Sarcolemmal permeability changes during ischaemia and reperfusion: release of survival factors

Abstract

Enzyme release by ischaemic myocardium has been used as a hallmark of the infarction process for several decades: in the clinical setting, deterioration of cell membrane integrity, as evidenced by the release of macromolecules such as creatine kinase and lactate dehydrogenase, has been used as quantitative indication of myocardial infarction. Leakage of membrane-impermeable molecules due to sarcolemmal rupture is considered to be the most prominent feature of irreversible injury, and the main mechanisms proposed to underlie this phenomenon are energy deficiency and calcium overload.1,2 However, changes in sarcolemmal permeabililty have been demonstrated to occur after exposure of the heart to relatively short periods of ischaemia. Using NMR spectroscopy, Askenasy et al. 3 showed that sarcolemmal integrity deteriorated as a function of the duration of ischaemia and that even after as short a period as 10 min ischaemia cellular membrane permeability to osmolytes increased, although myocytes remained impermeable to polar and large molecules. Interestingly, before the onset of irreversible injury, enzyme release by the ischaemic perfused heart can be manipulated by the substrate present: for example, glucose reduces fatty acid-induced enzyme release, possibly via provision of glycolytic ATP.4,5 With the discovery of the phenomenon of ischaemic pre-conditioning, attention was again drawn to the potential of the myocardium to release a variety of substances (autocoids) after exposure to very short periods of ischaemia and reperfusion (e.g. 5 min), which may have either beneficial or detrimental effects on the heart. However, the causal stimulus for and the … *Corresponding author. Tel: +27 21 938 9391; fax: +27 21 938 9476. E-mail address : alo{at}sun.ac.za