Cardioprotective effect of nicorandil in histidine-tryptophan-ketoglurate solution during the cold storage of isolated hearts

We compared the efficacy of using histidine-tryptophan-ketoglurate (HTK) solution with that of University of Wisconsin (UW) solution for heart preservation in an isolated rat heart preparation, Nicorandil (NCR) exerts its action as an ATP sensitive potassium channel opener at low extracellular potassium concentrations, and HTK solution has a low potassium concentration. Therefore, we also investigated the efficacy of using HTK solution with NCR following 12-hr preservation, Hearts isolated from male Wistar rats were mounted on a Langendorff apparatus to estimate baseline aortic flow (AF), coronary flow (CF), cardiac output (GO), heart rate (HR), systolic pressure (SP), aortic mean pressure, and the rate-pressure product (RPP). The hearts were divided into four groups: group 1, 8-hr storage in UW solution; groups 2 and 3, 8- or 12-hr storage in HTK solution, respectively; and group 4, 12-hr storage in HTK solution with NCR, They were arrested and stored at 4 degrees C in each preservation solution, Following storage, they were reperfused and postpreservative function was measured to assess cardiac functional recovery, Concentrations of creatine phosphokinase, troponin-T, and lactate in the coronary perfusate were measured. Frozen tissue samples from groups 3 and 4 were analyzed for adenylate content and cGMP. The myocardial water content was also measured. The recovery of AF, CF, CO, SP, and RPP in group 2 was significantly improved compared with that in group 1 (P<0.05), The recovery of AF, CF, CO and HR in group 4 was significantly better than that in group 3 (P<0.05). Creatine phosphokinase leakage in group 2 and troponin-T leakage in group 4 were significantly reduced (P<0.05 vs, groups 1 and 3, respectively). Total adenine nucleotides and the adenylate energy charge in group 4 were well sustained (P<0.05 vs, group 3), These results suggest that HTK solution is more effective than UW solution for cardiac preservation, and that NCR provides still better protection.