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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Pleomorphic ventricular tachycardia is characterized by QRS complexes with repeated variation in polarity, amplitude, and regularity. When associated with prolongation of the QT interval, the term torsades de pointes is used to describe the arrhythmia. It usually is seen clinically in association with class IA antiarrhythmic drugs such as quinidine and procainamide, bradycardia, hypokalemia, and, much less often, other drugs and electrolyte disorders as well as a result of congenital and neurogenic causes. It also may accompany acute myocardial infarction or ischemia. We describe four patients in whom pleomorphic ventricular tachycardia was observed as the presenting rhythm or during the course of resuscitation in out-of-hospital cardiac arrest. In all four patients, acute myocardial ischemia appeared to be the provocative mechanism. Therapeutic implications include an awareness of the unusual behavior of this arrhythmia, especially its propensity to terminate spontaneously. Such awareness may prevent the delivery of unnecessary defibrillatory shocks.
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PMID:Out-of-hospital pleomorphic ventricular tachycardia and resuscitation: association with acute myocardial ischemia and infarction. 833 47

Although quinidine has been reported to induce QT interval prolongation and torsades de pointes clinically, the only experimental model currently available for quinidine-induced torsades de pointes requires the concurrent use of ischemia, reperfusion and cardiac pacing of the isolated, perfused heart. Our purpose in this study was to determine the circumstances under which quinidine might elicit torsades de pointes consistently in the intact dog. We found that maintenance of therapeutic plasma quinidine concentrations, alone, did not induce the arrhythmia. Rather, arrhythmia induction required the additional application of aconitine, which induces early afterdepolarizations and triggered activity. When aconitine was applied to two epicardial sites in dogs having quinidine-induced QT interval prolongation greater than 10%, torsades de pointes occurred in 80% of instances. When QT prolongation was less than 10%, aconitine-induced torsades de pointes was seen in only 21% of animals. Our results suggest that in a previously healthy heart quinidine-induced QT prolongation is, itself, insufficient to induce torsades de pointes consistently, and two independent sites of ectopic activity are needed as well. The ectopic foci appear to modulate one another's impulse initiation or activation sequence, thereby giving rise to the classical "twisting of the points" associated with the arrhythmia.
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PMID:A canine model of torsades de pointes. 246 11

Electrophysiologic studies were performed in 21 patients who had torsades de pointes. This ventricular tachyarrhythmia, characterized by rapid (200-250 beats/min) and irregular paroxysms and progressively varying QRS amplitude and polarity, occurred in the absence of electrolyte disturbance, antiarrhythmic drug therapy or acute ischemia. The QTc interval was prolonged in seven of 21 patients. Electrophysiologic study included ventricular pacing with the introduction of one to three extrastimuli and rapid ventricular pacing. The effect of i.v. procainamide or quinidine in these patients was also studied. Torsades de pointes was inducible n 19 of 21 patients. Induced episodes closely resembled spontaneous episodes. Torsades de pointes spontaneously progressed to ventricular tachycardia with a uniform morphology in three patients and to ventricular fibrillation in four. In eight patients, procainamide or quinidine converted torsades de pointes into typical reentrant ventricular tachycardia. Our data suggest that torsades de pointes in this setting may be a rapid reentrant ventricular tachycardia closely related to recurrent sustained ventricular tachycardia and a precursor to ventricular fibrillation and sudden death.
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PMID:Torsades de pointes: electrophysiologic studies in patients without transient pharmacologic or metabolic abnormalities. 747 73

Drugs that prolong cardiac refractoriness exert antiarrhythmic effects, probably by reducing dispersion of refractoriness and thereby reducing the likelihood of reentrant excitation. This electrophysiologic effect can be achieved in fast-response tissues by sodium channel block or by action potential prolongation; drugs with either attribute can exert antiarrhythmic effects. However, both types of drugs can also cause proarrhythmic effects. For sodium channel blockers, proarrhythmic actions can be attributed to conduction slowing and include increased frequency of episodes of ventricular tachycardia as well as slowing of atrial flutter with 1:1 atrioventricular conduction and increases in ventricular rate. In addition, sodium channel block has been implicated as the mechanism underlying increased mortality with sodium channel blockers in the Cardiac Arrhythmia Suppression Trial (CAST); some data suggest that intercurrent ischemia increases this risk. For drugs that prolong action potentials, torsades de pointes is the most common proarrhythmic syndrome, occurring most often with underlying bradyarrhythmias and hypokalemia. The mechanism(s) underlying normal refractoriness and its modulation by antiarrhythmic drugs, as well as the mechanism(s) underlying these proarrhythmic syndromes, are discussed.
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PMID:Ionic mechanisms for prolongation of refractoriness and their proarrhythmic and antiarrhythmic correlates. 878 Mar 24

