Abstract
Changes in myocardial purine metabolism were studied after temporary coronary artery occlusion and subsequent reperfusion in the dog. Sequential myocardial biopsies were performed to allow for measurements of ATP, adenine nucleotide, nucleoside, and base concentrations after 15 min of ischemia, and after 90 min and 72 hr of reperfusion following this period of ischemia. Control, nonischemic sites were also sampled. After 15 min of coronary occlusion, subendocardial ATP concentrations (reported in nmol/mg of protein; mean +/- SEM) were depressed in the ischemic zone at 19.9 +/- 3.5 compared to 38.1 +/- 2.8 in the nonischemic zone (P < 0.001). Subepicardial ATP concentrations also were depressed at 27.0 +/- 2.2 in ischemic sites compared to subepicardial nonischemic sites (40.0 +/- 4.0, P < 0.005). After 90 min of reperfusion ATP concentrations remained depressed in the previously ischemic subendocardium 26.8 +/- 4.2 (P < 0.025 vs. nonischemic sites). After 72 hr of reperfusion, ATP was still depressed in the previously ischemic subendocardium at 29.2 +/- 2.5 (P < 0.025 vs. nonischemic) and subepicardium (27.9 +/- 3.3, P < 0.05 vs. nonischemic). Total purines were determined as the sum of ATP, ADP, AMP, adenosine, inosine, and hypoxanthine. After 15 min of occlusion, the total purine pool in the ischemic subendocardium tended towards being lower than in the nonischemic zone (42.0 +/- 5.9 vs. 53.8 +/- 5.2, not significant) but in the ischemic subepicardium the total purine pool was similar to that in the nonischemic zone. After 90 min of reperfusion the previously ischemic subendocardial purine pool was reduced compared to the nonischemic zone (39.0 +/- 4.8, P < 0.025). Total purines were also depleted in both the subendocardium and subepicardium of previously ischemic zones after 72 hr of reperfusion (44.5 +/- 2.9 and 40.0 +/- 4.4, respectively, P < 0.05). Histologic analysis of the previously ischemic tissue revealed no evidence of necrosis. Therefore, brief temporary coronary artery occlusions not associated with anatomic evidence of necrosis may result in prolonged abnormalities of ATP concentration and significant depletion of the total purine pool.
MeSH Terms
Adenosine Diphosphate/analysis
Adenosine Monophosphate/analysis
Adenosine Triphosphate/analysis
Animals
Biopsy
Dogs
Hypoxanthines/analysis
Inosine/analysis
Myocardial Infarction/metabolism,pathology
Myocardium/metabolism,ultrastructure
Necrosis/pathology
Purines/metabolism
Chemicals
Hypoxanthines
Purines
Adenosine Monophosphate
Inosine
Adenosine Diphosphate
Adenosine Triphosphate
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
DeBoer L W
Ingwall J S
Kloner R A
Braunwald E
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