Beneficial effect of beraprost, a prostacyclin‐mimetic agent, on post‐hypoxic recovery of cardiac function and metabolism in rabbit isolated hearts

Abstract

1 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 pM 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 (0.50uM) 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 posthypoxic recovery of cardiac function and metabolism. Since the observed effects on post-hypoxic contractile recovery were exerted at a concentration of approximately 0.50pM of these agents (a concentration far from the physiological range) the underlying mechanism appears to be different from the physiological action of prostacyclin.

Effects of beraprost on the transmembrane potentials of guinea‐pig ventricular muscles during normoxia and hypoxia‐reoxygenation

“…Although the concentrations of beraprost (0.1 to 1 ytmol 1') which induced significant cardioprotective effects seem to be higher than those of prostacyclin released during acute myocardial ischaemia determined in the blood from coronary vein (Coker et al, 1981), the concentration in the ischaemic tissue might be much higher. However, it cannot be denied that the effects of beraprost were only demonstrated at pharmacological concentrations and this does not suggest a physiological role for prostacyclin in the ischaemic heart, which confirms the original findings of Tanonaka et al (1991).…”

“…improvement of the recovery of cardiac function. Furthermore, even under conditions with severe damage to cardiac contractile function and metabolism, treatment with beraprost was shown to be beneficial for post-hypoxic recovery of cardiac function (Tanonaka et al, 1991), although these workers only investigated the release of ATP metabolites. Therefore, the cardioprotective effects of beraprost during reoxygenation may have resulted from some mechanisms which spare ATP consumption during hypoxia.…”

Improvement of exercise capacity of rats with chronic heart failure by long‐term treatment with trandolapril

“…High‐energy phosphates and energy metabolites in the gracilis muscle of rats with CHF and sham‐operated rats with and without exercise were extracted with a solution containing 0.3 N perchloric acid and 0.25 m M EDTA as described previously ( Tanonaka et al ., 1991 ). The resultant supernatant fluid was sampled for determination of tissue ATP, CP, lactate and pyruvate contents.…”