Nicorandil, a Hybrid Between Nitrate and ATP-Sensitive Potassium Channel Opener, Preconditions Human Heart to Ischemia During Percutaneous Transluminal Coronary Angioplasty

Takenori Yasuda, MD; Kazuhiko Hashimura, MD; Yasuhiko Matsu-ura, MD; Yoji Kato, MD; Tetsuya Ueda, MD; Isao Mori, MD; Yoshiyuki Kijima, MD*

Abstract
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 i n flations 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 (6mg/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 -98.0±37.3%, p<0.01). The ratio of the sum of the ST elevation in the precordial leads during the second inflation (·ST-2, 0.94±0.66mV) to that during the first inflation (·ST-1, 1.43±1.17mV) 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±41.6 vs LERpost-2, -43.5±51.1%; ·ST-1, 1.38±0.80 vs ·ST-2, 1.46±0.90mV). 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±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.
(Jpn Circ J 2001; 65: 526 -530)

Key Words: ATP-sensitive potassium channel; Ischemic preconditioning; Nicorandil; Percutaneous transluminal coronary angioplasty

Mailing address: Yoshiyuki Kijima, MD, PhD, Department of Cardiology, Higashi-osaka City General Hospital, 3-4-5 Nishi Iwata Higashi-osaka, Osaka 578-8588, Japan. E-mail: ykijima@yo.rim.or.jp