Comparative Effects of Verapamil, Diltiazem and Felodipine during Experimental Digitalis-Induced Arrhythmias

Abstract

We compared the abilities of three different calcium (Ca²⁺) entry blockers, verapamil, diltiazem and felodipine to abolish ouabain-induced ventricular ectopy (100 × ectopic/total beats, VE) in anesthetized, closed-chest dogs. Ventricular tachycardia (VT) was produced in anesthetized, bilaterally vagotomized, closed-chest dogs by an average dose of 65 ± 19 μg/kg ouabain. 30 min after establishing VT, either verapamil (25–50 μg/kg + 5–10 μg/kg/min), diltiazem (50–100 μg/kg + 20–50 μg/kg/min), felodipine (3 μg/kg + 0.3 μg/kg/min) or saline was administered for another 30 min. Verapamil, at the higher dose utilized, practically abolished ouabain-induced VT (97 ± 3 to 8 ± 19% VE); diltiazem was moderately effective (96 ± 4 to 50 ± 8% ectopy) at 100 μg/kg, and felodipine exerted no antiarrhythmic effects in this model. All three Ca²⁺ entry blockers lowered mean aortic pressure, felodipine lowering this parameter most prominently. Thus, these structurally and electrophysiologically dissimilar Ca²⁺ entry blockers differed in their abilities to abolish the digitalis glycoside-induced arrhythmias in vivo. The superiority of verapamil may be related to its multiple, additional electrophysiologic effects.

The Electrophysiological Effects of Cardiac Glycosides in Human iPSC-derived Cardiomyocytes and in Guinea Pig Isolated Hearts

“…The blockade of L-type Ca 2+ channel with a compound like nifedipine can mitigate the cardiotoxicity induced by cardiac glycosides [25,26]. Thus, if the increased Ca 2+ -wave amplitude reflects the Ca…”

Cardiotoxicity of digitalis glycosides: roles of autonomic pathways, autacoids and ion channels

“…All these data suggest that verapamil exerts a protective effect against the development of digitalis‐induced cardiac arrhythmias. Bush, Evans, Gaul & D'Alonzo (1987) have demonstared that verapamil abolished ouabain‐induced ventricular tachycardia, diltiazem was moderately effective, and felodipine exerted no antiarrhythmic effects against ouabain‐induced arrhythmias in anaesthetized, bilaterally vagotomized dogs. However, Komori, Ishii & Hashimoto (1985) reported that verapamil, diltiazem, and bepridil were ineffective on digitalis arrhythmia in dogs, although the maximum hypotensive doses were used.…”