Effects of Moracizine Combined with Metoprolol on Hemodynamic Indices of the Left Atrium and Quality of Life in Patients with Atrial Fibrillation.

BACKGROUND: Drugs are the first choice of treatment for atrial fibrillation (AF), but there is currently a lack of efficient drug treatment options. The aim of this study was to investigate a combination drug treatment plan which may serve as a reference for the treatment of AF. METHODS: A total of 316 AF patients admitted to Jiaozhou Central Hospital in Qingdao from October 2020 to October 2022 were selected for this retrospective study. They were divided into a control group (CG, metoprolol, n = 156) and an observation group (OG, moracizine combined with metoprolol, n = 160) based on the treatment they received. The CG and OG groups were compared for clinical efficacy, occurrence of AF, cardiac output (CO), cardiac indexes (CI), stroke volume (SV), stroke indexes (SI) and improvement in QOL. RESULTS: The OG had a better effective rate of treatment, higher levels of CO, CI, SV and SI, and higher QOL scores compared to the CG, as well as a lower AF recurrence rate and AF burden (all p < 0.05). CONCLUSION: Moracizine combined with metoprolol is an effective treatment for AF patients. This drug combination was found to reduce the AF recurrence rate and burden in AF patients, and to improve their hemodynamic indices and QOL.

Moricizine (Ethmozine) Can Break Electrical Coupling between Rat Right Atrial Working Cardiomyocytes In Vitro.

A previously popular antiarrhythmic drug moricizine (ethmozine) is known for its blocking action on the fast sodium channels in cardiomyocytes. Its effects were examined only in isolated cardiomyocytes or in vivo. Here, the effect of moricizine (10 µM) was examined in vitro on perfused right atrial preparation, where it completely reproduced all the previously observed phenomena and disturbed electrical coupling between the working cardiomyocytes in 35.3±3.4 min, which arrested generation of action potentials. During washing, the cardiomyocytes restored rhythmic firing in 34.1±3.7 min. Inhibition of firing in the working atrial cardiomyocytes was not accompanied by suppression of rhythmic activity in the pacemaker cells of sinoatrial node as attested by rhythmic miniature spikes in the records of resting (diastolic) potential of these cardiomyocytes. Thus, moricizine disturbed conduction between the working atrial cardiomyocytes without affecting the pacemaker activity.

Time course of moricizine's effect on signal-averaged and 12 lead electrocardiograms: insights into mechanism of action.

The mechanism of action of moricizine, a new antiarrhythmic agent used in the Cardiac Arrhythmia Suppression Trial, is incompletely characterized. In addition, because moricizine is extensively metabolized, plasma moricizine concentration has an unknown relation to myocardial drug effect. Signal-averaged and standard electrocardiograms (ECGs) were used to monitor moricizine's myocardial effects in 16 patients with frequent ventricular premature complexes taking 600 to 900 mg daily. Three signal-averaged ECG variables were measured: total filtered QRS duration (fQRS), root-mean-square voltage in the terminal 40 ms of the QRS complex (V40) and the terminal low amplitude duration less than 40 microV (LAS). At steady state, plasma samples were collected and serial recordings of signal-averaged and standard ECGs were taken at 0, 1, 2, 4, 6 and 8 h after moricizine administration. A 24 h ambulatory ECG was recorded throughout the test period. Moricizine prolonged the fQRS (p less than 0.05) and decreased the V40 (p less than 0.05) of the signal-averaged ECG and prolonged the QRS (p less than 0.05) and corrected JT (JTc) intervals (p less than 0.05) of the standard ECG. The time course of the signal-averaged and standard ECG variables paralleled plasma moricizine concentration; that is, the maximal changes occurred at 1 to 2 h and declined to time 0 values at 8 h. The maximal changes were: fQRS (+8%), V40 (-33%), QRS (+8%) and JTc (+4%). Thus, dynamic changes were observed for intraventricular conduction (fQRS, QRS) and ventricular repolarization (JTc) over the dosing interval.(ABSTRACT TRUNCATED AT 250 WORDS)

Events in the Cardiac Arrhythmia Suppression Trial (CAST): mortality in the entire population enrolled.

