Ultrastructural assessment of myocardial necrosis occurring during ischemia and 3-h reperfusion in the dog

To determine whether myocardial necrosis may occur during postischemic repe rfusion, electron microscopy was used to identify morphological features of irreversible injury in myocardial samples taken from anesthetized dogs wit h 90-min ischemia and 0-, 5-, 90-, or 180-min reperfusion. In samples witho ut detectable collateral blood flow, necrosis was almost complete, whether or not the myocardium was reperfused. In samples with collateral flow, necr osis was more frequent after 180-min reperfusion than in the absence of rep erfusion, despite similar collateral flows in the two groups. Excess of nec rosis after 180-min reperfusion was evident in endocardium (ischemia only: 4 of 13, 180-min reflow: 14 of 20; P = 0.03) and midwall (ischemia only: 9 of 25, 180-min reflow: 29 of 45; P = 0.02). Multiple logistic regression wi th variables of collateral flow and transmural position was used to determi ne risk of irreversible injury in 111 samples from ischemic myocardium with out reperfusion (model predictive accuracy = 75%, P < 0.00001) and to predi ct risk of necrosis in myocardium reperfused for 180 min. Of 65 samples fro m endocardium and midwall with detectable collateral flow, the model predic ted necrosis in 23 samples but necrosis was observed in 43 samples (P < 0.0 1). Reperfusion duration was a determinant of frequency of irreversible inj ury. Multiple logistic regression for 186 samples from myocardium reperfuse d for 5, 90, or 180 min showed that reperfusion duration was an independent predictor of irreversible injury (P = 0.0003) when collateral flow and tra nsmural location were accounted for. These findings are consistent with the occurrence of necrosis during reperfusion in myocardium exposed to substan tial, prolonged ischemia but with sufficient residual perfusion to avoid ne crosis during the period of flow impairment.