Ultrastructural evaluation of postischemic cell death (lethal reperfusion injury) in porcine hearts

Abstract

This study investigated whether reperfusion results in an increase of ultrastructurally determined myocardial injury in pig hearts. The left anterior descending coronary artery (LAD) was distally occluded in 12 pigs for 35–45 minutes and then reperfused for 3 hours. At the end of ischemia, as well as after 3 hours of reperfusion, one transmural biopsy was removed from the center of the risk region and subdivided into four specimens, representing the subendocardial (I), subendo-midmyocardial (II), subepi-midmyocardial (III), and subepicardial layers (IV). The degree of injury was assessed by electronmicroscopy and was scored as reversible (1), an almost equal mixture of reversible and irreversible (2), and totally irreversible (3) damage. In addition, infarct size was determined as the ratio of infarcted (tetrazolium stain) to ischemic (dye technique) myocardium. Infarct sizes ranged from 29.3% to 93% (mean 61.2%). The scores of injury of the four tissue layers before and after reperfusion did not differ significantly: layer I, 2.4 ± 0.8/2.3 ± 0.9; layer II, 2.2 ± 0.9/2.0 ± 0.9; layer III, 1.8 ± 0.9/2.0 ± 0.9; and layer IV, 1.6 ± 0.9/1.3 ± 0.6. The means of the four layers were almost identical at the end of ischemia (2.1 ± 0.8) and after 3 hours of reperfusion (2.0 ± 0.6). A linear regression analysis with 95% confidence limits of the score values before and after reperfusion indicated that maximally 25% of a mean final infarct size of about 50% may be due to lethal reperfusion injury. This study suggests that cell death in regional ischemia and reperfusion occurs predominantly during ischemia and not during reperfusion.