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Cardioprotective Effects of Nicorandil in Coronary Artery Bypass Graft Surgery
Shinichi Yamamoto, M.D.; Tatsuya Yamada, M.D.; Yoshifumi Kotake, M.D.; Ryoichi Ochiai, M.D.; Junzo Takeda, M.D.
Department of Anesthesiology, School of Medicine, Keio University, Tokyo, Japan
Short episodes of transient ischemia have been shown to protect the myocardium against future prolonged ischemia; a phenomenon known as ischemic preconditioning. Nicorandil is a hybrid drug that combines characteristics of nitrates and ATP-sensitive potassium channel activators. The ATP-sensitive potassium channel has been shown to be involved in myocardial preconditioning, and the beneficial effects of nicorandil for myocardial protection have been demonstrated experimentally, but there have been few clinical studies of nicorandil. In this study, we assessed whether intraoperative administration of nicorandil provides effective myocardial protection in patients undergoing coronary artery bypass surgery.

METHOD: After obtaining IRB approval and informed consent, 20 patients undergoing elective coronary artery bypass surgery were included in the study. Using a randomized, double-blind design, patients were assigned to receive nicorandil (nicorandil group; n=10) or normal saline (placebo group; n=10). The nicorandil group received a loading dose of 0.1mg/kg of nicorandil followed by a infusion of 0.1mg/kg/h until the end of surgery; the placebo group received a matching volume of normal saline. To record changes in levels of the cardiac isozymes Troponin T (TnT) and creatinine kinase-MB (CK-MB), blood samples were taken at the following five stages: 1) before cardiopulmonary bypass (CPB) (baseline), 2) immediately after CPB, 3) at the end of surgery, 4) 1POD, and 5) 3POD. Differences between baseline and the other stages were assessed with ANOVA, applying Bonferroni's correction. Differences between the two groups were evaluated using Student's t-test. A P value < 0.05 was considered significant.

RESULT: There were no differences between the groups in aortic clamp or CPB times, nor in duration of operation or anesthesia. TnT concentrations increased significantly from baseline to peak levels at 1 POD in both the placebo and nicorandil groups. The TnT concentrations increased significantly at the end of surgery and remained elevated at 3 POD. CK-MB concentrations significantly increased at the end of surgery and until 1 POD, with peak levels at 1 POD in both groups. Although there was no difference between groups in peak concentrations of CK-MB, peak TnT concentrations were significantly higher in placebo compared to the nicorandil group (0.42+0.29ng/ml vs. 0.18+0.07ng/ml, respectively; P=0.028).

CONCLUSION: Patients in the nicorandil group had lower concentrations of TnT following coronary artery bypass surgery. There was, however, no significant difference between the groups in CK-MB concentrations, which might be attributable to differences in the diagnostic sensitivity and specificity of TnT and CK-MB for myocardial infarction. Our results suggest that intraoperative administration of nicorandil may provide a degree of myocardial protection in coronary artery bypass surgery.

REFERENCES: 1) Am J Physiol Heart Circ Physiol 2001;280:H256, 2) Ann Thorac Surg 200;70:595, 3) Crit Care Med 2001;29:1880.

Anesthesiology 2002; 96: A162