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Ann Surg. 2019 Jun 7. doi: 10.1097/SLA.0000000000003407. [Epub ahead of print]

Resolvin D1 Attenuates the Organ Injury Associated With Experimental Hemorrhagic Shock.

Author information

1
Queen Mary University of London, William Harvey Research Institute, Barts and The London School of Medicine & Dentistry, London, UK.
2
Department of Pharmacology, Universidade Federal de Santa Catarina, Florianópolis, Brazil.
3
Department of Drug Science and Technology, University of Turin, Turin, Italy.
4
Department of Public Health and Pediatric Sciences, University of Turin, Italy.
5
Lipid Mediator Unit, Queen Mary University of London, William Harvey Research Institute, Barts and The London School of Medicine & Dentistry, London, UK.
6
Queen Mary University of London, Blizard Institute of Cell and Molecular Sciences, Barts and the London School of Medicine, London, UK.
7
Queen Mary University of London, Centre for Inflammation and Therapeutic Innovation, London, UK.

Abstract

OBJECTIVE:

To evaluate the potential changes in the plasma levels of resolvin D1 (RvD1) in patients with trauma and hemorrhage. Having found that trauma results in a profound reduction in plasma RvD1 in patients, we have then investigated the effects of RvD1 on the organ injury and dysfunction associated with hemorrhagic shock (HS) in the rat.

BACKGROUND:

HS is a common cause of death in trauma due to excessive systemic inflammation and multiple organ failure. RvD1 is a member of the resolvin family of pro-resolution mediators.

METHODS:

Blood samples were drawn from critically injured patients (n = 27, ACITII-prospective observational cohort study) within 2 hours of injury for targeted liquid chromatography tandem mass spectrometry. HS rats (removal of blood to reduce arterial pressure to 30 ± 2 mm Hg, 90 minutes, followed by resuscitation) were treated with RvD1 (0.3 or 1 μg/kg intravenous (i.v.)) or vehicle (n = 7). Parameters of organ injury and dysfunction were determined.

RESULTS:

Plasma levels of RvD1 (mg/dL) were reduced in patients with trauma+HS (0.17 ± 0.08) when compared with healthy volunteers (0.76 ± 0.25) and trauma patients (0.62 ± 0.20). In rats with HS, RvD1 attenuated the kidney dysfunction, liver injury, and tissue ischemia. RvD1 also reduced activation of the nuclear factor (NF)-κB pathway and reduced the expression of pro-inflammatory proteins such as inducible nitric oxide synthase, tumor necrosis factor-α, interleukin-1β, and interleukin-6.

CONCLUSION:

Plasma RvD1 is reduced in patients with trauma-HS. In rats with HS, administration of synthetic RvD1 on resuscitation attenuated the multiple organ failure associated with HS by a mechanism that involves inhibition of the activation of NF-κB.

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