Newborn resuscitation with pure oxygen may be associated with long-term detrimental effects. Due to the change in attitude toward use of less oxygen upon resuscitation, there is a need to study effects of intermediate hyperoxia. The aim was to study dose-response correlation between inspiratory fraction of oxygen used for resuscitation and urinary markers of oxidative damage to DNA and amino acids. Hypoxemia was induced in newborn piglets following a standardized model; they were resuscitated for 15 min with either 21%, 40%, 60% or 100% oxygen and observed for 1 h. Urine samples were collected. Urinary elimination of 8-hydroxy-2=-deoxyguanosine (8-oxo-dG), 2=deoxyguanosine (2dG), orthotyrosine (o-Tyr) and phenylalanine (Phe) were determined by HPLC and tandem mass spectrometry (HPLC-MS/MS). Quotient of 8-oxo-dG/ 2dG and o-Tyr/Phe ratios were significantly and dose-dependant higher in piglets resuscitated with supplementary oxygen. T he transition from fetal to neonatal life contains complex and rapid physiologic changes. Usually, these changes are spontaneous, but approximately 10% of newborn babies require some assistance to begin breathing, and about 1% requires extensive resuscitation (1).Compared with the intrauterine pO 2 at about 3.3 kPa every child comes out to a relative hyperoxia and the values will normally spontaneously rise to about 8kPa during the first 30 min pp. Excessive hyperoxia may disturb a tuned equilibrium in the oxidative-antioxidative system. Exposure to hyperoxia generates significant higher levels of free radicals, and even more when preceded by hypoxia (2).In the neonatal literature an increasing number of studies focusing on supplementary oxygen shows how oxidative stress influences both mortality and morbidity (3,4). Moreover, babies exposed to high oxygen concentrations in the first minutes of postnatal life have been shown to be at higher risk of childhood leukemia and cancer (5,6) making it mandatory to search for the causal connection.We wanted to explore possible reasons for long-term effects of oxidative stress as well as to search for signs of oxidative damage to DNA and proteins and have chosen two biomarkers of oxidative stress; 8-hydroxy-2=-deoxyguanosine (8oxodG) and ortho-tyrosine (o-Tyr). Urinary excretion of modified nucleosides/bases i.e., 8oxodG can be measured to assess oxidative damage on the level of the whole organism (7) and has been used to evaluate oxidative stress in patients (8). O-tyr is known to be formed entirely upon reaction of Phe with hydroxyl radicals and can also be measured in urine (9).In addition, we also wanted to study the effect of re oxygenation with different oxygen concentrations to see if there is a dose-dependency or if there could be a threshold beyond which supplementary oxygen seems to be detrimental.We hypothesized that resuscitation of piglets with supplementary oxygen (40%, 60% or 100%) would cause increased oxidative stress, more reactive oxygen species (ROS), and more damage to proteins and DNA than 21% oxygen.
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