Serna D L, King B O, Huh J, Jalal R, Tran L, Chen J C
Department of Surgery, University of California, Irvine Medical Center, Orange 92868, USA.
J Investig Med. 1998 Aug;46(6):279-83.
Left ventricular assist devices (VAD) have improved survival in patients with end-stage heart failure. Past studies have shown that interactions between blood and synthetic surfaces promote initial bleeding and later thromboembolism. The exact mechanism of blood activation during VAD circulation remains unclear. The purpose of this study was to test the hypothesis that platelet glycoprotein (GP) IIb/IIIa receptor degradation occurs during clinical use of ventricular assist devices.
Five in vitro nonpulsatile centrifugal VAD circuits were simulated for 4 days using 450 mL of fresh human whole blood. Temperature, activated clotting time, pH, pCO2, pO2, Ca++, and glucose were maintained at physiologic values. Flow was maintained at a constant 2.0 L/min/m2. We examined whole blood platelet aggregation induced by ristocetin, collagen, and adenosine diphosphate (ATP). We also examined whole blood platelet degranulation induced by collagen and ADP.
Platelet aggregation in response to ristocetin, collagen, and ADP irreversibly and progressively declined with prolonged circulation in the VAD. While ADP-induced aggregation declined within the first hour, ristocetin and collagen-induced aggregation declined after 10 hours. Collagen-induced platelet degranulation decreased similar to aggregation, whereas ADP-induced degranulation continued and was preserved throughout the experiment.
These results suggest prolonged circulation of human blood in a VAD circuit irreversibly impair platelet aggregation. The response of circulating platelets to individual agonists suggests that this platelet degradation is partially receptor specific. In our VAD system, ADP-stimulated platelet aggregation is more rapidly degraded with circulation. These results offer preliminary evidence that circulation of human blood in a VAD circuit leads to early degradation of the platelet GP IIb/IIIa complex. GP IIb/IIIa complex degradation is likely to be the mechanism of early VAD associated bleeding.
左心室辅助装置（VAD）已提高了终末期心力衰竭患者的生存率。过去的研究表明，血液与合成表面之间的相互作用会引发早期出血和后期血栓栓塞。VAD循环期间血液激活的确切机制仍不清楚。本研究的目的是检验心室辅助装置临床使用期间血小板糖蛋白（GP）IIb/IIIa受体降解这一假设。
使用450毫升新鲜人体全血对五个体外非搏动性离心VAD回路进行4天的模拟。温度、活化凝血时间、pH值、pCO2、pO2、Ca++和葡萄糖维持在生理值。流量维持在恒定的2.0升/分钟/平方米。我们检测了由瑞斯托菌素、胶原蛋白和二磷酸腺苷（ADP）诱导的全血血小板聚集。我们还检测了由胶原蛋白和ADP诱导的全血血小板脱颗粒。
随着在VAD中循环时间的延长，对瑞斯托菌素、胶原蛋白和ADP的血小板聚集不可逆地逐渐下降。虽然ADP诱导的聚集在第一小时内下降，但瑞斯托菌素和胶原蛋白诱导的聚集在10小时后下降。胶原蛋白诱导的血小板脱颗粒与聚集类似地减少，而ADP诱导的脱颗粒持续存在并在整个实验中保持。
这些结果表明，人体血液在VAD回路中的长时间循环会不可逆地损害血小板聚集。循环血小板对个别激动剂的反应表明，这种血小板降解部分是受体特异性的。在我们的VAD系统中，ADP刺激的血小板聚集随着循环更快地降解。这些结果提供了初步证据，表明人体血液在VAD回路中的循环导致血小板GP IIb/IIIa复合物的早期降解。GP IIb/IIIa复合物降解可能是早期VAD相关出血的机制。
