Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0151744 (myocardial ischemia)
 31,282 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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

Pharmacologic action of antiarrhythmic agents in hypoxia was studied with the microelectrode using the guinea pig papillary muscle. Tyrode solution saturated with 95% O2 and 5% CO2 provided normoxic condition and that with 95% N2 and 5% O2 hypoxic condition. The parameters measured were as follows: 1) Vmax: the maximum rate of rise of the action potential, 2) ERP: effective refractory period, 3) ERP/APD90%: the ratio of effective refractory period to action potential duration at 90% repolarization. [1] When the papillary muscle was perfused more than 15 minutes with the hypoxic solution, irreversible changes ensued inevitably. Accordingly, a perfusion with the hypoxic solution for 15 minutes was succeeded by that with the normoxic solution for 30 minutes. This was then followed by another perfusion with the hypoxic solution. [2] Flecainide was examined in 7 cases. The rate of the depression of Vmax by flecainide was significantly (p less than 0.01) increased in hypoxia (16.3 +/- 4.2%) than in normoxia (7.4 +/- 2.0%). There were no significantly differences in the rate of the change of ERP between both conditions. The rate of ERP/APD90% was significantly (p less than 0.01) increased by flecainide during hypoxia (2.2 +/- 0.8%) than during normoxia (0.1 +/- 2.1%). [3] The depression of Vmax and the increase of ERP/APD90% by flecainide occurred in a dose-dependent manner in normoxia. it was concluded that the depression of Vmax by flecainide over the concentration of 2 micrograms/dl were ascribed to its inhibitory effect on the fast Na channel and that its depressive effects were enhanced during hypoxic condition. This inhibitory action was regarded as the main antiarrhythmic action of flecainide. From the above results, it is expected that flecainide could be effective in the treatment of ventricular arrhythmias in the ischemic heart disease.
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PMID:[A design of the electrophysiological model on the action of antiarrhythmic agent in hypoxic condition and the electrophysiological study of flecainide]. 190 36

Flecainide, a Class IC antiarrhythmic agent, was used in 12 patients with an average age of 57 years to treat spontaneous monomorphic sustained ventricular tachycardia (S-VT, n = 9), with a ventricular rhythm of 203 +/- 41 bpm (5 right bundle branch and 4 left bundle branch block pattern) and non-sustained ventricular tachycardia (NS-VT, n = 3). The patients had ischaemic heart disease (n = 5, including 2 cases of aneurysm), idiopathic dilated cardiomyopathy (n = 1), ventricular dysplasia (right, n = 1; left n = 2; biventricular, n = 1). The remaining 2 patients had no overt cardiac disease on coronary angiography. None of the patients had signs of cardiac failure; the left ventricular ejection fraction was 0.49 +/- 0.7. Before treatment, programmed ventricular stimulation (PVS) induced 12 S-VT (214 +/- 41 bpm) which reproduced the clinical VT in 8 out of 10 cases. A second series of electrophysiological studies was performed after an average of 5 weeks treatment with Flecainide 300 mg/day (200-400 mg). It was not possible to induce VT in 2 patients (17% total prevention); NS-VT replaced S-VT in 4 patients (33%); S-VT was less rapid in 5 patients (at least 50 bpm slower) (41%); one patient had S-VT as rapid as before treatment (9%). The 12 patients were prescribed long-term Flecainide therapy. During follow-up there were 4 early (7, 10 and 15 days) and one late recurrence (16 months) (42% failure rate) whilst the other 7 patients had no further attacks of VT (follow-up of 19.1 +/- 5 months) (58% success rate).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Estimation of the long-term efficacy of anti-arrhythmia treatment with flecainide in ventricular tachycardia]. 210 8

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

Our study group included 12 patients (4 males, 8 females), mean age 60 yr, with symptomatic or threatening tachyarrhythmias (Lown classes IV A, B, V); 2 patients were suffering from mitral valve prolapse syndrome, 2 from ischemic heart disease; 4 from cardiac insufficiency caused by hypertensive or ischemic heart disease; 4 had no evident clinical signs of cardiopathy. Patients suffering from: cardiac insufficiency (F.C. III e IV NYHA); II and III degree BAV; atrial flutter and fibrillation; long QT syndrome; acute ischemic heart disease were excluded from the study. During short-term treatment, patients received placebo for four days and subsequently flecainide 200 mg daily for four days. During medium-term treatment patients received flecainide 200 mg daily (for six months). Several Holter/24-hour monitorings were performed for evaluation of therapy. No significant reduction in the number of ectopic ventricular beats (B.E.V.) was found with placebo whereas reductions of B.E.V. number (97% and 95%, respectively) were found during short and medium-term treatment with flecainide. Flecainide produced: changes in Lown class: from IV A, B and V to II and I; a marked reduction of subjective symptoms (dyspnea, giddiness syncope, precordial pain); ECG changes: increases in: PR: 5-25%; QRS: 11-12%; QT: 11-22%. Flecainide produced no pro-arrhythmic effects or changes in echocardiographic ventricular function index. Flecainide can be considered one of the most effective new antiarrhythmic drugs.
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PMID:[Short- and medium-term treatment of ventricular hyperkinetic arrhythmia with flecainide]. 252 12

