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 antiarrhythmic and proarrhythmic effects of flecainide were assessed in 21 anesthetized cats. Ventricular arrhythmias can be reproducibly induced in cats by the combination of acute myocardial ischemia and sympathetic stimulation. Premature ventricular contractions (PVCs), sustained (sVT) and nonsustained (nsVT) ventricular tachycardia (VT), or ventricular fibrillation (VF) may be induced by a 1-minute left stellate ganglion stimulation during a 3-minute coronary artery occlusion. After three trials yielding consistent results, flecainide (2 mg/kg intravenous bolus plus 2 mg.kg-1.hr-1 intravenous infusion) was injected and two additional trials performed. Eight cats also underwent two trials after propranolol (0.2 mg/kg) administered while flecainide infusion was maintained. Flecainide decreased heart rate and blood pressure and slightly prolonged JTc (9%, p < 0.05). It markedly augmented QRS duration (61%, p < 0.0001), which was increased by an additional 61% (p < 0.0001) during sympathetic stimulation. VF was observed in 8 animals and never after flecainide (p < 0.05). However, after drug administration all cats had VT (2 nsVT and 6 sVT), and 5 required cardiac massage. Flecainide did not prevent the occurrence of nsVT in 6 cats, and it worsened arrhythmias by inducing VT (4 nsVT and 2 sVT) in 6 cats with only PVCs or without arrhythmias in the control trials. Propranolol, administered while flecainide infusion was maintained, prevented the increase in heart rate and the marked QRS prolongation during sympathetic stimulation (4 +/- 3 vs 52 +/- 16 msec, p < 0.05) and abolished the proarrhythmic effect of flecainide in 4 of 5 animals. Thus flecainide, despite an antifibrillatory effect, does not prevent and actually may favor the occurrence of sVT during acute myocardial ischemia and enhanced sympathetic activity. Propranolol, by countering the increase in heart rate during sympathetic stimulation, prevented the rate-dependent conduction delay and abolished the proarrhythmic effect of flecainide. The exacerbation, whenever a transient ischemic episode is accompanied by elevated sympathetic activity, of the ischemia-induced conduction delay caused by flecainide may in part explain the mortality data in the Cardiac Arrhythmia Suppression Trial.
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PMID:Malignant arrhythmias and acute myocardial ischemia: interaction between flecainide and the autonomic nervous system. 752 95

The antifibrillatory effects of flecainide 1 mg/kg + 0.05 mg/kg/min intravenously (i.v.), bretylium 6 mg/kg i.v., D-sotalol 2 mg/kg + 0.1 mg/kg/min i.v., and E-4031, a new class III drug, 50 micrograms/kg + 5 micrograms/kg/min i.v. were compared with three different methods of determining ventricular fibrillation threshold (VFT) in anesthetized open-chest dogs. In protocol 1, VFT was determined with 2-S, 50-Hz continuous pulses. Flecainide (n = 7) prolonged intraventricular conduction time (CT) and ventricular effective refractory period (ERP) and increased VFT significantly. Bretylium (n = 6) prolonged ERP slightly, but did not increase VFT significantly. Both D-sotalol (n = 6) and E-4031 (n = 6) prolonged ERP and increased VFT. In protocol 2, VFT was determined with the extrastimulus technique in dogs, with localized ventricular necrosis produced with protease. Flecainide (n = 10), D-sotalol (n = 8), and E-4031 (n = 8) restored VFT, which had been decreased by protease injection, to the baseline level, whereas bretylium (n = 8) did not. In protocol 3, the train pulse method with 100-Hz train pulses covering the vulnerable period was used in the same dogs used for protocol 2. Flecainide, bretylium, and D-sotalol increased VFT, but E-4031 did not. The antifibrillatory effects of class III drugs differ depending on the method of VFT determination. The present data suggest that the antifibrillatory effects of antiarrhythmic drugs should be assessed by different methods of VFT determination.
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PMID:Antifibrillatory effects of class III antiarrhythmic drugs: comparative study with flecainide. 768 97

