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.

[Effect of etmosin on biliary motility disorders in patients with ischemic heart disease]. / Vplyv etmozynu na porushennia motoryky zhovchovyvidnykh shliakhiv u khvorykh na ishemichnu khvorobu sertsia.

We have studied the influence of Etmosin medication on severity of IHD clinical presentations and comprised biliary motility in 162 patients aged 26 to 60. Dynamic echocholecystography (DECG) has been applied. The obtained data suggest using Etmosin in patients with ischemic heart disease and comprised biliary motility makes for normalizing tonus of the Odi sphincter and decreasing the rate of episodes of angina pectoris, although was not found any influence of Etmosin on gall-bladder motility. The use of Etmosin enables in patients with IHD and comprised biliary motility to decrease reflex angina pectoris.

Moricizine induced increase in pacing threshold.

A 72-year-old woman who was experiencing incessant ventricular tachycardia and recurrent automatic implantable cardioverter defibrillator (AICD) firing despite amiodarone therapy was referred to the Cleveland Clinic Foundation. Myocardial ischemia and infarction were ruled out by standard means. Several antiarrhythmic medications were tried previously without success. Moricizine, 200 mg three times daily, was initiated and controlled the ventricular tachycardia. However, after the dose of moricizine was titrated upward, the patient became symptomatically bradycardic and the ECG exhibited 2:1 block of her paced rhythm and an increased ventricular pacing threshold.

Efficacy and safety of moricizine in the maintenance of sinus rhythm in patients with recurrent atrial fibrillation.

Maintenance of sinus rhythm is the primary goal of antiarrhythmic drug therapy for recurrent atrial fibrillation (AF). However, concern about proarrhythmic and negative inotropic effects has led to increasing reluctance to administer antiarrhythmic agents for this non-life-threatening arrhythmia. Moricizine is well tolerated in a wide variety of patients, and therefore, may be a safe and effective agent for treating AF. We retrospectively assessed the efficacy and safety of moricizine (mean dose 609 +/- 9 mg/day) in 85 consecutive patients with recurrent AF (2.6 +/- 0.5 years duration, 1.6 +/- 1 failed antiarrhythmic drugs). Structural heart disease was present in 69 (81%), but no recent myocardial infarct (< or =90 days) was present; mean left atrial size was 46 +/- 1 mm, and mean left ventricular ejection fraction was 0.51 +/- 0.01. Moricizine was discontinued because of unsuccessful direct-current cardioversion (n = 5) or clinically unacceptable side effects (n = 6); 6 patients developed transient side effects not requiring discontinuation. Of the 74 patients continuing therapy, 68% remained in sinus rhythm after 6 months, and 59% after 12 months. During a follow-up (21 +/- 2 months), there were neither deaths nor adverse effects requiring discontinuation of therapy. Thus, moricizine was effective, safe, and well tolerated in our patient cohort with AF.

[Effect of the sympathetic nervous system activation on the antifibrillatory efficacy of various anti-arrhythmia agents]. / Vliianie aktivatsii simpaticheskoi nervnoi sistemy na antifibrilliatornoe deistvie protivoaritmicheskikh sredstv raznykh klassov.

Experiments with a 7-min occlusion followed by reperfusion of the left coronary artery in narcotized rats showed that antiarrhythmic drugs of various classes--ethacizin (class I), AL-275 (class III), and CM-345 (class V)--produce pronounced antifibrillatory and antiarrhythmic effects. AL-275 and CM-345, in contrast to ethacizin, retained their efficacy under the conditions of isoproterenol-induced stimulation of beta-adrenoceptors. This difference in behavior is probably explained by dissimilar effects of the antiarrhythmics on the ion channels of cardiomyocite membranes.

[The pharmacology of the new combined anti-arrhythmia preparation metatsizin]. / K farmakologii novogo kombinirovannogo antiaritmicheskogo preparata metatsizina.

The combined antiarrhythmic effect of ethmosin and ethacisin in various dose ratios was studied in conscious dogs with two-stage ligation of the coronary artery (after Harris). A 6:1 ratio was found to be optimal for manifestation of the antiarrhythmic effect. In such a ratio of the doses the antiarrhythmic effect of a combination of ethmosin and ethacisin is essentially higher than the activity of each component. On the grounds of these data a combined antiarrhythmic drug methacisin was developed. It possesses a broad spectrum of antiarrhythmic activity. The drug is effective on models of arrhythmias specific of class I, III, and IV antiarrhythmics. Metacisin does not change hemodynamics and activity of the heart. Study of metacisin pharmacokinetics showed that it possesses bioavailability twice that of ethmosin tablets taken separately and four times that of ethasicin.