To test the hypothesis that suppression of ventricular arrhythmias by antiarrhythmic drugs after myocardial infarction improves survival, the Cardiac Arrhythmia Suppression Trial (CAST) was initiated. Suppression was evaluated before randomization during an open label titration period. Patients whose arrhythmias were suppressed were randomized in the main study and those whose arrhythmias were partially suppressed were randomized in a substudy. Overall survival and survival free of arrhythmic death or cardiac arrest were lower [corrected] in patients treated with encainide or flecainide than in patients treated with placebo. However, the death rate in patients randomized to placebo therapy was lower than expected. This report describes the survival experience of all patients enrolled in CAST and compares it with mortality in other studies of patients with ventricular arrhythmias after myocardial infarction. As of April 18, 1989, 2,371 patients had enrolled in CAST and entered prerandomization, open label titration: 1,913 (81%) were randomized to double-blind, placebo-controlled therapy (1,775 patients whose arrhythmias were suppressed and 138 patients whose arrhythmias were partially suppressed during open label titration); and 458 patients (19%) were not randomized because they were still in titration, had died during titration or had withdrawn. Including all patients who enrolled in CAST, the actuarial (Kaplan-Meier) estimate of 1-year mortality was 10.3%. To estimate the "natural" mortality rate of patients enrolled in CAST, an analysis was done that adjusted for deaths that might be attributable to encainide or flecainide treatment either during prerandomization, open label drug titration or after randomization. Because the censoring procedure excluded patients treated with encainide or flecainide after randomization, the mortality estimate will be less than the unadjusted mortality estimate of 10.3%.(ABSTRACT TRUNCATED AT 250 WORDS)

Events in the Cardiac Arrhythmia Suppression Trial (CAST): mortality in patients surviving open label titration but not randomized to double-blind therapy.

The patient characteristics and outcomes were studied in the 318 patients who survived open label drug titration in the Cardiac Arrhythmia Suppression Trial (CAST) and who were not randomized to double-blind therapy and in 942 patients, who were randomized to double-blind placebo therapy. The patients randomized to placebo therapy had a lower total mortality or resuscitated cardiac arrest rate (4% vs. 8.5%). However, at baseline, nonrandomized patients were dissimilar from patients randomized to placebo in the following ways: older; lower left ventricular ejection fraction; greater use of digitalis, diuretic drugs and antihypertensive agents; lesser use of beta-adrenoceptor blocking agents and more frequent prior cardiac problems, including runs of ventricular tachycardia and left bundle branch block. A matched comparison that took these inequities into account showed no significant differences in mortality or rate of resuscitation from cardiac arrest between nonrandomized patients and clinically equivalent patients randomized to placebo. Cox regression analysis indicated that two factors significantly increased the hazard ratio for arrhythmic death or resuscitated cardiac arrest in the nonrandomized patients: female gender (4.7, p less than 0.05) and electrocardiographic events (ventricular tachycardia, proarrhythmia, widened QRS complex, heart block, bradycardia) during open label titration (7.0, p less than 0.005). However, some potentially important differences between men and women were not included in the Cox regression model. Of the nonrandomized patients, approximately 70% were not randomized because of lack of suppression of ventricular premature depolarizations or adverse events, or both, and the remaining 30% because of patient or private physician request with no indication of another reason.(ABSTRACT TRUNCATED AT 250 WORDS)

The Cardiac Arrhythmia Suppression Trial: first CAST ... then CAST-II.

