Rodney Daniels, MD
Assistant Professor, Pediatric Critical Care Medicine and Biomedical Engineering
Univ of Michigan Health System
Ann Arbor, MI
Disclosure information not submitted.
Mohamad Tiba, MD, MS
Research Assistant Professor, Department of Emergency Medicine
University of Michgan, MCIRCC, United States
Disclosure information not submitted.
Brandon Cummings, BS
Clinical Research Associate
University of Michigan, Michigan Center for Integrative Research in Critical Care (MCIRCC), United States
Disclosure information not submitted.
Yan Rou Yap, n/a
Research Associate, Department of Pediatrics
University of Michigan, United States
Disclosure information not submitted.
Sardar Ansari, PhD
Research Assistant Professor, Department of Emergency Medicine
University of Michigan, MCIRCC, United States
Disclosure information not submitted.
Brendan McCracken, MS
Research Laboratory Specialist, Department of Emergency Medicine
University of Michigan, MCIRCC, United States
Disclosure information not submitted.
Kevin Ward, MD
Professor, Department of Emergency Medicine
University of Michigan, MCIRCC, United States
Disclosure information not submitted.
Kathleen Stringer, PharmD
Professor of Pharmaceutics, College of Pharmacy
University of Michigan, MCIRCC, United States
Disclosure information not submitted.
Title: Redox Potential in Swine Shock Correlates to Metabolite Changes Active in Oxidative Stress Responses
Introduction: Oxidation-reduction (redox) reactions and the redox potential (RP) that must be maintained for cell function lie at the heart of physiologic processes in critical illness, with changes in RP reflecting systemic oxidative stress. Blood RP has been shown to correlate with oxygen debt over time, and we hypothesize that RP will reflect changing concentrations of metabolites involved in oxidative stress. To test this hypothesis, we compared blood and urine RP with concentrations of multiple metabolites in a swine hemorrhagic shock model to identify significant relationships.
Methods: Seven swine were subjected to hemorrhagic shock. Mixed venous (MV) RP, urine RP, and MV/urine metabolite concentrations were assessed at baseline, max O2 Debt (80mL/kg), end resuscitation, and 2 hrs post resuscitation. RP was measured at collection via open circuit potential using nanoporous gold electrodes with Ag/AgCl reference. Metabolites (n=34, each sample) were quantified by 1H-nuclear MR spectroscopy. MV and urine RP were compared with time-matched metabolites across all swine. LASSO regression with leave-one-out cross validation was used to determine significant RP/metabolite relationships. Metabolites must maintain magnitude and direction of coefficients across 6 or more swine to be significant.
Results: Significant metabolite relationships (and coeff) with MV RP include: ATP (-3.63), Glycine (5.22), ADP (2.88), Glucose (15.67), Formate (-15.34), Pyruvate (5.99), and Taurine (-9.86). Significant relationships with urine RP are: Taurine (6.73), Glycine (-5.76) Creatine (10.02), Betaine (5.5), Urea (5.68), 3-Hydroxyisobutyrate (-6.81), N-Phenylacetylglycine [PAG] (-17.03), Hippurate (14.73), and Formate (-5.37). These metabolites scavenge extracellular peroxide (pyruvate), inhibit ROS and activate cellular antioxidant defense (taurine), act as indicators of antioxidant mobilization against oxidative stress (glycine + PAG), and reflect renal hydroxyl radical trapping (hippurate), among others.
Conclusions: Real-time RP measures demonstrate significant relationships with metabolites attributable to metabolic pathways involved in systemic responses to oxidative stress. As a direct measure of redox state, RP may be a useful biomarker and clinical tool in guiding diagnosis and therapy in states of increased oxidative stress.