Document Detail


A potent opiate agonist protects against myocardial stunning during myocardial ischemia and reperfusion in rats.
MedLine Citation:
PMID:  16118547     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
OBJECTIVE: Opioids have a cardioprotective effect during ischemia. Previously, we showed in an ex-vivo model of myocardial ischemia and reperfusion that 2',6'-dimethyltyrosine-D-Arg-Phe-Lys-NH2, a highly potent and long-acting opioid peptide analgesic with fewer side effects than morphine, provides improved cardioprotection compared with morphine. The purpose of this study was to confirm, in an in-vivo model, the cardioprotective effect of 2',6'-dimethyltyrosine-D-Arg-Phe-Lys-NH2. METHODS: Rats (n=6/group) were randomized to 2',6'-dimethyltyrosine-D-Arg-Phe-Lys-NH2 therapy (intravenous 10 nmol bolus 30 min before ligation and 10 nmol/h continuous infusion), morphine (100 nmol bolus and 100 nmol/h infusion), or placebo, and underwent left anterior descending (LAD) ligation for 10 min followed by reperfusion for 30 min. Continuous transesophageal echocardiogram and electrocardiogram were monitored. Fractional shortening and systolic wall thickening of the ischemic area were calculated. Time to recovery of left ventricular function was the duration of time needed for fractional shortening to recover to 90% of baseline following reperfusion. Duration of reperfusion arrhythmia was the time to the cessation of salvo (at least three consecutive premature ventricular contractions (PVCs)) following reperfusion. RESULTS: Time to recovery of left ventricular function was significantly shorter in the 2',6'-dimethyltyrosine-D-Arg-Phe-Lys-NH2 (4.4+/-2.2 min) and morphine groups (6.0+/-2.5 min) than in the controls (10.5+/-2.2 min; p<0.01). The 2',6'-dimethyltyrosine-D-Arg-Phe-Lys-NH2 group showed significantly higher fractional shortening and systolic wall thickening of the ischemic area than the control group. Duration of reperfusion arrhythmia was also significantly shorter in the 2',6'-dimethyltyrosine-D-Arg-Phe-Lys-NH2 (2.8+/-1.7 min) and morphine groups (5.8+/-3.9 min) than in the controls (11.8+/-2.0 min; p<0.05). CONCLUSION: 2',6'-Dimethyltyrosine-D-Arg-Phe-Lys-NH2 provides a cardioprotective effect against myocardial ischemia and reperfusion in vivo.
Authors:
Woohyuk Song; Jinho Shin; Jaeung Lee; Hyunjoong Kim; Dongjoo Oh; Jay M Edelberg; S Chiu Wong; Hazel Szeto; Mun K Hong
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Publication Detail:
Type:  Comparative Study; Journal Article    
Journal Detail:
Title:  Coronary artery disease     Volume:  16     ISSN:  0954-6928     ISO Abbreviation:  Coron. Artery Dis.     Publication Date:  2005 Sep 
Date Detail:
Created Date:  2005-08-24     Completed Date:  2006-02-28     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  9011445     Medline TA:  Coron Artery Dis     Country:  England    
Other Details:
Languages:  eng     Pagination:  407-10     Citation Subset:  IM    
Affiliation:
Department of Internal Medicine, Weill Medical College of Cornell University, New York 10021, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Disease Models, Animal
Echocardiography
Myocardial Reperfusion Injury / complications*
Myocardial Stunning / etiology,  physiopathology,  prevention & control*
Oligopeptides / pharmacology*
Random Allocation
Rats
Rats, Sprague-Dawley
Receptors, Opioid / agonists
Stroke Volume / drug effects
Systole / drug effects,  physiology
Ventricular Function, Left / drug effects
Chemical
Reg. No./Substance:
0/2',6'-dimethyltyrosyl-arginyl-phenylalanyl-lysinamide; 0/Oligopeptides; 0/Receptors, Opioid

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


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