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Antiarrhythmic drugs prolong the effective refractory period and depress conduction. To determine the exact role played by these two electrophysiologic effects in the termination of reentry, the effects of disopyramide, flecainide, propafenone and E-4031, a new class III drug, were examined in a canine model of atrial flutter (cycle length 120 +/- 4 to 131 +/- 3 ms) caused by reentry. Atrial flutter was induced in 32 anesthetized open chest dogs after placement of an intercaval crush. The excitable gap ranged from 9 +/- 2% to 11 +/- 4% of the basic flutter cycle length. The effective refractory period in the reentrant circuit during atrial flutter was estimated by subtracting the excitable gap from the basic flutter cycle length. Prolongation of flutter cycle length by the test drugs was proportional to the interatrial conduction time (r = 0.87, p less than 0.001). Atrial flutter was terminated by each test drug in all dogs except for flecainide and propafenone in one dog each. E-4031 prolonged the refractory period during atrial flutter to 129 +/- 6 ms, which did not differ significantly from the flutter cycle length immediately before termination (134 +/- 4 ms). The refractory period during atrial flutter after injection of the other drugs was shorter than the flutter cycle length before termination of atrial flutter (for example, flecainide 126 +/- 5 vs. 179 +/- 11 ms, p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Methoxamine, an alpha adrenoreceptor agonist, and sleep abolished repetitive nonsustained monomorphic ventricular tachycardia in a 41-year-old man without detectable underlying heart disease. Detailed pacing studies revealed that the occurrence of ventricular tachycardia was totally dependent on the basic heart rate. Sleep and the alpha adrenoreceptor agonist abolished the ventricular tachycardia by slowing the basic heart rate. Verapamil, propranolol, and disopyramide were able to decrease the upper limit of the tachycardia-initiating heart rate, but none of them were able to increase the lower limit (75/min). Failure to increase the lower limit of the tachycardia-initiating heart rate was a major reason why these conventional antiarrhythmic drugs were unable to suppress his daytime episodes of repetitive ventricular tachycardia.

The efficacies and side effects of disopyramide and mexiletine used alone and in combination were assessed in 29 patients with chronic ventricular arrhythmias. In combination therapy, one half or two thirds of the conventional doses of each drug were administered. Each patient underwent Holter electrocardiographic monitoring during 4 different periods: baseline, disopyramide alone, mexiletine alone and combination of the two drugs. The mean baseline number of ventricular premature complex per hour was 783 +/- 521 (mean +/- SD), which was significantly reduced with all three therapies. Disopyramide alone significantly reduced the ventricular premature complex frequency in patients with organic heart disease (P less than 0.05), but did not significantly reduce the ventricular premature complex frequency in patients with no apparent heart disease. In contrast, mexiletine alone significantly decreased the ventricular premature complex frequency in no apparent heart disease patients (P less than 0.05), but did not significantly reduce the ventricular premature complex frequency in organic heart disease patients. With disopyramide alone, patients having a significant reduction in ventricular premature complexes (greater than or equal to 83% reduction in ventricular premature complexes) or elimination of ventricular tachycardias tended to be more frequently found in organic heart disease than in no apparent heart disease. The opposite was observed with mexiletine alone. QTc interval with disopyramide alone was significantly prolonged, and the prematurity index of ventricular premature complexes was significantly lowered as compared to mexiletine alone or combination therapy (P less than 0.01 for disopyramide versus mexiletine; P less than 0.05 for disopyramide versus combination therapy). During combination therapy, no patients withdrew from the study due to side effects. However, 3 patients receiving single drug therapy withdrew from the study due to severe side effects. Consequently, disopyramide is suggested to be more effective on ventricular premature complexes in organic heart disease than in no apparent heart disease patients, whereas the opposite was true for mexiletine. A combination of disopyramide and mexiletine in smaller doses may provide almost the same or enhanced antiarrhythmic effects, no aggravation of electrocardiographical parameters and less incidence of side effects when compared to the conventional dose of each drug alone.