The Cardiac Arrhythmia Suppression Trial (CAST) was a study designed to test the hypothesis that suppression of ventricular premature complexes after a myocardial infarction would improve survival. Preliminary results showed that suppression of ventricular premature complexes with encainide and flecainide worsened survival, and the CAST continued as the CAST-II with moricizine compared with its placebo. The protocol for the CAST-II was changed to attempt to enroll patients more likely to experience serious arrhythmias. The enrollment time was narrowed to 4 to 90 days after myocardial infarction; the qualifying ejection fraction was lowered to less than or equal to 0.40; a higher dose of moricizine could be used; early titration itself was double-blind with a placebo, and the definition of disqualifying ventricular tachycardia was changed to allow patients with more serious arrhythmias to be entered into the trial. The Cardiac Arrhythmia Suppression Trial-II was subsequently terminated prematurely because 1) patients treated with moricizine had an excessive cardiac mortality rate during the 1st 2 weeks of exposure to the drug, and 2) there appeared to be little chance of showing a long-term survival benefit from treatment with moricizine. This report outlines the rationale behind the Cardiac Arrhythmia Suppression Trial and the reasons for selection of the drugs used in the CAST and CAST-II.

Predicting mortality after myocardial infarction from the response of RR variability to antiarrhythmic drug therapy.

OBJECTIVES: This study was designed to test the hypothesis that antiarrhythmic drugs that decrease RR variability will predict all-cause mortality during follow-up after myocardial infarction. BACKGROUND: RR variability, a noninvasive indicator of autonomic nervous system activity, predicts death after acute myocardial infarction independently of other risk predictors and changes substantially in response to some drugs. A previous study in patients with chronic heart disease and frequent ventricular premature complexes reported that flecainide decreased vagal modulation of RR intervals but amiodarone did not. The investigators of that study speculated that changes in RR variability during antiarrhythmic drug therapy predict an increased mortality rate during long-term drug treatment. To explore this hypothesis further, we compared the effects of encainide and flecainide, which increase long-term mortality substantially, on RR variability with the effects of placebo and moricizine, which have no significant effect on mortality during long-term treatment of unsustained ventricular arrhythmias after myocardial infarction. METHODS: The 24-h power spectral density was computed from the baseline electrocardiographic recordings and drug evaluation tapes, and six frequency domain measures of RR variability were calculated: ultra-low frequency (< 0.0033 Hz), very low frequency (0.0033 to < 0.04 Hz), low frequency (0.04 to < 0.15 Hz) and high frequency power (0.15 to < 0.40 Hz), plus total power (< 0.40 Hz) and the ratio of low to high frequency power. Changes in power spectral measures were related to drug treatment and to mortality. RESULTS: In the placebo group, values for RR interval and RR variability increased because of recovery from the effects of acute myocardial infarction. Contrasting placebo treatment with all three active antiarrhythmic drug treatments taken together showed that of all the measures of RR variability, only NN50, pNN50 and low frequency power changed significantly during drug treatment (Bonferroni adjusted p value < 0.025); these variables all decreased during drug therapy. Contrasting encainide and flecainide with moricizine, we found that the encainide and flecainide groups taken together showed a larger decrease in dLF than moricizine, but the difference was of borderline significance (Bonferroni adjusted p value < 0.08). Survival was significantly worse in the groups treated with encainide and flecainide than in the groups treated with placebo or moricizine (relative risk > 2.0, adjusted p < 0.05). The antiarrhythmic drug-induced change in measures of RR variability was not a significant predictor of all-cause mortality during a year of follow-up after myocardial infarction. CONCLUSIONS: Encainide, flecainide and moricizine all caused a decrease in RR variability in patients studied approximately 1 month after acute myocardial infarction. Encainide and flecainide caused a significant increase in mortality rates; placebo and moricizine did not. Baseline measurements of RR variability also predicted all-cause mortality after myocardial infarction. The decrease in RR variability produced by the three antiarrhythmic drugs did not predict mortality during follow-up.

Circadian pattern of arrhythmic death in patients receiving encainide, flecainide or moricizine in the Cardiac Arrhythmia Suppression Trial (CAST).

