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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 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.
Insights
Verapamil and diltiazem, calcium entry blockers, effectively reduced ouabain-induced ventricular arrhythmias in dogs. Felodipine showed no antiarrhythmic effects, highlighting differing drug capabilities in treating digitalis-induced arrhythmias.
Area of Science:
- Cardiovascular Pharmacology
- Cardiac Electrophysiology
Background:
- Ouabain overdose can cause life-threatening ventricular arrhythmias.
- Calcium entry blockers are a class of drugs used to manage various cardiovascular conditions.
- Understanding the comparative efficacy of different calcium entry blockers in treating specific arrhythmias is crucial for clinical practice.
Purpose of the Study:
- To compare the effectiveness of verapamil, diltiazem, and felodipine in abolishing ouabain-induced ventricular arrhythmias in a canine model.
- To investigate the antiarrhythmic properties of structurally and electrophysiologically distinct calcium entry blockers.
Main Methods:
- Anesthetized, vagotomized dogs were used to induce ventricular tachycardia (VT) with ouabain.
- Verapamil, diltiazem, felodipine, or saline were administered to dogs with established VT.
- Ventricular ectopy (VE) and mean aortic pressure were monitored before and after drug administration.
Main Results:
- Verapamil significantly reduced ouabain-induced VT (97% to 8% VE) at higher doses.
- Diltiazem showed moderate effectiveness (96% to 50% ectopy) at a dose of 100 micrograms/kg.
- Felodipine demonstrated no antiarrhythmic effects, while all blockers lowered aortic pressure, with felodipine having the most prominent effect.
Conclusions:
- Verapamil and diltiazem exhibit significant antiarrhythmic effects against ouabain-induced VT in dogs.
- Felodipine lacks efficacy in this specific arrhythmia model.
- The superior antiarrhythmic action of verapamil may be attributed to its additional electrophysiologic properties beyond calcium channel blockade.