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

本项目研制了超紧凑、全植入式全人工心脏（TAH）和心室辅助系统，包括脉动型和非脉动型，并在犊牛体内和体外对其性能进行了评价。TAH是一种一体式设计，将紧凑的机电致动器夹在左右推板式血泵之间。血泵行程长度为12mm，行程容积为55cc。VAD的设计使用了与TAH相同的组件，用背板覆盖了TAH的右侧。TAH的尺寸为直径90mm，厚度70mm，体积400cc，重量450g， VAD的尺寸为90mm， 56mm, 275cc, 460g。VAD和TAH比目前临床可用的系统要小得多。(在设备性能方面，TAH和VAD的最大流量均为8L/min。VAD的功率要求在5到8瓦之间，当泵的后负荷为100mmhg时产生4到8l /min的流量。另一方面，TAH需要大约10到15瓦，当泵的左右后负荷分别为100mmhg和25mmHg时产生4到8l /min的流量。VAD的最大电液转换效率为23%，TAH为13.5%。作为全植入式系统的配套部件，合规室和充电电池也进行了设计和组装。VAD顺应腔的容积为75cc， TAH顺应腔的容积为55cc。柔度室的柔性膜片采用浸涂工艺制备。VAD和TAH的解剖拟合和生存研究分别在1只小牛的VAD和6只小牛的TAH中进行。对于VAD，血液从左心室尖部流出，通过VAD回流到降主动脉。顺应腔植入胸腔，驱动线在皮肤下穿隧至体外并与驱动器连接。由于手术过程中出现心室颤动，这只动物只能存活24小时。然而，整个植入过程已经成功完成。对于TAH，在前2例小腿进行了解剖拟合研究，随后在其余4例小腿进行了TAH植入。行心肺旁路手术切除原心，然后植入TAH。在最后一头小牛# 0107中，所有的手术都成功地在TAH下存活了30个小时。这只动物拔了气管，自己站了起来。由于左泵血流减少，术后30小时处死动物。需要改进左右血流平衡程序，以更好地控制左右心房压和左泵流量。我们将继续对TAH进行体内评估，重点关注耐久性和生物相容性方面，以开发临床可用的完全植入式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血泵。泵的性能、溶血试验以及两个月的耐久性研究来评估其作为左心室辅助装置的可行性。我们将在下一阶段进行动物实验。为了对植入人工心脏的患者进行监测，研制了一种反射式光学传感器，用于监测人工心脏内的血红蛋白含量和血氧饱和度。尽管体外实验已显示出良好的结果，但必须进行动物试验来评估其在体内的长期性能。少

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