OBJECTIVES: The purpose of this study was to assess the effect of antiarrhythmic drugs on the timing of arrhythmic death. BACKGROUND: Sudden cardiac death remains a problem of epidemic proportions. Delineating its pathophysiology is an important step in devising preventive measures. Previous studies have shown a circadian pattern of onset of sudden cardiac death. The effect of antiarrhythmic drugs on this pattern has not been systematically studied. METHODS: The Cardiac Arrhythmia Suppression Trial (CAST) was a multicenter double-blind, placebo-controlled study designed to determine whether suppression of ventricular ectopic activity by means of antiarrhythmic drugs (encainide, flecainide or moricizine) after acute myocardial infarction would reduce the incidence of arrhythmic death. RESULTS: The trial was terminated prematurely because of an unexpectedly high mortality rate in the active treatment group. The onset of arrhythmic death in this group (in patients not receiving beta-adrenergic blocking agents) displayed a bimodal variation, with significant peaks in midmorning and late afternoon/early evening. More than half of the symptomatic events were accompanied by anginalike symptoms. Approximately 30% of all events occurred within 2 h of awakening. CONCLUSIONS: Our data suggest the possibility of a complex interaction among antiarrhythmic drugs, sympathetic nervous system activation and acute myocardial ischemia. Planning of future antiarrhythmic drug trials will need to take this information into account.

Relations between heart failure, ejection fraction, arrhythmia suppression and mortality: analysis of the Cardiac Arrhythmia Suppression Trial.

OBJECTIVES: We studied the relations between heart failure, ejection fraction, arrhythmia suppression and mortality. BACKGROUND: Both left ventricular ejection fraction and functional class of heart failure are strongly associated with mortality after acute myocardial infarction. Both are also related to the presence of ventricular arrhythmias and have been identified as factors related to the ability to suppress ventricular arrhythmias. Little has been reported about the relations between these two factors and arrhythmia suppression or mortality. METHODS: Baseline data from the Cardiac Arrhythmia Suppression Trial were used to define several categories of heart failure and to relate both the resulting categories and ejection fraction to arrhythmia suppression and mortality using logistic and survival regression analytic methodologies. RESULTS: Regardless of the prospective baseline definition of heart failure used, the data consistently showed that heart failure was a more powerful predictor of subsequent congestive heart failure events and arrhythmia suppression and was equally powerful in predicting death. However, each variable provided incremental information when included in the prediction model. Heart failure and ejection fraction appeared to be independent predictors of death. Interactions were observed: A low ejection fraction was more predictive of failure of arrhythmia suppression in patients with than without evidence of heart failure before or at baseline; a low ejection fraction was more predictive of subsequent congestive heart failure events in patients without than with evidence of heart failure before or at baseline. CONCLUSIONS: Although heart failure as a prognostic feature appears to be somewhat superior to ejection fraction, both are powerful predictors of arrhythmia suppression and cardiac events in patients with ventricular arrhythmia after myocardial infarction. Each provides incremental prediction.

Congestive heart failure induced by six of the newer antiarrhythmic drugs.

The incidence of drug-induced congestive heart failure with several newer antiarrhythmic agents including encainide, ethmozine, lorcainide, mexiletine, propafenone and tocainide was determined in a group of 407 patients who underwent 1,133 drug tests. The incidence rate ranged from 0.7% with lorcainide to 4.7% with propafenone. Congestive heart failure was present in 167 patients (41%) who underwent 491 drug trials. Congestive failure was induced in 15 (9%) of these 167 patients and involved 19 (3.9%) of the 491 tests. Left ventricular ejection fraction was 20 +/- 8% in patients who developed congestive failure, in contrast to 39 +/- 19% in those who did not (p less than 0.001). It is concluded that each of the six antiarrhythmic drugs examined has the potential to aggravate congestive heart failure in patients with reduced left ventricular ejection fraction or a history of congestive heart failure, but the incidence rate is low and its occurrence unpredictable.

Differential modulation of autonomic activity by ethmozin and ethacizin (analog of ethmozin) on the canine sinus node and atrioventricular junction.

