Effects of the specific bradycardic agent zatebradine on hemodynamic variables and myocardial blood flow during the early postresuscitation phase in pigs

Abstract

Cardiopulmonary resuscitation (CPR) leads to an excessive stimulation of the sympathetic nervous system that may result in tachycardia and malignant arrhythmias in the postresuscitation phase. The attenuation of this reaction by a specific bradycardic agent has not been compared to β-blockade and placebo. After 4 min of ventricular fibrillation, and 3 min of CPR, 21 pigs were randomized to receive 45 μg/kg epinephrine in combination with either a specific bradycardic agent (0.5 mg/kg zatebradine; n=7), or a β-blocker (1 mg/kg esmolol; n=7), or placebo (normal saline; n=7). Two minutes after drug administration, defibrillation was performed to restore spontaneous circulation (ROSC). Hemodynamic variables, left ventricular contractility, right ventricular function, and myocardial blood flow were studied at prearrest, and for 3 h after ROSC. In comparison with esmolol and placebo, zatebradine resulted in a significant reduction in heart rate during the postresuscitation period, and reduced the number of premature ventricular contractions in the first 5 min after ROSC. This reduction in heart rate was associated with a significantly higher right ventricular ejection fraction, stroke volume, and endocardial/epicardial perfusion ratio at 5 min after ROSC. In comparison with placebo, esmolol administration decreased heart rate only moderately, but significantly reduced right ventricular stroke volume and cardiac output at 5 min after ROSC. Although only one dose and only one administration pattern of zatebradine has been investigated, we conclude that zatebradine administration during CPR effectively reduced heart rate without compromising myocardial contractility during the postresuscitation phase in pigs.