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) myocardia l ischemic contracture, (ii) the reperfusion syndrome and lipid peroxi dation upon reperfusion, and (iii) the activity of enzymes involved in reactive oxygen species elimination. Hearts from male Wistar rats age d 4 (adults), 16 (old) or 24 months (senescent) were subjected to 20-m in zero flow ischemia and 30-min reperfusion ex vivo. Cardiac activity of superoxide dismutase, catalase, and glutathione peroxidase, as wel l as cardiac content of thiobarbituric acid reactants were assessed in frozen heart samples. The effects of ageing on ischemic contracture o f the sarcomeres were assessed on electromicrographs of tissues taken at the end of ischemia. In our experimental conditions, ischemic contr acture of the sarcomeres increased progressively during ageing. In con trast, the severity of the reperfusion syndrome increased between 4 an d 16 months of age, and then decreased up to 24 months of age. We prop ose that the peak of susceptibility of the myocardium to reperfusion o bserved during moderate ageing might be related to a decrease in the a bility of cardiomyocytes to dismutate hydrogen peroxide as suggested b y the observed decrease in catalase activity. Finally, the better resi stance to the reperfusion syndrome exhibited by senescent rats compare d to old rats might be due to a natural selection of a subpopulation o f rats which is particularly resistant to oxidative stress. (C) 1998 E lsevier Science Ireland Ltd. All rights reserved.