Levosimendan improves postresuscitation outcomes in a rat model of CPR

Abstract

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 β-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 μg kg⁻¹ over a 10-minute period, followed by infusion of 0.3 μg kg⁻¹ min⁻¹ over the next 230 minutes. Dobutamine was continuously infused at a dosage of 3 μg 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.