PLATELETS PROTECT AGAINST MYOCARDIAL DYSFUNCTION AND INJURY-INDUCED BY ISCHEMIA AND REPERFUSION IN ISOLATED RAT HEARTS

Platelets are a source of vasoactive mediators that regulate vascular tone. Platelets also play a role in intravascular thrombus formation a nd dynamic coronary constriction that result in myocardial ischemia. H owever, effects of platelets on myocardial function after ischemia and reperfusion are unknown. In this study, we examined the effects of pl atelets on myocardial dysfunction caused by ischemia/reperfusion. Buff er-perfused isolated rat hearts, after global ischemia (15 minutes) an d reperfusion (10 minutes), developed marked myocardial dysfunction, i ndicated by a 65+/-4% decrease in the force of cardiac contraction (FC C) and a 26+/-7% increase in coronary perfusion pressure (CPP). Ischem ia/reperfusion was also associated with release of creatine kinase (CK ) and ATP metabolites in the coronary effluents. Perfusion of hearts w ith buffer containing washed rat platelets (3-8x10(7) cells/ml) protec ted hearts against dysfunction from ischemia/reperfusion, indicated by minimal changes in CPP (-1+/-1%) and FCC (-1+/-3%). Release of CK in the coronary effluent was also reduced, as was the release of ATP meta bolites in the platelet-perfused hearts. Perfusion of hearts with sero tonin receptor antagonist LY53,857 (10(-6) M), thromboxane A2 receptor antagonist SQ29,548 (10(-6) M), adenine nucleotide scavenger apyrase (0.4 units/ml), or nitric oxide synthetase inhibitor N(G)-monomethyl-L -arginine (2x10(-4) M) attenuated (p<0.05) the platelet-mediated cardi oprotective effects. Perfusion of the hearts with L-arginine (2x10(-4) M) instead of platelets also showed modest protective effects on FCC (-4.3+/-13%), CPP (+18+/-7%), and CK release. Prolongation of the isch emic period to 30 minutes and reperfusion to 20 minutes also demonstra ted marked cardiac dysfunction (FCC, -58+/-10%; CPP, +36+/-8%) in buff er-perfused hearts. Perfusion of hearts with platelets in this setting of prolonged ischemia/reperfusion also exhibited protective effects o n FCC (-24+/-10%), CPP (+12+/-6%), and CK release. Thus, platelets pro tect myocardium from ischemia/reperfusion-induced injury, and these pr otective effects of platelets are evident regardless of the duration o f ischemia/reperfusion. Furthermore, these cardioprotective effects of platelets seem to be related to the release of serotonin, thromboxane A2, and adenine nucleotides. These substances most likely elicit rele ase of endothelium-derived relaxing factor, with its attendant tissue- protective effects, from the microvascular endothelium of hearts.