Increasing the inotropic effect and toxic dose of digitalis by the administration of antikaliuretic drugs--further evidence for a cardiac effect of diuretic agents.

In prior studies, we have shown that the antikaliuretic drugs, triamterene and amiloride, through a direct cardiac effect reduce the loss of cardiac potassium induced by the administration of digitalis. Since loss of myocardial potassium is thought to underlie digitalis arrhythmias, this study was performed to determine whether triamterene and amiloride also extend the toxic dose and thus the therapeutic effect of digitalis. In twelve dogs, acetylstrophanthidin was infused (100 ug per minute) serially at 2.5-hour intervals. Trimterene (400 mg. in divided doses) was infused before the third acetylstrophanthidin infusion. This extended the dose required to produce a toxic arrhythmia by 110 per cent. In fourteen additional studies, nine dogs received 400 mg. of triamterene prior to the third acetylstrophanthidin infusion and five animals received 100 mg. of amiloride during the same period. In these fourteen studies, not only was the toxic dose of digitalis extended, but its inotropic effect (see article) (common peak developed isovolumic ventricular pressure) was also increased. These studies have demonstrated that through a cardiac effect, by reducing the digitalis-induced loss of cardiac potassium, the potassium-sparing drugs, triameterene and amiloride, extend the toxic dose of digitalis and thus permit txtension of its inotropic activity.