure of 6 atm. Our study suggested that undersized balloons of diameters 0.25 or 0.5 mm less than the reference diameter might be effective in not only expanding the calcified lesion but also reducing the risk of dissection.

BACKGROUND: The postmarket surveillance system plays a vital role in managing residual risks and identifying safety signals in real-world clinical practice. The Food and Drug Administration (FDA) can order postmarket surveillance studies when safety concerns are raised. We conducted a thorough investigation of device characteristics, study statuses, and the outcomes of US postmarket surveillance studies. METHODS: As of April 2017, we identified 338 orders, corresponding to 394 studies using the FDA database. Additional searches were conducted to identify safety issues or reasons for orders. RESULTS: Completed and active studies were limited. Fifteen of the 394 (3.8%) studies have been completed, and one study resulted in a recommendation of a labeling change. Forty-one (10.4%) studies were active. The majority of the studies (84.3%) were inactive. Three hundred fourteen (93%) orders were issued for implantable devices. The devices for use in women accounted for 144 (43%) orders. The mean from the first premarket approval or 510(k) clearance to 522 orders were 2968 days (n = 9) and 3320 days (n = 326), respectively, and the longest lag was 13,186 days. CONCLUSIONS: Our investigation highlighted that postmarket surveillance study orders resulted in the weeding out of many of the subject medical devices. There were little clinical data produced under the program. Timely and transparent feedback from the postmarket studies are critical for informed decisions by patients and medical practitioners and in expediting patient access to innovative or advanced medical devices.

This paper proposes an automatic method for classifying Aortic valvular stenosis (AS) using ECG (Electrocardiogram) images by the deep learning whose training ECG images are annotated by the diagnoses given by the medical doctor who observes the echocardiograms. Besides, it explores the relationship between the trained deep learning network and its determinations, using the Grad-CAM.In this study, one-beat ECG images for 12-leads and 4-leads are generated from ECG's and train CNN's (Convolutional neural network). By applying the Grad-CAM to the trained CNN's, feature areas are detected in the early time range of the one-beat ECG image. Also, by limiting the time range of the ECG image to that of the feature area, the CNN for the 4-lead achieves the best classification performance, which is close to expert medical doctors' diagnoses.Clinical Relevance-This paper achieves as high AS classification performance as medical doctors' diagnoses based on echocardiograms by proposing an automatic method for detecting AS only using ECG.

BACKGROUND: Underfilled transcatheter aortic-valve implantation with ad hoc post-dilation is a therapeutic option for patients with borderline annuli to avoid acute complication. The effects of this technique on valve leaflet behavior, hydrodynamic performances, and paravalvular leakage (PVL) using patient-specific three-dimensional (3D) aortic-valve models were investigated. Methods and Results: A female octogenarian patient was treated with this technique by using a 23-mm Sapien-XT. Patient-specific models were constructed from pre-procedure computed tomography (CT) data. Change in aortic annulus areas during systolic/diastolic phases and post-procedure stent areas were adjusted to those of the patient. The following was performed: (1) -3 cc initial and -2 cc underfilled post-dilation to the scale-down model by adjusting percent oversizing; and (2) -1 cc initial underfilling, nominal volume, and repeat nominal volume post-dilation using the patient-specific model. Underfilling was associated with higher %PVL. Observation using a high-speed camera revealed distorted leaflets after underfilled implantation, with a longer valve-closing time and smaller effective orifice areas, especially in the -3 cc underfilled implantation. Micro-CT analysis revealed that the transcatheter valves shifted to the opposite side of the large annulus calcification after post-dilation and reduced the malapposition there. CONCLUSIONS: Excessive underfilled implantation showed unacceptable acute hemodynamics. Abnormal leaflet motions after underfilled implantation raised concerns about durability. Flow simulations using patient-oriented 3D models could help to investigate hemodynamics, leaflet motions, and the PVL mechanism.

OBJECTIVES: To evaluate, in vitro, SB stenting techniques after failed provisional stenting. We aimed to compare flows and stent strut apposition of T and protrusion (TAP) versus Reversed String (RS) techniques using a flow simulator, optical coherence tomography (OCT) using silicon bifurcation phantoms with different bifurcation angulations. BACKGROUND: While bifurcation coronary artery stenoses are preferably treated with provisional T-stenting strategy, the preferred bailout two stents technique to treat the side branch remains unclear. METHODS AND RESULTS: Eleven 30°-angle and ten 60°-angle bifurcation phantoms were used. After performing provisional stenting, TAP and RS techniques were compared in six phantoms with 30° and five with 60° angles. Flow measurement was performed using absolute coronary flow and particle image velocimetry techniques. Strut apposition was evaluated using OCT. Flow analyses showed that disturbed flow regions were observed in the vicinity of floating struts protruded into the lumen both regardless of TAP and RS techniques. OCT analysis showed a higher proportion of floating struts protruding into the main branch with TAP compared to RS, respectively (13% vs. 1%; P <0.001) in both angles. CONCLUSIONS: RS reduces the proportion of floating struts protruding into the main branch compared to TAP, at comparable flow rates. Clinical studies are needed to evaluate feasibility and potential clinical benefit of this technique.

The evaluation of strain induced in a blood vessel owing to contact with a medical device is of significance to examine the causes leading to vascular injury and rupture. The development of a method to assess strain in largely deformed elastic materials is expected. This study's scope was to measure strain in deformed tubular elastic mock vessels using tomographic particle image velocimetry (tomo-PIV), and to show the applicability of this measurement method by comparing the results with data derived from a finite element analysis (FEA). Strain distribution was calculated from the displacement distribution, which in turn was measured by tracking fluorescent 13 μm particles in a transparent tubular elastic model using tomo-PIV. The von Mises strain distribution was calculated for a model whose inner diameter was subjected to a pressure load, because of which it expanded from 25 to 27.5 mm, adjusting to the diameter change of a human aorta during heartbeat. An FEA simulating the experiment was also conducted. Three-dimensional strain was successfully measured by using the tomo-PIV method. The radial strain distribution in the model linearly decreased outward (from the its inner to its outer side), and the result was consistent with the data obtained from the FEA. The mean von Mises strain measured using tomo-PIV was comparable with that obtained from the FEA (tomo-PIV: 0.155, FEA: 0.156). This study demonstrates the feasibility of utilizing tomo-PIV to quantitatively assess the three-dimensional strain induced in largely deformed elastic models.

Assembling three-dimensional (3D) tissues from single cells necessitates the use of various advanced technological methods because higher-density tissues require numerous complex capillary structures to supply sufficient oxygen and nutrients. Accordingly, creating healthy culture conditions to support 3D cardiac tissues requires an appropriate balance between the supplied nutrients and cell metabolism. The objective of this study was to develop a simple and efficient method for low-temperature cultivation (< 37 °C) that decreases cell metabolism for facilitating the buildup of 3D cardiac tissues. We created 3D cardiac tissues using cell sheet technology and analyzed the viability of the cardiac cells in low-temperature environments. To determine a method that would allow thicker 3D tissues to survive, we investigated the cardiac tissue viability under low-temperature culture processes at 20-33.5 °C and compared it with the viability under the standard culture process at 37 °C. Our results indicated that the standard culture process at 37 °C was unable to support higher-density myocardial tissue; however, low-temperature culture conditions maintained dense myocardial tissue and prevascularization. To investigate the efficiency of transplantation, layered cell sheets produced by the low-temperature culture process were also transplanted under the skin of nude rats. Cardiac tissue cultured at 30 °C developed denser prevascular networks than the tissue cultured at the standard temperature. Our novel findings indicate that the low-temperature process is effective for fabricating 3D tissues from high-functioning cells such as heart cells. This method should make major contributions to future clinical applications and to the field of organ engineering.

As transcatheter aortic valve implantation (TAVI) requires multidisciplinary collaboration, operators and the entire heart team must overcome a steep learning curve. A web-based screening and traditional on-site proctoring system were developed for the introduction of TAVI in Japan. To assess the learning curve involved with the introduction of TAVI under the supervision of a novel proctoring system. We divided 749 consecutive patients enrolled in the OCEAN-TAVI study between October 2013 and August 2015 into the trans-femoral (TF, n = 608) and transapical (TA, n = 141) approach groups to compare outcomes in patients who underwent TAVI during the early proctoring period (proctoring group) and after the procedures began to be performed independently (independent group). The primary endpoint was the rate of composite events regarding early safety (at 30 days) according to the valve academic research consortium-2 criteria. For TF-TAVI, the logistic EuroSCORE and the rate of peripheral artery disease were significantly lower during the independent period. The rate of device success significantly increased during the independent period (90.5 vs. 81.8%, p = 0.005). The rate of the primary endpoint was significantly reduced during the independent period compared to that during the proctoring period for TA-TAVI (21.3 vs. 37.9%, p = 0.031); however, no difference was observed for TF-TAVI (16.8 vs. 13.1%, p = 0.283). No deaths occurred within 30 days during the proctoring period for TF-TAVI. After adjustment using propensity score matching, the procedure time for TF-TAVI (88 ± 43 vs. 102 ± 36 min, p = 0.004) and the rate of life-threatening bleeding for TA-TAVI (3.6 vs. 25%, p = 0.026) reduced during the independent period compared to the values during the proctoring period. During the introduction of TAVI under the supervision of a new proctoring system in Japan, clinical outcomes and technical aspects improved significantly. There are differences in the steepness of the learning curve between TF-TAVI and TA-TAVI.

We analyzed the adverse events associated with an off-label use of arterial stents and CE-marked iliac vein stents for the treatment of iliac venous thromboembolism and investigated their relationships with the anatomical features of the iliac vein, to gain insights into the development of a better iliac vein stent. Reports of adverse events following the use of stents in the iliac vein were retrieved from the Manufacturer and User Facility Device Experience (MAUDE) database that contain suspected device-associated complications reported to the Food and Drug Administration. Data from 2006 to 2016 were investigated. The literature analysis was also conducted using PubMed, Cochrane Library, EMBASE, and Web of Science focusing on English articles published up to 4 October 2016. The analysis of 88 adverse events from the MAUDE database and 182 articles from the literature revealed that a higher number of adverse events had been reported following the use of arterial stents in the iliac vein compared to CE-marked iliac vein stents. While stent migration and shortening were reported only for the arterial stents, stent fracture and compression occurred regardless of the stent type, even though a vein does not pulsate. A study of the anatomical features of the iliac vein implies that bending, compression, and kink loads are applied to the iliac vein stents in vivo. For designing, developing, and pre-clinical testing of stents intended for use in the iliac vein, the above mechanical load environments induced by the anatomical features should be considered.

BACKGROUND: Quantitative assessment of post-transcatheter aortic valve replacement (TAVR) aortic regurgitation (AR) remains challenging. We developed patient-specific anatomical models with pulsatile flow circuit and investigated factors associated with AR after TAVR. METHODS: Based on pre-procedural computed tomography (CT) data of the six patients who underwent transfemoral TAVR using a 23-mm SAPIEN XT, anatomically and mechanically equivalent aortic valve models were developed. Forward flow and heart rate of each patient in two days after TAVR were duplicated under mean aortic pressure of 80mmHg. Paravalvular leakage (PVL) volume in basal and additional conditions was measured for each model using an electromagnetic flow sensor. Incompletely apposed tract between the transcatheter and aortic valves was examined using a micro-CT. RESULTS: PVL volume in each patient-specific model was consistent with each patient's PVL grade, and was affected by hemodynamic conditions. PVL and total regurgitation volume increased with the mean aortic pressure, whereas closing volume did not change. In contrast, closing volume increased proportionately with heart rate, but PVL did not change. The minimal cross-sectional gap had a positive correlation with the PVL volumes (r=0.89, P=0.02). The gap areas typically occurred in the vicinity of the bulky calcified nodules under the native commissure. CONCLUSIONS: PVL volume, which could be affected by hemodynamic conditions, was significantly associated with the minimal cross-sectional gap area between the aortic annulus and the stent frame. These data may improve our understanding of the mechanism of the occurrence of post-TAVR PVL.

This is a consensus document from the European Bifurcation Club concerning bench testing in coronary artery bifurcations. It is intended to provide guidelines for bench assessment of stents and other strategies in coronary bifurcation treatment where the United States Food and Drug Administration (FDA) or International Organization for Standardization (ISO) guidelines are limited or absent. These recommendations provide guidelines rather than a step-by-step manual. We provide data on the anatomy of bifurcations and elastic response of coronary arteries to aid model construction. We discuss testing apparatus, bench testing endpoints and bifurcation nomenclature.

