Allopurinol Improves Myocardial Efficiency in Patients With Idiopathic Dilated Cardiomyopathy
Abstract
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 (MV̇ o 2 ), peak rate of rise of left ventricular pressure (dP/dt max ), stroke work (SW), and efficiency (dP/dt max /MV̇ o 2 and SW/MV̇ o 2 ) 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 MV̇ o 2 (peak effect, −16±5%; P <0.01; n=9) with no parallel decrease in dP/dt max or SW and no change in ventricular load. The net result was a substantial improvement in myocardial efficiency (peak effects: dP/dt max /MV̇ o 2 , 22±9%, n=9; SW/MV̇ o 2 , 40±17%, n=6; both P <0.05). These effects were apparent despite concomitant treatment with standard heart failure therapy, including ACE inhibitors and β-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.
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Extensive evidence supports a role of XO in the development of cardiovascular disease.
“Extensive evidence supports a role of XO in the development of cardiovascular disease (137, 148, 157, 282, 430, 466, 561, 633).”
From Sources of Vascular Nitric Oxide and Reactive Oxygen Species and Their Regulation (2019) · cites this paper as [148]
In small trials, pharmacological inhibition of XO with allopurinol/oxypurinol improved cardiovascular conditions in heart failure, dilated cardiomyopathy, and diabetes.
“In small trials, the pharmacological inhibition of XO with allopurinol/oxypurinol improved cardiovascular conditions in several pathologies, including heart failure (58, 278), dilated cardiomyopathy (148), and diabetes (137, 224).”
From Sources of Vascular Nitric Oxide and Reactive Oxygen Species and Their Regulation (2019) · cites this paper as [148]
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- Authors
- Cappola, T. P., Kass, D. A., Nelson, G. S., Berger, R. D., Rosas, G. O., Kobeissi, Z. A., Marbán, E., & Hare, J. M.
- Affiliations
- Johns Hopkins University (US)
- From the Department of Medicine, Division of Cardiology, Johns Hopkins Medical Institutions, Baltimore, Md.
- Venue
- Circulation
- Published
- 2001-11-13
- Volume
- 104
- Issue
- 20
- Pages
- 2407-2411
- ISSN
- 0009-7322 (ISSN-L)
- 1524-4539
- OpenAlex
- W2129194977
- Cited by
- 436
- References
- 31
- Citations by year
- 2026: 3 · 2025: 9 · 2024: 12 · 2023: 7 · 2022: 12 · 2021: 14 · 2020: 17 · 2019: 12 · 2018: 12 · 2017: 17 · 2016: 12 · 2015: 17 · 2014: 21 · 2013: 27 · 2012: 25
- FWCI
- 11.93
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Circulation (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Johns Hopkins University
- National Institutes of Health
- National Heart, Lung, and Blood Institute (K08HL003238, K08-HL-03238, R01 HL65455, R01HL065455)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Function and Risk Factors
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiomyopathy and Myosin Studies
- Health Sciences › Medicine › Nephrology › Gout, Hyperuricemia, Uric Acid
- Keywords
- allopurinol, idiopathic dilated cardiomyopathy, xanthine oxidase inhibition, myocardial energy metabolism, myocardial oxygen consumption, stroke work, heart failure treatment, xanthine dehydrogenase, oxidative stress
- MeSH terms
- Allopurinol, Cardiomyopathy, Dilated, Enzyme Inhibitors, Female, Hemodynamics, Humans, Male, Middle Aged, Myocardial Contraction, Myocardium, Oxygen Consumption, Xanthine Oxidase, Oxidative Stress, Ventricular Dysfunction, Left
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