benzofurans and Tachycardia--Ventricular

Implantable cardioverter-defibrillators (ICDs) remain the treatment of choice for the prevention of life-threatening arrhythmias. However, many patients with ICDs require additional antiarrhythmic therapy to reduce the morbidity associated with recurrent arrhythmia-triggered ICD interventions.. Our study aimed to evaluate the safety and efficacy of celivarone in reducing these interventions.. A total of 153 eligible ICD recipients were randomized to receive either placebo or celivarone 100 or 300 mg once daily for 6 months. The primary end point was the prevention of arrhythmia-triggered ICD therapies.. Fewer ventricular tachycardia and ventricular fibrillation episodes were observed in the 300-mg celivarone group than in the placebo group, with a relative risk reduction of 46%, which was not statistically significant. The analysis of all-cause shocks showed a trend toward a decreased number of events in the celivarone 300-mg group. A post hoc analysis of the primary end point in a subgroup of patients in the celivarone 300-mg group, who had received ICD therapy within 1 month of randomization, showed a significant benefit (P = .032). Celivarone was not associated with an increased risk of torsades de pointes, thyroid dysfunction, or pulmonary events. More heart failure events were reported in the celivarone groups than in the placebo group, but the difference was not statistically significant.. Celivarone tends to reduce ventricular tachycardia-/ventricular fibrillation-triggered ICD therapies. This effect was not statistically significant. There was a trend toward greater efficacy in the 300-mg group, especially in patients undergoing ICD therapy within 30 days prior to randomization. Overall, celivarone was well tolerated.

Topics: Aged; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Benzofurans; Defibrillators, Implantable; Double-Blind Method; Female; Follow-Up Studies; Heart Ventricles; Humans; Male; Middle Aged; Tachycardia, Ventricular; Ventricular Fibrillation

Celivarone is a new antiarrhythmic agent developed for the treatment of ventricular arrhythmias. This study investigated the efficacy and safety of celivarone in preventing implantable cardioverter-defibrillator (ICD) interventions or death.. Celivarone (50, 100, or 300 mg/d) was assessed compared with placebo in this randomized, double-blind, placebo-controlled, parallel-group study. Amiodarone (200 mg/d after loading dose of 600 mg/d for 10 days) was used as a calibrator. A total of 486 patients with a left ventricular ejection fraction ≤40% and at least 1 ICD intervention for ventricular tachycardia or ventricular fibrillation in the previous month or ICD implantation in the previous month for documented ventricular tachycardia/ventricular fibrillation were randomized. Median treatment duration was 9 months. The primary efficacy end point was occurrence of ventricular tachycardia/ventricular fibrillation-triggered ICD interventions (shocks or antitachycardia pacing) or sudden death. The proportion of patients experiencing an appropriate ICD intervention or sudden death was 61.5% in the placebo group; 67.0%, 58.8%, and 54.9% in the celivarone 50-, 100-, and 300-mg groups, respectively; and 45.3% in the amiodarone group. Hazard ratios versus placebo for the primary end point ranged from 0.860 for celivarone 300 mg to 1.199 for celivarone 50 mg. None of the comparisons versus placebo were statistically significant. Celivarone had an acceptable safety profile.. Celivarone was not effective for the prevention of ICD interventions or sudden death.. http://www.clinicaltrials.gov. Unique identifier: NCT00993382.

Topics: Aged; Amiodarone; Anti-Arrhythmia Agents; Benzofurans; Death, Sudden, Cardiac; Defibrillators, Implantable; Dose-Response Relationship, Drug; Double-Blind Method; Drug Therapy, Combination; Female; Follow-Up Studies; Humans; Incidence; Kaplan-Meier Estimate; Male; Middle Aged; Tachycardia, Ventricular; Treatment Outcome; Ventricular Fibrillation

