| ZP123 increases gap junctional conductance and prevents reentrant ventricular tachycardia during myocardial ischemia in open chest dogs. | |
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MedLine Citation:
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PMID: 12776869 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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INTRODUCTION: The aim of this study was to determine if the stable antiarrhythmic peptide (AAP) analogue ZP123 increases gap junctional intercellular conductance and prevents reentrant ventricular tachycardia (VT) during coronary artery occlusion. METHODS AND RESULTS: Voltage clamp experiments demonstrated that 10 nM ZP123 improved gap junctional intercellular conductance by 69% +/- 20% in pairs of guinea pig ventricular myocytes. VT was induced by programmed stimulation in alpha-chloralose anaesthetized open chest dogs 1 to 4 hours after coronary artery occlusion. Three-dimensional activation mapping was done using six bipolar electrograms on each of 23 multipolar needles in the risk zone. When VT was reproducibly induced, dogs were randomly assigned to receive either saline or ZP123 cumulatively at three dose levels (intravenous bolus followed by 30-min infusion per dose). Attempts to induce VT were repeated in each infusion period. Mass spectrometry was used to measure ZP123 plasma concentrations. Twenty-six dogs with reentrant VT were included. ZP123 significantly prevented reentrant VT at all plasma concentrations vs saline: 1.0 +/- 0.2 nM: 6/12 vs 0/12; 7.7 +/- 0.6 nM: 7/13 vs 1/12; and 69.2 +/- 5.4 nM: 9/13 vs 1/13. The preventive effect of ZP123 on reentrant VT was closely correlated to reversal of functional, unidirectional conduction block. ZP123 did not affect effective refractory period, surface ECG parameters, mean arterial pressure, or infarct size. CONCLUSION: The stable AAP analogue ZP123 increased gap junctional intercellular conductance and specifically prevented the induction of reentrant VT during ischemia in a broad dose range without proarrhythmic or hemodynamic side effects. ZP123 is a promising candidate for use in preventing ischemia-induced VT. |
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Authors:
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Dezhi Xing; Anne Louise Kjølbye; Morten S Nielsen; Jørgen S Petersen; Kenneth W Harlow; Niels-Henrik Holstein-Rathlou; James B Martins |
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Publication Detail:
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Type: Comparative Study; Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S. |
Journal Detail:
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Title: Journal of cardiovascular electrophysiology Volume: 14 ISSN: 1045-3873 ISO Abbreviation: J. Cardiovasc. Electrophysiol. Publication Date: 2003 May |
Date Detail:
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Created Date: 2003-06-02 Completed Date: 2003-10-09 Revised Date: 2007-11-15 |
Medline Journal Info:
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Nlm Unique ID: 9010756 Medline TA: J Cardiovasc Electrophysiol Country: United States |
Other Details:
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Languages: eng Pagination: 510-20 Citation Subset: IM |
Affiliation:
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Department of Internal Medicine, University of Iowa College of Medicine and VA Medical Center, Iowa City, Iowa 52242, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Blood Pressure / physiology Cell Membrane / drug effects, metabolism Disease Models, Animal Dogs Dose-Response Relationship, Drug Electrocardiography Female Gap Junctions / drug effects* Heart Block / metabolism, physiopathology, prevention & control Heart Conduction System / drug effects, metabolism, physiopathology Incidence Infusions, Intravenous Male Models, Cardiovascular Myocardial Ischemia / metabolism, physiopathology* Myocytes, Cardiac / drug effects, ultrastructure Oligopeptides / administration & dosage, pharmacology, therapeutic use* Reproducibility of Results Statistics as Topic Tachycardia, Ventricular / metabolism, physiopathology*, prevention & control* |
| Chemical | |
Reg. No./Substance:
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0/Oligopeptides; 355151-12-1/rotigaptide; 81771-37-1/antiarrhythmic peptide |
| Comments/Corrections | |
Comment In:
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J Cardiovasc Electrophysiol. 2003 May;14(5):521-3
[PMID:
12776870
]
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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