Class IA Antiarrhythmic Agents Research Articles

771-1 Role of Intracellular Calcium In the Antiarrhythmic Effect of Procalnamide During Ventricular Fibrillation In Rat Hearts

Intracellular calcium ([Ca 2+ ]i) overload is considered one of the factors that cause ventricular fibrillation (VF). In addition, VF itself causes and maintains [Ca 2+ ]i overload. We tested whether the class IA antiarrhythmic agent procainamide can reduce [Ca 2+ ]i overload during VF and if so, whether such reduction is responsible for the recovery of left ventricular function. For this purpose, we measured the effects of 0.1 mM (0.03 mg/ml) procainamide perfusion on left ventricular developed pressure (LVP), heart rate, and [Ca 2+ ]i during pacing-induced VF in isolated rat hearts. [Ca 2+ ]i was assessed by surface fluorometry after Indo-1/AM-loading. The concentration of procainamide was selected in a way that about half of the hearts would recover from VF (criteria: recovery of LVP > 67%). During perfusion with 0.1 mM procainamide, 6 hearts recovered from VF (●), whereas 8 hearts did not recover (&z.squf;, recovery of LVP < 33%). In the untreated control group (○, n = 5), no heart recovered from VE Procainamide effects on heart rate (left panel) and [Ca 2+ ]i (right panel) are shown (mean ± SEM; † p < .05 vs. control; * p < 0.05 vs. no recovery): We conclude that procainamide can reduce [Ca 2+ ]i overload during VF. In addition, the reduction of the [Ca 2+ +] i overload might be responsible for the recovery of the left ventricular function. This reduction appeared to be dependent on the fibrillation rate (use-dependent) rather than on the decrease of heart rate.

Effects of ajmaline on non-sodium ionic currents in guinea pig ventricular myocytes.

The lack of currently available data stimulated us to investigate the electrophysiological effects of ajmaline, a classical class Ia antiarrhythmic agent, on various currents responsible for the action potential plateau and repolarization phases. The whole cell patch clamp recording technique was applied to guinea pig ventricular myocytes. Ajmaline suppressed the Ca2+ current (Ica) in a dose-dependent manner (Kd = 1.2 x 10(-5) M) without affecting the steady-state inactivation kinetics and the voltage dependency of the current-voltage relationship. Ajmaline inhibited the inward portion of the inward rectifying K+ current (IKl). Ajmaline decreased the delayed rectifier K+ current (IK) without altering the activation or deactivation time courses. All these inhibitory effects of ajmaline prolonged the action potential duration in a dose dependent manner. The inhibitory actions of ajmaline on the action potential upstroke and various currents responsible for the plateau and repolarization may contribute to the observed suppression of depolarization-induced abnormal automaticities by this agent.

A CASE OF WPW SYNDROME ASSOCIATED WITH MITRAL STENOSIS AND REFRACTORY ATRIAL FIBRILLATION

A 60 year-old man with Wolff-Parkinson-White (WPW) syndrome was admitted to our hospital because of atrial fibrillation and heart failure. He had a history of paroxysmal atrial fibrillation which had increased in frequency as mitral stenosis progressed over a period of 10 years. Since heart rate-dependent torsades de pointes appeared after DC defibrillation due to class IA antiarrhythmic agents, the drug was withdrawn and an intravenous infusion of isoproterenol was started. Sinus rhythm was restored and maintained by restarting the administration of the class I A antiarrhythmic agent. Electrophysiological examination revealed a single accessory conduction pathway and no retrograde conduction, the effective refractory period was prolonged to 330 msec. After the heart failure had improved, mitral valve replacement and transection of the bundle of Kent were performed. Because of the possibility of grave hemodynamic derangement induced by marked tachycardia, surgical treatment should be seriously considered in patients with mitral stenosis when associated with WPW syndrome and atrial fibrillation, even in those not classified as high risk patients.

