The transmural progression of the no-reflow phenomenon in globally ischemic hearts

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Abstract
A no-reflow phenomenon (NRP) develops in hearts subjected to global ischemia and prevents reperfusion of the subendocardial myocardium upon restoration of arterial supply. In the present study the transmural progression of the NRP across the left ventricular wall in globally ischemic rat hearts was quantitatively defined by using autoradiographic nuclear track emulsion (NTE) as an indicator of microvascular competence. Rat hearts were isolated and perfused for 10 min with oxygenated Krebs-Henseleit buffer, then were made completely globally ischemic for from 0 to 60 min and were maintained at 37°C. They were then fixed by perfusion with glutaraldehyde after which NTE was injected into the coronary arteries. Transverse sections through the left ventricles were examined by scanning electron microscopy using back-scattered electron imaging and the vessels in a standard transmural contiguous series of photomicrographs were classified according to whether they did or did not permit the flow of NTE. Non-ischemic control myocardium showed a mean proportion of filled vessels of 99.4±0.5% SD, and those subjected to 15 min of ischemia showed only a slight overall reduction. After 30 min of ischemia 96±3% of vessels in the subepicardial third could be reperfused, but the proportion progressively diminished across the myocardium to total no-reflow near the endocardium. From 45–60 min of ischemia the totally non-reperfusible region remained confined to the subendocardial third but there was a significant reduction in the proportion of reperfusible vessels in the subepicardial third to 40%±27%. Ischemia thus progressively reduces the capacity of myocardium to be reperfused. This reduction occurs across the entire width of the left ventricular free wall but develops more slowly and is less severe in the middle and outer thirds than in the subendocardium where the capacity for microvascular reperfusion is totally lost.