Effect of preprocedural pharmacologic cardioversion on pulmonary vein isolation in patients with persistent atrial fibrillation.

BACKGROUND: The optimal strategy for catheter ablation of persistent atrial fibrillation (PeAF) remains unknown. A preprocedural additive treatment for patients undergoing pulmonary vein isolation (PVI) alone to optimize catheter ablation should be investigated. OBJECTIVE: The purpose of this study was to determine whether pharmacologic cardioversion with a fixed low-dose antiarrhythmic drug (AAD) before ablation could stratify the long-term outcome of a PVI-alone strategy. METHODS: We conducted a prospective cohort study of PeAF patients who underwent PVI using contact force-sensing catheters. No substrate modification was performed. Fixed low-dose bepridil was administered before ablation for cardioversion and patients were classified into 2 groups based on obtaining sinus rhythm (SR). The rate of recurrence of atrial fibrillation (AF) and/or atrial tachycardia (AT) within 36 months was compared between the 2 groups. RESULTS: Among the 303 PeAF patients who received the AAD, 102 returned to SR (SR group), and the other 201 had persistence of AF (non-SR group). AF persistence duration at baseline and during bepridil administration was similar between the 2 groups. The SR group had a significantly lower 36-month AF/AT recurrence rate than the non-SR group (17 [22.2%] vs 55 [34.0%], log-rank P = .022). AT-type recurrence was observed in 16 patients (2 [3.3%] in the SR group vs 14 [8.9%] in the non-SR group; log-rank P = .051). Nonresponse to AAD was an independent predictor of AF/AT recurrence after adjusting for other risk factors (hazard ratio 1.34; 95% confidence interval 1.01-1.77; P = .040). CONCLUSION: Preprocedural pharmacologic cardioversion could be a useful determinant for patients with treatable PeAF by PVI alone.

Characterization of microminipig as a laboratory animal for pharmacological study by analyzing bepridil-induced cardiovascular responses.

Since microminipig is becoming attractive model for various cardiac electropharmacological applications, which may meet consideration of 3Rs. We characterized microminipigs by analyzing how multi-ionic channel inhibitor bepridil may affect their in situ hearts in comparison with dogs. Bepridil in doses of 0.3 and 3.0 mg/kg were intravenously administered over 10 min under halothane anesthesia (n = 4). Microminipigs may be less sensitive for ICaT inhibition of bepridil, whereas they are more responsive to INa, IKr and IKs suppression than dogs. This information would help predict cardiovascular effects of a drug in patients with the remodeled hearts having similar electrophysiological profile to microminipigs.

Efficacy of hybrid therapy using prior administration of bepridil hydrochloride and cryoballoon ablation in patients with persistent atrial fibrillation.

BACKGROUND: Rhythm control before catheter ablation for persistent atrial fibrillation (PeAF) can improve clinical outcomes. We sought to investigate the efficacy of pretreatment with bepridil prior to cryoballoon ablation (CBA) with respect to clinical outcomes in patients with PeAF. METHODS: We retrospectively analyzed 65 consecutive patients with PeAF who underwent CBA following pretreatment with bepridil hydrochloride (bepridil). Electrical cardioversion was additionally performed in cases involving failure of pharmacological sinus restoration before CBA. The primary endpoint was survival free from atrial tachyarrhythmia at the one-year follow-up, and the secondary endpoints were changes in P-wave morphology and left atrium diameter (LAD) before CBA. RESULTS: At the one-year follow-up, 51 patients (78.5%) achieved the primary endpoint (non-recurrence group). Compared to the P-wave duration (Pdur) and dispersion at the time of sinus restoration, they significantly shortened at the time of CBA in the non-recurrence group, while they did not change in the recurrence group. There were no changes in LAD in both groups. Multivariate analysis revealed that refractoriness of bepridil (p = 0.03, odds ratio = 4.72, 95% confidence interval = 1.18-18.92), and longer Pdur at admission for CBA (p = 0.003, odds ratio = 1.08, 95% confidence interval = 1.01-1.14) were independent predictors of recurrence. CONCLUSIONS: Rhythm control with bepridil induced electrical reverse remodeling; bepridil may improve clinical outcomes after CBA.

Time-to-Onset Analysis of Drug-Induced Long QT Syndrome Based on a Spontaneous Reporting System for Adverse Drug Events.

