Effect of sotalol on human atrial action potential duration and refractoriness: cycle length dependency of class III activity

Abstract

Using intracardiac electrophysiological techniques the effects of sotalol hydrochloride were studied in the right atrium in eight patients with paroxysmal supraventricular atrial arrhythmias. Atrial action potential duration was recorded from two well separated standard sites via endocardial contact electrodes before and for 30 minutes after intravenous sotalol (1 mg X kg-1). Atrial effective refractory period and vulnerability to atrial arrhythmia initiation were assessed by premature extrastimulation. All patients developed a prolonged action potential duration (mean +6%, p less than 0.01 in high atrial site; +8%, p less than 0.01 in low atrial site), with similar increases in atrial effective refractory period (mean +9%, p less than 0.01). The small regional difference in action potential duration detected between these well separated recording sites was minimally decreased, indicating no tendency towards increased regional inhomogeneity of repolarisation. The relatively refractory zone as denoted by the gap between atrial effective refractory period and action potential duration was slightly reduced, and transient repetitive atrial depolarisations, initially provoked by extrastimuli in two patients, were abolished. The relation between atrial interval and duration, investigated using two modes of paced cycle length modification, showed that a gradual reduction in pacing cycle length was more potent in shortening action potential duration than was isolated premature extrastimulation. Sotalol was significantly more effective in opposing shortening of the action potential duration caused by progressive cycle length reduction than that caused by isolated extrastimulation. The class III antiarrhythmic activity of sotalol, confirmed in the atrium, is dependent on cycle length and mode of cycle length alteration. Under study conditions, there was no tendency to increase atrial vulnerability or regional non-uniformity of repolarisation.

Cellular electrophysiological effects of d‐and dl‐sotalol in guinea‐pig sinoatrial node, atrium and ventricle and human atrium: differential tissue sensitivity

“…Increases of 8.7% and 10% in APD90 were seen with DL-sotalol 10;JM and D-sotalol 10IM, respectively. These are consistent with increases in atrial monophasic action potential duration of 16% seen by Echt et al (1982) and 6-8% found by Hayward & Taggart (1986) following acute administration of DL-sotalol intravenously. Blood levels were presented only for the first of these studies where peak plasma sotalol levels were approximately 5-991M.…”

“…Levels up to approximately 40 JAM have been found in patients immediately following acute intravenous injection of DL-sotalol (Nademanee et al, 1985) but it is unlikely that the concentrations would remain so high for long (Campbell et al, 1985). Indeed, severe toxicity has been described at blood levels of 25 gM and 53 JM following deliberate overdosage (Elonen et al, 1979 Effects on human atrial cells DL-Sotalol has been shown to be beneficial in the treatment of atrial tachyarrhythmias in man at concentrations below 10 JAM (Campbell et al, 1985) and to prolong human atrial repolarization in similar concentrations (measured as monophasic action potential duration; Echt et al, 1982;Hayward & Taggart, 1986). These facts strongly suggest the possibility that human atrial cells may be more sensitive than those of rabbits or guinea-pigs to the class III actions of solatol.…”

Prolonged Atrial Action Potential Durations and Polymorphic Atrial Tachyarrhythmias in Patients with Long QT Syndrome

“…Atrial APD was longer in LQTS patients than in the control group and longer than in published control groups 17–19 . Comparable action potential prolongation is caused by potassium channel (sotalol) or sodium channel (ibutilide) blocking drugs in the human atrium 6 , 20 . Repolarizing currents that determine atrial repolarization include the transient outward current I to , calcium currents, the late inward sodium current I Na , and the two components of the delayed rectifier (I Kr and I Ks ) 5,6 , 21 , 22 .…”

Die medikamentöse Anfallsprophylaxe bei symptomatischem paroxysmalem Vorhofflimmern/-flattern

“…Hierzu gehört die Verlängerung der effektiven und absoluten Refraktärzeit sowohl im Vorhof-und Ventrikelmyokard als auch im Erregungsleitungssystem (7,39). Die Wirksamkeit in der Unterdrückung von Vorhofflimmern wird dabei vor allem der Wirkung am Vorhofmyokard zugeschrieben (18). Es konnte in randomisierten, doppelblinden und placebokontrollierten Studien die Wirksamkeit von Sotalol als Anfallsprophylaxe bei häufigem paroxysmalem Vorhofflimmern (> 1× im Monat auftretend) nachgewiesen werden, wobei die Gabe von 2× 160 mg/Tag der Dosis 2× 80 mg/Tag deutlich überlegen war (8,42).…”