Profound hypothermia (15 degrees C) was induced in 36 mogrel dogs anesthetized with nitrous oxide-oxygen-d-tubocurarine. Prcpranolol (0.3 mg/kg) or MJ 1999(0.8 mg/kg) was administered intravenously 10 minutes prior to the start of cooling. Significant protection against ventricular fibrillation was provided by MJ 1999, but not by propranolol. With available evidence that hypothermia causes increased catecholamine release and that MJ 1999 is more specific in its beta-adrenergic blocking prcperties than propranolol, the authors findings suggest that ventricular fibrillation during hypothermia is due to beta-adrenergic hyperactivity.
Animals ; Dogs* ; Hypothermia* ; Propranolol* ; Sotalol* ; Ventricular Fibrillation*

BACKGROUND AND OBJECTIVES: The action potential duration (APD) restitution kinetics has been known to play a crucial role in the initiation and maintenance of ventricular tachycardia (VT)/fibrillation (VF). We hypothesized that "the anti-arrhythmic and proarrhythmic effects of d,l-sotalol are mediated by changing the APD restitution (APDR) kinetics". MATERIALS AND METHODS: The purposes of this study were: 1) to assess the effects of d,l-sotalol on the APDR kinetics, and 2) to correlate the anti-arrhythmic and proarrhythmic action using the APDR kinetics. We recorded the transmembrane potentials (TMPs), using the microelectrode technique, in seven isolated perfused swine right ventricles, at the baseline, and with 1, 5, 10 and 20 mg/L of d,l-sotalol, with a washout period of 1 hour. The ventricular effective refractory periods (VERP), APD at 90% repolarization (APD90), spontaneous defibrillation rate and VF inducibility were measured at each concentration. We plotted APDR curves of S1-S2 pacing against VF, and calculated the maximal slopes (Smax) of the APDR. RESULTS: Sotalol (10 mg/L) prolonged the APD90 (p<0.001) by reducing the Smax of the APDR (by S1-S2 pacing, p<0.01; during VF, p<0.05). Accordingly, 41.7% of the VT/VF was terminated spontaneously, and VT/VF inducibility reduced from 91.1% at the baseline to 25% with 10 mg/L sotalol. A higher dose of sotalol (20 mg/L) increased the Smax, despite continuous prolongation of the VERP and APD90, resulting in the increase in the VT/VF inducibility (36.4%). CONCLUSION: Sotalol produces its anti-fibrillatory effect by APD prolongation in parallel with a flattening of the Smax at therapeutic doses. However, a higher concentration of sotalol increased the Smax and VF inducibility in isolated swine ventricular tissue.
Action Potentials* ; Heart Ventricles ; Kinetics* ; Membrane Potentials ; Microelectrodes ; Sotalol ; Swine ; Tachycardia, Ventricular ; Ventricular Fibrillation

Multifocal atrial tachycardia (MAT) is a rare arrhythmia in the newborn. MAT can be difficult to diagnose; it is frequently confused with atrial fibrillation. MAT is difficult to treat but often resolves spontaneously within the first year of life. A newborn with a rapid and irregular pulse rate was diagnosed with multifocal atrial tachycardia by eletrocardiography (ECG) using a hand-made transesophageal electrode. Treatment with propranolol was attempted but ineffective. Treatment with digoxin and sotalol was attempted. The heart rhythm gradually reverted to a sinus rhythm with this treatment. We report our experience managing a neonate with MAT diagnosed by ECG using a hand-made transesophageal electrode.
Arrhythmias, Cardiac ; Atrial Fibrillation ; Digoxin ; Electrocardiography ; Electrodes ; Heart ; Heart Rate ; Humans ; Infant, Newborn ; Propranolol ; Sotalol ; Tachycardia

BACKGROUND AND OBJECTIVES: Atrial fibrillation(AF) is the most frequently encountered arrhythmia in clinical practice. Pharmacologic therapy has been advocated for both immediate restoration of sinus rhythm and prevention of recurrent AF. Because conventional antiarrhythmic therapy is often ineffective in maintaining sinus rhythm or is associated with adverse side effects in patients with AF, recent interest has focused on the use of class III antiarrhythmic agents. This study investigated the efficacy and safety of sotalol and amiodarone for conversion of chronic AF and prevention of recurrent AF. MATERIALS AND METHOD: Thirty six patients with AF were firstly received sotalol by prospective study protocol. The patients were classified as having paroxysmal AF(PAF, N=2) or chronic AF(CAF, N=4) based on AF pattern. If the patients with CAF did not convert to sinus rhythm or the patients with PAF recurred in AF, the patients were received second agents(amiodarone). Patients were followed up for one year. RESULTS: Among the 12 patients with PAF receiving sotalol, 10(83.3%) patients remained in normal sinus rhythm for average 9.4+/-3.6 months. Sotalol was replaced by amiodarone in the remaing 2 patients with arrhythmia recurrence and 1 of the 2 patients remained in sinus rhythm during the follow-up period. In the case of 24 patients with CAF, conversion to sinus rhythm was achieved in 5(20.8%) patients with sotalol. Among the patients with CAF who were not respond to sotalol, 17 patients received amiodarone subsquently and 3 patients successfully converted to sinus rhythm. There were no proarrhythmic effects related to both agents during the study period. CONCLUSION: Both sotalol and amiodarone appear to be less effective in the termination of CAF, but sequential use of these two agents seem to be very effective for the prevention of recurrence of PAF.
Amiodarone* ; Arrhythmias, Cardiac ; Atrial Fibrillation* ; Follow-Up Studies ; Humans ; Prospective Studies ; Recurrence ; Sotalol*

