Document Detail

Allopurinol enhances the contractile response to dobutamine and exercise in dogs with pacing-induced heart failure.
MedLine Citation:
PMID:  11156889     Owner:  NLM     Status:  MEDLINE    
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.
T Ukai; C P Cheng; H Tachibana; A Igawa; Z S Zhang; H J Cheng; W C Little
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Circulation     Volume:  103     ISSN:  1524-4539     ISO Abbreviation:  Circulation     Publication Date:  2001 Feb 
Date Detail:
Created Date:  2001-02-22     Completed Date:  2001-05-24     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  0147763     Medline TA:  Circulation     Country:  United States    
Other Details:
Languages:  eng     Pagination:  750-5     Citation Subset:  IM    
Cardiology Section, Wake Forest University School of Medicine, Medical Center Boulevard, Winston-Salem, NC, USA.
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MeSH Terms
Allopurinol / pharmacology*
Blood Pressure / drug effects
Cardiac Pacing, Artificial / adverse effects
Cardiotonic Agents / pharmacology
Dobutamine / pharmacology*
Drug Interactions
Free Radical Scavengers / pharmacology
Heart Diseases / etiology,  physiopathology*
Heart Rate / drug effects
Myocardial Contraction / drug effects*
Physical Conditioning, Animal / physiology
Grant Support
Reg. No./Substance:
0/Cardiotonic Agents; 0/Free Radical Scavengers; 315-30-0/Allopurinol; 34368-04-2/Dobutamine

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