Abstract
Myocardial injury following ischemia and reperfusion is increased in the aging heart, including in the aging 24 mo Fischer 344 rat (mean survival 29 mo) compared to the Fischer 344 adult (6 mo). Adenosine (ADO) has been increasingly appreciated as a cardioprotective agent in myocardial ischemia. We hypothesized that a potential mechanism of the increased injury in the aging heart is decreased production of ADO in response to ischemia. Isolated buffer perfused (glucose 5 mM — insulin 5 μ /1) hearts from aging and adult Fischer 344 rats were subjected to stop-flow ischemia for either 2, 5, 10, 15 or 25 min after a 15 min equilibration phase. ADO and hypoxanthine (HX) were measured by HPLC. Tissue total adenylates, ATP, glycogen and lactate were measured. Ischemia Pre-ischemia 2 min 5 min 10 min 15 min 25 min (n = 5) (n = 5) (n = 5) (n = 5) (n = 5) (n = 5) ADO 6 mo 0.2 ± 0.1 0.7 ± 0.1 0.7 ± 0.1 2.2 ± 0.2 37 ± 0.6 4.5 ± 0.3 24 mo 0.2 ± 0.1 05 ± 0.1 0.3 ± 0.1 * 1.1 ± 0.3 * 2.1 ± 0.3 * 3.5 ± 0.4 HX 6 mo 2.0 ± 0.2 1.6 ± 0.2 2.3 ± 0.3 2.2 ± 0.1 25 ± 0.2 2.8 ± 0.2 24 mo 1.9 ± 0.2 1.4 ± 0.1 1.4 ± 0.2 * 2.1 ± 0.2 2.2 ± 0.8 3.5 ± 0.3 (Mean ± SE, nmol/mg protein) * p < 0.05 vs 6 mo ADO levels were 50% lower in the aging heart at 5 and 10 min, remained depressed at 15 min and had not fully equalized to adult levels by 25 min of ischemia. HX was decreased at 5 min, consistent with decreased ADO production at that time. The change in total adenylate pool was similar in both groups. The decrease in tissue glycogen and increase in lactate were similar during ischemia in both groups, suggesting comparable glycolytic activity. ATP levels were decreased in aging hearts at 5 min (11.1 ± 2.3 vs 18.7 ± 1.9 nmol/mg protein), but reached levels similar to adult hearts as ischemia progressed. Thus, decreased ADO levels during early ischemia may reflect reduced production of ADO in the aging heart, and increase the susceptibility of the aging heart to damage during ischemia and reperfusion.
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