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Aims To assess the efficacy and safety of adjunctive antiarrhythmic drug therapy for preventing implantable cardioverter defibrillator (ICD) therapies. [ABSTRACT FROM PUBLISHER]

Aims In patients with persistent atrial fibrillation (AF), the efficacy and safety of two anti-arrhythmic drugs in preventing the recurrence of AF after successful direct current (DC) cardioversion was prospectively assessed in a multi-centre double-blind, placebo-controlled, randomised trial using daily trans-telephonic monitoring.Methods and results 1182 patients with persistent AF were prospectively enrolled, 848 patients were successfully cardioverted and then randomised to either sotalol (383 patients), quinidine plus verapamil (377 patients) or placebo (88 patients). The primary outcome parameter was AF recurrence or death. All patients received an event recorder (Tele-ECG) and had to record and transmit via telephone at least one ECG per day during follow-up.The mean follow-up period was 266 days. A total of 191,103 Tele-ECGs were recorded and transmitted. The primary outcome parameter (AF recurrence of any kind or death) was observed in 572 patients (67%) in whom at least one episode of AF recurrence was documented during follow-up, in 348 patients (41%) AF recurrence was persistent. The recurrence rates after one year for any AF were 83% for placebo, 67% for sotalol and 65% for quinidine plus verapamil, the latter being statistically superior to placebo but not different from sotalol. The recurrence rates for the secondary outcome parameter persistent AF were 77%, 49% and 38%, respectively. Quinidine plus verapamil was significantly superior to placebo and to sotalol. About 95% of all AF recurrences were initially detected in the daily Tele-ECG, about 70% of all AF recurrences occurred completely asymptomatic. Adverse events on sotalol and quinidine plus verapamil were comparable with the exception that all torsade de pointes tachycardias occurred on sotalol.Conclusion Anti-arrhythmic treatment after DC cardioversion of persistent AF significantly decreases the recurrence rates of persistent AF compared to placebo with superiority of quinidine plus verapamil compared to sotalol. Symptoms were not reliable as clinical surrogates to detect episodes of AF. [ABSTRACT FROM PUBLISHER]

Aims Arrhythmogenic right ventricular dysplasia is a rarely diagnosed cardiomyopathy, but a frequent cause of ventricular arrhythmia and sudden cardiac death. QT interval dispersion, measured as an interlead variability of QT, is a marker of dispersion of ventricular repolarization and, hence, of electrical instability. The present study was conducted to assess the occurrence of QT dispersion and its modulation during treatment with sotalol.Methods Twenty-five patients with the diagnosis of arrhythmogenic right ventricular dysplasia were studied retrospectively. Fourteen patients were considered low risk for malignant ventricular arrhythmia and sudden cardiac death, and 11 high risk due to documented sustained ventricular arrhythmia, cardiac arrest, or sudden cardiac death. Twenty five healthy volunteers served as control subjects.Results Dispersion of repolarization was significantly higher in patients than in control subjects (QTd and JTd:P<0·05). Dispersion of repolarization was equal in patients both with and without malignant arrhythmias. There was no significant change in dispersion after treatment with sotalol. Adjacent QT dispersion between leads V3–V4, V4–V5and V5–V6, respectively, was higher in patients than in control subjects (P<0·05), while no differences were seen in leads V1–V2and V2–V3.Conclusion QT interval dispersion is increased in patients with arrhythmogenic right ventricular dysplasia. However, the degree of dispersion is not related to the severity of symptoms, nor is it influenced by treatment with sotalol. [ABSTRACT FROM PUBLISHER]