We wished to examine selected class I antiarrhythmic agents for their potential to exhibit proarrhythmic or antifibrillatory actions. Quinidine, lidocaine, aprindine, and flecainide were evaluated in an experimental model that made use of rabbit isolated perfused heart. Hearts were stabilized with oxygenated buffer (95% O2/5% CO2) with or without pinacidil (1.25 microM) and then were subjected to hypoxia (95% N2/5% CO2) for 12 min, followed by 40-min normoxic perfusion (95% O2/5% CO2). Test drugs were added to the perfusion medium 5 min before hypoxia was induced. Prevention of spontaneous ventricular fibrillation (VF) was determined. To characterize the electrophysiologic effects of the selected antiarrhythmic agents, we determined the changes in threshold current and effective refractory period (ERP) before and after drug treatment. Addition of the potassium channel agonist, pinacidil, to the perfusion medium invariably resulted in VF during the hypoxic interval or shortly after reoxygenation. Pretreatment of the heart with glibenclamide prevented pinacidil-induced VF. Quinidine, aprindine, lidocaine, and flecainide each were studied at a single concentration. The respective drug concentrations were selected to produce comparable changes in ventricular refractory period. Of the class I agents selected for study, only quinidine prolonged the ventricular ERP and provided significant protection against pinacidil-induced VF. In contrast, aprindine and lidocaine decreased ventricular ERP and did not prevent VF induced by the combination of pinacidil and hypoxia. Quinidine, aprindine, and lidocaine did not exhibit proarrhythmic effects in the presence of hypoxia when pinacidil was not added to the perfusion medium. Flecainide, when added to the perfusion medium without pinacidil elicited proarrhythmic activity leading to VF when the hearts were made hypoxic. Flecainide-induced VF was antagonized by glibenclamide. The data suggest that VF can be provoked by the potassium channel agonist pinacidil or by flecainide under conditions that reduce intracellular ATP concentration. Glibenclamide, a selective antagonist of the KATP channel prevented the profibrillatory actions of pinacidil and flecainide. Quinidine, but not lidocaine and aprindine, prevented VF induced by pinacidil and hypoxia.
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PMID:Antifibrillatory and profibrillatory actions of selected class I antiarrhythmic agents. 768 39

To test whether fatal deterioration of defibrillation efficiency during antiarrhythmic therapy can be prevented by avoiding extreme decrease in ventricular prevented by avoiding extreme decrease in ventricular conduction or toxic plasma drug levels, we determined the defibrillation threshold (DFT) before and during infusion of incremental doses of disopyramide (n = 8), mexiletine (n = 9), or flecainide (n = 9) in anesthetized dogs. Disopyramide did not alter DFT [from 4.4 +/- 1.5 to 4.4 +/- 1.6 J (3.1 +/- 1.2 micrograms/ml)]. Mexiletine tended to increase DFT [from 4.6 +/- 1.2 to 6.1 +/- 2.0 J (1.8 +/- 0.6 micrograms/ml); p < 0.05], and defibrillation eventually was unsuccessful in 3 of the 9 dogs. Although the plasma mexiletine level before refractory fibrillation was far beyond the human therapeutic range, prolongation of intraventricular conduction time (CT) was moderate (16 +/- 3%). Flecainide increased DFT from 4.2 +/- 1.3 to 6.1 +/- 1.5 J at a plasma level of 1.04 +/- 0.37 micrograms/ml (p < 0.0005). In 3 of 5 dogs that developed refractory fibrillation, plasma flecainide level before terminal ventricular fibrillation (VF) was not toxic, but prolongation of CT in the 5 dogs was remarkable (30 +/- 9%). Thus, VF resistant to defibrillation is not necessarily associated with both toxic plasma drug level and remarkably decreased conduction. Reliability of these valuables as indicators of fatally deteriorated defibrillation efficiency may vary among antiarrhythmic agents.
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PMID:Prolongation of intraventricular conduction time associated with fatal [correction of fetal] impairment of defibrillation efficiency during treatment with class I antiarrhythmic agents. 775 44

