Transmural cellular damage and blood flow distribution in early ischemia in pig hearts

Abstract

Transmural histological changes were determined morphometrically in the left ventricular free wall of 20 pigs after ligation of distal left anterior descending coronary artery for 10, 20, 40, and 120 minutes. Hemodynamics were recorded and regional blood flow distribution was measured in the ischemic zone. Coronary occlusion produced regional transmural ischemia without producing significant systemic hemodynamic change. The microsphere blood flow technique revealed that blood flow was less than 0.05 ml/min per g in all layers of the ischemic zone, i.e., inner, middle, and outer thirds. Ischemic cellular damage was classified and quantified from grade 0 to grade 5 (0 being normal and 5 being the most severe damage) with light microscopy and confirmed by electron microscopy. Layers of 200 μm immediately beneath the endocardium and epicardium showed minimal ischemic damage of less than grade 1.4 regardless of duration of ischemia in all hearts. In the ischemic left ventricular wall, except for the above layers, a definite transmural gradient of the cellular damage existed from the inner third (grade 2.3 ± 0.1) to the outer third (grade 1.3 ± 0.2) at 20 minutes of ischemia and at 40 minutes of ischemia (grades 3.6 ± 0.1 and 1.9 ± 0.3, respectively). The transmural ischemic damage gradient disappeared at 120 minutes of ischemia, where the inner and outer third ischemic grades were both 5.0 ± 0.1. The data suggest that the limited ischemic damage which occurs in the few cell layers beneath endocardium and epicardium may be explained by regional collateral blood flow. An early ischemic damage wavefront phenomenon does exist in the pig myocardium and is independent of myocardial blood flow and its distribution. The transmural cell damage gradient may be the result of transmural gradients of wall stress and intramyocardial pressure in vivo. Therefore, it appears that factors other than blood flow are the major determinants of ischemic cellular damage in the left ventricular wall of hearts lacking a collateral blood supply.