Bepridil for drug-refractory ventricular tachyarrhythmias. (57/127)

AIMS: To avoid frequent discharges of implantable cardioverter defibrillators, antiarrhythmic drugs may be needed in some patients with ventricular tachyarrhythmias. For ventricular tachyarrhythmias refractory to conventional antiarrhythmic drugs, we evaluated the efficacy of bepridil, a multiple ion-channel blocker. METHODS AND RESULTS: Sixteen patients with structural heart disease and ventricular tachyarrhythmias refractory to multiple antiarrhythmic drugs (4.1+/-1.6 drugs including class III drugs) were enrolled. Bepridil was prescribed at a mean dose of 156+/-40 mg/day. Bepridil prolonged the QT/QTc interval without affecting heart rate or the QRS duration. During a mean follow-up of 52+/-44 months, bepridil completely suppressed ventricular tachyarrhythmias in 6 of the 16 patients (38%) and the drug decreased the frequency of ventricular tachyarrhythmia recurrences by >75% in 3 of the other 10 patients. The markers of complete suppression of ventricular tachyarrhythmias during bepridil treatment included a smaller number of VT morphologies, a better NYHA functional class, and a greater drug-induced prolongation of the QT/QTc interval. The result of electrophysiologic study-guided evaluation of bepridil was closely associated with the clinical efficacy of bepridil in 7 of 8 patients. CONCLUSION: Bepridil appears to be useful to suppress drug-refractory ventricular tachyarrhythmia recurrence.  (+info)

Amiodarone and bepridil inhibit anthrax toxin entry into host cells. (58/127)

Anthrax lethal toxin is one of the fundamental components believed to be responsible for the virulence of Bacillus anthracis. In order to find novel compounds with anti-lethal toxin properties, we used a cell-based assay to screen a collection of approximately 500 small molecules. Nineteen compounds that blocked lethal toxin-mediated killing of RAW 264.7 macrophages were identified, and we report here on the characterization of the two most potent antitoxic compounds, amiodarone and bepridil. These drugs are used to treat cardiac arrhythmia or angina in humans at doses similar to those that provide protection against lethal toxin in vitro. Our results support a model whereby the antitoxic properties of both drugs result from their ability to block endosomal acidification, thereby blocking toxin entry. Amiodarone was tested in vivo and found to significantly increase survival of lethal toxin-challenged Fischer rats.  (+info)

Efficacy and safety of the additional bepridil treatment in patients with atrial fibrillation refractory to class I antiarrhythmic drugs. (59/127)

BACKGROUND: Bepridil has multiple ion-channel blocking effects and is expected to be useful for managing atrial fibrillation (AF). The purpose of this study was to clarify the efficacy and safety of additional treatment with bepridil in patients with AF who had been treated with class I antiarrhythmic drugs (AADs). METHODS AND RESULTS: Bepridil (50-200 mg/day) was given to 76 patients with either paroxysmal (n=49) or persistent AF (n=27). All patients had been treated with class I AADs (1.9+/-0.9 drugs/patient) that failed to control the AF. With the addition of bepridil, the frequency of symptomatic AF episodes decreased to less than 10% in 38 (78%) patients with paroxysmal AF, and sinus rhythm was restored within 3 months and maintained during the follow-up in 20 (74%) patients with persistent AF. Efficacy was usually obtained with a small to moderate dose (50-150 mg/day) of bepridil. During a mean follow-up period of 27+/-22 months, no potential complications occurred in any of the patients. CONCLUSIONS: The addition of bepridil to class I AADs is effective and safe for AF, but careful observation using periodic ECG recordings is essential for avoiding torsades de pointes caused by QT prolongation.  (+info)

Inhomogenic effect of bepridil on atrial electrical remodeling in a canine rapid atrial stimulation model. (60/127)

BACKGROUND: The antiarrhythmic or reverse remodeling effects of bepridil, a multi-ion channel blocker, have been recently reported, but inhomogeneity of the electrical remodeling and effects of bepridil have been observed in previous reports. In this study, the effect of long-term administration of bepridil on atrial electrical remodeling was evaluated in a comparison of the right and left atrium (RA and LA) in a canine rapid atrial stimulation model. METHODS AND RESULTS: In 10 beagle dogs, rapid atrial pacing (400 beats/min) was delivered for 6 weeks and the atrial effective refractory period (AERP), conduction velocity (CV) and inducibility of atrial fibrillation (AF) were evaluated every week. In 5 of the pacing dogs, bepridil (10 mg . kg(-1) . day(-1)) was administered orally, starting 2 weeks after the initiation of the rapid pacing. At the end of the protocol, the hemodynamic parameters and extent of tissue fibrosis were evaluated and the mRNA of SCN5A, Kv4.3, the L-type Ca2+ channel (LCC) and connexin (Cx) 40, 43, and 45 in both atria were examined by quantitative real-time reverse transcriptase-polymerase chain reaction. In the pacing control group, AERP shortening, decreased CV, increased AF inducibility and downregulation of the expression of SCN5A and LCC were observed. In the bepridil group, the AERP exhibited a relatively quick recovery after bepridil was started in the first week and continued to recover gradually until the end of the protocol, but that recovery was smaller in the LA than in the RA. The CV was not affected by bepridil administration. AF inducibility was well suppressed in the RA in the bepridil group, but the induction of short-duration AF could not be suppressed in the LA. The mRNA downregulation of the LCC and SCN5A was negated by bepridil administration in the RA; but not in the LA; however, the data showed similar tendencies. There were no significant differences in the hemodynamic parameters or tissue fibrosis and the mRNA expression of Kv4.3, Cx40, 43, and 45 between the pacing control and bepridil groups. CONCLUSION: Bepridil exhibited an anti-electrical remodeling effect in this study as previously reported, but the effect was inhomogeneous between the RA and LA, with the LA appearing to be more resistant to the effect of bepridil.  (+info)

