Controlled nicorandil administration for myocardial protection during coronary artery bypass grafting under cardiopulmonary bypass

Nicorandil is a hybrid potassium channel opener, and recent experimental studies have demonstrated its efficacy in myocardial protection against ischemia-reperfusion. This clinical study was designed to examine the myocardial protective effect of nicorandil administered during cardiopulmonary bypass. Seventy adult patients, 53 men and 17 women, undergoing elective coronary artery bypass grafting were randomly assigned to two groups, one receiving nicorandil during cardiopulmonary bypass (group N, n = 35) and the other receiving no nicorandil for control (group C, n = 35). Nicorandil was administered at each dose of 0.1 mg/kg into the cardiopulmonary bypass circuit according to the following schedule: (1) bolus injection at the initiation of cardiopulmonary bypass, (2) continuous infusion for 5 min before aortic cross-clamping, (3) bolus administration at 5 min before reperfusion, and (4) continuous infusion for 5 min before reperfusion. The time required for achieving cardiac arrest after the initial cardioplegia was significantly reduced in group N in comparison with that in group C. After aortic unclamping, the number of patients showing a significant ST segment change on the electrocardiogram was significantly fewer in group N, whereas the number of patients showing spontaneous recovery of heart beat was significantly greater. As for the myocardial protective effect, group N showed lower plasma levels of malondialdehyde, human-heart fatty acid-binding protein, and peak creatine kinase-MB, and required lower doses of catecholamine. Our results suggest that nicorandil administration during cardiopulmonary bypass provides enhanced myocardial protective effects against ischemia-reperfusion in patients undergoing coronary artery bypass grafting.