Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0042510 (ventricular fibrillation)
 10,091 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effect of intravenous bepridil, a new calcium antagonist with class I and III properties, was tested in 21 patients with sustained ventricular tachyarrhythmias refractory to a mean of five antiarrhythmic agents as assessed by programmed right ventricular stimulation. At control electrophysiologic study without antiarrhythmic agents, sustained monomorphic ventricular tachycardia (VT) was initiated in 20 patients and ventricular fibrillation (VF) was initiated in one patient. After 3 mg/kg of bepridil was administered, VT was still inducible in 19 patients (3 patients had self-terminating VT); the other 2 patients had no inducible VT after bepridil. Bepridil prolonged significantly the QTc interval, the effective refractory period, and the cycle length of induced ventricular tachycardia. Two patients with no inducible VT after intravenous bepridil were placed on oral bepridil (300 mg/day). One patient died suddenly and one patient died of progressive heart failure. The results seem to indicate that the efficacy of bepridil in patients with refractory ventricular tachycardia is limited.
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PMID:Electrophysiologic effects of bepridil in patients with refractory ventricular tachycardia assessed by programmed electrical stimulation. 228 30

The effects of the two calcium antagonists bepridil and nifedipine on induced ventricular tachyarrhythmias were studied by programmed electrical stimulation in 15 dogs, 4-8 days after myocardial infarction. Recordings from the infarcted and normal anterior wall of the left ventricle were obtained with an epicardial implanted 'composite' electrode. Bepridil (5 mg/kg) or nifedipine (0.025 mg/kg) were administered i.v. on different days and testing was repeated. Sustained ventricular tachycardia was prevented or significantly slowed by bepridil in 11/12 experiments compared with none of 9 experiments with nifedipine. Paradoxically, in 10/15 dogs nifedipine accelerated arrhythmias or even provoked ventricular fibrillation. Bepridil prolonged refractoriness of infarcted myocardium by 15 +/- 4% (mean +/- SD, p less than 0.01), which was greater than the increase it produced in the effective refractory period of normal tissue (9.0 +/- 3.8%) or QTc interval (11 +/- 5.5%). In contrast, nifedipine significantly shortened these parameters. Both drugs did not influence conduction in infarcted and normal zones as indicated by unchanged late potentials, QRS duration and normal-zone electrograms, respectively. The data indicate that the antiarrhythmic action of bepridil was predominantly related to the prolongation of ventricular refractoriness and repolarization (class III effects).
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PMID:Bepridil versus nifedipine for ventricular tachycardia induced in the late postinfarction phase in conscious dogs. 278 99

Fourteen patients with established atrial fibrillation (longer than three months) that was refractory to treatment were studied to compare the clinical and electrophysiological effects of amiodarone and bepridil. All patients initially received bepridil for three weeks (200-600 mg/day), followed by amiodarone for two to three months (100-400 mg/day). Bepridil seemed to be slightly more effective than amiodarone in converting the fibrillation to sinus rhythm (nine of fourteen compared with four of ten). The ventricular response in atrial fibrillation was equally well controlled by bepridil and amiodarone, both at rest and during exercise. Bepridil was associated with the development of ventricular arrhythmias in eight of fourteen patients; two had torsade de pointes, which in one degenerated into fatal ventricular fibrillation. These arrhythmias seemed to be associated with bepridil induced prolongation of the QTc interval. No ventricular arrhythmias were seen during amiodarone treatment. Although bepridil seems to be an effective antiarrhythmic agent for the management of atrial fibrillation, its arrhythmogenic actions make it unsuitable for this purpose.
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PMID:A comparison of bepridil with amiodarone in the treatment of established atrial fibrillation. 349 25