Percutaneous coronary intervention for the treatment of a severe calcified lesion is still one of the most technically challenging areas of interventional cardiology. Calcified lesions are a cause of stent underexpansion, which significantly increases the subsequent risks of in-stent restenosis and thrombosis, even when drug-eluting stents are used. In this report, we describe the usefulness of prolonged inflations using a scoring balloon catheter (Scoreflex) for severe calcified lesions. Prolonged inflation using a scoring balloon enables an adequate dilation for treatment of a severe calcified plaque that was unresponsive to conventional technique with or without rotational atherectomy.

Thrombus formation at the interface between connectors and tubes is a potential risk factor for complications. We investigated time-dependent relationships between formation of thrombus and hemodynamic factors at the interface between connectors and tubes using optical coherence tomography (OCT) under pulsatile flow. A swept-source OCT with the center wavelength of 1330 nm was employed. The sequential process of thrombus formation at the interface of connectors and tubes in the inlet and outlet was investigated. Connectors with and without tapers were tested using identical 50-ml air-contactless circuits. Fresh human blood from healthy volunteers was circulated under pulsatile flow. Thrombus initially formed at the interface between the connector tip and the tube. Geometries of thrombus growth were different between the 2 connectors, and between the inlet and the outlet. Growth of thrombus was observed at the interface between the connectors and tubes over time in 60 min circulation, except at the outlet part of connector without tapers. At the connector without tapers outlet, thrombus propagation length from the connector edge toward the flow downstream was comparable at 10 and 60 min (0.55 ± 0.35 vs. 0.51 ± 0.32 mm, p = 0.83). Analysis using particle image velocimetry showed the presence of a flow reattachment point 1.5 mm downstream from the connector edge. These results suggest that the flow reattachment point inhibits downstream thrombus growth. We quantitatively demonstrated sequential thrombus process at the interface between the connectors and tubes under pulsatile flow of human blood using OCT.

Our aim was to conduct a scoping review of the regulations for hemodialyzers in the safety evaluation in Japan and the United States, and to evaluate the criteria for premarketing clinical trials and postmarketing safety reports to inform the development of a sophisticated premarketing evaluation in Japan. Regulations for approval of hemodialyzers were identified from the databases of the Ministry of Health, Labor and Welfare in Japan and the Federal Drug Agency (FDA) in the United States (US). The criteria for premarket clinical trials and postmarketing safety reports were evaluated for both countries. Standards in Japan required evaluation of blood compatibility and reporting of acute adverse effects by a premarketing clinical trial in 6 of 86 applications with semipermeable membrane materials deemed to be different to those of previously approved devices from 1983 to 31 August 2015. By comparison, the clinical trial was required in one of 545 approvals in the US from 1976 to 29 January 2016, but blood compatibility was not the point. All postmarketing adverse effects identified in Japan were included in the set of 'warnings'. The more stringent requirements for evaluation of blood compatibility and acute adverse effects in Japan seemed to be related to differences in the history of quality management systems for medical devices between the two countries. This study revealed that there were differences between Japan and the US in requiring the premarketing clinical trials for the hemodialyzers. Our findings could be useful for constructing sophisticated premarketing safety evaluation.

Stent struts protruding into ostial side branch called "jailed strut" at bifurcation lesions is a likely cause of thrombus formation. We aimed to investigate the influences of multiple kissing balloon inflation (KBI) for stent expansion, and stent platform design, respectively, on the reduction of incomplete stent apposition area (ISA area) caused by jailed struts at a side-branch ostium, using a three-dimensional elastic left main (LM) bifurcated coronary artery model. The referenced LM bifurcation angle data of 209 patients were stratified by tertiles focusing on the angle between the LM trunk (LMT) and left anterior descending artery (LAD). A bifurcation model was fabricated with angles of 129°, 122.2°, and 76.4° for LMT-LAD, LMT-left circumflex (LCx), and LAD-LCx, respectively, and with diameters of 5, 3.75, and 3.5 mm for LMT, LAD, and LCx, respectively; these diameters fulfill Murray's law. A 75 % stenosis was included along the LMT. One-time and three-time KBIs were conducted using two-link Nobori and three-link Xience Xpedition (n = 6 each). The ISA area was quantified using micro-CT. Three-time KBI was effective in reducing the ISA area compared with one-time KBI for both the Nobori (p = 0.05) and Xience Xpedition (p = 0.07). The ISA area was smaller in the Nobori than in the Xience Xpedition, both in one-time and three-time KBI (one-time KBI: p = 0.003; three-time KBI: p = 0.001). Our findings of this study on reducing the ISA area by focusing on an interventional technique and stent design may help to improve coronary bifurcation intervention for a possibly better long-term clinical outcome.

BACKGROUND: The mechanical interaction between blood vessels and medical devices can induce strains in these vessels. Measuring and understanding these strains is necessary to identify the causes of vascular complications. This study develops a method to measure the three-dimensional (3D) distribution of strain using tomographic particle image velocimetry (Tomo-PIV) and compares the measurement accuracy with the gauge strain in tensile tests. METHODS AND FINDINGS: The test system for measuring 3D strain distribution consists of two cameras, a laser, a universal testing machine, an acrylic chamber with a glycerol water solution for adjusting the refractive index with the silicone, and dumbbell-shaped specimens mixed with fluorescent tracer particles. 3D images of the particles were reconstructed from 2D images using a multiplicative algebraic reconstruction technique (MART) and motion tracking enhancement. Distributions of the 3D displacements were calculated using a digital volume correlation. To evaluate the accuracy of the measurement method in terms of particle density and interrogation voxel size, the gauge strain and one of the two cameras for Tomo-PIV were used as a video-extensometer in the tensile test. The results show that the optimal particle density and interrogation voxel size are 0.014 particles per pixel and 40 × 40 × 40 voxels with a 75% overlap. The maximum measurement error was maintained at less than 2.5% in the 4-mm-wide region of the specimen. CONCLUSIONS: We successfully developed a method to experimentally measure 3D strain distribution in an elastic silicone material using Tomo-PIV and fluorescent particles. To the best of our knowledge, this is the first report that applies Tomo-PIV to investigate 3D strain measurements in elastic materials with large deformation and validates the measurement accuracy.

BACKGROUND: Blood-contacting devices have contributed to improving the treatment of patients. However, thrombus formation at the interface between a connector and tube is still a potential source of thrombus-related complications that induce stroke or myocardial infarction. We aimed to develop a non-blood-contacting real-time method for visualizing thrombus formation, and to experimentally investigate the time-dependent phenomenon of thrombus formation at the interface between a connector and a tube in a medical device. METHODS AND FINDINGS: An optical coherence tomography device with a center wavelength of 1330 nm was used to visualize thrombus formation during porcine blood circulation for 50 min in a closed 50-mL circulation system isolated from ambient air. The thrombus formation sites at the interface between a tube and connector were visualized. The area of the thrombus formation at the interface between the inlet of the connector and the tube was found to be 0.012 ± 0.011 mm2. Conversely, at the interface between the outlet of the connector and the tube, the area was found to be 0.637 ± 0.306 mm2. Thus, significantly larger amounts of thrombus were formed at the outlet interface (p < 0.01). The thrombus formation area at the outlet interface increased over time. Conversely, the area of thrombus formation showed repeated increasing and decreasing behavior at the inlet interface. Flow visualization with particle image velocimetry showed the presence of a flow separated area in the minimal flow phase at the inlet interface and a large recirculating slow flow region at the outlet interface in the minimal flow phase. These data suggested that the recirculating stagnant flow region contributed to thrombus growth. CONCLUSIONS: The method presented here was effective in quantitatively assessing time-dependent phenomena of thrombus formation at the connector-tube interface. The method may contribute to the assessment of thrombogenicity of a novel design of connector.

<p>【目的】医療機器においてソフトウェアは広く使われるようになっている。一方、米国における医療機器リコールの原因の上位をソフトウェア設計が占めるなど、医療機器ソフトウェアには安全面に課題がある。本研究の目的は、医療機器ソフトウェアにおける安全対策を分析することである。</p><p>【方法】日米欧3極の法規制・ガイダンスから、現状の医療機器ソフトウェアに対する安全対策を抽出し（A）、産業分野に依存しないソフトウェアの安全対策を「ソフトウェアエンジニアリング知識体系ガイド（SWEBOK）」・「ソフトウェア品質知識体系（SQuBOK）」から抽出した（B）。Bを基準にAを3点スコアリングで評価した。（Bにおける安全対策がAにおいて十分言及（3点）、ある程度言及（2点）、言及無し（1点））</p><p>【結果】法規制・ガイダンス等から28件の安全対策を抽出した。また、SWEBOKから26項目、SQuBOKから16項目を安全対策として抽出した。スコアリングの結果は、対SWEBOKで1.4点、対SQuBOKで1.5点であった。</p><p>【考察】スコアリングの結果は、リスクマネジメントやソフトウェアライフサイクルプロセスの面では比較的充実しているが、具体的セーフティ技法は不足しており、全体として医療機器ソフトウェアにおける安全対策に不足の面があることを示唆している。</p><p>【結論】医療機器におけるソフトウェアの安全対策を他産業におけるそれと比較分析し、現状の課題を示した。</p>

<p>【背景】我々の人工血管置換術用手術ナビゲーションシステムは、2006年にプロトタイプ機による臨床応用を開始した。当該システムによる100症例の臨床経験を通して、精度向上や使いやすさの工夫を重ね、新規ナビゲーションシステムが再構築された。新システムの臨床応用を2016年6月に開始したので、本稿ではその経験について報告する。【方法】新システムを胸腹部大動脈人工血管置換術6例に適用した。患者の体位決定後、消毒前に患者と事前に取得した画像データとのレジストレーションを行い、術者の目標血管へのアプローチ法を決定した。皮膚切開及び癒着部の剥離を経て、術野を確保した後、目標血管周辺に存在する特徴点に基づいて患者と画像とのずれを補正し、肋間動脈を同定した。【結果】ナビゲーションは全例でスムーズに運用できた。ナビゲーションに要した時間は、皮膚切開前のアプローチ方法の決定に9.8±1.7分、術野における血管同定に6.4±1.5分であった。皮膚切開前のナビゲーションでは左胸から目標血管へ向かう方向のアプローチを画像で確認するために十分な精度が得られ、剥離後も肋間動脈の目標血管の位置及び走行を確認できた。【結論】新システムは、現在良好に運用できている。今後は、新システムを解剖学的に特異的な症例にも適用し、ナビゲーションが広く使用できることを示していきたい。</p>

UNLABELLED: Tissue-engineering approaches have a great potential to improve the treatment of tendon injuries that affect millions of people. The present study tested the hypothesis that introduction of a tendon derived stem/progenitor cell (TSC) sheet accelerates tendon healing and tendon regeneration in a rat model. TSC sheets were produced on temperature-responsive culture dishes. Then, they were grafted on unwounded Achilles tendons and at sites of a 3mm of Achilles tendon defect. At 2 and 4weeks after implantation tendons were examined by histology, immunohistochemistry, transmission electron microscopy (TEM) and mechanical testing. The results showed that the implanted TSC sheet remained stably attached on the tendon surface at 4 weeks after implantation. Moreover, in the tendon defect model, tendon defect area where TSC sheet was implanted was well regenerated and had better organized collagen fibers with elongated spindle shaped cells, compared to relatively disorganized collagen fibers and round shaped cells in the control group. TEM observations revealed longitudinally aligned collagen fibers and thick collagen fibrils in the TSC sheet implanted group. Finally, at 4weeks mechanical property of the TSC sheet implanted tendon had better ultimate load than the control. In conclusion, this study demonstrates the feasibility of implanting TSC sheets on tendons in vivo. Introduction of the cell sheets into a tendon defect significantly improved histological properties and collagen content at both 2 and 4 weeks after implantation, indicating that TSC sheets may effectively promote tendon remodeling in the early stages of tendon healing. STATEMENT OF SIGNIFICANCE: Tendon injury is a highly prevalent clinical problem that debilitates millions of people worldwide in both occupational and athletic settings. It also costs billions of healthcare dollars in treatment every year. In this study, we showed the feasibility of using tendon derived stem cell sheet to deliver biologically active tenogenic-constructs and promote tendon regeneration. This work has the potential to impact the orthopaedic surgery and sports medicine fields in the treatment of tendon injury.

