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 and dynamic coronary constriction that result in myocardial ischemia. However, effects of platelets on myocardial function after ischemia and reperfusion are unknown. In this study, we examined the effects of platelets on myocardial dysfunction caused by ischemia/reperfusion. Buffer-perfused isolated rat hearts, after global ischemia (15 minutes) and reperfusion (10 minutes), developed marked myocardial dysfunction, indicated by a 65 +/- 4% decrease in the force of cardiac contraction (FCC) and a 26 +/- 7% increase in coronary perfusion pressure (CPP). Ischemia/reperfusion was also associated with release of creatine kinase (CK) and ATP metabolites in the coronary effluents. Perfusion of hearts with buffer containing washed rat platelets (3-8 x 10(7) cells/ml) protected 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 metabolites in the platelet-perfused hearts. Perfusion of hearts with serotonin 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 NG-monomethyl-L-arginine (2 x 10(-4) M) attenuated (p < 0.05) the platelet-mediated cardioprotective effects. Perfusion of the hearts with L-arginine (2 x 10(-4) M) instead of platelets also showed modest protective effects on FCC (-4.3 +/- 13%), CPP (+18 +/- 7%), and CK release. Prolongation of the ischemic period to 30 minutes and reperfusion to 20 minutes also demonstrated marked cardiac dysfunction (FCC, -58 +/- 10%; CPP, +36 +/- 8%) in buffer-perfused hearts. Perfusion of hearts with platelets in this setting of prolonged ischemia/reperfusion also exhibited protective effects on FCC (-24 +/- 10%), CPP (+12 +/- 6%), and CK release. Thus, platelets protect myocardium from ischemia/reperfusion-induced injury, and these protective effects of platelets are evident regardless of the duration of 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 release of endothelium-derived relaxing factor, with its attendant tissue-protective effects, from the microvascular endothelium of hearts.
Department of Medicine, University of Florida College of Medicine, Gainesville 32610-0277.
B C
BC
Yang
R
R
Virmani
W W
WW
Nichols
J L
JL
Mehta
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001120:Arginine / Q000494:pharmacology; D001792:Blood Platelets / Q000502:physiology*; D003402:Creatine Kinase / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D009200:Myocardial Contraction; D017202:Myocardial Ischemia / Q000097:blood* / Q000378:metabolism; D015428:Myocardial Reperfusion Injury / Q000097:blood* / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism*; D010477:Perfusion; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000502:physiology; D013928:Thromboxane A2 / Q000502:physiology
D009569:Nitric Oxide; D012701:Serotonin; D013928:Thromboxane A2; D000255:Adenosine Triphosphate; D001120:Arginine; D003402:Creatine Kinase