The aim of this study was to investigate the protective effect of Chuanxiong-pathalide A on the injury of endothelial cell induced by ischemia and reperfusion in isolated rat hearts.. The isolated rat hearts were perfused under constant pressure with Chuanxiong-pathalide A at the concentrations of 0.012 5 mg x mL(-1), 0.025 mg x mL(-1) and 0.05 mg x mL(-1) within 10 min followed by a 10-min washout period before the induction of a 30-min normothermic global ischemia and 60 min reperfusion.. Pretreatment with Chuanxiong-pathalide A produced a reduction in the incidence of reperfusion-induced ventricular fibrillation (VF) and ventricular tachycardia (VT). Pretreatment of the hearts with high dose of Chuanxiong-pathalide A (0.05 mg x mL(-1)) prior to the ischemia and reperfusion, reduced the incidence of reperfusion-induced VF and VT to 37.5% as compared with non-pretreated control group (P < 0.05). The duration of occurrence of VF and VT in the group pretreated with Chuanxiong-pathalide A at dosages of 0.012 5 mg x mL(-1), 0.025 mg x mL(-1) and 0.05 mg x mL(-1) were (7.50 +/- 1.61), (1.64 +/- 0.67) and (1.06 +/- 0.70) min respectively, which were significantly shorter than (23.51 +/- 3.99) min in non-pretreated control group; 0.05 mg x mL(-1) of Chuanxiong-pathalide A increased coronary flow in comparison with the control group. The content of SOD in the group pretreated with 0.05 mg x mL(-1) of Chuanxiong-pathalide A was (59.6 +/- 18.7) U x mg(-1), significant lower than (92.3 +/- 19.0) U x mg(-1) in the non-pretreated group. The contents of LDH and MDA were (2 378.0 +/- 196.3) U x g(-1) and (12.1 +/- 1.3) nmol x mg(-1) in the non-pretreated group, which were much higher than the values of (1 669.4 +/- 192.5) U x g(-1) and (6.9 +/- 0.8) nmol x mg(-1) in the group pretreated with Chuanxiong-pathalide A respectively. In addition, enzymeimmunoassays showed an decreased production of IL-1beta and the ratio of TXB2/6-Keto-PGF1alpha.. Our results show that chuanxiong-pathalide A pretreatment can protect the endothelial function from the injury caused by ischemia and reperfusion.

Topics: Animals; Benzofurans; Coronary Vessels; Drugs, Chinese Herbal; Endothelial Cells; In Vitro Techniques; Interleukin-1beta; Ischemic Preconditioning, Myocardial; L-Lactate Dehydrogenase; Ligusticum; Malondialdehyde; Myocardial Reperfusion Injury; Myocardium; Plants, Medicinal; Rats; Rats, Sprague-Dawley; Regional Blood Flow; Tachycardia, Ventricular; Ventricular Fibrillation

We compared the ability of a new amiodarone-like agent, SR 33589, with that of amiodarone, D,L-sotalol, and lignocaine to reduce the incidence of ventricular fibrillation (VF) and associated arrhythmias caused by acute coronary artery occlusion in anesthetized pigs. Ischemia was induced by occlusion of the left coronary descending artery (LAD) for 30 min. Premature ventricular complexes (PVCs), ventricular tachycardia (VT), and ventricular fibrillation (VF) were recorded during coronary occlusion. SR 33589 (1.25, 2.50, and 5 mg/kg intravenously, i.v.) markedly reduced the occurrence of ventricular arrhythmias during ischemia. The incidence of VF was reduced from 90% in the control group to 30% (p < 0.05) with 1.25 mg/kg, to 10% (p < 0.001) with 2.50 mg/kg, and to 20% (p < 0.01) with 5 mg/kg. In addition, SR 33589, especially at the two higher doses, caused a sustained reduction in both the incidence of VT and the number of PVCs per minute. In comparison, amiodarone 10 and 20 mg/kg i.v. reduced the incidence of VF (40 and 50%, respectively), but these reductions never reached a level of statistical significance. The incidence of VT and the number of PVCs per minute were also decreased significantly by amiodarone. D,L-sotalol 3 mg/kg i.v. exerted significant anti-arrhythmic activity; the incidence of VF was reduced 20% (p < 0.01), and both the incidence of VT and number of PVC per minute were also reduced. In contrast, lignocaine given as a 2-mg/kg bolus followed by an infusion at 70 micrograms/kg/min had no antiarrhythmic or antifibrillatory activity in this preparation.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Amiodarone; Analysis of Variance; Animals; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Benzofurans; Death, Sudden, Cardiac; Disease Models, Animal; Dronedarone; Female; Lidocaine; Male; Myocardial Ischemia; Sotalol; Stereoisomerism; Swine; Tachycardia, Ventricular; Ventricular Fibrillation