New technology related to artificial organs is most attractive for worldwide researchers. We believe they must contribute for the future patients against untreatable diseases. Regulatory science is a new science to establish 'social acceptance' of new technology into the clinical market as soon as possible. In the history of silicone breast implants, we could recognize risks many times; however, we missed such chances to prevent a subsequent crisis. We analyzed the trend of published literature related to silicone breast implants to review the medical professionals' interests on such risks. This trend showed, despite issues of a social acceptance of silicone breast implants in a few countries, other countries' medical professionals had no interest. Our hypothesis is 'medical professionals face the government and do not have contributed to re-establish the social acceptance of new technologies for patients'. Any technology does not have the complete evidence of safety, efficacy and quality, despite regulatory authorities' review and approval with clinical evidences. medical professionals need to conduct subsequently the epidemiological study, to take a meta-analysis periodically and to create/update the guidance for their patients under their professional ethics after the marketing of new technologies. We need to take seriously the 'lesson learned' from the history of silicone breast implants for all kind of new technologies existed in the present.

BACKGROUND: Clinical studies for assessing the effectiveness and safety in a premarketing setting are conducted under time and cost constraints. In recent years, postmarketing data analysis has been given more attention. However, to our knowledge, no studies have compared the effectiveness and the safety between the pre- and postmarketing settings. In this study, we aimed to investigate the importance of the postmarketing data analysis using clinical data. METHODS AND FINDINGS: Studies on capsule endoscopy with rich clinical data in both pre- and postmarketing settings were selected for the analysis. For effectiveness, clinical studies published before October 10, 2015 comparing capsule endoscopy and conventional flexible endoscopy measuring the detection ratio of obscure gastrointestinal bleeding were selected (premarketing: 4 studies and postmarketing: 8 studies) from PubMed (MEDLINE), Cochrane Library, EMBASE and Web of Science. Among the 12 studies, 5 were blinded and 7 were non-blinded. A time series meta-analysis was conducted. Effectiveness (odds ratio) decreased in the postmarketing setting (premarketing: 5.19 [95% confidence interval: 3.07-8.76] vs. postmarketing: 1.48 [0.81-2.69]). The change in odds ratio was caused by the increase in the detection ratio with flexible endoscopy as the control group. The efficacy of capsule endoscopy did not change between pre- and postmarketing settings. Heterogeneity (I2) increased in the postmarketing setting because of one study. For safety, in terms of endoscope retention in the body, data from the approval summary and adverse event reports were analyzed. The incidence of retention decreased in the postmarketing setting (premarketing: 0.75% vs postmarketing: 0.095%). The introduction of the new patency capsule for checking the patency of the digestive tract might contribute to the decrease. CONCLUSIONS: Effectiveness and safety could change in the postmarketing setting. Therefore, time series meta-analyses could be useful to continuously monitor the effectiveness of medical device in clinical practices.

冠動脈ステントの破断は, 再狭窄やステント血栓症のリスクとして認識されている. しかし, 実際の発生頻度は明確になっていない. 本研究は, 査読付き論文を調査することによって国内におけるステント破断の発生状況を評価し, 不具合報告の現状を明らかにすることを目的としている. 2014年4月1日にPubMedおよび医学中央雑誌 (医中誌) を用いてステント破断の発生に関する文献分析を実施した. PubMedでは, 「stent fracture」を検索単語として使用した. 医中誌では, 「冠動脈」「ステント」「fracture」「破断」「破損」を検索単語として使用した. PubMed検索で895報が検索された. これらの中で, 日本以外の施設にて実施された文献が792報, 冠動脈が対象ではない文献が45報, ステント破断とは関係のない文献が17報, 同一症例を対象としていると考えられる文献が11報あった. これらを除外し, 14報の観察研究および16報の症例報告で合計30報を解析対象とした. 査読付き論文では643病変でのステント破断, 不具合報告では105病変でのステント破断が報告されていた. 14報の観察研究から, ステント破断の発生頻度は5.4% (10,927病変中595病変) であった. 不具合報告から得られたステント破断の発生件数は, 文献分析によって得られた発生件数より6.1倍少なかった. これらの結果から, 不具合報告によって把握できる発生状況は, 実臨床で発生している状況の一部分を表しているに過ぎないことが定量的に示された.

<p>ソフトウェア医療機器 (Software as a Medical device, SaMD) は患者との接触がないため, 従来の医療機器ソフトウェア (Non-SaMD) のような直接的な危害ではなく, 間接的な危害を引き起こし得る. 本研究の目的は, 上記2種類に分類される, ソフトウェアを含む医療機器の間接的危害の実態をアメリカのリコールデータから分析することである. アメリカにおける医療機器のリコールのうち, 米国食品医薬品局がソフトウェア起因としたものを対象に, 各リコール製品がSaMDか否かに分類した. また, フィジカルなもの (Group 1), 情報に関係するもの (Group 2), データに関係するもの (Group 3), その他 (Group 4) の4つの故障モードに分類した. 2009～2014年の全リコール (6,393件) からソフトウェア起因のリコールとして抽出した712件に対して分類を行った結果, 間接的危害に繋がり得るGroup 2が408件 (57%) で第1位を占めており, 直接的危害に繋がり得るGroup 1が122件 (17%) で続いた. Group 2の408件中387件 (95%) がリコールクラスⅡとなっており, 6件 (1%) はリコールクラスⅠとなっていた. 6件のうち4件はNon-SaMDにて, 2件がSaMDにて起きていた. 本研究によって明らかになったこの事実は, 情報提示機能の安全性について今後さらに理解を深めていくことの重要性および安全対策が課題であることを示唆している.</p>

<p>A navigation system with high accuracy is required for performing precise surgery. To obtain high accuracy, three factors should be considered: acquiring precise image data of patient, measuring an accurate intraoperative patient position and reducing registration error. Although it spends a lot of efforts to set up the system during surgery, its performance does not always satisfy surgeons.</p><p> During this decade, we have developed a surgical navigation system for aortic aneurysm repair and utilized it in one hundred clinical cases. It has been found that this system has needed to improve the usability and the reliability in registration process to show valuable information for surgery. Our recent system adopts a two-phased approach with different goals. Before thoracotomy, it exhibits the location of a target intercostal artery in the thorax and supports a surgeon to determine an appropriate approach to repair aortic aneurysm in each patient setup and anatomy. After adhesiolysis, it narrows the range of existing area of the artery within five millimeters and assists him to identify the artery. </p><p> In 2016, its improved system is ready to use for clinical pre-trial with approval from Hospital Ethics Committee of Tokyo Women's Medical University. In the next two years, it is hoped that the improved system provides the clinical benefit.</p>

Treatment of coronary bifurcation lesions remains an ongoing challenge for interventional cardiologists. Stenting of coronary bifurcations carries higher risk for in-stent restenosis, stent thrombosis, and recurrent clinical events. This review summarizes the current evidence regarding application and use of biomechanical modeling in the study of stent properties, local flow dynamics, and outcomes after percutaneous coronary interventions in bifurcation lesions. Biomechanical modeling of bifurcation stenting involves computational simulations and in vitro bench testing using subject-specific arterial geometries obtained from in vivo imaging. Biomechanical modeling has the potential to optimize stenting strategies and stent design, thereby reducing adverse outcomes. Large-scale clinical studies are needed to establish the translation of pre-clinical findings to the clinical arena.

Bench testing of stents used in bifurcations can provide information on the general properties that influence performance including crossing profile, radial strength, recoil, flexibility and radiopacity. Problems with device delivery can be clarified. Bench testing identified that side branch dilatation caused stent distortion and elucidated correction strategies. Bench testing led to a stent design change adding connectors between hoops to help overcome the clinical problem of longitudinal distortion. Testing on the bench can determine best deployment strategies and showed that a two-step post-dilatation strategy produced the best deployment with "crush" stenting. Scanning electron microscopy showed that withdrawal of a coronary guidewire trapped between a stent (or scaffold) and a mock arterial wall during a provisional side branch stenting strategy caused only mild linear polymer coating damage. Stent fracture can cause adverse clinical events and our repetitive bend test identified the stents most resistant to fracture. Causes of obstruction of the passage of a balloon over a wire through the side of a stent include damage to the catheter tip, complex cell geometry and inadvertent passage of a wire behind a strut. Bench testing plays a major role in validation of computer modelling of bifurcation treatments and flow alterations.

迷走神経刺激装置（Vagus Nerve Stimulation system）は完全植込み型の電気刺激装置で，左側の迷走神経を電気的に刺激することで薬剤抵抗性のてんかん発作を抑制したり軽減したりするものである．本邦では承認されてから3年が経過し，500例以上が植え込まれたものの直接医療費の変化については未だ報告が見られない．そこで本邦においてVNS植え込みの前後2年間の直接医療費を比較することでその変化が見られるかを検討した．聖隷浜松病院は2010年7月の承認以後2013年11月までに87例を植え込んだ．2年以上の迷走神経刺激治療を受けた患者の直接医療費を後方視的に調査するとともに，植込み前2年間と植込み後2年間の薬剤費も調査した．17症例（平均年齢28.6歳，16-56歳）がこの基準に達した．総直接医療費は薬剤費を除いて，植込み前2年間では\21,519,870だったが，植込み後2年間では\11,597,610だった．この医療費減少は，てんかん診療に係る診察費や脳波等の検査費および画像診断費の節減に負うところが大きい．4種類の新しい抗てんかん薬が2006年以降非常に高い薬価が付いて承認されたために迷走神経刺激による薬剤費の変化を論じることはできなかった．この調査により迷走神経刺激以降は薬剤費を除く直接医療費に変化が生じていることが明示された．しかしながら費用対効果を論じるまでには至っていない．加えて本調査は植え込み前2年間と植え込み後2年間の医療費の比較のために，調査期間が短く，そのために医療費が電池寿命による交換費用が含まれていない．今後は植え替えを含めた長期調査が必要と思われる．

Introduction: Coronary stent fracture is recognized as causes of restenosis or thrombosis. We conducted finite element analysis (FEA) of coronary stent to predict fatigue failure under cyclic bend loading. Methods: Matched with manufacturing steps of coronary stent, a stent with a diameter, length and thickness of 1.8mm, 18mm, and 81&mu;m was modeled. The stent was crimped on a balloon by applying enforced displacement until the outer diameter became 1.0mm. Next, the stent was deployed into a bended coronary artery model with an angulation of 125 degrees. Then, cyclic bend from 125 degrees to 105 degrees was applied to the stent. Results and Discussions: FEA of alternating stress, mean stress, and fatigue safety factor showed that there were nodes in unsafe zone in Goodman diagram. FEA suggested a threshold of cyclic bend angulation of the coronary stent on fatigue failure. Fracture locations observed in the cyclic-bend accelerated durability tests was consistent with the nodes of the stents which exceeded fatigue safety factor of 1. Conclusion: The comparison between FEA and accelerated durability tests indicated that FEA was useful to predict fatigue failure of the coronary stent.layer and gas layer.

AIMS: To define the optimal kissing balloon inflation (KBI) after single-stent deployment in a coronary bifurcation model. METHODS AND RESULTS: We deployed stents in main vessels (MV) followed by KBI in various conditions and compared the stent configurations. A) KBI at the operator's discretion vs. under the guidelines of minimal balloon overlapping (MBO). Various stent configurations were observed after the former option, whereas similar maximal dilation points were observed under the MBO guidelines. B) Long balloon overlapping (LBO) vs. MBO with proximal MV dilated by a large balloon. The proximal MV was dilated to an ideal round shape with MBO versus an oval shape with LBO. C) Two-link vs. 3-link stents. Although the 2-link stent was advantageous to open the side branch, it incurred a risk of overdilatation of the proximal struts, whereas the 3-link stent preserved its structure. Computed simulations of coronary flow were analysed in the following left main coronary models: circle with a diameter of 4 and 5.5 mm, ellipse with longitudinal direction and tilt position. They revealed that the overdilated side was exposed to low shear stress regardless of its shape. CONCLUSIONS: Optimal KBI can be achieved with MBO and proximal dilatation by an optimally sized balloon.

