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[Recurrent syncope in a 34-year-old woman triathlete].

HISTORY: Some weeks previously a 34-year old athlete, specializing in the triathlon, had 6 syncopes in one day. They had caused abrasions and contusions resulting from the falls. At another hospital paroxysmal atrial fibrillation had been diagnosed and treatment with disopyramide (2 x 200 mg) initiated, but she had about 15 further syncopes within 2 weeks. She was admitted for establishing their cause. INVESTIGATIONS: Initial ECGs and neurological examination failed to provide a diagnosis and she was discharged with an "event recorder". DIAGNOSIS, TREATMENT AND COURSE: Three weeks after discharge she had another syncope. The event recorder was activated by the patient's partner and revealed polymorphous ventricular tachycardia. She underwent extensive invasive cardiological tests, including a right ventricular biopsy, but no abnormality was demonstrated. However, a provocation test with ajmaline produced ST segment elevations in V1 and V2 typical of the syndrome previously described by the Brugadas (right bundle branch block, precordial ST elevations in V1-V3 and sudden cardiac death). A cardioverter-defibrillator was implanted. During the subsequent observation period of 2 month the ICD delivered one countershock, triggered by the onset of polymorphous ventricular tachycardia with syncope. CONCLUSION: In patients with serious ventricular arrhythmias but no diagnostic findings, including a normal resting ECG, a drug provocation test should be performed to exclude a Brugada syndrome.

Adult↗

[Neurocardiogenic syncopes in patients with implanted pacemakers].

BACKGROUND AND OBJECTIVE: Recently the tilting table test (tilting up to 70 degrees angle) has established itself for the diagnosis of neurocardiogenic syncope (NS). Usually patients with bradycardic arrhythmias or asystole are treated by pacemaker implantation. But if the syncope is of neurocardiogenic aetiology other therapeutic alternatives must be chosen. We here report on seven patients in whom a pacemaker had been implanted in the treatment of syncopes, in ignorance of their neurocardiogenic aetiology, yet they had recurred. PATIENTS AND METHODS: Pacemakers had been implanted in eight patients: two with sick sinus syndrome, three with sinus bradycardia, one with brady-tachyarrhythmia, one with asystole and one with Mobitz-type 2 degrees AV block. All patients continued to have syncopes, when sitting or standing, months to years after the pacemaker implantation. The tilting table test (up to 30 min at an angle of 70 degrees) was positive in all patients. There was no case of pacemaker malfunction. RESULTS: One patient declined further treatment. The remaining seven patients were symptom-free in the tilting table test on various medications: theophylline up to 2 x 350 mg, metoprolol up to 2 x 100 mg or disopyramide 3 x 100 mg. CONCLUSION: Patients with syncope while sitting or standing should undergo the tilting table test to determine whether the cause is neurocardiogenic so that pacemaker implantation can be avoided. The majority of patients with NS can be successfully treated by drugs. But in some patients pacemaker implantation may have to considered if drug treatment has failed.

Aged↗

Position statement and practice guidelines on the use of multi-dose activated charcoal in the treatment of acute poisoning. American Academy of Clinical Toxicology; European Association of Poisons Centres and Clinical Toxicologists.

