The development and progression of myocyte injury at the margins of experimental myocardial infarcts

Abstract

Distinct differences in the extent and progression of the lateral and epicardial boundaries of evolving regional infarcts were demonstrated in isolated rabbit hearts. Ischemia was produced by interrupting (0-240 minutes) flow in the ventral interventricular branch of the left coronary artery, whilst the remainder of the heart was continuously perfused with oxygenated Krebs-Henseleit bicarbonate buffer. Perfusion fixed blocks were freeze-fractured then examined using back-scattered electron imaging in a scanning electron microscope. Control myocytes showed relatively smooth, continuous internal fracture faces. After 30 min of ischemia myocytes showed evidence of mild, probably reversible, injury in the form of prominence of pits and channels. Severe injury, characterized by separation of organelles and prominent intracellular spaces, developed after 60 or more min of ischemia, first in the subendocardial two thirds, and after 120 min across the full thickness of the ventricular wall. At the lateral margins of infarcts there was a distinct cell-to-cell boundary between control and severely injured myocytes, with only a few scattered mildly injured cells within 30 mu of the infarct. Although transmural progression of necrosis provides the potential for recovery of the external aspect of the myocardium in the ischemic zone by reperfusion, corresponding regions of salvageable myocytes at lateral infarct margins are very narrow.