Thrombogenic reactions under multiple interactions of pharmacological agents, doses, and materials have not been well understood yet. The aim of this study was to investigate the ability to simultaneously compare thrombogenic reactions to different combinations of anticoagulants, doses, and blood-contacting materials, in a single human blood using an in vitro test method. Four venous blood samples were drawn from each of six healthy volunteers into syringes that contained two different amounts of heparin and argatroban to set the activated clotting time (ACT) to approximately 200 or 500 s, respectively. The four blood samples from each volunteer were immediately poured into two clinical-grade extracorporeal circulation tubes: a polyvinyl chloride (PVC) tube and a poly(2-methoxyethyl acrylate)-coated (PMEA) PVC tube. These tubes with an inner diameter of 12.7 mm were rotated at 183 rpm in a 37°C chamber for 10 min. The results indicated that the in vitro thrombogenicity test method was capable of assessing differences in platelet factor 4 and β-thromboglobulin increases among different combinations of the two materials, two anticoagulants, and two ACTs. Higher amounts of total plasma proteins were absorbed on PVC tubes than on PMEA-coated tubes when using the same anticoagulant and dose. These data elucidate that the in vitro thrombogenicity test method is useful for the simultaneous quantitative evaluation of the influences of various combinations of materials, pharmacological agents, and doses on thrombogenicity in a single human blood.

It is clinically recognized that percutaneous coronary intervention (PCI) treatment for proximal left anterior descending (LAD) artery disease is resulting in less satisfactory in comparison with other lesions. However, the reason has not yet clarified. The purpose of this study is to investigate the mechanical loading conditions in proximal LAD artery. This study hypothesized that the coronary artery is prestretched in the heart. In order to investigate the pre-stretched value, porcine heart was obtained from a local slauterhouse. Two points were marked at coronary artery and its distance was measured. Two-dimensional distances (L1) between the dots marked on vessel centerline were measured with digital microscope. The coronary artery was separated from the heart, the distance between the points was measured again (L2). Pre-stretched ratio was calculated as (L1-L2)/L2 ×100%. 101 consecutive patients of coronary CT were taken in Hokkaido Cardiovascular Hospital from September 2012 in order to investigate dynamic loads acting on coronary artery. The distance of proximal LAD artery was measured in diastolic phase (Ld) and systolic phase (Ls) from a stretch view taken from CT. Shortening ratio was defined as (Ld-Ls)/Ld ×100%. The twist angle was defined as a sum of the following two angles and mesured in end-systolic and end-diastolic phase. One is tha angle between the line connecting the centers of LAD and left circumflex (LCX), and the perpendicular line toward abdominal to dorsal. The other is the angle between the line connecting the centers of LAD and the first septal branch, and the perpendicular line. Twisting ratio was calculated as θ/Ld ×100%.Results showed that the pre-stretched ratio was calculated to be 7.6±2.9% (mean±SD) in porcine LAD artery. The length of proximal LAD artery of human coronary artery was 26.6 ± 9.3mm (mean±SD). Shortening ratio was calculated to be 6.1 ± 6.2% (mean±SD). And the mean twisting ratio was calculated to be 0.6 °/mm. This study revealed the pre-stretched value of proximal LAD artery due to restrain from the myocardium. Moreover shortening and twisting motions in proximal LAD artery were quantified.

Trifurcated arch grafts (3-branch grafts) are now being used to repair the thoracic aorta in addition to conventional arch grafts (4-branch grafts). The anatomical shape of the 3-branch graft is different from the original vessel, so it is necessary for clinical application to evaluate blood flow distribution in the graft to assess whether there is adequate blood flow to the target organs. To achieve this, we developed a computational fluid dynamics (CFD) method to evaluate blood flow distribution in the grafts. Aortic blood flow was measured by phase-contrast magnetic resonance imaging (PC-MRI), and flow distribution into the branched vessels was obtained. The MRI image was used to create a patient-specific image model that represents the geometry of the aortic arch. The CFD analysis method was employed to determine a boundary condition of the blood flow analysis in the aorta using a patient-specific image model. We also created simplified models of 4-branch and 3-branch grafts and used our CFD analysis method to compare blood flow distribution among simplified models. It was found that blood flow distribution in the descending aorta was 71.3 % for the 4-branch graft and 67.7 % for the 3-branch graft, indicating that a sum of branching flow in the 3-branch graft was almost the same as the one in the 4-branch graft. Therefore, there is no major concern about implanting a new 3-branch graft. Our CFD analysis method may be applied to estimate blood flow distribution of a newly developed vascular graft prior to its clinical use and provide useful information for safe use of the graft.

The Japanese medical device industry's stagnation over the years can be attributed to the uncertainty related to device development. The purpose of this study is to identify the major factors that impact development. We studied the ventricular assist device EVAHEART through interviews with the persons involved and created a development model using system dynamics. There are at least six stages in the device development process, including interactions with academia and the government. Through a simulation and comparison to Novacor, it was determined that the satisfaction of academia leads to government action in the subsequent measures. Our trial simulation of EVAHEART suggests that it has the potential to clarify unclear relationships in the development of devices.

The goal of effective interprofessional education (IPE) is high-quality patient-care delivery and attaining a high level of patient satisfaction in clinical settings. We aimed to examine if alumni who have studied in an IPE program at a pre-licensure stage maintain a positive attitude toward collaborative practice (CP) in the postgraduate clinical experience. This paper presents a cross-sectional descriptive study which employed the modified attitudes toward health care teams scale (ATHCTS) to examine the relationship between exposure to clinical practice and the attitudes toward interprofessional healthcare teams. Results indicated that the overall mean score of alumni was significantly lower than that of undergraduate students on the modified ATHCTS. Only "team efficacy" had a significantly lower regression factor score in alumni than undergraduate students. Our findings suggest that changes in professional identity in a team may be due to contact with patients after graduation in the postgraduate clinical healthcare experience. The reduction of attitudes toward healthcare teams in the postgraduate clinical experience may be related to "team efficacy". We emphasize the need for in-service IPE for sustaining attitudes and providing a useful CP, which results in good clinical outcome.

Purpose: We have reconstructed aortic valves using autologous pericardium treated with glutaraldehyde since April 2007. However, the strength of the human pericardium has not been confirmed. We compared tensile strength between glutaraldehyde-treated human pericardium and aortic valve leaflets with various degrees of calcification to determine their suitability for use in aortic valve reconstruction.
Methods: We measured the ultimate tensile strength and elasticity of samples of glutaraldehyde-treated pericardia (n = 8), non-calcified (n = 12), calcified (n = 9) and decalcified (n = 21) aortic leaflets collected from 23 patients who underwent aortic valve surgery. Aortic valves were decalcified using a cavitational ultrasonic surgical aspirator. The pericardium was immersed in 0.6% buffered glutaraldehyde for 10 minutes and then rinsed three times for 6 minutes each in normal saline.
Results: The ultimate tensile strength of the glutaraldehyde-treated human pericardium, non-calcified, calcified and decalcified leaflets was 10, 2.8, 1.0 and 0.8 MPa, respectively.
Conclusions: The ultimate tensile strength of glutaraldehyde-treated human pericardium was 4 times higher than non-calcified leaflets, indicating its suitability for application to aortic valve reconstruction. Calcified leaflets were slightly stronger than decalcified leaflets. Thus, calcification can be removed without altering the tensile strength of valve materials.

The interprofessional education (IPE) program at Gunma University, Maebashi, Japan, implements a lecture style for the first-year students and a training style for the third-year students. Changes in the scores of modified Attitudes Toward Health Care Teams Scale (ATHCTS) and those of modified Readiness of health care students for Interprofessional Learning Scale (RIPLS) at the beginning and the end of the term were evaluated in the 2008 academic year. Two hundred and eighty-five respondents of a possible 364 completed the survey. In both the scales, the overall mean scores declined significantly after the lecture-style learning in the first-year students, while the scores improved significantly after the training-style learning in the third-year students. Exploratory factor analysis revealed that the modified ATHCTS was composed of three subscales, and the modified RIPLS two subscales. Analyses using regression factor scores revealed that the scores of "quality of care delivery" subscale in the modified ATHCTS and those of "expertise" subscale in the modified RIPLS declined significantly in the first-year students. Consequently, IPE programs may be introduced early in the undergraduate curriculum to prevent stereotyped perceptions for IPE, and comprehensive IPE curricula may result in profound changes in attitudes among participating students.

Background and aim of the study: The study aim was to develop a novel stentless mitral valve (SMV) and to evaluate its performance, using an original pulsatile simulator developed specifically to analyze the hydrodynamic function of the mitral valve.
Methods: The SMV developed at the authors' institution consists of two major components: a large anterior leaflet with commissures, and a small posterior leaflet. The valve is formed by suturing the leaflets (made from bovine pericardium) to a flexible (Duran) ring. The SMV, constructed with a 27 mm flexible ring, was installed into the mitral valve simulator, after which the four papillary flaps of the two leaflets were sutured to artificial papillary muscles. The artificial ventricle was driven pneumatically at a pulse rate of 70 beats/min, with a systolic fraction of 35%. The mean flow, aortic pressure, and atrial pressure were adjusted to 4.5 l/min, 120/80 mmHg, and 10 mmHg, respectively. A 27 mm mechanical valve (MEV; St. Jude Medical Inc.) was employed as a control. The hydrodynamic performance of the SMV and MEV were investigated and compared. An echo-Doppler study was also performed.
Results: The waveforms of the SMV and MEV showed a similar pattern. The mean transvalvular flow was 4.7 +/- 0.4 l/min for the SMV, and 3.55 +/- 0.13 l/min for the MEV (p &lt;0.001). Mitral regurgitation was 5.07 +/- 1.15 and 3.78 +/- 0.35 ml/beat, respectively (p &lt;0.05). Echocardiographic data indicated that the regurgitant jet towards the left atrial model was none or trivial for the SMV, and trivial for the MEV.
Conclusion: Within the environment of the mitral valve simulator, the novel SMV prepared from bovine pericardium demonstrated excellent performance characteristics, and may represent a potential future alternative for bioprosthetic stented mitral valves.

A durability test of the implantable Left Ventricular Assist System EVAHEART was conducted to demonstrate that the EVAHEART Blood Pump can be run for 2 years without failing. This testing was useful to indicate potential for BTT and possibly DT applications. We developed a custom durability test mock circulation loop which generates a pulsatile flow simulating the native left ventricle. This mock circulation loop includes components which mimic the left ventricle (LV chamber) and compliance in the aorta (aortic column), and a loop which connects the blood pump to both the LV chamber (inlet) and the aortic column (outlet). The LV chamber has two one-way valves and a linear motor connected to a rolling seal, allowing it to generate pulsatile flow. The blood pump speed was tuned to achieve clinically relevant flow, based on the need to supplement a failing heart. The simulated heart rate (stroke rate of the linear actuator) cycled through 3 different settings each day to simulate changes in patient activity level. The sample size for the durability test was set to 18, and the test duration was 2 years. During the test, no critical blood pump failures were observed. There were no indications of significant decrease in pump performance or seal performance. Furthermore, no symptoms of failure, such as abnormal wear, were observed. In conclusion, the durability test successfully demonstrated that the EVAHEART Blood Pump achieved component reliability at a minimum of 90% reliability and 88% confidence interval over a mission life of two years.

Modern imaging technologies, such as computed tomography (CT) angiography, magnetic resonance (MR) angiography, and digital subtraction (DS) angiography are widely used for pretreatment evaluation of cerebral aneurysms, but the relative accuracies of these modalities are unclear. This study compared the measurements of aneurysm neck and dome height and width on CT angiography, time-of-flight (TOF)-MR angiography, and DS angiography using a three-dimensional workstation. An elastic model of a side-wall aneurysm was connected to an artificial heart pulsatile circuit system. The aneurysm model was prepared using a silicone membrane of 0.6-mm thickness under normal physiological circulation parameters. Using this aneurysm model, three-dimensional TOF-MR angiography, contrast-enhanced CT angiography, and DS angiography were performed. Source images were post-processed on a dedicated workstation to calculate the aneurysm size. DS angiography measurements were found to be the most accurate. In contrast, aneurysm neck sizes measured on CT angiography were significantly wider than actual values (p &lt; 0.05) and aneurysm heights measured using TOF-MR angiography were significantly lower than actual values (p &lt; 0.01). In this in-vitro model, at least one aneurysm dimension measured with CT angiography and with TOF-MR angiography differed significantly from actual values. Aneurysm neck width markedly affects therapeutic planning, as a wide neck requires craniotomy or endovascular treatment using an adjunctive device, so inaccuracies should be considered when aneurysm treatment is planned using modern methods of visualization.