Aim To compare the efficacy of sotalol versus amiodarone for long-term treatment of ventricular tachyarrhythmias. Methods Patients (n=75) with spontaneous, sustained ventricular tachyarrhythmias secondary to remote myo-cardial infarction were studied. After intravenous electrophysiological testing, both sotalol and amiodarone were predicted to be ineffective in 50 (67%) patients. Five patients were excluded. Forty-five patients were randomized to receive sotalol (n=22) or amiodarone (n=23) for maintenance therapy. The primary outcome variable was the time to first recurrence of sustained ventricular tachyarrhythmia. Results At 36 months, 75% of those allocated sotalol remained free of ventricular tachyarrhythmia compared with 38% of those allocated amiodarone (P=0·05). On multivariate analysis the risk of recurrence of ventricular tachyarrhythmia for patients on amiodarone was 5·9 times higher (P=0·008) than that for patients on sotalol. Conclusion Sotalol is superior to amiodarone for long-term treatment of ventricular tachyarrhythmia secondary to coronary artery disease when both drugs have been predicted to be ineffective at intravenous electrophysiological testing. Randomized trials in larger numbers of patients with ventricular tachyarrhythmia need to be performed comparing the two agents directly. [ABSTRACT FROM PUBLISHER]

Control of recurrent symptomatic atrial fibrillation should be directed at: (1) alleviation of symptoms associated with atrial fibrillation and (2) reduction of the risk of embolization. Approximately 50–60% of patients treated with conventional agents such as quinidine will develop recurrent atrial fibrillation in the first year of treatment. Because of this relapse rate and the side effects associated with quinidine and other type la antiarrhythmic agents, it is important to investigate the efficacy and safety of newer antiarrhythmic agents such as propafenone and sotalol. In our institution, 100 patients with recurrent symptomatic atrial fibrillation who had failed therapy with at least one type Ia agent were randomized to propafenone or sotalol. Propafenone and sotalol were equally effective in preventing recurrent atrial fibrillation at 6 and 12 months after onset of therapy independent of arrhythmia pattern or left atrial size. Both agents were well tolerated with only 10% of patients discontinuing therapy due to side effects.We combined data from this randomized study with a stepped care trial of propafenone and sotalol to examine risk factors for the development of recurrent atrial fibrillation. In patients treated with propafenone or sotalol, there was no significant difference in response to therapy based on age, gender, or aetiology of heart disease. Patients with dual-chamber pacing had improved maintenance of sinus rhythm as compared to those individuals without pacemakers. Left atrial size did not significantly influence the likelihood of maintaining sinus rhythm in these trials.Pharmacological management of the patient with recurrent symptomatic atrial fibrillation remains a difficult problem. Patient symptom severity and the clinical profile should be examined prior to instituting antiarrhythmic therapy in any given patient. These studies indicate that propafenone and sotalol are equally effective when used to maintain sinus rhythm in our population. As more data on the merits and risks of antiarrhythmic therapy for the treatment of atrial fibrillation become available, the role of propafenone and sotalol in the treatment of this disorder will be better understood. [ABSTRACT FROM PUBLISHER]

In 90 consecutive patients with coronary artery disease and sustained monomorphic ventricular tachycardia, who were treated with oral sotalol and underwent programmed stimulation to determine drug effectiveness, the influence of sotalol on induced ventricular tachycardia morphology was retrospectively examined. In 54 patients (60%) sotalol rendered the tachycardia non-inducible. However, contrary to drug-testing with class I antiarrhythmic agents, induction of multiple morphologies at baseline study did not predict failure of subsequent drug-testing with sotalol. In the remaining 36 patients (40%), in whom sotalol did not modify inducibility, 21 patients (i.e. a total of 23%) manifested at least one new morphology during electropharmacological testing on sotalol. This effect was independent of the degree of left ventricular dysfunction, infarct location and numbers of morphologies at baseline, but corresponded with drug-induced changes in refractoriness. This observation may be related to a proarrhythmic effect of sotalol. Slowing of ventricular tachycardia rate and changes in morphology may have implications in patients receiving implantable cardioverter-defibrillators or those undergoing ablative procedures. [ABSTRACT FROM PUBLISHER]

Atrial fibrillation may be paroxysmal or chronic. The paroxysmal form presents in the form of attacks of short duration but may last for up to 3–4 days. Episodes of atrial fibrillation of longer duration are considered as chronic. The diagnosis is made by ECG. [ABSTRACT FROM PUBLISHER]