In preparing this Position Statement, all relevant scientific literature was identified and reviewed critically by acknowledged experts using agreed criteria. Well-conducted clinical and experimental studies were given precedence over anecdotal case reports and abstracts were not usually considered. A draft Position Statement was then produced and subjected to detailed peer review by an international group of clinical toxicologists chosen by the American Academy of Clinical Toxicology and the European Association of Poisons Centres and Clinical Toxicologists. The Position Statement went through multiple drafts before being approved by the Boards of the two societies. The Position Statement includes a summary statement for ease of use and is supported by detailed documentation which describes the scientific evidence on which the Statement is based. Although many studies in animals and volunteers have demonstrated that multiple-dose activated charcoal increases drug elimination significantly, this therapy has not yet been shown in a controlled study in poisoned patients to reduce morbidity and mortality. Further studies are required to establish its role and the optimal dosage regimen of charcoal to be administered. Based on experimental and clinical studies, multiple-dose activated charcoal should be considered only if a patient has ingested a life-threatening amount of carbamazepine, dapsone, phenobarbital, quinine, or theophylline. With all of these drugs there are data to confirm enhanced elimination, though no controlled studies have demonstrated clinical benefit. Although volunteer studies have demonstrated that multiple-dose activated charcoal increases the elimination of amitriptyline, dextropropoxyphene, digitoxin, digoxin, disopyramide, nadolol, phenylbutazone, phenytoin, piroxicam, and sotalol, there are insufficient clinical data to support or exclude the use of this therapy. The use of multiple-dose charcoal in salicylate poisoning is controversial. One animal study and 2 of 4 volunteer studies did not demonstrate increased salicylate clearance with multiple-dose charcoal therapy. Data in poisoned patients are insufficient presently to recommend the use of multiple-dose charcoal therapy for salicylate poisoning. Multiple-dose activated charcoal did not increase the elimination of astemizole, chlorpropamide, doxepin, imipramine, meprobamate, methotrexate, phenytoin, sodium valproate, tobramycin, and vancomycin in experimental and/or clinical studies. Unless a patient has an intact or protected airway, the administration of multiple-dose activated charcoal is contraindicated. It should not be used in the presence of an intestinal obstruction. The need for concurrent administration of cathartics remains unproven and is not recommended. In particular, cathartics should not be administered to young children because of the propensity of laxatives to cause fluid and electrolyte imbalance. In conclusion, based on experimental and clinical studies, multiple-dose activated charcoal should be considered only if a patient has ingested a life-threatening amount of carbamazepine, dapsone, phenobarbital, quinine, or theophylline.

Acute Disease↗

Changes in external Na induce a membrane current related to the Na-Ca exchange in cesium-loaded frog heart cells.

The effects of transient alterations in Nao were investigated under voltage clamp conditions in frog heart cells previously loaded with Cs. Tetrodotoxin and Cs were used to inhibit Na and K currents. On applying a Na-poor solution (39.2 mM), an outward current was generated during both depolarizations and hyperpolarizations. The current amplitude described a U-shaped function of the membrane potential. On reapplying the standard solution after 15 min equilibration, an inward current was then induced that exhibited a bell-shaped function of the membrane potential. Current amplitude was sensitive to the external Ca concentration. Increasing pHi by 10 mM NH4Cl enhanced this current, while the internal acidification that occurred on switching back to the control solution greatly reduced it. Variations in the amplitude of this current during repetitive stimulations or long pauses are best explained by subsequent alterations in Nai and pHi; no evidence for a time dependence was found. This current was inhibited by La3+, Co2+, and D600, and was sensitive to adriamycin, quinidine, and disopyramide; lidocaine, another local anesthetic, and nifedipine had no effect. These observations extend previous work on intact heart cells and sarcolemmal vesicles. They suggest that the Na-Ca exchange may generate a current that is outward when Ca ions are moving into the cell.

Amiloride↗

Kinetics of onset of rate-dependent effects of Class I antiarrhythmic drugs are important in determining their effects on refractoriness in guinea-pig ventricle, and provide a theoretical basis for their subclassification.

The kinetics of onset of rate-dependent depression of maximum rate of depolarisation (Vmax) of guinea-pig ventricular action potentials were studied for nine Class I anti-arrhythmic drugs using standard microelectrode techniques. The drugs were found to fall into three well-demarcated subgroups with "fast" (lignocaine, tocainide and mexiletine), "intermediate" (quinidine, disopyramide and procainamide) and "slow" (flecainide, encainide and lorcainide) kinetics. The "fast" drugs were found to share the ability to markedly prolong the effective refractory period (ERP) relative to the action potential duration (APD). The "slow" drugs had only minor effects on this parameter. The "intermediate" drugs produced small to moderate increases in ERP relative to APD but in addition significantly prolonged APD, which was shortened by the "fast" drugs. Thus, using the parameters of speed of onset of rate-dependent depression of Vmax and APD it was possible to subdivide the nine Class I drugs into three distinct subclasses.

Action Potentials↗

Selective depression of conduction of premature action potentials in canine Purkinje fibres by class Ib antiarrhythmic drugs: comparison with Ia and Ic drugs.

