Possible involvement of membrane-stabilizing action in beneficial effect of beta adrenoceptor blocking agents on hypoxic and posthypoxic myocardium

S Takeo, H Yamada, K Tanonaka, M Hayashi and N Sunagawa

Department of Pharmacology, Tokyo College of Pharmacy, Japan.

The present study was designed to elucidate a possible involvement of membrane-stabilizing action of beta blocking agents in posthypoxic recovery of cardiac contractile function and myocardial metabolism. Propranolol and acebutolol, which possess a membrane-stabilizing action, and atenolol and metoprolol, which lack this action, were used in the isolated, perfused rabbit heart. The membrane-stabilizing effects of these agents were assessed on the basis of the effects on the maximal driving frequency of the left atria. Reoxygenation of hearts for 45 min following 20-min hypoxia resulted in little recovery of cardiac contractile force, sustained rise in resting tension, insufficient recovery of myocardial high-energy phosphates, accumulation of the tissue calcium and sodium and marked release of creatine kinase and ATP metabolites from the hearts. Treatment of hypoxic hearts with either 100 microM propranolol, 200 microM acebutolol, 200 microM atenolol or 100 microM metoprolol was commenced when the contractile force declined to 30% of the initial level and terminated at 20-min hypoxia. Treatment with either propranolol or acebutolol produced a significant posthypoxic recovery of cardiac contractile force, resting tension and myocardial high-energy phosphates, and a profound suppression of the tissue calcium and sodium accumulation and the loss of ATP metabolites from perfused hearts. In contrast, neither atenolol nor metoprolol affected these changes induced by the hypoxic insult and the following reoxygenation. The results suggest that membrane-stabilizing action of beta blocking agents plays an important role in the protection against posthypoxic cardiac contractile dysfunction and metabolic disturbances.

Volume 254, Issue 3, pp. 847-856, 09/01/1990
Copyright © 1990 by American Society for Pharmacology and Experimental Therapeutics

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