TOWARD COMMERCIALIZATION OF TOTALLY IMPLANTABLE, ULTRACOMPACT TOTAL ARTIFICIAL HEART AND VENTRICULAR ASSIST SYSTEMS

迈向完全植入式、超紧凑型全人工心脏和心室辅助系统的商业化

• 批准号: 11558102
• 负责人: TAKATANI Setsuo
• 金额: $ 8.51万
• 依托单位: TOKYO MEDICAL AND DENTAL UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 1999
• 资助国家: 日本
• 起止时间: 1999 至 2000
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-11558102/
• 关键词: Electromechanical TAH; Electromechanical VAD; Heart Transplantation; Continuous Flow Pumps; Centrifugal Blood Pump; Biocompatibility; Durability; Compliance Chamber; Ti-6Al-7Nbチタン合金; 解剖学的適合性; 流れの可視化; モータ駆動全置換型人工心臓; モータ駆動補助人工心臓; 循環制御; エネルギー変換

In this project, ultracompact, totally implantable total artificial heart (TAH) and ventricular assist system, pulsatile and nonpulsatile, have been developed and their performances were evaluated in vitro and in vivo using calves. The TAH is a one-piece design sandwiching a compact electromechanical actuator between the left and right pusher-plate type blood pumps. The stroke length and stroke volume of the blood pump are 12mm and 55cc. The VAD was designed using the same components as those of TAH by covering the TAH's right side with a back-plate. The dimensions of the TAH are 90mm diameter, 70mm thickness, 400cc volume and 450g weight, while those of the VAD are 90mm, 56mm, 275cc and 460g. The VAD and TAH are much smaller than the currently clinically available systems. (As for performance of the devices, both TAH and VAD generated the maximum flow of 8L/min. The power requirement for VAD ranged from 5 to 8 watts to generate the flow of 4 to 8 L/min against the pump afterload 100mm … More Hg. On the other hand, the TAH required approximately 10 to 15 watts to generate the flowof 4 to 8 L/min against the left and right afterload of 100 and 25mmHg, respectively. The maximum electrical to hydraulic conversion efficiency was 23% for VAD, while for TAH 13.5%. As the associated components for totally implantable system, compliance chamber and rechargeable batteries were also designed and assembled. The displaced volume of the compliance chamber for VAD is 75cc, while for TAH 55cc. The flexing diaphragm of the compliance chamber was made of polyurethane through dip-coating technique.The anatomical fitting and survival studies with VAD and TAH were performed in one calf for VAD and a total of 6 calves for TAH. As for VAD, the blood was drained from the left ventricular apex and returned to the descending aorta through the VAD. The compliance chamber was implanted in the thoracic cavity and drive line was tunneled underneath the skin to outside the body and connected to the driver. Because of the ventricular fibrillation developed during the surgery, the animal could survive only 24 hours. However, entire implantation procedure has been worked out successfully. Concerning TAH, in the first two calves anatomical fitting study was carried out, followed with TAH implantation in the remaining 4 calves. The heart-lung bypass was performed to excise the native heart, followed with implantation of the TAH. In the last calf # 0107, all the procedure successfully worked out to obtain 30 hour survival with the TAH. The animal was extubated and stood up on his own. The animal was sacrificed 30 hour postoperatively due to reduced left pump flow. Left-right flow balance procedure needs to be improved to better control left and right atrial pressure together with left pump flow. We will continue with in vivo evaluation of the TAH, focusing on durability and biocompatibility aspects, to develop clinically usable totally implantable TAH system.In addition to pulsatile systems, we also designed and evaluated a single pivot bearing supported centrifugal blood pump. Pump performance, hemolysis test as well as two month durability studies were carried out to evaluate its feasibility as a left ventricular assist device. We will move onto animal study in the next phase.In order to monitor the patients implanted with artificial heart systems, a reflectance type optical sensor was developed to monitor hemoglobin content and oxygen saturation of the blood inside the artificial heart. Although excellent results have been shown in vitro, animal evaluation must be conducted to evaluate its long term performance in vivo. Less

