Effect of atrial electrical remodeling on the efficacy of antiarrhythmic drugs: comparison of amiodarone with I(Kr)- and I(to)/IKur-blockade in vivo.

Effect of atrial electrical remodeling on the efficacy of antiarrhythmic drugs: comparison of amiodarone with I(Kr)- and I(to)/IKur-blockade in vivo. Research Abstract Details 

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Effect of atrial electrical remodeling on the efficacy of antiarrhythmic drugs: comparison of amiodarone with I(Kr)- and I(to)/IKur-blockade in vivo. Abstract Text:

Dominik K Linz,Freni Afkham,Gabi Itter,Hartmut ,Klaus J Wirth,Dominik K Linz,Freni Afkham,Gabi Itter,Hartmut ,Klaus J Wirth,

INTRODUCTION: Amiodarone is the gold standard in the prevention of recurrence of atrial fibrillation (AF), but the causes for its superior clinical efficacy are not understood. We hypothesized that atrial electrical remodeling increases the atrial efficacy of amiodarone. METHODS AND RESULTS: We investigated the effect of an acute intravenous dose of amiodarone on atrial refractory periods (AERP) in sinus rhythm (SR) and after 5, 24, and 72 hours of atrial tachypacing in comparison with the I(Kr) blocker dofetilide and the I(to)/IKur blockers AVE1231 and AVE0118 in five instrumented goats. Electrical remodeling progressively increased the AERP-prolonging effect of 3 mg/kg of AVE1231 and AVE0118 (2-fold increase in AERP at 72 hours vs SR, P < 0.01), but strongly decreased that of 10 mug/kg dofetilide (<0.5-fold, P < 0.05, at 300 and 400 ms basic cycle length). After 5 and 24 hours of tachypacing, the effect of 3 mg/kg amiodarone strongly increased (2-fold, P < 0.01 after 24 hours vs SR). This early gain in AERP prolongation was confirmed in anesthetized pigs with 3.5 hours of atrial tachypacing (2.4-fold increase, P < 0.01). At 72 hours of atrial tachypacing in the goat, however, the early gain was lost and the effect of amiodarone was similar again to that in SR. CONCLUSION: Atrial electrical remodeling changed the efficacy of the antiarrhythmic agents in a different way. The favorable efficacy profile of amiodarone during electrical remodeling, particularly the marked increase in AERP prolongation in early electrical remodeling, may explain its superior clinical efficacy over existing antiarrhythmic drugs.

Effect of atrial electrical remodeling on the efficacy of antiarrhythmic drugs: comparison of amiodarone with I(Kr)- and I(to)/IKur-blockade in vivo. Publishing Authors By Initials

DK Linz,F Afkham,G Itter,H ,KJ Wirth,DK Linz,F Afkham,G Itter,H ,KJ Wirth,

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Effect of atrial electrical remodeling on the efficacy of antiarrhythmic drugs: comparison of amiodarone with I(Kr)- and I(to)/IKur-blockade in vivo. Journal Published:

PUBLICATION TYPE: Journal Article

Journal: Journal of cardiovascular electrophysiology

VOLUME: 18

Page Numbers: 1313-20

Journal Abbreviation: J. Cardiovasc. Electrophysiol.

ISSN: 1540-8167

DAY: 4

MONTH: 10

YEAR: 2007

Effect of atrial electrical remodeling on the efficacy of antiarrhythmic drugs: comparison of amiodarone with I(Kr)- and I(to)/IKur-blockade in vivo. Information

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LANGUAGE: eng

NlmUniqueID: 9010756

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AFFILIATION: Sanofi-Aventis Deutschland GmbH, Frankfurt, Germany.

Country: United States

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MEDLINETA: J Cardiovasc Electrophysiol

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