| Allopurinol enhances the contractile response to dobutamine and exercise in dogs with pacing-induced heart failure. | |
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MedLine Citation:
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PMID: 11156889 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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BACKGROUND: Superoxide (O(2)(-)) generated by enhanced xanthine oxidase (XO) activity may contribute to the increased myocardial oxidative stress in heart failure (CHF). Because blocking XO with allopurinol augments myofilament Ca(2+) sensitivity in reperfusion injury and CHF, we hypothesized that it may improve adrenergic inotropic responsiveness in CHF. METHODS AND RESULTS: We studied the effect of allopurinol on the contractile response to dobutamine and exercise in 7 chronically instrumented conscious dogs before and after producing CHF by rapid pacing. Left ventricular (LV) contractile performance was measured by the slopes of the LV end-systolic pressure-volume relation (E(ES)) and stroke work-end-diastolic volume relation (M(SW)). Before CHF, allopurinol produced no change in LV contractile performance and did not alter the response to dobutamine or exercise. After CHF, allopurinol produced significant (P:<0.05) increases in E(ES) (5.0+/-0.6 versus 3.3+/-0.6 mm Hg/mL) and M(SW). Dobutamine and allopurinol produced greater increases in E(ES) (5.4+/-0.6 versus 7.4+/-0.6 mm Hg/mL) and M(SW) (60.1+/-7.4 versus 73.7+/-4.4 mm Hg) than did dobutamine alone. After allopurinol, dP/dt(max), stroke volume, and M(SW) were higher during CHF exercise. LV diastolic pressures were lower during CHF exercise after allopurinol. CONCLUSIONS: Allopurinol has no discernable effects on LV contractile function or adrenergic responsiveness in normal, conscious animals. In pacing-induced CHF, however, allopurinol improves LV systolic function at rest and during adrenergic stimulation and exercise. |
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Authors:
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T Ukai; C P Cheng; H Tachibana; A Igawa; Z S Zhang; H J Cheng; W C Little |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
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Title: Circulation Volume: 103 ISSN: 1524-4539 ISO Abbreviation: Circulation Publication Date: 2001 Feb |
Date Detail:
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Created Date: 2001-02-22 Completed Date: 2001-05-24 Revised Date: 2007-11-14 |
Medline Journal Info:
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Nlm Unique ID: 0147763 Medline TA: Circulation Country: United States |
Other Details:
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Languages: eng Pagination: 750-5 Citation Subset: IM |
Affiliation:
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Cardiology Section, Wake Forest University School of Medicine, Medical Center Boulevard, Winston-Salem, NC, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Allopurinol
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pharmacology* Animals Blood Pressure / drug effects Cardiac Pacing, Artificial / adverse effects Cardiotonic Agents / pharmacology Dobutamine / pharmacology* Dogs Drug Interactions Free Radical Scavengers / pharmacology Heart Diseases / etiology, physiopathology* Heart Rate / drug effects Myocardial Contraction / drug effects* Physical Conditioning, Animal / physiology |
| Grant Support | |
ID/Acronym/Agency:
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R01-HL-53541/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Cardiotonic Agents; 0/Free Radical Scavengers; 315-30-0/Allopurinol; 34368-04-2/Dobutamine |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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