The chronotropic and dromotropic actions of ethmozin and its diethylamine analog ethacizin were studied in the presence and absence of combined muscarinic, beta- and alpha-adrenoreceptor blockade in the intact canine heart in situ (n = 38). Injections of ethacizin, 5, 10 and 25 micrograms/ml, into the sinus node artery caused an immediate and significant (p less than 0.001) sinus bradycardia of 2, 6 and 11%, respectively. Injection of 25 and 50 micrograms/ml of ethacizin into the atrioventricular (AV) node artery significantly (p less than 0.001) prolonged AV conduction time with occasional second degree heart block. Conduction delay was located exclusively during the AH interval of the His bundle electrogram. Autonomic blockade did not alter the negative chronotropic or negative dromotropic effects of ethacizin. Ethacizin, 25 micrograms/ml, injected into the sinus node artery immediately reduced the sinus node response to vagal stimulations by 30% and the effect of acetylcholine, 0.1 micrograms/ml, injected into the sinus node artery by 50%. Ethacizin, 25 micrograms/ml, injected into the AV node artery immediately reduced the duration of complete AV block elicited by vagal stimulation or intranodal acetylcholine, 0.5 micrograms/ml, by 90%. Ethacizin caused a minor reduction in sinus node response to right stellate stimulations without, however, altering the sinus node response to intranodal norepinephrine. Ethmozin injections of up to 50 micrograms/ml into the sinus and AV node arteries had no chronotropic or dromotropic effects. Ethmozin had a minor and variable vagolytic action but significantly (p less than 0.05) reduced the sinus node response to sympathetic nerve stimulation. Hence, ethacizin, in contrast to ethmozin, has a direct depressing action on both the sinus node and the AV junction.(ABSTRACT TRUNCATED AT 250 WORDS)

Cimetidine inhibition of ethmozine metabolism.

Ethmozine, a phenothiazine antiarrhythmic, is effective in atrial and ventricular arrhythmias. Because of the extensive hepatic metabolism of ethmozine, we investigated the effects of the potent hepatic enzyme inhibitor cimetidine on the kinetics and dynamics of ethmozine. Eight healthy men 22 to 40 years old (means = 27.6 years) received a single, oral, 500 mg dose of ethmozine. Ethmozine dosing was repeated 15 days later after cimetidine, 300 mg four times a day for 7 days. Plasma samples were drawn over the next 24 hours for measurement of ethmozine. ECGs were obtained 1, 2, 4, 8, and 24 hours after each dose. After cimetidine, ethmozine clearance fell from 38.2 +/- 10.7 to 19.7 +/- 4.2 ml/kg/min and the t1/2 increased from 3.3 +/- 1.3 to 4.6 +/- 1.6 hours. Ethmozine prolonged the PR and QRS intervals, but there was no detectable further increase after cimetidine. Heart rate and blood pressure were not altered by ethmozine either alone or in the combination. We conclude that cimetidine increases plasma concentrations of ethmozine but did not induce any detectable further increase in the PR or QRS intervals.

Efficacy, safety, hemodynamic effects, and pharmacokinetics of high-dose moricizine during short- and long-term therapy.

Moricizine, 15 mg/kg, was given to 10 patients with frequent ventricular ectopic depolarizations, eight of whom had previously been treated unsuccessfully with antiarrhythmic drugs. A single-blind inpatient study was followed by therapy for up to 6 months. Two patients developed aggravation of arrhythmia during inpatient therapy. Of the eight patients who completed the inpatient study, seven achieved greater than or equal to 80% suppression of total ventricular ectopic depolarizations (P less than 0.001). During inpatient therapy the mean of the individual patients' suppression of total ventricular ectopic depolarizations was 87.9%, paired ventricular beats 99.3%, nonsustained ventricular tachycardia 99.6%, and premature atrial contractions 89.0%. Suppression was maintained during long-term therapy. The PR interval increased 27% (P less than 0.001), QRS interval increased 10% (P less than 0.0001), QTc increased 1% (P not significant), and JTc decreased 2% (P not significant). Heart rate, blood pressure, and left ventricular performance at rest and exercise were unchanged by moricizine. Moricizine half-life was 9.2 +/- 3.4 hours. Plasma levels of moricizine decreased after 10 days of therapy, suggesting induction of metabolic enzyme systems.

