Propranolol effects on myocardial ultrastructure and high energy phosphates in anesthetized dogs subjected to ischemia and reperfusion

Abstract

The effects of propranolol (1–5 mg/kg) on the ultrastructure and high energy phosphate content of dog myocardium were investigated after 2 h of ischemia and 2 h of reperfusion. Two adjoining major ventricular branches of the left circumflex coronary artery were occluded to produce ischemia. Propranolol was administered intravenously just before occlusion of the coronary arteries in all the experiments. Two hours of ischemia caused structural changes and significantly reduced creatine phosphate (CrP) and ATP contents, and increased AMP levels. Propranolol (5 mg/kg) had no effect on these ischemic changes.Propranolol was found to protect the myocardium from structural damage usually observed after 2 h of reperfusion. The size and number of amorphous electron-dense mitochondrial granules, which are considered to contain calcium, observed after reperfusion, were reduced in propranolol-treated animals. Stores of ATP and total nucleotides (ATP + ADP + AMP), and the ATP:AMP ratio were significantly higher in propranolol (5 mg/kg) treated dogs in comparison with the untreated controls after 2 h of reperfusion. There was, however, no difference between the CrP levels of propranolol-treated and untreated preparations. The study shows that propranolol is effective in reducing the reperfusion-dependent changes in ischemic myocardium. Reduction in the intracellular calcium overload as well as maintenance of the structural integrity of the cell, particularly that of mitochondria, may be involved in these protective effects of propranolol.