ABSTRACT
Oxidative damage of the isolated perfused rat heart was caused by addition of 90 microM H2O into Krebs-Henseleit solution. After 20 min of H2O2 addition an elevation of diastolic pressure (irreversible contracture) was observed followed by decrease of developed tension and heart work. Addition of phosphocreatine (10 mM) at constant total sodium concentration prevented the development of contracture and diminished the decrease of cardiac work. This protective effect is probably related to the elevation of structural order of phospholipids by phosphocreatine.
Subject(s)
Heart/drug effects , Hydrogen Peroxide/toxicity , Myocardial Reperfusion Injury/prevention & control , Phosphocreatine/therapeutic use , Animals , Drug Evaluation, Preclinical , Heart/physiopathology , In Vitro Techniques , Male , Microscopy, Electron , Myocardial Contraction/drug effects , Myocardial Contraction/physiology , Myocardial Reperfusion Injury/pathology , Myocardial Reperfusion Injury/physiopathology , Myocardium/ultrastructure , Perfusion/methods , Rats , Rats, Inbred StrainsABSTRACT
To study the character of the mechanism of protective action of phosphocreatine on ischemic myocardium the effects of phosphocreatine (PCr) and phosphoarginine (PArg) were compared. PCr and PArg were shown to expose identical Ca2+-chelating properties and were used as their Na-salts. Only PCr protected the cardia function during ischemia and simultaneously inhibited the accumulation of lysophosphoglycerides, products of phospholipid degradation. PArg failed to exert both of these effects. By an EPR probe method PCr was shown to increase the order of structural organization of phospholipids in the cardiac sarcolemmal vesicles. The results show that the effect of PCr on ischemic myocardium is not due to nonspecific changes in the ion composition of a solution, but most probably due to highly specific effect of phosphocreatine on the phospholipid membrane of the cardiac cells sarcolemma.