Bernabei A, Gikakis N, Maione T E, Kowalska M A, Yan Z, Niewiarowski S, Edmunds L H
Harrison Department of Surgery, School of Medicine, University of Pennsylvania, Philadelphia, USA.
J Thorac Cardiovasc Surg. 1995 Apr;109(4):765-71. doi: 10.1016/s0022-5223(95)70359-4.
The ability of recombinant platelet factor 4 and protamine to neutralize heparin after cardiopulmonary bypass was compared in anesthestized baboons. Clotting titration curves of heparinized baboon blood demonstrate an anticoagulant effect of protamine that is not seen with recombinant platelet factor 4. Neither drug caused meaningful changes in central pressures or cardiac output within 30 minutes after injection. After 30 minutes of cardiopulmonary bypass, recombinant platelet factor 4 normalized thrombin times and activated partial thromboplastin times within minutes of injection, but protamine did not. Neither drug altered bleeding times. Recombinant platelet factor 4 caused a species-specific leukopenia in baboons and significantly increased activated complement protein 3 (C3a) more than protamine. However, the increase in plasma C3a was small and neither drug caused a significant increase in plasma neutrophil elastase-alpha 1 proteinase inhibitor complex. We conclude that recombinant platelet factor 4 is effective and safe in baboons, does not have an anticoagulant effect with excess concentration, and reverses in vivo heparin more rapidly than protamine. The data support progression to a clinical trial.
在麻醉的狒狒中比较了重组血小板因子4和鱼精蛋白在体外循环后中和肝素的能力。肝素化狒狒血液的凝血滴定曲线显示鱼精蛋白具有抗凝作用，而重组血小板因子4则没有。注射后30分钟内，两种药物均未引起中心压力或心输出量的显著变化。体外循环30分钟后，注射重组血小板因子4后几分钟内凝血酶时间和活化部分凝血活酶时间恢复正常，但鱼精蛋白则没有。两种药物均未改变出血时间。重组血小板因子4在狒狒中引起了物种特异性白细胞减少，并且比鱼精蛋白更显著地增加了活化补体蛋白3（C3a）。然而，血浆C3a的增加很小，两种药物均未导致血浆中性粒细胞弹性蛋白酶-α1蛋白酶抑制剂复合物显著增加。我们得出结论，重组血小板因子4在狒狒中有效且安全，在浓度过高时没有抗凝作用，并且比鱼精蛋白能更快地在体内逆转肝素作用。这些数据支持开展临床试验。