Several new antiarrhythmic compounds with pure class III activity are currently under development and seem to possess considerable antiarrhythmic potential. The primary electrophysiological action of class III agents is selective prolongation of repolarization without conduction slowing. This effect is usually mediated by block of one or more potassium currents which results in prolongation of the action-potential duration and refractoriness in both atrial and ventricular myocardium. The magnitude of increases in effective refractory period decreases as the heart rate is increased, i.e. these drugs display ‘reverse use-dependence’.Initial animal and clinical studies have shown that class III agents are effective against re-entrant supraventricular and ventricular arrhythmias without having any important negative inotropic effect in the compromized ventricle. Animal studies have also suggested thai these drugs may be useful in suppressing postinfarction arrhythmias and preventing arrhythmic sudden death. However, concerns have been raised by reports of substantial proarrhythmic tendency associated with these drugs, mainly in the form oftorsade depointes. Careful clinical evaluation is required to establish the clinical benefits of these potentially promising new compounds. [ABSTRACT FROM PUBLISHER]

It is only in the last few years that the broad-spectrum antiarrhythmic properties of sotalol have become increasingly recognized. Racemic sotalol has potent beta-blocking and class III antiarrhythmic properties, and it has been reported that this drug is able to control supraventricular and ventricular arrhythmias. Recently, several studies performed with the d-sotalol isomer, which is almost devoid of the beta-blocking effects compared to the racemate, suggest significant antiarrhythmic efficacy and good tolerance of the dextro-isomer. In this paper we review and discuss the effects of sotalol and d-sotalol in patients with ventricular tachycardia (VT), ventricular fibrillation (VF) or cardiac arrest in whom VTor VF was induced by programmed electrical stimulation (PES) [ABSTRACT FROM PUBLISHER]

Antiarrhythmic agents with class I action have been available for decades, and those with class III mode of action for mon than 10 years. However, no randomized, controlled, direct comparison between agents with class I and class III mode of action was performed until recently. In patients with successful DC conversion of chronic atrial fibrillation, sotalol proved to be as effective as quinidine in maintaining sinus rhythm but was better tolerated and provided beneficial rate control during atrial fibrillation in those patients who relapsed. In other clinical settings, such as the pharmacological conversion os acute or paroxysmal atrial fibrillation and the termination of and/or prophylaxis against atrial fibrillation after coronary artery bypass surgery, less reliable data is available. Both commonly-available agents with a class III mode of action, amiodarone and sotalol, also have other significant antiarrhythmic properties; for sotalol, the combination of class III activity ana beta blockade may prove to be favourable. Therefore, the available data is not necessarily representative of a pure class III mode of action. Ongoing studies with d-sotalol in patients with atrial fibrillation will provide the first important information on the clinical usefulness of a class III mode of action without subsidiary effects. Whether d-sotalol or other new class III agents will, in the future, be compared to class I agents still remains an open question. [ABSTRACT FROM PUBLISHER]

d.l-Sotalol is a racemic drug composed of equimolar amounts of d-(+)-sotalol and l-(−)-sotalol. The l-(−)-enantiomer has both beta-blocking (class II) activity and potassium-channel-blocking (class III) properties. The d-(+)-enantiomer has class III properties similar to those of l-sotalol. However, the affinity of d-sotalol for beta-adrenergic receptors is 30 to 60 times lower than the affinity of l-sotalol.The pharmacokinetics of d,l-sotalol are linear. Following oral administration, absorption and bioavailability are almost complete; apparent elimination half-life ranges from 7 to 18 hours. More than 80% of racemic sotalol elimination occurs by renal excretion of unchanged drug. Sotalol is not metabolized, nor is it significantly bound to plasma proteins. Thus, steadystate plasma concentration is reached within 3 days of treatment onset in patients without renal insufficiency. Dosage of sotalol should be adjusted to creatinine clearance. The pharmacokinetic profile of d-sotalol is similar to that of the racemate.Plasma concentrations of racemic sotalol associated with beta-adrenergic blockade are similar to those associated with its class III actions. QT interval prolongation with d,l-sotalol is dose- and concentration-dependent and decreases at rapid heart rates. Also, QT interval prolongation at a given plasma concentration during repeated dosing tends to be less pronounced than QT prolongation at the same plasma concentration during single dosing. The class III actions of d-sotalol in the sinus node are associated with slowing of sinus heart rate, whereas additional beta blockade contributes to the decrease in heart rate observed with I- or d,I sotalol. Preliminary studies indicate that racemic sotalol reduces dispersion of repolarization following myocardial infarction. Finally, d-sotalol exerts positive inotropic actions that may disappear in ischemic tissues, whereas d,l-sotalol has a potential to decrease contractility due to its additional beta-blocking properties. [ABSTRACT FROM PUBLISHER]

