Ethmozin, a new antiarrhythmic drug for suppressing ventricular premature complexes.

Podrid, Philip J.; Lyakishev, A.A.; Lown, Bernard; Мазур, Н. А.

doi:10.1161/01.cir.61.2.450

Cited by 82 publications

(13 citation statements)

References 19 publications

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“…Conclusions Moricizine (1) prolongs the atrial flutter cycle length, primarily by slowing conduction in an area of slow conduction in the reentrant circuit, (2) terminates atrial flutter by causing block of the circulating reentrant wave front in an area of slow conduction of the reentrant circuit, and (3) effectively interrupts otherwise stable atrial flutter in this canine model. The reason for these effects of moricizine are not readily explained by its effects on global atrial conduction times and refractoriness studied during sinus rhythm.…”

Section: Methods and Resultsmentioning

confidence: 86%

Mechanism of interruption of atrial flutter by moricizine. Electrophysiological and multiplexing studies in the canine sterile pericarditis model of atrial flutter.

et al. 1994

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BACKGROUND Moricizine is said to have potent effects on cardiac conduction but little or no effect on cardiac refractoriness. METHODS AND RESULTS The effects of moricizine (2 mg/kg IV) on induced atrial flutter were studied 2 to 4 days after the creation of sterile pericarditis in 11 dogs. Ten episodes of stable atrial flutter before and after the administration of moricizine were studied in 9 dogs in the conscious, nonsedated state, and 7 episodes were studied in 6 dogs in the anesthetized, open chest state. In the conscious state, the effects of moricizine on atrial excitability, atrial effective refractory period, and intra-atrial conduction times were studied by recording during overdrive pacing of sinus rhythm from epicardial electrodes placed at selected atrial sites. Moricizine prolonged the atrial flutter cycle length in all the episodes, from a mean of 133 +/- 9 to 172 +/- 27 milliseconds (P < .001), and then terminated 7 of the 10 episodes. Moricizine increased the atrial threshold of excitability from a mean of 2.3 +/- 1.4 to 3.3 +/- 2.2 mA (P < .01) and prolonged intra-atrial conduction times (measured from the sulcus terminalis to the posteroinferior left atrium) from a mean of 58 +/- 6 to 64 +/- 5 milliseconds (P < .005). Prolongation of the atrial effective refractory period from 166 +/- 20 to 174 +/- 24 milliseconds (P < .05) was observed only at the sulcus terminalis site. In the open chest studies, administration of moricizine prolonged the atrial flutter cycle length from a mean of 150 +/- 15 to 216 +/- 30 milliseconds (P < .001) and then terminated the atrial flutter in all 7 episodes. As demonstrated by simultaneous multisite mapping from 95 bipolar sites on the right atrial free wall, the atrial flutter cycle length prolongation was either due to further slowing of conduction in an area of slow conduction in the reentrant circuit of the atrial flutter (5 episodes) or further slowing of conduction in an area of slow conduction plus the development of a second area of slow conduction (2 episodes). The change in conduction times in the rest of the reentrant circuit was negligible (10.9 +/- 8.7% of the total change). In all 7 episodes, the last circulating reentrant wave front blocked in an area of slow conduction. CONCLUSIONS Moricizine (1) prolongs the atrial flutter cycle length, primarily by slowing conduction in an area of slow conduction in the reentrant circuit, (2) terminates atrial flutter by causing block of the circulating reentrant wave front in an area of slow conduction of the reentrant circuit, and (3) effectively interrupts otherwise stable atrial flutter in this canine model. The reason for these effects of moricizine are not readily explained by its effects on global atrial conduction times and refractoriness studied during sinus rhythm. Local changes in conduction in an area(s) of slow conduction are responsible for both cycle length prolongation and atrial flutter termination rather than the traditional wavelength concept of head-tail interaction.

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Section: Methods and Resultsmentioning

confidence: 86%

Mechanism of interruption of atrial flutter by moricizine. Electrophysiological and multiplexing studies in the canine sterile pericarditis model of atrial flutter.

et al. 1994

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“…3336 Results of investigations in the United States indicate that ethmozine is an effective antiarrhythmic drug for suppressing VPDs with a low incidence of side effects. [37][38][39] Few clinical studies are available comparing the effectiveness and toxicity of ethmozine with the effectiveness and toxicity of currently available type I antiarrhythmic drugs.40 Since comparison of efficacy and toxicity are best done with the identical group of patients, this study reports the results of a double-blind longitudinal crossover trial comparing the relative efficacy of disopyramide and ethmozine in reducing VPDs.…”

mentioning

confidence: 99%

Comparative effect of disopyramide and ethmozine in suppressing complex ventricular arrhythmias by use of a double-blind, placebo-controlled, longitudinal crossover design.

