Effects of the gap junction modifier rotigaptide (ZP123) on atrial conduction and vulnerability to atrial fibrillation

Jose M. Guerra, Thomas Everett, Ken W. Lee, Emily Wilson, Jeffrey E. Olgin

Research output: Contribution to journalArticle

103 Citations (Scopus)

Abstract

BACKGROUND - Altered conduction is associated with increased atrial fibrillation (AF) vulnerability in canine models of chronic mitral regurgitation (MR) and heart failure (HF). Rotigaptide (ZP123) augments gap junction conductance, improving cell-to-cell coupling. We studied the effects of rotigaptide on atrial conduction and AF vulnerability in the canine MR and HF models. METHODS AND RESULTS - Twenty-one dogs in 3 groups were studied: control (n=7), chronic MR induced by mitral avulsion (n=7), and HF induced by ventricular tachypacing (n=7). Epicardial mapping of both atria was performed with a 512-electrode array at baseline and at increasing rotigaptide doses (10, 50, and 200 nmol/L). Conduction velocity increased in both atria in control animals and MR animals (maximum percentage increase: 24±5%, 38±6% [P<0.001, <0.001] in the left atrium and 19±9%, 18±3% [P<0.001, <0.001] in the right atrium). Conduction velocity did not change in the left atrium of the HF group and increased minimally in the right atrium (3±3%, 17±5% [P=NS, P=0.001]). AF duration was increased at baseline in MR and HF animals (control: 16±25 seconds, MR: 786±764 seconds, HF: 883±684 seconds; P=0.013). At 50 nmol/L of rotigaptide, duration of AF markedly decreased in the MR animals (96% reduction, P<0.001), reducing AF duration to that of control animals (control: 9±11 seconds, MR: 14±16 seconds, HF: 1622±355 seconds; P=0.04). CONCLUSIONS - Gap junction modulation with rotigaptide reduces AF vulnerability in a canine MR model of AF to a level similar to control animals but does not affect AF vulnerability in the canine HF model. This may be a novel therapeutic target in some forms of AF.

Original languageEnglish (US)
Pages (from-to)110-118
Number of pages9
JournalCirculation
Volume114
Issue number2
DOIs
StatePublished - Jul 2006
Externally publishedYes

Fingerprint

Gap Junctions
Mitral Valve Insufficiency
Atrial Fibrillation
Heart Failure
Heart Atria
Canidae
Epicardial Mapping
rotigaptide
Electrodes
Dogs

Keywords

  • Atrium
  • Conduction
  • Electrophysiology
  • Fibrillation

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Cite this

Effects of the gap junction modifier rotigaptide (ZP123) on atrial conduction and vulnerability to atrial fibrillation. / Guerra, Jose M.; Everett, Thomas; Lee, Ken W.; Wilson, Emily; Olgin, Jeffrey E.

In: Circulation, Vol. 114, No. 2, 07.2006, p. 110-118.

Research output: Contribution to journalArticle

Guerra, Jose M. ; Everett, Thomas ; Lee, Ken W. ; Wilson, Emily ; Olgin, Jeffrey E. / Effects of the gap junction modifier rotigaptide (ZP123) on atrial conduction and vulnerability to atrial fibrillation. In: Circulation. 2006 ; Vol. 114, No. 2. pp. 110-118.
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abstract = "BACKGROUND - Altered conduction is associated with increased atrial fibrillation (AF) vulnerability in canine models of chronic mitral regurgitation (MR) and heart failure (HF). Rotigaptide (ZP123) augments gap junction conductance, improving cell-to-cell coupling. We studied the effects of rotigaptide on atrial conduction and AF vulnerability in the canine MR and HF models. METHODS AND RESULTS - Twenty-one dogs in 3 groups were studied: control (n=7), chronic MR induced by mitral avulsion (n=7), and HF induced by ventricular tachypacing (n=7). Epicardial mapping of both atria was performed with a 512-electrode array at baseline and at increasing rotigaptide doses (10, 50, and 200 nmol/L). Conduction velocity increased in both atria in control animals and MR animals (maximum percentage increase: 24±5{\%}, 38±6{\%} [P<0.001, <0.001] in the left atrium and 19±9{\%}, 18±3{\%} [P<0.001, <0.001] in the right atrium). Conduction velocity did not change in the left atrium of the HF group and increased minimally in the right atrium (3±3{\%}, 17±5{\%} [P=NS, P=0.001]). AF duration was increased at baseline in MR and HF animals (control: 16±25 seconds, MR: 786±764 seconds, HF: 883±684 seconds; P=0.013). At 50 nmol/L of rotigaptide, duration of AF markedly decreased in the MR animals (96{\%} reduction, P<0.001), reducing AF duration to that of control animals (control: 9±11 seconds, MR: 14±16 seconds, HF: 1622±355 seconds; P=0.04). CONCLUSIONS - Gap junction modulation with rotigaptide reduces AF vulnerability in a canine MR model of AF to a level similar to control animals but does not affect AF vulnerability in the canine HF model. This may be a novel therapeutic target in some forms of AF.",
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T1 - Effects of the gap junction modifier rotigaptide (ZP123) on atrial conduction and vulnerability to atrial fibrillation

