32 Hyperoxic Resuscitation Gives Increased Oxidative Stress in Lung Tissue and Influence the Capacity to Repair Base Lesions on Dna

Abstract

Background/aims: Newborn resuscitation with pure oxygen may induce short- and long term pathological changes via oxidative stress. Oxygen can adversely affect all tissues of the body. We studied DNA repair activities in lung-, liver- and brain tissue 9 hours(h) after preceding hypoxia and reoxygenation. In lung tissue antioxidant capacity and DNA repair activity was assessed at both 1 and 9 h.

Methods: Hypoxemia was induced by ventilation of 8% O₂ in N₂ and maintained until Base Excess reached -20mmol/L or mean arterial blood pressure decreased below 15mmHg. The piglets, n=5-10 in each group, were resuscitated for 15 or 30 min by ventilation with 21 or 100% O₂ and observed for 1 or 9 h before lung-, liver and brain tissue samples were removed and snap-frozen. Controls went through surgery, stabilization and ventilation, but were not exposed to hypoxia and reoxygenation.

Results: One hour after end of resuscitation the total antioxidant capacity in lung tissue was significant lower in the group resuscitated with 100% O₂ compared to 21% (p< 0.02), but after 9h there were no difference. The DNA repair activity was significantly reduced 1h after resuscitation; in the 100% group 55% reduction vs controls(p=0.008) and 28% vs room air(p=0.047). After 9h there was still a tendency to reduced base lesion repair on DNA in tissue from the lung and prefrontal cortex.

Conclusions: Hypoxia and subsequent resuscitation with 100% O₂ causes increased oxidative stress and risk of cell damage and long term consequences such as accumulation of mutations in the genome.

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