The effectiveness of the calcium entry blocker bepridil in protecting the myocardium from ischemic injury, was assessed in a canine model of regional ischemia and in a feline model of global ischemia. Bepridil administration (5 mg/kg or 15 mg/kg/24 h intravenously) did not reduce ultimate infarct size as assessed in anesthetized, open-chest dogs subjected to 90 min of occlusion of the left circumflex coronary artery and 24 h of reperfusion. Bepridil (5 mg/kg administered intravenously to a blood donor cat) did not provide any protection of the isolated blood-perfused cat heart from 90 min of normothermic global ischemia and 60 min of reperfusion. Treatment of the perfused cat heart with bepridil did not prevent tissue accumulation of calcium or loss of tissue potassium and ATP. Bepridil, however, significantly reduced reperfusion tachyarrhythmias in the dog model for assessing ultimate infarct size and prevented reperfusion-induced ventricular fibrillation of the cat isolated heart. These results indicate that the calcium entry blocker, bepridil, as assessed in the models employed, does not protect the myocardium from ischemic reperfusion injury. However, it does prevent reperfusion-induced tachyarrhythmias and ventricular fibrillation.
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PMID:Effects of bepridil on regional and global myocardial ischemia/reperfusion-induced injury. 387 4

The antidysrhythmic effects of a new antianginal agent, bepridil, were compared with those of disopyramide, a known antidysrhythmic drug. Bepridil (20, 50, and 100 mg/kg, i.p.) conferred little protection against aconitine-induced dysrhythmias in mice, whereas similar doses of disopyramide exerted a marked dose-dependent antidysrhythmic effect. Intravenous administration of either bepridil (2 mg/kg) or disopyramide (10 mg/kg) significantly reduced the number of ventricular extrasystoles and completely abolished the occurrence of ventricular fibrillation following coronary artery ligation in the rat. Local anesthetic and electrophysiological effects in vitro of bepridil were also investigated. A marked but slowly developing reduction in action potential height of desheathed frog sciatic nerves was observed at concentrations of 0.01-0.05 mM. In sheep Purkinje fibres, a similar decrease in action potential height, associated with a pronounced reduction in the maximum rate of depolarization of phase zero of the action potential (MRD) was seen with bepridil (0.5-2 X 10(-5) M). Higher concentrations (2-8 X 10(-5) M) were required to reduce MRD of guinea pig ventricular muscle. The antidysrhythmic actions of bepridil may at least in part be explained by the electrophysiological effects observed.
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PMID:Antidysrhythmic and electrophysiological effects of a new antianginal agent, bepridil. 617 86

1 The effects of agents which produce membrane stabilization (class I), beta 1-adrenoceptor blockade (class II), prolongation of the cardiac action potential (class III) or inhibition of the slow inward current (class IV) were investigated for their ability to increase the ventricular fibrillation threshold (VFT) or to modify the fall in VFT consequent upon coronary artery ligation in the anaesthetized rat. 2 The class I agent, Org6001, increased VFT of normal myocardium and in lower doses reduced the postligation fall in VFT. 3 The class II agent, metoprolol, failed to increase VFT of normal myocardium but reduced the postligation fall. 4 The class III agent, melperone, increased VFT of both normal and ischaemic myocardium whereas the class IV agent, nifedipine failed to influence VFT in either region. 5 Bepridil (class I and IV) was similar to Org6001 and sotalol (class II and III) in that it increased VFT of normal myocardium and in lower doses reduced the postligation fall in VFT. 6 Measurement of VFT before and after coronary artery ligation in the rat constitutes a rapid and reproducible screen to detect antifibrillatory activity. 7 The results also suggest that in the rat, the low currents used (approximately 400 microA) do not release substantial quantities of catecholamines whereas these may be released by coronary artery ligation.
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PMID:Effects of antiarrhythmic drugs on ventricular fibrillation thresholds of normal and ischaemic myocardium in the anaesthetized rat. 682 12

The antiarrhythmic effects of a novel antianginal agent, bepridil, were compared with four reference products. Bepridil increased the effective refractory period in isolated guinea-pig atria slightly more than hydroquinidine, and much more than disopyramide and lidocaine. Amiodarone was without effect. The doses of bepridil necessary for correcting atrial fibrillation induced by local application of aconitine, were similar for hydroquinidine, higher than for lidocaine and disopyramide but lower than for amiodarone. Bepridil depressed the tachycardia and ventricular fibrillation induced by perfusing aconitine in anesthetized guinea-pigs at doses of the same order of magnitude as for disopyramide and hydroquinidine. Lidocaine only exerted weak activity in this system, while amiodarone was without effect. Bepridil was less active than the four reference products, particularly disopyramide, on rhythm disorders induced by coronary artery ligation.
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PMID:Comparative antidysrhythmic profiles of bepridil, amiodarone and disopyramide in the guinea-pig and dog. 697 33