ATP catabolism and adenosine generation during ischemia in the aging heart.
Myocardial injury following ischemia and reperfusion is increased in the 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-perfused hearts from adult (6 months old) and aging (24 months old) Fischer 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 each ischemic time at each age). ATP level were decreased at preischemic baseline in aging hearts. ATP levels remained lower in the aging heart throughout ischemia (P < 0.001) with a similar pattern of decrease in both age groups. The decrease in tissue glycogen and increase in lactate contents was similar during ischemia in both age groups, suggesting that comparable glycogen utilization occurred during ischemia in adult and aging hearts. ATP catabolism leads to ADP, AMP and then adenosine. Tissue levels of adenosine, an important cardioprotective metabolite, were measured during ischemia. Tissue adenosine levels were decreased 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, increased ischemic injury in the aging heart is not related to differences in glycogen consumption. Lower tissue ATP levels and decreased adenosine levels were observed during ischemia. The differences in ATP content between adult and aging hearts occurred only during early ischemia and are unlikely to provide a mechanism for the increased damage observed following more prolonged periods of ischemia in the aging heart. The potential contribution of these decreases in tissue adenosine content to the increased injury observed in the aging heart will require further study.
Ramani
K
K
Department of Medicine, Case Western Reserve University School of Medicine, University Hospitals of Cleveland, OH, USA.
Lust
W D
WD
Whittingham
T S
TS
Lesnefsky
E J
EJ
D000241:Adenosine / Q000378:metabolism*; D000255:Adenosine Triphosphate / Q000378:metabolism*; D000375:Aging / Q000378:metabolism*; D000818:Animals; D002317:Cardiovascular Agents / Q000378:metabolism*; D006003:Glycogen / Q000378:metabolism*; D008297:Male; D017202:Myocardial Ischemia / Q000378:metabolism*; D051381:Rats; D011916:Rats, Inbred F344
D002317:Cardiovascular Agents; D000255:Adenosine Triphosphate; D006003:Glycogen; D000241:Adenosine