| Effects of the gap junction modifier rotigaptide (ZP123) on atrial conduction and vulnerability to atrial fibrillation. | |
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MedLine Citation:
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PMID: 16818812 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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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Authors:
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Jose M Guerra; Thomas H Everett; Ken W Lee; Emily Wilson; Jeffrey E Olgin |
Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural Date: 2006-07-03 |
Journal Detail:
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Title: Circulation Volume: 114 ISSN: 1524-4539 ISO Abbreviation: Circulation Publication Date: 2006 Jul |
Date Detail:
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Created Date: 2006-07-11 Completed Date: 2006-08-14 Revised Date: 2007-11-14 |
Medline Journal Info:
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Nlm Unique ID: 0147763 Medline TA: Circulation Country: United States |
Other Details:
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Languages: eng Pagination: 110-8 Citation Subset: AIM; IM |
Affiliation:
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Cardiac Electrophysiology, Division of Cardiology and the Cardiovascular Research Institute, University of California, San Francisco, CA 94143, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Anti-Arrhythmia Agents / therapeutic use* Atrial Fibrillation / prevention & control* Disease Models, Animal Disease Susceptibility Dogs Gap Junctions / drug effects* Heart Atria / drug effects, physiopathology Heart Conduction System / drug effects* Oligopeptides / therapeutic use* Tachycardia, Ventricular / drug therapy |
| Grant Support | |
ID/Acronym/Agency:
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R01 HL072854-04/HL/NHLBI NIH HHS; R01-HL072854/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Anti-Arrhythmia Agents; 0/Oligopeptides; 355151-12-1/rotigaptide |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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