| Electrophysiologic actions of BRB-I-28 in ischemically injured canine myocardium. | |
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MedLine Citation:
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PMID: 7681911 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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We examined the electrophysiologic actions of BRB-I-28 using two in vivo and two in vitro models of myocardial ischemic injury. In intact canine heart studied 4 days after anterior descending coronary artery occlusion, BRB-I-28 (3 and 6 mg/kg, i.v.) prolonged refractoriness in ischemically injured epicardium to an extent similar to that caused by lidocaine (3 and 6 mg/kg i.v.). BRB-I-28 produced less rate-dependent epicardial delay and, unlike lidocaine, failed to facilitate reentrant arrhythmia formation. Lidocaine and BRB-I-28 (3 and 6 mg/kg i.v.) produced similar rate-dependent prolongation of HV intervals in the normal His-Purkinje system, and produced both tonic and use-dependent conduction block in the ischemically injured His-Purkinje system studied 2 h after anteroseptal coronary artery ligation. In isolated superfused ventricular epicardium studied 1-4 days after anterior descending coronary artery ligation, BRB-I-28 reduced action potential amplitude (APA) and maximum phase 0 upstroke (Vmax) in normal (3.2 mg/L) and ischemically injured (1 and 3.2 mg/L) tissue, with marked tonic and use-dependent conduction block (3.2 mg/L). AP potential duration (APD) was unaltered. In isolated, superfused, ischemically injured canine endocardium studied 24 h after anterior descending coronary artery occlusion, BRB-I-28 (3.2 and 10 ml/L) reduced APA and Vmax and prolonged refractoriness and conduction times in ischemically injured tissue without altering APD. Tonic block was more prominent, and use-dependent block was observed at lower drug concentrations in ischemically injured tissue. The data demonstrate selective conduction depression and prolongation of refractoriness for BRB-I-28 in ischemically injured tissues. Both use-dependent and tonic conduction block contribute to the decrease in conduction observed with BRB-I-28 in ischemically injured myocardium, with more prominent tonic conduction block present in ischemically injured epicardium and His-Purkinje tissue at 2-24 h after coronary artery occlusion than in ischemically injured left ventricular (LV) epicardium studied 4 days after coronary artery occlusion. |
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Authors:
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E Patterson; B J Scherlag; K D Berlin; R Lazzara |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
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Title: Journal of cardiovascular pharmacology Volume: 21 ISSN: 0160-2446 ISO Abbreviation: J. Cardiovasc. Pharmacol. Publication Date: 1993 Apr |
Date Detail:
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Created Date: 1993-05-05 Completed Date: 1993-05-05 Revised Date: 2007-11-14 |
Medline Journal Info:
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Nlm Unique ID: 7902492 Medline TA: J Cardiovasc Pharmacol Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 637-46 Citation Subset: IM |
Affiliation:
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Department of Pharmacology, University of Oklahoma Health Sciences Center, Oklahoma City. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Anti-Arrhythmia Agents / pharmacology* Bicyclo Compounds / pharmacology* Bicyclo Compounds, Heterocyclic* Dogs Electrophysiology Heart / drug effects, physiology* Heart Conduction System / drug effects* Heart Rate / drug effects Lidocaine / pharmacology* Myocardial Infarction / physiopathology* Myocardial Ischemia / physiopathology* |
| Grant Support | |
ID/Acronym/Agency:
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HL-32191/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Anti-Arrhythmia Agents; 0/Bicyclo Compounds; 0/Bicyclo Compounds, Heterocyclic; 137-58-6/Lidocaine; 89398-06-1/7-benzyl 3-thia-7-azabicyclo(3.3.1)nonane |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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