Although discovered more than two decades ago, the clinical applications of sotalol are still a matter of debate. Together with amiodarone, sotalol is considered a prototype of a new class of antiarrhythmic agents characterized by repolarization-prolonging effects (class III). Lengthening of repolarization is associated with an increase in the effective refractory period of cardiac tissues. There is no change in the maximum rate of rise during phase 0, a finding that supports the lack of sotalol effect on the fast sodium channel. The electrophysiologic action of the drug in humans provides evidence for direct cardiac effects of sotalol in addition to beta blockade. The beta-blocking properties play a major role in the sinus-rate slowing and lengthening of the atrioventricular nodal conduction time observed after sotalol administration. However, the drug also prolongs refractoriness in atria, His-Purkinje tissue, ventricular muscle and accessory atrioventricular connections. These latter changes are absent or minimal with conventional beta blockers and are likely to reflect sotalol-induced prolongation of cardiac repolarization. They result in an increase in the QT interval, an effect that is dose-dependent and more marked during chronic therapy.The dextrorotatory isomer, d-sotalol, shares a similar electrophysiologic profile. Lengthening of repolarization in cardiac cells following d-sotalol is of the same magnitude as that produced by the levoisomer. This finding provides further evidence for a class III action of sotalol, as the dextroisomer is almost devoid of beta-blocking properties. In humans, the electrical effects of both drugs are similar. However, d-sotalol-induced changes in sinus rate and atrioventricular nodal conduction are modest. Given that the repolarization-prolonging effects of sotalol are more prominent at slow rates (reverse use-dependency), one can speculate that d-sotalol may cause less proarrhythmi [ABSTRACT FROM PUBLISHER]

Tachyarrhythmias which originate above the bifurcation of the bundle of His or incorporate tissue proximal to it are classified as supraventricular tachyarrhythmias (SVT). Primary treatment of SVT attempts to influence the underlying disease. Therapy is subdivided into drug therapy, electrotherapeutic tools (e.g. antitachycardia pacemakers, catheter ablation) and antiarrhythmic surgery. Antiarrhythmic agents which slow conduction and suppress premature beats are efficient for emergency and long-term treatment of supraventricular tachycardias. We evaluated some of the most relevant antiarrhythmic drugs for SVT including propafenone, diprafenone, cibenzoline, lorcainide and sotalol; in addition, usage and efficacy of quinidine/verapamil, disopyramide, amiodarone, ajmaline, adenosine and flecainide are summarized.The principles for acute management of tachycardia episodes with narrow and broad complexes are outlined. The reason for the selection as well as the efficacy in the termination of the tachycardias is described for different antiarrhythmic agents including verapamil, adenosine, ajmaline, propafenone and flecainide. [ABSTRACT FROM PUBLISHER]

