Electrophysiological properties of acute intravenous sotalol in man

The electrophysiological properties of of 0,6 mg/Kg SOTALOL administered intravenously were studied in 15 subjects aged between 32 and 81 years. The following parameters were recorded: sinus rate (SR), corrected sinus node recovery time (SNRT), sinoatrial conduction time (SACT), PA interval, right atrial effective refractory period (ERP), right atrial functional refractory period (FRP), AH interval at rest, at 100 bpm, Luciani-Wenckebach point (LWP), AV node ERP and FRP, HV interval, His-Purkinje ERP, right ventricular ERP, corrected QT interval. At this dosage, intravenous SOTALOL displays two types of behaviour: --That common to the betablocker drugs: slowing SR by 16%, increasing the AV nodal conduction, increasing the AH interval at rest (5%), at 100 bpm (23%), increasing AV nodal ERP (26%) and FRP (20%), decreasing the LWP (18%). --Other properties: increasing intraatrial PA interval (3%), increasing right atrial ERP (II%), FRP (I7%), increasing right ventricular ERP (8%), increasing His-Purkinje ERP (when measurable) (about 6%), no change in corrected QT interval. At this dosage, SOTALOL exhibits electrophysiological behaviour similar to drugs in Class III (Touboul): those with a "wide electrophysiological spectrum".     

Electrophysiological effects of intravenous sotalol in acute myocardial infarction: a double-blind placebo-controlled study

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 QT 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.     

Hemodynamic effects of intravenous and oral sotalol

Beta-adrenergic blocking agents may have negative inotropic effects that are particularly worrisome in patients with depressed cardiac function. Their membrane-stabilizing properties may be a contributing factor. Sotalol is currently thought not to cause significant myocardial depression. Intravenous sotalol administration has minimal effects on resting stroke volume, although heart rate and consequently cardiac output are significantly decreased. Systolic blood pressure decreases, with a minimal change in diastolic or mean pressure. Hemodynamic effects are usually seen within 15 to 20 minutes of administration. Hemodynamic indexes are maintained even in patients with mildly depressed ejection fractions (mean ejection fraction of 43 +/- 15%) after oral sotalol administration. Although heart rate decreases, cardiac index is unchanged because of a significant increase in stroke volume index. The latter results from an increase in preload (secondary to bradycardia) and a decrease in afterload. Sotalol is well tolerated, although occasionally it may cause worsening heart failure. This is seen in patients with markedly depressed left ventricular function and inadequate cardiac reserve characterized by an inability to increase stroke volume and cardiac output with exercise. Long-term (1-year) patient follow-up reveals no significant hemodynamic deterioration from initial values obtained after oral administration.     

Electrophysiological effects soon after intravenous beta-methyldigoxin.

The digitalis derivative beta-methyldigoxin has been shown to be quickly and well absorbed from the gut and, in hemodynamic studies, to start acting rapidly after intravenous administration. However, when tested on 6 patients suffering from paroxysmal reciprocating atrioventricular tachycardia, or having an accessory pathway who might develop this disorder, there was no effect on induced tachycardias or on AV conduction during rapid atrial pacing or the extrastimulus test. One of the 6 patients showed some increase in refractoriness of conduction through the AV node within 25 min after the injection. Beta-methyldigoxin does not appear to be a satisfactory alternative to other effective agents available for the prompt correction of paroxysmal reciprocating atrioventricular tachycardia.     

The acute cardiac electrophysiological effects of intravenous sotalol hydrochloride

The cardiac electrophysiological effects of sotalol were studied in ten patients (pts) aged 20--65 years undergoing intracardiac stimulation studies for palpitations (7 pts) or dizzy spells (3 pts). The following measurements were made: 1. basic sinus cycle length (SCL): 2. SINUS NODE RECOVERY TIME (SNRT) following overdrive pacing; 3. intra-atrial (PA), atrio-His (AH) and His-ventricular (HV) conduction intervals during regular atrial pacing; 4. effective refractory periods of the atria (AERP), AV node (AVERP) and ventricular myocardium (VERP). AV nodal functional refractoriness (AVFRP) was also determined. All measurements were repeated 10--15 min after i.v. administration of 0.4 mg/kg of sotalol. Results were analysed by the Wilcoxon Signed Rank test. Significant increases in SCL (p less than 0.01), AH (p less than 0.01). SNRT (p less than 0.01), AVERP (p less than 0.02) and AVFRP (p less than 0.01) were observed. These effects are consistent with the beta-blocking action of sotalol. The acute increase in AERP (p less than 0.01) is, however, not a common property of other beta-blockers and may be related to the 'class III' cellular effect of sotalol. These results are discussed in relationship to the electrophysiological effects of other beta-blocking drugs.     