The changes produced by verapamil, bretylium and flecainide in both ventricular fibrillation threshold (VFT) and ventricular repetitive response threshold (VRRT) were studied in 20 closed-chest dogs anaesthetized with pentobarbital. Right ventricle endocardium thresholds were determined using bipolar electrode catheters. Increasing intensity stimulus trains (200 ms, 4 ms, 100 Hz, 1 mA steps) were delivered 50 ms after QRS; VRRT and VFT were calculated before and after drug administration. Three study groups were considered according to the drug assayed: (1) verapamil 0.15 mg.kg-1 n = 6; (2) flecainide 2.0 mg.kg-1 n = 7, and (3) bretylium 10.0 mg.kg-1 n = 7. Flecainide significantly increased VRRT (4.8 +/- 1.4 vs 9.4 +/- 1.5 mA, P < 0.05), but the latter failed to change in the other two groups. VFT remained unchanged with verapamil, increased slightly post-flecainide (10.3 +/- 4.6 vs 12.4 +/- 4.1, P < 0.05 mA) and markedly post-bretylium (10.3 +/- 4.6 vs 17.3 +/- 7.5, P < 0.05). VFT changes were significantly correlated (r = 0.77, P < 0.05) with the effective refractory period changes in the bretylium group. Thus, of the three drugs tested, bretylium induced the greatest VFT increases without modifying VRRT, whereas flecainide affected both parameters. Only in the bretylium series were ERP changes significantly correlated to the corresponding VFT changes. This suggests that ventricular fibrillation threshold increase is not a non-specific property of antiarrhythmic drugs. Changes in ventricular repetitive response threshold may provide additional information.
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PMID:Changes in canine ventricular fibrillation threshold induced by verapamil, flecainide and bretylium. 850 66

The antifibrillatory potential of BRL-32872, a novel antiarrhythmic compound with K+ and Ca2+ channel blocking activities, was examined in a minipig model of ischemia-induced arrhythmia. The effects of intravenous (i.v.) BRL-32872 (0.3 and 1.0 mg/kg, n = 8), dofetilide (0.3 mg/kg, n = 8), and flecainide (2.0 mg/kg, n = 8), were investigated on the incidence of ventricular fibrillation (VF) during a 20-min occlusion of the left anterior descending coronary artery (LAD). Ischemia-induced VF occurred in 6 of 9 vehicle-treated pigs. BRL-32872 reduced the incidence of ischemic VF to 13% at 0.3 mg/kg (p < 0.05) and to 0% at 1.0 mg/kg (p < 0.01). Dofetilide also prevented the occurrence of VF (0%, p < 0.01) In contrast, flecainide did not reduce the incidence of VF (63%). Indeed, flecainide shortened the time to onset of VF from 17 +/- 1 min in the vehicle group to 10 +/- 1 min (p < 0.001). The antifibrillatory effects of BRL-32872 and dofetilide were associated with a prolongation of QT interval on ECG. Flecainide did not prolong repolarization, but slowed the ventricular conduction velocity, as shown by significant increases in PR and QRS intervals. During early reperfusion, 1 of 8 surviving pigs in each group treated with BRL-32872 and 4 of 8 in the dofetilide group developed VF. This study demonstrated an antifibrillatory effect of BRL-32872 associated with prolonged ventricular repolarization and showed enhanced efficacy over dofetilide on reperfusion arrhythmias which is most likely a consequence of its Ca2+ blocking activity.
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PMID:Antifibrillatory effects of BRL-32872 in anesthetized Yucatan minipigs with regional myocardial ischemia. 856 27

The purpose of this study was to determine the anisotropic effects of sodium channel blockers on wavelength (WL) and proarrhythmia. In 18 anesthetized, open chest dogs, a 64-electrode array was placed on the left ventricle and the ventricle was constantly paced. Disopyramide, lidocaine or flecainide was intracoronarily administered. Conduction velocity (theta) and activation-recovery interval (ARI) were measured in the longitudinal (L) and transverse (T) directions. Flecainide markedly decreased thetaL, but did not alter thetaT or ARIs in either direction. As a result, the wavelength was significantly shortened only in the L direction. Disopyramide or lidocaine did not show direction-dependent effects on theta or WL. In 3 of 6 dogs with flecainide exposure, ventricular fibrillation (VF) developed. However, no VF occurred with disopyramide or lidocaine. Accordingly, the WL is dependent on the fiber orientation of myocardium. The anisotropic shortening of the WL may explain the character of the proarrhythmia observed with flecainide.
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PMID:Anisotropic effects of sodium channel blockers on the wavelength for ventricular excitation in dogs. 1098 54