Increased dispersion of ventricular recovery time is believed to be a substrate for serious ventricular arrhythmias. Class III antiarrhythmic drugs probably operate by decreasing dispersion through homogeneous prolongation of recovery time. A single surface QT value gives no information on recovery time dispersion but interlead variation in QT may be relevant. QTc dispersion was measured in 67 patients post myocardial infarction randomized to treatment with either sotalol or placebo. QTc dispersion was calculated as the difference between the maximum and minimum QTc in any surface electrocardiogram lead. Both maximum QTc and QTc dispersion varied considerably following infarction but throughout the 6-month follow-up period maximum QTc was significantly greater (P<0.05) and QTc dispersion significantly less (P < 0.05) in patients on sotalol compared with placebo. These findings are in accord with expected changes in ventricular recovery time and provide strong support for the hypothesis that surface electrocardiogram QT variation reflects regional differences in ventricular recovery time [ABSTRACT FROM PUBLISHER]

Controlled studies of the electrophysiological effects of beta-blockade in acute myocardial infarction have not previously been published. In this controlled, double-blind study 20 patients were randomized to treatment with placebo or sotalol administered as a continuous infusion for 12 h. Programmed electrical stimulation was performed from the right atrium. After 60 min of infusion in the sotalol-treated patients (n=10) there was a significant prolongation of sinus cycle length (+15%) and sinus node recovery time (+28%). The AV nodal effective refractory period was prolonged by 15% after 45 min of infusion. Variables reflecting myocardial repolarization, atrial effective refractory period and Q T interval, were increased by 20% and 10%, respectively. In the placebo group, except at 12 h, there was a general pattern of slightly diminishing values for all measured variables. The electrophysiological changes in the sotalol-treated group could be explained by the combined Class II and III activities of this drug. The infusion of sotalol was well tolerated, and the anticipated electrophysiological and Class II and III antiarrhythmic effects were observed, despite the acute myocardial infarction. [ABSTRACT FROM PUBLISHER]

The effects of amiodarone and sotalol were studied with programmed electrical stimulation of the heart in 19 patients with inducible tachycardia (AV nodal tachycardia: 10 cases, circus movement tachycardia: 9 cases). Amiodarone was administered intravenously at a dose of 300 mg over 2min and sotalol at a dose of 1.5 mg kg over 10min. Both i.v. amiodarone and sotalol lengthened the transnodal conduction time, the effective refractory period of the AV node and the AV nodal Wenckebach cycle length. Only sotalol significantly lengthened the effective refractory periods of the right atrium and the right ventricle. Infused intravenously during tachycardia, amiodarone interrupted arrhythmia in five of six patients and sotalol in seven often cases. Tachycardia was stopped by blockade of the impulse into the AV node in three amiodarone patients and in five sotalol patients. In the remaining four cases, the weak link of the circuit was the accessory pathway. Thus i.v. sotalol exhibits electrophysiologic effects consistent with both class II and III activity, whereas the effects of i.v. amiodarone are the result of different activities throughout all areas of the cardiac tissue. [ABSTRACT FROM PUBLISHER]

Sotalol was compared with amiodarone in this open randomized multicentre study of patients with ventricular tachycardia or fibrillation not associated with acute myocardial infarction refractory to or intolerant of Class I drugs. 16 of 30 patients treated with amiodarone completed 12 months on therapy, five were withdrawn because of recurrent ventricular tachycardia and nine because of presumed adverse drug reactions, compliance problems or protocol violation. Four of those who were withdrawn died within 12 months. Sixteen of 29 patients completed 12 months on sotalol, one was withdrawn because of ventricular tachycardia and nine because of presumed adverse drug reactions, poor compliance or the need for coronary artery surgery. Three died on treatment and two after withdrawal but within 12 months of entering the study. When the results are analysed by intention to treat there was no significant difference in antiarrhythmic efficacy or in the incidence of side-effects severe enough to warrant withdrawal from the trial. There was an increase in left ventricular ejection fraction in those treated with sotalol, which, because of its pharmacokine-tics, is an attractive alternative to amiodarone for patients with malignant ventricular arrhythmias who can tolerate β-adrenergic blockade. [ABSTRACT FROM PUBLISHER]

