Bush L R, Evans R M, Gaul S L, D'Alonzo A J
Pharmacology. 1987;34(2-3):111-20. doi: 10.1159/000138260.
We compared the abilities of three different calcium (Ca2+) entry blockers, verapamil, diltiazem and felodipine to abolish ouabain-induced ventricular ectopy (100 X 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 micrograms/kg ouabain. 30 min after establishing VT, either verapamil (25-50 micrograms/kg + 5-10 micrograms/kg/min), diltiazem (50-100 micrograms/kg + 20-50 micrograms/kg/min), felodipine (3 micrograms/kg + 0.3 micrograms/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 micrograms/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.