Instantaneous cardiac death in the posthospital period after acute myocardial infarction

Sudden arrhythmic cardiac death is a major unresolved health problem, yet there is no agreement on the chronologic definition of sudden death. This retrospective study investigates the frequency distribution of the chronology of the terminal cardiac event in a large postinfarction population and identifies factors associated with instantaneous (<1 minute) cardiac death. This study involved 229 patients enrolled in the Multicenter Diltiazem Post-infarction Trial who died during 2-year follow-up and had quantitative information on the chronology of the terminal event. Thirty-two percent of the cardiac deaths occurred instantaneously. Patients who died instantaneously were more likely (p < 0.05) to be men, to have a baseline ejection fraction <0.40, and to have frequent (≥10/hour) and repetitive (≥3 in a row) ventricular ectopic complexes (VECs) on an ambulatory electrocardiogram than those who did not die instantaneously. Patients who died instantaneously received more digitalis and class IA antiarrhythmic agents and less β blockers in the week before death than those dying noninstantaneously. Logistic regression analysis identified 3 independent factors that differentiated instantaneous from noninstantaneous death (relative risk; 95% confidence interval): frequent VECs (2.15; 1.11 to 4.17); digitalis (2.57; 1.31 to 5.06); and no β blocker medication (2.90; 1.09 to 7.75). Instantaneous death (within 1 minute) was responsible for almost one third of the cardiac deaths that occurred in this postinfarction population. Frequent VECs, digitalis, and absence of β-blocker therapy distinguished patients who died instantaneously from those who died noninstantaneously.

Developmental Toxicity of Pirmenol in Rats and Rabbits

Pirmenol, a Class Ia antiarrhythmic agent, was evaluated for developmental toxicity in rats and rabbits. Suspensions of pirmenol in 0.5% methylcellulose were administered by gavage on gestation days (GD) 7 to 17 to groups of 40 rats (0, 75, 125 and 150 mg/kg) and on GD 6 to 18 to groups of 20 rabbits (0, 10, 25 and 50 mg/kg). 25 rats per group and all rabbits were euthan-atised near term (GD 21, rats; GD 30, rabbits) and fetuses were examined for external, visceral and skeletal variations and malformations. The remaining 15 rats per group were allowed to deliver and rear their offspring to postnatal (PN) day 21. Growth, survival, development, behaviour and reproductive performance were evaluated in the F1 group (offspring of the original animals). Maternal toxicity was observed during treatment at the 2 highest doses in rats (ataxia, hypoactivity, languid appearance, tremors, squinted eyes, and abnormal respiration) and in rabbits at the high (convulsion, mortality, bodyweight loss and significant suppression of food intake) and mid doses (suppression of bodyweight gain). Embryo/fetal or postnatal toxicity were not observed in rats. In rabbits, postimplantation loss was slightly increased at 25 and 50 mg/kg/day and the mean number of live fetuses was slightly decreased at 50 mg/kg/day. A statistically significant increase in the percentage of malformed fetuses per litter, observed at 50 mg/kg/day, was considered equivocal due to the limited number of surviving fetuses and litters (n = 5) at that dose. In conclusion, administration of pirmenol during organogenesis produced maternal, but not developmental, toxicity in rats at doses up to 150 mg/kg/day and maternal and developmental toxicity at doses less than 10 and 25 mg/kg/day or more, respectively, in rabbits.

Fertility and Perinatal/Postnatal Studies in Rats with the Antiarrhythmic Agent Pirmenol

