Platelet-derived adenosine contributes to the cardioprotective effects of platelets against ischemia-reperfusion injury in isolated rat heart.
Platelets have been shown to protect isolated perfused rat hearts from injury and dysfunction after ischemia and reperfusion. We examined the role of platelet-derived adenosine in the cardioprotective effects of platelets against reperfusion injury. Isolated perfused rat hearts were subjected to 40-min global ischemia followed by 30-min reperfusion. The buffer-perfused hearts developed dysfunction, as indicated by 40 +/- 4% decrease in force of cardiac contraction (FCC) and 24 +/- 3% increase in coronary perfusion pressure (CPP). Creatine kinase (CK) was released in coronary effluent during reperfusion, indicating myocardial injury. At the end of reperfusion, myocardial CK content and superoxide dismutase (SOD) activity were lower than in sham ischemia-reperfused hearts. Perfusion of hearts with washed platelets resulted in protection against myocardial dysfunction and injury after ischemia and reperfusion, indicated by preservation of FCC (-2 +/- 5%) and CPP (-3 +/- 2%) (both p < 0.01 vs. buffer-perfused hearts). Myocardial CK and SOD activity were also preserved, and release of CK in the coronary effluent was minimal (all p < 0.05 vs. buffer-perfused hearts). The cardioprotective effects of platelets were attenuated by preincubation of platelets with adenosine deaminase. Perfusion with adenosine or the adenosine2 receptor agonist N6-[2-(3,5-dimethoxyphenyl)-2-(2- methylphenyl)-ethyl]adenosine (DPMA) also protected heart from myocardial dysfunction and injury after ischemia and reperfusion. Both adenosine and DPMA had salutary effects on indexes of cardiac injury. Platelet-derived adenosine contributes at least in part to the cardioprotective effects of platelets against ischemia and reperfusion in isolated rat heart.
Yang
B C
BC
Department of Medicine, College of Medicine, University of Florida, Gainesville 32610-0277.
Mehta
J L
JL
D000241:Adenosine / Q000031:analogs & derivatives / Q000494:pharmacology* / Q000627:therapeutic use; D000243:Adenosine Deaminase / Q000494:pharmacology / Q000627:therapeutic use; D000704:Analysis of Variance; D000818:Animals; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism*; D003402:Creatine Kinase / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D015428:Myocardial Reperfusion Injury / Q000473:pathology / Q000517:prevention & control*; D009206:Myocardium / Q000201:enzymology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013482:Superoxide Dismutase / Q000378:metabolism
C056426:CGS 24012; D013482:Superoxide Dismutase; D003402:Creatine Kinase; D000243:Adenosine Deaminase; D000241:Adenosine