Beneficial effect of YM-12617, a new adrenoceptor alpha-1 blockerl on hypoxia-induced cardiac contractile failure

The present study was designed to determine whether 1-form of YM-12617, a new adrenoceptor alpha-1 blocker, may prevent hypoxia-induced cardiac contractile failure. Hypoxic perfusion of isolated rabbit hearts for 25 min induced cessation of cardiac contractile force, depletion of myocardial high-energy phosphates and, release of creatine kinase and ATP metabolites from the heart. Subsequent reoxygenation of hearts for 45 min resulted in little recovery of cardiac contractile force and myocardial high-energy phosphates and appreciable accumulation of tissue calcium. Administration of YM-12617 at the infusion rate of 200μg/min during the hypoxic period resulted in a significant recovery of cardiac contractile force and myocardial high-energy phosphates at 45 min-reoxygenation. The release of creatine kinase and ATP metabolites from the perfused heart and the accumulation of tissue calcium were also depressed by the treatment with the agent. The results suggest that YM-12617 is capable for protecting the myocardium from oxygen deficiency-induced derangement in cardiac function and energy metabolism.