Study on the establishment of a therapeutic system for severe cardiac failure by means of artificial heart as a bridge to heart transplantation

1. 本研究所与爱新精机公司共同研制了由电液直线执行器和隔膜式血泵组成的左心室辅助装置，并对该装置的控制系统进行了设计和试验。根据血泵内的压力容积曲线计算Ea/Ees。在该控制系统中，通过对VAD的冲程体积、速率、上占率、下占率和收缩率进行多元回归分析，使Ea/Ees尽可能接近1。为了推测包括VAD在内的人工循环中凝血和纤溶对植入供心和受体的影响，我们检测了体外循环（CPB）期间和之后凝血和纤溶的变化：血小板、β - tg、ATIII、FPA、PLG、d -二聚体、alpha_2PI等。CPB过程中凝血和纤溶均被激活。而甲磺酸那莫司他（NM）则能抑制这些活性。我们认为，在心室辅助期间，多给药可预防血栓栓塞和出血发作。为了研究细胞介导的免疫反应是否会被CPB或心室辅助作用抑制或激活，我们研究了人工循环过程中外周血淋巴细胞亚群和抗体依赖的细胞介导的细胞毒性。总淋巴细胞（okt3和okt11 +）数量无明显变化。抑制/细胞毒性T细胞（OKT8+）和NK细胞（Leu 7+和Leu 11+）数量显著增加。辅助/诱导T细胞（okt4 +）和B细胞（Leu 12+）数量减少。混合淋巴细胞反应和NK细胞毒性也被激活。由此可见，体外循环心脏直视手术与细胞毒性细胞介导免疫的激活有关。在接受VAD作为桥梁的心脏移植受者中，血液凝固、纤维蛋白溶解和细胞毒性细胞介导的免疫会被激活，因此血栓栓塞发作和急性排斥反应的发生率可能比单纯心脏移植增加。少

1. Left ventricular assist device composed of electrohydraulic linear actuator and diaphram type blood pump has been investigated in this institute together with Aisin Seiki LTD.In this study series, the control system of this VAD was designed and examined. From the pressure volume curve obtained in the blood pump Ea/Ees was calculated. It was possible to get Ea/Ees as near to 1 as possible by controling stroke volume, rate, upper duty, lower duty and % systole of the VAD using multiple regression analysis in this control system.2. In order to speculate the effect of coagulation and fibrinolysis during artificial circulation including VAD on the implanted donor heart and recipient, changes of coagulation and fibrinolysis were examined during and after Cardiopulmonary bypass(CPB) : thrombocytes, beta-TG, ATIII, FPA, PLG, D-dimer, alpha_2PI etc. Both coagulation and fibrinolysis were activated during CPB.Nafamostat Mesilate(NM), however, inhibited these activities. It is considered that … More NM administration might prevent thromboembolic and hemorrhagic episodes during ventricular assist.3. In order to study whether cell mediated immunity responses would be suppressed or activated by the effect of CPB or ventricular assist, peripheral blood lymphocyte subsets and antibody dependent cell mediated cytotoxicity were investigated during artificial circulation. The total lymmphocyte (OKT 3 and OKT 11+) number did not change significantly. Suppressor/cytotoxic T cell(OKT8+) and NK cell (Leu 7+ and Leu 11+) numbers remarkably increased. But helper/inducer T cell(OKT 4+) and B cell(Leu 12+) numbers decreased. Mixed lymphocyte reaction and NK cytotoxicity were also activated during this study. It may be concluded that open heart surgery using CPB is associated with the activation of cytotoxic cell mediated immunity.4. Inthe recipient of heart transplanation who undergoes VAD as a bridge, blood coagulation, fibrinolysis and cytotoxic cell mediated immunity would be activated and therefore the incidence of thromboembolic episode and acute rejection might increase compared with simple heart transplantation. Less