Pratt¹,

Young²,

Francis³

et al. 1984

Circulation

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This placebo-controlled, double-blind, longitudinal crossover study compares the efficacy of disopyramide and ethmozine, a new investigational drug, in suppressing frequent (40 or more per hour) ventricular premature depolarizations (VPDs) in 27 patients completing a 37 day protocol. Although both drugs significantly reduced VPDs relative to placebo, ethmozine was a superior antiarrhythmic drug in achieving near-total abolition of VPDs (30% of patients), which was never observed during disopyramide dosing (p < .05). At the 80% VPD reduction level, ethmozine was effective in 56% of all patients compared with an effectiveness in only 22% of patients during disopyramide therapy (p < .05). The mean peak plasma level of ethmozine was 0.66 + 0.8 gg/ml, which significantly fell to a trough level of 0.1 + 0.08 gg/ml (p < .001). Mean peak and trough plasma levels of disopyramide exhibited less fluctuation (2.6 + 0.9 ,ug/ml vs 2.2 0.9 gg/ml). Ethmozine had no effect on the QTC interval, whereas disopyramide prolonged it significantly. Importantly, while disopyramide produced serious side effects in 30% of patients, ethmozine was well tolerated with no statistically significant side effects compared with placebo. Circulation 69, No. 2, 288-297, 1984. EPIDEMIOLOGIC STUDIES in which 12-lead electrocardiograms have been used have documented an increased risk of sudden cardiac death in patients with coronary heart disease who have ventricular premature depolarizations (VPDs). 1-3 Ambulatory electrocardiographic recording has allowed a more systematic and complete quantification of these ventricular arrhythmias that are predictive of sudden cardiac death, especially in patients surviving myocardial infarction.±7The currently available antiarrhythmic drugs include the /3-blockers, some of which have well-defined efficacy for suppressing VPDs.8'9 A number of multi- 288center clinical trials using /3-blockers for patients in the late-hospitalization phase of acute myocardial infarction have shown an overall reduction of sudden cardiac death. I"2 None of these multicenter trials were designed specifically to define the mechanism of this reduction in sudden cardiac death that presumably was a result of preventing sustained ventricular tachycardia and ventricular fibrillation. MethodsProtocol. This randomized, placebo-controlled, doubleblind, crossover study was performed in 33 patients. The occurrence of .40 VPD/hr on at least two consecutive 24 hr ambulatory electrocardiographic recordings (screening) made up the entry criteria. Of the 33 patients randomized, 27 patients (18 men and nine women, ranging in age from 36 to 72 years) completed the protocol and the data from these patients form the basis of this report. Six patients were dropped from the study. Three of these patients, although having the qualifying arrhythmia during screening (_40 VPD/hr), failed to qualify on placebo monitoring. One patient had chronic heart failure that worsened during placebo and ethmozine dosing and was dropped from the study; invasiv...

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“…Since the study of antiarrhythmic drugs effects on sinus node (SN) function is of great practical importance (Carrasco et al, 1978;Coldberg et al, 1982;Jordan et al, 1979;LaBarre et al, 1979;Vera et al, 1982) and taking into account that during recent years ethmozin has been widely introduced into clinical practice (Chazov et al, 1984;Mahlers and Brikhead, 1982; Morganroth et al, Podrid et al, 1980;Pratt et al, 1983), we studied ethmozin electrophysiologic effects on sinus node function in patients with and without sinus node dysfunction.…”

Section: Introductionmentioning

confidence: 99%

Electrophysiologic effects of ethmozin on sinus node function in patients with and without sinus node dysfunction

Shugushev

Rosenshtraukh

Smetnev

1986

Clinical Cardiology

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Summary:To compare the effects of ethmozin on sinus node (SN) function in the presence (9 patients) and absence (1 7 patients) of SN dysfunction, sinus cycle length (SCL), maximal corrected sinus recovery time (CSRT), paced cycle length yielding peak SN suppression, and indirect sinoatrial SA conduction time (SACT) were determined before and after intravenous administration of ethmozin in the dose 2 mg/kg. The mean f SD SCL were significantly shortened in patients with normal SN and were not changed in patients with SN dysfunction after ethmozin administration. The mean maximal CSRT was 252f72 before and 284f86 ms after ethmozin administration in patients with normal SN function (p<0.05). In patients with SN dysfunction (p

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Ethmozin, a new antiarrhythmic drug for suppressing ventricular premature complexes.

Cited by 82 publications

References 19 publications

Mechanism of interruption of atrial flutter by moricizine. Electrophysiological and multiplexing studies in the canine sterile pericarditis model of atrial flutter.

Mechanism of interruption of atrial flutter by moricizine. Electrophysiological and multiplexing studies in the canine sterile pericarditis model of atrial flutter.

Comparative effect of disopyramide and ethmozine in suppressing complex ventricular arrhythmias by use of a double-blind, placebo-controlled, longitudinal crossover design.

Electrophysiologic effects of ethmozin on sinus node function in patients with and without sinus node dysfunction

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