Fertility and perinatal/postnatal studies were conducted in Sprague-Dawley rats with the Class Ia antiarrhythmic agent pirmenol. Doses of 25, 50 or 100 mg/kg/day were administered in the diet for both studies; untreated control groups received basal diet. Male rats in the fertility study were treated for 75 days prior to mating, while F0 female rats were treated for 15 days prior to mating, and also during mating, gestation and lactation. F0 female rats in the perinatal/postnatal study were treated from gestation day (GD) 15 to lactation day 21. Caesarean section was performed on half the fertility study females per group on GD 20, while the remaining half of the fertility study females and all perinatal/postnatal study females were allowed to deliver and raise the F1 offspring. The F1 generation was evaluated for survival, growth, development, behaviour and reproductive performance. Although bodyweight and food consumption of fertility study F0 parents were reduced at pirmenol 100 mg/kg/day, no treatment-related effects were observed on reproductive parameters, or on maternal and fetal parameters evaluated at caesarean section. Reduction in bodyweight occurred for fertility study F1 offspring of all treatment groups during the neonatal period, but not during maturation. Offspring were unaffected with regard to survival, development, behaviour or reproductive performance. Treatment-related effects observed in perinatal/postnatal study F1 females at pirmenol 50 and/or 100 mg/kg/day included clinical signs of toxicity, reduction of bodyweight gain and food consumption, and stomach lesions. Food spillage, indicative of a possible palatability problem, also occurred at 100 mg/kg. Viability of F1 offspring was decreased at 100 mg/kg/day, while the incidence of dilated renal pelvis was increased; treatment-related reduction of bodyweight and open field activity occurred at pirmenol 50 and 100 mg/kg/day. Results of these studies indicate that the nature, magnitude and duration of pirmenol-related effects differed according to treatment regimen.

Electrophysiologic Response to Moricizine in Patients with Sustained Ventricular Arrhythmias

To assess the short-term efficacy and safety of moricizine in patients receiving electrophysiologically guided therapy for sustained ventricular arrhythmias refractory to treatment with class IA antiarrhythmic agents. Uncontrolled clinical trial. Referral-based teaching medical center. Twenty-one patients (18 of whom had coronary artery disease) with a mean left ventricular ejection fraction of 32% +/- 11% who presented with sustained ventricular tachycardia (13 patients), syncope (4 patients), or cardiac arrest (4 patients). Moricizine, 743 +/- 85 mg daily. Electrophysiologic testing in the drug-free state and after administration of moricizine unless sustained arrhythmias occurred. Sustained ventricular tachycardia was inducible in the absence of antiarrhythmic drugs in 20 patients and was not suppressed by moricizine in any patient. Four patients had six episodes of spontaneous ventricular tachycardia while receiving moricizine. A probable proarrhythmic response occurred in four patients. In patients with compromised left ventricular function caused by coronary artery disease in whom class IA antiarrhythmics were ineffective, moricizine was ineffective in suppressing sustained ventricular arrhythmias and resulted in proarrhythmic effects in some patients.

Variability of the QT measurement in healthy men, with implications for selection of an abnormal QT value to predict drug toxicity and proarrhythmia

Torsades de pointes is the form of polymorphic ventricular tachycardia associated with prolongation of the QT interval that can occur as a proarrhythmic adverse response to a variety of drug treatments. 1,2 However, the degree of QT prolongation at rest 3,4 or during exercise 5 is not necessarily a good predictor of the occurrence of torsades de pointes. Prolongation of the QT interval duration is seen during therapy with many different types of drugs including class IA antiarrhythmic agents as well as ketanserin, amiodarone, bepridil, sotalol, antidepressants, phenothiazines, erythromycin, antihistamines and liquid protein diets. Quinidine is the drug most frequently implicated in this syndrome with a calculated incidence of 1 to 8%. 4 However, plasma drug level, absolute QT interval prolongation and the absolute QT C have not been found to be very good predictors of the development of torsades de pointes. 3,4 Data on the spontaneous variability of the QT interval over time in normal subjects have not been established. Thus, we determined the magnitude of spontaneous QT interval variability over just 1 day using ambulatory long-term electrocardiographic (Holter) monitoring. Knowledge of normal variability of the QT interval is important in that prolongation of the QT interval during drug therapy is considered to be a risk factor for the development of a potential proarrhythmic effect. However, knowledge of the daily spontaneous variability of the QT interval makes it possible to determine the magnitude of QT interval prolongation, which is clinically important with respect to its potential as a marker for risk of proarrhythmia.

