Frequency-dependent electrophysiologic effects of amiodarone in humans.

Sager, Philip T.; Uppal, Parveen; Follmer, C H; Antimisiaris, M.; Pruitt, Clara; Singh, Bramah N.

doi:10.1161/01.cir.88.3.1063

Cited by 100 publications

(37 citation statements)

References 62 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…However, it has been reported that some antiarrhythmic drugs induced postrepolarization refractoriness in the myocardium. [13][14][15] Although compared with the class I antiarrhythmic drugs, postrepolarization refractoriness would be less prominent in class III antiarrhythmic drugs, it could modulate the reasonable relationship between the ERP and ARI observed in the control state of the present study. To clarify this point, the same type of analysis was performed in patients treated with dl-sotalol, and the result showed that the ARI in the dl-sotalol group corresponded as well to the ERP as in the control group.…”

Section: Discussionmentioning

confidence: 75%

Correlation Between the Effective Refractory Period and Activation-Recovery Interval Calculated From the Intracardiac Unipolar Electrogram of Humans With and Without dl-Sotalol Treatment

Chinushi

Tagawa²,

Kasai³

et al. 2001

Jpn Circ J

View full text Add to dashboard Cite

eterogeneous distribution of ventricular repolarization can contribute to the construction of the arrhythmogenic substrate of ventricular tachyarrhythmia, and this has been well documentted in experimental studies of optical mapping and/or tridimensional repolarization analysis. 1-3 However, in clinical electrophysiologic studies (EPS), the beat-to-beat change in the distribution of intraventricular repolarization is difficult to analyze.Previous experimental studies reported that the activation -recovery interval (ARI) calculated from the unipolar electrogram was approximate to the local effective refractory period (ERP) under various conditions. 4,5 Thus, analysis of ARIs from intracardiac multipolar electrode catheters may be helpful in assessing the distribution of ventricular refractoriness from a clinical viewpoint. Because it has not been well clarified whether the ARI calculated from human intracardiac electrograms reasonably corresponds to local refractoriness, we examined the relationship between ERP and ARI during clinical EPS. The analysis was performed in patients treated with dl-sotalol, as well as in the control state, because dl-sotalol is commonly used in the treatment of sustained ventricular tachyarrhythmia, and its antiarrhythmic effect is considered to be mediated by prolongation of the refractoriness and homogenization of the dispersion of refractoriness of the heart. 6,7 Therefore, if the ARI calculated from the intracardiac unipolar electrogram was reasonably approximate to the local ERP under treatment with dlsotalol, the therapeutic effect of dl-sotalol could be evaluated by measuring the ARI in EPS. Methods SubjectsNineteen patients were enrolled and of these, an EPS was performed without any medication, except for diuretics In experimental studies and/or human body surface mapping, the activation -recovery interval (ARI) is used as a parameter to estimate local repolarization. However, it has not been clarified whether the ARI calculated from the intracardiac unipolar electrogram of humans reasonably represents the local effective refractory period (ERP). Measurement of ARIs at multiple ventricular sites can be helpful in assessing the dispersion of ventricular refractoriness of humans, so we examined the relationship between ERP and ARI in the control state and under treatment with dl-sotalol during clinical electrophysiologic studies (EPS). Of 19 patients, an EPS was performed in the control state in 12 and during treatment with dl-sotalol in the other 7. Quadripolar electrode catheters with an interelectrode distance of 5 mm were placed at the right atrium and in the right ventricle. Using atrial pacing, the heart rate was increased incrementally by 10 beats/min, and ERP and ARI were measured for each pacing rate. The ERP at the right ventricle was measured by single extrastimulation between the first and third distal electrodes of the catheter in the right ventricle, and the ARI was calculated from the second distal unipolar electrode of the same catheter as the interval between t...

show abstract

Section: Discussionmentioning

confidence: 75%

Correlation Between the Effective Refractory Period and Activation-Recovery Interval Calculated From the Intracardiac Unipolar Electrogram of Humans With and Without dl-Sotalol Treatment

Chinushi

Tagawa²,

Kasai³

et al. 2001

Jpn Circ J

View full text Add to dashboard Cite

show abstract

“…18,19 In humans, the prolongation of repolarization rarely exceeds 10% to 15%, as assessed with surface ECG 20 or monophasic action potential (MAP) recording. 21,22 Early on, Drvota and coworkers 4 performed in vitro experiments suggesting that the effects of DEA on cardiac electrical activity could depend on gene expression. In their extensive 1997 review, Kodama et al 15 expression of Kv1.5 (KCNA5) in rats treated with amiodarone.…”