Long QT syndrome (LQTS) is a disorder of the heart's electrical activity that infrequently causes severe ventricular arrhythmias such as a type of ventricular tachycardia called torsade de pointes (TdP) and ventricular fibrillation, which can be fatal. There have been no previous reports on the time-to-onset for LQTS based on data from spontaneous reporting systems. The aim of this study was to assess the time-to-onset of LQTS according to drug treatment. We analyzed the association between 113 drugs in 37 therapeutic categories and LQTS including TdP using data obtained from the Japanese Adverse Drug Event Report database. For signal detection, we used the reporting odds ratio (ROR). Furthermore, we analyzed the time-to-onset data and assessed the hazard type using the Weibull shape parameter. The RORs (95% confidence interval) for bepridil, amiodarone, pilsicainide, nilotinib, disopyramide, arsenic trioxide, clarithromycin, cibenzoline, donepezil, famotidine, sulpiride, and nifekalant were 174.4 (148.6-204.6), 17.3 (14.7-20.4), 52.0 (43.4-62.4), 13.9 (11.5-16.7), 69.3 (55.3-86.8), 54.2 (43.2-68.0), 4.7 (3.8-5.8), 19.9 (15.9-25.0), 8.1 (6.5-10.1), 3.2 (2.5-4.1), 7.1 (5.5-9.2), and 254.8 (168.5-385.4), respectively. The medians and quartiles of time-to-onset for aprindine (oral) and bepridil were 20.0 (11.0-35.8) and 18.0 (6.0-43.0) days, respectively. The lower 95% confidence interval of the shape parameter ß of bepridil was over 1 and the hazard was considered to increase over time.Our study indicated that the pattern of LQTS onset might differ among drugs. Based on these results, careful long-term observation is recommended, especially for specific drugs such as bepridil and aprindine. This information may be useful for the prevention of sudden death following LQTS and for efficient therapeutic planning.

Influences of rapid pacing-induced electrical remodeling on pharmacological manipulation of the atrial refractoriness in rabbits.

Electrical remodeling plays a pivotal role in maintaining the reentry during atrial fibrillation. In this study, we assessed influence of electrical remodeling on pharmacological manipulation of the atrial refractoriness in rabbits. We used an atrial electrical remodeling model of the rabbit, subjected to rapid atrial pacing (RAP; 600 beats/min) for 2-4 weeks, leading to shortening of atrial effective refractory period (AERP). Intravenous administration of dl-sotalol (6 mg/kg), bepridil (1 mg/kg), amiodarone (10 mg/kg) or vernakalant (3 mg/kg) significantly prolonged the AERP both in the control and RAP rabbits. The extents in the RAP rabbits were similar to those in the control animals. On the other hand, prolonging effects of intravenously administered ranolazine (10 mg/kg) or tertiapin-Q (0.03 mg/kg) on the AERP in the RAP rabbits were more potent than those in the control animals. These results suggest that rapid pacing-induced electrical remodeling effectively modified the prolonging effects of ranolazine and tertiapin-Q on the AERP in contrast to those of clinically available antiarrhythmic drugs, dl-sotalol, bepridil amiodarone and vernakalant.

Bepridil enhances aprindine-induced prolongation of atrial effective refractory period in a canine atrial rapid pacing model.

BACKGROUND: Bepridil in combination with aprindine could restore sinus rhythm in patients with persistent atrial fibrillation (AF). The present study aimed to investigate the electrophysiological mechanisms of the combined effects of bepridil and aprindine. METHODS: Subjects consisted of 6 dogs without and 6 dogs with atrial rapid pacing (ARP) carried out at 400 bpm for 2 weeks. Bepridil was administered for 1 week in both groups (ARP dogs were administered bepridil in the second week). The electrophysiological effects of the intravenous administration of aprindine (1mg/kg) were evaluated before and after the administration of bepridil. RESULTS: In non-paced dogs, the atrial effective refractory period (AERP) became longer after the administration of bepridil (from 151±10 ms to 170±7 ms, p<0.05); however, no additional AERP prolongation was observed after the acute administration of aprindine. In ARP dogs, the AERP shortened with ARP for a week, and tended to lengthen after the administration of bepridil (from 93±5 ms to 118±9 ms, p=0.08). In these dogs, the acute aprindine administration did not prolong the AERP before the administration of bepridil, although it did after the administration of bepridil (from 118±9 ms to 142±8 ms, p<0.01). AF duration did not change after the administration of bepridil, although it shortened significantly after the additional administration of aprindine (from 2.2±0.3s to 1.4±0.8s, p<0.05). CONCLUSIONS: Bepridil enhances the effect of aprindine for the prevention of AF by reversing atrial electrical remodeling.

