© 1999 American Heart Association, Inc.
Integrative Physiology |
Intravenous Allopurinol Decreases Myocardial Oxygen Consumption and Increases Mechanical Efficiency in Dogs With Pacing-Induced Heart Failure
From the Department of Medicine, Cardiology Division, Johns Hopkins Medical Institutions, Baltimore, Md.
Correspondence to Joshua M. Hare, MD, Johns Hopkins Hospital, Cardiology Division, 600 N Wolfe St, Carnegie 568, Baltimore, MD 21287-6568. E-mail jhare{at}welchlink.welch.jhu.edu
Abstract—Allopurinol, an
inhibitor of xanthine oxidase, increases myofilament
calcium responsiveness and blunts calcium cycling in isolated cardiac
muscle. We sought to extend these observations to conscious dogs with
and without pacing-induced heart failure and tested the prediction that
allopurinol would have a positive inotropic effect without increasing
energy expenditure, thereby increasing mechanical efficiency. In
control dogs (n=10), allopurinol (200 mg IV) caused a small positive
inotropic effect; (dP/dt)max increased from 3103±162 to
3373±225 mm Hg/s (+8.3±3.2%; P=0.01), but
preload-recruitable stroke work and ventricular elastance
did not change. In heart failure (n=5), this effect was larger;
(dP/dt)max rose from 1602±190 to 1988±251 mm Hg/s
(+24.4±8.7%; P=0.03), preload-recruitable stroke work
increased from 55.8±9.1 to 84.9±12.2 mm Hg (+28.1±5.3%;
P=0.02), and ventricular elastance rose from
6.0±1.6 to 10.5±2.2 mm Hg/mm (P=0.03).
Allopurinol did not affect myocardial lusitropic properties either in
control or heart failure dogs. In heart failure dogs, but not controls,
allopurinol decreased myocardial oxygen consumption (–49±4.6%;
P=0.002) and substantially increased mechanical
efficiency (stroke work/myocardial oxygen consumption; +122±42%;
P=0.04). Moreover, xanthine oxidase activity was
4-fold increased in failing versus control dog hearts (387±125
versus 78±72 pmol/min · mg–1;
P=0.04) but was not detectable in plasma. These data
indicate that allopurinol possesses unique inotropic properties,
increasing myocardial contractility while
simultaneously reducing cardiac energy requirements. The
resultant boost in myocardial contractile efficiency may prove
beneficial in the treatment of congestive heart failure.
Key Words: myocardial contractility • xanthine oxidase • oxidant stress • heart failure
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