Nijhawan N, Nicolosi A C, Montgomery M W, Aggarwal A, Pagel P S, Warltier D C
Department of Anesthesiology, Medical College of Wisconsin and the Clement J. Zablocki Veterans Affairs Medical Center, Milwaukee 53226, USA.
J Cardiovasc Pharmacol. 1999 Aug;34(2):219-28. doi: 10.1097/00005344-199908000-00007.
Levosimendan is a new myofilament calcium (Ca2+) sensitizer that increases myocardial contractility by stabilizing the Ca2+-bound conformation of troponin C. We tested the hypothesis that levosimendan enhances cardiac performance after cardiopulmonary bypass (CPB). Anesthesia was induced and maintained with midazolam, sufentanil, and vecuronium in 18 patients randomly assigned to receive levosimendan (18 or 36 microg/kg loading dose and 0.2 or 0.3 microg/kg/min infusion, respectively) or placebo 15 min before and continued for 6 h after CPB. Significant (p < 0.05) increases in heart rate (HR) and decreases in systemic vascular resistance (SVR) occurred 15 min after CPB in patients receiving placebo. Later increases in mean arterial pressure (MAP) and cardiac output (CO) and decreases in stroke volume (SV) and pulmonary vascular resistance also were observed. HR was greater in patients receiving high- but not low-dose levosimendan versus placebo immediately after CPB. MAP also was lower in patients treated with either dose of levosimendan compared with placebo after CPB. Levosimendan increased CO and decreased SVR (4.2 +/- 0.4 to 7.9 +/- 0.4 L/min and 1,150 +/- 99 to 512 +/- 42 dyn/s/cm5, respectively, 15 min after CPB; mean +/- SEM). CO and SV were higher and SVR was lower in patients receiving levosimendan versus placebo after CPB. No differences in arterial oxygenation and perioperative arrhythmias (Holter analysis) were observed between groups. The results indicate that levosimendan enhances cardiac performance after CPB in humans.
左西孟旦是一种新型的肌丝钙（Ca2+）敏化剂，它通过稳定肌钙蛋白C与钙结合的构象来增强心肌收缩力。我们检验了左西孟旦能改善体外循环（CPB）后心脏功能的假设。18例患者接受咪达唑仑、舒芬太尼和维库溴铵诱导并维持麻醉，随机分为两组，分别在CPB前15分钟给予左西孟旦（负荷剂量分别为18或36微克/千克，输注速度分别为0.2或0.3微克/千克/分钟）或安慰剂，并在CPB后持续给药6小时。接受安慰剂的患者在CPB后15分钟心率（HR）显著增加（p<0.05），全身血管阻力（SVR）降低。随后还观察到平均动脉压（MAP）和心输出量（CO）增加，每搏量（SV）和肺血管阻力降低。CPB后立即接受高剂量而非低剂量左西孟旦的患者HR高于接受安慰剂的患者。CPB后，接受任一剂量左西孟旦治疗的患者MAP也低于接受安慰剂的患者。左西孟旦增加了CO并降低了SVR（CPB后15分钟时分别为4.2±0.4至7.9±0.4升/分钟和1150±99至512±42达因/秒/平方厘米；均值±标准误）。CPB后接受左西孟旦的患者CO和SV较高，SVR较低。两组之间在动脉氧合和围手术期心律失常（动态心电图分析）方面未观察到差异。结果表明，左西孟旦可改善人体CPB后的心脏功能。
