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Protective Effect of Phosphatidylserine Blockade in Hemorrhagic Shock.


ABSTRACT:

Background

Phosphatidylserine (PS) is a key cell membrane phospholipid normally maintained on the inner cell surface but externalizes to the outer surface in response to cellular stress. We hypothesized that PS exposure mediates organ dysfunction in hemorrhagic shock. Our aims were to evaluate PS blockade on (1) pulmonary, (2) renal, and (3) gut function, as well as (4) serum lysophosphatidic acid (LPA), an inflammatory mediator generated by PS externalization, as a possible mechanism mediating organ dysfunction.

Materials and methods

Rats were either (1) monitored for 130 min (controls, n = 3), (2) hemorrhaged then resuscitated (hemorrhage only group, n = 3), or (3) treated with Diannexin (DA), a PS blocking agent, followed by hemorrhage and resuscitation (DA + hemorrhage group, n = 4). Pulmonary dysfunction was assessed by arterial partial pressure of oxygen, renal dysfunction by serum creatinine, and gut dysfunction by mesenteric endothelial permeability (LP). LPA levels were measured in all groups.

Results

Pulmonary: there was no difference in arterial partial pressure of oxygen between groups. Renal: after resuscitation, creatinine levels were lower after PS blockade with DA versus hemorrhage only group (P = 0.01). Gut: LP was decreased after PS blockade with DA versus hemorrhage only group (P < 0.01). Finally, LPA levels were also lower after PS blockade with DA versus the hemorrhage only group but higher than the control group (P < 0.01).

Conclusions

PS blockade with DA decreased renal and gut dysfunction associated with hemorrhagic shock and attenuated the magnitude of LPA generation. Our findings suggest potential for therapeutic targets in the future that could prevent organ dysfunction associated with hemorrhagic shock.

SUBMITTER: Cohan C 

PROVIDER: S-EPMC6900439 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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Publications

Protective Effect of Phosphatidylserine Blockade in Hemorrhagic Shock.

Cohan Caitlin C   Beattie Genna G   Brigode William W   Yeung Louise L   Miraflor Emily E   Victorino Gregory P GP  

The Journal of surgical research 20190906


<h4>Background</h4>Phosphatidylserine (PS) is a key cell membrane phospholipid normally maintained on the inner cell surface but externalizes to the outer surface in response to cellular stress. We hypothesized that PS exposure mediates organ dysfunction in hemorrhagic shock. Our aims were to evaluate PS blockade on (1) pulmonary, (2) renal, and (3) gut function, as well as (4) serum lysophosphatidic acid (LPA), an inflammatory mediator generated by PS externalization, as a possible mechanism me  ...[more]

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