Carotid artery stenting (CAS) is a minimally invasive surgical treatment for stenosis that is usually due to atherosclerotic plaque. Criteria to select an optimal stent for each clinical situation are lacking, however. Here we describe a surgical simulator that predicts vascular geometries after stenting using silicone rubber models of stenotic carotid arteries. Our objective was to develop the fabrication scheme of such vascular models. Herein, four CAS vascular models, or a soft plaque, two normal, and a hard one, were fabricated. By using rapid proto-typing of 3D CT angiographic data, we first made a patient-specific wax models with geometries that matched the lumen of carotid artery. Next, we fabricated a plaque model that matches patient-identical geometries. Then, we produced the each part using silicone rubber with different mechanical properties. In order to match the mechanical properties of the vessel model, pre- and post-stent geometry were compared in vivo and vitro using digital angiography. Moreover, we compared the stiffness of the vessel model by the Young's modulus. We first evaluated the mechanical properties of the vessel, and then that of the plaque. As for the former, the relationship between the expansion ratio and the stiffness parameter 11 was formulated by curve-fitting. We evaluated the mechanical properties of each plaque. It was found that the Young's modulus were 0.015, 0.092, 0.137, 0.503 N/m(2), for the soft, normal (two cases), and hard plaque, respectively. The largest difference was about 34 times for the soft and hard one. We achieved to develop a novel fabrication scheme for the carotid artery with atherosclerotic plaque. The validated vascular model featured two distinct mechanical properties for the vessel and plaque. Such models may help surgeons develop criteria to optimize CAS in a patient-specific manner.

Ventricular assist devices (VADs) are widely applied for end-stage congestive heart failure patients. Considering the shortage of organs donations in Japan, VADs tend to be used for longer period. The extracorporeal-type Toyobo VAD has been used. Because the guarantee period of the Toyobo VAD is one month due to a potential risk of thrombus formation inside the VAD, it is necessary to exchange the VAD periodically in a long time. In the VAD exchange, the cable-ties are removed and the VAD used including stainless-steel connectors are replaced with a new VAD. In the case of the patient for long-term-usage who can move, there is a danger that the connection parts will be detached just after VAD exchange in case some kinds of loads are added to the VAD. Therefore, it is necessary for both patients and nurses to understand the quantitative load for the detachment of the VAD.
In this study, we investigated the load required for the detachment of connectors from cannulae of the VAD before and after the VAD exchange. The VAD was incorporated in a mock circuit and pneumatically-driven in a 37 degrees C controlled water bath. In that condition, the load for the detachment of connectors from cannulae of the VAD was examined using a uni-axial tensile tester. As alternatives to cannulae used for a long time, plastically- deformed cannulae were prepared by heating at 120 degrees C for 7 hours. Influence of the tensile speed, direction of the load applied, and presence of liquid between the connectors and the cannulae on the loads necessary for the detachment were investigated.
The load necessary for the detachment in one hour after the VAD exchange was decreased to 50-60% of the load before one. However, in 24 hours after the exchange, the load was recovered to 80% of the load before the VAD exchange. When the perpendicular load of 8.5kgf was applied at the tensile speed of 500mm/min, the time required for the detachment was only 6 seconds.
It is important for nurses and patients to pay much attention in order to prevent load acting on the VAD newly changed, especially for one day after the VAD exchange.

Recently, researchers have challenged to create three-dimensional (3-D) tissues with tissue engineering technology in order to establish in vitro models and new therapy for damaged organ. Most popular approach of tissue engineering is using 3-D biodegradable scaffolds as alternatives of extracellular matrix. By contrast, we have bioengineered pulsatile myocardial tissues by stacking cardiomyocyte sheets, which were harvested from temperature-responsive culture dishes only by lowering temperature. However, the shortage of oxygen and nutrition limits the final tissue thickness. In this study, we tried to fabricate thicker myocardial tissues by promoting oxygen and nutrition permeation using a novel perfusion bioreactor. Triple-layer neonatal rat cardiomyocyte sheets were attached in the culture chamber. Chambers were perfused with 2.4mL/h culture media and 15mmHg pressure gradient was applied to perfuse the culture media through the construct. After 5-days culture, the construct in the bioreactor was thicker and cell-denser than in static condition. These results indicate that the perfusion bioreactor should contribute to myocardial tissue engineering in vitro.

Background: The mandatory interprofessional education programme at Gunma University was initiated in 1999. This paper is a statistical evaluation of the programme from 1999 to 2007.
Methods: A questionnaire of 10 items to assess the achievement levels of the programme, which was developed independently of other assessment systems published previously, was distributed, as well as two or three open-ended questions to be answered at the end of each annual module. A multivariate analysis of variance model was used, and the factor analysis of the responses was performed with varimax rotation.
Results: Over all, 1418 respondents of a possible 1629 students completed the survey, for a total response rate of 87.1%. Cronbach's alpha of 10 items was 0.793, revealing high internal consistency. Our original questionnaire was categorized into four subscales as follows: "Role and responsibilities", "Teamwork and collaboration", "Structure and function of training facilities", and "Professional identity". Students in the Department of Occupational Therapy reached a relatively lower level of achievement. In the replies to the open-ended questions, requests for the participation of the medical students were repeated throughout the evaluation period.
Conclusion: The present four subscales measure "understanding", and may take into account the development of interprofessional education programmes with clinical training in various facilities. The content and quality of clinical training subjects may be remarkably dependent on training facilities, suggesting the importance of full consultation mechanisms in the local network with the relevant educational institutes for medicine, health care and welfare.

Recently, researchers have challenged to create three-dimensional (3-D) tissues with tissue engineering technology in order to establish in vitro models and new therapy for damaged organ. We have developed cell-sheet based tissue engineering and successfully fabricated pulsatile 3-D myocardial tissues both in vivo and in vitro by layering cardiac cell sheets. However, in vitro scaling up of 3-D cell-dense tissues is limited due to lack of blood vessels supplying oxygen and nutrition and removing waste molecules. In this study, we have developed novel bioreactor culturing layered cell sheets on collagen-based microchannels and examined cell behavior between tissues and channels. Rat cardiac cells including endothelial cells were cultured on temperature responsible culture dishes for 4 days. By lowering temperature, confluent cardiac cells were harvested as an intact cell sheet and two cardiac cell sheets are layered. Collagen-based microchannels were engineered by gelling collagen around parallel stainless wires and extracting the wires. The double-layer cell sheets were put on the microchannels and the constructs were connected to the novel perfusion bioreactor. After 5 days of cultivation, the tissue sections were stained with Hematoxylin-Eosin and endothelial cell specific Isolectin B4. HE staining demonstrated that layered cell sheets tightly connected onto the collagen microchannels. The microchannels maintained their patency during culture period. The cardiac cells migrated into collagen gel and the number of migration increased flow-rate dependently. At higher flow-rate, some cardiac cells reached to microchannels and covered over their inner surface. Isolectin B4 staining showed endothelial cells formed networks within the cell sheets and also played as migrating cells. We have successfully fabricated 3-D tissues with perfused microchannels and tissue-originated cells migrated and communicated with the microchannels. These results showed new insights regarding in vitro vascular formation and indicated the possibility for fabricating vascularized 3-D tissues.

Recently, researchers have challenged to create three-dimensional (3-D) tissues with tissue engineering technology in order to establish in vitro models and new therapy for damaged organ. We have developed cell-sheet based tissue engineering and successfully fabricated pulsatile 3-D myocardial tissues both in vivo and in vitro by layering cardiac cell sheets. However, in vitro scaling up of 3-D cell-dense tissues is limited due to lack of blood vessels supplying oxygen and nutrition and removing waste molecules. In this study, we have developed novel bioreactor culturing layered cell sheets on collagen-based microchannels and examined cell behavior between tissues and channels. Rat cardiac cells including endothelial cells were cultured on temperature responsible culture dishes for 4 days. By lowering temperature, confluent cardiac cells were harvested as an intact cell sheet and two cardiac cell sheets are layered. Collagen-based microchannels were engineered by gelling collagen around parallel stainless wires and extracting the wires. The double-layer cell sheets were put on the microchannels and the constructs were connected to the novel perfusion bioreactor. After 5 days of cultivation, the tissue sections were stained with Hematoxylin-Eosin and endothelial cell specific Isolectin B4. HE staining demonstrated that layered cell sheets tightly connected onto the collagen microchannels. The microchannels maintained their patency during culture period. The cardiac cells migrated into collagen gel and the number of migration increased flow-rate dependently. At higher flow-rate, some cardiac cells reached to microchannels and covered over their inner surface. Isolectin B4 staining showed endothelial cells formed networks within the cell sheets and also played as migrating cells. We have successfully fabricated 3-D tissues with perfused microchannels and tissue-originated cells migrated and communicated with the microchannels. These results showed new insights regarding in vitro vascular formation and indicated the possibility for fabricating vascularized 3-D tissues.

A relationship between blood flows in cerebral aneurysms and their rupture remains obscure. In clinical practice, the size of aneurysms is one of the important factors for determining a strategy of treatment, but in our database three small aneurysms became ruptured during follow-up. Here, we aim to study their pre-ruptured hemodynamics, and differentiate them with those of six large unruptured aneurysms. All the aneurysms occurred in internal carotid artery, and their mean sizes were 6 and 10.8 mm for pre-ruptured and unruptured cases, respectively. We reproduced their replica as a patient-specific elastic model using clinical images obtained by digital subtraction angiography and a series of rapid proto-typing techniques. Flows were reproduced in vitro using a cerebral flow simulator, and visualized by Time-resolved Particle Image Velocimetry. All pre-ruptured cases showed the collision of an incoming flow at a distal neck, and formed a prominent jet stream directing towards the aneurismal head. In contrast, none of unruptured aneurysms had such a marked impingement, and their flows were most likely characterized by swirling patterns. All unruptured cases occurred in a twisted vessel, or carotid siphon, whereas pre-ruptured ones were located downstream whose geometries consisted of a simple curvature. These findings suggest that internal carotid artery has a regional dependency of the risk of aneurismal rupture. Furthermore, the presence of jet streams for small-sized aneurysms may be a substantial indicator of the rupture and immediate treatments.

Erythrocyte deformation by colliding with a rigid surface using a high-speed impinging jet was studied with microfluidic techniques. We aim to investigate the relevance of colliding erythrocytes with hemolysis. A micro-channel chip was made of polydimenthyl-siloxane (PDMS), which comprised a T- and V-shaped junction with a micro-nozzle and diffuser in order to attain a high-speed microflow with a jet velocity of m/s scale. A high-speed camera with a microscope imaged colliding erythrocytes by shadow imaging. Porcine erythrocyte with a hematocrit of 0.5% in phosphate buffer saline was utilized. At the Y-junction, erythrocytes showed buckling due to an impulsive, longitudinal, compressive deformation. Such anomalous phenomena were not detected at the T-junction, where erythrocytes underwent sequential compressions as approaching the colliding surface. Erythrocyte after buckling showed a hazy membrane while being released from the colliding surface, suggesting the ejection of hemoglobin out of the pore on a membrane. Flow-induced hemolysis has been considered as a model of viscous shear stress and exposure time. From our data, however, it was suggested that hemolysis due to a high-speed impinging flow characterized by mechanical heart valve flows may arise as an impulsive failure of erythrocyte membrane upon collision.

Prosthetic heart valves often induce blood cell trauma, but its mechanism is not clearly understood due to the complexity of dynamical flows. We herein propose a new challenge, termed macroscale modeling and microscale verification. This report is the former, and here we aim to clarify the physical interpretation of Reynolds stress for flowing cells. One polymer and two mechanical valves are compared, and the Reynolds stress is visualized using a novel analytical technique including time-resolved particle image velocimetry and continuous wavelet transform. The method enables to analyze the dynamics of Reynolds stress in a spatial and temporal domain. As a result, it is found that the Reynolds stress should be considered as an indicator of impinging flows for circulating cells. Such flows may impulsively apply a colliding force on a membrane of flowing cells. As microscale verification based on this new hypothesis, we are currently investigating such collision phenomena of flowing cells using high-speed microfluidic techniques.