Use of bepridil in combination with Ic antiarrhythmic agent in converting persistent atrial fibrillation to sinus rhythm. (61/127)

BACKGROUND: It has been reported that bepridil is as good as amiodarone in converting persistent atrial fibrillation (AF) to sinus rhythm (SR). The conversion effect of bepridil alone is not always satisfactory, however. The efficacy of pharmacological cardioversion by the combination of bepridil and a class Ic antiarrhythmic drug for persistent AF is studied. METHODS AND RESULTS: The participants comprised 37 consecutive patients in whom pharmacological cardioversion was conducted to treat persistent AF (duration 22.5+/-29.6 months). Each patient first received a class Ia or Ic antiarrhythmic drug, then bepridil alone, then a combined therapy of bepridil at 200 mg/day with a class Ic antiarrhythmic drug at a routine dose. Unaccompanied use of any of the antiarrhythmic drugs achieved pharmacological cardioversion in 14 (38%) of the 37 patients (single therapy group), whereas SR was restored by combination of bepridil and a class Ic antiarrhythmic drug in 22 (combined therapy group) of the remaining 23 patients. The duration of AF was significantly longer in the combined therapy group than in the single therapy group (28.3+/-31.0 vs 7.3+/-4.1 months). CONCLUSION: Combined therapy of bepridil and a class Ic antiarrhythmic drug is efficient for pharmacological cardioversion of refractory long-lasting persistent AF.  (+info)

Comparison of electropharmacological effects of bepridil and sotalol in halothane-anesthetized dogs. (62/127)

BACKGROUND: Bepridil is known to have a multiple ion channel-blocking property in the heart, which has been applied for the treatment of atrial fibrillation and drug-refractory ventricular tachyarrhythmias. In this study, the electro-pharmacological effects of bepridil were compared with those of dl-sotalol, a representative class III antiarrhythmic drug, using the halothane-anesthetized canine model. METHODS AND RESULTS: Cardiovascular and electrophysiological variables were measured under the halothane anesthesia. Intravenous administration of bepridil (0.3 mg/kg, n=4) delayed the intraventricular conduction and prolonged the ventricular effective refractory period, whereas dl-sotalol (0.3 mg/kg, iv, n=4) inhibited atrioventricular conduction and prolonged the atrial and ventricular effective refractory period. The additional administration of 10 times the higher dose of bepridil or dl-sotalol (ie, 3 mg/kg, iv, n=4 for each group) decreased blood pressure, suppressed ventricular contraction and sinus automaticity, and prolonged the atrial and ventricular effective refractory period and monophasic action potential duration, in addition to the effects of the low dose. CONCLUSIONS: The electropharmacological effects of bepridil and dl-sotalol were similar, although their potency for each cardiovascular variable varied significantly. These findings can be useful when selecting these drugs according to the pathophysiological condition of a patient.  (+info)

Two patients with bepridil-induced interstitial pneumonia. (63/127)

Two patients developed bepridil-induced interstitial pneumonia during treatment of arrhythmia. The first patient was a 69-year-old man who received bepridil to maintain sinus rhythm in atrial fibrillation and who developed dyspnea on the 20th day after administration. The second patient was a 72-year-old man who received bepridil for paroxysmal atrial fibrillation and who developed dyspnea on the 60th day after administration. They were diagnosed with interstitial pneumonia on the basis of physical and imaging findings. The first patient was discharged after steroid pulse therapy, and the second patient after improvement of physical and imaging findings when bepridil was discontinued. Although a limited number of cases of bepridil-induced interstitial pneumonia have been reported, the disorder should be kept in mind as an important adverse reaction when breathlessness or dyspnea develops during administration of the drug.  (+info)

Dose-response effects of bepridil in patients with persistent atrial fibrillation monitored with transtelephonic electrocardiograms: a multicenter, randomized, placebo-controlled,double-blind study (J-BAF Study). (64/127)

BACKGROUND: A multicenter, randomized, placebo-controlled, double-blind trial was conducted with patients with persistent atrial fibrillation (AF) to determine the dose-response effects and safety of bepridil, using every-day transtelephonic monitorings. METHODS AND RESULTS: A total of 90 patients were randomized to receive placebo, 100 mg/day and 200 mg/day of bepridil treatment for 12 weeks. After the treatment, those patients who converted to sinus rhythm was 3.4% in placebo, 37.5% in those who received 100 mg/day and 69.0% in those who received 200 mg/day, thus demonstrating a linear dose-response relationship for AF conversion. The conversion rate gradually reached a maximal value at approximately 6 weeks after initiation of bepridil. However, the AF recurrence rate was high (91.7% in those receiving 100 mg/day and 75.0% in those receiving 200 mg/day). Adverse events, presumably related to the drug, were also frequent: ventricular tachycardia in 2, QT prolongation in 4 and sinus bradycardia in 2 patients. In those patients treated with 200 mg/day group, 1 patient died suddenly because of ventricular tachycardia. CONCLUSIONS: This study demonstrated the dose response-relationships of bepridil for AF conversion to sinus rhythm. However, the high rate of AF recurrence and substantial drug-related adverse effects, including sudden death, raised caution about using bepridil to treat persistent AF. The balance between benefits and risks of the drug should be individualized.  (+info)