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

Cardiopulmonary resuscitation (CPR) leads to an excessive stimulation of th e sympathetic nervous system that may result in tachycardia and malignant a rrhythmias 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 pig s were randomized to receive 45 mu g/kg epinephrine in combination with eit her 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 mi nutes after drug administration, defibrillation was performed to restore sp ontaneous circulation (ROSC). Hemodynamic variables, left ventricular contr actility, right ventricular function, and myocardial blood flow were studie d at prearrest, and for 3 h after ROSC. In comparison with esmolol and plac ebo, zatebradine resulted in a significant reduction in heart rate during t he postresuscitation period, and reduced the number of premature ventricula r contractions in the first 5 min after ROSC. This reduction in heart rate was associated with a significantly higher right ventricular ejection fract ion, stroke volume, and endocardial/epicardial perfusion ratio at 5 min aft er ROSC. In comparison with placebo, esmolol administration decreased heart rate only moderately, but significantly reduced right ventricular stroke v olume and cardiac output at 5 min after ROSC. Although only one dose and on ly one administration pattern of zatebradine has been investigated, we conc lude that zatebradine administration during CPR effectively reduced heart r ate without compromising myocardial contractility during the postresuscitat ion phase in pigs. (C) 1999 Elsevier Science Ireland Ltd. All rights reserv ed.