392 Vol.34 No.3/May 2014 日本臨床麻酔学会第 32 回大会シンポジウム日臨麻会誌 Vol.34 No.3, 392 396, 2014 長期予後を考えた周術期管理とは? 周術期虚血性心疾患とニコランジル * 木下浩之 [ 要旨 ] ニコランジル投与が狭心症患者の長期予後を改善することは周知の事実である. 一方で, ニコランジル周術期投与の有用性については, 数少ない臨床研究で検討されているにすぎない. その一つが, オフポンプ冠動脈バイパス手術患者に対し, ニコランジルを麻酔中から翌日まで投与し冠動脈再灌流 15 時間後の血液中マーカーなどを検討したものであり, もう一つは, 非心臓手術患者で手術中のニコランジル静注が術後 5 日間までの心血管イベントに及ぼす作用を検討したものである. しかし, これらの研究では, ニコランジル投与は周術期に軽度の有効性を示すにとどまっている. 今後, その理由を明らかにする必要があると考えられる. キーワード :ニコランジル, 虚血性心疾患, 周術期, 長期予後 Ⅰ 虚血性心疾患の予後とニコランジル 10 IONA The impact of nicorandil in angina Lancet 1 5,126 1 40mg 2 1.6 図 1 2005 Ishii Circulation 2 ST 368 12mg 5 2007 Kitakaze 276 24 0.067mg/kg 1.67 g/kg/min 50kg 3mg 5mg/ hr 2.5 3 3 72 480-1195 1-1
393 4 Ⅱ 図 1 IONA 試験 5,126 1 40mg 2,565 2 2,561 1 ニコランジル周術期使用の効果 24 1 g/kg/min 50kg 3mg/hr 12 12 5 CPK-MB T heart fatty acidbinding protein HFABP 15 HFABP 321 13 0.06mg/kg/hr 50kg 1.8mg/ hr 5 ST-T 6 237 84 13 29 Ⅲ ニコランジルの心血管系へ及ぼす薬理作用 2 6mg/hr 6 30 150ng/ml 0.2mg/kg 5 0.2mg/kg/hr 48 600ng/ml 7
394 Vol.34 No.3/May 2014 図 2 ニコランジルのヒト冠動脈拡張作用 12mg 45 13 11 30 600ng/ ml 211.17 1.5 10-7 3 10-6 mol/l 8 ATP 10-6 mol/l 9 ATP GMP 10 Nakae 13 12mg 45 11 図 2 3mg/hr 180 50 ATP 12 10-6 mol/l ST 4mg 24 8mg/hr 3
395 8-epi-PGF2 6 13 15mg/day 6 12 malondialdehydemodified LDL hs-crp 14 Ⅳ 今後の検討課題とまとめ 参考文献 1) IONA Study Group:Effect of nicorandil on coronary events in patients with stable angina:the Impact Of Nicorandil in Angina(IONA)randomised trial. Lancet 359:1269-1275, 2002 2) Ishii H, Ichimiya S, Kanashiro M, et al.:impact of a single intravenous administration of nicorandil before reperfusion in patients with ST-segment-elevation myocardial infarction. Circulation 112:1284-1288, 2005 3) Kitakaze M, Asakura M, Kim J, et al.;j-wind investigators:human atrial natriuretic peptide and nicorandil as adjuncts to reperfusion treatment for acute myocardial infarction(j-wind):two randomised trials. Lancet 370:1483-1493, 2007 4) Iwakura K, Ito H, Okamura A, et al.:nicorandil treatment in patients with acute myocardial infarction:a meta-analysis. Circ J 73:925-931, 2009 5) Ito I, Hayashi Y, Kawai Y, et al.:prophylactic effect of intravenous nicorandil on perioperative myocardial damage in patients undergoing off-pump coronary artery bypass surgery. J Cardiovasc Pharmacol 44:501-506, 2004 6) Kashimoto S, Seki M, Ishiguro T, et al.:nicorandil decreases cardiac events during and after noncardiac surgery. J Clin Anesth 19:44-48, 2007 7) 医薬品インタビューフォーム. シグマート注 2mg, 12mg,48mg,2010 年 6 月 ( 改訂第 7 版 ) 8) 木下浩之 :ATP 感受性カリウムチャネルの基礎.Anet 9:18-21,2005 9) Shindo T, Yamada M, Isomoto S, et al.:sur2 subtype (A and B)-dependent differential activation of the cloned ATP-sensitive K + channels by pinacidil and nicorandil. Br J Pharmacol 124:985-991, 1998 10)Kuno A, Critz SD, Cohen MV, et al.:nicorandil opens mitochondrial K ATP channels not only directly but also through a NO-PKG-dependent pathway. Basic Res Cardiol 102:73-79, 2007 11)Nakae I, Matsumoto T, Horie H, et al.:effects of intravenous nicorandil on coronary circulation in humans:plasma concentration and action mechanism. J Cardiovasc Pharmacol 35:919-925, 2000 12)Ueda K, Goto C, Jitsuiki D, et al.:the nicorandil-induced vasodilation in humans is inhibited by miconazole. J Cardiovasc Pharmacol 45:290-294, 2005 13)Ono H, Osanai T, Ishizaka H, et al.:nicorandil improves cardiac function and clinical outcome in patients with acute myocardial infarction undergoing primary percutaneous coronary intervention:role of inhibitory effect on reactive oxygen species formation. Am Heart J 148:E15, 2004 14)Ishibashi Y, Takahashi N, Tokumaru A, et al.:effects of long-term nicorandil administration on endothelial function, inflammation, and oxidative stress in patients without coronary artery disease. J Cardiovasc Pharmacol 51:311-316, 2008
396 Vol.34 No.3/May 2014 Perioperative Ischemic Heart Disease and Nicorandil Hiroyuki KINOSHITA Department of Anesthesiology, Aichi Medical University School of Medicine Nicorandil clearly has beneficial effects on the long-term outcomes of patients with ischemic heart disease. However, only a few clinical studies have been conducted to evaluate the effect of this compound on the perioperative outcome of patients. One group examined the effects of nicorandil iv from the commencement of general anesthesia to 15 hrs after coronary reperfusion through levels of markers indicating cardiac injury in patients undergoing off-pump coronary artery bypass surgery. Others conducted a study which evaluated the effects of intraoperative nicorandil iv on cardiovascular events up to the 5th postoperative day in patients undergoing noncardiac surgery. These studies documented slight but significant beneficial effects of nicorandil iv on the outcome of patients. Further studies are needed to clarify the effects of perioperative nicorandil on the long-term outcomes of surgical patients. Key Words : Ischemic heart disease, Long-term outcome, Nicorandil, Perioperative period The Journal of Japan Society for Clinical Anesthesia Vol.34 No.3, 2014