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Query: UMLS:C0042510 (ventricular fibrillation)
 10,091 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The cardiac electrophysiology of flecainide a new antiarrhythmic agent, was studied in open-chested dogs. At plasma concentrations of 0.4 to 0.7 microgram/ml, flecainide significantly prolonged atrioventricular (AV) conduction. At plasma concentrations greater than 6.5 micrograms/ml, flecainide caused delay throughout the conduction system (77--240%). Low plasma levels of flecainide caused slight prolongation in atrial effective refractory period and AV nodal functional and relative refractory periods. At flecainide levels of 0.7 microgram/ml, ventricular response during atrial fibrillation was significantly slowed. The effects of flecainide on AV nodal and infranodal conduction and refractoriness were significantly enhanced by d,1-propranolol (0.5 mg/kg) but were unaffected by ouabain (0.01 mg/kg). The ventricular fibrillation threshold of supraventricular beats and ventricular premature beats increased with increasing plasma flecainide concentration (122% at 9.3 micrograms/ml and 172% at 1.3 micrograms/ml, respectively). Flecainide slowed ectopic atrial and ventricular pacemakers without affecting sinusor junctional pacemakers.
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PMID:Electrophysiological effects of a new antiarrhythmic agent, flecainide, on the intact canine heart. 9 20

The antiarrhythmic activity of flecainide acetate (R-818), 2 mg/kg, was investigated in anesthetized, open-chest pigs. Ventricular arrhythmias were provoked by reducing the flow in the left anterior descending coronary artery (LAD) to 25% of control during 30 min. During this period ventricular fibrillation occurred in 33% (11 out of 33) of control animals against 12.5% (1 out of 8) of animals treated with flecainide. Ventricular tachycardias were seen in 42% (14 out of 33) of the untreated animals as compared to none of the animals previously treated with flecainide. Total number of ventricular arrhythmias was significantly lower in the treated than in the untreated animals (p less than 0.05). However, when the LAD was occluded completely at its distal part, ventricular fibrillation occurred in all animals (5 untreated and 6 pretreated with flecainide). Time to onset of ventricular fibrillation was the same for both groups of animals, despite a lower incidence of preceding ventricular arrhythmias in the pretreated group. Flecainide depressed myocardial contractility (LVdP/dt max), caused hypotension, and increased QRS width. Both myocardial depression and widening of QRS are related to arterial plasma levels of flecainide. Therefore, a slower infusion rate than the 1 mg/kg per minute used in this study is advisable when myocardial function is impaired.
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PMID:Antiarrhythmic and hemodynamic actions of flecainide acetate (R-818) in the ischemic porcine heart. 9 25

Patients who have sustained greater than or equal to 1 myocardial infarcts are at high risk for sudden death or reinfarction; the risk is highest for those with lowest ventricular ejection fraction, continuing myocardial ischemia and asymptomatic high-density and complex premature ventricular contractions. At present, beta blockers when given prophylactically are the only agents that reduce the incidence of sudden death and reinfarction in survivors of myocardial infarction (MI) in the first 2 years. The beneficial effect was shown to correlate with a reduction in heart rate, the effect being absent or deleterious with beta blockers with marked sympathomimetic activity. The effects of beta blockers on ventricular fibrillation appeared to be dissociated from those on premature ventricular contractions. Trials with calcium antagonists indicate that these drugs had no effect or increased the mortality rate. The divergent effect of beta blockers and calcium antagonists is unexplained but may be due in part to a lack of bradycardiac effect of calcium antagonists; there were no differences in effect among different calcium antagonists. Data from trials involving class I antiarrhythmic agents indicate that agents acting by depression of cardiac conduction are either devoid of effect or produce a modest increase in mortality. Results of the Cardiac Arrhythmia Suppression Trial, employing the newer class I agents flecainide and encainide, were used to determine whether the suppression of premature ventricular contractions in the survivors of acute MI reduces mortality. Flecainide and encainide suppressed premature ventricular contractions greater than 80%, but resulted in an increased mortality rate undoubtedly due to a marked proarrhythmic effect. Whether these data can be extrapolated to all class I agents is uncertain. Preliminary data with class III antiarrhythmic agents suggest that these agents, especially amiodarone, similarly to beta blockers, have the potential to reduce mortality in survivors of MI. Evolving data suggest that in the secondary prevention of morbid events in the survivors of acute MI, the focus must shift away from antiarrhythmic agents that delay conduction and toward beta blockers and antifibrillatory actions resulting from a prolongation of refractoriness.
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PMID:Advantages of beta blockers versus antiarrhythmic agents and calcium antagonists in secondary prevention after myocardial infarction. 169