In recent years, the results of large randomized and controlled trials of antiarrhythmic agents for primary and secondary prevention of ventricular tachycardia and ventricular fibrillation have changed perceptions of the actions of antiarrhythmic agents regarding both efficacy and risk. The premature termination of the CAST trials of primary prevention in postinfarct patients highlighted the proarrhythmic risk and inefficacy of the sodium channel blockers (class I action), encainide, flecainide, and moricizine, in patients at relatively low risk for death in the long term. The excess mortality with therapy was attributed to proarrhythmia due to facilitation of reentry, especially during acute ischemia. About the same time, European trials with amiodarone, a complex agent with antiadrenergic action and powerful action to prolong refractoriness (class III action), indicated enhanced survival after infarction with amiodarone but not with agents with class I action. Recent verbal reports of larger and placebo-controlled trials (EMIAT and CAM-IAT) confirm a significant reduction in arrhythmia mortality, possibly with a favorable trend in total mortality. While an older trial with dl-sotalol (class III and beta-blocking actions) showed a trend toward improved survival after infarction, a recent trial with d-sotalol in patients with recent infarction or remote infarction and heart failure was prematurely terminated because of excess mortality attributed to proarrhythmia (torsades de pointes), indicating the importance of beta-blocking properties of a class III agent. A secondary prevention trial (ESVEM) in patients surviving an episode of VT or VF showed significant superiority of dl-sotalol compared to an array of agents that block sodium channels with respect to both efficacy and tolerance. Occurrence rates of arrhythmias treated with drugs tested for efficacy either by suppression of inducible arrhythmias or by suppression of spontaneous ectopy were higher and equivalent for both testing methods. A secondary prevention trial of amiodarone and multiple agents that block sodium channels in survivors of cardiac arrest (CASCADE) showed a significant increased efficacy of amiodarone but poorer long-term tolerance compared with the other agents. Comparative analysis of the results of the various trials suggests that class III action coupled with antiadrenergic action is more efficacious in both primary and secondary prevention of life-threatening ventricular arrhythmias and that lethal proarrhythmias may be the predominant effect in attempts at primary prevention in low-risk populations due to class I or so-called pure class III action.
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PMID:From first class to third class: recent upheaval in antiarrhythmic therapy--lessons from clinical trials. 878 Mar 26

It has been suggested that patients be admitted for the initiation of Class I and Class III antiarrhythmic drugs to avoid serious proarrhythmic consequences. The most clinically significant proarrhythmic response to Class IC agents is likely due to an interaction with acute ischemia, and hospitalization for initiation of drug therapy has little predictive or preventive value. Amiodarone has a low risk of proarrhythmia, and any proarrhythmic reactions are generally delayed. Class IA and Class III antiarrhythmic drugs cause acquired long QT syndrome arrhythmias, which can occur soon after initiation of therapy; however, only about half of the arrhythmic events occur within 3 days of initiation of therapy. It could be argued that all patients should be hospitalized to begin Class IA or Class III drugs; however, this approach has a low yield and is extremely expensive. An alternative is to use Class IA and Class III drugs for patients at low risk of torsades de pointes (e.g., males without heart failure, ventricular tachyarrhythmias, or active coronary disease), in whom hospitalization for drug initiation is not warranted. Higher risk patients are probably better treated with other agents, such as Class IC drugs or amiodarone for women without organic heart disease and amiodarone for patients with heart failure, a history of ventricular tachycardia, or active coronary disease. When a Class IA or Class III drug is required for patient with an increased risk of torsades de pointes, hospital admission for drug initiation may be indicated.
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PMID:Optimal management with Class I and Class III antiarrhythmic drugs should be done in the outpatient setting: protagonist. 1021 May 15