Endovascular treatments of stenosis in carotid artery often utilize a self-expanding stent. There are a variety of stents commercially available. The radial force of a stent is a key parameter to characterize its mechanical property, but there is no reliable evaluation to standardize the force measurement. In measuring the radial force accurately, the stent deformation has to be uniform for the whole structure so as to ensure the force balance. Here we aim to develop such a measuring system of stent radial force, and compare the results with those obtained by conventional techniques.
A developed device consisted of a tubular stent holder and a load measuring system. The Precise, Protege and Easy Wall stents with a diameter (D) of 10 mm were placed by a delivery system. Radial forces were measured with D = 8, 6, 5, and 4 mm at a temperature of 37 degrees. Maintaining the circular shape of stents was found to influence substantially the magnitude of radial force. The value increased about 80% at maximum for those measured by conventional techniques. These data show that the radial force has to be uniformly applied in a circumferential direction. Also, the Easy Wall stent showed a distinct tendency in contrast to the Precise and Protege stent. The Easy Wall stent was found to be placed with eliminating the axial variation of mesh geometries.
These results indicate that the radial force measurements of stents have to ensure the uniform mesh geometry in both the axial and circumferential direction. It was concluded that our device can ensure the reliable measurement of stent radial forces.

The Seldinger technique is a well-established medical procedure to insert an indwelling device into blood vessel. Although the method is widely performed, various adverse effects due to the procedure have been reported. In order to improve safety, some hospitals originally compiled important reminders based on their experiences in an operation manual. The aim of our research is to provide evidences supporting failure behaviors with a mock system to promote awareness in clinical practice. This paper presents results of a newly developed test method to evaluate the possibility of perforation while inserting the dilator to the cervical vein after the guidewire placement.
A tensile tester (AGI-250kN, Shimadzu Corp.) equipped with a load cell (SLBL-50N, Shimadzu Corp.) was utilized to measure the insertion force of a dilator to vein. The porcine vein was prepared to be aligned with 15mm and to be cut opened to expose the medial wall, and it was mounted on a custom-made device. A guidewire and a dilator were vertically suspended from the upper side of the tensile tester. During the dilator was approaching down to the vein through the guidewire at the constant velocity, the insertion force was measured and the tissue surface was observed simultaneously. The perforation force was examined in relation to the insertion angle from 15degrees to 60degrees.
While veins were pressed only by a guidewire, perforation was not identified at all degrees. After inserting a dilator, veins were torn at 45degrees and at 60degrees more than ION. It was suggested that vessel wall could be thinner and be torn by multiple insertion. It is concluded that the usage situation of a guidewire and a dilator was assessed objectively and the angle-load relationship was quantified. The test would be helpful to propose safe approach for patients.

Aim: High rates of stent fracture have been reported in the treatment of diseased superficial femoral artery (SFA). Understanding of in-vivo mechanical-loading environments, therefore, draws serious attention. We have developed a novel multi-loading durability tester which can apply cyclic twist and stretch on stents. Here, in-vitro stent fracture patterns were compared with stent fracture observed in vivo. Methods: The angle of cyclic twist as well as cyclic stretch exerted to the stents was regulated to physiologic conditions by utilizing referenced data of MR angiography of SFAs obtained in the spine and fetal position. Stiffness of the silicone vessel models were regulated to that of SFAs. As the SFAs are intrinsically stretched in vivo, stents were tested not only in the non-stretched vessel model but also in the 50% pre-stretched vessel model, respectively. The simultaneous cyclic multi-loads were exerted to the stents; under the mean luminal pressure of 100mmHg at 60 cycles per minute. Considering the data that average Japanese walk 7378 steps per day, the cyclic numbers of the in-vitro durability tests were converted to the equivalent durability in vivo. Results: Only minor fracture was observed at the stent strut after one-year-equivalent duration when the stents were tested using the non-stretched vessel models. However, employment of the novel pre-stretched vessel model resulted in complete stent fractures in the middle of longitudinal direction in 2-months-equivalent duration. Moreover, the fracture pattern was clearly coincident with the stent fracture in vivo. Conclusions: This is the first demonstration that the pre-stretch of vessel model is a requisite condition in durability tests of stents for SFA. Moreover, these results indicated that reproduction of multi-loading environments including cyclic twist and stretch is of great significance in order to obtain reliable durability data of endovascular stents for SFA.

We have studied noninvasive devices for measuring total hemoglobin and hemoglobin derivatives such as carboxyhemoglobin (COHb) and methemoglobin (MetHb). A calibration procedure needs to be developed to evaluate or calibrate these devices and pulse oximeters for clinical practice. However, people and animals are sometimes exposed to risk when they are used for calibration.
In this paper, we propose a new in vitro calibration system for a pulse photometer. This system has a novel double-layer pulsation flow-cell that incorporates both venous and arterial blood flow. Using the calibration system, we are able to measure the in vitro pulsatile optical density ratio (Phi vt). The measured Phi vt agrees well with the in vivo pulsatile optical density ratio (Phi vt). This system simulates an in vivo environment with high accuracy and enables safe calibration. Consequently, the calibration system is able to standardize the performance and accuracy of pulse photometry.

We have studied noninvasive devices for measuring total hemoglobin and hemoglobin derivatives such as carboxyhemoglobin (COHb) and methemoglobin (MetHb). A calibration procedure needs to be developed to evaluate or calibrate these devices and pulse oximeters for clinical practice. However, people and animals are sometimes exposed to risk when they are used for calibration.
In this paper, we propose a new in vitro calibration system for a pulse photometer. This system has a novel double-layer pulsation flow-cell that incorporates both venous and arterial blood flow. Using the calibration system, we are able to measure the in vitro pulsatile optical density ratio (Phi vt). The measured Phi vt agrees well with the in vivo pulsatile optical density ratio (Phi vt). This system simulates an in vivo environment with high accuracy and enables safe calibration. Consequently, the calibration system is able to standardize the performance and accuracy of pulse photometry.

Background-There is an essential demand for tissue engineered autologous small-diameter vascular graft, which can function in arterial high pressure and flow circulation. We investigated the potential to engineer a three-layered robust and elastic artery using a novel hemodynamically-equivalent pulsatile bioreactor.
Methods and Results-Endothelial cells (ECs), smooth muscle cells (SMCs), and fibroblasts were harvested from bovine aorta. A polyglycolic acid (PGA) sheet and a polycaprolactone sheet seeded with SMCs, and a PGA sheet seeded with fibroblast, were wrapped in turn on a 6-mm diameter silicone tube and incubated in culture medium for 30 days. The supporting tube was removed, and the lumen was seeded with ECs and incubated for another 2 days. The pulsatile bioreactor culture, under regulated gradual increase in flow and pressure from 0.2 (0.5/0) L/min and 20 (40/15) mm Hg to 0.6 (1.4/0.2) L/min and 100 (120/80) mm Hg, was performed for an additional 2 weeks (n=10). The engineered vessels acquired distinctly similar appearance and elasticity as native arteries. Scanning electron microscopic examination and Von Willebrand factor staining demonstrated the presence of ECs spread over the lumen. Elastica Van Gieson and Masson Tricrome Stain revealed ample production of elastin and collagen in the engineered grafts. Alpha-SMA and calponin staining showed the presence of SMCs. Tensile tests demonstrated that engineered vessels acquired equivalent ultimate strength and similar elastic characteristics as native arteries (Ultimate Strength of Native: 882 +/- 133 kPa, Engineered: 827 +/- 155 kPa, each n=8).
Conclusions-A robust and elastic small-diameter artery was engineered from three types of vascular cells using the physiological pulsatile bioreactor.

We have developed an extremely compact mock circulation system. This system can simulate artery blood circulation and generate a pulse wave with a very small amount of blood. We were also able to measure the in vitro pulsatile optical density ratio (phi vt) using this system with a flow cell [1]. Results showed a difference between phi vt and the in vivo pulsatile optical density ratio (phi vi) for the same oxygen saturations. To explain this difference, we proposed a new flow-cell model that includes venous flow and arterial flow. Because these systems can simulate the in vivo environment with very accurately, they can be applied to various pulse spectrophotometry studies. Moreover, the required blood volume is very small so the system can evaluate artificial blood or artificial red cells at very low cost. Thus, this system can reduce the time and cost of developing new pulse photometry techniques and other medical equipment.

A long-term durability of a ventricular assist device (VAD) is required due to a shortage of donor hearts for cardiac transplantation, but there is no analyzed pump data after long-term use. This study aimed to perform a comparative study between new VAD and VADs after long-term use. The hydrodynamic performance of the used Toyobo VADs (mean period of 5 months with the maximum of 12 months) was evaluated in a mock circulatory system, where a new VAD was used as a control. Although a remarkable difference was not observed in terms of mean flow rate, flow and pressure waveforms varied significantly. Then, the pressure-volume relationship of each pump was measured: It was found that the capacity of long-term VADs was reduced. Although a further study is required, these results suggested that a long-term use of VAD may cause a change in mechanical properties of polymer materials.

A long-term durability of a ventricular assist device (VAD) is required due to a shortage of donor hearts for cardiac transplantation, but there is no analyzed pump data after long-term use. This study aimed to perform a comparative study between new VAD and VADs after long-term use. The hydrodynamic performance of the used Toyobo VADs (mean period of 5 months with the maximum of 12 months) was evaluated in a mock circulatory system, where a new VAD was used as a control. Although a remarkable difference was not observed in terms of mean flow rate, flow and pressure waveforms varied significantly. Then, the pressure-volume relationship of each pump was measured: It was found that the capacity of long-term VADs was reduced. Although a further study is required, these results suggested that a long-term use of VAD may cause a change in mechanical properties of polymer materials.

A novel in vitro mock circulatory system, which enables to reproduce an inflow restriction, simulating blood volume pooling due to heart failure, was developed to evaluate a hydrodynamic performance of a pulsatile ventricular assist device (VAD) in practical conditions. The concept of this development was motivated by a difference of an inflow restriction between in vitro and in vivo environments. The major idea of this study is to reproduce an inflow restriction by using a centrifugal pump placed at an inflow side of a left ventricular model instead of a constant head reservoir in a conventional circuit. In the novel circuit, the maximum flow rate was obtained at lower systolic fraction as compared with a conventional circuit. This similar tendency by the novel one was observed in an acute animal experiment in sheep. This result suggests that a new mock circuit is effective to confirm a practical drive strategy of the VAD for various diseased conditions.

A pneumatic driven ventricular assist device (VAD) is not only designed for short-term usage of a "bridge to recovery" (BTR) in cardiac function recovery, but also developed to apply as a "bridge to transplantation" (BTT) for cardiac transplant. However, in the latter, the VAD must be exchanged before its expiries of guarantee. In this research, the authors have investigated the connector's strength between connector and cannula, and safety during the VAD exchange.

Total hemoglobin (tHb), carboxyhemoglobin (COHb), and methemoglobin (MetHb) are usually measured with a CO-oximeter. Noninvasive and continuous measurement of these blood components is expected to decrease the pain of a patient. Therefore, we developed an instrument to measure oxygen saturation (SpO(2)), tHb, COHb, and MetHb noninvasively. Multiwavelength LED (600, 625, 660, 760, 800, 940, and 1306 nm) and a combined detector (Si, InGaAs) were built into the instrument (Seven wavelengths transparent pulse spectrophotometer). We used the Waseda mock circulatory system, which can simulate blood circulation in tissues and generate a pulse wave mechanically, to estimate the instrument's performance. Furthermore we proposed new calculation formula including DC components of optical density (this method). Under conditions without any change of other components, the mean error standard deviation between this method and the CO-oximetry were SaO(2)=0.0 +/- 1.4%, tHb=0.0 +/- 0.0 g/dl, COHb = 0.0 +/- 2.0%, and MetHb=0.0 +/- 0.3%. When the concentration of other components was changed, this method showed mean errors and standard deviations of SaO(2)=0.2 +/- 1.6%, tHb=0.0 +/- 0.4 g/dl, COHb=0.5 +/- 4.1%, and MetHb = 0.0 +/- 03%.

Total hemoglobin (tHb), carboxyhemoglobin (COHb), and methemoglobin (MetHb) are usually measured with a CO-oximeter. Noninvasive and continuous measurement of these blood components is expected to decrease the pain of a patient. Therefore, we developed an instrument to measure oxygen saturation (SpO 2), tHb, COHb, and MetHb non-invasively. Multiwavelength LED (600, 625, 660, 760, 800, 940, and 1300 nm) and a combined detector (Si, InGaAs) were built into the instrument (Seven wavelengths transparent pulse spectrophotometer). We used the Waseda mock circulatory system, which can simulate blood circulation in tissues and generate a pulse wave mechanically, to estimate the instrument's performance. Furthermore we proposed new calculation formula including DC components of optical density (this method). Under conditions without any change of other components, the mean error ± standard deviation between this method and the CO-oximetry were SaO 2=0.0±1.4%, tHb=0.0±0.0 g/dl, COHb=0.0±2.0%, and MetHb=0.0±0.3%. When the concentration of other components was changed, this method showed mean errors and standard deviations of SaO 2=0.2±1.6%, tHb=0.0±0.4 g/dl, COHb=0.5±4.1%, and MetHb=0.0±0.3%. © 2006 IEEE.