Section: Comparison With Previous Studiesmentioning

confidence: 99%

Long-Term Amiodarone Administration Remodels Expression of Ion Channel Transcripts in the Mouse Heart

et al. 2004

View full text Add to dashboard Cite

Background-The basis for the unique effectiveness of long-term amiodarone treatment on cardiac arrhythmias is incompletely understood. The present study investigated the pharmacogenomic profile of amiodarone on genes encoding ion-channel subunits. Methods and Results-Adult male mice were treated for 6 weeks with vehicle or oral amiodarone at 30, 90, or 180 mg · kg Ϫ1 · d Ϫ1. Plasma and myocardial levels of amiodarone and N-desethylamiodarone increased dose-dependently, reaching therapeutic ranges observed in human. Plasma triiodothyronine levels decreased, whereas reverse triiodothyronine levels increased in amiodarone-treated animals. In ECG recordings, amiodarone dose-dependently prolonged the RR, PR, QRS, and corrected QT intervals. Specific microarrays containing probes for the complete ion-channel repertoire (IonChips) and real-time reverse transcription-polymerase chain reaction experiments demonstrated that amiodarone induced a dose-dependent remodeling in multiple ion-channel subunits. Genes encoding Na ϩ (SCN4A, SCN5A, SCN1B), connexin (GJA1), Ca 2ϩ (CaCNA1C), and K ϩ channels (KCNA5, KCNB1, KCND2) were downregulated. In patch-clamp experiments, lower expression of K ϩ and Na ϩ channel genes was associated with decreased I to,f , I K,slow , and I Na currents. Inversely, other K ϩ channel ␣-and ␤-subunits, such as KCNA4, KCNK1, KCNAB1, and KCNE3, were upregulated. Conclusions-Long-term amiodarone treatment induces a dose-dependent remodeling of ion-channel expression that is correlated with the cardiac electrophysiologic effects of the drug. This profile cannot be attributed solely to the amiodarone-induced cardiac hypothyroidism syndrome. Thus, in addition to the direct effect of the drug on membrane proteins, part of the therapeutic action of long-term amiodarone treatment is likely related to its effect on ion-channel transcripts. Key Words: antiarrhythmic agents Ⅲ ion channels Ⅲ molecular biology Ⅲ electrophysiology A miodarone, a widely used antiarrhythmic drug, has remarkable efficacy for the treatment of ventricular tachyarrhythmias and atrial fibrillation. However, the basis for its effectiveness is still poorly understood. The pharmacologic profile of this drug is complex, and much remains to be clarified about both short-and long-term actions. Amiodarone has been referred to as a class III antiarrhythmic agent, 1 but it also possesses electrophysiologic characteristics of class I and IV agents and minor class II effects. 2 The drug is also known to modify thyroid function extensively because of its iodinated nature. 3 The question arose as to whether the long-term effects of amiodarone might stem from its molecular interaction with thyroid hormone receptors or other mechanisms. In particular, it has been hypothesized that the effects of amiodarone could depend on modulation of transcript expression in addition to its direct effect on cell membrane channels. 4 Genomic techniques now bring gene expression studies to a genome scale, allowing investigators to examine simultaneous changes in th...

show abstract

“…5,8,22 The multiple ion channel interaction by amiodarone has been speculated to contribute to its minimal reverse use dependency and low incidence of clinical TdP arrhythmias, even in patients who develop TdP on other antiarrhythmics. 5,[22][23][24] Dronedarone, given either long-term or shortterm, has been suggested to possess a similar electrophysiological profile, but the effects of chronic dronedarone on specific cardiac ion channels are still unknown. [7][8][9] Arrhythmic Parameters: Dispersion…”

Section: Van Opstal Et Al Amiodarone In An Animal Model Of Acquired Lmentioning

confidence: 99%

Chronic Amiodarone Evokes No Torsade de Pointes Arrhythmias Despite QT Lengthening in an Animal Model of Acquired Long-QT Syndrome

et al. 2001

View full text Add to dashboard Cite

Background-Amiodarone is an effective antiarrhythmic drug rarely associated with torsade de pointes arrhythmias (TdP).The noniodinated compound dronedarone could resemble amiodarone and be devoid of the adverse effects. In the dog with chronic complete atrioventricular (AV) block (CAVB) and acquired long-QT syndrome, the electrophysiological and proarrhythmic properties of the drugs were compared after 4 weeks of oral treatment. Methods and Results-Amiodarone (nϭ7, 40 mg · kg Ϫ1 · d

show abstract

Frequency-dependent electrophysiologic effects of amiodarone in humans.

Cited by 100 publications

References 62 publications

Correlation Between the Effective Refractory Period and Activation-Recovery Interval Calculated From the Intracardiac Unipolar Electrogram of Humans With and Without dl-Sotalol Treatment

Correlation Between the Effective Refractory Period and Activation-Recovery Interval Calculated From the Intracardiac Unipolar Electrogram of Humans With and Without dl-Sotalol Treatment

Long-Term Amiodarone Administration Remodels Expression of Ion Channel Transcripts in the Mouse Heart

Chronic Amiodarone Evokes No Torsade de Pointes Arrhythmias Despite QT Lengthening in an Animal Model of Acquired Long-QT Syndrome

Contact Info

Product

Resources

About