Age-related decrease in cardiac tolerance to oxidative stress

Oxygen radical-mediated injury has been implicated in the process of cardia c aging. We investigated the tolerance to oxidative stress of hearts from r ats of different age. Langendorff-perfused hearts from 3-12-month-old rats received a 30 min infusion of the reactive oxygen specie hydrogen peroxide (H2O2, 60 mu M), followed by a 15 min wash-out. H2O2 infusion resulted in a significantly larger increase in end-diastolic pressure in hearts of 6- an d 12-month-old rats than 3 months (P<0.01). Tn addition, developed pressure and rate-pressure product decreased more evidently in 12-month-old hearts (P<0.01 vs 3 and 6 months). Arrhythmia analysis showed higher score in hear ts of 12- and 6-month-old rats with respect to 3-month-old animals (P<0.05) , Cardiac release of oxidized glutathione tan index of the ability of the h eart to inactivate oxygen metabolites) was significantly lower in hearts fr om rats of 6 and 12 months than in younger animals (P<0.001). Finally, card iac concentrations of the scavenger enzymes glutathione peroxidase and Mn-s uperoxide dismutase also significantly decreased with age. In conclusion, i n rat heart metabolic and functional tolerance toward oxidative stress decr eases with age. This phenomenon may contribute to the development of cardio vascular alterations with increasing age. (C) 1999 Academic Press.