The effects of oral sotalol were compared with the findings obtained in the baseline study of a group of 26 consecutive patients with sustained monomorphic ventricular tachycardia or ventricular fibrillation and inducible ven tricular tachycardia. The mean age was 62 years and the mean ejectionfraction 33%. The number of non-inducible patients after sotalol administration (mean dose of 251 ± 81 mg day) was 13 out of 21 (62%). The cycle length of the induced tachycardia changed from 293 ± 32 to 303 ± 41 ms (non-significant (NS)). The coupling interval ofthe first extrastimulus did not lengthen for the subgroup with persistent inducibility. The number of patients requiring defibrillation during the induction study did not decrease on (2/8) or off drugs (6/22). After the first administration of oral sotalol, two patients developed polymorphic ventricular tachycardia or torsade depointes and one suffered from left ventricular failure. Long-term treatment with sotalol was given to 15 non-inducible patients, and two inducible patients, combined with an AICD or a pacemaker. Over a mean follow-up period of 13 months, three recurrences were observed in these 17patients, including the patient with the AICD. This represents an efficacy of 82% for patients chronically treated with a low dose of oral sotalol. [ABSTRACT FROM PUBLISHER]

Sotalol is a non-selective beta-adrenergic blocking agent with class III antiarrhythmic properties. Our study was intended to assess the efficacy of sotalol on exercise-inducible arrhythmias by oral administration to out patients. Thirty patients with exercise-inducible arrhythmias (80% coronary artery disease, 20% congestive cardiomyopathy) were studied after two baseline bicycle ergometric stress tests performed in upright position. Twenty-five patients (including nine crossover cases of the lower dose protocol) were given sotalol in a daily dose of 320mg (group 1) and 14patients in a dose of 160mg (group 2). After 2 and 8 weeks, respectively, group 1 showed a mean reduction of the total number of inducible ventricular premature beats ( VPBs) of 50% (P = 00042) and 61% (P = 0.0107), respectively and a significantly improved Lown score (P = 00002 and 0.0006, respectively). A significant antiarrhythmic response was not demonstrable for group-2 patients. Because of inefficacy, nine patients were changed from group 2 to group 1. Reduction of arrhythmias on the higher dose was significant (P= 0.0147) in this group. There was the same significant reduction of the heart rate pressure product with the low and high dosage indicating that the beta-blocker effect is achieved with the lower dosage. We conclude that sotalol is a powerful drug for reducing the number and complexity of ventricular arrhythmias in a dose of 320 mg daily. As the beta-blocking effect in both groups was the same, we assume that the reduction of arrhythmias is mainly due to class III action. [ABSTRACT FROM PUBLISHER]

A young women had been on antiarrhythmic treatment with sotalol 80–160 mg daily for three years because of ventricular tachycardia. After a quarrel she ingested an overdose ofsotalol, estimated to be 13–14 g, and was immediately brought to hospital, where the first ECG was taken 25 minutes after the ingestion. The clinical course, including the relationship over time between pronounced bradycardia, QT prolongation and malignant ventricular tachyarrhythmias is described. Serum concentrations were obtained regularly between 11 and 54 hours after the ingestion. After initially very high levels, the concentrations decreased in a strictly exponential manner to arrive at therapeutic concentrations 39 hours after the ingestion. Calculations revealed that over 12 g of sotalol was absorbed into the circulation. while the half life was 9.2 h and the oral clearance 294 mg min. The heart rate normalized about 24 hours after the repolarization variables, which supports the opinion that the class III action of sotalol is unrelated to the beta-blockade. In sotalol intoxication, malignant tachy arrhythmias appearing during excessive prolongation of the QT interval, most often in combination with hypokalemia, ethanol intoxication or concomitant antiarrhythmic treatment, may need emergency defibrillation but seem to disappear within in a few hours. Thus, while massive sotalol intoxication may be fatal, early treatment promotes a successful outcome even when very high doses have been ingested. [ABSTRACT FROM PUBLISHER]