Experience with moricizine HCl in children with supraventricular tachycardia.

Eight children, age between 4.5 and 19 years were treated with moricizine for supraventricular tachycardia during the last 3 years. The tachycardia was documented by surface electrocardiogram (ECG), and/or by ambulatory ECG in all the children and the mechanism of tachycardia was determined by previously published surface ECG and electrophysiologic criteria in all but one child. Of the eight children, three had atrial ectopic tachycardia, three had automatic junctional ectopic tachycardia, one had atrioventricular (AV) nodal reentry tachycardia and one had atrial reentry. All the children except one had failed trial of two or more antiarrhythmic drugs prior to moricizine therapy. The duration of moricizine therapy ranged from 4 days to 25 months. In three of the eight children (patients 3, 5 and 7), who presented with AV nodal reentrant tachycardia, automatic junctional ectopic tachycardia and atrial ectopic tachycardia, respectively, moricizine therapy was effective in restoring sinus rhythm and controlling the clinical tachycardia. Only one child (patient 1) developed proarrhythmia, an episode of fast, narrow-QRS supraventricular tachycardia lasting for 30 s, on the third day of therapy. This was subsequently confirmed by electrophysiologic study to be AV nodal reentrant tachycardia. The other side effects noted were non-cardiac, not dose-dependant and did not require dis-continuation of therapy. Based on our small series and those of others, moricizine, a newer class I anti-arrhythmic agent, has a limited but useful role in the management of recalcitrant type of supraventricular tachycardia, such as ectopic atrial and junctional tachycardia in children.

The Cardiac Arrhythmia Suppression Trial: Implications for nursing practice.

BACKGROUND: Care of patients with ventricular arrhythmia after myocardial infarction requires careful nursing management, including assisting with arrhythmia monitoring and testing. Because ventricular premature depolarization is a known risk factor for sudden cardiac death, it was hypothesized that the suppression of asymptomatic or mildly symptomatic ventricular premature depolarization would improve survival in these patients. OBJECTIVE: To review the Cardiac Arrhythmia Suppression Trial findings and provide implications for nursing practice for patients after myocardial infarction. METHODS: The Cardiac Arrhythmia Suppression Trial was a multicenter, randomized, placebo-controlled trial designed to determine whether the suppression of ventricular premature depolarizations in postmyocardial infarction patients would improve survival. Three class I antiarrhythmic drugs were used: encainide, flecainide, or moricizine. Patients for whom the drug suppressed their arrhythmia 80% or more were randomly assigned to that drug and dose or its matching placebo and were followed every 4 months (main study). Patients with 1% to 79% suppression were randomly assigned to the drug or its placebo that best treated their arrhythmia and followed every 4 months. RESULTS: Suppression of asymptomatic or mildly symptomatic ventricular premature depolarization in patients using encainide, flecainide, or moricizine failed to improve patient survival and was even harmful in some cases. CONCLUSIONS: Our results showed that in the absence of effective antiarrhythmic drug therapy, supportive nursing care and arrhythmia monitoring is important until appropriate therapy for the management of these arrhythmias in patients who have had a myocardial infarction can be found. Clinical trials are essential to provide an evaluation of therapies and direction for further studies, as well as a basis for practicing clinicians.

Rate-dependent anisotropic conduction property in the epicardial border zone of canine myocardial infarcts and its modification by moricizine.

We evaluated anisotropic conduction properties, different conduction velocities depending on fiber orientation, in normal and infarcted myocardium and the effects of moricizine on anisotropic conduction. Various cycle lengths of stimulation were applied to 15 mongrel dogs, and epicardial mapping was performed using a 96-channel mapping electrode. Moricizine was then administered to seven dogs and the same procedure was performed. Conduction velocities were calculated from these maps. Programmed electrical stimulations were performed before and after moricizine administration to induce ventricular arrhythmias. Before moricizine administration, a rate-dependent decrease in longitudinal conduction velocity was observed in the infarcted zone. Moricizine suppressed longitudinal conduction in the normal zone significantly at 300 msec pacing, but not at slower rates. Moricizine at a dose of 4 mg/kg, on the other hand, suppressed longitudinal conduction in the infarcted zone significantly at all pacing cycle lengths. The effect of moricizine on transverse conduction was inconsistent. In three dogs, sustained ventricular tachycardia (VT) was induced either before or after moricizine administration. The mean cycle length of sustained VT was prolonged from 202 msec to 291 msec after 4 mg/kg of moricizine. Thus, the changes in cycle length of ventricular tachycardia observed were most likely the result of slowing of conduction velocity, especially in the longitudinal direction, in the infarcted myocardium. We conclude that the electrophysiologic nature of the subacute ischemic model was modified by moricizine, leading to depression of the conduction velocity of longitudinal conduction and the inducibility of ventricular arrhythmias.

