Huang Lei, Weil Max Harry, Sun Shijie, Cammarata Gianluca, Cao Lan, Tang Wanchun
Weil Institute of Critical Care Medicine, Rancho Mirage, CA 92270, USA.
J Lab Clin Med. 2005 Nov;146(5):256-61. doi: 10.1016/j.lab.2005.07.005.
In this study we sought to determine whether a calcium sensitizer, levosimendan, would have a more favorable effect on postresuscitation myocardial function and, consequently, postresuscitation survival than beta-adrenergic dobutamine. The extreme decrease in survival before hospital discharge of resuscitated victims is attributed, in part, to postresuscitation myocardial failure, and dobutamine has been recommended for the management of postresuscitation myocardial failure. We studied a total of 15 animals. Ventricular fibrillation was induced in Sprague-Dawley rats weighing 450 to 550 g. Cardiopulmonary resuscitation (CPR), including chest compressions and mechanical ventilation, was begun after 8 minutes of untreated cardiac arrest. Electrical defibrillation was attempted after 6 minutes of CPR. Each animal was resuscitated. Animals were randomized to undergo treatment with levosimendan, dobutamine, or saline-solution placebo. These agents were administered 10 minutes after the return of spontaneous circulation. Levosimendan was administered in a loading dose of 12 microg kg(-1) over a 10-minute period, followed by infusion of 0.3 microg kg(-1) min(-1) over the next 230 minutes. Dobutamine was continuously infused at a dosage of 3 microg kg(-1) min(-1). Saline-solution placebo was administered in the same volume and over the same amount of time as levosimendan. Levosimendan and dobutamine produced comparable increases in cardiac output and rate of left-ventricular pressure increase. However, administration of levosimendan resulted in lower heart rates and lesser increases in left ventricular diastolic pressure compared with both dobutamine and placebo. The duration of postresuscitation survival was significantly greater with levosimendan (16 +/- 2 hours), intermediate with dobutamine (11 +/- 2 hours) and least with saline-solution placebo (8 +/- 1 hour). Levosimendan and dobutamine both improved postresuscitation myocardial function. However, levosimendan produced more favorable postresuscitation myocardial function and increased the duration of postresuscitation survival.
在本研究中，我们试图确定钙增敏剂左西孟旦对复苏后心肌功能是否具有比β-肾上腺素能多巴酚丁胺更有利的影响，从而对复苏后存活产生更有利的影响。复苏后患者出院前存活率极低，部分原因是复苏后心肌衰竭，多巴酚丁胺已被推荐用于治疗复苏后心肌衰竭。我们共研究了15只动物。对体重450至550克的Sprague-Dawley大鼠诱发室颤。在未经治疗的心脏骤停8分钟后开始进行心肺复苏（CPR），包括胸外按压和机械通气。在CPR 6分钟后尝试电除颤。每只动物均成功复苏。动物被随机分为接受左西孟旦、多巴酚丁胺或生理盐水安慰剂治疗。这些药物在自主循环恢复后10分钟给药。左西孟旦以12微克/千克的负荷剂量在10分钟内给药，随后在接下来的230分钟内以0.3微克/千克·分钟的速度输注。多巴酚丁胺以3微克/千克·分钟的剂量持续输注。生理盐水安慰剂的给药体积和时间与左西孟旦相同。左西孟旦和多巴酚丁胺使心输出量和左心室压力上升速率有相似的增加。然而，与多巴酚丁胺和安慰剂相比，左西孟旦给药导致心率更低，左心室舒张压升高幅度更小。左西孟旦组复苏后存活时间显著更长（16±2小时），多巴酚丁胺组居中（11±2小时），生理盐水安慰剂组最短（8±1小时）。左西孟旦和多巴酚丁胺均改善了复苏后心肌功能。然而，左西孟旦产生了更有利的复苏后心肌功能，并延长了复苏后存活时间。