The Langendorff-perfused rat heart with regional ischemia is increasingly used for evaluating drugs for prevention of phase-1, ischemia-induced ventricular fibrillation (VF). Surprisingly, the effectiveness of Class I antiarrhythmics has not been characterized in this model. One lower and one higher concentration of quinidine (0.79 and 7.90 microM), lidocaine (3.88 and 12.93 microM), and flecainide (0.74 and 1.48 microM), representing the peak unbound plasma and total blood concentrations, respectively, at "therapeutic" dosage, were evaluated. The left main coronary artery was occluded for 30 min to elicit phase-1 VF, after which reperfusion-induced VF was examined. In hearts perfused with Krebs' solution containing 3 mM K(+), the higher concentrations of quinidine and lidocaine reduced the incidence of phase-1 VF from 92% to 0% and 17% respectively, (each p < 0.05). The lower drug concentrations were ineffective. Flecainide was equi-effective at low and high concentrations, with VF incidence reduced from 92% to 17% (p < 0.05). Neither low nor high concentrations of any of the drugs affected the incidence of reperfusion-induced VF. Using hearts perfused with Krebs' containing 5 mM K(+), sufficient to substantially reduce control phase-1 VF incidence, the experiment was repeated to test for possible proarrhythmic activity. None of the three drugs increased arrhythmia incidence. In this model, it was not possible to suppress ischemia-induced and reperfusion-induced VF with flecainide, lidocaine, or quinidine at concentrations equivalent to peak unbound plasma levels after clinical administration. This may explain the lack of clinical benefit with these drugs against sudden cardiac death. Because none of the drugs were proarrhythmic in ischemic hearts in which arrhythmia susceptibility had been lowered by high K(+), it would seem that clinical proarrhythmia seen with these drugs may not be related to exacerbation of phase-1, ischemia-induced VF.
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PMID:Limited antifibrillatory effectiveness of clinically relevant concentrations of class I antiarrhythmics in isolated perfused rat hearts. 1186 21

Commotio cordis or ventricular fibrillation caused by a blow to the chest is a rare cause of cardiac arrest in a well child. We report a case of a young child falling from a low height landing chest first with rapid onset of unconsciousness, apnoea and cyanosis. Cardiopulmonary resuscitation was given by parents under telephone instruction from an ambulance dispatch centre. On arrival of officers, 7 min after the fall, ventricular fibrillation was present but responded to defibrillation (biphasic 3 J/kg). No clinical or CT evidence of chest or brain trauma was present and investigations (ECGs, cardiac MRI, echocardiography, viral tests, metabolic tests, drug tests, serum electrolytes) did not reveal any cardiac illness or abnormal cardiac anatomy. Specifically, a long QT was absent and a Flecainide challenge for Brugada syndrome was negative. There was no family history of sudden death. No further dysrrhythmia occurred and the child recovered neurologically well after 3 days of therapeutic hypothermia (for cerebral ischaemia) and 7 days of mechanical ventilation.
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PMID:A case of Commotio cordis in a young child caused by a fall. 1816 18

We report the case of a 29-year-old male suffering from recurrent syncope and palpitations. He had a structurally normal heart and his baseline electrocardiogram was normal. His electrophysiologic study revealed an inducible, nonsustained polymorphic ventricular tachycardia on programmed electrical stimulation. With the administration of intravenous Flecainide, there was typical ST-segment elevation in leads V2 and V3, indicative of the Brugada syndrome. He underwent an implantable cardioverter defibrillator implantation. The cardioverter defibrillator delivered an appropriate shock when the patient suffered ventricular fibrillation during follow-up one year later. This report illustrates the role of pharmacologic challenge in the diagnosis of the Brugada syndrome.
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PMID:Brugada syndrome unmasked by sodium channel blockade. 1905 58


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