Daugherty A, Woodward B
Br J Pharmacol. 1985 Jul;85(3):621-7. doi: 10.1111/j.1476-5381.1985.tb10556.x.
The hypothesis that elevation of intracellular guanosine 3':5' 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 X 10(-7)M)-induced reduction in VFT.
通过测定大鼠离体灌流心脏的室颤阈值（VFT），对细胞内3':5'-环磷酸鸟苷（环磷酸鸟苷）浓度升高可能增加心肌电稳定性这一假说进行了检验。对心脏进行起搏以规避心动过缓的任何复杂影响。使用该系统，卡巴胆碱使VFT呈浓度相关降低。高浓度阿替洛尔（10⁻⁵M）并未显著改变卡巴胆碱引起的VFT降低，表明对室颤易感性增加并非心肌内储存的儿茶酚胺释放的间接后果。阿托品（10⁻⁶M）阻断了卡巴胆碱诱导的VFT降低。在用于降低VFT的卡巴胆碱浓度下，心肌环磷酸鸟苷浓度也升高。环磷酸鸟苷的二丁酰类似物（10⁻⁴M）模拟了卡巴胆碱降低VFT的作用。卡巴胆碱增强了肾上腺素（3×10⁻⁷M）诱导的VFT降低。
