Progression of Myocardial Necrosis During Reperfusion of Ischemic Myocardium

Abstract

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 14 C-2-deoxyglucose and 18 F-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 14 C- and 18 F-deoxyglucose and microspheres. With the use of a three-compartment model of 2-deoxyglucose uptake, the rate constant k 3 for phosphorylation of 14 C- and 18 F-2-deoxyglucose was calculated for each sample. Viability was defined as k 3 ≥ 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 ( k 3 =0.096±0.027 min -1 ). Among 164 samples from salvaged myocardium, 95% were viable after both 5 and 180 minutes of reperfusion ( k 3 =0.170±0.056 min -1 P <.01 versus no-reflow). Among 179 samples from infarcted myocardium, mean k 3 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 k 3 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.