The present study was undertaken to determine whether beraprost, a stable prostacyclin-mimetic agent, may exert a beneficial effect on post-hypoxic recovery of cardiac function and metabolism. Isolated rabbit hearts were perfused by the Langendorff method for 20 min under glucose-free hypoxic conditions, followed by 45 min reoxygenation in the presence of glucose, and their functional and metabolic changes with or without beraprost-treatment were examined. 2. Hypoxic insult induced cessation of cardiac contractile force, depletion of myocardial high-energy phosphates, accumulation of tissue calcium, and release of creatine kinase and ATP metabolites. Subsequent reoxygenation resulted in a poor recovery of cardiac contractile force (less than 10% of the pre-hypoxic value), a poor restoration of high-energy phosphates, and increase in calcium content. A further release of creatine kinase and ATP metabolites from the heart was observed during reoxygenation. 3. Treatment with 0.45 microM beraprost during the whole hypoxic period resulted in a significant suppression of the increase in tissue calcium, and the release of creatine kinase and ATP metabolites during hypoxic perfusion. This treatment also elicited a significant post-hypoxic recovery of the cardiac contractile force and the tissue high-energy phosphates. Reoxygenation-induced release of creatine kinase and ATP metabolites was also prevented by treatment with beraprost. 4. When hearts were treated with prostacyclin sodium (0.50 microM) in the same manner for the purpose of comparison, similar improvement of post-hypoxic contractile and metabolic recovery were observed. 5. These results demonstrate that treatment with either beraprost or prostacyclin is beneficial for post-hypoxic recovery of cardiac function and metabolism. Since the observed effects on post-hypoxic contractile recovery were exerted at a concentration of approximately 0.50 microM of these agents (a concentration far from the physiological range) the underlying mechanism appears to be different from the physiological action of prostacyclin.