The comparative aniiarrhythmic efficacy of three different intravenous drug regimens was evaluated in 12 symptomatic patients (mean age: 72 years) with chronic high frequency ventricular arrhythmias (mean: 834 PVCs h). In a cross-over study with latin square distribution the following drug regimens were administered intravenously to all patients (a) aprindine 2 mg kg, (b) sotalol 1.5 mg kg, (c) aprindine 1 mg kg & sotalol 0.75 mg kg. The mean percentage of PVC reduction was 41% (P <0.05) for aprindine 2 mg kg; 51% (P <0.05) for sotalol 1.5 mg kg and 72% (P <0.01) for the combined drug therapy (aprindine 1 mg kg and sotalol 0.75 mg kg). The mean plasma concentration was 1371 ng ml after administration of aprindine 2 mg kg and 1730 ng ml after infusion of sotalol 1.5 mg kg. After combined drug therapy, mean plasma levels were 942 ng ml for aprindine and 992 ng ml for sotalol. The different drug regimens were well tolerated in all patients and no side-effects occurred. Combination therapy consisting of a drug that prolongs action potential duration with an antiarrhythmic agent that has a high affinity for the inactivated channels may thus achieve an antiarrhythmic efficacy comparable to single agent therapy, permitting the use of lower dosages. [ABSTRACT FROM PUBLISHER]

There are few placebo controlled studies in acute myocardial infarction concerning the haemodynamic effects of beta blockade. In a controlled, double-blind randomized study, the haemodynamic effects of sotalol were evaluated in 20 patients with acute myocardial infarction within 24 hours of the onset. Sotalol was administered to 10 patients over 12 hours by a continuous infusion including three different infusion rates. A serum level around 1.4 microgram ml was achieved after one hour of infusion. The placebo patients were given saline infusion. The patients were monitored invasively using a thermodilution catheter in the pulmonary artery. In the sotalol group, there was a significant reduction in heart rate, systolic blood pressure, cardiac output and stroke volume compared to placebo. A slight increase in the mean pressures of right atrium, pulmonary artery systolic and diastolic pressures was also seen. The infusion was well tolerated and no adverse reaction was seen. [ABSTRACT FROM PUBLISHER]

The effects of sotalol, aprindine and the combination aprindine-sotalol in the intact dog heart were evaluated during constant atrial pacing with the use of monophasic action potential (MAP) recording. A first group of five dogs was given 1.5 mg kg body weight of sotalol, followed by a second infusion of 1.5 mg kg 30 min later. Both doses of sotalol produced a statistically significant increase in right atrial MAP duration at 50% of repolarization (RAMAP50) and right ventricular MAP duration at 90% of repolarization (RVMAP90). To a second group of six dogs aprindine 1 mg kg and aprindine 2 mg kg were administered intravenously. The infusion of aprindine did not alter right atrial and right ventricular MAP duration. The addition of 1.5 mg kg of sotalol to the dogs pretreated with aprindine 2 mg kg resulted a 25% increase in RAMAP50 and a 21% prolongation of RVMAP90. In summary, sotalol lengthens atrial and ventricular monophasic action potential duration and still prolongs repolarization of monophasic action potentials after previous administration of aprindine. A combination of sotalol, a beta-adrenergic blocker possessing class III efficacy, with a class I antiarrhythmic agent may be useful with respect to their electrophysiological action. [ABSTRACT FROM PUBLISHER]

Eighteen patients with sustained ventricular tachycardia underwent serial electrophysiological studies to establish the therapeutic efficacy of sotalol as compared to other available anti-arrhythmic agents. One or more acutely effective drug was found in 14 of the 18 patients (78%). Sotalol was tested in all 18 patients and was effective in 12 of them (67%). For assessment of the prophylactic efficacy of other anti-arrhythmic agents, an average of 3·5 additional studies per patient were performed resulting in successful prevention of ventricular tachycardia in a total of 10 of 63 (16%) additional trials. Nine patients were placed on chronic oral therapy with sotalol. In these nine patients long-term prophylaxis against ventricular tachycardia was documented over a mean follow-up period of 9·6 months (range 2–18 months). The study suggests that sotalol can provide effective prophylaxis against ventricular tachycardia in a significant proportion of patients refractory to other available drugs and that this prophylactic efficacy is predominantly due to its Class III anti-arrhythmic properties.Experimental studies were performed in eight conscious dogs 3–7 days following proximal LAD ligation. Epicardial recordings were obtained using implanted composite electrodes. Sotalol prevented sustained VT by a predominant increase in refractoriness of the infarcted zone. In vitro, sotalol caused a significant prolongation of the action potential of epicardial and endocardial fibres within both the infarcted and noninfarcted myocardium. Refractoriness of epicardial ventricular fibres was significantly more prolonged in ischemically damaged cells as compared to normal fibres. [ABSTRACT FROM PUBLISHER]

