Allopurinol improves myocardial efficiency in patients with idiopathic dilated cardiomyopathy

Thomas P. Cappola, David A. Kass, Gregory S. Nelson, Ronald D. Berger, Gisele O. Rosas, Zoulficar A. Kobeissi, Eduardo Marbán, Joshua M. Hare

Research output: Contribution to journalArticle

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 (MVo2), peak rate of rise of left ventricular pressure (dP/dtmax), stroke work (SW), and efficiency (dP/dtmax/MVo2 and SW/MVo2) 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 MVo2 (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/MVo2, 22±9%, n=9; SW/MVo2, 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.

Original languageEnglish (US)
Pages (from-to)2407-2411
Number of pages5
JournalCirculation
Volume104
Issue number20
DOIs
StatePublished - Nov 13 2001

Keywords

  • Free radicals
  • Heart failure
  • Hemodynamics

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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  • Cite this

    Cappola, T. P., Kass, D. A., Nelson, G. S., Berger, R. D., Rosas, G. O., Kobeissi, Z. A., Marbán, E., & Hare, J. M. (2001). Allopurinol improves myocardial efficiency in patients with idiopathic dilated cardiomyopathy. Circulation, 104(20), 2407-2411. https://doi.org/10.1161/hc4501.098928