Hypoglycémie induite par la cibenzoline chez le sujet âgé

Hypoglycaemia induced by class IA antiarrhythmic agents has been described. A case of cibenzoline-induced hypoglycaemia with favourable outcome is reported. The patient's age (84 years), increased renal impairment and malnutrition acted as facilitating factors. Blood insulin levels were normal in both absolute and relative values. Therapeutic overdosage in relation to age and renal function has been found in 20 out of 24 cases published or recorded by the French pharmacovigilance system. The mechanism of this hypoglycaemia is uncertain; absolute or relative hyperinsulinism has been detected in only 5 out of 14 controlled cases.

Electrophysiologic effects of FPL 13210 on canine Purkinje fiber action potential duration and Vmax comparison to disopyramide

The frequency-dependent effects of FPL 13210, a new disopyramide derivative, were examined in isolated canine cardiac Purkinje fibers paced at a frequency of 2 Hz and following abrupt changes in pacing cycle length. At 2 Hz, FPL 13210 depressed Vmax, while shortening action potential duration measured at 50% of repolarization (APD50) and not affecting duration measured at 90% of repolarization (APD90). These effects were concentration dependent over the range of 1-30 microM. The depression of Vmax produced by 5 microM FPL 13210 was not significantly different than that produced by 18 microM disopyramide while the preparations were paced constantly at 2 Hz. At these concentrations, recovery of Vmax was slowed by both FPL 13210 and disopyramide. The slow time constant estimated for this relation after exposure to FPL 13210 was approximately 6.5 times longer than that estimated following administration of disopyramide. In addition, APD90s evoked by early premature stimuli in the presence of 5 microM FPL 13210 were longer than those produced in the absence of drug when the diastolic intervals longer than 100 ms produced shorter APD90s after FPL 13210 administration. Therefore, when FPL 13210 is compared to disopyramide using concentrations selected to produce equivalent degrees of Vmax depression, FPL 13210 produced effects on APD90 that were opposite to those produced by disopyramide when the diastolic interval was longer than normal. These effects of FPL 13210 would suggest that this compound should be classified as a class Ic antiarrhythmic agent, unlike disopyramide, a class Ia antiarrhythmic agent.

Inefficacy and Proarrhythmic Effects of Flecainide and Encainide for Sustained Ventricular Tachycardia and Ventricular Fibrillation

To assess the efficacy of encainide and flecainide in treating patients with sustained ventricular arrhythmias. Patients were treated with encainide or flecainide. Efficacy was assessed by comparing the results of programmed ventricular stimulation while patients received therapy with the results while they were drug free. The electrophysiology laboratory of the University of California at San Francisco. Forty-nine patients with spontaneous or inducible sustained ventricular tachycardia or ventricular fibrillation for whom treatment with at least one class IA antiarrhythmic agent had failed. Patients were treated with encainide, 35 to 50 mg three or four times daily, or flecainide, 100 to 200 mg twice daily. Arrhythmia worsened early in 5 of 16 patients receiving encainide and 3 of 33 patients receiving flecainide. Patients with poor left ventricular function were more likely to exhibit proarrhythmia (P = 0.02). Nine of eleven patients receiving encainide and 23 of 28 patients receiving flecainide who had repeat programmed ventricular stimulation while receiving drug therapy still had inducible, poorly tolerated ventricular tachycardia. Encainide and flecainide have a low efficacy rate and a high incidence of worsening of arrhythmia in patients with sustained ventricular arrhythmias, particularly when this condition is associated with poor left ventricular function.

