Ultrastructural alterations to myocytes and associated microvascular functional changes at lateral margins of developing experimental myocardial infarcts

Abstract

Knowledge of the temporal and spatial patterns of development of irreversible injury at the margins of regional myocardial infarcts is a prerequisite for assessment of interventions aimed at preventing the transition from reversible to irreversible injury of myocytes. Regional ischaemia was modelled in 20 isolated rabbit hearts by ligation of the ventral interventricular branch of the left coronary artery for 0-240 min prior to perfusion fixation of the entire heart. Transmural blocks of fixed myocardium spanning the margins of the ischaemic region were cryofractured, freeze-dried, and fracture faces up to 1 cm2 examined by scanning electron microscopy (SEM). Evidence of irreversible injury was seen in the subendocardium by 60 min, with extension to epicardium by 120 min. No progression was seen at lateral margins, which showed a cell-to-cell demarcation of morphologically normal areas and severely injured myocardium. A very narrow discontinuous zone (less than or equal to 150 microns wide) at lateral margins showed less severe changes. Provided this zone does not advance with time, ischaemic myocardium potentially "salvageable" by reperfusion appears confined to the subepicardial zone in rabbit hearts. The advantages of SEM in assessing the extent of ischaemic injury are compared with those of previously utilised morphologic methods.