Amiloride moderates increased gut permeability and diminishes mesenteric lymph-mediated priming of neutrophils in trauma/hemorrhagic shock

Naohiko Fujiyoshi, Eleonora Feketeova, Qi Lu, Da Zhong Xu, G. Haskó, Edwin A. Deitch

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Background: Amiloride, an inhibitor of Na+/H+ exchangers and Na+ channels has been shown recently to ameliorate both gut and lung injury in rats subjected to a combined insult of trauma and hemorrhagic shock (T/HS). We have shown previously that mesenteric lymph duct ligation prevents T/HS-induced lung endothelial injury and neutrophil activation, suggesting that toxic inflammatory factors originating from the gut and carried in the lymph are responsible for the lung injury observed after T/HS. This study investigates whether the protective effect of amiloride against T/HS-induced lung injury was associated with decreased lymph toxicity and gut permeability. Methods: Male rats subjected to trauma (laparotomy) plus hemorrhagic shock (mean arterial pressure, 30 mm Hg × 90 min) (T/HS) or trauma plus sham shock (T/SS) and treated with amiloride or its vehicle had their mesenteric lymph duct catheterized. Mesenteric lymph collected before and after shock was assayed for biologic activity on endothelial cells (cytotoxicity and permeability) and neutrophils (respiratory burst activity). Gut permeability was assessed by monitoring plasma concentrations of the fluorescent dye FITC-dextran after its injection into the ileum. Results: Amiloride administration reduced the capacity of post-shock mesenteric lymph to prime neutrophils for an increased respiratory burst. Amiloride failed to decrease the ability of mesenteric lymph to kill endothelial cells or increase their permeability. Amiloride decreased gut permeability. Conclusions: The mechanisms of the lung protective effect of amiloride in rats undergoing T/HS may be secondary to decreased neutrophil activation, diminished gut permeability, or an effect on the end organ.

Original languageEnglish
Pages (from-to)810-817
Number of pages8
JournalSurgery
Volume140
Issue number5
DOIs
Publication statusPublished - Nov 2006

Fingerprint

Hemorrhagic Shock
Amiloride
Lymph
Permeability
Neutrophils
Wounds and Injuries
Lung Injury
Shock
Neutrophil Activation
Respiratory Burst
Adult Respiratory Distress Syndrome
proctolin
Endothelial Cells
Sodium-Hydrogen Antiporter
Poisons
Fluorescent Dyes
Ileum
Laparotomy
Ligation
Arterial Pressure

ASJC Scopus subject areas

  • Surgery

Cite this

Amiloride moderates increased gut permeability and diminishes mesenteric lymph-mediated priming of neutrophils in trauma/hemorrhagic shock. / Fujiyoshi, Naohiko; Feketeova, Eleonora; Lu, Qi; Xu, Da Zhong; Haskó, G.; Deitch, Edwin A.

In: Surgery, Vol. 140, No. 5, 11.2006, p. 810-817.

Research output: Contribution to journalArticle

Fujiyoshi, Naohiko ; Feketeova, Eleonora ; Lu, Qi ; Xu, Da Zhong ; Haskó, G. ; Deitch, Edwin A. / Amiloride moderates increased gut permeability and diminishes mesenteric lymph-mediated priming of neutrophils in trauma/hemorrhagic shock. In: Surgery. 2006 ; Vol. 140, No. 5. pp. 810-817.
@article{44d3c4c3454d48e7856192cd3849b584,
title = "Amiloride moderates increased gut permeability and diminishes mesenteric lymph-mediated priming of neutrophils in trauma/hemorrhagic shock",
abstract = "Background: Amiloride, an inhibitor of Na+/H+ exchangers and Na+ channels has been shown recently to ameliorate both gut and lung injury in rats subjected to a combined insult of trauma and hemorrhagic shock (T/HS). We have shown previously that mesenteric lymph duct ligation prevents T/HS-induced lung endothelial injury and neutrophil activation, suggesting that toxic inflammatory factors originating from the gut and carried in the lymph are responsible for the lung injury observed after T/HS. This study investigates whether the protective effect of amiloride against T/HS-induced lung injury was associated with decreased lymph toxicity and gut permeability. Methods: Male rats subjected to trauma (laparotomy) plus hemorrhagic shock (mean arterial pressure, 30 mm Hg × 90 min) (T/HS) or trauma plus sham shock (T/SS) and treated with amiloride or its vehicle had their mesenteric lymph duct catheterized. Mesenteric lymph collected before and after shock was assayed for biologic activity on endothelial cells (cytotoxicity and permeability) and neutrophils (respiratory burst activity). Gut permeability was assessed by monitoring plasma concentrations of the fluorescent dye FITC-dextran after its injection into the ileum. Results: Amiloride administration reduced the capacity of post-shock mesenteric lymph to prime neutrophils for an increased respiratory burst. Amiloride failed to decrease the ability of mesenteric lymph to kill endothelial cells or increase their permeability. Amiloride decreased gut permeability. Conclusions: The mechanisms of the lung protective effect of amiloride in rats undergoing T/HS may be secondary to decreased neutrophil activation, diminished gut permeability, or an effect on the end organ.",
author = "Naohiko Fujiyoshi and Eleonora Feketeova and Qi Lu and Xu, {Da Zhong} and G. Hask{\'o} and Deitch, {Edwin A.}",
year = "2006",
month = "11",
doi = "10.1016/j.surg.2006.03.003",
language = "English",
volume = "140",
pages = "810--817",
journal = "Surgery",
issn = "0263-9319",
publisher = "Elsevier BV",
number = "5",

