Effect of acute xanthine oxidase inhibition on myocardial energetics during basal and very high cardiac workstates

Joseph Lee, Qingsong Hu, Abdul Mansoor, Forum D Kamdar, Jianyi J Zhang

Research output: Contribution to journalArticlepeer-review

3 Scopus citations


Myocardial ischemia is associated with reduced myocardial adenosine triphosphate (ATP) and increased free adenosine diphosphate (ADP) similar to the normal heart at very high cardiac workstates (HCW). We examined whether acute xanthine oxidase inhibition (XOI) in vivo can decrease myocardial free ADP in normal hearts functioning at basal cardiac workstates (BCW) or very HCW (catecholamine-induced). Myocardial high-energy phosphate (31P magnetic resonance spectroscopy), blood flow (radioactive microspheres), and oxygen consumption (MVO2) were measured in an open-chest canine model before and after infusion of vehicle or an XO inhibitor (allopurinol or febuxostat; n=10 in each group) during BCW and infusion of dobutamine + dopamine to induce a very HCW. During BCW, both allopurinol and febuxostat resulted in higher phosphocreatine (PCr)/ATP, corresponding to lower ADP levels. During vehicle infusion, HCW caused a decrease of PCr/ATP and an increase in myocardial free ADP. Although XOI did not prevent an increase in free ADP during catecholamine infusion, the values in the allopurinol or febuxostat groups (0.141±0.012 and 0.136±0.011 μmol/g dry wt, respectively) remained significantly less than in the vehicle group (0.180±0.017; P<0.05). Thus, at a given rate of ATP synthesis, XOI decreased the free ADP level needed to drive ATP synthesis, suggesting a more energy-efficient status. As contractile dysfunction in ischemia is characterized by increase of myocardial free ADP and energy deficiency, the data suggest that XOI might be a potential therapy for improving energy efficiency during myocardial ischemia.

Original languageEnglish (US)
Pages (from-to)504-513
Number of pages10
JournalJournal of cardiovascular translational research
Issue number4
StatePublished - Aug 1 2011


  • Allopurinol
  • Febuxostat
  • Magnetic resonance spectroscopy
  • Myocardial high-energy phosphates
  • Reactive oxygen species

Fingerprint Dive into the research topics of 'Effect of acute xanthine oxidase inhibition on myocardial energetics during basal and very high cardiac workstates'. Together they form a unique fingerprint.

Cite this