Complex ventricular arrhythmias associated with the mitral valve prolapse syndrome. Effectiveness of moricizine (Ethmozine) in patients resistant to conventional antiarrhythmics.

On the basis of epidemiologic studies, more than 10 million Americans have echocardiographic evidence of mitral valve prolapse. Although ventricular arrhythmias occur frequently (over 50 percent of patients with mitral valve prolapse), they rarely result in sustained ventricular tachycardia or sudden cardiac death. However, a common problem in clinical practice is a patient with mitral valve prolapse and symptomatic complex ventricular arrhythmias refractory or intolerant to both beta blockers and conventional type I antiarrhythmics. These drugs are known to have frequent side effects, toxicity, and proarrhythmic effects. In 17 patients with mitral valve prolapse who presented with symptomatic complex ventricular arrhythmias and who were unresponsive to an average of the three conventional agents, moricizine (Ethmozine) was effective in suppressing 90 percent of ventricular premature depolarizations, 99 percent of nonsustained runs of ventricular tachycardia, as well as all sustained runs of ventricular tachycardia, resulting in abolition of palpitations, dizziness, and syncopal episodes. Its efficacy as well as its low frequency of minor side effects makes it ideal for future consideration in the population with mitral valve prolapse, who are frequently young and may therefore require therapy for many years.

Drug interactions with Ethmozine (moricizine HCl).

Moricizine HCl, a phenothiazine derivative synthesized in the USSR in 1964, has been shown to be an orally effective antiarrhythmic drug. Moricizine HCl has demonstrated a low incidence of generally mild and transient side effects. Studies of possible drug interaction between it and other drugs most likely to be administered to cardiovascular patients are currently being conducted in US drug trials. Possible interactions between moricizine HCl and cimetidine, and between moricizine HCl and digoxin, are reviewed. The coadministration of moricizine HCl had no effect on the pharmacokinetics of cimetidine; in contrast, cimetidine administration slowed the elimination of moricizine HCl. The implications of greater therapeutic and/or toxic effects of moricizine HCl must be considered for patients receiving cimetidine and moricizine HCl concomitantly. No significant interactions were observed when monitoring serum levels of moricizine HCl and digoxin in patients with normal renal function receiving digoxin therapy for congestive heart failure or atrial fibrillation. Moricizine HCl in therapeutic dosages (10 mg/kg daily) demonstrated antiarrhythmic efficacy without significant alterations in serum digoxin levels.

Pharmacokinetics of moricizine HCl.

Moricizine HCl is a phenothiazine derivative with antiarrhythmic properties. It was developed in the USSR and is now undergoing clinical evaluation. Although preliminary work has shown moricizine HCl to be effective in treating both atrial and ventricular arrhythmias, little is known of its pharmacokinetics. There is a 4-fold variability in range for its elimination half-life and in volumes of distribution and clearance. There is a linear relation for peak plasma levels and area under the plasma concentration/time curve with regard to single-dose administration of moricizine HCl. The bioavailability of moricizine HCl connotes extensive first-pass effect, or presystemic metabolism. Very little of moricizine is excreted unchanged; it is extensively metabolized to certain compounds that are present in plasma for extended periods. Moricizine is extensively (92% to 95%) bound to plasma protein. Its coadministration with cimetidine leads to additive systemic effects; however, there is no evidence of alterations in steady-state levels when moricizine HCl is coadministered with digoxin. Because moricizine is a drug with active metabolites, its concentration/effect profile is complex; this poses a challenge for accurate dose titration. This may, however, be a helpful challenge in that the metabolites may one day prove useful in therapy. This surmise warrants further study.

Clinical development of moricizine as an antiarrhythmic agent.

