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

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.

• Authors: Regina Sordi, Fausto Chiazza, Debora Collotta, Giuseppe Migliaretti, Romain A Colas, Paul Vulliamy, Karim Brohi, Jesmond Dalli, Massimo Collino, Christoph Thiemermann
• Journal: Annals of surgery (Ann Surg) Vol. 273 Issue 5 Pg. 1012-1021 (05 01 2021) ISSN: 1528-1140 [Electronic] United States
• PMID: 31188196 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Chemical References

• Biomarkers
• Cytokines
• resolvin D1
• Docosahexaenoic Acids

Topics

• Animals
• Biomarkers (blood)
• Cytokines (blood)
• Disease Models, Animal
• Docosahexaenoic Acids (pharmacology)
• Immunohistochemistry
• Male
• Multiple Organ Failure (blood, drug therapy, etiology)
• Rats
• Rats, Wistar
• Shock, Hemorrhagic (blood, complications, drug therapy)