Flecainide acetate is a recently approved class 1c antiarrhythmic agent indicated for patients with serious ventricular arrhythmias. Because flecainide may be used in patients with automatic implantable defibrillators, we assessed the effect of flecainide on ventricular defibrillation energy requirements in a pig model. Different doses of flecainide maintaining plasma levels in the "subtherapeutic" (six pigs), "therapeutic" (eight pigs), and "supratherapeutic" (eight pigs) range were administered to three groups of pigs. A fourth group (six pigs) served as a time control and was given normal saline only. Episodes of ventricular fibrillation were induced and then terminated using sequential truncated trapezoidal direct current shocks delivered by a tripolar internal defibrillator system. Energy requirements for defibrillation were assessed by measuring defibrillation threshold and also by comparing shifts in the curves relating energy with percent successful defibrillation. Flecainide failed to alter defibrillation requirements at any dose. We conclude that ventricular defibrillation energy requirements are not affected by flecainide in our pig model. Both the defibrillation threshold technique and the comparison of curves relating success of defibrillation to energy yielded similar results suggesting that either can be used to assess energy requirements for defibrillation.
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PMID:Flecainide acetate does not alter the energy requirements for direct ventricular defibrillation using sequential pulse defibrillation in pigs. 246 36

To assess flecainide's ability to suppress ventricular fibrillation during reperfusion, we compared flecainide acetate (2 mg/kg i.v.) with saline placebo in 50 pentobarbital-anesthetized dogs undergoing proximal anterior descending coronary artery occlusion for 20 min followed by sudden release. Treatment selection was blinded and randomized. Flecainide (1 mg/kg) was given for 5 min before ligation and 1 mg/kg over the 20 min occlusion period. Heart rate, blood pressure, myocardium at risk, and QRS duration before drug infusion were similar between treatment groups. Flecainide prolonged the QRS duration 12% with no effect on heart rate or blood pressure. Dogs successfully cardioverted from ventricular fibrillation during occlusion were subjected to reperfusion. One of the 25 dogs treated with placebo fibrillated during occlusion, whereas 13 of the 25 dogs treated with flecainide fibrillated during occlusion and 10 of these 13 could not be resuscitated. Thirteen of the 25 dogs in the placebo group fibrillated during reperfusion, whereas 3 of the remaining 15 dogs in the flecainide treatment group fibrillated during reperfusion. The proarrhythmic effects of flecainide during occlusion confound interpretation of its antiarrhythmic activity during reperfusion. Thus, although flecainide may have prevented ventricular fibrillation during reperfusion, it clearly caused ventricular fibrillation during occlusion in this preparation of acute myocardial ischemia.
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PMID:Effects of flecainide on occlusion and reperfusion arrhythmias in dogs. 247 Sep 90

