COMBINATION ETHACIZIN AND ETHMOZIN TREATMENT OF RESISTANT VENTRICULARECTOPY - THEORETICAL, EXPERIMENTAL, AND CLINICAL-STUDY

Ethmozin (Moricizine HCl) and ethacizin are two class I antiarrhythmic drugs with different rate constants of interaction with the sodium ch annel. Computer simulation using the ''guarded-receptor'' model predic ted that the combination of ethacizin and ethmozin should exert a grea ter decrease in excitability and conduction at short coupling interval s, but little effect at normal heart rates (HR). To test this predicti on, we measured intraventricular conduction delay in canine hearts in vivo. In agreement with the model, the combination more potently prolo nged the delay only at intervals <600 ms as compared with ethacizin al one. Combination therapy was tested in 6 patients with idiopathic vent ricular ectopic depolarizations (VEDs). Three patients were resistant to either ethmozin or ethacizin monotherapy, and three could not toler ate effective doses because of side effects. Quantitative continuous E CG monitoring showed that petal VEDs in the resistant group decreased 0 and 17 +/- 13% for 400 and 800 mg/day ethmozin and 18 +/- 12 and 55 +/- 12% for 100 and 200 mg/day ethacizin, respectively. Combined thera py with ethmozin (400 mg/day) and ethacizin (100 mg/day) reduced the n umber of VEDs by 78 +/- 2% in these patients without side effects. In the ''nonresistant'' but intolerant group of patients, use of the comb ination allowed relief of symptomatic ectopy without side effects. A t heoretical model correctly predicted an effective combination of class I antiarrhythmic drugs, one with ''fast-off' and one with ''slow-off' kinetics, which may provide a general rationale for choosing drug com binations.