ROLE OF ZATEBRADINE AND PROPRANOLOL IN ATTENUATION OF TACHYCARDIA PRODUCED BY DOBUTAMINE IN PIGS

Background: Zatebradine is a new specific bradycardic agent that selec tively slows the depolarization in the pacemaker cells of the sinoatri al node. The purpose of our investigation was to determine whether the tachycardia induced by dobutamine can be attenuated by the administra tion of zatebradine. The results were compared with those produced by propranolol, which is used in the treatment of sinus tachycardia. Meth ods: Twelve pigs were anesthetized with sodium pentobarbital, intubate d, and ventilated. After baseline hemodynamic measurements were obtain ed, dobutamine was administered until the heart rate reached 25% above baseline. Animals were randomized to one of two groups. Group I recei ved zatebradine, 0.5 mg/kg IV, and Group II received propranolol, 0.5 mg/kg IV. Results: Dobutamine 10 mu g.kg(-1).min(-1) increased the hea rt rate (HR) by 25%, and increased mean arterial blood pressure (MAP), left ventricular (LV) dP/dt, and cardiac output (CO) (P<0.05). Zatebr adine decreased the HR to baseline (P<0.05) without affecting left ven tricular systolic pressure (LVSP), left ventricular end diastolic pres sure (LVEDP), LV dP/dt, or CO. Stroke volume (SV) increased significan tly (P<0.05). Propranolol also reduced HR to baseline, but decreased L V dP/dt, LVSP, CO, and SV (P<0.05). Conclusion: Zatebradine effectivel y attenuates the tachycardia caused by dobutamine in anesthetized pigs , without reducing cardiac performance.