Combination therapy of cilostazol and bepridil suppresses recurrent ventricular fibrillation related to J-wave syndromes.

BACKGROUND: Brugada syndrome and idiopathic ventricular fibrillation (VF) associated with inferolateral early repolarization patterns are termed "J-wave syndromes." In such patients, an implantable cardioverter-defibrillator (ICD) is first-line therapy for prevention of sudden cardiac death. However, frequent ICD shocks due to recurrent VF remain serious problems. OBJECTIVE: The purpose of this study was to ascertain if combination therapy of cilostazol and bepridil could suppress recurrent VF. METHODS: We enrolled 7 patients with J-wave syndromes who experienced ICD shocks due to recurrent VF after ICD implantation. At first, cilostazol was instituted. In all subjects, palpitations due to sinus tachycardia caused by cilostazol were symptomatic. Addition of bepridil attenuated cilostazol-induced palpitations and maintained the suppressive effect of cilostazol against VF (87 ± 12 bpm to 66 ± 7 bpm, P < .01). RESULTS: Six patients remained free of VF. Three patients underwent replacement of the ICD generator 4-5 years after ICD placement. Cilostazol was discontinued 2 days before replacement because of its antiplatelet effects. In all 3 patients, temporary discontinuation of cilostazol led to the reappearance of J waves, culminating in VF and an appropriate ICD shock in 1 patient. J waves disappeared with reinstitution of cilostazol. CONCLUSION: These data suggest that combination therapy of cilostazol and bepridil may be effective and safe in suppressing VF recurrence in some cases of J-wave syndromes.

Contributing factors to the apparent clearance of bepridil in patients with paroxysmal or persistent atrial fibrillation: analysis using population pharmacokinetics.

BACKGROUND: Bepridil is used as an antiarrhythmic drug due to its class I, class III, and class IV electrophysiological properties, but it has serious adverse effects such as QT prolongation and torsade de pointes. Bepridil has complex pharmacokinetic (PK) properties with large interindividual differences in plasma concentrations. The aim of this study was to evaluate the contributing factors to changes in the dose-concentration relationship of bepridil and the risk factors for excessive QT prolongation in patients with paroxysmal or persistent atrial fibrillation (AF). METHODS: A population PK analysis was performed by using NONMEM based on 425 concentration points from 76 patients receiving bepridil. A 1-compartment model approximating an intravenous model was used to examine the interindividual variability of the apparent systematic clearance (CL/F) of bepridil. A population PK-pharmacodynamic analysis was performed using the linear regression. RESULTS: Age was a contributing factor to the CL/F of bepridil in AF patients. The QTc interval increased as the area under the plasma bepridil concentration time curve (AUC) increased. The AUC in patients without a bundle branch block, the baseline QT interval, and the existence of structural heart disease in patients with a bundle branch block were explanatory variables of excessive QTc prolongation (QTc > 500 ms) during bepridil therapy. CONCLUSIONS: Using population PK methodology, this study showed that age was a contributing factor to the apparent clearance of bepridil in Japanese patients with AF and that excessive QT prolongation might be related to a larger AUC.

Correlation between inflammation state and successful medical cardioversion using bepridil for refractory atrial fibrillation.

