Prolonged depletion of ATP because of delayed repletion of the adenine nucleotide pool following reversible myocardial ischemic injury in dogs.

Abstract

Sixty-five percent of the ATP and 50% of the total adenine nucleotide (sigma Ad) pool is lost from the subendocardial myocardium after 15 min of severe ischemia induced by circumflex artery occlusion in open-chest dogs (12). In the present experiment, we assessed the effects of various periods of arterial reflow following 15 min of ischemic injury on resynthesis of ATP and sigma Ad. The circumflex artery was occluded for 15 min and reperfused for 20 or 60 min or 24 or 96 hr. The mean ATP after 15 min of ischemia was reduced 62% from 5.42 +/- 0.33 to 2.08 +/- 0.21 mumol/g; and the total nucleotide content was reduced by 50%. ATP content recovered slightly during the first 20 min of reperfusion but remained markedly depressed for at least 24 hr because of the initial depletion of adenine nucleotides and because minimal salvage of de novo repletion occurred in the injured muscle during this time period. By 4 days, ATP and total adenine nucleotides were still slightly depressed but had recovered to 88% and 91% of control. Electrolyte changes and an increased inulin-diffusible space, which are characteristic of irreversibly injured myocardium, reperfused for 20 or 60 min, were not observed. Also, tissue necrosis was absent in the hearts reperfused for 24 or 96 hr. These observations indicate that the marked depression of ATP and adenine nucleotides and the slow recovery of these metabolites occurred in myocardium that nevertheless was reversibly injured in terms of cellular viability.