Both microvascular damage and myocardial cell injury occur after coronary occlusion, but the relationship of these two events is unclear; specifically, it is unknown whether microvascular damage causes myocardial cell injury. Dogs were subjected to coronary occlusion for 20, 40, 60, 90 or 180 minutes, after which subendocardial and subepicardial biopsies were obtained for electron and light microscopy of 1-mu sections. Of 312 biopsies of ischemic myocadium, 181 showed myocardial cell injury with no microvascular damage; 131 showed myocardial cell injury and microvascular damage; but none showed microvascular damage without myocardial cell injury. Although ultrastructural evidence of myocardial cell damage was present in the subendocardium after 20-40 minutes of ischemia, ultrastructural evidence of microvascular damage was not prominent until 60-90 minutes after coronary artery occlusion. Morphologic ultrastructural evidence of microvascular damage lagged behind myocardial cell injury, suggesting that ultrastructural microvascular damage is not a primary cause of ultrastructural myocardial cell injury.

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...

Pyruvate protects myocardium from ischemic and anoxic injury, effects that have been attributed to beneficial metabolic alterations. Pyruvate also reacts with hydrogen peroxide in vitro, and pyruvate prevents free radical injury in other organs. Hearts supplied with 2 mM of pyruvate with glucose during reperfusion recovered significantly more mechanical function (81%) than those provided with 2 mM of acetate (which does not react with free radicals) and glucose (49%) or glucose alone (27%). Pyruvate significantly reduced free radical generation during reperfusion as measured with electron spin resonance using the spin-trap 5,5-dimethyl-1-pyrroline-1-oxide. In a model of direct oxidant stress, hearts were perfused with 0.28 mM of hydrogen peroxide. In this model, loss of function was almost entirely prevented by addition of 2 mM of pyruvate. From these results we conclude an important mechanism of protection when pyruvate is supplied during reperfusion is limitation of oxygen-derived free radical damage.

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