Teng C L, Kim J S, Port F K, Wakefield T W, Till G O, Yang V C
College of Pharmacy, University of Michigan, Ann Arbor 48109-1065.
ASAIO Trans. 1988 Jul-Sep;34(3):743-6.
Heparin employed in extracorporeal circuits often leads to hemorrhagic complications. Protamine employed for heparin neutralization can cause adverse hemodynamic responses. To control both types of complications, the authors propose an approach that consists of placing a filter device containing immobilized protamine (defined as a protamine filter) at the termination of the extracorporeal blood circulation (ECBC) procedure. This protamine filter would remove heparin from the extracorporeal circuit before heparin is returned to the patient. Meanwhile, the filter would also permit external protamine treatment. Since protamine toxicity generally results from the interaction of protamine with certain cells present in the liver, lungs, and tissues, the use of external protamine would minimize its potential adverse effects. Protamine was immobilized on a hollow fiber bundle obtained from a conventional hemodialyzer. Preliminary studies show that the protamine bound bundle is capable of neutralizing the anticoagulant activity of heparin both in vitro and in vivo. In addition, the protamine filter has abolished the hypotensive response normally associated with protamine reversal of heparin, as indicated by the insignificant changes in blood pressure, pulse rate, pulmonary artery systolic/diastolic pressures, and cardiac output. Further in vivo studies involving the use of dogs, as well as investigation of the activation of the complement system by the protamine filter, are currently being conducted.
体外循环中使用的肝素常常会引发出血并发症。用于中和肝素的鱼精蛋白可能会引起不良的血流动力学反应。为了控制这两种并发症,作者提出了一种方法,即在体外血液循环(ECBC)程序结束时放置一个装有固定化鱼精蛋白的过滤装置(定义为鱼精蛋白过滤器)。这个鱼精蛋白过滤器会在肝素回流到患者体内之前从体外循环中去除肝素。同时,该过滤器还允许进行体外鱼精蛋白治疗。由于鱼精蛋白毒性通常是由鱼精蛋白与肝脏、肺和组织中某些细胞的相互作用导致的,使用体外鱼精蛋白将使其潜在的不良影响最小化。鱼精蛋白被固定在从传统血液透析器获得的中空纤维束上。初步研究表明,结合了鱼精蛋白的纤维束在体外和体内都能够中和肝素 的抗凝活性。此外,鱼精蛋白过滤器消除了通常与鱼精蛋白逆转肝素相关的低血压反应,血压、脉搏率、肺动脉收缩/舒张压和心输出量的变化不明显即表明了这一点。目前正在进行涉及使用狗的进一步体内研究,以及对鱼精蛋白过滤器激活补体系统的研究。