Association between ease of suppression of ventricular arrhythmia and survival.

BACKGROUND: We tested the hypothesis that patients whose ventricular arrhythmias are easy to suppress have a lower rate of arrhythmic death, defined as arrhythmic death and nonfatal cardiac arrest, the primary end point in the Cardiac Arrhythmia Suppression Trials (CAST-I and CAST-II), than patients whose ventricular arrhythmias are hard to suppress. In addition, we evaluated the association between ease of suppression of ventricular arrhythmias and mortality of all causes. METHODS AND RESULTS: CAST-I investigated the effect on arrhythmic death of ventricular premature depolarization (VPD) suppression achieved by three drugs, encainide, flecainide, and moricizine, at two different dose levels; CAST-II investigated the same effect, using moricizine alone at three dose levels. If suppression was achieved, patients were randomized to the effective active drug or corresponding placebo. To examine the independence of easily suppressed ventricular arrhythmias as a predictor of arrhythmic death, we adjusted statistically for other variables that were related both to ease of suppression and arrhythmic death. Patients with ventricular arrhythmias (n = 1778) that were easy to suppress had fewer arrhythmic deaths during follow-up than those with ventricular arrhythmias that were hard to suppress (n = 1173) (relative risk, .59; P = .003). Patients whose VPDs were easily suppressed were older and had a lower frequency of prior history of heart failure and myocardial infarction. They also had a higher incidence of anterior myocardial infarction, VPD frequency, and average ejection fraction. After adjusting for these variables, we found that easily suppressed ventricular arrhythmias were still significant predictors of arrhythmic death (relative risk, .66; P = .013). CONCLUSIONS: This study shows that the ease of VPD suppression identifies a subgroup of postmyocardial infarction patients who have low risk of arrhythmic death.

Moricizine and quality of life in the Cardiac Arrhythmia Suppression Trial II (CAST II).

The Cardiac Arrhythmia Suppression Trial II (CAST II) was a double-masked placebo-controlled randomized trial that compared the survival effects of moricizine to placebo in postmyocardial infarction arrhythmia patients. The quality-of-life outcome measures were designed prospectively for CAST and were previously shown to have high reliability and clinical discriminative validity. The CAST quality-of-life instrument detected significant differences between moricizine and placebo. In particular, moricizine was most strongly associated with inferior social activity and satisfaction scores (p = .014) and lower scores for overall contentment with life (p = .007). Moreover, the quality-of-life measures improved significantly for both the moricizine and placebo treatment groups after entry into the clinical trial. These results indicate that the CAST quality-of-life instrument is sensitive for assessing pharmacological therapies in the treatment of heart disease.

Interaction of baseline characteristics with the hazard of encainide, flecainide, and moricizine therapy in patients with myocardial infarction. A possible explanation for increased mortality in the Cardiac Arrhythmia Suppression Trial (CAST).

BACKGROUND: The Cardiac Arrhythmia Suppression Trial (CAST) was designed to test the hypothesis that suppression of ventricular ectopy with antiarrhythmic drugs after a myocardial infarction reduces the incidence of sudden arrhythmic death. Patients in whom ventricular ectopy could be suppressed with encainide, flecainide, or moricizine were randomly assigned to receive either active drug or placebo. The encainide and flecainide arms of the study were discontinued in 1989 (CAST-I) and the moricizine arm in 1991 (CAST-II) because of excess mortality. To explore the mechanisms of these adverse outcomes, we examined the interaction of baseline characteristics with the hazard of therapy with encainide, flecainide, or moricizine compared with their respective placebos. METHODS AND RESULTS: CAST-I comprised 755 patients assigned to flecainide or encainide and 743 patients assigned to placebo, whereas in CAST-II, 502 patients received moricizine and 491 patients received placebo. Clinical and laboratory baseline variables of patients receiving active drug and those receiving placebo were similar. In CAST-I patients, there was a significant interaction of active therapy with both all-cause death/cardiac arrest and arrhythmic death/cardiac arrest for non-Q-wave myocardial infarction (total mortality hazard ratios, 1.8 versus 7.9 for Q-wave versus non-Q-wave infarction, P = .03). Ventricular premature depolarization (VPD) frequency > or = 50/h and heart rate > or = 74 beats per minute each interacted significantly with total mortality/cardiac arrest only. In the sicker CAST-II patients (ejection fraction < or = 40%), only diuretic use at baseline interacted significantly with moricizine use for both all-cause death/cardiac arrest and arrhythmic death/cardiac arrest (total mortality hazard ratios, 1.9 versus 0.7 for diuretic use versus no use, P = .01). CONCLUSIONS: Although active treatment in CAST-I was associated with greater mortality than placebo with respect to almost all baseline variables, the therapeutic hazard was more than expected in patients with non-Q-wave myocardial infarction and (for total mortality) frequent premature VPDs and higher heart rates, suggesting that the adverse effect of encainide or flecainide therapy is greater when ischemic and electrical instability are present. The relative hazard of therapy with moricizine in the sicker CAST-II population was greater in those using diuretics. Thus, although these drugs have the common ability to suppress ventricular ectopy after myocardial infarction, their detrimental effects on survival may be mediated by different mechanisms in different populations, emphasizing the complex, poorly understood hazards associated with antiarrhythmic drug treatment.

