Cardioprotective effects of platelets against ischaemia-reperfusion injury are related in part to platelet glutathione redox cycle.
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 dehydroepiandrosterone, 1,3-bis (2-chloroethyl)-1-nitrosurea, or 1-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.
Yang
B C
BC
Department of Medicine, College of Medicine, University of Florida, Gainesville 32610-0277.
Mehta
A
A
Mehta
J L
JL
D000818:Animals; D001792:Blood Platelets / Q000502:physiology*; D003402:Creatine Kinase; D005980:Glutathione Reductase / Q000378:metabolism*; D006339:Heart Rate; D008297:Male; D009200:Myocardial Contraction; D010477:Perfusion; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000201:enzymology / Q000517:prevention & control*
D005980:Glutathione Reductase; D003402:Creatine Kinase