Antifibrillatory and electrophysiologic actions of moricizine alone and in combination with lidocaine: a prospective, randomized trial.
OBJECTIVE
The Cardiac Arrhythmia Suppression Trial II showed that moricizine acutely increases the occurrence of sudden cardiac death. Thus the objective of this investigation was to evaluate the antifibrillatory properties of moricizine (a new antiarrhythmic agent) alone and in combination with lidocaine (an established antifibrillatory agent).


METHODS
Prospective, double-blind, randomized, placebo-controlled trial.


METHODS
Laboratory at a large, university-affiliated medical center.


METHODS
Eighteen domestic farm swine with a mean weight of 39 +/- 5 kg.


METHODS
After pentobarbital anesthesia, the animals were instrumented. A bipolar pacing catheter was placed in the right ventricular apex and a pig-tail catheter was placed in the aortic arch for induction of ventricular fibrillation and aortic blood pressure monitoring. Subsequently, the pigs were randomized to moricizine or control (0.9% saline) groups. Each group underwent three treatment phases: baseline, drug (moricizine 2 mg/kg loading dose, 1.5 mg/kg/hr infusion, or saline bolus and infusion), and drug combined with lidocaine (5 mg/kg loading dose, 4 mg/kg/hr infusion). Ventricular fibrillation threshold was determined every 5 to 10 mins over a 1-hr period during each treatment phase.


RESULTS
Ventricular fibrillation threshold values in the animals randomized to control were 16.8 +/- 7.6, 18.1 +/- 8.9, and 23.9 +/- 10.4 mA at baseline during saline infusion, and when saline was combined with lidocaine, respectively. The values during the saline-lidocaine combination treatment phase were significantly greater than the values at baseline and during saline treatment alone (p < .001). Ventricular fibrillation threshold values in the animals randomized to receive moricizine were 15.5 +/- 4.4, 18.1 +/- 5.1, and 21.1 +/- 8.4 mA at baseline, during moricizine infusion, and when moricizine was combined with lidocaine. The values during the lidocaine-moricizine combination treatment phase were significantly greater than values at baseline (p = .005), but not during moricizine treatment alone (p = .16). The increase in ventricular fibrillation threshold from baseline to moricizine (17%) was similar to the increase from baseline to saline (7%), p = .37. The increase in ventricular fibrillation threshold when lidocaine was added to moricizine (13%) was less than the increase with lidocaine alone (32%), p = .05.


CONCLUSIONS
In this experimental model, moricizine, at the dose studied, lacked antifibrillatory properties. Moreover, moricizine did not contribute to the antifibrillatory effects of lidocaine.
Ujhelyi
M R
MR
University of Connecticut College of Pharmacy, Storrs.
O'Rangers
E A
EA
Fan
C
C
Kluger
J
J
Chow
M S
MS
D000818:Animals; D001794:Blood Pressure; D004195:Disease Models, Animal; D004311:Double-Blind Method; D004562:Electrocardiography; D008012:Lidocaine / Q000008:administration & dosage* / Q000494:pharmacology; D016293:Moricizine / Q000008:administration & dosage* / Q000494:pharmacology; D011446:Prospective Studies; D011897:Random Allocation; D013552:Swine; D014693:Ventricular Fibrillation / Q000503:physiopathology* / Q000517:prevention & control*
D016293:Moricizine; D008012:Lidocaine