Microelectrodes were used to record action potentials and to estimate their conduction velocity in canine Purkinje fibres 8-15 mm long mounted in a tissue bath. The effects of varying stimulation rates and protocols were studied in the presence of nine different class I antiarrhythmic drugs at each of two concentrations (high and low therapeutic range). In all cases, as stimulation rate increased (range of cycle lengths 1000 ms to 200 ms), conduction velocity in the presence of a drug fell progressively below that in control solution at the same rate. No major differences in rate dependent behaviour at steady state were observed between the subclasses Ia, Ib, and Ic. Differences were apparent, however, in the rate at which conduction velocity fell after a sudden decrease in cycle length. This was studied using two protocols. In the first of these, the conduction velocity was recorded of each action potential of a 20 beat train induced after a long rest period. In the presence of class Ib drugs (lignocaine, tocainide, and mexiletine) there was a rapid decline within 2-3 beats to a new equilibrium level of conduction velocity. Class Ia drugs (quinidine, disopyramide, and procainamide) required 12-16 beats to achieve equilibrium, and class Ic agents (flecainide, encainide, and lorcainide) produced slow falls in conduction velocity that did not reach equilibrium within the 20 beat trains. The second protocol involved interpolation of increasingly premature extrastimuli. Class Ib drugs progressively slowed conduction of premature beats as the diastolic interval was reduced below 300-400 ms.(ABSTRACT TRUNCATED AT 250 WORDS)

Action Potentials↗

Cardiodepressive effects of antiarrhythmic drugs.

Negative inotropic effects of antiarrhythmic drugs are ultimately mediated by alterations of intracellular Ca++. With class I antiarrhythmic drugs a strong correlation between the Na+ inward current and the Ca++ influx exists whereby Ca++ influx is changed by an exponent, n, of approximately 3. Generally, the longer the duration of Na+ -channel blockade the more pronounced is negative inotropy. Antiarrhythmic drugs of class I may be subdivided into those with a short recovery time of Na+ channels (lidocaine-type), those with an intermediate recovery time, such as quinidine and newer antiarrhythmics such as flecainide and propafenone, and those with a recovery time greatly exceeding 1 s, such as disopyramide and prajmaline. The degree of cardiodepression is modulated by peripheral circulatory effects such as vasoconstriction and vasodilation. In order to differentiate between general cardiodepressive effects and true negative inotropy, sophisticated methods, for example, volume-pressure relationship curves, have to be applied to determine the degree of pre- and afterload alterations, also accounting for cardiodepressive effects. The net effect of cardiodepression is due to several factors: true negative inotropy, additional influences on the peripheral circulation, the functional state of the myocardium, and the beneficial or detrimental effects on the prevailing arrhythmia. Based on these theoretical considerations, combined drug therapy of arrhythmias has to be installed under the aspect of cardiodepressive side-effects, especially in an already impaired heart.

Anti-Arrhythmia Agents↗

Beat-to-beat variability of ventricular late potentials in the unaveraged high resolution electrocardiogram--effects of antiarrhythmic drugs.

The aim of this study was to assess variability of ventricular late potentials (VLP) in patients with and without inducible ventricular tachycardia (VT), and the effects of antiarrhythmic drugs on VLP variability in the high-resolution electrocardiogram (HRECG). In 27 patients 90 s of unaveraged HRECGs were analysed before and 2 h after oral administration of 200 mg disopyramide, 400 mg mexiletine, 300 mg propafenone and 160 mg DL-sotalol. The duration of the QRS (QRSD) and the duration of the terminal low amplitude signal (LASD) was measured from each beat. Beat-to-beat variability was defined as standard deviation of the differences between consecutive beats. Patients with inducible sustained VT (n = 9) showed higher LASD variability than patients without inducible VT (12.3 vs 9.3 ms.beat-1, P < 0.01). Patients with VLP (n = 17), as defined by the signal averaged ECG, also had higher QRSD and LASD variability (11.8 vs 9.5 ms.beat-1, P < 0.05; 11.5 vs 8.2 ms.beat-1, P < 0.01, respectively) compared to those without VLP. All class I drugs lengthened QRSD and LASD in terms of the absolute values, but only propafenone increased QRSD and LASD variability (9.7 to 12.0 ms.beat-1, P < 0.01; 8.9 to 11.9 ms.beat-1, P < 0.01, respectively). In patients with inducible VT, sotalol decrease LASD variability from 14.3 to 9.3 ms.beat-1 (P < 0.05). We conclude that beat-to-beat VLP variability is increased in patients at a high risk of malignant arrhythmias.(ABSTRACT TRUNCATED AT 250 WORDS)

Action Potentials↗

Antiarrhythmic drugs and torsade de pointes.

