Inhibition of quinidine-propranolol elevation of the ventricular fibrillation threshold by bilateral stellectomy+vagotomy in the anesthetized dog.
The antiarrhythmic potentiation that occurs with the coadministration of quinidine-propranolol has been attributed to propranolol-induced cardiac beta adrenergic receptor blockade. That this may not be the sole mechanism, however, is suggested by the finding that sotalol, pronethalol and practolol fail to potentiate quinidine in some antiarrhythmic tests. Thus, in the present experiments, the influence of bilateral stellectomy + vagotomy on quinidine-propranolol antiarrhythmic activity was studied in the anesthetized dog. Antiarrhythmic activity was determined as elevation of the electrical ventricular fibrillation threshold (VFT) when the left ventricle was stimulated directly with 60 Hz, 6 msec and varying mA for 2 sec. The increase in VFT produced by quinidine-propranolol (5 + 0.2 mg/kg, i.v.) was significantly reduced when the heart was subsequently denervated by bilateral stellectomy + vagotomy. The cardiac denervation did not significantly reduce the elevation of VFT that had been produced by prior administration of propranolol 0.4 mg/kg or sotalol. In other groups with prior bilateral stellectomy + vagotomy, the separate administration of propranolol 0.4 mg/kg or quinidine 5 mg/kg failed to significantly elevate the VFT although the VFT was increased by propranolol 0.8 mg/kg. The results indicate that the action of quinidine-propranolol to elevate the VFT may be dependent in part upon an intact nerve supply to the heart.
D000758:Anesthesia; D000818:Animals; D003714:Denervation; D004285:Dogs; D004558:Electric Stimulation; D005260:Female; D006321:Heart / Q000294:innervation; D008297:Male; D011433:Propranolol / Q000494:pharmacology*; D011802:Quinidine / Q000494:pharmacology*; D013015:Sotalol / Q000494:pharmacology; D013233:Stellate Ganglion / Q000502:physiology*; D014628:Vagotomy; D014693:Ventricular Fibrillation / Q000503:physiopathology*
D011433:Propranolol; D013015:Sotalol; D011802:Quinidine