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

99 Scopus citations

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

Keywords

  • Contraction
  • Heart failure
  • Mice
  • Myocardial
  • Oxygen

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

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