Moricizine concentration to guide arrhythmia treatment: with attention to elderly patients.

To test the relationship between plasma moricizine concentration and the electrocardiogram (ECG) and arrhythmia suppression, 17 symptomatic cardiac patients with 30 or more ventricular premature complexes per hour were studied. Seven patients were mature adults, less than 60 years of age; and ten were elderly adults, more than 60 years of age. During steady-state moricizine therapy, patients had plasma moricizine concentration determined over a dosing interval, and had standard 12-lead ECG and a 24-hour ambulatory ECG recorded. The mean moricizine dose was 215 +/- 29 mg every 8 hours; mean maximal moricizine concentration was 1.4 +/- 0.84 micrograms/ml; and mean t1/2 beta was 1.5 +/- 0.7 hours. Baseline age-related differences were found, including prolonged electrocardiographic intervals (PR and QRS) (P < .05), increased ventricular arrhythmias (P < .05), and reduction in creatinine clearance (P < .05) in the elderly. Compared with pretreatment values, PR (P < .05) and QRS (P < .05) prolongation was observed, and was more marked in elderly patients. Over a dosing interval, there were dynamic changes on the ECG that paralleled plasma moricizine concentration; that is, peak and nadir intact moricizine concentration occurred simultaneously with ECG changes: QRS and JTc prolonged (P < .05), and PR prolongation approached significance (P = 0.09). Suppression of ventricular premature complexes of 80% or more occurred in 15 patients, and ventricular tachycardia was abolished in 10 of 12 patients. Probit analysis revealed that the therapeutic antiarrhythmic concentration ranged from 0.20 to 3.6 micrograms/ml.(ABSTRACT TRUNCATED AT 250 WORDS)

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

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.

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.

Combination ethacizin and ethmozin treatment of resistant ventricular ectopy: 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 channel. Computer simulation using the "guarded-receptor" model predicted that the combination of ethacizin and ethmozin should exert a greater decrease in excitability and conduction at short coupling intervals, but little effect at normal heart rates (HR). To test this prediction, we measured intraventricular conduction delay in canine hearts in vivo. In agreement with the model, the combination more potently prolonged the delay only at intervals < 600 ms as compared with ethacizin alone. Combination therapy was tested in 6 patients with idiopathic ventricular ectopic depolarizations (VEDs). Three patients were resistant to either ethmozin or ethacizin monotherapy, and three could not tolerate effective doses because of side effects. Quantitative continuous ECG monitoring showed that total 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 therapy with ethmozin (400 mg/day) and ethacizin (100 mg/day) reduced the number of VEDs by 78 +/- 2% in these patients without side effects. In the "nonresistant" but intolerant group of patients, use of the combination allowed relief of symptomatic ectopy without side effects. A theoretical 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 combinations.

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.

A new class of antiarrhythmic--defibrillatory compounds.

Ventricular fibrillation (VF) is a major cause of sudden cardiac death in humans. Currently used antiarrhythmic drugs are aimed at preventing initiation of VF by decreasing the incidence of arrhythmias which can lead to VF. This approach today seems to be insufficient. On the basis of reports that VF can terminate spontaneously in various mammals, and even in humans, we propose pharmaceutical enhancement of self-ventricular defibrillation as a new therapeutical approach. Data obtained over the last decade indicate that a high cardiac extraneuronal noepinephrine level during VF facilitates self-defibrillation. Dibenzazepines (tricyclic antidepressants) and phenothiazines elevate norepinephrine level by inhibiting norepinephrine reuptake and were found to exhibit defibrillatory activity. The relationship of chemical structure to defibrillatory activity was studied in a group of dibenzazepine and phenothiazine compounds.