title: Dose-dependent prophylactic effect of nicorandil, an ATP-sensitive potassium channel opener, on intra-operative myocardial ischaemia in patients undergoing major abdominal surgery.
abstract: Nicorandil, a nicotinamide nitrate derivative, relaxes vascular smooth muscle and reduces cardiac muscle contractility by increasing membrane potassium conductance, probably by activating ATP-sensitive potassium channels. In this prospective, randomized, double-blind, placebo-controlled clinical study, we examined the dose-dependent prophylactic effect of nicorandil on intra-operative myocardial ischaemia in 248 patients who had pre-operative risk factors for ischaemic heart disease and were undergoing major abdominal surgery. Patients in group HD (n=81) received a bolus dose of nicorandil 0.08 mg kg(-1) and a continuous infusion of 0.08 mg kg(-1) h(-1). Patients in group LD (n=87) received nicorandil 0.04 mg kg(-1) and 0.04 mg kg(-1) h(-1). Patients in the placebo (P) group (n=80) received the same volumes of saline. The patients were monitored with a three-lead clinical ECG monitor with an ST trending device from arrival in the operating theatre to the end of anaesthesia. Intra-operative myocardial ischaemia occurred significantly less frequently in the HD group (one patient, 1.2%) than in the LD (11 patients, 12.6%) and P groups (21 patients, 26.3%) (P<0.01), and in group LD significantly less than in group P (P<0.05). Administration of nicorandil had little effect on the patients' heart rate or arterial pressure. Three patients in group P and none in either treatment group developed myocardial infarction after surgery.
authors.affiliation: Department of Anesthesiology, Tokyo Medical and Dental University, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Kaneko
authors.forename: Y
authors.initials: Y
authors.lastname: Saito
authors.forename: Y
authors.initials: Y
authors.lastname: Hikawa
authors.forename: K
authors.initials: K
authors.lastname: Yasuda
authors.forename: K
authors.initials: K
authors.lastname: Makita
mesh_terms: D000005:Abdomen / Q000601:surgery; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D007431:Intraoperative Complications / Q000517:prevention & control*; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000517:prevention & control; D017202:Myocardial Ischemia / Q000517:prevention & control*; D020108:Nicorandil / Q000627:therapeutic use*; D011183:Postoperative Complications / Q000517:prevention & control; D011446:Prospective Studies; D012307:Risk Factors; D014665:Vasodilator Agents / Q000627:therapeutic use*
chemical_list: D000959:Antihypertensive Agents; D014665:Vasodilator Agents; D020108:Nicorandil