In the past decade there has been much progress in understanding the clinical features and associations of drug-induced long QT syndromes, their inter-relationships with other long QT syndromes, and electrophysiological mechanisms that may be involved in the development of torsade de pointes, the major proarrhythmic correlate of prolonged repolarization. The most likely electrophysiologic basis for torsade de pointes is the development of after-depolarizations facilitated by hypokalemia, bradycardia and lengthened QT intervals. Torsade de pointes can be produced by all antiarrhythmic agents that lengthen repolarization, although the precise incidence varies with different agents and is not quantitatively related to the degree of QT prolongation. Quinidine, disopyramide and procainamide (with its metabolite N-acetyl procainamide) are strongly concordant in the production of torsade de pointes. Such concordance suggests that there is an individual predisposition to the induction of early after-depolarizations (EAD) with exposure to agents that prolong repolarization. However, concordance with agents or other classes, such as sotalol, is less certain, and amiodarone appears to be discordant. The discordance between potency in prolonging the QT interval and the proclivity to induce torsade de pointes may hold the key to separating the salutary therapeutic antiarrhythmic effects from adverse proarrhythmic effects of class III agents. There is an optimistic perception that the development of new agents that potently prolong repolarization will give a modern realization of the old concept that prolongation of refractoriness is a uniquely powerful anti-re-entrant, antitachyarrhythmic action.

Action Potentials↗

Using the right drug: a treatment algorithm for regular supraventricular tachycardias.

Despite the recent advent of and the successful results from catheter ablation, pharmacological therapy is still used by most clinicians as the first line therapy in patients with regular supraventricular tachycardias. Before prescribing an antiarrhythmic agent, documentation of the arrhythmia using a 12-lead electrocardiogram (ECG) is necessary to identify the type of tachycardia. The ECG diagnosis is based on the presence and polarity of the P wave, the P to QRS relationship, the presence of QRS alternation and the effect of bundle branch block on tachycardia rate. Most regular supraventricular tachycardias use the atrioventricular node either passively, as in atrial tachycardias or flutter, or actively, as paroxysmal junctional tachycardias. The Sicilian Gambit approach attempted to introduce some rationale in the choice of an antiarrhythmic agent, taking into account tachycardia mechanism, by defining the critical components of the tachycardia and the vulnerable parameter, i.e. the component that may readily be affected by an appropriate antiarrhythmic agent. For this approach, an electrophysiological study is particularly useful. The most common regular paroxysmal supraventricular tachycardias include atrioventricular nodal re-entrant tachycardias and atrioventricular re-entrant tachycardias which use an overt or concealed accessory atrioventricular connection (Kent bundle) or atriofascicular connection (Mahaim). For acute termination of paroxysmal junctional tachycardia, intravenous adenosine is the drug of choice. For the prevention of the tachycardia attacks in atrioventricular nodal re-entrant tachycardia, the agents with a depressive effect on the antegrade slow pathway, such as calcium channel blockers or beta-blockers, are likely to be effective. If they fail, sodium channel blockers (propafenone or flecainide) may be indicated. In tachycardias involving accessory connections, agents that affect fast channel dependent tissue (propafenone, flecainide, cibenzoline, disopyramide or hydroquinidine) are effective. Potassium current blockers, such as sotalol or amiodarone, represent an alternative therapy. In atrial tachycardias, the use of propafenone, flecainide or sotalol constitute a logical choice. In drug-resistant cases, amiodarone is the most potent agent. Radiofrequency ablation of the slow atrioventricular nodal pathway, of an accessory connection or of an atrial focus, is indicated in drug-resistant or drug-intolerant patients and is increasingly offered as an alternative therapy.

Algorithms↗

Delayed ventricular repolarization as an anti-arrhythmic principle.

Depolarization of cardiac muscle is achieved by 'fast inward current' through channels which are inactivated within about 1 ms. When the cells are repolarized the process of inactivation of fast channels is rapidly reversed. The class 1 anti-arrhythmic drugs delay the disappearance of inactivation until long after repolarization is complete. In theory, it should be possible to produce a similar extension of refractory period by delaying the repolarization itself. Quinidine and disopyramide caused minor delays of repolarization, but both were primarily class 1 agents, and in addition had undesirable anticholinergic activity. Amiodarone, already in use for many years as an antianginal drug, prolonged action potential duration (APD) and was shown to have an anti-arrhythmic action in rabbits, dogs and man. Although prolongation of APD lengthens QT, a long QT may be caused by phenomena other than prolonged APD, such as heterogeneity of sympathetic drive. Association of long QT with arrhythmia does not, therefore, invalidate the principle that homogeneously prolonged APD should be anti-arrhythmic. In practice, amiodarone, bretylium, sotalol, thyroidectomy, and long-term beta-blockade prolong APD, and are associated with low incidence of arrhythmia. Many mechanisms controlling cardiac repolarization have been proposed, but how repolarization is delayed by individual agents is not fully elucidated.

