Document Detail


Effects of adenosine and acadesine on interstitial nucleosides and myocardial stunning in the pig.
MedLine Citation:
PMID:  10535674     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
5-Amino-4-imidazolecarboxamide riboside (AICAr) or acadesine has been proposed to exert cardioprotection by enhancing adenosine production in ischemic myocardium. However, there are conflicting reports on acadesine's effects in ischemic myocardium and few studies in which myocardial adenosine levels have been measured. The purpose of this study was to determine whether acadesine increases interstitial fluid adenosine levels and attenuates myocardial stunning or potentiates the effects of adenosine in the intact pig. In pentobarbital-anesthetized pigs, myocardial stunning was induced by 10 min left anterior descending coronary artery occlusion and 90 min reperfusion. Regional ventricular function was assessed by measuring systolic wall thickening, and interstitial nucleosides were estimated by cardiac microdialysis. Control hearts were compared with hearts treated with acadesine, adenosine, and adenosine plus acadesine. Adenosine pretreatment (100 microg x kg(-1) x min(-1), intracoronary) immediately prior to ischemia increased interstitial adenosine levels 9-fold and improved postischemic functional recovery from a control value of 17.6 +/- 4.1% to 43.6 +/- 3.4% of preischemic systolic wall thickening. In contrast, acadesine (20 mg/kg i.v. bolus 10 min prior to ischemia + 0.5 mg x kg (-1) x min(-1), i.v. infusion through 60 min reperfusion) had no effect on interstitial fluid adenosine levels or the recovery of regional function (21.5 +/- 5.9% recovery), nor were the functional effects of adenosine potentiated by acadesine. These findings indicate that acadesine does not enhance myocardial adenosine levels, attenuate myocardial stunning, or potentiate the cardioprotective effects of adenosine in the pig.
Authors:
R D Lasley; M P Randhawa; J O Hegge; R M Mentzer
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Canadian journal of physiology and pharmacology     Volume:  77     ISSN:  0008-4212     ISO Abbreviation:  Can. J. Physiol. Pharmacol.     Publication Date:  1999 Apr 
Date Detail:
Created Date:  1999-11-04     Completed Date:  1999-11-04     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  0372712     Medline TA:  Can J Physiol Pharmacol     Country:  CANADA    
Other Details:
Languages:  eng     Pagination:  259-67     Citation Subset:  IM    
Affiliation:
Department of Surgery, University of Wisonsin School of Medicine, Madison 53792, USA. rlasley@pop.uky.edu
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MeSH Terms
Descriptor/Qualifier:
Adenosine / analysis,  pharmacology*
Aminoimidazole Carboxamide / analogs & derivatives*,  pharmacology
Animals
Coronary Circulation
Extracellular Space / chemistry*
Female
Heart / drug effects*
Male
Myocardial Stunning / drug therapy*,  physiopathology
Perfusion
Renal Dialysis
Ribonucleosides / pharmacology*
Swine
Grant Support
ID/Acronym/Agency:
HL 34579-08/HL/NHLBI NIH HHS; HL08666-02/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Ribonucleosides; 2627-69-2/acadesine; 360-97-4/Aminoimidazole Carboxamide; 58-61-7/Adenosine

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


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