1. The anti-arrhythmic properties of the alpha-adrenoceptor blocking drug indoramin were compared with the effect of disopyramide and placebo in a randomised, single-blind, cross-over study. Two doses of indoramin were tested, 25 mg and 50 mg and the dose of disopyramide was 150 mg. All treatments were administered three times daily. 2. Forty patients with benign ventricular arrhythmia were studied. 3. Assessment was by 24 h ambulatory electrocardiography at entry and at the end of each 2 week treatment period. 4. Indoramin was found to have a significant anti-arrhythmic effect compared with placebo, but only at the higher dose tested. 5. The anti-arrhythmic effect was less than that achieved with disopyramide. 6. The mechanism for this anti-arrhythmic effect is unknown but these results suggest that alpha-adrenoceptor blockade may merit further attention as an anti-arrhythmic treatment.

Ventricular arrhythmia suppression trials were performed to compare the efficacies and side effects of disopyramide and mexiletine used alone and in combination, and to compare the efficacies and side effects of mexiletine and propranolol used alone and in combination, in patients with chronic ventricular premature contractions (VPCs, greater than or equal to 3000 beats/day). The study on the combination of disopyramide and mexiletine included 26 patients (19 men and 7 women). Disopyramide 100 mg tid or mexiletine 150 mg tid was administered as single-drug therapy, and disopyramide 50 mg plus mexiletine 100 mg tid was administered as combination therapy. Each patient underwent Holter monitoring during four different periods: baseline, disopyramide alone, mexiletine alone, and combination therapy. The mean number of VPCs/hr at baseline was 796 +/- 522 (mean +/- SD), which was significantly decreased with all three therapies (p less than 0.01 in each) to a) 415 +/- 480 with disopyramide alone, b) 341 +/- 368 with mexiletine alone, and c) 345 +/- 408 with the combination therapy. The number of patients demonstrating a significant reduction in VPCs (greater than or equal to 75%) and the elimination of ventricular tachycardia (VT; three or more consecutive VPCs) did not differ significantly among the three therapies. The prematurity index (PI), vulnerability index (VI), and QTc tended to be aggravated by disopyramide therapy alone, but these values were corrected by combination therapy. No patients withdrew from the study due to side effects during combination therapy, although three patients withdrew from the study due to severe side effects during single-drug therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

The authors report the results of an open randomized study to compare the efficacy of oral slow-release and immediate-release disopyramide, in the treatment of patients with chronic stable ventricular arrhythmias, evaluated with two Holter recordings. Twelve patients, selected after positive acute intravenous test, had been randomly assigned to slow-release (500 mg/day) and immediate-release (400 mg/day) disopyramide. Ten days later, a Holter recording was performed and then all patients were treated with slow-release disopyramide (500 mg/day); After one month drug efficacy has been evaluated by Holter recording. Total ectopic beats and arrhythmic Lown modified score were the end points. Immediate-release disopyramide significantly reduced both total beats and arrhythmic score; the slow-release formulation did not modify total beats and reduced the arrhythmic score, but only at the first Holter control. One month later there was no significant difference in arrhythmic score either. Low plasma drug levels could explain these results in some patients.

The aim of this study was to assess the effect of delayed release Disopyramide 500 mg daily on sinus node function in 12 subjects with sinus node dysfunction and supraventricular and/or ventricular excitability. An ECG, Holter monitoring and electrophysiological studies of sinus node function with an oesophageal electrode were performed before and after 5 days treatment. The drug had to be discontinued in 1 patient because of urinary retention. The Disopyramide suppressed the clinical tachyarrhythmias in 8 out of the 11 subjects. The maximal sinus pause observed on Holter monitoring did not change significantly. It only increased in one subject. The mean sinus cycle length during electrophysiological study slightly decreased but there was a global increase in sinoatrial conduction time from 309 +/- 164 to 413 +/- 125 msec and of the corrected sinus mode recovery time from 470 +/- 168 to 605 +/- 303 msec. However, these changes were not significant. This study of delayed released Disopyramide shows a discordance between the tendency for sinus node function to deteriorate when assessed by electrophysiological studies and good clinical tolerance as assessed by Holter monitoring in the bradycardia-tachycardia syndrome.

The efficacy of 7 well-known Class I antiarrhythmic agents were retrospectively and by+crossover compared in 2 groups of patients treated in hospital in different years for ventricular arrhythmias. Class IC agents proved to be the most potent in the two groups of patients. The following algorithm is proposed to choose Class I agents: if quinidine or mexiletine is beneficial in the same patients, the other drugs will be also effective. If disopyramide fails to be beneficial, allapinin , ethacizine , propaphenon will be the most effective. When allapinin produces effects, ethacizine and propaphenon show their highest potency, but when each of them fails, a combination of antiarrhythmic agents should be used.

