Karamercan 2013 Shock

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Karamercan MA, Weiss SL, Villarroel JP, Guan Y, Werlin E, Figueredo R, Becker LB, Sims C (2013) Can peripheral blood mononuclear cells be used as a proxy for mitochondrial dysfunction in vital organs during hemorrhagic shock and resuscitation? Shock 40:476-84.

» PMID: 24088987 Open Access

Karamercan MA, Weiss SL, Villarroel JP, Guan Y, Werlin E, Figueredo R, Becker LB, Sims CA (2013) Shock

Abstract: Although mitochondrial dysfunction is thought to contribute to the development of posttraumatic 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.

Using a fixed-pressure HS model, Long-Evans rats were bled to a mean arterial pressure of 40 mmHg. When blood pressure could no longer be sustained without intermittent fluid infusion (decompensated HS), lactated Ringer's solution was incrementally infused to maintain the mean arterial pressure at 40 mmHg until 40% of the shed blood volume was returned (severe HS). Animals were then resuscitated with 4× total shed volume in lactated Ringer's solution over 60 min (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 PBMCs 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 analysis of variance and Pearson correlations were performed.

Mitochondrial oxygen consumption decreased in all tissues, including PBMCs, following decompensated HS, severe HS, and resuscitation. However, the degree of impairment varied significantly across tissues during hemorrhagic shock and resuscitation. 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.

All tissues including PBMCs demonstrated significant mitochondrial dysfunction following hemorrhagic shock and resuscitation. 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 PBMCs as a proxy for tissue-specific cellular respiration.

Keywords: Hemorrhagic shock, Mitochondrial dysfunction, Resuscitation, Vital organ, PBMC

O2k-Network Lab: US PA Philadelphia Sims C


Labels: MiParea: Respiration  Pathology: Other 

Organism: Rat  Tissue;cell: Heart, Liver, Kidney, Blood cells, Lymphocyte  Preparation: Intact cells, Isolated mitochondria 


Coupling state: LEAK, ROUTINE, OXPHOS, ET  Pathway: N, S, CIV  HRR: Oxygraph-2k