Cardioprotective effects of platelets against ischaemia-reperfusion injury are related in part to platelet glutathione redox cycle

Abstract

Objective: Washed platelets have been shown to protect isolated buffer perfused rat hearts from injury and dysfunction following ischaemia-reperfusion. This study was designed to investigate whether platelet glutathione redox cycle contributes to the protective effect of platelets. Methods: Isolated rat hearts were perfused with Krebs-Henseleit buffer alone, buffer containing platelets, or buffer containing platelets pretreated with inhibitors of glutathione redox cycle. All hearts were subjected to 40 min of global ischaemia followed by 30 min of reperfusion. Results: Following ischaemia and reperfusion, hearts perfused with buffer alone showed a marked reduction in force of cardiac contraction and heart rate, an increase in coronary perfusion pressure and diastolic tone, and a release of creatine kinase in the coronary effluent. Myocardial creatine kinase, superoxide dismutase activity, and glutathione content all fell. Perfusion of hearts with washed platelets provided significant protection from ischaemia-reperfusion related myocardial injury and dysfunction. The cardioprotective effects of platelets were attenuated when they were preincubated with the glutathione redox cycle inhibitors dehydroepiandros-terone, 1,3-bis (2-chloroethyl)-l-nitrosurea, or l-chloro-2,4-dinitrobenzene. Pretreatment of platelets with glutathione redox cycle inhibitors did not affect the platelet mediated preservation of myocardial superoxide dismutase activity. Conclusions: Platelet glutathione redox cycle contributes in part to the cardioprotective effects of platelets against ischaemia-reperfusion injury and dysfunction in the isolated rat heart.

Cardiovascular Research 1994;28:1586-1593

platelet, myocardial ischaemia, glutathione, antioxidants