ENHANCEMENT OF CARDIAC-FUNCTION BY CYCLOCREATINE IN MODELS OF CARDIOPULMONARY BYPASS

This study tests the hypothesis that the administration of cyclocreatine prior to global ischemia enhances recovery of cardiac function during reperfusion. Two models were used. First, in a Langendorff-working heart model of normothermic cardioplegic arrest, rats (n=6 per group) were injected intravenously with saline or cyclocreatine (600, 300, or 150 mg/kg). After 30 min or 2 h, hearts were excised and perfused in the Langendorff mode for 5 min and then in the working heart mode for 20 min. Normothermic arrest was induced by infusing warm St, Thomas solution once; then hearts were kept at 37 degrees C for 40 min. Following arrest, hearts were reperfused in the Langendorff mode for 15 min and then in the working mode for 30 min. Cyclocreatine consistently produced significantly better recovery of aortic now and cardiac output compared to that of saline hearts. Second, in an intact canine model of cold cardioplegic arrest, adult mongrel dogs (n=3 to 6 per group) underwent aortic cross-clamping for 1 h, followed by reperfusion on bypass for 45 min and off bypass for 4 h. Dogs were injected intravenously with saline or cyclocreatine (500 mg/kg) for 1 h before experiment. Post-bypass segmental contractility and cardiac output were significantly better in cyclocreatine hearts compared to that of controls. In a limited study, after a 3 h aortic cross-clamp time, cyclocreatine hearts achieved 91% baseline function while control hearts failed after 2 h, Results of this study suggest that cyclocreatine, without inotropic or chronotropic effect, protects the heart from global ischemic injury.