Adrenergic beta-Antagonists↗

Pharmacokinetics of roxithromycin in renal and hepatic failure and drug interactions.

In patients with renal insufficiency roxithromycin pharmacokinetic parameters are significantly altered. In particular, the Cmax, the AUC and the T1/2 are increased and the Clr is reduced. In alcoholic cirrhotic patients the blood half-life is dosage higher than in normals. In spite of this, in these types of patients the usual roxithromycin dosage should not be modified. Potential pharmacokinetic drug interactions that involve roxithromycin are very few and concern only disopyramide and theophylline. Theophylline concentrations should be monitored if the pretreatment blood level is greater than 15 mg/l.

Aged↗

Prolonged cardiac arrest and complete AV block during upright tilt test in young patients with syncope of unknown origin--prognostic and therapeutic implications.

The purpose of this study was to define the history and prognosis of 12 patients (8 males, 4 females) with syncope of unknown origin (5 to 15 episodes), who developed prolonged asystole or complete AV block during the upright tilt test (UTT). The mean age (+/- SD) of the patients was 29 +/- 7.4 years, and all had normal neurological and cardiological findings on evaluation. These patients were selected from a larger group of 92 cases with positive UTT out of a total of 136 subjects who were referred for recurrence of syncope. Neither clinical nor autonomic nervous system evaluation distinguished these 12 patients from those with positive UTT. Following UTT, therapy was initiated and consisted of transdermal scopolamine in four, disopyramide in two, and beta-blockers in four patients. During follow-up (mean, 17 +/- 5.4 months), four patients had recurrences but none experienced episodes of life-threatening syncope. These patients do not show an enhanced risk of sudden death, and drug therapy seems to improve their clinical course. Only long-term follow-up would correctly identify a subgroup at higher risk.

Adult↗

A specific effect of lidocaine and tocainide on ventricular conduction of mid-range extrasystoles.

Lidocaine and tocainide had no effect on ventricular conduction of extrasystoles with coupling intervals longer than 500 msec in isolated blood-perfused dog hearts, but caused interval-related increases in conduction time of extrasystoles in the range of 250--400 msec, here called mid-range extrasystoles (MRE). Quinidine, procainamide, disopyramide, and methyl lidocaine increased conduction times of extrasystoles at all coupling intervals, and no additional slowing of MRE was observed. The slowing of MRE specific to lidocaine and tocainide was confirmed in the intact dog heart. During acute myocardial ischemia in the intact dog heart, conduction was slowed and additional slowing of MRE was found. Lidocaine and tocainide caused further slowing of conduction of MRE. This unique effect of lidocaine and tocainide on the conduction of MRE may be important in the suppression of reentrant arrhythmias. However, lidocaine and tocainide were also found to be arrhythmogenic when extrasystoles were introduced, after acute coronary occlusion, in those animals in which such occlusion alone did not allow demonstration of arrhythmias due to extrasystoles.

Anilides↗

Effect of antiarrhythmic drugs on the cycle length-dependent action potential duration in dog Purkinje and ventricular muscle fibers.

We examined the steady-state action potential duration (APD) within a wide range of cycle lengths (CL) in cardiac dog Purkinje (P) and ventricular (V) muscle fibers in the presence of: lidocaine (L) 4 and 8 micrograms/ml, mexiletine (M) 4 and 8 micrograms/ml, flecainide (F) 1 and 4 micrograms/ml, disopyramide (D) 3.1 and 10 micrograms/ml, quinidine (Q) 2.5, 5, and 10 micrograms/ml, bretylium tosylate (B) 5 and 10 micrograms/ml, and sotalol (S) 5 micrograms/ml. In the P fibers, all drugs except for B and S shortened plateau duration, increased slope of phase 2 and decreased slope of phase 3 repolarization, and either shortened (L, M, Q, F) or prolonged (D) APD. B and S lengthened APD and did not change significantly the slopes of phase 2 and 3 of repolarization. Each drug altered the relation between APD and Cl according to one of the following three patterns: (a) L, M, Q, and F shortened APD more at long than at short CL; (b) D lengthened APD more at short than at long CL; (c) B and S lengthened APD more at long that at short CL. In the V fibers, APD was lengthened by F, Q, and B, and shortened by L and M. The drug-induced changes in the relation between APD and CL were as in the P fibers. The results suggest that the drug-induced changes in the relation between APD and CL can be predicted from the drug effects on the course of repolarization.

