Do verapamil, flecainide, or bretylium alter ventricular fibrillation threshold and ventricular repetitive response threshold in a canine model?
In a canine model, bretylium significantly increases ventricular fibrillation threshold without affecting ventricular repetitive response threshold, whereas flecainide increases both parameters.
The changes produced by verapamil, bretylium and flecainide in both ventricular fibrillation threshold (VFT) and ventricular repetitive response threshold (VRRT) were studied in 20 closed-chest dogs anaesthetized with pentobarbital. Right ventricle endocardium thresholds were determined using bipolar electrode catheters. Increasing intensity stimulus trains (200 ms, 4 ms, 100 Hz, 1 mA steps) were delivered 50 ms after QRS; VRRT and VFT were calculated before and after drug administration. Three study groups were considered according to the drug assayed: (1) verapamil 0.15 mg.kg-1 n = 6; (2) flecainide 2.0 mg.kg-1 n = 7, and (3) bretylium 10.0 mg.kg-1 n = 7. Flecainide significantly increased VRRT (4.8 +/- 1.4 vs 9.4 +/- 1.5 mA, P < 0.05), but the latter failed to change in the other two groups. VFT remained unchanged with verapamil, increased slightly post-flecainide (10.3 +/- 4.6 vs 12.4 +/- 4.1, P < 0.05 mA) and markedly post-bretylium (10.3 +/- 4.6 vs 17.3 +/- 7.5, P < 0.05). VFT changes were significantly correlated (r = 0.77, P < 0.05) with the effective refractory period changes in the bretylium group. Thus, of the three drugs tested, bretylium induced the greatest VFT increases without modifying VRRT, whereas flecainide affected both parameters. Only in the bretylium series were ERP changes significantly correlated to the corresponding VFT changes. This suggests that ventricular fibrillation threshold increase is not a non-specific property of antiarrhythmic drugs. Changes in ventricular repetitive response threshold may provide additional information.
Quesada et al. (1993) studied this question.