Defects in Mitochondrial Oxidative Phosphorylation in Hearts Subjected to Ischemia-Reperfusion Injury

Abstract

Although several studies have shown impairment of mitochondrial respiratory and oxidative phosphorylation activities in the ischemic-reperfused (I/R) hearts, the mechanisms of these alterations are not fully understood. Recently, we have shown that the I/R-induced changes in mitochondrial function were attenuated by an oxyradical scavenging system or antioxidants such as N-acetyl-l-cysteine and N-(2-mercaptopropionyl)-glycine. On the other hand, perfusion of hearts with an oxyradical generating system or H2O2, a well known oxidant, simulated the I/R induced mitochondrial dysfunction. Furthermore, intracellular Ca2+-overload induced by perfusing the Ca2+-depleted hearts with Ca2+-containing medium produced changes in mitochondrial respiratory and oxidative phosphorylation activities similar to those seen due to I/R injury. Mitochondrial dysfunction was also observed upon incubating these organelles with high concentrations of Ca2+. These observations support the view that mitochondrial dysfunction with respect to energy production due to I/R injury, occurs as a result of oxidative stress and intracellular Ca2+-overload. It is also evident that mitochondrial alterations in the I/R hearts lead to the depletion of high-energy phosphate stores and thus may play a critical role in the development of cardiac dysfunction.