TOLERANCE TO OXIDATIVE STRESS IN AGING HEART

Abstract

PURPOSE To determine the effects of aging on the ability of the heart to tolerate exposure to hydrogen peroxide (H2O2), a pro-oxidant and activator of cell signaling pathways. METHODS Isolated perfused working hearts from young (2.5-mo, n=7), adult (8-mo, n=8), and aged (23-mo, n=9) male F344 rats were initially perfused with H2O2-free buffer to establish baseline function, then with 150 μM H2O2 for 20 min, followed by a 10-min washout with H2O2-free buffer. RESULTS H2O2 progressively decreased cardiac performance in all groups; however, the decline in the oldest group was significantly attenuated. After 20 min exposure, cardiac output × systolic pressure was 22.2±3.5%, 20.1±2.4%, and 37.7±4.9% of pre-H2O2 baseline in the 2.5-, 8-, and 23-mo groups, respectively. Leakage of lactate dehydrogenase (LDH), a marker of tissue necrosis, increased above baseline in only the 8-mo group (1.8 fold, P < 0.05) during the 20-min H2O2 exposure. LDH release increased in all groups during the 10-min washout period; however, the amount released was much lower in the 23-mo group: final values (mU/min/g) were 70.7±2.6, 142.2±11.5, and 35.7±5.4 in 2.5-, 8-, and 23-mo groups, respectively (P < 0.05 vs any group). Glutathione peroxidase activity was similar in all ages. Catalase activity was similar at 8- and 23-mo and approximately 50% higher than at 2.5- mo. Unlike H2O2 exposure, when perfused with the glutathione peroxidase substrate, tert-butyl hydroperoxide, aged hearts released more LDH than adults. CONCLUSION Aged rat hearts tolerate H2O2 better than hearts from younger animals and the improved tolerance from adulthood to old age is not due to changes in antioxidant enzymes. Supported by Am. Heart Assoc. TX Affiliate