Document Detail


Pharmacologic evidence for the involvement of central and peripheral opioid receptors in the cardioprotective effects of fentanyl.
MedLine Citation:
PMID:  17000787     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: We investigated the involvement of central and peripheral opioid receptors (OR) in the cardioprotective effects of fentanyl (FENT) in a model of myocardial ischemia/reperfusion injury associated with pharmacologically induced sympathetic overactivity in anesthetized rabbits. METHODS: Central sympathetic stimulation was achieved through intracerebroventricular injection of l-glutamate in animals submitted to 35 min of coronary occlusion followed by 120 min of reperfusion. Rabbits received naloxone HCl intracerebroventricularly or naloxone methiodide IV, a quaternary compound that does not cross the blood-brain barrier, 5 min before FENT treatment (5 or 50 microg/kg, IV). RESULTS: Infarct area was reduced only by FENT 50 (from 51% +/- 2% to 24% +/- 2%). This protective effect was abolished by peripheral (42% +/- 4%), but not central, OR blockade (32% +/- 3%). The number of premature ventricular complexes during the ischemic period (54 +/- 3) was reduced by FENT 50 (19 +/- 7), an effect blunted by central (40 +/- 3) but not peripheral (18 +/- 7) blockade of OR. During reperfusion, the number of premature ventricular complexes (134 +/- 50) was reduced to 9 +/- 5 by FENT 50 and was prevented by central (42 +/- 4) as well as peripheral (20 +/- 11) OR blockade. The mortality rate (50%) and incidence of ventricular tachycardia (55%) were completely abolished by FENT 50. CONCLUSIONS: We conclude that fentanyl's effects for limiting myocardial ischemic injury are mediated via peripheral ORs while opioid's antiarrhythmic actions are mediated via central OR agonism.
Authors:
Marcos A Lessa; Eduardo Tibiriçá
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Anesthesia and analgesia     Volume:  103     ISSN:  1526-7598     ISO Abbreviation:  Anesth. Analg.     Publication Date:  2006 Oct 
Date Detail:
Created Date:  2006-09-26     Completed Date:  2006-10-26     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  1310650     Medline TA:  Anesth Analg     Country:  United States    
Other Details:
Languages:  eng     Pagination:  815-21     Citation Subset:  AIM; IM    
Affiliation:
Department of Physiology and Pharmacodynamics, Oswaldo Cruz Institute, FIOCRUZ, Rio de Janeiro, Brazil.
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MeSH Terms
Descriptor/Qualifier:
Animals
Arrhythmias, Cardiac / prevention & control
Cardiotonic Agents / pharmacology*
Dose-Response Relationship, Drug
Female
Fentanyl / pharmacology*
Hemodynamics / drug effects
Male
Myocardial Infarction / prevention & control*
Myocardial Ischemia
Myocardial Reperfusion Injury / prevention & control*
Naloxone / pharmacology
Narcotic Antagonists / pharmacology
Rabbits
Receptors, Opioid / antagonists & inhibitors,  drug effects,  physiology*
Chemical
Reg. No./Substance:
0/Cardiotonic Agents; 0/Narcotic Antagonists; 0/Receptors, Opioid; 437-38-7/Fentanyl; 465-65-6/Naloxone

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


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