Abstract
Dick M et at (1) reported increased arrhythmias from digitalis in patients receiving reserpine therapy. Roberts et al(2) reported that reserpine treatment increased the amount of acetylstrophanthin required to produce ventricular arrhythmias in the dog. On the other hand, Nash et al(3) reported that ouabain lethality was decreased with reserpine pre treatment in rats. Takagi et al(4) also reported decreased lethality of digoxin with reserpine pretreatment in dogs. From these various reports, it would appear that although reserpine may increase the possibility of arrhythmias induced by digitalis glycosides it also decreases lethal potential of the glycosides.
Considering the known central and peripheral effects of reserpine, the current study was therefore undertaken to investigate possible effects of reserpine on the lethality of digitoxigenin. The latter compound was selected since it is a potent convulsant and was the most toxic of various structurally-related compounds when intravenously administered to the mouse(5).
Methods. Crystalline digitoxigenin was obtained from Lachat Chemicals, Inc., Chicago, Ill., and was dissolved in a final solution of 47.5% ethanol in 0.9% saline. Solubilized reserpine, supplied as Serpasil in water for injection, was supplied by Ciba Pharmaceutical Co., Summit, N. J. Norepinephrine was freshly prepared in 0.9% saline as a 100 μg per ml solution.
Adult male Swiss-Webster mice, weighing 20-30 g, were maintained in local animal facilities for at least 4 days prior to use. Wayne Lab Blox and tap water were allowed ad libitum both before and after injection and each animal was used only once. All agents except norepinephrine were injected in a dose volume of 2 ml/kg. Digitoxigenin and norepinephrine were administered by tail vein, whereas the reserpine was injected sub-cutaneously in the scruff of the neck. The norepinephrine dose was 100 μg/kg.
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