allopurinol and Tetralogy-of-Fallot

To determine effects of allopurinol administration on outcomes following intracardiac repair of tetralogy of Fallot (TOF).. Fifty patients undergoing TOF repair were randomized to 2 groups of 25 each: the allopurinol group (n = 25) and the placebo group (n = 25). Postoperatively, inotropic score, rhythm, duration of mechanical ventilation, cardiac output, intensive care unit (ICU) stay, and hospital stay were assessed. Plasma troponin-I, superoxide dismutase (SOD), interleukin (IL) 1-ß, IL-6, and malondialdehyde were measured serially.. Inotropic score was lower in the allopurinol compared with placebo group (11.04 ± 5.70 vs 17.50 ± 7.83; P = .02). Duration of ICU and hospital stay was lower in the allopurinol group. Plasma levels of SOD preoperative were (2.87 ± 1.21 U/mL vs 4.5 ± 2.08 U/mL; P = .012), immediately following release of crossclamp (2.32 ± 0.98 U/mL vs 5.32 ± 2.81 U/mL; P < .001), and after termination of CPB (2.18 ± 1.0.78 U/mL vs 3.44 ± 1.99 U/mL; P = .003) between the placebo versus allopurinol group, respectively. Postoperative levels of IL1-ß and IL-6 were lower in the allopurinol group. Malondialdehyde levels following CPB were lower in the allopurinol group (11.80 ± 2.94 pg/mL in the placebo vs 9.16 ± 3.02 g/mL in the allopurinol group; P < .001).. Allopurinol administration in patients undergoing intracardiac repair of TOF is associated with reduced inotropic scores, duration of mechanical ventilation, ICU stay, and hospital stay and favorable biochemical markers of inflammation. Further studies in multiple setups are needed before recommending it as a routine practice.

Topics: Allopurinol; Cardiac Surgical Procedures; Child; Child, Preschool; Drug Monitoring; Female; Free Radical Scavengers; Humans; Infant; Intensive Care Units; Interleukins; Length of Stay; Male; Malondialdehyde; Myocardial Contraction; Myocardial Reperfusion Injury; Perioperative Care; Postoperative Complications; Respiration, Artificial; Tetralogy of Fallot; Treatment Outcome; Troponin I

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).. 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).. 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).. 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.

Topics: Adaptation, Physiological; Adolescent; Allopurinol; Biomarkers; Cardiopulmonary Bypass; Child; Child, Preschool; Double-Blind Method; Drug Administration Schedule; Female; Free Radical Scavengers; Humans; Hypoxia; Hypoxia-Inducible Factor 1, alpha Subunit; Infant; Male; Myocardial Reperfusion Injury; Myocardium; Oxidative Stress; Tetralogy of Fallot

Topics: Allopurinol; Data Interpretation, Statistical; Humans; Postoperative Period; Research Design; Tetralogy of Fallot

Previous studies from this institution using human cell cultures have suggested that University of Wisconsin solution is preferred for prolonged hypothermic storage for cardiac transplantation. The primary objective of this study was to evaluate the effectiveness of extended cardiac preservation with University of Wisconsin solution by assessing the time-related changes of purine metabolites using two different models of cold storage. Isolated rat hearts (n = 6/group) or human ventricular myocyte cultures (n = 7 dishes/group) were assessed after 0, 6, 12, and 24 hours in University of Wisconsin solution at 0 degrees C using high-performance liquid chromatography. Adenosine triphosphate content decreased from 18.1 +/- 5.4 to 9.6 +/- 2.7 mumol/g dried weight by 12 hours and to 1.0 +/- 0.6 mumol/g by 24 hours (p < 0.0001 by analysis of variance) in the rat model. Adenosine triphosphate content decreased from 0.64 +/- 0.42 to 0.14 +/- 0.11 nmol/micrograms DNA at 6 hours and to 0.04 +/- 0.03 nmol/micrograms DNA by 24 hours (p < 0.00001) in the cardiomyocytes. Inosine monophosphate content increased from 0.1 +/- 0.2 to 10.8 +/- 1.0 by 24 hours (p < 0.0001) in the rat studies. Inosine monophosphate values tended to increase up to 12 hours (p = 0.06) in the cell cultures and then declined. Adenosine concentration increased from 0.3 +/- 0.3 to 2.3 +/- 0.9 mumol/g at 6 hours and declined thereafter (p < 0.0005) in the rodent hearts. Adenosine concentration increased from 0.03 +/- 0.02 to 1.53 +/- 0.72 nmol/micrograms DNA at 6 hours (p < 0.0001) in the cardiomyocytes.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adenosine; Adenosine Diphosphate; Adenosine Monophosphate; Adenosine Triphosphate; Allopurinol; Animals; Cardioplegic Solutions; Cell Survival; Cryopreservation; Energy Metabolism; Glutathione; Graft Survival; Heart Transplantation; Humans; Insulin; Myocardium; Organ Preservation; Organ Preservation Solutions; Raffinose; Rats; Rats, Sprague-Dawley; Solutions; Tetralogy of Fallot