Abstract
BackgroundMyocardial dysfunction is a major cause of poor outcomes in the post-cardiac arrest period. Omecamtiv mecarbil (OM) is a selective small molecule activator of cardiac myosin that prolongs myocardial systole and increases stroke volume without apparent effects on myocardial oxygen demand. OM administration is safe and improves cardiac function in patients with acute heart failure. Whether OM improves post-resuscitation myocardial dysfunction remains unclear. This study investigated the effect of OM treatment on post-resuscitation myocardial dysfunction and outcomes.Methods and resultsAdult male rats were resuscitated after 9.5 min of asphyxia-induced cardiac arrest. OM and normal saline was continuously intravenously infused after return of spontaneous circulation (ROSC) at 0.25 mg/kg/h for 4 h in the experimental group and control group, respectively (n = 20 in each group). Hemodynamic parameters were measured hourly and monitored for 4 h after cardiac arrest. Recovery of neurological function was evaluated by neurological functioning scores (0–12; favorable: 11–12) for rats 72 h after cardiac arrest. OM treatment prolonged left ventricular ejection time and improved post-resuscitation cardiac output. Post-resuscitation heart rate and left ventricular systolic function (dp/dt40) were not different between groups. Kaplan-Meier analysis showed non-statistically higher 72-h survival in the OM group (72.2% [13/18] and 58.8% [10/17], p = 0.386). The OM group had a higher chance of having favorable neurological outcomes in surviving rats 72 h after cardiac arrest (84.6% [11/13] vs. 40% [4/10], p = 0.026). The percentage of damaged neurons was lower in the OM group in a histology study at 72 h after cardiac arrest (55.5±2.3% vs. 76.2±10.2%, p = 0.004).ConclusionsOM treatment improved post-resuscitation myocardial dysfunction and neurological outcome in an animal model. These findings support further pre-clinical studies to improve outcomes in post-cardiac arrest care.
Highlights
Cardiopulmonary resuscitation (CPR) has been developed for more than 50 years, sudden cardiac arrest still carries a high mortality rate
Left ventricular ejection time was prolonged in the Omecamtiv mecarbil (OM) group compared to that in the control group from 1 h to 4 h after return of spontaneous circulation (ROSC)
Cardiac output decreased after cardiac arrest and cardiopulmonary resuscitation (CPR) and was undetectable immediately after ROSC
Summary
Cardiopulmonary resuscitation (CPR) has been developed for more than 50 years, sudden cardiac arrest still carries a high mortality rate. Cardiac arrest survivors experience persistent global ischemia-reperfusion injury for up to 72 h or longer during the post-cardiac arrest period. This injury leads to post-cardiac arrest syndrome, which is a complex combination of pathophysiological processes comprising postcardiac arrest cerebral injury and myocardial dysfunction and contributes to multiple organ failure and mortality [3, 4]. Laurent et al reported that resuscitated patients with a persistent low cardiac index at 24 h were more likely to experience multi-organ failure and early death [3]. Improving post-cardiac arrest myocardial dysfunction may ameliorate hemodynamic instability and survival outcomes. Myocardial dysfunction is a major cause of poor outcomes in the post-cardiac arrest period. This study investigated the effect of OM treatment on post-resuscitation myocardial dysfunction and outcomes
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
