Beneficial Effects of Ivabradine on Post-Resuscitation Myocardial Dysfunction in a Porcine Model of Cardiac Arrest.

Abstract

ABSTRACTBackground:Ivabradine selectively inhibits the If current, reducing the heart rate and protecting against myocardial ischemia/reperfusion injury. We investigated the effects of ivabradine on post-resuscitation myocardial function in a porcine model of cardiopulmonary resuscitation.Methods and Results:Ventricular fibrillation was induced and untreated for 8 min while defibrillation was attempted after 6 min of cardiopulmonary resuscitation in anesthetized domestic swine. Then the animals were randomized into ivabradine and placebo groups (n = 5 each). Ivabradine and saline were administered at the same volume 5 min after Return of Spontaneous Circulation, followed by continuous intravenous infusion at 0.5 mg/kg for 480 min. Hemodynamic parameters were continuously recorded. Myocardial function was assessed by echocardiography at baseline and at 60, 120, 240, 480 min and 24 h after resuscitation. The serum levels of N-terminal pro-brain natriuretic peptide (NT-proBNP) and cardiac troponin I (cTnI) were measured by commercial enzyme-linked immunosorbent assay kits. Animals were killed 24 h after resuscitation, and all myocardial tissue was removed for histopathological analysis. The heart rate was significantly reduced from 1 h after resuscitation in the ivabradine group (all P < 0.05). The post-resuscitation mitral E/A and E/e′ velocity ratios and left ventricular ejection fraction were significantly better in the ivabradine than placebo group (P < 0.05). The serum levels of myocardial injury biomarkers (NT-proBNP, cTnI) and the myocardial biopsy scores were significantly lower in the ivabradine than placebo group (P < 0.05). Neurological deficit scores were lower in the IVA group at PR 24 h (P < 0.05).Conclusions:Ivabradine improved post-resuscitation myocardial dysfunction, myocardial injury, and post-resuscitation cerebral function, and also slowed the heart rate in this porcine model.