piperidines and Wolff-Parkinson-White-Syndrome

Lorcainide is a type I antiarrhythmic drug of the local anesthetic type. It can be given either intravenously or orally, and its pharmacokinetic properties allow relatively long (12 hours) dosing intervals with oral administration. A slowly eliminated metabolite, norlorcainide, probably contributes to the effects of orally administered lorcainide in chronically treated patients. In mainly short term studies, lorcainide has been shown to suppress ventricular ectopy in about 80% of patients treated either orally or intravenously. Preliminary evidence suggests that its efficacy in suppressing ectopy in the setting of acute myocardial infarction is comparable with that of lignocaine (lidocaine). It is of variable efficacy in preventing recurrent ventricular tachycardia and has been shown to be effective in some patients who have failed to respond to other antiarrhythmic drugs. Experience is limited in treating supraventricular arrhythmia, but initial results in patients with Wolff-Parkinson-White syndrome have been favourable. Adverse cardiac effects are infrequent. Abnormal sinus node function may be exacerbated by lorcainide treatment, however, and bundle branch block may be precipitated in patients with pre-existing conduction system disease. Exacerbation of pre-existing arrhythmias is uncommon, and clinically important myocardial depression has not been observed. The most frequent side effect is disturbed sleep during the initiation of oral treatment, which may occur in the majority of patients but usually responds to treatment with a benzodiazepine and subsides with time. Thus, lorcainide appears useful against a variety of arrhythmias. With its convenient dosage schedule and apparently low incidence of serious side effects it should become a useful addition to the antiarrhythmic agents available, although longer term studies are needed to confirm its continued efficacy and lack of unexpected side effects when used for long periods.

Topics: Animals; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Benzeneacetamides; Biological Availability; Clinical Trials as Topic; Drug Interactions; Electrophysiology; Half-Life; Hemodynamics; Humans; Kinetics; Piperidines; Wolff-Parkinson-White Syndrome

We sought to determine the effect of remifentanil on sinus node function and the atrial-His (AH) interval in pediatric patients undergoing radiofrequency catheter ablation.. Sixty pediatric patients with Wolff-Parkinson-White syndrome were prospectively enrolled in this study. General anesthesia was induced and maintained with a continuous infusion of propofol. We recorded the calculated sinoatrial conduction time (CSACT), corrected sinus node recovery time (CSNRT), and AH interval when the patients were in a stable anesthetic state and compared the values before and during remifentanil administration at a moderate dose (0.2 μg · kg(-1) · min(-1)) or a high dose (0.4 μg · kg(-1) · min(-1)). Data are expressed as mean (95% confidence interval).. At the moderate dose, remifentanil prolonged CSNRT (from 177 [117-237] milliseconds to 245 [167-322] milliseconds after administration; P=0.016), but had no effect on either CSACT (P=0.59) or AH interval (P=0.11). However, high-dose remifentanil prolonged both CSNRT (from 201 [144-260] milliseconds to 307 [232-382] milliseconds after administration; P=0.019) and CSACT (from 48 [31-65] milliseconds to 78 [59-96] milliseconds after administration; P=0.038), but had no effect on the AH interval (P=0.058). The interaction in CSNRT between remifentanil administration and its dose was not different (P=0.44).. Remifentanil may inhibit both intraatrial conduction and sinus node automaticity, but it has no effect on conduction through the atrioventricular node. Dose dependency was not observed within the range of 0.2 to 0.4 μg · kg(-1) · min(-1) of remifentanil.

Topics: Action Potentials; Age Factors; Analgesics, Opioid; Anesthetics, Intravenous; Bundle of His; Catheter Ablation; Child; Female; Heart Atria; Humans; Infusions, Intravenous; Japan; Male; Periodicity; Piperidines; Propofol; Prospective Studies; Refractory Period, Electrophysiological; Remifentanil; Sinoatrial Node; Time Factors; Wolff-Parkinson-White Syndrome