Effect of class Ia antiarrhythmic agents on fasciculoventricular fibers

In four patients with fasciculoventricular (FV) fibers, the electrocardiographic and electrophysiologic characteristics were studied based on their response to class Ia antiarrhythmic agents. Three patients had paroxysmal atrial fibrillation, and one showed atrioventricular nodal Wenckebach-type block with dual pathways. Three of the four patients showed complete block of FV fibers after administration of disopyramide 0.28–0.60 mg/kg, procainamide 1.7–2.6 mg/kg, and ajmaline 0.18–0.26 mg/kg, respectively. Normalization in the remaining patient was not seen after disopyramide 2 mg/kg or procainamide 10 mg/kg, but was achieved by ajmaline 0.86 mg/kg. Ventricular preexcitation beats showed initial q waves (3 patients) or a decrease in the height of the r wave (1 patient) in V1, no initial q wave in V6 (4 patients), and ST-T changes (1 patient). Since these findings resemble ischemic change or intraventricular conduction disturbance, drug testing is necessary for precise diagnosis and proper clinical management.

Idiopathic ventricular fibrillation

A review of the literature dealing with sudden death revealed 19 articles in which ostensibly healthy patients with documented VF unrelated to any known cardiac or noncardiac etiology are reported. Fifty-four patients fulfilling the criteria for idiopathic VF, including 14 patients investigated at our institution, are described. The mean age of patients for studies that reported age data was 36 years, with a male-to-female ratio of 2.5 to 1. Over 90% of the patients required resuscitation, while syncope due to nonsustained VF occurred in the rest. Diagnosis of VF was preceded by syncope in one fourth of the patients. Holter monitoring and exercise stress tests were often unrewarding. Available electrophysiologic data revealed a 69% inducibility rate of sustained ventricular tachyarrythmias using nonaggressive protocols of ventricular stimulation in most cases. Induced tachyarrhythmias were poorly tolerated, and were mostly of polymorphic configuration. Class IA antiarrhythmic agents were highly effective in preventing reinduction of these arrhythmias. Available figures suggest an 11% rate of sudden death within 1 year of diagnosis. Appropriate antiarrhythmic therapy appears to improve prognosis. Reviewed data suggest that idiopathic VF represents an underestimated cause of sudden cardiac death in ostensibly healthy patients. An international registry of patients with idiopathic VF is warranted.

Suppressant effects of conventional beta blockers and sotalol on complex and repetitive ventricular premature complexes

Beta-blocking drugs have been shown to reduce the overall mortality and risk of sudden cardiac death in survivors of acute myocardial infarction. It is not known whether such an effect is mediated by suppression of ventricular premature complexes (VPCs). The circadian rhythmicity of ventricular arrhythmia can also be suppressed by β-blocking drugs, and this may help reduce the risk of sudden cardiac death during the morning hours. Recent studies have also shown that β blockers can provide a safe and effective combination with class IA antiarrhythmic agents when arrhythmias cannot be controlled with class IA agents alone. Sotalol, a nonselective β antagonist, has unique electrophysiologic properties, and several studies have shown it to be more effective than conventional β blockers in suppressing ventricular arrhythmias. However, direct comparative studies of the suppression of VPCs are lacking. In a recent double-Mind, placebo-controlled, parallel study, the antiarrhythmic effects of sotalol and propranolol were compared in 172 patients with >30 VPCs/ hour. After the initial 1-week washout and 1-week placebo period, patients were randomly assigned to either 160 mg of sotalol administered twice daily (76 patients) or 40 mg of propranolol administered 3 times daily (91 patients). Those responding to therapy (decreases >75% VPCs) continued to take these closes, but nonresponders were given higher doses, 320 mg of sotalol twice daily or 80 mg of propranolol 3 times daily, respectively. The baseline mean hourly VPC count, derived from two 24-hour Holter recordings during the placebo phase, was 274 for sotalol and 255 for propranolol patients and was reduced to 54 (80% decrease) for sotalol and 104 (59% decrease) for propranolol-treated patients at 6 weeks (p < 0.002). A significantly greater percentage of patients (56%) responded to sotalol compared with those who responded to propranolol (29%) (p < 0.001). The class III antiarrhythmic activity of sotalol may account for its superiority over propranolol.

