Document Detail


Effects of neuropeptide Y2 receptor blockade on ventricular arrhythmias in rats with acute myocardial infarction.
MedLine Citation:
PMID:  17451678     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Excessive sympathetic activity is believed to be the key arrhythmogenic factor both in the setting of acute myocardial infarction and during chronic heart failure. The aim of this study was to evaluate the effect of neuropeptide Y2 blockade on malignant ventricular arrhythmias in rats with acute myocardial infarction. Vagotonic dose-finding study for neuropeptide Y2 receptor antagonist, (S)-N2-[2-[4-[(R,S)-5,11-dihydro-6(6h)-oxodibenz[b,e]azepin-11-yl]-1-piperazinyl]-2-oxoethyl] cylopentyl] acetyl]-N-[2-[1,2-dihydro-3,5 (4H)-dioxo-1,2-diphenyl-3H-1,2,4-triazol-4-yl]ethyl]-argininamid (AR-H05359) was conducted in guinea pigs (n=50) and rats (n=3). Induction of postinfarction arrhythmias was conducted in Sprague-Dawley rats that were randomized into 3 groups. Neuropeptide Y2 antagonist treated rats (n=7), placebo group (n=10) and amiodarone treated rats (n=8). Myocardial infarction was induced by ligation of the left coronary artery. Computerized telemetric ECG tracings were obtained continuously before induction of myocardial infarction and up to 120 min postinfarction. Occurrence of ventricular arrhythmias was analyzed according to a 10-point arrhythmia score. There was no difference in the arrhythmia scores between the neuropeptide Y2 and the saline group. The amiodarone treated animals had lower score compared to the neuropeptide Y2 and the placebo group (p<0.05). The blockade of receptors does not reduce ventricular arrhythmias in the rats with acute myocardial infarction. Further studies are needed to evaluate whether increasing vagal tonus during sympathetic activation may be valuable anti-arrhythmic strategy to prevent sudden death in patients with myocardial infarction and heart failure.
Authors:
Elmir Omerovic; Truls Råmunddal; Malin Lorentzon; Margareta Nordlander
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2007-03-12
Journal Detail:
Title:  European journal of pharmacology     Volume:  565     ISSN:  0014-2999     ISO Abbreviation:  Eur. J. Pharmacol.     Publication Date:  2007 Jun 
Date Detail:
Created Date:  2007-05-28     Completed Date:  2007-07-26     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  1254354     Medline TA:  Eur J Pharmacol     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  138-43     Citation Subset:  IM    
Affiliation:
Wallenberg Laboratory at Sahlgrenska Academy, Göteborg University, 413 45, Gothenburg, Sweden. elmir@wlab.gu.se
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MeSH Terms
Descriptor/Qualifier:
Animals
Arrhythmias, Cardiac / etiology*,  prevention & control
Guinea Pigs
Male
Myocardial Infarction / complications*
Rats
Rats, Sprague-Dawley
Receptors, Neuropeptide Y / antagonists & inhibitors,  physiology*
Chemical
Reg. No./Substance:
0/Receptors, Neuropeptide Y; 0/neuropeptide Y2 receptor

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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