• Lance B Becker, Scott L Weiss, Mehmet Akif Karamercan, Jose Paul Perales Villarroel, Evan Werlin, and Ronald Figueredo.
• 1 Gazi University School of Medicine, Department of Emergency Medicine. Ankara/TURKEY (makaramercan@gazi.edu.tr) 2 Children's Hospital of Philadelphia, Anesthesiology, Critical Care and Pediatrics, Perelman School of Medicine at the University of Pennsylvania (weisss@email.chop.edu) 3 Division of Traumatology, Critical Care and Acute Care Surgery. University of Pennsylvania, Philadelphia/USA (jose.peralesvillarroel@uphs.upenn.edu); (Yuxia.Guan@uphs.upenn.edu); (Ronald.Figueredo@uphs.upenn.edu); (Carrie.Sims@uphs.upenn.edu) 4 University of Pennsylvania, Perelman School of Medicine. Philadelphia/USA (evan.werlin@gmail.com) 5 Center for Resuscitation Science. University of Pennsylvania, Philadelphia/USA (Lance.Becker@uphs.upenn.edu).
• Shock. 2013 Jul 17.

IntroductionAlthough mitochondrial dysfunction is thought to contribute to the development of post-traumatic organ failure, current techniques to assess mitochondrial function in tissues are invasive and clinically impractical. We hypothesized that mitochondrial function in peripheral blood mononuclear cells (PBMCs) would reflect cellular respiration in other organs during hemorrhagic shock and resuscitation (HS&R).MethodsUsing a fixed pressure HS model, Long Evan's rats were bled to a mean arterial pressure (MAP) of 40 mmHg. When blood pressure could no longer be sustained without intermittent fluid infusion (Decompensated HS), Lactated Ringer's (LR) was incrementally infused to maintain the MAP at 40 mmHg until 40% of the shed blood volume was returned (Severe HS). Animals were then resuscitated with 4X total shed volume in LR over 60 minutes (Resuscitation). Control animals underwent the same surgical procedures, but were not hemorrhaged. Animals were randomized to Control (n=6), Decompensated HS (n=6), Severe HS (n=6) or Resuscitation (n=6) groups. Kidney, liver, and heart tissues as well as PBMC's were harvested from animals in each group to measure mitochondrial oxygen consumption using high resolution respirometry. Flow cytometry was used to assess mitochondrial membrane potential (Ψm) in PBMCs. One-way ANOVA and Pearson correlations were performed.ResultsMitochondrial oxygen consumption decreased in all tissues, including PBMC's, following Decompensated HS, Severe HS, and Resuscitation. However, the degree of impairment varied significantly across tissues during HS&R. Of the tissues investigated, PBMC mitochondrial oxygen consumption and Ψm provided the closest correlation to kidney mitochondrial function during HS (complex I: r =0.65; complex II: r=0.65; complex IV: r=0.52; p<0.05). This association, however, disappeared with resuscitation. A weaker association between PBMC and heart mitochondrial function was observed but no association was noted between PBMC and liver mitochondrial function.ConclusionAll tissues including PBMC's demonstrated significant mitochondrial dysfunction following HS&R. Although PBMC and kidney mitochondrial function correlated well during hemorrhagic shock, the variability in mitochondrial response across tissues over the spectrum of hemorrhagic shock and resuscitation limits the usefulness of using PBMC's as a proxy for tissue-specific cellular respiration.

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