By choosing antiarrhythmic therapy, ritmilen, 3 mg/kg, was given to 30 patients with atrial, atrioventricular, reciprocal and ventricular tachycardias. The agent was found to have the highest effect on atrial myocardial refractoriness in patients with atrial tachycardias and on ventricular refractoriness in patients with ventricular tachycardias (longer effective and functional refractory periods). Intraventricular pathways are the major site of ritmilen's effect on anterograde conduction. Profound changes were found in patients with atrial and ventricular tachycardias. The cholinolytic action of ritmilen on the atrioventricular node was detected in 20% of the patients, whereas sinus rhythm increased in 90%, which may be attributable to asymmetric vagus innervation of sinoatrial and atrioventricular nodes.

Moricizine chlorhydrate (Ethmozine), a relatively unknown antiarrhythmic agent in France, is a derivative of Phenothiazine, related to the Vaughan-Williams Class IB drugs. A randomised, double-blind, crossover trial with Disopyramide 600 mg/day after a placebo period in 10 patients with ventricular extrasystoles, half of whom had underlying cardiac disease, showed that moricizine 750 mg/day significantly reduced (p less than 0.05) the overall number of ventricular extrasystoles by 81 +/- 46% (disopyramide 72 +/- 69%; NS) and that this drug is effective in 2/3 of patients by suppressing 70 to 100% of ventricular extrasystoles, whereas disopyramide was effective in only 40% of the same patients and never gave better results than Moricizine. Cardiac and extracardiac tolerance of Moricizine was good in this study, confirming previously reported results and its superiority when compared with disopyramide (20% of unwanted effects in this series).

Two children with left ventricular outflow tract obstruction due to myocardial hypertrophy received oral disopyramide as a negative inotrope. Both showed rapid improvement in clinical signs and by echo Doppler examination. Nearly complete abolition of severe left ventricular outflow tract obstruction was documented in each case. This experience may prompt further application of disopyramide as a therapeutic agent to relieve dynamic muscular subaortic obstruction in children.

Rhythm conversion in patients with post-thyrotoxic atrial fibrillation (AF) has been performed with disopyramide in order to evaluate the conversion rate and to test its effect on the maintenance of sinus rhythm after cardioversion. The duration of AF ranged from 9 to 122 months (mean 31.8 months). Of 81 patients, 12 (15%) with relatively short duration AF were converted to sinus rhythm with disopyramide. The remaining 69 patients required DC cardioversion, which restored sinus rhythm in 58 patients. The 58 DC-converted patients were divided into two groups: a disopyramide group (D group) and a non-disopyramide group (non-D group). The D group received disopyramide 300 mg per day for 3 months after DC cardioversion and the non-D group did not receive anti-arrhythmic drugs. During the early observation period, only one patient relapsed in the D group into AF, but 5 successive patients in the non-D group reverted to AF, forcing discontinuation of the non-D protocol. A second DC cardioversion performed on 3 of those 5 patients was followed by maintenance therapy with disopyramide 300 mg per day, and they remained in sinus rhythm. With the inclusion of those three subjects, sinus rhythm was still present in 44 of the total of 58 patients converted by DC (76%) at the time of follow-up (64 months). Thus, disopyramide was effective in rhythm conversion and it was essential for the maintenance of sinus rhythm after cardioversion in patients with post-thyrotoxic AF.

Purpose: Vasovagally mediated hypotension and bradycardia are believed to be common, but difficult to diagnose, causes of syncope. Upright tilt-table testing has been proposed as a possible way to test for vasovagal episodes. This study investigated the clinical utility of this technique in the evaluation and management of patients with syncope of unknown origin., Patients and Methods: Twenty-five patients with recurrent unexplained syncope and six control subjects were evaluated by use of an upright tilt-table test for 30 minutes, with or without an infusion of isoproterenol (1 to 3 micrograms/minute given intravenously), in an attempt to provoke bradycardia, hypotension, or both. Of the 25 patients, there were 14 males and 11 females, with a mean age of 50 +/- 16 years. Six control patients with no history of syncope were also studied. All tilt-positive patients received therapy with either beta-blockers, disopyramide, transdermal scopolamine, or hydroflurocortisone, the efficacy of which was evaluated by another tilt-table test., Results: Syncope occurred in six patients (24%) during the baseline tilt and in nine patients (36%) during isoproterenol infusion (total positives, 60%). None of the controls had syncope during the test. All patients who had positive test results eventually became tilt-table-negative by therapy, and over a mean follow-up period of 16 +/- 2 months no further episodes have occurred., Conclusion: From this study we conclude that upright tilt-table testing combined with isoproterenol infusion is clinically useful in the diagnosis of vasovagal syncope and the evaluation of pharmacologic therapy.