Flecainide has unusual electrophysiologic properties and a high potency for the suppression of ventricular tachyarrhythmias. Little is known about its inotropic and hemodynamic actions. In isolated rabbit papillary muscle, it produced a concentration-dependent depression of contractile force, the threshold concentration being 1.0 micrograms/ml. In patients undergoing coronary angiography for ischemic heart disease and given 1 (n = 11) and 2 mg/kg (n = 11) of flecainide acetate i.v., there was no change in heart rate or mean arterial pressure. The vehicle in which i.v. flecainide was suspended had no significant effects in 6 patients in whom it was tested. Both doses produced comparable hemodynamic effects irrespective of the level of the left ventricular ejection fraction. The mean right atrial pressure increased by 12% (p less than 0.05) after 1 mg/kg and by 15% (p less than 0.01) after 2 mg/kg of the drug. The corresponding increases in mean wedge pressure were 44% (p less than 0.05) and 33% (p less than 0.05), in mean pulmonary artery pressure 27% (p less than 0.01) and 28% (p less than 0.05), in systemic vascular resistance 10% (p less than 0.05) and 9% (not significant [NS]) and in pulmonary vascular resistance 6% (NS) and 49% (p less than 0.05). Significant decreases in cardiac index (8 and 12%, p less than 0.05), stroke volume index (11 and 15%, p less than 0.01) and stroke work index (12%, p less than 0.05, and 21%, p less than 0.01) as well as in left ventricular ejection fraction (15 and 16%, p less than 0.01) were also induced by the 2 doses of flecainide.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of flecainide on ventricular function: clinical and experimental correlations. 669 22

The Authors present their experience, based on 180 patients, concerning the treatment of chronic ventricular tachycardia. According to the underlying etiology, about 1/3 of the cases were considered idiopathic (most of all in form of salvos), 1/3 were ischemic with a prior myocardial infarction (ventricular tachycardias in the setting of acute myocardial infarction were not considered) and 1/3 had miscellaneous cardiac diseases. Prophylactic treatment of ventricular tachycardia recurrences was divided in three steps: classic antiarrhythmic drugs used in monotherapy (Quinidine or Quinidine-like, betablockers, Verapamil); Amiodarone or recent class I antiarrhythmics (Flecainide, Propafenone); drug combinations. The results of medical treatment were different according to the underlying etiology: the first two steps achieved control of the arrhythmia in 2/3 of patients with idiopathic ventricular tachycardia, in 45% of ventricular tachycardia due to miscellaneous cardiopathy and only in 35% of cases with post-myocardial infarction ventricular tachycardia. Four patients were referred for antiarrhythmic surgery and 3 received a palliative electrical device. During a mean follow-up period of 5 years, there were no deaths in the group with idiopathic ventricular tachycardia, 10% of deaths in the group with miscellaneous cardiopathy and 17% in the group with post-myocardial infarction ventricular tachycardia. Idiopathic ventricular tachycardias seem to bear a minimal risk, and the need to treat them depends only on the severity of functional signs and on the frequency of arrhythmic episodes. In patients with severe underlying cardiopathy, particularly ischemic heart disease, active search for an effective treatment is mandatory, due to the high risk of death.
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PMID:[How and why treat ventricular hyperkinetic arrhythmias]. 673 20

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

Flecainide and pilsicainide, Class IC antiarrhythmic drugs with slow kinetics, were administered to a 64-year-old man experiencing ventricular tachycardia. Both drugs suppressed the arrhythmia, but caused ST segment elevation in leads II, III, and aVF. No evidence of ischemic heart disease was detected. Withdrawal of the drugs eliminated the ST change. Because these drugs frequently are used to treat tachyarrhythmias in patients who may present with chest pain, this rare ECG manifestation of Class IC drugs should be recognized to avoid misdiagnosis of acute inferior myocardial infarction.
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PMID:Class IC antiarrhythmic drugs, flecainide and pilsicainide, produce ST segment elevation simulating inferior myocardial ischemia. 972 64

Flecainide is a class Ic antiarrhythmic agent that has an important role as part of rhythm control strategies in patients with atrial fibrillation (AF). Early clinical data on the use of flecainide showed an increase in arrhythmias and mortality compared with placebo in patients with a previous myocardial infarction and asymptomatic or mildly symptomatic ventricular arrhythmias. These findings only apply to a specific group of patients with left ventricular dysfunction and ischaemic heart disease, but had a negative impact on the use of class Ic antiarrhythmics across all indications and patient groups. The aim of this review was to evaluate the available safety data for flecainide in the literature and to assess its current use in patients with AF. Current European guidelines now recommend the use of flecainide in carefully selected groups of patients with AF who do not have structural heart disease. This includes for the cardioversion of recent-onset AF, pretreatment prior to direct current cardioversion, out-of-hospital acute oral therapy ('pill-in-the-pocket' approach) and for the ongoing maintenance of sinus rhythm. Potential cardiac adverse effects of flecainide include proarrhythmia, conduction abnormalities and negative inotropic effects. Dizziness is the most frequent non-cardiac side effect, followed by blurred vision and difficulty focusing; these are almost all mild, transient and tolerable. Data from recent clinical trials in patients with supraventricular arrhythmias suggest that flecainide has a good tolerability profile in groups of appropriately selected patients. Caution is required when using flecainide in patients with renal dysfunction, and there are a number of drug interactions, but these are well documented and manageable. Overall, flecainide is a good choice for the pharmacological management of AF. It has a good safety record and low incidence of adverse effects, rare end-organ toxicity and a low risk of ventricular proarrhythmia. To ensure that the benefits of treatment outweigh any potential risks, careful patient selection and monitoring is required.
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PMID:Safety of flecainide. 2243 43


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