Electrophysiological effects of intravenous MDL 17.043

MDL 17.043, a nonglycoside, noncatecholamine imidazolone derivative with phosphodiesterase inhibiting activity, has been shown to possess both positive inotropic and vasodilator properties. In the present study, the electrophysiological effects of intravenous MDL 17.043 were assessed in 10 patients undergoing programmed right atrial stimulation for diagnostic purposes. MDL 17.043 was administered as a single intravenous bolus injection of 1.5 mg/kg body weight over 4 min followed by an intravenous infusion of 0.75 mg/kg body weight over 20 min. With the dosage schedule used, the MDL 17.043 plasma levels achieved were similar to those previously reported to be associated with significant hemodynamic improvement of congestive heart failure. Electrophysiological measurements were performed before and during MDL 17.043 administration. MDL 17.043 consistently shortened basic sinus cycle length, sinus node recovery time and sinuatrial conduction time and decreased Wenckebach cycle length, atrioventricular and atrial refractoriness leading to positive chronotropic and dromotropic effects.     

Haemodynamic effects of intravenous sotalol in acute myocardial infarction

There are few placebo controlled studies in acute myocardialinfarction concerning the haemodynamic effects of beta blockade.In a controlled, double-blind randomized study, the haemodynamiceffects of sotalol were evaluated in 20 patients with acutemyocardial infarction within 24 hours of the onset. Sotalolwas administered to 10 patients over 12 hours by a continuousinfusion including three different infusion rates. A serum levelaround 1.4 microgram ml^–1 was achieved after one hourof infusion. The placebo patients were given saline infusion.The patients were monitored invasively using a thermodilutioncatheter in the pulmonary artery. In the sotalol group, therewas a significant reduction in heart rate, systolic blood pressure,cardiac output and stroke volume compared to placebo. A slightincrease in the mean pressures of right atrium, pulmonary arterysystolic and diastolic pressures was also seen. The infusionwas well tolerated and no adverse reaction was seen.     

Electrophysiological effects of intravenous prostacyclin in man

The electrophysiological effects of prostacyclin (PGI₂) werestudied in 10 normal patients. Programmed stimulation was performedbefore and after infusion of 2.5, 5, 10ng kg^–1 min^–1of PGI₂. Then, 0.2 mg kg^–1 of propranolol was added tothe higher dose of PGI₂.We observed a net decrease of the systolicand diastolic arterial blood pressure beginning with the lowestdose. There was no effect on sinus node recovery time, atrial,His-Purkinje and ventricular effective refractory periods, AHand HV intervals. Atrioventricular (AV) nodal effective andfunctional refractory periods could be measured in 5 patientsand were decreased in all cases. Sinus cycle length and anterogradeand retrograde Wenckebach cycle lengths were significantly decreasedby PGI₂ in a dose dependant manner. The injection of propranololincreased all these values but did not suppress entirely theeffects of PGI₂.In conclusion, the electrophysiological effectsof PGI₂ were marked decreases of sinus cycle length and AV nodalrefractoriness which may be partly related to enhanced sympatheticactivity.     

Electrophysiological effects of intravenous magnesium sulfate in man

Magnesium salts have been used for many years to correct a wide variety of arrhythmias. A few experimental studies have been devoted to their electrophysiological effects, but these remain poorly documented in man, hence this study. An electrophysiological investigation was conducted in 24 patients before, and immediately after a bolus intravenous injection of magnesium sulphate in doses of 1.5 g to 12 patients (group I) and 3 g to 12 other patients (group II), followed by a continuous infusion at the rate of 1 mg/min. The drug had no influence on heart rate, duration of QRS, QT and QTc intervals and ventricular refractory period. A small, but statistically significant prolongation of HV (from 57 to 59 ms, p less than 0.05) was observed in group II. Analysis of the results in group I revealed a moderate but significant prolongation of the PR and AH intervals. The electrophysiological effects were distinctly more pronounced in group II patients, with significant prolongation of: PR and AH intervals, effective refractory period of the right atrium and AV node, Wenckebach's point, corrected sinus node recovery time and sinoatrial conduction time. These results demonstrate that magnesium sulphate principally acts on the sinus node, the AV node and the atrium, suggesting a blocking effect on calcium channels.     

