Circulation. 2001;104:2407-2411
doi: 10.1161/hc4501.098928
doi: 10.1161/hc4501.098928
(Circulation. 2001;104:2407.)
© 2001 American Heart Association, Inc.
Clinical Investigation and Reports |
Allopurinol Improves Myocardial Efficiency in Patients With Idiopathic Dilated Cardiomyopathy
From the Department of Medicine, Division of Cardiology, Johns Hopkins Medical Institutions, Baltimore, Md.
Correspondence to Joshua M. Hare, MD, Johns Hopkins Hospital, Division of Cardiology, 600 N Wolfe St, Carnegie 568, Baltimore, MD 21287-6568. E-mail jhare{at}mail.jhmi.edu
Background— Dilated cardiomyopathy is characterized by an imbalance between left ventricular performance and myocardial energy consumption. Experimental models suggest that oxidative stress resulting from increased xanthine oxidase (XO) activity contributes to this imbalance. Accordingly, we hypothesized that XO inhibition with intracoronary allopurinol improves left ventricular efficiency in patients with idiopathic dilated cardiomyopathy.
Methods and Results— Patients (n=9; ejection fraction, 29±3%) were instrumented to assess myocardial oxygen consumption (M
O2), peak rate of rise of left ventricular pressure (dP/dtmax), stroke work (SW), and efficiency (dP/dtmax/M O2 and SW/MO2) at baseline and after sequential infusions of intracoronary allopurinol (0.5, 1.0, and 1.5 mg/min, each for 15 minutes). Allopurinol caused a significant decrease in MO2 (peak effect, -16±5%; P<0.01; n=9) with no parallel decrease in dP/dtmax or SW and no change in ventricular load. The net result was a substantial improvement in myocardial efficiency (peak effects: dP/dtmax/M O2, 22±9%, n=9; SW/M O2, 40±17%, n=6; both P<0.05). These effects were apparent despite concomitant treatment with standard heart failure therapy, including ACE inhibitors and ß-blockers. XO and its parent enzyme xanthine dehydrogenase were more abundant in failing explanted human myocardium on immunoblot.
Conclusions— These findings indicate that XO activity may contribute to abnormal energy metabolism in human cardiomyopathy. By reversing the energetic inefficiency of the failing heart, pharmacological XO inhibition represents a potential novel therapeutic strategy for the treatment of human heart failure.
Key Words: heart failure • hemodynamics • free radicals
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