Chronic treatment with allopurinol boosts survival and cardiac contractility in murine postischemic cardiomyopathy

Linda B. Stull, Michelle K. Leppo, Luke Szweda, Wei Dong Gao, Eduardo Marbán

Research output: Contribution to journalArticle

96 Citations (Scopus)

Abstract

Oxidative stress is a hallmark of systemic illnesses, including heart failure. Nevertheless, the overall importance of radical production in the heart remains conjectural; is it merely a marker of illness, or can intervention alter the progression of disease? This question was addressed by blocking xanthine oxidase (XO), a superoxide-generating enzyme that is upregulated in animal models of heart failure. In a randomized prospective trial design, we administered the XO inhibitor allopurinol orally to mice that had undergone massive myocardial infarction (MI). Cardiac XO activity was elevated in untreated mice after MI; allopurinol suppressed the XO activity to levels comparable to those in sham-operated mice. Eighty-one percent of untreated mice died of advanced heart failure over 2 to 4 weeks of follow-up. Survival doubled in the allopurinol-treated mice, whereas cardiac contractile function (both in vivo and in isolated muscle) was markedly improved. Response to isoproterenol was restored to near-normal levels in the allopurinol group but was attenuated in untreated mice. Oxidative modifications to proteins were prevented in the allopurinol-treated mice. Our findings indicate that targeted blockade of just one source of oxidants, XO, impacts dramatically on the progression of postischemic cardiomyopathy in mice and prevents oxidative protein modifications.

Original languageEnglish (US)
Pages (from-to)1005-1011
Number of pages7
JournalCirculation Research
Volume95
Issue number10
DOIs
StatePublished - Nov 12 2004

Fingerprint

Allopurinol
Cardiomyopathies
Xanthine Oxidase
Heart Failure
Myocardial Infarction
Isoproterenol
Oxidants
Superoxides
Disease Progression
Proteins
Oxidative Stress
Animal Models
Muscles
Enzymes

Keywords

  • Contraction
  • Heart failure
  • Mice
  • Myocardial
  • Oxygen

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

Chronic treatment with allopurinol boosts survival and cardiac contractility in murine postischemic cardiomyopathy. / Stull, Linda B.; Leppo, Michelle K.; Szweda, Luke; Gao, Wei Dong; Marbán, Eduardo.

In: Circulation Research, Vol. 95, No. 10, 12.11.2004, p. 1005-1011.

Research output: Contribution to journalArticle

Stull, Linda B. ; Leppo, Michelle K. ; Szweda, Luke ; Gao, Wei Dong ; Marbán, Eduardo. / Chronic treatment with allopurinol boosts survival and cardiac contractility in murine postischemic cardiomyopathy. In: Circulation Research. 2004 ; Vol. 95, No. 10. pp. 1005-1011.
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