Angelo D'alessandro1, Travis Nemkov1, Hunter B Moore2, Ernest E Moore2,3, Matthew Wither1, Trevor Nydam3, Annie Slaughter2, Christopher C Silliman4,5, Anirban Banerjee2, Kirk C Hansen1. 1. Department of Biochemistry and Molecular Genetics, University of Colorado Denver School of Medicine, University of Colorado Denver, Aurora, CO, United States of America. 2. Department of Surgery, University of Colorado Denver School of Medicine, University of Colorado Denver, Aurora, CO, United States of America. 3. Department of Surgery, Denver Health Medical Center, Denver, CO, United States of America. 4. Department of Paediatrics, University of Colorado, Aurora, CO, United States of America. 5. Bonfils Blood Centre, Denver, CO, United States of America.
Abstract
BACKGROUND: Water-soluble components in mesenteric lymph have been implicated in the pathophysiology of acute lung injury and distal organ failure following trauma and haemorrhagic shock. Proteomics analyses have recently shown similarities and specificities of post-trauma/haemorrhagic shock lymph and plasma. We hypothesise that the metabolic phenotype of post-trauma/haemorrhagic shock mesenteric lymph and plasma share common metabolites, but are also characterised by unique features that differentiate these two fluids. MATERIALS AND METHODS: Matched samples were collected from 5 brain-dead organ donors who had suffered extreme trauma/haemorrhagic shock. Metabolomics analyses were performed through ultra-high performance liquid chromatography mass spectrometry. RESULTS: Overall, 269 metabolites were identified in either fluid. Despite significant overlapping, metabolic phenotypes of matched lymph or plasma from the same patients could be used to discriminate sample fluid or biological patient/traumatic-injury origin. Metabolites showing relatively high levels in both fluids included markers of haemolysis and cell lysis secondary to tissue injury. DISCUSSION: High positive correlations were observed between the quantitative levels of markers of systemic metabolic derangement following traumatic/haemorrhagic hypoxaemia, such as succinate, oxoproline, urate and fatty acids. These metabolites might contribute to coagulopathies of trauma and neutrophil priming driving acute lung injury. Future studies will investigate whether the observed compositional specificities mirror functional or pathological adaptations after trauma and haemorrhage.
BACKGROUND:Water-soluble components in mesenteric lymph have been implicated in the pathophysiology of acute lung injury and distal organ failure following trauma and haemorrhagic shock. Proteomics analyses have recently shown similarities and specificities of post-trauma/haemorrhagic shock lymph and plasma. We hypothesise that the metabolic phenotype of post-trauma/haemorrhagic shock mesenteric lymph and plasma share common metabolites, but are also characterised by unique features that differentiate these two fluids. MATERIALS AND METHODS: Matched samples were collected from 5 brain-dead organ donors who had suffered extreme trauma/haemorrhagic shock. Metabolomics analyses were performed through ultra-high performance liquid chromatography mass spectrometry. RESULTS: Overall, 269 metabolites were identified in either fluid. Despite significant overlapping, metabolic phenotypes of matched lymph or plasma from the same patients could be used to discriminate sample fluid or biological patient/traumatic-injury origin. Metabolites showing relatively high levels in both fluids included markers of haemolysis and cell lysis secondary to tissue injury. DISCUSSION: High positive correlations were observed between the quantitative levels of markers of systemic metabolic derangement following traumatic/haemorrhagic hypoxaemia, such as succinate, oxoproline, urate and fatty acids. These metabolites might contribute to coagulopathies of trauma and neutrophil priming driving acute lung injury. Future studies will investigate whether the observed compositional specificities mirror functional or pathological adaptations after trauma and haemorrhage.
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