Hypertonic sodium bicarbonate partially reverses QRS prolongation due to flecainide in rats

Hypertonic (1M) sodium bicarbonate can partially reverse the cardiac toxicity of some Class IA antiarrhythmic agents, presumably by antagonizing sodium channel inhibition. We studied the effects of 1M sodium bicarbonate on toxicity due to the Class IC drug flecainide. Anesthetized rats received i.v. loading and maintenance doses of flecainide to produce QRS prolongation of 76% that was stable over the 60 min study period. 20 min after the start of the maintenance infusion, groups of 8 rats received an i.v. infusion of 1M sodium bicarbonate (6 meq/kg) or an equal volume of 0.9% saline. QRS prolongation was reduced by 1M sodium bicarbonate but not only 0.9% saline (% change −12.2±10.0 v. +3.0 ±2.7, p=0.001). Expressed as a percent of the flecainide-induced QRS prolongation, bicarbonate reduced this prolongation by 26.5%. The improvement in QRS duration persisted until sacrifice 30 min later. Compared to controls, the bicarbonate group has a significantly higher blood pH (7.55±0.06 v. 7.44±0.05) and serum sodium concentration (149±5 v. 137±2 meq/l). Serum flecainide concentrations were similar. These data suggest that 1M sodium bicarbonate can partially reverse flecainide-induced conduction delay in rats. This effect may be due to changes in the extracellular pH and sodium concentration. 1M sodium bicarbonate may be useful in assessing the role of sodium channel inhibition in mediating the toxicity of flecainide or other Class IC drugs.

P-234 - Interactions of class Ia antiarrhythmic agents with cardiac muscarinic receptors

P-234 - Interactions of class Ia antiarrhythmic agents with cardiac muscarinic receptors

Oral flecainide for prophylaxis of paroxysmal atrial fibrillation

This study was designed to assess the clinical efficacy of oral flecainide for the prevention of paroxysmal attacks of atrial fibrillation (AF). Forty patients with frequent, very symptomatic AF were selected for study; 31 had vagally induced AF. All patients were considered to be drug resistant. Each had recurrences of AF despite previous antiarrhythmic therapy that included high doses of amiodarone given alone or in combination with a class IA antiarrhythmic agent. In 6 patients, very high doses of amiodarone were efficacious in the prevention of AF; however, the doses had to be reduced because of adverse effects, which resulted in the recurrence of the arrhythmia. Patients were followed up for a period of 18 months and assessed by both symptom development and Holter monitor recordings. Patients received flecainide at an initial dose of 300 mg/day, which was increased to 400 mg/day in case of failure. If the initial dose was successful, the dose was reduced until the lowest one required to prevent recurrences of the arrhythmia was found. Amiodarone was also reduced or withdrawn whenever possible. The results show that AF in 32 of 40 patients was controlled with flecainide given alone (11 of 32) or in combination with amiodarone (21 of 32). Only 8 patients were considered to be drug resistant. The mean dose required to prevent recurrences of AF was also determined for each drug. The combined administration of flecainide and amiodarone allowed a significant reduction in the daily dose of amiodarone (p < 0.005). On the other hand, daily doses of flecainide given with or without amiodarone were not significantly different (204 vs 209 mg/day). It is concluded that flecainide acetate is a very potent antiarrhythmic agent at the atrial level and may prevent recurrences of paroxysmal AF in patients who were previously considered to be drug resistant. It also allows a significant reduction in the daily dose of amiodarone in patients who require combined drug therapy.

Effects of procainamide and lidocaine on electrically inducible ventricular tachycardia studied with programmed ventricular stimulation in post myocardial infarction.