The primary development of moricizine as an antiarrhythmic agent has occurred in the Soviet Union and the United States. The data in this presentation are based on the 1,844 subjects/patients (1,817 adults and 27 pediatric patients) who participated in 34 controlled studies and 3 uncontrolled compassionate-use programs conducted in the United States. Of the 1,817 adults, 443 received only placebo or comparative agents and 1,374 received moricizine in daily doses of 50 to 1,800 mg. A total of 1,190 adult patients (mean age 59 years) had ventricular arrhythmias classified as either benign (8%), potentially lethal (58%) or lethal (33%). Most patients had a history of greater than or equal to 1 cardiovascular disease, including coronary artery disease, previous myocardial infarction and congestive heart failure. Antiarrhythmic activity was assessed by four methods: 24-hour ambulatory electrocardiographic monitoring, programmed electrical stimulation, exercise tolerance tests, and global evaluation (only for some patients in the compassionate-use program). In addition, the effects of moricizine on symptoms associated with ventricular arrhythmias were assessed. The safety variables evaluated included adverse experiences, proarrhythmia, congestive heart failure, other cardiovascular effects, death, chest x-ray, ophthalmic examinations, neuroleptic phenothiazine effects and clinical laboratory tests.

Placement of moricizine in the selection of antiarrhythmic drug therapy.

The selection of antiarrhythmic drug therapy requires a careful assessment of the benefits of ventricular arrhythmia suppression compared with the risks of antiarrhythmic drug use. Since reduction in sudden cardiac death from ventricular arrhythmia suppression has not been demonstrated, the only indications for antiarrhythmic drug suppression involve the reduction of hemodynamic symptoms such as syncope (a major benefit) or the reduction of nonhemodynamic symptoms such as palpitations or dizziness (a minor benefit). Noncardiac adverse effects and organ toxicity as well as cardiac side effects must be considered when antiarrhythmic drug therapy is initiated. For reduction of nonhemodynamically important symptoms in patients with benign or potentially lethal ventricular arrhythmias, beta blockers are chosen as first-line therapy. Because of moricizine's relatively high effectiveness in suppressing ventricular arrhythmias and its low potential for noncardiac adverse effects and organ toxicity as well as a low incidence of induced proarrhythmia and heart failure, moricizine is selected as the next drug in line. All other class I antiarrhythmic drugs either have been shown to have the potential for increasing sudden cardiac death or have major rates of noncardiac adverse effects or organ toxicity that preclude their use in these patient groups except in special circumstances. In patients with malignant ventricular arrhythmias who present with hemodynamic consequences such as syncope or worse, moricizine also is preferred as an initial drug for consideration. When compared to drugs with class IA and IB action, moricizine has comparable efficacy yet lower rates of noncardiac adverse effects, organ toxicity, proarrhythmia and heart failure.(ABSTRACT TRUNCATED AT 250 WORDS)

Fast and slow idioventricular rhythms in the canine heart: a study of their mechanism using antiarrhythmic drugs and electrophysiologic testing.

Complete heart block in dogs was induced by injecting the His bundle with formalin. For the 1st few days after surgery, a fast idioventricular rhythm (cycle length 471 +/- 37 ms, mean +/- standard error of the mean) occurred either as the only ventricular rhythm or interspersed with a slow idioventricular rhythm (cycle length 1,307 +/- 17 ms). The response to cardiac pacing, lidocaine, ethmozin and verapamil in conscious dogs was studied 1 day and 1 to 2 weeks after surgery. The fast idioventricular rhythm could not be suppressed by overdrive pacing, and at times its rate actually increased after pacing. The basic length of the fast idioventricular rhythm was prolonged by ethmozin but not by verapamil or lidocaine. The recovery cycle length ( that is, that of the first beat after cessation of overdrive pacing) was prolonged by ethmozin and verapamil, but not lidocaine. The slow rhythm was suppressed by overdrive pacing and its rate was decreased by lidocaine, unaltered by ethmozin and increased by verapamil. The recovery cycle length of the slow rhythm also was prolonged by lidocaine, unaltered by ethmozin and decreased by verapamil. The results are consistent with the slow rhythm resulting from normal automaticity (that is, that which occurs at high levels of membrane potential and is overdrive-suppressed) and the fast rhythm resulting from an abnormal automatic mechanism (that which occurs at low membrane potentials and is not overdrive-suppressed). The results obtained with verapamil are consistent with drug-induced catecholamine release.