Document Detail


Comparison of three different A1 adenosine receptor antagonists on infarct size and multiple cycle ischemic preconditioning in anesthetized dogs.
MedLine Citation:
PMID:  14634049     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
A(1) adenosine receptor (AR) antagonists are effective diuretic agents that may be useful for treating fluid retention disorders including congestive heart failure. However, antagonism of A(1)ARs is potentially a concern when using these agents in patients with ischemic heart disease. To address this concern, the present study was designed to compare the actions of the A(1)AR antagonists CPX (1,3-dipropyl-8-cyclopentylxanthine), BG 9719 (1,3-dipropyl-8-[2-(5,6-epoxynorbornyl)]xanthine), and BG 9928 (1,3-dipropyl-8-[1-(4-propionate)-bicyclo-[2,2,2]octyl]xanthine) on acute myocardial ischemia/reperfusion injury and ischemic preconditioning (IPC) in an in vivo dog model of infarction. Barbital-anesthetized dogs were subjected to 60 min of left anterior descending coronary artery occlusion followed by 3 h of reperfusion, after which infarct size was assessed by staining with triphenyltetrazolium chloride. IPC was elicited by four 5-min occlusion/5-min reperfusion cycles produced 10 min before the 60-min occlusion. Multiple-cycle IPC produced a robust reduction ( approximately 65%) in infarct size; this effect of IPC on infarct size was not abrogated in dogs pretreated with any of the three AR antagonists. Surprisingly, in the absence of IPC, pretreatment with CPX or BG 9928 before occlusion or immediately before reperfusion resulted in significant reductions ( approximately 40-50%) in myocardial infarct size. However, treatment with an equivalent dose of BG 9719 had no similar effect. We conclude that the A(1)AR antagonists BG 9719, BG 9928, and CPX do not exacerbate cardiac injury and do not interfere with IPC induced by multiple ischemia/reperfusion cycles. We discuss the possibility that the cardioprotective actions of CPX and BG 9928 may be related to antagonism of A(2B)ARs.
Authors:
John A Auchampach; Xiaowei Jin; Jeannine Moore; Tina C Wan; Laura M Kreckler; Zhi-Dong Ge; Jayashree Narayanan; Eric Whalley; William Kiesman; Barry Ticho; Glenn Smits; Garrett J Gross
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.     Date:  2003-11-21
Journal Detail:
Title:  The Journal of pharmacology and experimental therapeutics     Volume:  308     ISSN:  0022-3565     ISO Abbreviation:  J. Pharmacol. Exp. Ther.     Publication Date:  2004 Mar 
Date Detail:
Created Date:  2004-02-26     Completed Date:  2004-04-06     Revised Date:  2011-10-04    
Medline Journal Info:
Nlm Unique ID:  0376362     Medline TA:  J Pharmacol Exp Ther     Country:  United States    
Other Details:
Languages:  eng     Pagination:  846-56     Citation Subset:  IM    
Affiliation:
Department of Pharmacology and Toxicology, Medical College of Wisconsin, Milwaukee, WI 53226, USA. jauchamp@mcw.edu
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MeSH Terms
Descriptor/Qualifier:
Adenosine A1 Receptor Antagonists
Anesthesia
Animals
Disease Models, Animal
Dogs
Ischemic Preconditioning, Myocardial
Myocardial Infarction / prevention & control*
Myocardial Ischemia / complications
Myocardial Reperfusion Injury / prevention & control*
Radioligand Assay
Receptor, Adenosine A2A / drug effects,  metabolism
Xanthines / therapeutic use*
Grant Support
ID/Acronym/Agency:
R01 HL060051-08/HL/NHLBI NIH HHS; R01 HL08311/HL/NHLBI NIH HHS; R01 HL60051/HL/NHLBI NIH HHS; T32 HL07792/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/1,3-dipropyl-8-(2-(5,6-epoxy)norbornyl)xanthine; 0/Adenosine A1 Receptor Antagonists; 0/Receptor, Adenosine A2A; 0/Xanthines; 102146-07-6/1,3-dipropyl-8-cyclopentylxanthine
Comments/Corrections

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