We assessed the effects and therapeutic implications of disopyramide on left ventricular systolic and diastolic functions in 19 patients with non-obstructive hypertrophic cardiomyopathy by Doppler echocardiography. All patients were in sinus rhythm. Parameters measured were fractional shortening (FS (%)), mean velocity of circumferential fiber shortening (mean Vcf (circ/sec)), ejection fraction (EF (%)), peak left ventricular outflow velocity (peak-LVOT (cm/sec)), peak rapid filling inflow velocity (peak-R (cm/sec)), peak late filling inflow velocity (peak-A (cm/sec)) and peak-A/peak-R ratio (A/R ratio). These values were compared before and after infusion of disopyramide (2 mg/kg). There was no significant difference in heart rate, systolic and diastolic blood pressures before and after infusion of disopyramide. Following the intravenous drip infusion of disopyramide, FS decreased from 38.1 +/- 5.4 to 33.2 +/- 4.9 (p less than 0.05) and the mean Vcf decreased from 1.285 +/- 0.181 to 1.141 +/- 0.188 (NS). EF and peak-LVOT also decreased from 67.7 +/- 6.3 to 61.9 +/- 7.0 (p less than 0.05), and from 107.6 +/- 29.5 to 92.4 +/- 25.2 (p less than 0.01), respectively. The infusion of disopyramide increased the peak-R from 47.3 +/- 18.2 to 55.5 +/- 19.2 (p less than 0.05), and decreased peak-A from 52.0 +/- 13.6 to 40.2 +/- 12.6 (p less than 0.01), resulting in a decrease of A/R ratio from 1.277 +/- 0.537 to 0.818 +/- 0.475 (p less than 0.01). These results suggest that disopyramide improved left ventricular diastolic function, although systolic function decreased slightly. In conclusion, disopyramide can be also used beneficially in non-obstructive hypertrophic cardiomyopathy without arrhythmias.

Over the past 30 years, knowledge of the natural history and effects of therapy in patients with hypertrophic cardiomyopathy has expanded greatly, but progress has been hampered by its variable patterns of expression. Many but not all patients show symptomatic improvement with medical treatment. Chronic beta blockage does not appear to affect long-term survival, whereas results with calcium channel blockade by verapamil have been encouraging; however, they await confirmation, and verapamil may be hazardous in some patients with severe left ventricular (LV) outflow tract obstruction and elevated LV end-diastolic pressure. Reported beneficial effects of amiodarone on survival also require further study. Surgical therapy has become the treatment of choice for medically refractory patients with proven outflow tract obstruction. In several centers, the operative risk is low, and long-term follow-up demonstrates prolonged symptomatic relief. It is hoped that work currently underway will provide more definitive information on the long-term effects of the role of calcium channel blockers, antiarrhythmic medications, and the long-term effects of surgical therapy on survival of patients with this disorder.

The relative safety and efficacy of intravenous administration of adenosine, lignocaine, disopyramide, flecainide, and sotalol for termination of stable, induced ventricular tachycardia was assessed in serial trials. Ventricular tachycardia was terminated by pacing if it persisted 10-15 min after the end of drug administration. 24 patients with recurrent ventricular tachycardia were studied. Ventricular tachycardia was terminated by a drug in 35 of 105 trials. In 6 patients no drug terminated the arrhythmia. Adenosine did not terminate tachycardia or have any serious adverse effect in any patient; both flecainide and disopyramide were significantly more effective than lignocaine, but flecainide had significantly more severe adverse effects than lignocaine. Lignocaine was the safest drug and should continue to be used as first-line drug therapy for stable ventricular tachycardia. Disopyramide should be considered as second-line treatment. DC cardioversion is necessary for unstable ventricular tachycardia, and its availability must be ensured before attempted pharmacological intervention.