本课题研制了超紧凑型、全植入式全人工心脏(TAH)和脉动型和非脉动型人工心脏辅助系统，并对其性能进行了体内外评价。TAH是一种一体式设计，在左侧和右侧推板式血泵之间夹有一个紧凑型机电执行器。血泵的行程长度和行程容量分别为12 mm和55cc。VAD的设计使用了与TAH相同的组件，即用背板覆盖TAH的右侧。TAH的直径为90 mm，厚度为70 mm，体积为400cc，重量为450g，而VAD的尺寸为90 mm，56 mm，275cc和460g。VAD和TAH比目前临床上可用的系统小得多。(至于器件的性能，TAH和VAD都产生了8L/分钟的最大流量。VAD的功率要求为5至8瓦，以产生4至8 L/分钟的流量，而泵的后负载为100 mm…更多的汞。另一方面，TAH需要大约10到15瓦才能产生4到8 L/分钟的流量，而左、右后负荷分别为100和25毫米汞柱。最大电-液转换效率，VAD为23%，TAH为13.5%。作为全植入系统的附属部件，还设计并组装了顺应室和充电电池。VAD的顺应室的位移体积为75cc，而TAH的顺应室的位移体积为55cc。柔顺室的屈曲隔膜采用浸渍涂层技术，用VAD和TAH分别在1头小牛和6头TAH小牛上进行解剖匹配和成活研究。对于VAD，血液从左室心尖部引流，通过VAD返回降主动脉。顺应室被植入胸腔，驱动线在皮肤下隧道通向体外，并连接到司机。由于在手术过程中出现了室颤，这只动物只能存活24小时。然而，整个植入过程已经成功制定。对于TAH，前两个小腿进行了解剖匹配研究，其余4个小腿进行了TAH植入。心肺转流手术切除自体心脏，然后植入TAH。在最后一头小牛#0107中，所有的程序都成功地完成了与TAH的30小时存活。这只动物拔掉了气管，自己站了起来。术后30小时因左心泵流量减少而处死动物。需要改进左右流量平衡程序，以便更好地控制左、右房压力和左泵流量。我们将继续对TAH进行体内评估，重点放在耐用性和生物相容性方面，以开发临床可用的全植入型TAH系统。除了脉动系统外，我们还设计并评估了单枢轴轴承支撑的离心式血泵。通过泵性能、溶血试验和两个月的耐久性研究，评估其作为左心室辅助装置的可行性。下一阶段我们将进行动物实验。为了监测植入人工心脏系统的患者，研制了一种反射式光学传感器来监测人工心脏内血液的血红蛋白含量和氧饱和度。虽然在体外已经显示了良好的结果，但必须进行动物评估才能评估其在体内的长期表现。较少

项目成果

Ohuchi K, Nakamura M, Sakamoto T, Takatani S. et al: "Automatics control of implantable centrifugal blood pump based on the analysis of motor current waveform"Journal of Congestive Heart Failure and Circulatory Support. 1(4). 431-435 (2001)

Ohuchi K、Nakamura M、Sakamoto T、Takatani S.等人：“基于电机电流波形分析的植入式离心血泵的自动控制”充血性心力衰竭和循环支持杂志。

Yuhki A, Takatani S, et al.: "Detection of the suction and regurgitation of the implantable centrifugal pump besed on the motor current waveform analysis and its application to optimization of pump flow"Artificial Organs. 23・6. 532-537 (1999)

Yuhki A、Takatani S 等人：“基于电机电流波形分析的植入式离心泵的吸入和反流检测及其在泵流量优化中的应用”Artificial Organs 23・6。 ）

Takatani S,Sakamoto T: "Mechanical circulatory support devices for bridge to heart transplantation, bridge to recovery or destination therapy."J Artificial Organs. 3. 75-84 (2000)

Takatani S，Sakamoto T：“用于心脏移植、恢复或目的地治疗桥梁的机械循环支持装置。”J Artificial Organs。

Ohuchi K, Yuhki A, Nakamura N, Sakamoto T, Takatani S: "Development of a compact, seal-less, trj-pod supported centrifugal blood pump"Journal of Congestive Heart Failure and Circulatory Support. 1(4). 413-417 (2001)

Ohuchi K、Yuhki A、Nakamura N、Sakamoto T、Takatani S：“开发紧凑型、无密封、trj-pod 支持的离心血泵”充血性心力衰竭和循环支持杂志。

Takatani S, Nakamura M, Ohuchi K, Nogawa M, Sakamoto T: "Ultracompact, Completely Implantable Electro-mechanical permanent TAH"Journal of Congestive Heart Failure and Circulatory Support. 1(4). 161-166 (2001)

Takatani S、Nakamura M、Ohuchi K、Nokawa M、Sakamoto T：“超紧凑、完全植入式机电永久 TAH”充血性心力衰竭和循环支持杂志。