The effects of flecainide on defibrillation thresholds in 21 open chest, anesthetized dogs were studied. Defibrillation was accomplished using nontruncated exponential pulses delivered through two epicardial patches. Multiple shocks of varying energy were administered after 10 s of ventricular fibrillation in random order. The percent success was plotted against the energy delivered for each dog. A sigmoidal curve was fit to the data and the energy associated with 50% success (E50) calculated. Flecainide (n = 16) or saline solution (n = 5) was then infused and E50 again determined. Flecainide infusion produced mean (+/- standard error of the mean) plasma levels of 610 +/- 111 ng/ml. Defibrillation thresholds were obtainable in 10 of 16 dogs that received flecainide infusion. Flecainide infusion increased E50 by 75% (from 6.5 +/- 1.9 to 11.4 +/- 2.6 J) (P less than 0.05). Infusion of saline solution did not significantly affect defibrillation energy. Of 16 dogs that received flecainide infusion, 12 had one or more complications: 6 had ventricular fibrillation resistant to defibrillation, 6 developed severe hypotension after successful defibrillation and 5 had spontaneous ventricular fibrillation after successful defibrillation. These effects were not seen in any control dogs. Flecainide infusion significantly increases defibrillation threshold and has important adverse arrhythmic and hemodynamic effects in this experimental preparation.
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PMID:Effects of flecainide on defibrillation thresholds in the anesthetized dog. 250 99

Flecainide has been reported to be effective in suppressing chronic ventricular arrhythmias in clinical studies, but the electrophysiological mechanisms of its action are not understood. We therefore studied its effects on re-entrant ventricular arrhythmias in eight dogs with 7 day old infarction. Epicardial mapping and local refractory periods were obtained using 48 channel bipolar electrodes attached to the epicardium. Epicardial conduction velocity was significantly depressed by flecainide (2 mg.kg-1 intravenously), from 49.3 (SD 11.9) cms-1 to 35.3(11.2) cm s-1 (p less than 0.01). Flecainide prolonged effective refractory periods (ERP) in the normal, border and infarct zones: normal (n = 93), from 189.5 (15.9) to 219.3 (17.7) ms, p less than 0.01; border (n = 54) from 187.4(24.0) to 225.2 +/- 32.5 ms, p less than 0.01; and infarct (n = 93), from 197.7 (30.6) to 247.1 (34.2) ms, p less than 0.01. However, the percent change in refractoriness was greater in the infarct zone than in the normal zone, at 25.7(17.1)% v 16.2 (10.3)%, p less than 0.01. Furthermore, an area of functional unidirectional conduction block developed within the infarct zone where the maximal dispersion of ERP was observed. Inducible sustained ventricular tachycardia (SVT) was prevented in one dog and slowed (300 to 150 beats.min-1) in another by flecainide, while ventricular fibrillation remained inducible in one dog. Pro-arrhythmic effects were observed in two of five dogs without inducible SVT. In conclusion, flecainide significantly depressed conduction velocity and prolonged local refractoriness in the epicardial myocardium.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Electrophysiological effects of flecainide in a canine 7 day old myocardial infarction model. 251 8

The antiarrhythmic and antifibrillatory actions of the class IC antiarrhythmic agent flecainide acetate were examined in urethane-anesthetized dogs with recent myocardial infarction. The intravenous administration of flecainide in a loading dose of 1.0 mg/kg (n = 7) or 2.0 mg/kg (n = 6), followed by a maintenance infusion of 1.0 mg/kg/h to achieve plasma drug concentrations considered clinically therapeutic, failed to significantly elevate the electrical threshold current required to provoke ventricular fibrillation at infarct zone, border zone and non-infarct zone stimulation sites in postinfarction dogs. In 8 dogs which responded to baseline programmed stimulation with inducible sustained ventricular tachycardia, flecainide administered as 1.0 or 2.0 mg/kg loading doses followed by a 1.0 mg/kg/h maintenance infusion failed to prevent ventricular tachycardia initiation in any animal tested, although the post-treatment ventricular tachycardia cycle lengths were prolonged compared to baseline values (pre: 178 +/- 11 ms vs post: 202 +/- 17 ms, p less than 0.05). Flecainide administration apparently facilitated the induction of newly sustained ventricular tachycardia in 3 previously noninducible postinfarction dogs. The development of acute posterolateral ischemia at a site remote from previous anterior myocardial infarction resulted in the development of ventricular fibrillation in 4 of 11 (36%) saline-treated postinfarction dogs vs a cumulative 10 of 12 (83%) flecainide-treated, baseline noninducible postinfarction dogs (p less than 0.05 vs saline-treated). The incidence of sudden ischemic ventricular fibrillation was 7 of 7 (100%) among flecainide-treated baseline inducible postinfarction dogs. These data suggest that flecainide acetate may have only limited efficacy in preventing ventricular tachycardia or ventricular fibrillation soon after myocardial infarction.
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PMID:Effects of flecainide acetate on ventricular tachyarrhythmia and fibrillation in dogs with recent myocardial infarction. 311 99

