Kanemitsu Shinji, Nishikawa Masakatsu, Onoda Koji, Shimono Takatsugu, Shimpo Hideto, Yazaki Akira, Tanaka Kuniyoshi, Shiku Hiroshi, Yada Isao
Department of Thoracic and Cardiovascular Surgery, Mie University School of Medicine, 2-174 Edobashi, Tsu, Mie 514-8507, Japan.
J Thorac Cardiovasc Surg. 2003 Aug;126(2):428-35. doi: 10.1016/s0022-5223(02)73288-1.
Contact between blood and the synthetic surfaces of a cardiopulmonary bypass circuit leads to platelet activation, and resultant platelet dysfunction contributes to postoperative bleeding. We compared the effects of various platelet inhibitors on preservation of platelet function during simulated cardiopulmonary bypass circulation.
Fresh human blood was recirculated in an in vitro cardiopulmonary bypass model circuit. We measured various platelet activation markers including expressions of PAC-1 and P-selectin, annexin V binding, and microparticle formations by means of whole-blood flow cytometry.
Two types of glycoprotein IIb/IIIa complex antagonists, peptide-mimetic FK633 and abciximab and prostaglandin E(1), significantly prevented platelet loss and the increase in binding of PAC-1, an antibody specific for fibrinogen receptor on activated platelets, during extracorporeal circulation of heparinized blood. These antagonists significantly suppressed but did not abolish P-selectin expression, annexin V binding, and microparticle formation. Anti-von Willebrand factor monoclonal antibody and aurin tricarboxylic acid (an inhibitor of glycoprotein Ib) had no effect on platelet activation during simulated cardiopulmonary bypass circulation. These data suggest that inhibition of fibrinogen binding glycoprotein IIb/IIIa complex is partly effective in attenuating platelet activation in a heparinized cardiopulmonary bypass model circuit. The direct thrombin inhibitor argatroban prevented platelet loss and expression of P-selectin significantly more than did heparin. A combination of FK633 with argatroban as a substitute for heparin further prevented platelet loss and platelet secretion during simulated cardiopulmonary bypass circulation, although the inhibition of microparticle formation was less.
The inhibition of both platelet adhesion and thrombin may be effective to preserve platelet number and function during cardiopulmonary bypass circulation.
血液与体外循环回路的合成表面接触会导致血小板活化，而由此产生的血小板功能障碍会导致术后出血。我们比较了各种血小板抑制剂在模拟体外循环期间对血小板功能保存的影响。
新鲜人血在体外循环模型回路中再循环。我们通过全血流式细胞术测量了各种血小板活化标志物，包括PAC-1和P-选择素的表达、膜联蛋白V结合以及微粒形成。
两种糖蛋白IIb/IIIa复合物拮抗剂，肽模拟物FK633和阿昔单抗以及前列腺素E(1)，在肝素化血液的体外循环期间，显著防止了血小板损失以及活化血小板上纤维蛋白原受体特异性抗体PAC-1结合的增加。这些拮抗剂显著抑制但并未消除P-选择素表达、膜联蛋白V结合和微粒形成。抗血管性血友病因子单克隆抗体和金精三羧酸（糖蛋白Ib抑制剂）在模拟体外循环期间对血小板活化没有影响。这些数据表明，在肝素化体外循环模型回路中，抑制纤维蛋白原结合糖蛋白IIb/IIIa复合物在减轻血小板活化方面部分有效。直接凝血酶抑制剂阿加曲班比肝素更能显著防止血小板损失和P-选择素表达。FK633与阿加曲班联合作为肝素的替代品，在模拟体外循环期间进一步防止了血小板损失和血小板分泌，尽管对微粒形成的抑制作用较小。
抑制血小板黏附和凝血酶可能对在体外循环期间保存血小板数量和功能有效。