Electrophysiological effects of flecainide and sotalol in the human atrium during persistent atrial fibrillation

Aims Atrial fibrillation (AF) shortens the atrial action potential and the atrial refractory period. These changes promote persistence of AF. Pharmacological prolongation of atrial action potential duration (APD) may therefore help to prevent recurrent AF. In addition to prolonging APD, sodium channel blockers may prevent AF by inducing post–repolarization refractoriness (PRR). We studied whether two antiarrhythmic drugs (sotalol, flecainide) prolong APD or induce PRR in the fibrillating human atrium. Methods In 12 patients with persistent AF (11 male, 58 ± 5 yrs, 27 ± 7 months duration of AF), we recorded monophasic action potentials from the right atrial appendage and inferior right atrium at baseline and 15 minutes after intravenous administration of sotalol (1.5 mg/kg) or flecainide (2 mg/kg). APD and effective refractory periods (ERP) were determined. Results Both drugs prolonged APD90 during AF (flecainide from 109 ± 7 ms to 137 ± 10 ms, sotalol from 108 ± 6 ms to 131 ± 8 ms, both p < 0.05 vs. baseline). Sotalol prolonged ERP in parallel to APD (from 119 ± 8 ms to 139 ± 8 ms, p < 0.05). Flecainide induced PRR by prolonging ERP more than APD90 (from 134 ± 9 ms to 197 ± 28 ms, p < 0.05 vs. baseline and vs. sotalol). Conclusions Flecainide and sotalol prolong the atrial action potential during atrial fibrillation in humans. In addition, flecainide induces atrial PRR. These electrophysiological effects may reduce AF recurrences and prevent their persistence.Drs. Kirchhof, Engelen and Breithardt are Members of the Kompetenznetz Vorhofflimmern     

Effects of intravenous sotalol in patients with atrioventricular accessory pathways

Effects of intravenous injection of 0.6 mg/kg sotalol, a beta-blocking agent with additional class III properties, were studied by means of electrophysiologic techniques in 14 patients, seven with the Wolff-Parkinson-White syndrome and seven with concealed atrioventricular (AV) accessory pathways. Sotalol brought about a significant increase in the retrograde effective refractory period of the anomalous pathway, whereas changes in the antegrade effective refractory period were more variable. In five of nine patients with electrically induced reciprocating tachycardia sotalol prevented the initiation of sustained reentry. In most cases the suppression of the circus movement was the result of the development of AV nodal block. Thus our data support the use of sotalol for the treatment of tachycardias incorporating anomalous AV conduction pathways.     

Electrophysiological properties of intravenous metoprolol in man.

Electrophysiological changes produced by intravenous (0.1 mg/kg) metoprolol, a new selective beta 1-blocking agent devoid of intrinsic activity, were studied in 16 subjects with estimated normal impulse formation and conduction. The most important effects were sinus bradycardia, mild increase of sinoatrial conduction time, depression of intranodal conduction, and prolongation of AV node refractory periods. Sinus node recovery time and atrial refractory periods were unmodified. Infranodal conduction and the refractory periods of the His-Purkinje system, as well as of the bundle-branches, were unchanged. These effects are compared with those observed after intravenous propranolol, pindolol, and oxprenolol.     

Electrophysiological properties of intravenous metoprolol in man.

Electrophysiological changes produced by intravenous (0.1 mg/kg) metoprolol, a new selective beta 1-blocking agent devoid of intrinsic activity, were studied in 16 subjects with estimated normal impulse formation and conduction. The most important effects were sinus bradycardia, mild increase of sinoatrial conduction time, depression of intranodal conduction, and prolongation of AV node refractory periods. Sinus node recovery time and atrial refractory periods were unmodified. Infranodal conduction and the refractory periods of the His-Purkinje system, as well as of the bundle-branches, were unchanged. These effects are compared with those observed after intravenous propranolol, pindolol, and oxprenolol.