Optical properties of living tissues have not been well established even today, and bioopticinstrumentations have to be based on empirical formulae. In order to examine optical properties of the tissue having pulsating blood perfusion, we investigated the relation between optical density (defined as O.D.) of whole blood and hematocrit by transmission spectrophotometry. We used Waseda mock circulatory system that simulates blood circulation in the tissue. It was found that with increasing light path length, O.D. per unit light path length due to scattering and absorption effect, tended to become constant in each hematocrit. For wavelengths of 660, 805 and 940 nm, the relations between O.D. of whole blood and hematocrit predicted by Twersky&#039;s equation, Loewinger&#039;s equation and photon diffusion equation fitted to the data obtained. Meanwhile, for 1300 nm, the relation predicted by Loewinger&#039;s equation gave the best fit to the data. © 2005 IEEE.

Stentless valvular bioprostheses have been used clinically for over 8 years and the excellent properties of the bioprostheses have been demonstrated in clinical studies. The present study examined how differing elastic conditions around the bioprosthesis at the aortic position affect the hydrodynamic characteristics of the bioprosthesis. Bioprosthesis implantation is typically performed using either the subcoronary or the full-root technique. These procedures for implanting a stentless prosthetic heart valve at the aortic root were hydrodynamically evaluated in a mock circulatory system. Forward flow rate was 11% greater with the subcoronary technique than with the full-root technique. In a high-speed video camera study, the orifice area at full opening was 12% larger for the subcoronary technique than for the full-root technique. Evaluation of bioprosthetic characteristics in terms of mechanical conditions is important when considering surgical options.

The undulation pump total artificial heart (UPTAH) is a unique, implantable, total artificial heart (TAH) that uses undulation pumps. To achieve long-term survival in animals with physiologic hemodynamic conditions, a control method based on conductance and arterial pressure was applied to UPTAH. With this control method, called 1/R control, survival periods of 50 days (No. 0016, 49.6 kg) and 54 days (No. 0030, 42.5 kg) were obtained in adult female goats. In No. 0016, 1/R control was applied to the left pump, whereas in No. 0030, it was applied to the right pump. Another pump was used for left-right balance control. The control stability was better in No. 0030 than in No. 0016. The sucking effect of the left atrium was remarkable in No. 0016, possibly because of a time delay when left-right balance control was performed with the right pump. In No. 0016, the cause of death was probably a thrombus flown from a panus in the left atrium. It is possible that the left atrial suction effect influenced the thrombus and panus formation in the left atrium. In No. 0030, the cause of death was a small rupture of the membrane in the right pump. The rupture may have been caused by excessive negative pressure inside the pump. This pressure resulted from suction of the right atrium because of an unexpected control excursion, which was probably caused by a software bug. It will be necessary to redesign the undulation pump and improve the software to achieve longer survival periods for animals with physiologic hemodynamic conditions.

The final goal of this study is to realize a low-cost pulsatile blood pump especially for patients with acute heart failure or postoperative low cardiac output syndrome. In support of the pump, two types of polymer bileaflet valves with different configuration of the valve seats were developed. Influence of the leaflet thickness on the hydrodynamics of the prototype was preliminarily investigated among 70 mum, 100 mum, and 150 mum. As to the valves with the thinner leaflets, buckling of the leaflets was observed, which induced a large amount of regurgitation at valve closure. However, by thickening the leaflet to 150 mum, the mean flow of the prototype and the second model could be successfully comparable to the Medtronic-Hall valve. Moreover, accelerated fatigue tests showed that reinforcement of the valve seat with the additional spokes in the second model extended the durability by four times as compared with the prototype, equivalent to an in vivo duration of over one month.

The undulation pump total artificial heart (UPTAH) is a small implantable total artificial heart. As the UPTAH generates outflow and inflow at the same time, control of the UPTAH is very difficult. Therefore suitable control methods specifically for the UPTAH should be established. Various motor control, left-right flow balance control, and physiological control methods were examined and tried for the UPTAH control in this study. The control system is divided into seven categories. It has a hierarchical structure and all control modes work at the same time. The UPTAH with the newly developed control method has been implanted into the chest cavities of 48 goats. Until now, six goats survived for more than one month, including 63 days in the longest case. The good condition of the UPTAH implanted animal could be maintained with the newly developed control scheme, consisting of the 1/R control and several other additional controls.

The undulation pump is a small, continuous flow displacement type blood pump, and the undulation pump total artificial heart (UPTAH) is a unique, implantable total artificial heart based on this pump. To improve the durability of the UPTAH for investigating long-term pathophysiology with UPTAH, a third model (UPTAH3) has been developed. UPTAH3 was designed to separate the left and right undulation shafts and to be more durable. The undulation pumps were also redesigned. UPTAH3 was implemented with a diameter of 76 mm, width of 78 or 79 mm, total volume of 292 ml, and weight of 620 g. The priming volumes of the left and right pumps are 26 and 21 ml, respectively. The atrial cuffs and outflow cannulae were also redesigned for UPTAH3. The maximum output against an arterial pressure load of 100 mm Hg is about 11 L/min. The maximum pump efficiency is about 15% in the left pump and 18% in the right pump, giving a maximum total efficiency for both of about 11%. To date, UPTAH3 has been tested in 17 goats, and the longest survival period was 46 days. This third model will be useful for investigating pathophysiology with UPTAH.

The final goal of this study is to realize a low-cost pulsatile blood pump especially for patients with acute heart failure or postoperative low cardiac output syndrome. In support of the pump, two types of polymer bileaflet valves with different configuration of the valve seats were developed. Influence of the leaflet thickness on the hydrodynamics of the prototype was preliminarily investigated among 70 mum, 100 mum, and 150 mum. As to the valves with the thinner leaflets, buckling of the leaflets was observed, which induced a large amount of regurgitation at valve closure. However, by thickening the leaflet to 150 mum, the mean flow of the prototype and the second model could be successfully comparable to the Medtronic-Hall valve. Moreover, accelerated fatigue tests showed that reinforcement of the valve seat with the additional spokes in the second model extended the durability by four times as compared with the prototype, equivalent to an in vivo duration of over one month.

The Jellyfish Valve is one of the most promising polymer valves for artificial hearts. The present problems to be solved are 1) how to prevent a membrane fracture and 2) how to eliminate a calcification, because both of these problems were observed in experiments with goats after 312 days and 414 days of pumping. Finite element analysis demonstrated that mechanical tensile strain induced in the membrane at valve closure was clearly consistent with the fracture location as well as calcification area in in vivo experiments. Based on this finding, a new valve seat with an additional concentric ring 14 mm in diameter and 0.5 mm in width was finally developed. The maximum strain was dramatically reduced to 52% by the design improvement. Moreover, accelerated fatigue tests demonstrated that the improved valve was 10 times more durable as compared with the original valve, which was equivalent to an in vivo duration of 8.3 years. In animal experiments, including 31days and 46 days use in a total artificial heart (TAH), no thrombus was found despite the lack of anticoagulant or antiplatelet therapies. These results indicate that the improved Jellyfish Valve might be one of the most durable polymer valves, able to perform in artificial hearts for a long period of time.

The goal of this research is to establish a reliable methodology for accelerated fatigue tests of prosthetic heart valves. A polymer valve was the subject, and the influence of various drive parameters on durability was investigated in three different machines. Valve lifetime was notably shortened by increasing the cyclic rate or stroke even though the maximum pressure difference at valve closure was maintained at 120 mm Hg. These results demonstrate that adjustment of the maximum transvalvular pressure is not sufficient to ensure tests are conducted under the same conditions and indicate that measurement of the dynamic load would be more efficacious. Moreover, the locations of tears sustained in the accelerated tests differed from those encountered in an animal experiment although in both cases the locations were entirely consistent with the areas of strain concentration revealed by finite element analysis. These findings should be discussed during a revision of ISO 5840.

An undulation pump total artificial heart (UPTAH) in which the revolutions of the motor are converted to undulation motion of a disk has been developed. In an experiment, a goat using the UPTAH survived for 54 days. However, a large ripple was observed in the device's output pressure and flow waveform. In calculating the spectrum of the ripple, we found that the ripple mainly comprised 2 frequency sine waves: 1 having the same frequency as and 1 having double the frequency of the motor revolutions. To reduce the ripple, 2 sine waves, 1 having the same frequency as and 1 having double the frequency of the motor revolutions. were provided to the motor current to modulate the pulse width of the pulse width modulation controlling the: motor revolutions. This ripple control method reduced the pressure ripple by 90% in a mock circulation and by 70% in animal experiments. These results revealed that the ripple generated in the UPTAH could be controlled through the use of motor control software.

Development of an inexpensive artificial organs is one of the most important issues. The final goal of this research is to realize such a low-cost pulsatile blood pump, especially for use in acute congestive heart failure or postoperative low cardiac output syndrome. In this study, design of the pneumatically-driven Spiral Vortex (SV) pump, which was originally developed in Australia, Was adopted. The specific feature is low hemolysis, because a continuous spiral flow is generated inside the pump without any stagnation. First, for the purpose of establishing a mass production system, vacuum forming technique was employed for fabrication of the pump. Each quality-controlled pump could be manufactured in one hour including assembling process, corresponding 1/15 times as compared with that by conventional injection-molding and/or solution casting technique. Second, in order to achieve blood compatibility, a novel phospholipid polymer composed of 2 methacryloxyethyl phosphorylcoline (MPC) was coated on the whole internal surface of the pump. A preliminary comparative in vitro test exhibited a superior blood compatibility of the MPC-coated pump, as compared with the non-coated one. At this stage, the final design is under investigation by the use of computational fluid dynamics. Third, the polymer Jellyfish valve has been developed to realize a low-cost pulsatile blood pump. Comparison between finite element analysis and animal experimental results of the original Jellyfish Valve indicated that reduction of strain concentration in the leaflet would be of great benefit in a prevention of fracture and calcification, observed after 10 months in an animal experiment. Based on the findings, a new valve seat was designed aiming to effectively reduce the strain concentration. The modified valve was hydrodynamically comparable with the Medtronic-Hall valves, while durability of the modified one was dramatically extended over 10 times as compared with the original, that was equivalent to an in vivo duration of 8.3 years. Moreover, an excellent anti-thrombogenicity as well as anti-calcification was achieved throughout a 240 day animal experiment. The data above are encouraging to continue development of a clinical quality inexpensive SV ventricular assist system.

In a previous communication, we reported a leaflet fracture in a Jellyfish valve that was incorporated into a blood pump, after a 312-day animal implant duration. Subsequent finite element analysis revealed that the fracture location was consistent with an area of maximum strain concentration. Therefore, the aim of this study was to improve the durability in the light of these findings. Based on the engineering analysis results, a new valve seat having a concentric ring, of 0.5-mm width, located at a radius of 7.0 mm, was designed and fabricated. Accelerated fatigue tests, conducted under the conditions recommended by ISO 5840, demonstrated that the durability of this new prototype was extended by a factor of 10, as compared to the original valve. Moreover, further finite element analysis indicated that the maximum equivalent elastic strain of the proposed new valve was reduced by 52.3% as compared to the original valve. Accordingly, it has been confirmed that the modified Jellyfish valve is suitable for use in long-term artificial hearts.

Calcification on a blood-contacting polymer surface in an artificial heart is one of the most serious problems. Recently, we maintained a goat with a total artificial heart (AH) for 532 days without systemic anticoagulation. Sac-type blood pumps coated with segmented polyurethane and incorporating jellyfish valves, thin polymer membrane valves, were used in the experiment. The pump was exchanged for a new one on the 312th day on the left side and the 414th day on the right side. They were analyzed with a scanning electron microscope (SEM) and an X-ray microanalyzer. The valve membrane after 312 days of pumping revealed plastic deformation expanding toward upstream between the spokes by creep fatigue with blood pressure difference when the valve closed. Calcification on the membrane was concentrated in the limited portions that received a strong stretching force: the upstream side of the membrane between the spokes and downstream side of the membrane on the spokes. Slight or no calcification was observed on the opposite side of the membrane that received a compression force, and no calcification was found on nonmoving parts such as the center of the membrane and spokes. A new hypothesis on the mechanism of calcification at the portion that received repeated stretching force was raised. The repeated stretching force would extend the polymer membrane, causing some loosening between polymer molecules and generating microgaps. The blood protein and phospholipid would invade into these microgaps, which would then attract Ca ions followed by phosphate ions to make their complexation. The hypothesis could well explain the calcification phenomena on a blood-contacting polymer surface, and gave a good clue on how to protect from calcification.