A 62-year-old woman with a history of supraventricular tachycardia, paroxysmal atrial tachycardia, and premature ventricular contractions was admitted with palpitations and anxiety. Previous therapy with antiarrhythmics had resulted in intolerable adverse effects or no effect on the arrhythmia. She had been taking rifampin prior to admission for acid-fast bacilli. Disopyramide was started on admission for supraventricular tachycardia. Subtherapeutic disopyramide blood concentrations were noted with concomitant administration of rifampin and disopyramide at normal doses. This case report demonstrates a possible drug interaction between these two drugs and the importance of careful monitoring. It was found that it takes three to five days after rifampin is discontinued before the enzyme induction of disopyramide disappears and disopyramide concentrations return to normal.

Susceptibility to transient hypotension-bradycardia of neurally mediated origin has been attributed in part to accentuated afferent neural traffic arising from cardiopulmonary mechanoreceptors, and consequently, may be diminished by agents with anticholinergic and negative inotropic effects, such as disopyramide phosphate. This study assessed electrocardiographic and hemodynamic responses to upright tilt testing (alone or during isoproterenol infusion) before and after disopyramide therapy in 10 patients (age range 16 to 74 years) with recurrent syncopal episodes of neurally mediated origin. Untreated, syncope occurred at less than or equal to 7 minutes of tilt alone (6 patients) or tilt plus isoproterenol at less than or equal to 3 micrograms/min (4 patients) and was associated with hypotension (mean arterial pressure, 40 +/- 16 mm Hg vs baseline 76 +/- 10 mm Hg, p less than 0.001) and inappropriate heart rate slowing (mean heart rate, 59 +/- 39 beats/min vs baseline 88 +/- 18 beats/min, p less than 0.005). After oral disopyramide 150 mg 3 times daily (mean plasma level, 3.0 +/- 0.64 micrograms/ml), all patients tolerated 10 minutes of both tilt and tilt plus isoproterenol (maximum dose, 3 micrograms/min) without symptoms, hypotension (mean arterial pressure; tilt 1 min, 79 +/- 7 mm Hg vs tilt 10 min, 77 +/- 8 mm Hg, difference not significant) or bradycardia (mean heart rate; tilt 1 min, 81 +/- 12 beats/min vs tilt 10 min, 83 +/- 11 beats/min, difference not significant). Furthermore, during subsequent 20 +/- 5 months of disopyramide therapy, all but 1 patient remain asymptomatic. Thus, oral disopyramide may be effective for preventing inducible and spontaneous neurally mediated syncope.

The efficacy of verapamil and disopyramide phosphate for the termination and prevention of paroxysmal supraventricular tachycardia (PSVT) were studied electrophysiologically in 32 patients with inducible sustained PSVT (17 patients received verapamil, 15 patients received disopyramide). Twelve patients had atrioventricular nodal tachycardia, 7 had concealed and 13 had overt Wolff-Parkinson-White syndrome. Intravenous verapamil (0.15 mg/kg) terminated the sustained PSVT in 15 of the 17 patients (88%) by production of AV block in 13 patients, VA block in one, and a ventricular premature beat in one. PSVT could not be induced in any of these 15 patients after they had received verapamil. In the remaining 2 patients, PSVT could not be terminated by the use of verapamil, but the cycle lengths of PSVT were lengthened. Long-term oral dosages of verapamil of 120-240 mg/day were administered in 13 of the 17 patients. All patients except two, whose PSVT was unable to be effected by intravenous verapamil, were well controlled: PSVT disappeared in 7 patients and decreased in 4. Intravenous disopyramide (1.5 mg/kg) terminated induced PSVT in 10 of the 15 patients (67%) by production of VA block. Although PSVT could not be reinitiated in 5 of these 10 patients, non-sustained PSVT was induced in 2 and sustained PSVT was induced in 3 after having received disopyramide. PSVT was induced in all of the 5 patients who failed to respond to disopyramide. The cycle lengths of PSVT after administration of disopyramide remained unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)