BACKGROUND: It has been reported that inflammation is associated with long-term maintenance of sinus rhythm after electrical cardioversion for non-valvular atrial fibrillation (AF). However, the relation between high-sensitive C-reactive protein (hs-CRP) and the recurrence of AF after medical cardioversion is unknown. On the other hand, bepridil is very effective in restoring sinus rhythm for patients with refractory AF. METHODS AND RESULTS: In 119 patients with non-valvular AF lasting >6 months who failed to maintain sinus rhythm after medical cardioversion without bepridil or electrical cardioversion, we prescribed bepridil. We divided our patients into success group who maintained sinus rhythm for at least 6 months using bepridil and failure group, and compared the following parameters, which were measured just before prescription of bepridil, between the two groups: hs-CRP as a marker of inflammation, left ventricular end-diastolic dimension, ejection fraction, and left atrial dimension as echocardiographic markers, and the incidence of dyslipidemia, hypertension, and diabetes mellitus. After the treatment with bepridil, 57 patients converted to sinus rhythm; however, 12 patients among these 57 patients could not maintain sinus rhythm. Therefore, the success group consisted of 45 patients (38%). Univariate analysis revealed that left atrial dimension and the value of hs-CRP were significantly lower and ejection fraction was significantly higher in the success group than the failure group. Multivariate analysis showed that hs-CRP and left atrial dimension were independent factors for AF recurrence. CONCLUSIONS: Bepridil is effective in restoring sinus rhythm for refractory AF patients. Inflammation, in addition to left atrial dimension, may be associated with successful cardioversion using bepridil.

Pharmacological conversion of atrial fibrillation in the patients of Graves' disease.

BACKGROUND: Hyperthyroidism is one of the common causes of atrial fibrillation (AF), and AF is associated with increased morbidity and mortality due to thromboembolism. The sinus rhythm maintenance rate of hyperthyroidism-induced AF patients after conversion to sinus rhythm is excellent. The present study was undertaken to assess the efficacy and safety of bepridil, a multichannel blocker, in patients with hyperthyroidism-induced persistent AF. METHODS AND RESULTS: Sixty-two patients with hyperthyroidism-induced persistent AF were treated with bepridil. Oral bepridil therapy resulted in conversion to sinus rhythm in 32 (51.6%) of the 62 patients. There were no significant differences in clinical characteristics between the responders and non-responders. At the observation period of an average of 23.9 months, the sinus rhythm maintenance rate was found to be 81.3%. Adverse effects consisted of abnormal QTc prolongation in 3 patients and sinus bradycardia in 10 patients. There was one death in which a causal association with bepridil could not be ruled out. CONCLUSIONS: Bepridil is as beneficial treatment to convert AF for the patients with hyperthyroidism-induced persistent AF as it is for the patients with AF due to other causes. However, bepridil should be used with caution to avoid serious side effects.

Effectiveness of amiodarone versus bepridil in achieving conversion to sinus rhythm in patients with persistent atrial fibrillation: a randomised trial.

AIMS: Pharmacological conversion to sinus rhythm is generally difficult to achieve, particularly in long-lasting persistent atrial fibrillation (AF). The purpose of this study is to compare the effectiveness of two agents, amiodarone and bepridil, in achieving conversion to sinus rhythm in patients with persistent AF. METHODS AND RESULTS: Amiodarone (A) or bepridil (B) was administered to 40 consecutive patients (36 male subjects, age 61 years) with persistent AF in a prospective, randomised, open label fashion. The pharmacological effects in bringing about conversion to sinus rhythm and subsequently maintaining sinus rhythm were evaluated. If sinus rhythm was not restored within 3 months, direct current (DC) cardioversion was performed. The incidence of adverse effects was also evaluated. Sinus rhythm was restored in seven (35%) of 20 patients in group A (average follow-up of 3.2 months) and in 17 (85%) of 20 in group B (average follow-up of 2.3 months) (p<0.05). After pharmacological or DC cardioversion, sinus rhythm could be maintained in 10 (50%) of 20 patients in group A (average follow-up of 14.7 months) and 15 (75%) of 20 patients in group B (average follow-up of 15.6 months). QT interval and QTc were significantly prolonged compare with the baseline values in group B, but no torsade de pointes was recognised in any of the patients. One patient in the group B developed interstitial pneumonia, but steroid therapy cured the condition. CONCLUSIONS: Bepridil was superior to amiodarone in achieving sinus conversion and in maintaining sinus rhythm after cardioversion in patients with persistent AF. Even so, we must be watchful for potentially serious adverse complications when administering bepridil.

Combined effects of up- and downstream therapies on atrial fibrillation in a canine rapid stimulation model.

