title: Effect of allopurinol on oxidative stress and hypoxic adaptation response during surgical correction of tetralogy of fallot.
abstract: OBJECTIVE
  to analyze the role of allopurinol in reducing the ischemia-reperfusion injury, and to confirm the HIF-1 binding activity changes during the surgical correction of tetralogy of fallot (TF).
  
  
  METHODS
  randomized, double-blind experimental study on patients undergoing surgical correction of TF in the Integrated Cardiovascular Services, Cipto Mangunkusumo Hospital from September 2009-May 2010. Patients were randomly divided into two groups. The first group was given 10 mg/kg body weight of allopurinol 3 times before undergoing operation (n=13) and the other group was given placebo (n=13). Tissue specimen from right ventricular muscle were taken for measurement of reactive oxygen species (ROS) expression and blood specimens from intra-coronary sinus for measurement of TNF-, superoxide dismutase (SOD), and malondialdehyde (MDA).
  
  
  RESULTS
  cardiomyocytes expressing ROS in placebo group increased (41.37±29.29%; 42.61±22.82% and 53.81±25.76%), while in allopurinol group decreased (44.68±19.79%, 56.87±15.50%, and 47.98±22.52%). Concentration of TNF- tend to decrease in allopurinol group, while it tended to increase in the placebo goup. Concentration of SOD increased in the allopurinol group, while in the placebo group there were no significant changes. Concentration of MDA was highly increased in the placebo group (1.75 pmol/mg; 2.37 pmol/mg; 2.72 pmol/mg; 4.82 pmol/mg), but statistically it was not significant. On the other hand, there was no significant change of MDA concentration in the allopurinol group. Expression of HIF-1 in TF patients decreased significantly (p=0.026) from pre ischemic phase to ischemic phase, but it increased in the reperfusion phase (0.95 OD/mg protein, 0.52 OD/mg protein, 0.9 OD/mg protein).
  
  
  CONCLUSIONS
  pre-surgical oral allopurinol treatment reduced ischemia-reperfusion injury during TF surgical correction, as indicated by the decrease in the number of cardiomyocytes expressing ROS, reducing TNF-, SOD, and MDA concentration in blood. There was a decrease in HIF-1 concentration in cardiomyocytes of the right ventricle during ischemic phase.
authors.affiliation: Department of Surgery, Faculty of Medicine, University of Indonesia-Cipto Mangunkusumo Hospital, Jakarta, Indonesia. fathemadr@gmail.com
authors.forename: Fathema D
authors.initials: FD
authors.lastname: Rachmat
authors.forename: Jusuf
authors.initials: J
authors.lastname: Rachmat
authors.forename: Sudigdo
authors.initials: S
authors.lastname: Sastroasmoro
authors.forename: Septelia I
authors.initials: SI
authors.lastname: Wanandi
mesh_terms: D000222:Adaptation, Physiological / Q000187:drug effects*; D000293:Adolescent; D000493:Allopurinol / Q000494:pharmacology / Q000627:therapeutic use*; D015415:Biomarkers / Q000378:metabolism; D002315:Cardiopulmonary Bypass; D002648:Child; D002675:Child, Preschool; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D016166:Free Radical Scavengers / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D000860:Hypoxia / Q000209:etiology / Q000503:physiopathology; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D007223:Infant; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control*; D009206:Myocardium / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D013771:Tetralogy of Fallot / Q000601:surgery*
chemical_list: D015415:Biomarkers; D016166:Free Radical Scavengers; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D000493:Allopurinol