Anti-Arrhythmia Agents ; therapeutic use ; Arrhythmias, Cardiac ; drug therapy ; Child ; Humans ; Sotalol ; therapeutic use

BACKGROUNDTorsade de pointes (TdP) is a form of polymorphic ventricular tachycardia featuring prolonged QT intervals. Female gender is associated with an increased risk of TdP. However, the causes of the sex difference in risk are poorly understood. Recently, transmural dispersion of repolarization (TDR) has been implicated in the genesis of TdP. Consequently, we compared TdP incidence and TDR between male and female rabbit hearts in order to investigate the mechanism of sex difference in TdP risk in rabbits in vitro.

METHODSBy means of monophasic action potential recording techniques, the monophasic action potential of the epicardium, midmyocardium, and endocardium were simultaneously recorded using specially designed plunge-needle electrodes placed across the left ventricular free wall of both female (n = 8) and male (n = 8) rabbit hearts purfused by the Langendorff method. TdP was induced by bradycardia, d-sotalol, and low-K+, Mg2+ Tyrode solution.

RESULTSTDR measurements in all three myocardial layers of male and female rabbit hearts were (18 +/- 2) ms and (21 +/- 2) ms, respectively (n = 8, P > 0.05). After perfusion with d-sotalol, the 90% monophasic action potential duration was prolonged in both male and female rabbits. TDR in male and female rabbit hearts increased to (29 +/- 2) ms and (61 +/- 2) ms, respectively, a difference that is significant. Eight female rabbit hearts had early afterdepolarization and 7 of them developed TdP. Seven male rabbit hearts had early after depolarization, but only one of these hearts developed TdP.

CONCLUSIONGreater TDR may play an important role in the higher incidence of TdP in female rabbit hearts.

Action Potentials ; Animals ; Electrocardiography ; Female ; Male ; Rabbits ; Risk ; Sex Characteristics ; Sotalol ; Torsades de Pointes ; etiology ; physiopathology

OBJECTIVEAlthough after pacing animal and human studies have demonstrated a rate-dependent effect of sotalol on ventricular repolarization, there is little information on the effects of sotalol on ventricular repolarization during exercise. This study attempted to show the effects of sotalol on ventricular repolarization during physiological exercise.

METHODSThirty-one healthy volunteers (18 males, 13 females) were enrolled in the study. Each performed a maximal treadmill exercise test according to the Bruce protocol after random treatment with sotalol, propranolol and placebo.

RESULTSSotalol significantly prolonged QTc (corrected QT) and JTc (corrected JT) intervals at rest compared with propranolol (QTc 324.86 ms vs 305.21 ms, P<0.001; JTc 245.04 ms vs 224.17 ms, P<0.001) and placebo (QTc 324.86 ms vs 314.06 ms, P<0.01; JTc 245.04 ms vs. 232.69 ms, P<0.001). The JTc percent reduction increased progressively with each stage of exercise and correlated positively with exercise heart rate (r=0.148, P<0.01). The JTc percent reduction correlation with exercise heart rate did not exist with either propranolol or placebo.

CONCLUSIONSThese results imply that with sotalol ventricular repolarization is progressively shortened after exercise. Thus the specific class III antiarrhythmic activity of sotalol, present as delay of ventricular repolarization, may be attenuated during exercise. Such findings may imply the need to consider other antiarrythmic therapy during periods of stress-induced tachycardia.

Adult ; Exercise ; physiology ; Exercise Test ; Female ; Heart ; drug effects ; physiopathology ; Heart Rate ; drug effects ; physiology ; Humans ; Male ; Sotalol ; pharmacology

Recently several adrenergic beta receptor blocking agents such as dichloroisoprenaline, pronethalol, INPEA, H13/57, propranolol, sotalol, tolamolol, practolol and butoxamine were reported. It has been postulated for some time that there are two subgroups of beta receptors: cardiac receptors (beta 1-eceptor) and peripheral receptors (beta 2-receptor) responsible for vasodilatation and broncholdilatation. More recently, the cardioselective beta blockers have been developed; for example, practolol, and talamolol. Rabbits were anesthetized by the peritoneal injection of urethane 1 gm/kg and observed for 30 minutes. Arrhythmias were produced with lanatocide-C and norepinephrine through the ear vein of the anesthetized rabbits. Arrhythmias such as premature ventricular contraction and ventricular tachycardia were present within 7 minutes to 20 minutes after the injection of lanatocide-C 0.9mg, and within 15 seconds to 2 minutes after the injection of norepinephrine 150ug. Propranolol or practolol were injected before and after the production of the arrhythmias and so Lead II of the electrocardiogram was obtained from nedle electrodes inserted into the skin. Practolol was compared with propranolol on the changes of the heart rates and the arrhytmias produced by the injection of norepinephrine and lanatocide-C. The intravenous injection of propranolol and practolol reduced the heart rate but practolol reduced much lesser than propranolol. All of arrhythmias produced by lanatocide-C in anesthetzedrabbits were not abolished by practolol, but it blocked and prevented the development of arrhythmias in anesthetized rabbits on the administration of norepinephrine.
Arrhythmias, Cardiac* ; Butoxamine ; Ear ; Electrocardiography ; Electrodes ; Heart Rate ; Injections, Intravenous ; Norepinephrine ; Practolol* ; Propranolol ; Rabbits ; Skin ; Sotalol ; Tachycardia, Ventricular ; Urethane ; Vasodilation ; Veins ; Ventricular Premature Complexes