BACKGROUND: Recent reports suggest angiotensin receptor blockers (ARBs) and some antiarrhythmic agents affect atrial remodeling in atrial fibrillation (AF). We evaluated the effect of combination therapy with olmesartan (Olm) and bepridil (Bep) in a canine model of AF. METHODS AND RESULTS: An atrial stimulation device was implanted in 10 dogs undergoing 6-week pacing at 400 bpm. They were divided into Olm (2 mg/kg/day) (n=5) and Olm+Bep (Olm, 2 mg/kg/day; Bep, 10 mg/kg/day) groups (n=5). Atrial effective refractory period (AERP), conduction velocity (CV), and AF inducibility were evaluated weekly, and hemodynamics, atrial histology, and mRNA expression and protein expression of ion-channel and gap junction-related molecules at 6 weeks. Data were compared between groups and with non-pacing control and pacing-control groups from our previous report. The pacing-control group exhibited shortened AERP, decreased CV, increased AF inducibility and tissue fibrosis, and down-regulated L-type Ca(2+) channel (LCC), SCN5A, Kv4.3 and connexin43 (Cx43). By comparison, the Olm group exhibited suppression of the decrease in CV and of the increase in AF inducibility, but no change in AERP shortening. The Olm+Bep group exhibited suppression of AERP shortening as well as the greatest decrease in AF inducibility. Histologically, tissue fibrosis was suppressed in Olm and Olm+Bep groups. Down-regulation of Cx43 was partly suppressed in the Olm group while that of LCC, SCN5A, and Cx43 was suppressed in the Olm+Bep group. CONCLUSION: Olm and Bep in combination suppressed AF inducibility more strongly than Olm alone, and may be more useful in the suppression of AF.

Repetitive evaluation of fibrillation cycle length predicts the efficacy of bepridil for interruption of long-lasting persistent atrial fibrillation.

Although bepridil is effective for conversion of long-lasting persistent atrial fibrillation (AF) to sinus rhythm, it sometimes takes a long time to interrupt AF and there is no feasible index to predict its efficacy.In 60 patients with long-lasting persistent AF, bepridil (100-200 mg/day) was administered and continued for 8 weeks while body surface ECG was recorded every 2 weeks. The fibrillation cycle length (FCL) was evaluated using the spectral analysis of the fibrillation waves in each ECG. AF was interrupted in 32 patients receiving bepridil. The conversion was observed at 2 weeks in 4, at 4 weeks in 7, at 6 weeks in 7, and at 8 weeks in 14 patients. When comparing these responders and nonresponders, clinical background characteristics other than the dosage of bepridil did not show any difference and neither did temporal changes in QT parameters and heart rate. In contrast, the FCL and ΔFCL (prolongation in FCL from baseline) became significantly larger in responders than in nonresponders at later observation points (FCL: 177 ± 17 versus 164 ± 19 ms, P = 0.018, and ΔFCL: 38 ± 16 versus 22 ± 12 ms, P < 0.001, at 4-week point; FCL: 188 ± 17 versus 169 ± 19 ms, P = 0.004, and ΔFCL: 49 ± 18 versus 27 ± 14 ms, P < 0.001, at 6-week point).Repetitive evaluation of FCL using spectral analysis of fibrillation waves can be a feasible index to predict the efficacy of bepridil therapy.

Efficacy of low-dose bepridil for prevention of ventricular fibrillation in patients with Brugada syndrome with and without SCN5A mutation.

It has been reported that bepridil prevents ventricular fibrillation (VF) in patients with Brugada syndrome, but the comparative efficacy with and without mutation in the SCN5A gene has not been elucidated. The purpose of this study was to assess the efficacy of low-dose bepridil (100 mg/day) for VF prevention in patients with Brugada syndrome with and without SCN5A mutation. Among 130 patients with Brugada-type electrocardiogram (ECG), low-dose bepridil was administered to seven patients because of repetitive VF episodes, including three with and four without SCN5A mutation. Preventive effect for VF recurrence and changes of the ECG and the signal-averaged ECG were evaluated. Frequencies of VF episodes were reduced after treatment with low-dose bepridil in all three patients with the SCN5A mutation (before: 0.33 versus after: 0.02 episodes/month, P < 0.01), but not in all four patients without the SCN5A mutation (before: 0.43 versus after: 2.94 episodes/month, P = nonsignificant). Levels of ST-segment elevation at J points and duration of low-amplitude signals less than 40 µV in the terminal filtered QRS complex (LAS40) in signal-averaged ECG were improved exclusively in patients with the SCN5A mutation. Treatment with bepridil prevented recurrence of VF along with improvement of ST elevation and LAS40 in patients with Brugada syndrome with the SCN5A mutation.

