Heindl B, Zahler S, Welsch U, Becker B F
Institute of Physiology, Ludwig-Maximilians-University, Munich, Germany.
Cardiovasc Res. 1998 May;38(2):383-94. doi: 10.1016/s0008-6363(98)00032-7.
Beside the major effect of acute thrombus formation, little is known about the interaction of platelets with the coronary endothelium in an ischaemia-reperfusion situation. The present study was designed to investigate, separately, the consequences of platelet adhesion and degranulation during myocardial reperfusion.
Isolated guinea pig hearts perfused with Krebs-Henseleit buffer and performing pressure-volume work were used. We infringed myocardial function by imposing ischaemia (20 min of low-flow perfusion with 1 ml/min and 10 min of global ischaemia) and reperfusion (15 min with 5 ml/min). During low-flow perfusion, the coronary endothelium was stimulated by thrombin before and during infusion of a bolus: 10(8) washed human platelets +/- the Arg-Gly-Asp (RGD) analogon lamifiban, the supernatant of 10(8) thrombin-stimulated platelets, fibrinogen (2 microM), lamifiban (2 microM) or Tyrode's solution (control group). The parameter external heart work (EHW), determined pre- and postischaemically, served as criterion for recovery of myocardial function. Additionally, the formation of capillary transudate was measured during the reperfusion phase to assess coronary permeability. Coronary perfusion pressure was monitored continuously and myocardial production of lactate and consumption of pyruvate were measured. Electron microscopy of hearts was performed after platelet application to verify platelet adhesion in the coronary system.
Recovery of EHW by hearts without platelet application was 64 +/- 3% and was significantly reduced to 49 +/- 5% by platelet infusion (n = 8 each). Infusion of supernatant of thrombin-stimulated platelets did not impair recovery of heart work. In the reperfusion phase (6th-10th min), hearts that either had received platelets or supernatant of platelets exhibited a significantly reduced production of capillary transudate (70 microliters/min vs. 180 microliters/min for the controls). Intracoronary bolus application of fibrinogen or lamifiban also reduced coronary leak. Coronary perfusion pressure and metabolic parameters were not statistically different between the groups at any time.
Platelet adhesion to the coronary endothelium in a situation of myocardial ischaemia impairs cardiac recovery, whereas constituents released by platelets may have beneficial effects on the integrity of the coronary endothelium. In particular, fibrinogen seems to contribute to the permeability reducing effect, possibly by interaction with endothelial receptors recognising the RGD sequence.
除急性血栓形成的主要影响外，关于血小板在缺血再灌注情况下与冠状动脉内皮的相互作用知之甚少。本研究旨在分别探讨心肌再灌注期间血小板黏附和脱颗粒的后果。
使用灌注 Krebs-Henseleit 缓冲液并进行压力-容积功的离体豚鼠心脏。通过施加缺血（1 ml/min 的低流量灌注 20 分钟和全心缺血 10 分钟）和再灌注（5 ml/min 灌注 15 分钟）来损害心肌功能。在低流量灌注期间，在推注前和推注期间用凝血酶刺激冠状动脉内皮：10⁸ 个洗涤过的人血小板 ± 精氨酸-甘氨酸-天冬氨酸（RGD）类似物拉米非班、10⁸ 个凝血酶刺激的血小板的上清液、纤维蛋白原（2 μM）、拉米非班（2 μM）或 Tyrode's 溶液（对照组）。缺血前后测定的参数心脏外部功（EHW）用作心肌功能恢复的标准。此外，在再灌注阶段测量毛细血管渗出液的形成以评估冠状动脉通透性。连续监测冠状动脉灌注压力并测量心肌乳酸生成和丙酮酸消耗。在应用血小板后对心脏进行电子显微镜检查以验证冠状动脉系统中的血小板黏附。
未应用血小板的心脏 EHW 恢复率为 64 ± 3%，而血小板输注后显著降低至 49 ± 5%（每组 n = 8）。输注凝血酶刺激的血小板上清液并未损害心脏功的恢复。在再灌注阶段（第 6 - 10 分钟），接受血小板或血小板上清液的心脏毛细血管渗出液的产生显著减少（对照组为 180 μl/min，而前者为 70 μl/min）。冠状动脉内推注纤维蛋白原或拉米非班也减少了冠状动脉渗漏。各组之间在任何时候冠状动脉灌注压力和代谢参数均无统计学差异。
心肌缺血情况下血小板与冠状动脉内皮的黏附会损害心脏恢复，而血小板释放的成分可能对冠状动脉内皮的完整性有有益影响。特别是，纤维蛋白原似乎有助于降低通透性，可能是通过与识别 RGD 序列的内皮受体相互作用。
