Postischemic injury in isolated rat hearts is not aggravated by prior depletion of myocardial glutathione.
The aim of this study was to test the hypothesis that a decreased myocardial concentration of reduced glutathione (GSH) during ischemia renders the myocardium more susceptible to injury by reactive oxygen species generated during early reperfusion. To this end, rats were pretreated with L-buthionine-S,R-sulfoximine (2 mmol/kg), which depleted myocardial GSH by 55%. Isolated buffer-perfused hearts were subjected to 30 min of either hypothermic or normothermic no-flow ischemia followed by reperfusion. Prior depletion of myocardial GSH did not lead to oxidative stress during reperfusion, as myocardial concentration of glutathione disulfide (GSSG) was not increased after 5 and 30 min of reperfusion. In addition, prior depletion of GSH did not exacerbate myocardial enzyme release, nor did it impair the recoveries of tissue ATP, coronary flow rate and left ventricular developed pressure during reperfusion after either hypothermic or normothermic ischemia. Even administration of the prooxidant cumene hydroperoxide (20 microM) to postischemic GSH-depleted hearts during the first 10 min of reperfusion did not aggravate postischemic injury, although this prooxidant load induced oxidative stress, as indicated by an increased myocardial concentration of GSSG. These results do not support the hypothesis that a reduced myocardial concentration of GSH during ischemia increases the susceptibility to injury mediated by reactive oxygen species generated during reperfusion. Apparently, myocardial tissue possesses a large excess of GSH compared to the quantity of reactive oxygen species generated upon reperfusion.
Verbunt
R J
RJ
Department of Cardiology, University Hospital Leiden, The Netherlands.
Van Dockum
W G
WG
Bastiaanse
E M
EM
Egas
J M
JM
Van der Laarse
A
A
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001555:Benzene Derivatives / Q000633:toxicity; D019328:Buthionine Sulfoximine; D005978:Glutathione / Q000172:deficiency / Q000502:physiology*; D008297:Male; D008717:Methionine Sulfoximine / Q000031:analogs & derivatives / Q000633:toxicity; D015428:Myocardial Reperfusion Injury / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism*; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism
D001555:Benzene Derivatives; D017382:Reactive Oxygen Species; D008717:Methionine Sulfoximine; D019328:Buthionine Sulfoximine; D000255:Adenosine Triphosphate; D005978:Glutathione; C007164:cumene hydroperoxide