Prolonged derangements of canine myocardial purine metabolism after a brief coronary artery occlusion not associated with anatomic evidence of necrosis

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 b 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. It is generally assumed that the myocardium of patients who experience temporary myocardial ischemia, such as occurs in angina pectoris, and who recover from this event without developing electrocardiographic, enzymatic, or radioisotopic evidence of myocardial infarction, rapidly returns to normal. There are experimental studies that support this assumption. Thus, after temporary coronary artery occlusion in animals in which the myocardium is ischemic for less than 20 min, no necrosis develops when the coronary artery is released. Hence this myocardium has been considered to be reversibly injured (1). On the other hand, when the temporary coronary occlusion is maintained for a longer period of time (40-60 min), histologic evidence of necrosis develops in the subendocardium and, by definition, these cells may be considered to be irreversibly injured (1). Although brief coronary arter...

RETRACTED: Recovery from prolonged abnormalities of canine myocardium salvaged from ischemic necrosis by coronary reperfusion.

“…At 72 hr after release of a 15-min coronary occlusion, the ATP concentration in reperfused previously ischemic myocardium was significantly reduced (by 22% of normal), the percentage of systolic shortening of reperfused left ventricular segments was reduced (by 42% ofnormal), and ultrastructural abnormalities were present, despite the absence of necrosis (1,3). However, it was not known whether these changes ever were reversed to normal after longer periods of reperfusion and, if so, what the time course of the recovery is.…”

“…Previous studies from this laboratory have shown that brief (15 min) coronary occlusions followed by reperfusion do not cause necrosis but do result in prolonged abnormalities in myocardial biochemistry, function, and ultrastructure (1)(2)(3). At 72 hr after release of a 15-min coronary occlusion, the ATP concentration in reperfused previously ischemic myocardium was significantly reduced (by 22% of normal), the percentage of systolic shortening of reperfused left ventricular segments was reduced (by 42% ofnormal), and ultrastructural abnormalities were present, despite the absence of necrosis (1,3).…”

Myocardial reperfusion: a double-edged sword?

“…After 15 min of coronary occlusion, myocardial ATP concentration decreases substantially; it remains significantly depressed for many hours to days of reperfusion and usually returns to normal by 7 d (25,66,67). In other studies, creatine phosphate was shown also to fall markedly within minutes following coronary occlusion but to return to normal quite rapidly during coronary reperfusion.…”

“…In addition to the prolonged postischemic left ventricular dysfunction outlined above, biochemical abnormalities persist following reperfusion (66,67). After 15 min of coronary occlusion, myocardial ATP concentration decreases substantially; it remains significantly depressed for many hours to days of reperfusion and usually returns to normal by 7 d (25,66,67).…”

Noninvasive assessment myocardial viability: Current status and future directions

“…Based on experimental and clinical studies, the concepts of myocardial stunning [6][7][8][9][10] and hibernation [11][12][13] were developed and studied. Stunning refers to temporary depression of cardiac contraction following a bout of ischemia.…”