July 8, 2019ShockOpen Access

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

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Why the study?

Ivabradine reduces heart rate and protects against ischemia/reperfusion injury, prompting investigation into its effects on post-resuscitation myocardial function after cardiac arrest.

Does ivabradine improve post-resuscitation myocardial dysfunction and injury in a porcine model of cardiac arrest?

Structured PICO

Does ivabradine improve post-resuscitation myocardial dysfunction and injury in a porcine model of cardiac arrest?

Population

10 healthy male domestic pigs weighing 35 kg to 40 kg (3-4 months old), mixed breed, subjected to 8 minutes of untreated ventricular fibrillation followed by 6 minutes of cardiopulmonary resuscitation and defibrillation.

Intervention

Ivabradine 5-mg loading dose administered by right femoral vein injection 5 minutes after return of spontaneous circulation (ROSC), followed by continuous intravenous infusion at 0.5 mg/kg for 480 minutes.

Comparator

Saline (placebo) administered at the same volume as a bolus injection into the right femoral vein 5 minutes after ROSC.

Outcome

Post-resuscitation myocardial function (LVEF, mitral E/A ratio, and E/e' velocity ratio) assessed by echocardiography at baseline and at 60, 120, 240, 480 minutes and 24 hours after resuscitation.surrogate

In a porcine model of cardiac arrest, ivabradine administration after return of spontaneous circulation significantly improved myocardial systolic and diastolic function and reduced myocardial injury biomarkers.

Limitations

Our porcine model of CA and resuscitation does not fully represent clinical conditions in humans
The survival rate of animals needs to be investigated, and larger randomized studies should be performed
The long-term treatment outcomes and prognosis of IVA therapy after ROSC require further studies
The optimal dose and target HR management of IVA in the clinical setting are worthy of further studies

Implication

May support ivabradine investigation post-arrest in animals; leaves open human translation and trials.

Abstract

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 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.