The 4-aminopyridine (4-AP)-sensitive transient outward current (Ito) has been reported to play an important role in the ischemia- or high [Ca2+]o-induced reentrant ventricular arrhythmias. However, the role of 4-AP sensitive Ito in reperfusion arrhythmia remains unknown. Rat hearts were perfused with Tyrode solution (control), and treated with 0.5 micromol/L verapamil, 1 micromol/L glibenclamide, 10 micromol/L E-4031 or 2 mmol/L 4-AP. After a 10-min perfusion, hearts were subjected to 30-min global ischemia followed by 10-min reperfusion. The effects of the ion-channel blockers on the incidence of ventricular tachycardia (VT), torsades de pointes (Tdp) and ventricular fibrillation (VF) during the reperfusion period were investigated. Verapamil and 4-AP abolished VF and Tdp. The incidence of VT was also attenuated by verapamil, but not by 4-AP. Glibenclamide and E-4031 (a blocker of a rapidly activating component of delayed rectifier K+ current) did not affect the incidence of those tachyarrhythmias. Accordingly, (1) the underlying mechanism of VF or Tdp is different from that of VT, and (2) 4-AP sensitive Ito is required for the occurrence of reperfusion Tdp or VF in the present model.
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PMID:4-aminopyridine inhibits the occurrence of ventricular fibrillation but not ventricular tachycardia in the reperfused, P6olated rat heart. 1095 57

Dofetilide has been shown to be effective and safe in maintaining sinus rhythm in patients with persistent atrial fibrillation and congestive heart failure. Because of serious side effects of an increase in the QT interval causing torsades de pointes, dofetilide must be initiated with close monitoring of the QT interval in an inpatient setting. However, little has been reported about conditions surrounding the change in QT interval after the steady state is achieved that may have implications in the safety and efficacy of the drug. We report marked QT prolongation and torsades de pointes in a setting of flash pulmonary edema resulting from acute myocardial ischemia in a patient who was being treated with dofetilide for atrial fibrillation. Our case reminds the clinicians that the adverse and proarrhythmic effects of dofetilide can occur due to changes in the arrhythmic substrate during acute severe ischemia.
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PMID:Marked QT prolongation and torsades de pointes secondary to acute ischemia in an elderly man taking dofetilide for atrial fibrillation: a cautionary tale. 1621 Dec 8

Dronedarone is a noniodinated benzofuran derivative that has been developed to overcome the limiting iodine-associated adverse effects of the commonly used antiarrhythmic drug, amiodarone. It displays a wide cellular electrophysiological spectrum largely similar to amiodarone, inhibiting the potassium currents I(Kr), I(Ks), I(KI), I(KACh), and I(sus), as well as sodium currents and L-type calcium currents in isolated cardiomyocytes. In addition, dronedarone exhibits antiadrenergic properties. In vivo, dronedarone has been shown to be more effective than amiodarone in several arrhythmia models, particularly in preventing ischemia- and reperfusion-induced ventricular fibrillation and in reducing mortality. However, an increased incidence of torsades de pointes with dronedarone in dogs shows that possible proarrhythmic effects of dronedarone require further evaluation. The clinical trails DAFNE, EURIDIS, and ADONIS indicated safety, antiarrhythmic efficacy and low proarrhythmic potential of the drug in low-risk patients. In contrast, the increased incidence of death in the dronedarone group of the discontinued ANDROMEDA trial raises safety concerns for patients with congestive heart failure and moderate to severe left ventricular dysfunction. Dronedarone appears to be effective in preventing relapses of atrial fibrillation and atrial flutter. Torsades de pointes, the most severe adverse effect associated with amiodarone, has not yet been reported in humans with dronedarone. Unlike amiodarone, dronedarone had little effect on thyroid function and hormone levels in animal models and had no significant effects on human thyroid function in clinical trials. In conclusion, dronedarone could be a useful drug for prevention of atrial fibrillation and atrial flutter relapses in low-risk patients. However, further experimental studies and long-term clinical trials are required to provide additional evidence of efficacy and safety of dronedarone.
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PMID:The novel antiarrhythmic drug dronedarone: comparison with amiodarone. 1625 15

We report 2 patients in whom transient marked QT prolongation occurred after successful emergent percutaneous coronary intervention (PCI) for acute coronary syndrome. One patient developed torsades de pointes. In both cases, the QT interval became markedly prolonged within 24 hours after PCI, and this prolongation persisted for 4 days. The T waves had a giant and bizarre negative shape with a prolonged T-wave peak to T-wave end interval. No new-onset ischemia or congenital long QT syndrome was related to the episodes. The patients had not taken any drugs that could have prolonged the QT interval, and their serum potassium levels were within normal limits. Torsades de pointes following successful PCI for acute coronary syndrome is uncommon, but acquired long QT syndrome should be considered and treated in patients in whom giant and bizarre negative T waves and QT prolongation develop after PCI.
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PMID:Torsades de pointes related to transient marked QT prolongation following successful emergent percutaneous coronary intervention for acute coronary syndrome. 1832 36


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