In order to investigate the usefulness of antiarrhythmic drugs in patients with dilated cardiomyopathy (DCM), 42 patients with DCM were studied using 24 h ambulatory ECG monitoring, echocardiography and right ventricular endomyocardial biopsy. All 42 patients had ventricular arrhythmias with a Lown's classification of grade II or greater (grade IVb, 25; IVa, 7; III, 7; II, 3). The patients with grade IV arrhythmias tended to have greater dilating of the left ventricle and more pronounced interstitial myocardial fibrosis than patients with lower grades. Following procainamide and/or disopyramide treatment the severity of the ventricular arrhythmias improved in 12 (29%) of the 42 patients, did not change in 27 patients (64%), and deteriorated in 3 patients (7%). Treatment with aprindine or mexiletine was effective in 7 (50%) of the 14 patients who did not respond to procainamide and/or disopyramide. Although there were no significant differences in left ventricular dimension and contractility between patients in each group who did and did not respond to antiarrhythmic treatment, those who did respond had less interstitial myocardial fibrosis. Thus, in the procainamide and/or disopyramide treated group the percent interstitial fibrosis in responding vs nonresponding patients was 10.3 +/- 4.1% vs 18.7 +/- 8.3% (p less than 0.05) respectively, while in the group treated with aprindine or mexiletine these figures were 13.0 +/- 3.2% vs 26.1 +/- 7.9% (p less than 0.02), respectively. In conclusion, the effect of antiarrhythmic drugs in DCM was dependent on the severity of the pathological changes in the myocardium, and antiarrhythmic drugs should be appropriately used for the management of ventricular arrhythmias in DCM.

The study was designed to assess the influences of antiarrhythmic therapy on exercise tolerance in patients with coronary artery disease and ventricular arrhythmias. Subjects for this study were subdivided into 3 groups: group I - 46 patients treated with amiodarone 1,200 mg daily during 10 days and 200-600 mg daily within next days, group II - 79 patients receiving disopyramide 300-600 mg daily, group III - 129 patients with combined administration of disopyramide 300-600 mg daily and propranolol 30-240 mg daily. propranolol 30-240 mg daily. Submaximal exercise stress testing was performed in each patient before treatment and after the medication for 4 weeks (group I) and for 2 weeks (groups II, III). The following parameters have been evaluated: maximal archived workload, maximal heart rate blood pressure response, double product (maximal heart rate x maximal systolic blood pressure), reasons for ending the test (target heart rate, typical angina, exhaustion, ST-segment depression greater than or equal to 2 mm, occurrence of ventricular arrhythmia, blood pressure greater than 250/120 mm Hg, significant drop in systolic pressure). Positive result of exercise ECG was defined: horizontal or down-sloping ST-segment depression greater than or equal to 1 mm and/or typical chest pain. The data from the first and second tests were estimated for significance of differences between the mean values with following results: 1) maximal achieved workload, 86 +/- 46 and 103 +/- 49 W (p less than 0.02) in group I; 101 +/- 64 and 106 +/- 50 W (NS) in group II; 107 +/- 55 and 119 +/- 54 W, W (p less than 0.01) in group III.(ABSTRACT TRUNCATED AT 250 WORDS)

Comparative trials of a new drug with standard antiarrhythmic agents are important for establishing relative efficacy and tolerance. For moricizine, such trials have included comparisons with propranolol, disopyramide and quinidine. Furthermore, the Cardiac Arrhythmia Pilot Study compared moricizine in postinfarction patients with encainide and flecainide. These trials show moricizine to be superior in efficacy to a beta blocker (propranolol) and disopyramide and equivalent to quinidine. Although the class IC drugs (encainide and flecainide) showed somewhat greater efficacy in the Cardiac Arrhythmic Pilot Study, they are now known to increase the risk of mortality in postinfarction patients. Moricizine was also shown to be well tolerated in these trials and associated with fewer discontinuations than propranolol, disopyramide and quinidine. Thus, moricizine is a promising new agent when profiled against other drugs frequently used for therapy of chronic ventricular arrhythmias.

The effectiveness was assessed of the antiarrhythmic treatment with Palpitin in 30 patients with ischaemic heart disease (IHD). The control group comprised 15 patients with IHD and arrhythmia, treated with propranolol. In all patients ECG recording by Holter's method was done before the treatment and after 14 days of the treatment. The effectiveness of Palpitin was expressed as improvement in 66% of cases (reduction of ectopic beats by 75%), and in 40% of cases complete regression of arrhythmia was achieved. These results were slightly better than in the group treated with propranolol (improvement in 60% of cases). Palpitin during the treatment caused no increase in the manifestations of cardiac failure and produced no disturbances of atrioventricular conduction. Fairly frequently the patients complained about mucosal dryness and sporadically about dyspeptic symptoms, but these symptoms were not disturbing the course of the treatment.

