DISPARATE EFFECTS OF ADHESION AND DEGRANULATION OF PLATELETS ON MYOCARDIAL AND CORONARY FUNCTION IN POSTISCHEMIC HEARTS

Objective: Beside the major effect of acute thrombus formation, little is known about the interaction of platelets with the coronary endothe lium in an ischaemia-reperfusion situation. The present study was desi gned to investigate, separately, the consequences of platelet adhesion and degranulation during myocardial reperfusion. Methods: Isolated gu inea pig hearts perfused with Krebs-Henseleit buffer and performing pr essure-volume work were used. We infringed myocardial function by impo sing 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 lo w-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 108 thr ombin-stimulated platelets, fibrinogen(2 mu M), lamifiban (2 mu M) or Tyrode's solution (control group). The parameter external heart work ( EHW), determined pre- and postischaemically, served as criterion for r ecovery of myocardial function. Additionally, the formation of capilla ry transudate was measured during the reperfusion phase to assess coro nary permeability. Coronary perfusion pressure was monitored continuou sly and myocardial production of lactate and consumption of pyruvate w ere measured. Electron microscopy of hearts was performed after platel et application to verify platelet adhesion in the coronary system. Res ults: Recovery of EHW by hearts without platelet application was 63 +/ - 3% and was significantly reduced to 49 +/- 58 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-1 0th min), hearts that either had received platelets or supernatant of platelets exhibited a significantly reduced production of capillary tr ansudate (70 mu l/min vs. 180 mu l/min for the controls). Intracoronar y bolus application of fibrinogen or lamifiban also reduced coronary l eak. Coronary perfusion pressure and metabolic parameters were not sta tistically different between the groups at any time. Conclusions: Plat elet 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 per meability reducing effect, possibly by interaction with endothelial re ceptors recognising the RGD sequence. (C) 1998 Elsevier Science B.V. A ll rights reserved.