Lorcainide is a type I antiarrhythmic drug of the local anesthetic type. It can be given either intravenously or orally, and its pharmacokinetic properties allow relatively long (12 hours) dosing intervals with oral administration. A slowly eliminated metabolite, norlorcainide, probably contributes to the effects of orally administered lorcainide in chronically treated patients. In mainly short term studies, lorcainide has been shown to suppress ventricular ectopy in about 80% of patients treated either orally or intravenously. Preliminary evidence suggests that its efficacy in suppressing ectopy in the setting of acute myocardial infarction is comparable with that of lignocaine (lidocaine). It is of variable efficacy in preventing recurrent ventricular tachycardia and has been shown to be effective in some patients who have failed to respond to other antiarrhythmic drugs. Experience is limited in treating supraventricular arrhythmia, but initial results in patients with Wolff-Parkinson-White syndrome have been favourable. Adverse cardiac effects are infrequent. Abnormal sinus node function may be exacerbated by lorcainide treatment, however, and bundle branch block may be precipitated in patients with pre-existing conduction system disease. Exacerbation of pre-existing arrhythmias is uncommon, and clinically important myocardial depression has not been observed. The most frequent side effect is disturbed sleep during the initiation of oral treatment, which may occur in the majority of patients but usually responds to treatment with a benzodiazepine and subsides with time. Thus, lorcainide appears useful against a variety of arrhythmias. With its convenient dosage schedule and apparently low incidence of serious side effects it should become a useful addition to the antiarrhythmic agents available, although longer term studies are needed to confirm its continued efficacy and lack of unexpected side effects when used for long periods.

Topics: Animals; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Benzeneacetamides; Biological Availability; Clinical Trials as Topic; Drug Interactions; Electrophysiology; Half-Life; Hemodynamics; Humans; Kinetics; Piperidines; Wolff-Parkinson-White Syndrome

For eight weeks 30 psychotic patients with a healthy cardiovascular system received 3 X 50 mg 1-[3-(10,11-dihydro=5H-dibenz[b,f]-azepin-5-yl]-propyl]-4-piperidiono-piperdine-4-carboxamide dihydrochloride-monohydrate (carpipramine) per day with a placebo phase of three weeks either previous to the medication of succeeding it. In addition there was a group of similar patients without any medication. From this study it was concluded that carpipramide has no depressive effect on the cardiovascular system. The differences in blood pressure and heart rate after the change from medication to placebo indicate a certain vegetative lability in this phase. In the ECG, no irregularities of the atrioventricular and intraventricular conduction and its repolarisation in form of a lengthening were observed; only the WPW-syndrome noticed with one patient might be related to the medication since it occurred at the end of the three weeks during which carpipramine had been administered.

Topics: Adult; Antidepressive Agents, Tricyclic; Blood Pressure; Clinical Trials as Topic; Depression; Dibenzazepines; Electrocardiography; Heart; Heart Rate; Humans; Male; Middle Aged; Piperidines; Wolff-Parkinson-White Syndrome

The case of a 64-year-old man with Wolff-Parkinson-White syndrome and permanent atrial fibrillation (AF) is reported. The patient was admitted due to electrocardiographic feature of AF with rapid conduction over the left-sided accessory pathway. Administration of pirmenol effectively suppressed the ventricular response via an accessory pathway. A transesophageal echocardiography detected an uncertain thrombus in the left atrial appendage. During the 33-month follow-up period, the ventricular response via an accessory pathway was progressively facilitated. Radiofrequency catheter ablation using a transseptal approach was performed during AF, resulting in complete elimination of the antegrade accessory pathway conduction.

Topics: Anti-Arrhythmia Agents; Atrial Fibrillation; Bundle of His; Catheter Ablation; Electrocardiography; Follow-Up Studies; Humans; Male; Middle Aged; Piperidines; Wolff-Parkinson-White Syndrome

