Mechanisms of ischemic injury in the heart

Cardiac ischemia is characterized by rapid deterioration of cardiac function, which has been linked to the fall in intracellular pH, increased levels of inorganic phosphate and reduction in free energy change of ATP-hydrolysis. Biochemical events responsible for irreversible myocardial injury involve various mechanisms which change the properties of the cardiac cell membrane (disorders in lipid metabolism, free radical formation). Recent evidence suggests that in the heart, xanthine oxidase is a major source of free radical formation. During ischemia, adenine-nucleotide breakdown in the cardiomyocyte proceeds only to the stage of inosine. Due to the localisation of nucleoside phosphorylase and xanthine-oxidase in vascular endothelium, further degradation of inosine to hypoxanthine, xanthine and uric acid occurs predominantly in the vascular space. It is therefore conceivable that the primary site of reperfusion injury in the ischemic heart may be the coronary endothelium damaged by free radicals.