Progression of myocardial necrosis during reperfusion of ischemic myocardium

Background - The occurrence of myocyte necrosis during reperfusion of ischemic myocardium is controversial. This study measured myocardial 2- deoxyglucose uptake, correlated with histology, to determine whether loss of viability occurred during reperfusion of ischemic myocardium. Methods and Results - In 12 anesthetized dogs, the left anterior descending coronary artery was occluded for 90 minutes before 4 hours reperfusion. Myocardial blood flow was measured by microspheres and the tracers ¹⁴C-2-deoxyglucose and ¹⁸F-2-deoxyglucose were injected intravenously after 5 and 180 minutes of reperfusion, respectively. After 240 minutes, the heart was stained with thioflavin-S (size of no-reflow zone) and triphenyl-tetrazolium chloride (TTC, extent of necrosis). Samples from normal, salvaged, and necrotic myocardium were counted for ¹⁴C- and ¹⁸F-2-deoxyglucose and microspheres. With the use of a three-compartment model of 2-deoxyglucose uptake, the rate constant k₃ for phosphorylation of ¹⁴C- and ¹⁸F-2-deoxyglucose was calculated for each sample. Viability was defined as k₃ ≤ 0.125 min^-1 (predictive accuracy 88% versus electron microscopy and 97% versus TTC). Among 58 samples from no-reflow regions, 97% were nonviable after 5 minutes of reperfusion (k₃=0.096 ± 0.027 min^-1). Among 164 samples from salvaged myocardium, 95% were viable after both 5 and 180 minutes of reperfusion (k₃=0.170 ± 0.056 min^-1 P<.01 versus no-reflow). Among 179 samples from infarcted myocardium, mean k₃ after 5 minutes of reperfusion was 0.184 ± 0.070 min^-1 and 65% of samples were viable, but after 180 minutes of reperfusion mean k₃ had decreased to 0.077 ± 0.032 min^-1 (P<.0001) and 98% of samples were nonviable. Conclusions - A large proportion of samples from infarcted myocardium are viable at the end of the ischemic period but lose viability during the first hours of reperfusion.