Omecamtiv mecarbil treatment improves post-resuscitation cardiac function and neurological outcome in a rat model

• Published in: PloS one 2022-02, Vol.17 (2), p.e0264165-e0264165
• Main Authors: Wu, Shih-Ni, Tsai, Min-Shan, Huang, Chien-Hua, Chen, Wen-Jone
• Format: Article
• Language: English
• Subjects: Animal models; Animals; Asphyxia; Biology and Life Sciences; Blood circulation; Blood pressure; Cardiac function; Cardiac output; Cardiopulmonary Resuscitation - adverse effects; Care and treatment; Congestive heart failure; CPR (First aid); Defibrillators; Emergency medical care; Experiments; Heart; Heart Arrest - complications; Heart failure; Heart rate; Hemodynamics; Histology; Hospitals; Laboratory animals; Male; Medical schools; Medicine; Medicine and Health Sciences; Mortality; Myocardial Contraction - drug effects; Myosin; Nervous System Diseases - etiology; Nervous System Diseases - prevention & control; Oxygen; Oxygen demand; Patient outcomes; Rats; Rats, Wistar; Resuscitation; Stroke Volume; Systole; Urea - analogs & derivatives; Urea - pharmacology; Veins & arteries; Ventilators; Ventricle; Ventricular Dysfunction - etiology; Ventricular Dysfunction - prevention & control; Ventricular Function, Left - drug effects
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0264165

Myocardial 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. Adult 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). OM 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.