The effects of procainamide and lidocaine, representative of class IA and IB antiarrhythmic agents, on electrically inducible ventricular tachycardia (VT) were studied using programmed ventricular stimulation in 47 post myocardial infarction patients at an average of 1.5 months after the onset. The mean doses of administered procainamide and lidocaine were 1050 mg and 161 mg, and their mean plasma concentrations were 7.5 micrograms/ml and 3.1 micrograms/ml respectively. The induction of sustained VT was suppressed in 15 of 29 patients (52%) by procainamide, but in none by lidocaine. The induction of nonsustained VT was suppressed in 6 of 18 patients (33%) by procainamide, and in 1 of 8 patients (13%) by lidocaine. The efficacy rate of procainamide was significantly higher than that of lidocaine in suppression of VT induction (21/47 vs 1/14 p less than 0.01). Procainamide significantly prolonged the effective refractory period of the right ventricle as well as the HV and QRS interval, however lidocaine did not affect them significantly. On the other hand, the worsening effect which changed nonsustained VT inducible in the baseline into sustained VT inducible post drug administration was demonstrated in 8 of 18 procainamide cases (44%), and in 3 of 8 lidocaine cases (38%). Between the procainamide effective and ineffective or worsening patients, there were no differences found in the electrophysiologic variables either in the baseline or post procainamide administration. We concluded that procainamide was more effective than lidocaine for the prevention of potential life-threatening VT induction in post myocardial infarction patients, although its efficacy was considerably limited, and to confirm the effectiveness and exclude the worsening effects of the class IA and IB antiarrhythmic agents, drug testing using programmed ventricular stimulation appeared to be valuable.

Clinical significance of vanghan williams classification for treatment of ventricular tachycardia. Study of class IA and IB antiarrhythmic agents.

Ninety-eight cases of ventricular tachycardia (VT) were studied using clinical electrophysiological (EP)-pharmacological assessment to compare the efficacy of class IA (disopyramide-DP, procainamide-PA) and class IB (mexiletine-Mex, Lidocaine-Lid, aprindine-AP) agents available in Japan, and to evaluate the clinical significance of class subdivisions for the treatment of VT. In assessing the efficacy of drugs, we evaluated their ability to prevent and terminate induced sustained VT as well as their ability to suppress spontaneous premature ventricular beats (VPB). I. EP properties: DP significantly extended QTc, ERPRV, and the coupling interval by which VT or repetitive ventricular response (RVR) was induced. On the other hand, Mex and AP had no effect. Although no significant extension of QRS width was found, the significant extension of the interval from extrastimulus to the first induced VT or RVR complex by the three drugs indicates that all have suppressive effects on conduction velocity within the reentry circuit. II. Correspondence of preventive effects was 67% for DP and PA (class IA), 54% for Mex and Lid (class IB), 55% for DP and Mex, 27% for AP and Mex, and 25% for AP and DP. Correspondence of terminating effect was 85% for DP and PA, 80% for DP and AP, 77% for DP and Mex, 75% for Mex and Lid, and 63% for Mex and AP. For suppression of spontaneous VPB's, correspondence rate was 100% for DP and PA, 39% for DP and Mex, 64% for Mex and Lid, 61% for Mex and AP, and 69% for DP and AP.(ABSTRACT TRUNCATED AT 250 WORDS)

Electrophysiologic properties of falipamil (AQA-39)--a new bradycardiac agent.

Falipamil hydrochloride (AQA 39) is a new antiarrhythmic agent structurally related to verapamil. We evaluated the electrophysiologic properties of intravenous falipamil (1.5 mg kg-1 within 20 minutes) in 12 patients. The spontaneous cycle length was significantly (P less than 0.001) prolonged (+79 +/- 59 ms). Atrioventricular conduction was significantly (P less than 0.001) shorter due to AH interval shortening (-17 +/- 14 ms), most probably related to an anticholinergic effect. Similarly, the anterograde Wenckebach point occurred at a significantly (P less than 0.06) higher rate after falipamil (+10 +/- 7 beats min-1). No statistically significant effect was noted on the refractory periods of the AV node, although there was a trend to shortening. The refractoriness of the right atrium and ventricle was significantly prolonged. It is concluded that falipamil is a bradycardiac agent with electrophysiologic properties quite different from those of verapamil and similar to those of class IA antiarrhythmic agents.