The thromboresistant mechanism of Heparin Surface and its application to membrane oxygenator

在体外循环的临床管理中，例如在心血管手术中的心肺转流中，预防血栓形成，即维持抗凝是相当重要的问题。虽然表面肝素化回路是一种新开发的抗血栓材料，据报道可有效维持体外循环期间的抗凝作用，但尚未将其引入常规临床实践。到目前为止，肝素的全身给药长期以来一直用于预防体外循环管理中回路中的血栓形成。在体外循环结束时使用鱼精蛋白逆转肝素抗凝期间，已报告了各种不良反应，如低血压、肺动脉高压或血小板减少症。虽然鱼精蛋白的这种不良血流动力学效应对某些患者可能是关键的，但其确切机制尚未完全阐明。我们 ...更多信息 因此，采用等长张力记录方法研究了鱼精蛋白对血管平滑肌和内皮的影响。然后发现，只有鱼精蛋白本身，而不是肝素-鱼精蛋白复合物，对血管平滑肌和内皮都具有抑制作用。鱼精蛋白对血管平滑肌的抑制作用可能是通过刺激内皮细胞释放EDRF、抑制平滑肌细胞内Ca^2+内流和抑制平滑肌细胞内Ca^2+释放等途径实现的。此外，从肝素的实验中可以看出，鱼精蛋白对血管平滑肌和内皮的抑制作用可能是由于其正电荷，鱼精蛋白可能不进入平滑肌细胞而直接发挥血管舒张作用。以往的报道表明，在肝素逆转过程中，除了肝素-鱼精蛋白复合物外，血液中还存在游离鱼精蛋白。综上所述，鱼精蛋白对血管平滑肌和内皮细胞的抑制作用可能部分解释了肝素抗凝过程中鱼精蛋白的不良血流动力学效应，提示在肝素抗凝过程中，应尽量减少鱼精蛋白的缓慢给药。最后，我们目前的数据强烈表明，确定精确逆转肝素抗凝所需的鱼精蛋白量的重要性，以及早期引入“肝素表面”回路的必要性，该回路不需要在体外循环结束时给予鱼精蛋白，进入临床环境。少

It is quite an important issue to prevent thrombus formation,i.e. to maitain anticoagulation in the clinical management of an extracorporeal circulation, such as a cardiopulmonary bypass in the cardovascular surgery. Although a surface-heparinized circuit, a newly developed thromboresistant material, has been reported to be effective to maintain anticoagulation during the extracorporeal circulation, it has not yet been introduced into the routine clinical practice. Until now, systemic administration of heparin has long been used to prevent thrombus formation in the circuit in the management of the extracorporeal circulation. Various adverse responses, such as hypotension, pulmonary hypertension, or thrombocytopenia, have been reported during the protamine reversal of heparin anticoagulation at the end of the extracorporeal circulation. Although such adverse hemodynamic effects of protamine can be critical in some patients, their precise mechanisms have not yet been fully elucidated. We … More , therefore, investigated the effects of protamine on vascular smooth muscle and endothelium, employing isometric tension recording methods. It was then found that only protamine itself, but not a heparin-protamine complex, has inhibitory actions on both vascular smooth muscle and endothelium. It was also suggested that protamine exert its inhibitory effects on vascular smooth muscle probably by stimulating the endothelium to release EDRF,by inhibiting the Ca^<2+> influx into the smooth muscle cell, and by inhibiting the Ca^<2+> release from the intracellular store of smooth muscle cell. Furthermore, it was suggested from the experiments with heparin that the inhibitory effects of protamine on vascular smooth muscle and endothelium are probably due to its positive charge, and that protamine presumably exert its direct vasodilating action without entering the smooth muscle cell. Previous reports have shown that free protamine exists in the blood during the heparin reversal besides a heparin-protamine complex. Putting the above findings together, it is suggested that the observed in vitro inhibitory effects of protamine on vascular smooth muscle and endothelium may partly explain the adverse hemodynamic effects of protamine occurred during the heparin reversal, and that the minimum possible amount of protamine should be administered slowly to reverse the heparin anticoagulation. Finally, our present data strongly suggest the importance of the determination of the amount of protamine required for the precise reversal of heparin anticoagulation, and the necessity of the early introduction of the "heparin-surfaced" circuit, which does not require the administration of protamine at the end of the extracorporeal circulation, into the clinical setting. Less