BACKGROUND AND OBJECTIVES: The aging population is rapidly increasing, and atrial fibrillation (AF) is becoming a significant public health burden in Asia, including Korea. This study evaluated current treatment patterns and guideline adherence of AF treatment. METHODS: In a prospective observational registry (COmparison study of Drugs for symptom control and complication prEvention of Atrial Fibrillation [CODE-AF] registry), 6,275 patients with nonvalvular AF were consecutively enrolled between June 2016 and April 2017 from 10 tertiary hospitals in Korea. RESULTS: The AF type was paroxysmal, persistent, and permanent in 65.3%, 30.0%, and 2.9% of patients, respectively. Underlying structural heart disease was present in 11.9%. Mean CHA2DS2-VASc was 2.7±1.7. Oral anticoagulation (OAC), rate control, and rhythm control were used in 70.1%, 53.9%, and 54.4% of patients, respectively. OAC was performed in 82.7% of patients with a high stroke risk. However, antithrombotic therapy was inadequately used in 53.4% of patients with a low stroke risk. For rate control in 192 patients with low ejection fraction (< 40%), β-blocker (65.6%), digoxin (5.2%), or both (19.3%) were adequately used in 90.1% of patients; however, a calcium channel blocker was inadequately used in 9.9%. A rhythm control strategy was chosen in 54.4% of patients. The prescribing rate of class Ic antiarrythmics, dronedarone, and sotalol was 16.9% of patients with low ejection fraction. CONCLUSION: This study shows how successfully guidelines can be applied in the real world. The nonadherence rate was 17.2%, 9.9%, and 22.4% for stroke prevention, rate control, and rhythm control, respectively.
Aging ; Asia ; Atrial Fibrillation* ; Calcium Channels ; Digoxin ; Guideline Adherence* ; Heart Diseases ; Humans ; Korea ; Prospective Studies* ; Public Health ; Sotalol ; Stroke ; Tertiary Care Centers

OBJECTIVETo evaluate the effects of W-7, a calmodulin inhibitor, on transmural dispersion of repolarization (TDR), early after depolarization (EAD) and torsade de pointes (TdP) induction after administration of d-sotalol in isolated rabbit heart.

METHODSTdP was induced by d-sotalol (30 micromol/L), bradycardia, and hypokalemic (1.5 mmol/L)/hypomagnesaemic (0.35 mmol/L) solution in isolated female rabbit hearts. Thirty six rabbit hearts were divided into 4 groups (n = 9 each): d-sotalol alone, d-sotalol + W-7 (20 micromol/L), d-sotalol + W-7 (50 micromol/L), and d-sotalol + W-7 (100 micromol/L). Monophasic action potentials (MAPs) of the left ventricular epimyocardium (Epi), midmyocardium (M), and endomyocardium (Endo) were recorded simultaneously with ECG. The incidence of EAD and TdP were observed as well.

RESULTSTreatment with d-sotalol alone prolonged ventricular MAP duration and QT interval, increased TDR, and evoked high incidence of EAD (9/9) and spontaneous TdP (7/9) in hypokalemic/hypomagnesaemic solution in female rabbit heart. W-7 concentration-dependently decreased incidence of TdP (4/9 in 20 micromol/L; 2/9 in 50 micromol/L; 1/9 in 100 micromol/L). This effect of W-7 coincided with the decreased incidence of EAD (5/9 in 20 micromol/L; 4/9 in 50 micromol/L; 1/9 in 100 micromol/L). However, the d-sotalol-induced prolongation of QT interval and TDR was not significantly altered by W-7 at the three concentration used.

CONCLUSIONSIn isolated female rabbit hearts, calmodulin antagonist W-7 suppresses d-sotalol-induced TdP without altering TDR but does suppress EAD. The effects observed with W-7 also suggest a possible important role for calmodulin-activated enzymes in the induction of TdP.

Animals ; Calmodulin ; antagonists & inhibitors ; Enzyme Inhibitors ; therapeutic use ; Female ; In Vitro Techniques ; Rabbits ; Sotalol ; adverse effects ; Sulfonamides ; therapeutic use ; Torsades de Pointes ; chemically induced ; prevention & control