Metabolomic Analysis of Hemorrhagic Shock

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DESCRIPTION (provided by applicant): Despite decades of research on resuscitative strategies, hemorrhagic shock from civilian or military trauma can progress to irreversible shock and claims the lives of thousands annually. The cause of progression to irreversibility is incompletely understood. The long term goal of this research is to better define the mechanisms underlying the onset, progression, and outcome of hemorrhagic shock. With funding from the Office of Naval Research, we have developed instrumentation for monitoring tissue phosphoenergetics using phosphorous nuclear magnetic resonance (NMR) spectroscopy and tissue oxygen indices using near infrared (NIR) spectroscopy in a porcine model of severe hemorrhagic shock. These studies show that an observed increase in the phosphomonoester region of in vivo phosphorous NMR spectra is a consistent, early, and independent marker of mortality associated with hemorrhagic shock. In conjunction with these studies we have archived samples of liver, muscle, urine, and plasma from animals at baseline, after 90 minutes of hemorrhagic shock, and following resuscitation. We have analyzed a limited number urine, plasma, and tissue extract samples using high resolution NMR spectroscopy and have detected potentially important changes in metabolite profiles in response to hemorrhagic shock and resuscitation. However, a full investigation of these archived tissue and biofluid samples is beyond the scope of the original proposal. In this R03 Small Grant application we propose to analyze the full complement of our archived specimens and perform the control experiments necessary for identifying key metabolites in these NMR spectra. We anticipate that the studies proposed in this application will allow us to establish a relationship between our existing global physiologic and in vivo phosphoenergetic data that vary in hemorrhagic shock and more subtle but comprehensive metabolic profiles from the secondary analysis of the archived tissue specimens.