Age-dependent changes in myocardial susceptibility to zero flow ischemia and reperfusion in isolated perfused rat hearts: relation to antioxidant status.
Ageing is associated with an increase in myocardial susceptibility to ischemia and a decrease in post-ischemic recovery of function. In the present study, we have examined the effects of ageing on (i) myocardial ischemic contracture, (ii) the reperfusion syndrome and lipid peroxidation upon reperfusion, and (iii) the activity of enzymes involved in reactive oxygen species elimination. Hearts from male Wistar rats aged 4 (adults), 16 (old) or 24 months (senescent) were subjected to 20-min zero flow ischemia and 30-min reperfusion ex vivo. Cardiac activity of superoxide dismutase, catalase, and glutathione peroxidase, as well as cardiac content of thiobarbituric acid reactants were assessed in frozen heart samples. The effects of ageing on ischemic contracture of the sarcomeres were assessed on electromicrographs of tissues taken at the end of ischemia. In our experimental conditions, ischemic contracture of the sarcomeres increased progressively during ageing. In contrast, the severity of the reperfusion syndrome increased between 4 and 16 months of age, and then decreased up to 24 months of age. We propose that the peak of susceptibility of the myocardium to reperfusion observed during moderate ageing might be related to a decrease in the ability of cardiomyocytes to dismutate hydrogen peroxide as suggested by the observed decrease in catalase activity. Finally, the better resistance to the reperfusion syndrome exhibited by senescent rats compared to old rats might be due to a natural selection of a subpopulation of rats which is particularly resistant to oxidative stress.
Groupe de Physiopathologie Cellulaire Cardiaque, CNRS-ESA 5077, Université Joseph Fourier, Grenoble, France. francois.boucher@ujf-grenoble.fr
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Boucher
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Tanguy
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Besse
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Tresallet
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Favier
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de Leiris
D000375:Aging / Q000378:metabolism*; D000704:Analysis of Variance; D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D001783:Blood Flow Velocity; D004198:Disease Susceptibility; D066298:In Vitro Techniques; D008297:Male; D015428:Myocardial Reperfusion Injury; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism
D000975:Antioxidants; D017382:Reactive Oxygen Species