AU - Guerra, Jose M.

AU - Everett, Thomas

AU - Lee, Ken W.

AU - Wilson, Emily

AU - Olgin, Jeffrey E.

PY - 2006/7

Y1 - 2006/7

N2 - BACKGROUND - Altered conduction is associated with increased atrial fibrillation (AF) vulnerability in canine models of chronic mitral regurgitation (MR) and heart failure (HF). Rotigaptide (ZP123) augments gap junction conductance, improving cell-to-cell coupling. We studied the effects of rotigaptide on atrial conduction and AF vulnerability in the canine MR and HF models. METHODS AND RESULTS - Twenty-one dogs in 3 groups were studied: control (n=7), chronic MR induced by mitral avulsion (n=7), and HF induced by ventricular tachypacing (n=7). Epicardial mapping of both atria was performed with a 512-electrode array at baseline and at increasing rotigaptide doses (10, 50, and 200 nmol/L). Conduction velocity increased in both atria in control animals and MR animals (maximum percentage increase: 24±5%, 38±6% [P<0.001, <0.001] in the left atrium and 19±9%, 18±3% [P<0.001, <0.001] in the right atrium). Conduction velocity did not change in the left atrium of the HF group and increased minimally in the right atrium (3±3%, 17±5% [P=NS, P=0.001]). AF duration was increased at baseline in MR and HF animals (control: 16±25 seconds, MR: 786±764 seconds, HF: 883±684 seconds; P=0.013). At 50 nmol/L of rotigaptide, duration of AF markedly decreased in the MR animals (96% reduction, P<0.001), reducing AF duration to that of control animals (control: 9±11 seconds, MR: 14±16 seconds, HF: 1622±355 seconds; P=0.04). CONCLUSIONS - Gap junction modulation with rotigaptide reduces AF vulnerability in a canine MR model of AF to a level similar to control animals but does not affect AF vulnerability in the canine HF model. This may be a novel therapeutic target in some forms of AF.

AB - BACKGROUND - Altered conduction is associated with increased atrial fibrillation (AF) vulnerability in canine models of chronic mitral regurgitation (MR) and heart failure (HF). Rotigaptide (ZP123) augments gap junction conductance, improving cell-to-cell coupling. We studied the effects of rotigaptide on atrial conduction and AF vulnerability in the canine MR and HF models. METHODS AND RESULTS - Twenty-one dogs in 3 groups were studied: control (n=7), chronic MR induced by mitral avulsion (n=7), and HF induced by ventricular tachypacing (n=7). Epicardial mapping of both atria was performed with a 512-electrode array at baseline and at increasing rotigaptide doses (10, 50, and 200 nmol/L). Conduction velocity increased in both atria in control animals and MR animals (maximum percentage increase: 24±5%, 38±6% [P<0.001, <0.001] in the left atrium and 19±9%, 18±3% [P<0.001, <0.001] in the right atrium). Conduction velocity did not change in the left atrium of the HF group and increased minimally in the right atrium (3±3%, 17±5% [P=NS, P=0.001]). AF duration was increased at baseline in MR and HF animals (control: 16±25 seconds, MR: 786±764 seconds, HF: 883±684 seconds; P=0.013). At 50 nmol/L of rotigaptide, duration of AF markedly decreased in the MR animals (96% reduction, P<0.001), reducing AF duration to that of control animals (control: 9±11 seconds, MR: 14±16 seconds, HF: 1622±355 seconds; P=0.04). CONCLUSIONS - Gap junction modulation with rotigaptide reduces AF vulnerability in a canine MR model of AF to a level similar to control animals but does not affect AF vulnerability in the canine HF model. This may be a novel therapeutic target in some forms of AF.

KW - Atrium

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KW - Electrophysiology

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