Effect of flutonidine on ouabain-induced arrhythmias and lethality in guinea-pig.

Flutonidine (10, 20 and 40 micrograms/kg) was studied for its efficacy against the cardiotoxic effects induced by slow intravenous infusion of ouabain in guinea-pigs. Flutonidine increased the dose of ouabain required to cause ventricular premature beats, ventricular tachyarrhythmias and lethality. Flutonidine further inhibited the rate of ouabain-induced rise in blood pressure. Alpha 1 adrenoceptor antagonist, corynanthine (1 mg/kg), could not alter the protective action of flutonidine; whereas idazoxan (100 micrograms/kg), the alpha 2 adrenoceptor blocker, showed significant inhibition of this effect. It is suggested that the reduction in the arrhythmogenic and lethal effects of ouabain by flutonidine may be due to its ability to reduce sympathetic tone by interfering with the neural components of ouabain action mediated through alpha 2 adrenoceptors.