Beneficial effect of amosulalol and phentolamine on post-hypoxic recovery of contractile force and energy metabolism in rabbit hearts.

1. The effects of phentolamine, an alpha-adrenoceptor blocking agent and amousulalol, an alpha 1 and beta-adrenoceptor antagonist on hypoxia-induced impairment in cardiac function and metabolism were examined using the isolated heart Langendorff preparation of the rabbit. 2. Hypoxia induced cessation of cardiac contractile force, a rise in resting tension, a decrease in myocardial high-energy phosphates, an increase in tissue calcium content and the release of ATP metabolites from the heart. Subsequent reoxygenation resulted in little recovery of cardiac contractile force, and there were further increases in tissue calcium content and in the release of creatine kinase from the heart. 3. Treatment of hypoxic hearts with either 83 microM phentolamine or 45 microM amosulalol resulted in a suppression of the rise in resting tension, the tissue calcium accumulation and the release of creatine kinase and ATP metabolites during hypoxia. This treatment also elicited significant recovery of cardiac contractile force, restoration of myocardial high-energy phosphates, suppression of the release of creatine kinase and the accumulation of tissue calcium during reoxygenation. Both 83 microM phentolamine and 45 microM amosulalol a significant prolongation of the effective refractory period of rabbit isolated atria. 4. Lower concentrations of phentolamine (16 microM) and amosulalol) (9 microM), which are sufficient to exert an alpha-adrenoceptor blocking action, did not elicit an appreciable effect on the post-hypoxic recovery of cardiac contractile force. 5. These results suggest that phentolamine and amosulalol are capable of protecting the myocardium from hypoxia-induced derangements in cardiac function and metabolism. This effect is probably attributable to their membrane stabilizing effect, rather than to their alpha-adrenoceptor blocking action.