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Antifibrillatory and electrophysiologic actions of moricizine alone and in combination with lidocaine: a prospective, randomized trial.

Abstract：

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). DESIGN:Prospective, double-blind, randomized, placebo-controlled trial. SETTING:Laboratory at a large, university-affiliated medical center. SUBJECTS:Eighteen domestic farm swine with a mean weight of 39 +/- 5 kg. INTERVENTIONS: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. CONCLUSION:In this experimental model, moricizine, at the dose studied, lacked antifibrillatory properties. Moreover, moricizine did not contribute to the antifibrillatory effects of lidocaine.

journal_name

Crit Care Med

journal_title

Critical care medicine

authors

Ujhelyi MR,O'Rangers EA,Fan C,Kluger J,Chow MS

doi

10.1097/00003246-199310000-00029

subject

Has Abstract

pub_date

1993-10-01 00:00:00

pages

1577-84

issue

eissn

0090-3493

issn

1530-0293

journal_volume

pub_type

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Antifibrillatory and electrophysiologic actions of moricizine alone and in combination with lidocaine: a prospective, randomized trial.