The electrophysiologic effects of the intravenous administration of a new antiarrhythmic drug, lorcainide, were evaluated by programmed electrical stimulation of the heart in 20 patients with and without Wolff-Parkinson-White (WPW) syndromes. Lorcainide shortened the sinus cycle length from 721.0 +/- 125.9 to 649.5 +/- 100.1 ms (P less than 0.001), but did not influence sinus node function and AV node conduction and refractoriness, slightly increased atrial effective period (ERP) (P less than 0.02) and did not change ventricular ERP (P less than 0.2), obviously lengthened atrial conduction time, H, H-V interval and the width of V wave. Lorcainide caused complete antegrade block of the accessory pathway (AP) in six of 9 WPW patients and resulted in exclusive conduction over the AV nodal. His conduction in two patients with atrial flutter. It also prolonged the retrograde conduction time and refractoriness of AP, and prevented initiation of orthodromic atrioventricular tachycardia (O-AVRT) in six of 12 patients by blocking of the retrograde conduction of the AP, increased the cycle length of tachycardia from 321.7 +/- 43.6 to 361.7 +/- 54.9 ms (P less than 0.005) by marked prolongation of retrograde AP conduction time in 6 patients in whom O-AVRT could still be induced. It is concluded that intravenous lorcainide does not affect sinus node and AV node function, slightly influences atrial and ventricular refractoriness, obviously suppresses atrial, His bundle and intraventricular conduction, and is an effective antiarrhythmic drug for patients with WPW by blocking both the antegrade and retrograde conduction of the AP.

Topics: Adolescent; Adult; Anti-Arrhythmia Agents; Benzeneacetamides; Child; Electrophysiology; Female; Heart Conduction System; Humans; Male; Middle Aged; Piperidines; Tachycardia, Supraventricular; Wolff-Parkinson-White Syndrome

Lorcainide was used in 17 children and adolescents aged 14 days to 18 years (mean 6.8 years) with the preexcitation syndrome (W-P-W type). Lorcainide was able to control attacks of supraventricular tachycardia in eight of 11 patients with the W-P-W syndrome and tachyarrhythmias. Long-term maintenance therapy prevented new attacks of tachyarrhythmia for an average period of nine (5-15) months in all seven patients who tolerated lorcainide administration. Normalization of the W-P-W pattern was reached in nine of 11 children with the W-P-W syndrome who had tachyarrhythmias and in three of six asymptomatic children with the ECG pattern of W-P-W. Single effective doses ranged from 12.5 mg orally in the neonates to 100 mg in the adolescents. The effect of lorcainide on the ECG usually appeared 2 h after the oral administration of the drug. Dizziness in three with insomnia and vomiting in one patient complicated the treatment. No drug-associated abnormalities in blood cell counts and biochemical values were identified.

Topics: Adolescent; Anti-Arrhythmia Agents; Benzeneacetamides; Cardiac Complexes, Premature; Child; Child, Preschool; Electrocardiography; Female; Heart Conduction System; Humans; Infant; Infant, Newborn; Male; Piperidines; Tachycardia, Supraventricular; Wolff-Parkinson-White Syndrome

Flecainide acetate (Flecaine) is a new antiarrhythmic which has recently become available; its efficacity in treatment of ventricular rhythm disorders has been amply demonstrated. In this study we have evaluated its efficacity per os in treatment of auricular rhythm disorders refractory to the usual therapies, and its effects on the accessory routes of atrioventricular conduction. The results are very promising and better than those obtained with amiodarone in auricular disorders. They show that flecainide is a drug of importance among therapeutic agents used in treatment of auricular arrhythmia, and its action on Kent's bundle makes it a drug of choice in management of Wolff-Parkinson-White syndrome, especially as it seems equally efficacious in its action on the accessory routes with a short refractory period. Most of our patients did not present organic cardiopathy and the side-effects were generally benign. A non-negligible number of cases of paroxysmal hypertension were noted, in disagreement with literature data, and this point needs to be clarified by further study.

Topics: Adolescent; Adult; Aged; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Atrial Fibrillation; Atrial Flutter; Female; Flecainide; Heart Atria; Humans; Male; Middle Aged; Piperidines; Wolff-Parkinson-White Syndrome

