Carbachol and dibutyryl cyclic GMP on the vulnerability to ventricular fibrillation in rat isolated hearts

cyclic monophosphate (cyclic GMP) concentrations may increase electrical stability of the myocardium was examined by determination of ventricular fibrillation thresholds (VFT) on isolated perfused hearts of the rat. Hearts were paced to circumvent any complicating effects of bradycardia. Using this system, carbachol produced a concentration‐related reduction in VFT. The reduction in VFT produced by carbachol was not significantly modified by a high concentration of atenolol (10⁻⁵ M), indicating that the increased vulnerability to ventricular fibrillation was not an indirect consequence of catecholamine release from intramyocardial stores. Atropine (10⁻⁶ M) blocked the carbachol‐induced reduction in VFT. At the concentrations of carbachol used to reduce VFT, myocardial cyclic GMP concentrations were also elevated. The dibutyryl analogue of cyclic GMP (10⁻⁴ M) mimicked the effect of carbachol in reducing VFT. Carbachol potentiated the adrenaline (3 × 10⁻⁷ M)‐induced reduction in VFT. 1985 British Pharmacological Society