Nicorandil, a hybrid between nitrate and ATP-sensitive potassium channel opener, preconditions human heart to ischemia during percutaneous transluminal coronary angioplasty

The human heart progressively becomes more tolerant to ischemia after repeated balloon inflations during percutaneous transluminal coronary angioplasty (PTCA). The present study investigated whether nicorandil, a hybrid between nitrate and an ATP-sensitive potassium channel opener, affects this ischemic preconditioning. Sixteen patients with stable angina pectoris caused by left anterior descending artery lesions were subjected to 2 balloon inflations of 2-min duration with a 3-min reperfusion period. Seven of these patients served as the control group and in the remaining 9 patients, nicorandil was administered intravenously (6 mg/h) throughout the PTCA procedure (nicorandil group). The lactate extraction ratio (LER) was obtained at 30s after each ischemic event (LERpost-1 and LERpost-2) in both groups. In the control group, LERpost-1 was more negative than LERpost-2 (-185.7 +/- 74.2 vs -98 +/- 37.3%, p < 0.01). The ratio of the sum of the ST elevation in the precordial leads during the second inflation (<Sigma>ST-2, 0.94 +/- 0.66 mV) to that during the first inflation (Sigma ST-1, 1.43 +/- 1.17 mV) was 0.72 +/- 0.16 in the control group; which was less than the ratio in the nicorandil group (1.06 +/- 0.13, p < 0.01). Nicorandil abolished the difference between the 2 ischemic events (LERpost-1, -45.1 <plus/minus> 41.6 vs LERpost-2, -43.5 +/- 51.1%; Sigma ST-1, 1.38 +/- 0.80 vs Sigma ST-2, 1.46 +/- 0.90 mV). LER was less negative in the nicorandil group than that in the control group (LERpost-1, -45.1 +/- 41.6 vs -185.7 +/- 74.2%, p < 0.01; LERpost-2, -43.5 <plus/minus> 51.1 vs -98.0 +/- 37.3%, p < 0.05). Thus, nicorandil improved lactate metabolism during PTCA without significantly influencing ST-elevation In conclusion, intravenous pre-administration of nicorandil appears to precondition the human heart during PTCA.