Six patients with reproducible inducible atrial flutter randomly received, in double-blinded fashion, 77 mg of S(+)-disopyramide and R(-)-disopyramide over 20 min by intravenous infusion on two occasions separated by at least 24 h. The S(+) enantiomer prevented the inducibility of atrial flutter in five of the six patients; atrial flutter was inducible following R(-) enantiomer administration in all six patients (p less than 0.05). The mean (+/- SD) antiarrhythmic unbound serum concentration range of S(+)-disopyramide was 0.55 +/- 0.31-0.90 +/- 0.81 mg/L. The binding of disopyramide was stereoselective: the mean unbound fractions of S(+)- and R(-)-disopyramide were 0.207 +/- 0.119 and 0.338 +/- 0.214 (p less than 0.05). Binding of the individual enantiomers in some patients was markedly concentration dependent. The data suggest that the antiarrhythmic activity associated with racemic disopyramide resides in the S(+) enantiomer.

1) Palpitin has distinguishable antiarrhythmic effect in different type of cardiac arrhythmias of both supraventricular and ventricular origin, and of various ethiopathogeneses. 2) Antiarrhythmic effect is observed in most patients, already 24 hours after initiation of treatment. 3) Untoward effects, although occurring relatively frequently, usually do not cause such severe alterations which lead to a discontinuance of therapy. 4) Palpitin may be used in long-term treatment of outpatients.

Seven patients with normal specialized conduction system and three patients with the Wolff-Parkinson-White (WPW) syndrome were studied using programmed stimulation of the heart before and after the administration of intravenous disopyramide. The principal effect of this drug was to prolong the effective refractory period of the atria and ventricles, and to prolong the effective refractory period of the anomalous pathway in the WPW syndrome. In addition, it prolonged the conduction time in the anomalous pathway in the WPW syndrome. These findings suggest that disopyramide would be a useful and safe drug in the management of certain atrial and ventricular arrhythmias and in the management of the Wolff-Parkinson-White syndrome with atrial fibrillation.

The objective of this study was to prove the efficacy of intravenous disopyramide in the treatment of paroxysmal supraventricular tachycardia resistant to vagal maneuvers. Nine patients with this condition were admitted to the emergency service of the Instituto Nacional de Cardiología Ignacio Chávez. They were given an intravenous bolus of 2 mg/kg of the drug a maintenance dose of 0.4 mg/kg during 3 hours. The undesirable effects of the drug were arterial hypotension, dizziness, dry mouth, transient A-V dissociation and scape-capture rhythm. In conclussion, disopyramide is an excellent drug in the treatment of paroxysmal supra-ventricular tachycardia resistant to vagal maneuvers, but an strict monitorization of the arterial pressure and electrocardiogram should be kept during its administration.

Ten patients who suffered spontaneous paroxysms of atrial flutter were investigated by electrophysiological techniques. Two had overt Wolff-Parkinson-White syndrome; three Lown-Ganong-Levine syndrome; and one a concealed accessory atrioventricular connection. Atrial flutter was initiated, at study, by right atrial pacing and electrograms from the right atrium and coronary sinus were observed for at least five minutes to ensure stable flutter in both atria. Atrial flutter was terminated by 2.5 s or 5 s bursts of atrial pacing at rates 10, 50, or 100 beats/min faster than the intrinsic flutter rate in only two patients. Atrial flutter, which was reinitiated in two patients, was then treated with intravenous disopyramide phosphate, 2 mg/kg body weight, infused over five minutes. In all 10 patients the atrial rate slowed from a mean of 310 +/- 39 beats/min to 217 +/- 27 beats/min and atrial flutter terminated in one case. Though the mean ventricular rate fell from 161 +/- 52 beats/min to 156 +/- 45 beats/min the atrioventricular conduction ratio fell from 2.17 +/- 0.86 to 1.55 +/- 0.59 and four patients were left with symptomatically significant increases of ventricular rate. In seven of nine patients overdrive atrial pacing, repeated after disopryamide, resulted in the conversion of atrial flutter to sinus rhythm. In this study, overdrive atrial pacing and intravenous disopyramide, singly and in combination, terminated atrial flutter in nine of the 10 patients and it is suggested that this method may provide an effective alternative to direct current cardioversion.

