Ischaemia-induced damage in the working rat heart preparation: The effect of perfusate substrate composition upon subendocardial ultrastructure of the ischaemic left ventricular wall

Abstract

Ultrastructural modifications occuring in the subendocardium of the severely ischaemic part of the left ventricular wall following left coronary artery ligation, were studied in isolated working rat hearts perfused with different substrates. Substrates used were: glucose, glucose plus albumin, palmitate bound to albumin, and palmitate-albumin together with glucose and/or insulin. Non-ischaemic control hearts perfused with glucose as substrate showed a typical morphology. In contrast, control hearts perfused with either glucose-albumin or palminate-albumin exhibited dilatations of most of the unspecialized regions of the intercalated discs. In ischaemic hearts marked ultrastructural modifications were observed; these included extensive intracellular oedema, altered myofibrils, tubular system and nucleus as well as glycogen depletion and mitochondrial swelling. These changes occurred with all substrates. Moreover, typical mitochondrial changes occured which appeared to be dependent upon the nature of the substrate. In palmitate-perfused hearts, amorphous electron dense opacities appeared within 47% of the mitochondria. Such opacities were never observed in glucose or glucose-albumin perfused hearts and their number was considerably reduced when glucose and/or insulin, but mainly glucose, was added to palmitate-albumin solutions. These findings illustrate that in isolated working rat heart ischaemia-induced ultrastructural damage can be partly determined by the nature of the substrate.