Four patients with recurrent, symptomatic ventricular tachycardia (VT) refractory to conventional antiarrhythmic agents were given flecainide acetate to control arrhythmias. Ventricular stimulation studies were performed in all patients before and 1 to 2 weeks after initiation of oral flecainide therapy. Before flecainide, all patients had easily inducible VT that was morphologically identical to their spontaneously occurring arrhythmia. Flecainide increased the mean PR interval (from 0.17 to 0.23 second), mean QRS duration (from 0.08 to 0.12 second) and mean ventricular effective refractory period (from 235 to 270 ms). Mean corrected QT interval did not change (0.51 second). In 2 patients, VT could not be induced during follow-up stimulation studies. One patient has been treated successfully for 10 months, with no clinically apparent episodes of VT. One patient had recurrent nonsustained VT and was withdrawn from the study as a treatment failure after 6 months of therapy. Two patients had inducible, polymorphous VT that degenerated into ventricular fibrillation that required 2 countershocks before the successful restoration of sinus rhythm. One of these patients had VT stimulation by atrial pacing at a cycle length of 320 ms in the postflecainide electrophysiologic study. VT was not inducible by atrial pacing during this patient's preflecainide study. Thus, sustained oral flecainide administration may precipitate serious electrical instability in susceptible patients, and ventricular stimulation studies and other clinical variables may be useful in selecting patients with recurrent VT who may benefit or may be endangered by oral flecainide therapy.
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PMID:Clinical and electrophysiologic assessment of oral flecainide acetate for recurrent ventricular tachycardia: evidence for exacerbation of electrical instability. 662 66

Clinical and experimental studies indicate that ventricular arrhythmias, especially ventricular fibrillation, are in almost all cases the mechanism for sudden death occurring during the first 24 hours after the onset of an ischaemic myocardial event. Therefore a higher survival rate seems to depend on advances in antiarrhythmic therapy. The present study investigates the efficacy of the new local anaesthetic compound Flecainide in reducing or preventing ventricular arrhythmias and primary ventricular fibrillation, using a standardized experimental canine preparation. Our findings demonstrate that ventricular arrhythmias due to severe transmural myocardial infarction are reduced by 80-90% following the application of Flecainide. In some cases a complete abolition of the arrhythmias can be observed. The striking reduction in ventricular ectopics includes decreases in ventricular salves and R-on-T phenomena, which may lead to sudden death by precipitating ventricular fibrillation. The beneficial antiarrhythmic and antifibrillatory actions of Flecainide affect only the arrhythmias resulting from transmural necrosis of the myocardium ("in-hospital arrhythmias", 2nd-phase arrhythmias"), whereas the incidence of early ventricular arrhythmias, especially ventricular fibrillation occurring in the very inception of myocardial ischaemia ("pre-hospital arrhythmias", "1st-phase arrhythmias") is not prevented. Changes in hemodynamics and contractility due to Flecainide are not severe, even in myocardial infarction. Thus, our results indicate that the application of Flecainide in acute myocardial infarction in man may be successful in reducing therapy-resistant ventricular dysrhythmias.
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PMID:[Antiarrhythmic therapy with flecainide in acute experimental myocardial infarction (author's transl)]. 722 6


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