The acute electrophysiologic effects of pirmenol are reported in 8 normal subjects and in 8 patients with Wolff-Parkinson-White (WPW) syndrome. Standard electrophysiologic testing was performed before and after a 50-mg intravenous bolus and a 60-minute infusion of 150 mg of pirmenol. After pirmenol administration, AH interval, atrial refractory period, atrioventricular (AV) nodal functional refractory period and Wenckebach cycle length did not change; however, sinus cycle length decreased from 743 +/- 169 to 650 +/- 133 ms (p less than 0.001), sinoatrial conduction time from 103 +/- 35 to 78 +/- 37 ms (p less than 0.05) and AV nodal effective refractory period from 308 +/- 51 to 272 +/- 23 ms (p less than 0.01). Pirmenol increased the HV interval from 43 +/- 5 to 48 +/- 6 ms (p less than 0.05) and ventricular functional refractory period from 247 +/- 21 to 260 +/- 21 ms (p less than 0.005). Anterograde effective refractory period of the accessory AV pathway increased in 4 of 6 patients with ventricular preexcitation and retrograde effective refractory period increased in all patients. Pirmenol treatment prolonged the shortest preexcited RR interval from 253 +/- 38 to 459 +/- 19 ms (p less than 0.05) and the average RR interval from 354 +/- 26 to 421 +/- 60 ms (p less than 0.01) during atrial fibrillation in all 6 patients with preexcitation. Pirmenol did not influence the inducibility or cycle length of AV reciprocating tachycardia in the patients with WPW syndrome. The pirmenol infusions were well tolerated.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Anti-Arrhythmia Agents; Atrioventricular Node; Female; Humans; Male; Middle Aged; Piperidines; Reference Values; Sinoatrial Node; Tachycardia; Wolff-Parkinson-White Syndrome

The response of sustained supraventricular tachycardia to intravenous and oral flecainide acetate was investigated in 5 children, aged 5.5 to 11.5 years, who had tachycardias associated with Wolff-Parkinson-White syndrome. All children had failed to respond to at least 2 conventional agents. The effect of flecainide was studied using intracardiac techniques. Intravenous flecainide terminated tachycardia in all 5 patients. After drug infusion, slow, sustained tachycardia could be initiated in 1 patient. With oral treatment, slow, sustained tachycardia was started in 2 children and nonsustained in 2. One child had no inducible tachycardias. In 4 of 5 patients, long-term treatment has reduced the frequency of episodes and the drug is well tolerated. Thus, flecainide may be used to terminate and suppress junctional tachycardias in children who have failed to respond to conventional therapy.

Topics: Administration, Oral; Anti-Arrhythmia Agents; Child; Child, Preschool; Electrocardiography; Female; Flecainide; Humans; Injections, Intravenous; Male; Piperidines; Tachycardia; Wolff-Parkinson-White Syndrome

Although anterograde conduction through a Kent bundle with a short refractory period was suppressed by 300 mg of flecainide acetate, the infusion of small amounts of isoproterenol caused the reappearance of WPW and permitted the induction of an atrial tachycardia with 1/1 conduction through the accessory pathway at a rate of 260 beats min-1. This case shows that the effect of isoproterenol may be maintained after apparently successful flecainide therapy.

Topics: Adult; Anti-Arrhythmia Agents; Electrocardiography; Female; Flecainide; Heart Block; Heart Conduction System; Heart Rate; Humans; Isoproterenol; Piperidines; Wolff-Parkinson-White Syndrome

Flecainide, a new Vaughan-Williams Class Ic anti-arrhythmic agent, was used in 21 patients with an accessory AV conduction pathway which was apparent in 16 cases (WPW syndrome), latent in 1 case and concealed in 4 cases (block in the anterograde direction). Seventeen patients had spontaneous and inducible arrhythmias; 13 supraventricular tachycardias (SVT) due to orthodromic reentry including the accessory AV pathway and 4 atrial arrhythmias. Intravenous flecainide (2 mg/kg over 5 minute period) terminated the 13 cases of SVT in an average of 3 minutes by depressing then blocking retrograde conduction in the accessory pathway and 3 out of 4 cases of atrial arrhythmias. Conduction in the accessory pathway was blocked in the anterograde direction in 75% of cases and depressed in the rest; it was blocked in the retrograde direction in about half the cases and depressed in the rest. Intravenous flecainide completely prevented the induction or arrhythmias in 13 out of 17 patients (76%). Oral flecainide blocked the accessory pathway in the anterograde direction in 68.7%, and in the retrograde direction in 62% of patients, and prevented arrhythmias during provocative testing in 82% of patients (14 out of 17). With an average follow-up of 20.7 +/- 2.6 months with oral doses adapted to body weight and to the response to IV flecainide only one recurrence of atrial fibrillation was observed, a 100% prevention of spontaneous SVT and 94% prevention of all arrhythmias (16 out of 17 cases). The predictive value for the response to oral therapy of the tests of regularisation of SVT by IV flecainide and of the tests of non-provocation of SVT with oral or IV flecainide was excellent (100%). The cardiac tolerance was very good in these 21 patients (17 of whom had no valvular or myocardial lesion). There were 6 minor cases of general intolerance to oral therapy which were not dose related, only 1 of which required interruption of therapy. Flecainide appears one of the best choices for the treatment of preexcitation syndromes and their related arrhythmias at the present time.

