Einfluss einer Beatmung mit 100% Sauerstoff auf die Ausbildung von DNA-Strangbrüchen und die Parameter des oxidativen Stress im Langzeitmodell des septischen Schocks beim Schwein

Abstract

The letality of the septic shock did not decrease during the last decade and is still at about 50 %. Because of an increasing cost pressure there is a new focus on therapies, like ventilation with pure oxygen, which is easy and cheap to administer, but which also bears beside the positive effects potentially substantial risks: The stabilization of the circulation is opposed to the possible enhancement of the oxidative stress and the resulting organ, cell and DNA damage. Even though there was a lot of investigations on the effects of oxygen breathing on the formation of DNA damage in healthy organisms there is no knowledge about this in septic animals. In this study the genotoxic effects of different kinds of ventilation with pure oxygen were investigated in a hyperdynamic long time model of septic shock in swine. The peritonitis was induced by inoculation of autologous faeces in the abdomen. 12 and 24 hrs after the induction of sepsis DNA strand breaks were measured using the comet assay and the parameters of nitrosative and oxidative stress were analysed. At the end of the experiment the activity of the antioxidative enzymes SOD and catalase in lung and liver tissue were measured and a microbiological investigation of blood and ascites samples was done. To investigate the sensitivity of septic animals on an additional oxidative stress and to evaluate the capacity of DNA repair isolated lymphocytes were HBO exposed and monitored for two additional hours. The investigations showed that sepsis itself lead to a nitrosative and oxidative stress which leads to DNA strand breaks. Though, the hyperoxia did not lead to an additional increase in any of these parameters and also the antioxidative enzymes SOD and catalase did not show any difference. The ex vivo experiment with isolated lymphocytes sowed the same findings: However, HBO exposure lead to DNA damage but hyperoxia did not have any further influence on the amount of DNA strand breaks or on the DNA repair.