Importance of morphological changes in T-U waves during bepridil therapy as a predictor of ventricular arrhythmic event.

BACKGROUND: Although bepridil is a useful anti-arrhythmic agent for atrial fibrillation, the appearance of serious ventricular arrhythmia, such as torsades de pointes, might be a problem. In this study, T-U wave morphology was evaluated during bepridil therapy and was examined as a predictor of ventricular arrhythmic events. METHODS AND RESULTS: The study population consisted of 113 patients on bepridil therapy. They were divided into 2 groups with and without ventricular arrhythmic events. Morphological changes in T-U waves were analyzed in leads V(2-5). During bepridil treatment, the QTc interval was prolonged from 0.45+/-0.01 to 0.49+/-0.01 s(1/2) in all patients (P<0.0001) and any type of T-U wave change (fused U, slurred, bifid, biphasic or negative) appeared in 73% of event-free and 100% of event groups. In univariate analysis, QTc interval before bepridil (P=0.028), a wide QRS complex (P=0.042) before bepridil, biphasic (P=0.027) or negative (P=0.002) T-U waves in the stable phase, and the new appearance of biphasic (P=0.004) or negative (P<0.0001) T-U waves exhibited significant differences. In multivariate analysis, only newly appeared negative T-U wave exhibited a significant difference (odds ratio 10.13, 95% confidence interval = 0.031-2.302, P=0.041). CONCLUSIONS: In patients with stable bepridil treatment, a change in T-U wave morphology might be a useful predictor of ventricular arrhythmia assisting the QT interval.

Candesartan decreases type III procollagen-N-peptide levels and inflammatory marker levels and maintains sinus rhythm in patients with atrial fibrillation.

This study has evaluated whether candesartans prevent the recurrence of atrial fibrillation (AF) and decrease type III procollagen-N-peptide (PIIINP) levels. A total of 153 patients with AF were enrolled in this study. Three groups of patients were compared; candesartan group was treated with candesartan plus bepridil (n = 52); and carvedilol group with carvedilol plus bepridil (n = 51); and bepridil group with bepridil alone (n = 50). The primary end point was length of time to the recurrence of AF and all patients were ultimately followed-up for 730 days. Serum levels of the biomarkers were measured at baseline and after 24 months. Maintenance of sinus rhythm was achieved in 25 (50%) patients in bepridil group, 37 (73%) in candesartan group, and 34 (67%) in carvedilol group, giving a bepridil group/candesartan group hazard ratio of 0.36 (95% confidence interval 0.21-0.63; P = 0.03). Candesartan significantly decreased PIIINP levels at 24 months than at baseline in sinus rhythm group (0.57 +/- 0.02 vs. 0.64 +/- 0.05 U/mL, P = 0.04) and did not decrease PIIINP levels in the recurrence group. In conclusions, PIIINP might be related to the possibility of the atrial fibrosis for AF. However, further studies are needed to clarify the relationship between PIIINP and AF.

Use of bepridil in combination with Ic antiarrhythmic agent in converting persistent atrial fibrillation to sinus rhythm.

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.

[Role of apoptosis in the kidney after reperfusion]. / Az apoptosis szerepe a vesében reperfúzió során.

UNLABELLED: Organ transplantation is one of the most important achievements of medicine in the 20th century. Ischaemia-reperfusion has a great impact on both: immediate organ function and long-term survival. Organ transplantation can be regarded as a clinical model of ischaemia-reperfusion phenomenon. AIM: The prevention of ischaemia-reperfusion damages. Apoptosis plays a key-role in these processes. METHODS: Apoptosis was investigated in the course of human kidney transplantation. In animal experiments the characteristics of apoptosis were analysed after short ischaemia. Calcium antagonists: verapamil, nifedipine, bepridil, fendiline and (-)-deprenyl, an irreversible selective inhibitor of monoamino oxidase type B, (-)-deprenyl, were administered to prevent apoptosis. RESULTS: The observations showed that in the course of human kidney transplantation necrotic, apoptotic and proliferating renal tubular cells can be observed. All calcium channel blockers and (-)-deprenyl decreased the occurrence and degree of apoptosis in rat kidney. CONCLUSIONS: The functional capacity of tubular cells is a significant factor in the adequate kidney function. The reduction of the apoptosis of tubular cells possibly could improve the function of transplanted kidneys.

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

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.