Beneficial Effects of Ivabradine on Post-Resuscitation Myocardial Dysfunction In A Porcine Model of Cardiac Arrest.

Yang, Min; Che, Limin; Hua, Tianfeng; Zou, Yangyang; Yang, Zhengfei

BACKGROUND 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 minutes while defibrillation was attempted after 6 minutes 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 minutes after ROSC (Return of Spontaneous Circulation), followed by continuous intravenous infusion at 0.5 mg/kg for 480 minutes. Hemodynamic parameters were continuously recorded. Myocardial function was assessed by echocardiography at baseline and at 60, 120, 240, 480 minutes and 24 hours 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 hours after resuscitation, and all myocardial tissue was removed for histopathological analysis. The heart rate was significantly reduced from 1 hour 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 hours (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.