}

TY - JOUR

T1 - Amiloride moderates increased gut permeability and diminishes mesenteric lymph-mediated priming of neutrophils in trauma/hemorrhagic shock

AU - Fujiyoshi, Naohiko

AU - Feketeova, Eleonora

AU - Lu, Qi

AU - Xu, Da Zhong

AU - Haskó, G.

AU - Deitch, Edwin A.

PY - 2006/11

Y1 - 2006/11

N2 - Background: Amiloride, an inhibitor of Na+/H+ exchangers and Na+ channels has been shown recently to ameliorate both gut and lung injury in rats subjected to a combined insult of trauma and hemorrhagic shock (T/HS). We have shown previously that mesenteric lymph duct ligation prevents T/HS-induced lung endothelial injury and neutrophil activation, suggesting that toxic inflammatory factors originating from the gut and carried in the lymph are responsible for the lung injury observed after T/HS. This study investigates whether the protective effect of amiloride against T/HS-induced lung injury was associated with decreased lymph toxicity and gut permeability. Methods: Male rats subjected to trauma (laparotomy) plus hemorrhagic shock (mean arterial pressure, 30 mm Hg × 90 min) (T/HS) or trauma plus sham shock (T/SS) and treated with amiloride or its vehicle had their mesenteric lymph duct catheterized. Mesenteric lymph collected before and after shock was assayed for biologic activity on endothelial cells (cytotoxicity and permeability) and neutrophils (respiratory burst activity). Gut permeability was assessed by monitoring plasma concentrations of the fluorescent dye FITC-dextran after its injection into the ileum. Results: Amiloride administration reduced the capacity of post-shock mesenteric lymph to prime neutrophils for an increased respiratory burst. Amiloride failed to decrease the ability of mesenteric lymph to kill endothelial cells or increase their permeability. Amiloride decreased gut permeability. Conclusions: The mechanisms of the lung protective effect of amiloride in rats undergoing T/HS may be secondary to decreased neutrophil activation, diminished gut permeability, or an effect on the end organ.

AB - Background: Amiloride, an inhibitor of Na+/H+ exchangers and Na+ channels has been shown recently to ameliorate both gut and lung injury in rats subjected to a combined insult of trauma and hemorrhagic shock (T/HS). We have shown previously that mesenteric lymph duct ligation prevents T/HS-induced lung endothelial injury and neutrophil activation, suggesting that toxic inflammatory factors originating from the gut and carried in the lymph are responsible for the lung injury observed after T/HS. This study investigates whether the protective effect of amiloride against T/HS-induced lung injury was associated with decreased lymph toxicity and gut permeability. Methods: Male rats subjected to trauma (laparotomy) plus hemorrhagic shock (mean arterial pressure, 30 mm Hg × 90 min) (T/HS) or trauma plus sham shock (T/SS) and treated with amiloride or its vehicle had their mesenteric lymph duct catheterized. Mesenteric lymph collected before and after shock was assayed for biologic activity on endothelial cells (cytotoxicity and permeability) and neutrophils (respiratory burst activity). Gut permeability was assessed by monitoring plasma concentrations of the fluorescent dye FITC-dextran after its injection into the ileum. Results: Amiloride administration reduced the capacity of post-shock mesenteric lymph to prime neutrophils for an increased respiratory burst. Amiloride failed to decrease the ability of mesenteric lymph to kill endothelial cells or increase their permeability. Amiloride decreased gut permeability. Conclusions: The mechanisms of the lung protective effect of amiloride in rats undergoing T/HS may be secondary to decreased neutrophil activation, diminished gut permeability, or an effect on the end organ.

UR - http://www.scopus.com/inward/record.url?scp=33750488771&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33750488771&partnerID=8YFLogxK

U2 - 10.1016/j.surg.2006.03.003

DO - 10.1016/j.surg.2006.03.003

M3 - Article

C2 - 17084725

AN - SCOPUS:33750488771

VL - 140

SP - 810

EP - 817

JO - Surgery

JF - Surgery

SN - 0263-9319

IS - 5

ER -