Drug Therapy Digitalis Glycosides
- TW SMITH
- N Engl J Med
Digitalis glycosides have been implicated in increased vulnerability to ventricular fibrillation in man. In order to investigate the genesis and occurrence of ventricular fibrillation in the presence of digitalis, the effects of both acetylstrophanthidin and ouabain on the ventricular fibrillation threshold (VFT) were studied in the open-chest anesthetized dog. The current required to induce ventricular fibrillation was determined by passing a train of 12 constant current pulses through epicardial electrodes during the vulnerable period of the cardiac cycle. It was found that an intravenous bolus infusion of acetylstrophanthidin (0.050-0.097 mg/kg) or ouabain (0.035-0.075 mg/kg) in intact innervated dog hearts raised the VFT from 40% to 260% above control values. Continuous infusions of acetylstrophanthidin to toxic levels also resulted in an elevated VFT. Vagotomy alone did not qualitatively change the effects of acetylstrophanthidin on VFT. However, following vagotomy and stellate sympathectomy, infusions of both toxic and subtoxic doses of acetylstrophanthidin resulted in a decrease in the VFT from 40 to 80% below control values. In denervated animals in which the peripheral ramifications of the left stellate ganglion nerves were stimulated, the VFT decreased below control values in the absence of acetylstrophanthidin, but during stellate stimulation in the presence of acetylstrophanthidin the VFT was increased above control values. These studies demonstrated that the increase in VFT by digitalis in the healthy, innervated heart was mediated via an associated increase in sympathetic activity; in the absence of neural influences digitalis decreased the VFT.