Topics: Administration, Oral; Adolescent; Adult; Aged; Anti-Arrhythmia Agents; Electrocardiography; Electrophysiology; Female; Flecainide; Heart Conduction System; Humans; Infusions, Parenteral; Male; Middle Aged; Neural Pathways; Piperidines; Tachycardia; Wolff-Parkinson-White Syndrome

Flecainide is reported to be effective in patients with paroxysmal tachycardias, but its effect on rapid ventricular response over accessory atrioventricular pathway during atrial fibrillation is not known. The influence of flecainide on various electrophysiological properties of the accessory pathway with special emphasis on ventricular rate during atrial fibrillation was investigated in 9 patients with severe symptomatic Wolff-Parkinson-White syndrome. The shortest ventricular response during atrial fibrillation increased from 218 (190-270) to 320 (240-block) ms. In 4 patients sustained rapid atrial fibrillation converted to sinus rhythm. The rate of circus movement tachycardia decreased from 166/min to 130/min after flecainide, due to a lengthening of retrograde ventriculoatrial conduction time over the accessory pathway. Flecainide caused a significant prolongation of the effective refractory period of the accessory pathway in our subgroup with extremely fast AV conduction during atrial fibrillation and induced a depressant effect on retrograde accessory pathway conduction. This makes the drug very promising for the emergency treatment of dangerous rapid tachyarrhythias complicating this syndrome.

Topics: Adolescent; Adult; Anti-Arrhythmia Agents; Atrial Fibrillation; Cardiac Pacing, Artificial; Electrocardiography; Female; Flecainide; Heart Rate; Humans; Infusions, Parenteral; Male; Middle Aged; Piperidines; Wolff-Parkinson-White Syndrome

The acute effects of intravenous flecainide on electrically-induced paroxysmal supraventricular tachycardia and the safety and efficacy of long term prophylaxis with orally administered flecainide were assessed in 37 patients with paroxysmal supraventricular tachycardia refractory to treatment with 'conventional' antiarrhythmic drugs. Over a mean treatment period of 14.2 months, flecainide 200 to 400mg daily completely suppressed paroxysmal supraventricular tachycardia in 9 of 20 patients with paroxysmal supraventricular tachycardia due to Wolff-Parkinson-White syndrome, while 3 patients reported only transient episodes of paroxysmal supraventricular tachycardia, and 1 patient had a decreased ventricular response to chronic atrial fibrillation. Of 17 patients with paroxysmal supraventricular tachycardia due to atrioventricular nodal re-entry, flecainide 200 to 500mg daily for a mean period approaching 26 months totally prevented episodes of paroxysmal supraventricular tachycardia in 8, and reduced the frequency and duration of episodes of paroxysmal supraventricular tachycardia in 3 others. Flecainide prolonged action potential refractoriness in a few patients in each group; however, an increased frequency of occurrence of paroxysmal supraventricular tachycardia occurred due to a simultaneous decrease in the re-entry circuit conduction velocity. In both patient groups the acute electrophysiological effects of flecainide were often predictive of the long term efficacy of the drug in the prophylaxis of paroxysmal supraventricular tachycardia. Side effects usually involved the central nervous system and were most commonly manifested by disturbances in vision, balance, and taste and increased nervousness. These side effects generally subsided following 1 to 2 months' treatment with flecainide. No abnormal trends were observed in laboratory analysis of blood samples taken from patients during long term treatment with flecainide.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adolescent; Adult; Aged; Anti-Arrhythmia Agents; Female; Flecainide; Humans; Male; Middle Aged; Piperidines; Tachycardia, Paroxysmal; Wolff-Parkinson-White Syndrome

