Abstract 13281: The Combined Effect of Omecamtiv Mecarbil and Low-Dose Dobutamine for Post-Arrest Myocardial Dysfunction in a Rat Model of Cardiac Arrest

Abstract

Introduction: Post-arrest myocardial dysfunction attributes unstable hemodynamic and mortality in successfully resuscitated cardiac arrest victims. Studies demonstrated that low-dose dobutamine (LDb) and Omecamtiv Mecarbil (OM) improved post-arrest myocardial dysfunction and neurological recovery, respectively. Hypothesis: Whether the combination of LDb and OM synergistically improves post-arrest myocardial dysfunction? Methods: Asphyxial cardiac arrest was induced in adult male wistar rats and left untreated for 9.5 minutes followed by cardiopulmonary resuscitation. Successfully resuscitated animal were randomized into control group (without medication), OM group(0.25 mg/kg/h), LDb group (5 micrograms/Kg/min), and OM+LDb group, in which drugs or normal saline were continuously intravenously infused for 4 hours. Hemodynamic were monitored for 4 h after return of spontaneous circulation. Survival status and neurological recovery were observed for 72 h. The difference of biomarkers, histological examinations and mitochondrial function of myocardium between groups were evaluated. Results: As compared with the control group, the OM, LDb, and OM+LDb groups all demonstrated improved left ventricular systolic function (dp/dt40), better cardiac output, lower Troponin-I, higher 72-h survival, and more favorable neurological recovery. The LDb group showed a higher dp/dt40 and cardiac output than the OM group, whereas OM+LDb group did not demonstrated significant benefit when compared to OM and LDb, respectively. The OM, LDb, and OM+LDb mitigated post-arrest myocardial damage and cardiac mitochondrial injury, and ameliorated myocardial and hippocampus apoptosis. However, the OM+LDb group showed no superiority to the OM group or LDb group. Conclusions: Both OM and LDb improved post-arrest myocardial dysfunction, cardiac mitochondrial injury, survival, neurological recovery following cardiac arrest. However, OM+LDb group did not exert synergistic effect in ameliorate post-arrest myocardial dysfunction.