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 atianginal 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. [ABSTRACT FROM PUBLISHER]

To investigate and to compare the protective action of verapamil, nifedipine and diltiazem on the acutely infarcting myocardium, we studied effects on cellular damage and mechanical function in the isolated working rat heart preparation subjected to left main coronary artery ligation. First, the fall in the ventricular fibrillation threshold (VFT) was diminished by all three agents, but non-specific effects of these agents were operating at least in part. All three compounds afforded substantial dose-dependent reduction of lactate dehydrogenase release, which was taken as an index of cellular damage, and preserved ATP stores in the infarcting myocardium. The range of effective concentrations was small and close to doses which produced atrioventricular conduction disturbances (verapamil, diltiazem) or LV pump failure (nifedipine). It is argued that these concentrations may be therapeutically relevant, whereas the concentration of a β-adrenoceptor antagonist agent required comparably to inhibit enzyme release was supra-therapeutic (metoprolol 10−4M). There are substantial differences between such animal models and the situation in acute myocardial infarction in man, where preliminary data show benefits both forβ-adrenergic blockade by sotalol and for calcium antagonism by nifedipine. [ABSTRACT FROM PUBLISHER]

The case history of a patient is reported who had two episodes of unconsciousness while on anti-hypertensive therapy consisting of hydrochloroihiazide, hydralazine, and sotalol (480-640 mg as a single daily dose). Ventricular fibrillation which was successfully reverted to sinus rhythm was verified as the cause of the second episode. A ventricular arrhythmia might also have been the cause of the first attack. Marked prolongation of the Q- Tc interval (up to 0'68 s), which returned to normal after discontinuation of sotalol was observed in connection with the episodes. Except for sotalol, no other factors known to cause prolongation of the Q-T interval were found. Later, administration of a single dose of 640 mg of sotalol in the coronary care unit caused a reversible prolongation of the Q-T interval paralleling the course of sotalol concentration in the serum. Atenolol in a dose of 100 mg was associated with a reduction in the response of the pulse to tilting and nitroglycerin administration similar to that observed after sotalol administration, but prolongation of the Q-T interval did not occur after atenolol. Thus, the effect on the Q- T interval was not related to the beta-blocking effect of sotalol. These observations suggest that high therapeutic doses of sotalol can cause a marked prolongation of the Q-T interval which may be associated with ventricular arrhythmias [ABSTRACT FROM PUBLISHER]

Sotalol is the only beta-adrenergic blocking agent, that has been shown to produce delayed repolarization following acute administration. In this study an intravenous injection of 40–100 mg sotalol was given to eight patients with chronic atrial fibrillation. One patient was reverted to sinus rhythm, while the other patients were electro-converted 2 h after the injection. Three patients still in sinus rhythm 24 h later received chronic treatment for at least 12 weeks. They maintained sinus rhythm throughout the study. Identical electrophysiological investigations were performed after the acute injection and after chronic treatment. Following acute administration, sotalol produced a consistent increase in the ventricular repolarization time as measured from refractory periods and monophasic action potential duration, the change being of the magnitude of 13 to 17%. After chronic treatment the three remaining patients still showed an increase in the ventricular repolarization time, but no conclusions can be made from these few observations. However, the study confirms the existence of a class III mode of action at the cellular level following intravenous sotalol injections of40–100 mg in man. [ABSTRACT FROM PUBLISHER]