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 beta-blockade and placebo. After 4 min of
ventricular fibrillation, and 3 min of
CPR, 21 pigs were randomized to receive 45 microg/kg
epinephrine in combination with either a specific bradycardic agent (0.5 mg/kg
zatebradine; n = 7), or a beta-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.