ATP CATABOLISM AND ADENOSINE GENERATION DURING ISCHEMIA IN THE AGING HEART

Myocardial injury following ischemia and reperfusion is increased in t he aging heart. The mechanisms underlying the increased susceptibility of the aging heart to ischemic injury remain unknown. We investigated whether decreased glycogen utilization with a more rapid depletion of ATP occurred during ischemia in the aging heart. Isolated buffer-perf used hearts from adult (6 months old) and aging (24 months old) Fische r 344 rats were subjected to 0, 2, 5, 10, 15 or 25 min of global stop- flow ischemia following a 15 min equilibration period (n = 5-6 for eac h ischemic time at each age). ATP levels were decreased at preischemic baseline in aging hearts. ATP levels remained lower in the aging hear t throughout ischemia (P < 0.001) with a similar pattern of decrease i n both age groups. The decrease in tissue glycogen and increase in lac tate contents was similar during ischemia in both age groups, suggesti ng that comparable glycogen utilization occurred during ischemia in ad ult and aging hearts. ATP catabolism leads to ADP, AMP and then adenos ine. Tissue levels of adenosine, an important cardioprotective metabol ite, were measured during ischemia. Tissue adenosine levels were decre ased by 50% in the aging heart at 5 and 10 min, and remained depressed at 15 min and 25 min of ischemia compared to adult controls. Thus, in creased ischemic injury in the aging heart is not related to differenc es in glycogen consumption. Lower tissue ATP levels and decreased aden osine levels were observed during ischemia. The differences in ATP con tent between adult and aging hearts occurred only during early ischemi a and are unlikely to provide a mechanism for the increased damage obs erved following more prolonged periods of ischemia in the aging heart. The potential contribution of these decreases in tissue adenosine con tent to the increased injury observed in the aging heart will require further study.