REDUCED DNASE ENZYME ACTIVITY IN RESPONSE TO HIGH POST-INJURY MITOCHONDRIAL DNA CONCENTRATION PROVIDES A THERAPEUTIC TARGET FOR SIRS

BACKGROUND Cell free mitochondrial DNA (mtDNA) is pro-inflammatory and has been detected in high concentrations in trauma patients’ plasma. Deoxyribonuclease (DNase) is the free plasma enzyme responsible for the digestion of extracellular DNA. The relationship between mtDNA and DNase after major trauma is unknown. We hypothesized that DNase activity would be elevated after injury and trauma surgery, and would be associated with high concentrations of extracellular DNA. METHODS 2-year prospective study was performed on 103 consecutive trauma patients (Male 81%, Age: 38 IQR 30-59 years; ISS: 18 IQR 12-26) who underwent standardised major orthopaedic trauma surgical interventions. Blood was collected at 5 peri-operative time points (pre-op, post-op, 7hrs, 24hrs and 3 days post-operatively). Healthy control subjects (n=20) were also sampled. Cell free mtDNA and nuclear DNA(nDNA) was measured using quantitative polymerase chain reaction. DNase was also assayed in the same plasma samples. RESULTS Increased levels of mtDNA (from Pre-op 163±86ng/ml to 3 days 282±201ng/ml p

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