Topics: Administration, Oral; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Flecainide; Humans; Piperidines; Tachycardia, Paroxysmal; Wolff-Parkinson-White Syndrome

Topics: Anilides; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Atrial Fibrillation; Atrioventricular Node; Benzeneacetamides; Encainide; Flecainide; Heart Atria; Humans; Lidocaine; Piperidines; Tachycardia; Tocainide; Wolff-Parkinson-White Syndrome

Topics: Adolescent; Anti-Arrhythmia Agents; Benzeneacetamides; Child; Child, Preschool; Female; Humans; Infant; Infant, Newborn; Infant, Newborn, Diseases; Male; Piperidines; Wolff-Parkinson-White Syndrome

The effect of flecainide in 12 patients with the Wolff-Parkinson-White syndrome was analyzed with respect to the anterograde and retrograde conduction properties of the accessory pathway, the modes of initiation and termination of circus movement tachycardias, and the ventricular response during induced atrial fibrillation. The principal effect of this drug was to depress both anterograde and retrograde conduction of the accessory pathway. In 8/9 cases circus movement tachycardia was terminated by prolongation of the retrograde effective refractory period of the accessory pathway. Flecainide increased the shortest and the mean cycle length during induced atrial fibrillation. It is concluded that the drug may be of potential benefit in patients with paroxysmal supraventricular tachycardias in patients with the Wolff-Parkinson-White syndrome.

Topics: Adult; Electrophysiology; Female; Flecainide; Heart Conduction System; Humans; Male; Middle Aged; Piperidines; Tachycardia, Paroxysmal; Wolff-Parkinson-White Syndrome

The electrophysiologic effects of lorcainide, a class I antiarrhythmic agent with local anesthetic properties, were studied in 20 patients with the Wolff-Parkinson-White syndrome. After intravenous administration of lorcainide (2 mg/kg), the sinus cycle length decreased in all patients from 705 +/- 117 to 636 +/- 94 ms (p less than 0.001). The atrioventricular conduction time lengthened from 84 +/- 22 to 94 +/- 22 ms (p less than 0.01) and the QRS duration increased from 92 +/- 19 to 120 +/- 29 ms (p less than 0.001). The effective refractory period of the atrium increased from 230 +/- 27 to 243 +/- 35 ms (p less than 0.05), whereas the ventricular refractoriness was unaffected. Retrograde conduction over the accessory pathway was blocked in 5 of 18 patients after lorcainide; in the remaining 13 patients a prolongation from 107 +/- 32 to 162 +/- 57 ms (p less than 0.001) was found. Anterograde conduction over the accessory pathway was blocked in 6 patients, and in all other patients it increased considerably. Circus movement tachycardia could be induced in 14 patients before and in 10 patients after the drug. The shortest R-R interval during tachycardia lengthened from 326 +/- 40 to 364 +/- 67 ms (p less than 0.05). The tachycardia zone was unaffected by lorcainide. In 15 patients atrial fibrillation was induced. After lorcainide anterograde conduction during atrial fibrillation was blocked (n = 5). The shortest R-R interval over the accessory pathway during induced atrial fibrillation increased from 228 +/- 35 to 304 +/- 103 ms (p less than 0.05). Intravenous administration of lorcainide produced a pronounced negative dromotropic effect on the conduction properties of the accessory pathway. Lorcainide appears to be a promising new antiarrhythmic agent in patients with the Wolff-Parkinson-White syndrome.

Topics: Adolescent; Adult; Aged; Anti-Arrhythmia Agents; Atrial Fibrillation; Benzeneacetamides; Drug Evaluation; Electrocardiography; Female; Heart Conduction System; Humans; Male; Middle Aged; Piperidines; Tachycardia; Wolff-Parkinson-White Syndrome

Topics: Adult; Aged; Anti-Arrhythmia Agents; Benzeneacetamides; Cardiac Pacing, Artificial; Female; Heart Block; Heart Conduction System; Heart Rate; Humans; Male; Middle Aged; Piperidines; Sinoatrial Block; Sinoatrial Node; Time Factors; Wolff-Parkinson-White Syndrome