allopurinol and Bronchopulmonary-Dysplasia

A role of the oxygen radical generating system hypoxanthine-xanthine oxidase in hypoxia-reoxygenation injury was proposed 15 years ago. In recent years, however, new understanding of hypoxia-reoxygenation injury has been achieved and the significance of other oxygen radical generating systems has been acknowledged too. The hypothesis that an oxygen radical disease exists in preterm infants has recently been strengthened; an important observation is that preterm infants have lower activities of erythrocyte Cu/Zn superoxide dismutase compared to term babies. New actions of oxygen radicals have also been emphasized, and recently it has been demonstrated that the degree of protein oxidation of the lung of newborn infants is associated with chronic lung injury. The new insight into the interaction of oxygen radicals with other systems as excitatory amino acids and the NO system also increases the possibility to understand and hence prevent oxygen radical injury in the preterm infant as well as in adults exposed to an increased load of oxygen radicals.

Topics: Bronchopulmonary Dysplasia; Erythrocytes; Excitatory Amino Acids; Free Radicals; Humans; Infant, Newborn; Nitric Oxide; Reactive Oxygen Species; Respiratory Distress Syndrome, Newborn; Superoxide Dismutase; Xanthine Oxidase

Allopurinol, an inhibitor of xanthine oxidase (an enzyme capable of generating superoxide radicals following hypoxiaischaemia), was investigated in preterm infants to determine its ability to prevent the complications of neonatal intensive care which may be associated with oxidative injury. Four hundred infants of between 24 and 32 weeks' gestation were randomly allocated to receive enteral allopurinol (20 mg/ml) or an equivalent dose of placebo for seven daily doses. At admission, plasma hypoxanthine concentrations were significantly higher in infants who subsequently developed periventricular leucomalacia (PVL), bronchopulmonary dysplasia (BPD), or retinopathy of prematurity (ROP), but there was no difference in the primary endpoint (PVL) between the treated and control groups. The failure of allopurinol prophylaxis in this group of infants is probably related to the complex nature of the pathological processes and to the timing of treatment. If oxidant injury is an important mechanism of cellular injury in these preterm infants, an alternative biochemical modulator would be required, or a combination of agents might be effective.

Topics: Allopurinol; Bronchopulmonary Dysplasia; Drug Administration Schedule; Enzyme Inhibitors; Female; Humans; Hypoxanthines; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Leukomalacia, Periventricular; Male; Retinopathy of Prematurity; Treatment Failure; Xanthine Oxidase

To quantify oxyradical inflammatory markers in serial endotracheal tube aspirates obtained from premature neonates at risk for developing bronchopulmonary dysplasia, and to correlate these parameters with clinical manifestations of the disease.. Prospective cohort study.. Tertiary neonatal intensive care unit.. Twenty-eight intubated, premature infants, with 15 infants displaying simple respiratory distress syndrome and 13 infants eventually developing bronchopulmonary dysplasia.. Endotracheal tube aspirates were collected and clinical severity scores were calculated longitudinally from an inception cohort during the first week of life. Diagnosis of bronchopulmonary dysplasia by standard criteria was recorded at 30 days of life. Various biochemical analyses related to pulmonary oxyradical stress were determined on endotracheal tube aspirates and were normalized according to the magnitude of serum/aspirate urea ratios. The demographic, illness severity, and biochemical characteristics of infants with simple respiratory distress syndrome and those characteristics of infants developing bronchopulmonary dysplasia were evaluated by masked comparison.. Populations of respiratory distress syndrome and bronchopulmonary dysplasia infants could be differentiated during the first week of life by means of the following parameters: gestational age; birth weight; Score of Neonatal Acute Physiology; Neonatal Therapeutic Intervention Scoring System; epithelial lining fluid leukocytes; elastase; myeloperoxidase; xanthine oxidase and catalase enzyme activities; and total sulfhydryls.. Infants with simple respiratory distress syndrome could be segregated from those infants who developed bronchopulmonary dysplasia by the magnitude of the epithelial lining fluid oxyradical inflammation markers. While infants developing bronchopulmonary dysplasia typically exhibited increased concentrations of these markers during the first week of life, those infants with simple respiratory distress syndrome displayed low, uniform, or decreasing values of these markers over this interval. Infants developing bronchopulmonary dysplasia demonstrate an early pulmonary inflammatory response, and one key aspect of this response involves various oxyradical-generating systems.

Topics: alpha 1-Antitrypsin; Bronchi; Bronchopulmonary Dysplasia; Catalase; Cohort Studies; Epithelium; Female; Humans; Infant, Newborn; Inflammation Mediators; Leukocyte Elastase; Leukocytes; Male; Pancreatic Elastase; Peroxidase; Proteins; Pulmonary Alveoli; Reactive Oxygen Species; Respiratory Distress Syndrome, Newborn; Risk Factors; Suction; Sulfhydryl Compounds; Xanthine Oxidase