The undulation pump is a small continuous flow displacement-type blood pump. The undulation pump total artificial heart (UPTAH) is a unique implantable total artificial heart using undulation pumps. An adult female goat weighing 45.8 kg was used for implantation. The natural heart was replaced with the UPTAH under extracorporal circulation. The cardiac output (CO) was maintained to 100 ml/kg/min by controlling the right pump manually. To prevent lung edema, the left pump was controlled automatically to maintain the left atrial pressure below 20 mm Hg. The CO was maintained for 2 weeks. Thereafter, the CO gradually decreased. The goat suddenly died because of a brain stroke on the 31st postoperative day. At autopsy, the cavity of the left atrial cuff was almost occupied by the big pannus-like thrombus, which was thought to be the cause of death. Improvement of the atrial cuff is necessary to obtain longer survival and is being modified. No thrombus was found inside the pumps. However, temperature rise in a left motor was a problem. Improvement of the efficiency in a motor is necessary. Although many problems still remained, 1 month survival could be obtained with this unique implantable TAH using continuous flow displacement-type blood pumps.

Calcification on a blood-contacting polymer surface in an artificial heart is one of the most serious problems. Recently, we maintained a goat with a total artificial heart (AH) for 532 days without systemic anticoagulation. Sac-type blood pumps coated with segmented polyurethane and incorporating jellyfish valves, thin polymer membrane valves, were used in the experiment. The pump was exchanged for a new one on the 312th day on the left side and the 414th day on the right side. They were analyzed with a scanning electron microscope (SEM) and an X-ray microanalyzer. The valve membrane after 312 days of pumping revealed plastic deformation expanding toward upstream between the spokes by creep fatigue with blood pressure difference when the valve closed. Calcification on the membrane was concentrated in the limited portions that received a strong stretching force: the upstream side of the membrane between the spokes and downstream side of the membrane on the spokes. Slight or no calcification was observed on the opposite side of the membrane that received a compression force, and no calcification was found on nonmoving parts such as the center of the membrane and spokes. A new hypothesis on the mechanism of calcification at the portion that received repeated stretching force was raised. The repeated stretching force would extend the polymer membrane, causing some loosening between polymer molecules and generating microgaps. The blood protein and phospholipid would invade into these microgaps, which would then attract Ca ions followed by phosphate ions to make their complexation. The hypothesis could well explain the calcification phenomena on a blood-contacting polymer surface, and gave a good clue on how to protect from calcification.

The purpose of this study was to explore a valve selection criterion based on the impact force generated at valve closure, and to test a statistical mathematical model for comparing valve performance. The impact force generated at valve closure in the mitral position was measured continuously, using a load cell mounted in the left atrial section of a mock circulatory system. Eight clinical valves were tested. The data obtained from the in vitro test were subjected to multiregression analysis, to enable systematic comparison of the impact forces of these valves. Furthermore, class I quantification theory was applied to construct the statistical mathematical model. As a result, the following interaction effect was observed in the statistical model. (1) The impact force generated at valve closure had a lower value in valves of smaller diameter. (2) The ranking of 29-mm-diameter valves by impact force was different for the flow region. Under the physiological flow condition of 4-61/min, high impact forces were generated in all valves, in the order Björk-Shiley monostrut, ATS, St. Jude medical, CarboMedics. We consider that low impact force at valve closure is desirable, upon consideration of the influence on the annulus tissue at valve replacement. From these findings, the results of the multiregression analysis provide indications for choosing the optimal valve for patients with severe mitral insufficiency (MI).

Research of the distributed artificial heart is important not only to acquire the means of individual organ perfusion but also to clarify the characteristics of the organ and the mechanism of blood distribution. To investigate the distributed artificial heart, the miniature undulation pump was developed. The outer diameter and the thickness of the developed pump were 38 mm and 11 mm. respectively. The priming volume of the pump was 3.2 ml. The total size including the motor unit was 38 mm in diameter and 32 mm in length. The total weight was 67.5 g. The total volume was 27.5 ml. The pump was driven with pulse width modulation by using a 1 chip motor controller. More than 5 L/min of continuous output could be obtained. The results showed that the developed miniature undulation pump system had enough performance for individual organ perfusion.

Research of the distributed artificial heart is important not only to acquire the means of individual organ perfusion but also to clarify the characteristics of the organ and the mechanism of blood distribution. To investigate the distributed artificial heart, the miniature undulation pump was developed. The outer diameter and the thickness of the developed pump were 38 mm and 11 mm. respectively. The priming volume of the pump was 3.2 ml. The total size including the motor unit was 38 mm in diameter and 32 mm in length. The total weight was 67.5 g. The total volume was 27.5 ml. The pump was driven with pulse width modulation by using a 1 chip motor controller. More than 5 L/min of continuous output could be obtained. The results showed that the developed miniature undulation pump system had enough performance for individual organ perfusion.

高分子製人工弁の加速耐久試験方法に関してはISOでも規格が確立されていない。そこで, Jellyfish弁を使用し, 通常行われている圧力及び温度を基準とした加速耐久試験が高分子製人工弁に適用可能かを検討した。その結果, 1200BPMで行った加速耐久試験と105BPM程度で行った慢性動物実験では, 弁破断部位及び弁が破断に至るまでの開閉回数のいずれも一致しなかった。この弁破断位置の違いの原因を究明するために, 有限要素法を用いて力学的な解析を行った。その結果, 加速耐久試験では応力集中する部位で脆性破壊しているのに対し, 慢性動物実験では, 閉鎖時の変形によってひずみの集中する部位で延性破壊していることがわかった。したがって, 両者の破壊メカニズムは根本的に違うものであることがわかり, 現行のISOで定められた加速試験では, 高分子製弁の耐久性予測に限界があることが示唆された。

高分子製人工弁の加速耐久試験法はISOでもまだ確立されていない.そこでまず, Jellyfish弁の慢性動物実験で確認された弁葉破断部位を加速試験で再現できるような試験方法を検討することで, 信頼性のある加速耐久試験方法の確立を目指した.力学的な背景から, 弁閉鎖時の最大荷重および水温に着目して実験を行った.弁閉鎖時の最大荷重が標準的な拍動時の1/2の条件では, 作動流体の温度を40°Cから60°Cに上げても慢性動物実験で確認された弁葉破断部位を再現できなかった.しかし, 弁閉鎖時の最大荷重が標準的な拍動時の1/4の条件では, 水温を60°Cと高温に設定することではじめて慢性動物実験で確認された弁葉破断部位を再現することに成功した.したがって, 高分子製人工弁の加速耐久試験では, 弁閉鎖時の最大荷重および水温は最重要設定項目であることが判明し, さらに, 弁閉鎖時の最大荷重を下げ, 水温を上げることが重要であることがわかった.

多種の臨床用冠動脈ステントに対して同一条件下でのin-vitro試験を行い, そこで得られた力学的特性データをもとに, 冠動脈ステントの性能評価方法の確立を目指した。まず, 生体冠動脈と同等のヤング率を有する内径3mmのシリコンチューブを用い, ステント拡張直後のバルーン収縮に伴う径の変化率 (elastic recoil) および, チューブ外側の加圧に伴う径の変化率 (radial strength) を測定した。その結果, recoilは, 最大で6%程度の変化に留まり, radial strengthは0-200rnmHgの範囲では直線的に減少したが, 最大でも5%程度の低下であった。次に, 生理的な冠動脈圧, 流量が再現できる人工冠循環モデルを製作し, 拍動下におけるステントの外径変化を測定した。その結果, 径の変化率は最大1.5%で冠動脈流量と同期するように変化することが分かった。

多種の臨床用冠動脈ステントに対して同一条件下でのin-vitro試験を行い, そこで得られた力学的特性データをもとに, 冠動脈ステントの性能評価方法の確立を目指した。まず, 生体冠動脈と同等のヤング率を有する内径3mmのシリコンチューブを用い, ステント拡張直後のバルーン収縮に伴う径の変化率 (elastic recoil) および, チューブ外側の加圧に伴う径の変化率 (radial strength) を測定した。その結果, recoilは, 最大で6%程度の変化に留まり, radial strengthは0-200rnmHgの範囲では直線的に減少したが, 最大でも5%程度の低下であった。次に, 生理的な冠動脈圧, 流量が再現できる人工冠循環モデルを製作し, 拍動下におけるステントの外径変化を測定した。その結果, 径の変化率は最大1.5%で冠動脈流量と同期するように変化することが分かった。

筆者らは旋回渦流型血液ポンプの血栓形成や溶血に対する性能に優位性を示してきている。このポンプでは流出側の流れも旋回しているため同部位での弁選択は従来の単なる水力学的特性に加えて新たな規準が必要と考えられる。本研究ではまず基礎的検討として4種の人工弁を同ポンプの流出側に設置してin vitroで各弁の圧力損失を比較した。その結果, 弁葉の回転が可能なJyros弁の優位性が示唆された。さらに高速ビデオカメラによる解析の結果, 弁葉の回転は弁閉鎖開始の直前から生じ, 弁葉が回転しないように固定した場合に比べて圧力較差が有意に低下することが認められた。このように同弁における弁葉回転と圧力損失の関係を明示することができた。

多種の臨床用冠動脈ステントに対して同一条件下でのin-vitro試験を行い, そこで得られた力学的特性データをもとに, 冠動脈ステントの性能評価方法の確立を目指した。まず, 生体冠動脈と同等のヤング率を有する内径3mmのシリコンチューブを用い, ステント拡張直後のバルーン収縮に伴う径の変化率 (elastic recoil) および, チューブ外側の加圧に伴う径の変化率 (radial strength) を測定した。その結果, recoilは, 最大で6%程度の変化に留まり, radial strengthは0-200rnmHgの範囲では直線的に減少したが, 最大でも5%程度の低下であった。次に, 生理的な冠動脈圧, 流量が再現できる人工冠循環モデルを製作し, 拍動下におけるステントの外径変化を測定した。その結果, 径の変化率は最大1.5%で冠動脈流量と同期するように変化することが分かった。

In the University of Tokyo, various types of total artificial heart (TAH) have been studied. Based on the experiences of TAH research, the development of the undulation pump total artificial heart (UPTAH) started in 1994. The undulation pump is a small-size, continuous-flow, displacement-type blood pump, and the UPTAH is a unique implantable total artificial heart that uses the undulation pump. To date, three models of UPTAH have been developed. The first model, UPTAH1, was developed to investigate the possibility of reducing the size of the device so it could be implanted in small adults, such as Japanese patients, in 1994. The second model, UPTAH2, which was the prototype of the animal experimental model, was developed in 1996 to investigate the possibility of survival with the UPTAH. The third model, UPTAH3, which is the present model, was developed in 1998 to enable long-term survival in animal experiments and to investigate the pathophysiology of the UPTAH. From July 1996 to October 1999, 22 implantations of UPTAH2 or UPTAH3 were performed in goats. In spite of the limitation of their small chest cavity, the UPTAH could be implanted into the chest of all goats. Using UPTAH3, survival of 31 days could be obtained. The research and development of UPTAH are ongoing.

Jellyfish弁の耐久性を低下させる要因と考えられる弁葉へのカルシウム沈着の発生メカニズムを検討するため, 力学的特性に着目して弁閉鎖時の弁葉に生じるひずみを有限要素法を用いて解析した. 弁葉材料の物性値は単軸引張試験から取得し, 弁閉鎖荷重は動物実験から得た弁閉鎖時の平均大動脈圧を用いた. 4節点膜要素を使用し, 解析は幾何的対称性を考慮して全体の1/12のモデルについて行った. その結果, ひずみは主に2ヶ所で集中することが確認された. そこで, さらにこの2ヶ所の厚さ方向のひずみ分布を調べるために8節点六面体要素を使用して簡易化したモデルで弾性解析を行った. これらの結果, 解析で判明した高引張ひずみ域と動物実験結果で観察されたカルシウム沈着位置は見事に対応していた.<br>以上より, 変形によって生じる引張ひずみがカルシウム沈着現象の発生に大きな影響を与えるということが, 数値解析および動物実験の両面から明確にされた.