Villarroel 2013 J Trauma Acute Care Surg

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Villarroel JP, Guan Y, Werlin E, Selak MA, Becker LB, Sims CA (2013) Hemorrhagic shock and resuscitation are associated with peripheral blood mononuclear cell mitochondrial dysfunction and immunosuppression. J Trauma Acute Care Surg 75:24-31.

» PMID: 23778434 Open Access

Villarroel JP, Guan Y, Werlin E, Selak MA, Becker LB, Sims CA (2013) J Trauma Acute Care Surg

Abstract: Trauma and hypovolemic shock are associated with mitochondrial dysfunction and septic complications. We hypothesize that hypovolemic shock and resuscitation results in peripheral blood mononuclear cell (PBMC) mitochondrial dysfunction that is linked to immunosuppression.

Using a decompensated shock model, Long-Evans rats were bled to a MAP of 40 mmHg until the blood pressure could no longer be maintained without fluid infusion. Shock was sustained by incremental infusion of Lactated Ringer’s solution (LR) until 40% of the shed volume had been returned (severe shock). Animals were resuscitated with 4X the shed volume in LR over 60 minutes (resuscitation). Control animals underwent line placement, but were not hemorrhaged. Animals were randomized to control (n=5), severe shock (n=5), or resuscitation (n=6) groups. At each time point, PBMC were isolated for mitochondrial function analysis using flow cytometry and high resolution respirometry. Immune function was evaluated by quantifying serum IL-6 and TNF-α after PBMC stimulation with lipopolysaccharide (LPS). The impact of plasma on mitochondrial function was evaluated by incubating PBMC’s harvested following severe shock with control plasma. PBMC’s from control animals were likewise mixed with plasma collected following resuscitation. Student’s t-test and Pearson correlations were performed (significance: p<0.05).

Following resuscitation, PBMCs demonstrated significant bioenergetic failure with a marked decrease in basal, maximal, and ATP-linked respiration. Mitochondrial membrane potential also decreased significantly by 50% following resuscitation. Serum IL6 increased, while LPS stimulated TNF-α production decreased dramatically following shock and resuscitation. Observed mitochondrial dysfunction correlated significantly with IL6 and TNF-α levels. PBMCs demonstrated significant mitochondrial recovery when incubated in control serum, whereas control PBMCs developed depressed function when incubated with serum collected following severe shock.

Mitochondrial dysfunction following hemorrhagic shock and resuscitation was associated with the inhibition of PBMC response to endotoxin that may lead to an immunosuppressed state.

Keywords: Hemorrhagic shock, Long-Evans rats, Mitochondrial function, Membrane potential, Immune function, Peripheral blood mononuclear cell, PBMC

O2k-Network Lab: US PA Philadelphia Sims CA

Labels: MiParea: Respiration, Patients  Pathology: Other 

Organism: Rat  Tissue;cell: Blood cells, Lymphocyte  Preparation: Intact cells 

Coupling state: LEAK, ROUTINE, ET  Pathway: S, ROX  HRR: Oxygraph-2k