473 patients with suspected acute myocardial infarction were entered into a randomised, double-blind, placebo-controlled comparison of disopyramide phosphate, 150 mg three times a day, and oxprenolol, 40 mg three times a day. When analysed on an intension-to-treat basis there was no significant difference in 6-week mortality between the groups, but patients who were able to continue on the active medications fared better than the patients who had to be withdrawn. The withdrawal rate because of heart failure in patients randomised to receive disopyramide was significantly increased. Patients receiving this agent also showed a reduced number of arrhythmic episodes on 24-h tape recordings but this trend did not achieve statistical significance. The results show that the early use of either oxprenolol or disopyramide phosphate in patients with suspected acute myocardial infarction is unlikely to improve mortality.

Flecainide acetate is the first class IC antiarrhythmic agent marketed in the United States. In vitro, animal and human studies have shown that the drug markedly prolongs conduction and has minimal effect on repolarization. Efficacy trials have shown flecainide to be effective in a wide range of ventricular and selected atrial arrhythmias. The drug is generally well tolerated, although minor adverse effects are common. These generally are related to the central nervous system and respond to a reduction in dosage. Like other antiarrhythmic agents, flecainide may demonstrate proarrhythmic effects. It is excreted in the urine as the parent compound and inactive metabolites. The elimination half-life ranges from 12-27 hours in patients with normal renal function, allowing convenient dosing regimens of 100-200 mg twice daily in most patients. Flecainide has the potential for widespread use.

Interpreting the results of this study, propafenone (Rytmonorm), administered orally in a dose of 900 mg daily, was more effective than disopyramide in a dose of 600 mg daily, in the treatment of patients with complex premature ventricular contractions (PVCs). The study was performed in 12 patients, with several Holter ECG monitorings to obtain quantitative data of the effectiveness in the same patient of the new drug propafenone in comparison with disopyramide in a documented effective oral regimen. A quantitative analysis of PVCs was obtained with a computer assisted detection. Clinical effectiveness, considered as 70--80% reduction of total number of PVCs, was obtained in 8/12 patients for propafenone and 6/12 for disopyramide, or as 50% reduction with suppression of all complex PVCs (couplets, repetitive, multiform and bigeminy) was obtained in 11/12 for propafenone and 9/12 for disopyramide.

Maintenance of adequate serum blood levels is crucial to successful antiarrhythmic therapy. Serum levels of four antiarrhythmic agents (long-acting procainamide, quinidine sulfate, quinidine gluconate, and disopyramide) were determined in 98 consecutive ambulatory patients receiving long-term oral therapy. Medication dosages, dosing intervals, and time elapsed from last dosage until blood sampling were determined. Seventy-five patients (76.5 percent) had subtherapeutic blood levels (with mean levels less than 50 percent of the suggested minimum), and only 22 patients (22.5 percent) had therapeutic levels. Even among the 61 patients who claimed to have taken their medications within the six hours prior to blood sampling, 43 (70 percent) had subtherapeutic levels. These ratios held among all subgroups studied. Physicians should be aware of the high proportion of patients receiving long-term oral antiarrhythmic therapy with inadequate serum blood levels when planning therapeutic regimens.

The paper presents data on an electrophysiologic action of disopiramid injected intravenously in a dose of 2 mg/kg on the function of the atrioventricular conduction system in 11 patients with paroxysmal supraventricular tachycardias. Disopiramid reduced the length of the spontaneous cardiac cycle and slightly affected the corrected sinus node recovery time and sinoatrial conduction time. The drug prolonged the intraatrial conduction time, increased the refractoriness of the His-Purkinje system and accessory conduction pathways. It produced no significant action on the refractory period and the function of the A-V node.

In this multicentre study, 90 patients who left hospital in sinus rhythm after electroconversion of atrial fibrillation were randomized to double-blind treatment with either disopyramide (n = 44) or placebo (n = 46). The groups were comparable regarding age and sex distribution, duration of atrial fibrillation, heart volume and NYHA-classification. Life-table analysis was used to estimate the percentage of patients still in sinus rhythm and tolerating treatment at control visits after 1, 3, 6, 9 and 12 months. After 1 month there was already a significant difference (P less than 0.01) between the two groups (disopyramide 70%, placebo 39%), a difference that was still remaining after 12 months (disopyramide 54%, placebo 30%). Twenty-four patients, all relapsing to atrial fibrillation before six months on placebo, were converted to sinus rhythm once again. They were then treated with disopyramide in an open manner and after 12 months 37% were still in sinus rhythm. From the results of this study, disopyramide seems to be a useful drug in maintaining sinus rhythm after electroconversion of atrial fibrillation.