| Comparison of three different A1 adenosine receptor antagonists on infarct size and multiple cycle ischemic preconditioning in anesthetized dogs. | |
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MedLine Citation:
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PMID: 14634049 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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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:
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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:
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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:
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Created Date: 2004-02-26 Completed Date: 2004-04-06 Revised Date: 2011-10-04 |
Medline Journal Info:
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Nlm Unique ID: 0376362 Medline TA: J Pharmacol Exp Ther Country: United States |
Other Details:
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Languages: eng Pagination: 846-56 Citation Subset: IM |
Affiliation:
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Department of Pharmacology and Toxicology, Medical College of Wisconsin, Milwaukee, WI 53226, USA. jauchamp@mcw.edu |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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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:
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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:
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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 | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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