Allopurinol enhances the contractile response to dobutamine and exercise in dogs with pacing-induced heart failure.
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.


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.
Ukai
T
T
Cardiology Section, Wake Forest University School of Medicine, Medical Center Boulevard, Winston-Salem, NC, USA.
Cheng
C P
CP
Tachibana
H
H
Igawa
A
A
Zhang
Z S
ZS
Cheng
H J
HJ
Little
W C
WC
D000493:Allopurinol / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002304:Cardiac Pacing, Artificial / Q000009:adverse effects; D002316:Cardiotonic Agents / Q000494:pharmacology; D004280:Dobutamine / Q000494:pharmacology*; D004285:Dogs; D004347:Drug Interactions; D016166:Free Radical Scavengers / Q000494:pharmacology; D006331:Heart Diseases / Q000209:etiology / Q000503:physiopathology*; D006339:Heart Rate / Q000187:drug effects; D009200:Myocardial Contraction / Q000187:drug effects*; D010805:Physical Conditioning, Animal / Q000502:physiology
D002316:Cardiotonic Agents; D016166:Free Radical Scavengers; D004280:Dobutamine; D000493:Allopurinol