The DOI matches its Crossref record; 31 of the 31 references it cites were found in a registry or an index.
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.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“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 the citing paper
“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]
Citations
Cites
Oxygen-Derived Free Radicals in Postischemic Tissue Injury
Epstein, F. H., & McCord, J. M. (1985) · New England Journal of Medicine · doi:10.1056/nejm198501173120305 · Cited by 5,399
Validation of a Doppler guide wire for intravascular measurement of coronary artery flow velocity.
Doucette, J. W., Corl, P. D., Payne, H. M., Flynn, A. E., Goto, M., Nassí, M., & Segal, J. (1992) · Circulation · doi:10.1161/01.cir.85.5.1899 · Cited by 1,017
Activation of the Cardiac Calcium Release Channel (Ryanodine Receptor) by Poly-S-Nitrosylation
Xu, L., Eu, J. P., Meissner, G., & Stamler, J. S. (1998) · Science · doi:10.1126/science.279.5348.234 · Cited by 991
Effective arterial elastance as index of arterial vascular load in humans.
Kelly, R. P., Ting, C.-T., Yang, T. M., Liu, C. P., Maughan, W. L., Chang, M.-S., & Kass, D. A. (1992) · Circulation · doi:10.1161/01.cir.86.2.513 · Cited by 832
Self-citationSuga, H. (1990) · Physiological Reviews · doi:10.1152/physrev.1990.70.2.247 · Cited by 744
Enroth, C., Eger, B. T., Okamoto, K., Nishino, T., Nishino, T., & Pai, E. F. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.97.20.10723 · Cited by 733
A Dose-Dependent Increase in Mortality with Vesnarinone among Patients with Severe Heart Failure
Cohn, J. N., Goldstein, S., Greenberg, B., Lorell, B. H., Bourge, R. C., Jaski, B. E., Gottlieb, S. O., McGrew, F. A., DeMets, D. L., & White, B. G. (1998) · New England Journal of Medicine · doi:10.1056/nejm199812173392503 · Cited by 612
Keith, M. E., Geranmayegan, A., Sole, M. J., Kurian, R., Robinson, A., Omran, A., & Jeejeebhoy, K. N. (1998) · Journal of the American College of Cardiology · doi:10.1016/s0735-1097(98)00101-6 · Cited by 560
Elevated Levels of 8-iso-Prostaglandin F2αin Pericardial Fluid of Patients With Heart Failure
Mallat, Z., Philip, I., Lebret, M., Chatel, D., Maclouf, J., & Tedgui, A. (1998) · Circulation · doi:10.1161/01.cir.97.16.1536 · Cited by 458
Campbell, D. L., Stamler, J. S., & Strauss, H. C. (1996) · The Journal of general physiology · doi:10.1085/jgp.108.4.277 · Cited by 441
Single-Beat Estimation of End-Systolic Pressure-Volume Relation in Humans
Senzaki, H., Chen, C.-H., & Kass, D. A. (1996) · Circulation · doi:10.1161/01.cir.94.10.2497 · Cited by 395
Self-citationVitamin C Improves Endothelial Function of Conduit Arteries in Patients With Chronic Heart Failure
Hornig, B., Arakawa, N., Kohler, C., & Drexler, H. (1998) · Circulation · doi:10.1161/01.cir.97.4.363 · Cited by 389
Serum uric acid as an index of impaired oxidative metabolism in chronic heart failure.
Leyva, F., Anker, S., Swan, J. W., Godsland, I., Wingrove, C. S., Chua, T., Stevenson, J., & Coats, A. (1997) · European Heart Journal · doi:10.1093/oxfordjournals.eurheartj.a015352 · Cited by 366
Cardillo, C., Kilcoyne, C. M., Cannon, R. O., Quyyumi, A. A., & Panza, J. A. (1997) · Hypertension · doi:10.1161/01.hyp.30.1.57 · Cited by 246
Ekelund, U. E. G., Harrison, R. W., Shokek, O., Thakkar, R. N., Tunin, R. S., Senzaki, H., Kass, D. A., Marbán, E., & Hare, J. M. (1999) · Circulation Research · doi:10.1161/01.res.85.5.437 · Cited by 239
Self-citationHare, J. M., Loh, E., Creager, M. A., & Colucci, W. S. (1995) · Circulation · doi:10.1161/01.cir.92.8.2198 · Cited by 219
Self-citationNitric oxide inhibits creatine kinase and regulates rat heart contractile reserve.
