Inhaled nitric oxide does not increase lipid peroxidation in preterm infants.
Explore the source record for details and available documents.
Biomedical subjects
Publications and source records attributed to J A Drury.
Explore the source record for details and available documents.
1. In healthy humans, a balance exists between oxygen-derived free-radical production and their removal by antioxidants. In preterm infants inadequate antioxidant defences may contribute to the pathogenesis of some of the complications of prematurity. 2. Plasma total antioxidant status and malondialdehyde concentration were measured during the first 11 days of life in 25 infants to determine whether increased lipid peroxidation is associated with low extracellular antioxidant status. In a second group of infants, total antioxidant status was quantified within 12 h of birth, and subsequently on days 4 and 10 to investigate the hypothesis that adverse neonatal outcome is associated with low antioxidant status. 3. There may be a weak negative correlation between the total antioxidant status of infants and the lipid peroxidation marker malondialdehyde in plasma (r = -0.24, P = 0.056, n = 89) during the first 11 days of life. In the second group of infants, total antioxidant status was found to be significantly related to plasma urate and bilirubin levels, but not to adverse neonatal outcomes such as chronic lung disease, intraventricular haemorrhage, retinopathy of prematurity or death. 4. If adverse neonatal outcomes are due to inadequate antioxidant defences, these are likely to be intracellular or localized rather than general extracellular deficiencies.
AIM: To test the hypothesis that complications of neonatal intensive care are related to increased oxygen derived free radical activity, using breath pentane as a marker of lipid peroxidation. METHODS: Exhaled breath was collected daily from 57 ventilated preterm infants and pentane concentration measured by gas chromatography. RESULTS: High peak pentane exhalation was significantly associated with low gestational age, mortality, intraventricular haemorrhage and retinopathy of prematurity. Peak pentane was not significantly associated with the development of chronic lung disease. CONCLUSIONS: The demonstration that pentane exhalation is related to the course of neonatal disease and its outcome is consistent with the hypothesis that lipid peroxidation is associated with these illnesses, and may contribute to their severity. If this is a causal relation, antioxidant treatments could prove useful in reducing their severity. Measurement of breath pentane might assist in the assessment of antioxidant strategies prior to more extensive clinical trials.
Several diseases of prematurity are thought to be related to oxidative injury and many of the available markers are unsatisfactory. An assay was developed using HPLC with electrochemical detection for the quantitation of urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG) as a proposed indicator for oxygen-derived free radical injury to DNA in preterm infants. A median value of 3.79 micromol/mol creatinine was obtained for normal children (2-15 years old, n=14). Urinary 8-OHdG excretion in neonates ranged from 0-99 micromol/mol creatinine. There were no gestation or birthweight related differences in urinary 8-OHdG, and no correlation with urinary malondialdehyde. Mean 8-OHdG excretion increased with postnatal age (r=0.80, p < 0.0001, n=15), mirroring the growth velocity curve. These changes could also be due to changes in the activity of the enzyme responsible for 8-OHdG excision. Urinary 8-OHdG levels are unlikely to accurately reflect oxygen derived free radical activity given the strength of the relationship with growth.
The measurement of malondialdehyde (MDA) in biological fluids remains a popular method for the quantification of free radical damage to lipids in vivo. Several diseases of prematurity are thought to be related to oxidative injury and previous studies have found elevated MDA in plasma and urine in preterm infants. Our aim was to investigate the relationship between plasma and urinary MDA levels in preterm infants during the first week of life using a high-performance liquid chromatography (HPLC) based, thiobarbituric acid (TBA) assay with paired plasma and urine samples. We obtained 50 paired samples, and were unable to demonstrate a relationship between the two parameters after the first day of life. In 18 cases a further urine sample was collected 24 h later. There was a positive correlation (r = 0.54, P = 0.02) between plasma MDA and urinary MDA 24 h later. The finding that plasma changes in MDA are reflected in urine 24 h later validates the use of urinary MDA as a marker of whole body lipid peroxidation in populations without renal disease.
UNLABELLED: Frequent blood transfusions may produce changes in iron status which can give rise to oxygen-derived free-radical (ODFR) generation and oxidative injury. Preterm infants developing chronic lung disease (CLD) receive significantly more transfusions. A total of 73 very preterm infants had weekly estimations of serum iron, transferrin, transferrin saturation, ferritin, caeruloplasmin, bleomycin detectable ('free') iron (BDI), and thiobarbituric acid reacting substances (TBARS) made over the first 28 days. Thirty infants remained oxygen dependent at 36 weeks postmenstrual age and were termed as having CLD. They were significantly lighter and less mature at birth and received more than twice as many transfusions during the 1st month. They had significantly lower transferrin levels initially but similar total iron and transferrin saturations as non-CLD infants. Ferritin and caeruloplasmin levels rose to significantly higher levels over the 1st month in CLD infants, and ferritin levels were significantly related to the number of transfusions given. Infants with higher ferritin levels were more likely to show BDI, although this was not associated with increased lipid peroxidation as evidenced by higher TBARS. CONCLUSION: It is unlikely that oxidative injury from ODFRs induced by blood transfusion contributes to the risk of developing CLD in preterm infants.
The measurement of breath pentane as a marker of lipid peroxidation has recently been criticized. Problems encountered include the coelution of isoprene with pentane, contamination with exogenous pentane, and the influence of elevated oxygen concentration. The aim of this project was to investigate and evaluate the Chrompack 9001 Gas Chromatograph, using thermal desorption and cryofocussing and an Al2O3/KCl PLOT column with FID, for use in the measurement of breath pentane in ventilated preterm infants. We have clearly separated isoprene from n-pentane and used hydrocarbon free air to clear the airways and avoid contamination with exogenous pentane. Samples should be stored in Tedlar bags for a maximum of 48 h and on capped desorption tubes for no longer than 24 h. Patient variability was relatively high (mean 18%, n = 4); thus, all patients were sampled in duplicate. No correlation was found between fractional inspired oxygen concentration (FiO2) and exhaled pentane in preterm infants ventilated for respiratory distress syndrome. In conclusion, we feel that despite the pitfalls and technical difficulties, with careful attention to detail it is possible to reliably measure breath pentane in ventilated preterm infants as an index of lipid peroxidation.
Explore the source record for details and available documents.