Action Potentials↗

Effects of diet-induced hypokalaemia on the efficacy of antiarrhythmic drugs against ventricular arrhythmias evoked by coronary artery ligation in the anaesthetised rat.

The antiarrhythmic efficacies of intravenous quinidine (Q), disopyramide (D), prenylamine (P), bepridil (B), and practolol were compared in normokalaemic and dietary-induced hypokalaemic anaesthetised rats. Hypokalaemia markedly increased the severity of arrhythmias induced by coronary artery ligation and reduced the antiarrhythmic efficacy of all five drugs tested. After anaesthesia, hypokalaemia was associated with hypotension and bradycardia but not QTc prolongation. However, bradycardia was not seen in conscious hypokalaemic animals. Papillary muscles taken from hypokalaemic rats displayed a longer action potential duration but no increase in Vmax compared with tissue taken from normokalaemic animals. It is concluded that hypokalaemia in the rat causes electrophysiological disturbances which may contribute both to the observed exacerbation of ischaemia-induced arrhythmias and to the reduced efficacy of Q, D, P, and B. The reduced efficacy of practolol might be explained by other consequences of hypokalaemia.

Anesthesia↗

Cellular electrophysiology of the new antiarrhythmic agent recainam (Wy-42,362) in canine cardiac Purkinje fibers.

Recainam, [N-2,6-dimethylphenyl-N'-3-(1-methylethyl-amino)propylurea] hydrochloride (Wy-42,362), is a new class I antiarrhythmic agent that has been shown to be very effective in suppressing premature ventricular contractions in humans. To clarify the mechanism of antiarrhythmic action, the electrophysiologic effects of recainam were examined in canine cardiac Purkinje fibers using standard microelectrode techniques. Recainam at 3-100 microM (1-30 micrograms/ml) produced concentration-dependent decreases in action potential duration (APD), membrane responsiveness, and maximal upstroke velocity (Vmax). The reduction in Vmax was strongly modulated by the frequency of stimulation--i.e., Vmax block was use dependent. The rate of development of use-dependent block produced by recainam was much slower than typically seen with lidocaine, but comparable with that of the class Ia agents disopyramide and procainamide. However, unlike agents of the Ia subclass, recainam did not prolong APD at any concentration or cycle length tested. In summary, recainam appears to possess a novel cardiac cellular electrophysiologic profile, in that it shares characteristics with all three current class I antiarrhythmic subclasses.

Action Potentials↗

Antiarrhythmic and antifibrillatory properties of McN-4130 in several animal models.

McN-4130 is an experimental compound having antiarrhythmic and antifibrillatory activity in several animal models. In anesthetized, open-chest pigs subjected to total occlusion and subsequent reperfusion of the left anterior descending coronary artery, McN-4130 dose-dependently (2.5-10.0 mg/kg i.v.) protected against fibrillation and death. Mean arterial pressure was not significantly affected, but heart rate was dose-dependently reduced. In anesthetized normal dogs, McN-4130 increased ventricular fibrillation threshold for up to 45 min. This increase in fibrillation threshold was associated with concurrent increases in ventricular conduction time and ventricular effective refractory period. In conscious dogs subjected to occlusion of the left anterior descending coronary artery 24 h previously, McN-4130, 2.5 and 5.0 mg/kg i.v., significantly reduced the rate of ventricular arrhythmias for up to 45 min. McN-4130 was more effective and had a longer duration of action than comparable doses of lidocaine and disopyramide. McN-4130 was orally effective in this model at 10 mg/kg. These results indicate that McN-4130, a structurally unique experimental antiarrhythmic compound, may be useful as a ventricular antiarrhythmic agent with antifibrillatory properties.

Anesthesia↗