Gross, W. L., Bak, M. I., Ingwall, J. S., Arstall, M. A., Smith, T. W., Balligand, J., & Kelly, R. A. (1996) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.93.11.5604 · Cited by 199
New targets for heart-failure therapy: endothelin, inflammatory cytokines, and oxidative stress
Givertz, M. M., & Colucci, W. S. (1998) · The Lancet · doi:10.1016/s0140-6736(98)90017-4 · Cited by 143
Enhanced Expression and Activity of Xanthine Oxidoreductase in the Failing Heart
de Jong, J. W., Schoemaker, R. G., de Jonge, R., Bernocchi, P., Keijzer, E., Harrison, R., Sharma, H. S., & Ceconi, C. (2000) · Journal of Molecular and Cellular Cardiology · doi:10.1006/jmcc.2000.1240 · Cited by 120
Ukai, T., Cheng, C., Tachibana, H., Igawa, A., Zhang, Z.-S., Cheng, H.-J., & Little, W. C. (2001) · Circulation · doi:10.1161/01.cir.103.5.750 · Cited by 115
Relation between serum uric acid and lower limb blood flow in patients with chronic heart failure.
Anker, S., Leyva, F., Poole-Wilson, P., Kox, W., Stevenson, J., & Coats, A. (1997) · Heart · doi:10.1136/hrt.78.1.39 · Cited by 95
Novel Myofilament Ca 2+ -Sensitizing Property of Xanthine Oxidase Inhibitors
Pérez, N. G., Gao, W. D., & Marbán, E. (1998) · Circulation Research · doi:10.1161/01.res.83.4.423 · Cited by 95
Doehner, W., Rauchhaus, M., Florea, V. G., Sharma, R., Bolger, A. P., Davos, C. H., Coats, A. J. S., & Anker, S. D. (2001) · American Heart Journal · doi:10.1067/mhj.2001.114367 · Cited by 95
Comparison of ventricular pressure relaxation assessments in human heart failure
Senzaki, H., Fetics, B. J., Chen, C.-H., & Kass, D. A. (1999) · Journal of the American College of Cardiology · doi:10.1016/s0735-1097(99)00362-9 · Cited by 81
Self-citationMak, S. S., & Newton, G. E. (2001) · Circulation · doi:10.1161/01.cir.103.6.826 · Cited by 59
Marco, T. D., Chatterjee, K., Rouleau, J. L., & Parmley, W. W. (1988) · American Heart Journal · doi:10.1016/0002-8703(88)90883-6 · Cited by 47
Alteration in Energetics in Patients With Left Ventricular Dysfunction After Myocardial Infarction
Hayashi, Y., Takeuchi, M., Takaoka, H., Hata, K., Mori, M., & Yokoyama, M. (1996) · Circulation · doi:10.1161/01.cir.93.5.932 · Cited by 38
A Dose-Dependent Increase in Mortality with Vesnarinone Among Patients with Severe Heart Failure
Cohn, J. N., Goldstein, S., Greenberg, B., Lorell, B. H., Bourge, R. C., Jaski, B. E., Gottlieb, S. O., McGrew, F. A., DeMets, D. L., & White, B. G. (1999) · Survey of Anesthesiology · doi:10.1097/00132586-199910000-00011 · Cited by 37
Purification of Xanthine Oxidase from human heart
Abadeh, S., Case, P., & Harrison, R. (1993) · Biochemical Society Transactions · doi:10.1042/bst021099s · Cited by 28
[Changes in xanthine oxidase activity in patients with circulatory failure].
Bakhtiiarov, Z. A. (1989) · PubMed · Cited by 24
Shen, W., Ms, W., & Th, H. (1997) · PubMed · Cited by 18
Cited by
Sorted by citations
Oxygen, oxidative stress, hypoxia, and heart failure
Giordano, F. J. (2005) · Journal of Clinical Investigation · doi:10.1172/jci24408 · Cited by 1,515
Is There a Pathogenetic Role for Uric Acid in Hypertension and Cardiovascular and Renal Disease?
Johnson, R. J., Kang, D., Feig, D. I., Kivlighn, S. D., Kanellis, J., Watanabe, S., Tuttle, K. R., Rodríguez‐Iturbe, B., Herrera-Acosta, J., & Mazzali, M. (2003) · Hypertension · doi:10.1161/01.hyp.0000069700.62727.c5 · Cited by 1,354
Oxidative stress and heart failure
Tsutsui, H., Kinugawa, S., & Matsushima, S. (2011) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00554.2011 · Cited by 1,277
Pacher, P., Nivorozhkin, A., & Szabó, C. (2006) · Pharmacological Reviews · doi:10.1124/pr.58.1.6 · Cited by 1,218
Berry, C. E., & Hare, J. M. (2003) · The Journal of Physiology · doi:10.1113/jphysiol.2003.055913 · Cited by 925
Self-citation
Metadata
- 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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review