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(Circulation. 2001;103:750.)
© 2001 American Heart Association, Inc.
Basic Science Reports |
Allopurinol Enhances the Contractile Response to Dobutamine and Exercise in Dogs With Pacing-Induced Heart Failure
From the Cardiology Section, Wake Forest University School of Medicine, Medical Center Boulevard, Winston-Salem, NC.
Background—Superoxide (O2-) 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 Ca2+ 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 (EES) and stroke work–end-diastolic volume relation (MSW). 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 EES (5.0±0.6 versus 3.3±0.6 mm Hg/mL) and MSW. Dobutamine and allopurinol produced greater increases in EES (5.4±0.6 versus 7.4±0.6 mm Hg/mL) and MSW (60.1±7.4 versus 73.7±4.4 mm Hg) than did dobutamine alone. After allopurinol, dP/dtmax, stroke volume, and MSW 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.
Key Words: antioxidants • exercise • heart failure • receptors
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