Role of zatebradine and propranolol in attenuation of tachycardia produced by dobutamine in pigs.
BACKGROUND
Zatebradine is a new specific bradycardiac agent that selectively slows the depolarization in the pacemaker cells of the sinoatrial node. The purpose of our investigation was to determine whether the tachycardia induced by dobutamine can be attenuated by the administration of zatebradine. The results were compared with those produced by propranolol, which is used in the treatment of sinus tachycardia.


METHODS
Twelve pigs were anesthetized with sodium pentobarbital, intubated, and ventilated. After baseline hemodynamic measurements were obtained, dobutamine was administered until the heart rate reached 25% above baseline. Animals were randomized to one of two groups. Group I received zatebradine, 0.5 mg/kg i.v., and Group II received propranolol, 0.5 mg/kg i.v.


RESULTS
Dobutamine 10 micrograms.kg-1.min-1 increased the heart rate (FIR) by 25%, and increased mean arterial blood pressure (MAP) left ventricular (LV) dp/dt, and cardiac output (CO) (P < 0.05). Zatebradine decreased the HR to baseline (P < 0.05) without affecting left ventricular systolic pressure (LVSP), left ventricular end diastolic pressure (LVEDP), LV dP/dt, or CO. Stroke volume (SV) increased significantly (P < 0.05). Propranolol also reduced HR to baseline, but decreased LV dP/dt, LVSP, CO, and SV (P < 0.05).


CONCLUSIONS
Zatebradine effectively attenuates the tachycardia caused by dobutamine in anesthetized pigs, without reducing cardiac performance.
Neustein
S M
SM
Department of Anesthesiology, Mount Sinai Medical Center, New York, USA.
Dimich
I
I
Shiang
H
H
Mezrow
C
C
D000818:Animals; D001552:Benzazepines / Q000494:pharmacology*; D002316:Cardiotonic Agents / Q000494:pharmacology*; D004280:Dobutamine / Q000494:pharmacology*; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D008297:Male; D011433:Propranolol / Q000494:pharmacology*; D013552:Swine; D013610:Tachycardia / Q000139:chemically induced / Q000188:drug therapy*
D001552:Benzazepines; D002316:Cardiotonic Agents; D004280:Dobutamine; D011433:Propranolol; C043636:zatebradine