Effect of Allopurinol on Oxidative Stress and Hypoxic Adaptation Response During Surgical Correction of Tetralogy of Fallot

ABSTRACT: to analyze the role of allopurinol in reducing the ischemia-reperfusion injury, and to confrm 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 frst 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-α, 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-α 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 signifcant 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 signifcant. On the other hand, there was no signifcant change of MDA concentration in the allopurinol group. Expression of HIF-1α in TF patients decreased signifcantly (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). Conclusion: 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-α, SOD, and MDA concentration in blood. There was a decrease in HIF-1α concentration in cardiomyocytes of the right ventricle during ischemic phase.
Key words: allopurinol, tetralogy of fallot, reactive oxygen species, superoxide dismutase, TNF-a, HIF-1
Author: Fathema D. Rachmat, Jusuf Rachmat, Sudigdo Sastroasmoro, Septelia I. Wanandi
Journal Code: jpkedokterangg130256