Amiloride combined with small-volume resuscitation with hypertonic saline is superior in ameliorating trauma-hemorrhagic shock-induced lung injury in rats to the administration of either agent alone

Naohiko Fujiyoshi, Edwin A. Deitch, Eleonora Feketeova, Qi Lu, Tamara L. Berezina, Sergey B. Zaets, George W. Machiedo, Da Zhong Xu, G. Haskó

Research output: Contribution to journalArticle

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Abstract

Objective: Recognition of the limitations of standard crystalloid resuscitation has led to exploration for alternative resuscitation strategies that might better prevent the development of trauma-hemorrhage-induced organ dysfunction and systemic inflammation. Thus, the goal of this study was to compare the effects of two resuscitation strategies alone and in combination with that of standard resuscitation with Ringer's lactate. These two strategies were intravenous injection of amiloride, an inhibitor of Na+/VH + exchange and epithelial Na+ channels, and resuscitation with hypertonic saline. Design: Prospective animal study with concurrent control. Setting: Small animal laboratory. Subjects: Adult male Sprague-Dawley rats. Interventions: Rats injected with amiloride or its vehicle were subjected to trauma-hemorrhagic shock (T/HS) or trauma sham-shock (T/SS) and resuscitated with Ringer's lactate or hypertonic saline. The T/HS model consisted of a laparotomy plus 90 mins of shock (mean arterial pressure 30 mm Hg). Three hours after the end of the shock or sham-shock period, lung permeability, lung histology, pulmonary neutrophil sequestration, neutrophil CD11b expression, gut injury, and red blood cell rigidification were assessed. Measurements and Main Results: Both amiloride and hypertonic saline reduced T/HS-induced pulmonary permeability and neutrophil sequestration, and coadministration of these two agents was more efficacious than administration of the individual agents. In contrast, whereas gut injury was attenuated by both amiloride and hypertonic saline, combined administration of amiloride and hypertonic saline failed to further protect the gut. Additionally, hypertonic saline reduced both neutrophil CD11b expression and red blood cell rigidification, whereas amiloride was without effect. Conclusions: Combined administration of amiloride and small-volume resuscitation with hypertonic saline may be a strategy worthy of further evaluation in the therapy of shock-induced distant organ injury.

Original languageEnglish
Pages (from-to)2592-2598
Number of pages7
JournalCritical Care Medicine
Volume33
Issue number11
DOIs
Publication statusPublished - Nov 2005

Fingerprint

Hemorrhagic Shock
Amiloride
Adult Respiratory Distress Syndrome
Lung Injury
Resuscitation
Wounds and Injuries
Neutrophils
Shock
Permeability
Erythrocytes
Bronchopulmonary Sequestration
Epithelial Sodium Channels
Convulsive Therapy
Lung
Laboratory Animals
Intravenous Injections
Laparotomy
Sprague Dawley Rats
Histology
Arterial Pressure

Keywords

  • Hyperosmolarity
  • Hypertonic saline
  • Lung injury
  • Neutrophil activation
  • Red blood cell deformability
  • Resuscitation

ASJC Scopus subject areas

  • Critical Care and Intensive Care Medicine

Cite this

Amiloride combined with small-volume resuscitation with hypertonic saline is superior in ameliorating trauma-hemorrhagic shock-induced lung injury in rats to the administration of either agent alone. / Fujiyoshi, Naohiko; Deitch, Edwin A.; Feketeova, Eleonora; Lu, Qi; Berezina, Tamara L.; Zaets, Sergey B.; Machiedo, George W.; Xu, Da Zhong; Haskó, G.

In: Critical Care Medicine, Vol. 33, No. 11, 11.2005, p. 2592-2598.

Research output: Contribution to journalArticle

Fujiyoshi, Naohiko ; Deitch, Edwin A. ; Feketeova, Eleonora ; Lu, Qi ; Berezina, Tamara L. ; Zaets, Sergey B. ; Machiedo, George W. ; Xu, Da Zhong ; Haskó, G. / Amiloride combined with small-volume resuscitation with hypertonic saline is superior in ameliorating trauma-hemorrhagic shock-induced lung injury in rats to the administration of either agent alone. In: Critical Care Medicine. 2005 ; Vol. 33, No. 11. pp. 2592-2598.
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abstract = "Objective: Recognition of the limitations of standard crystalloid resuscitation has led to exploration for alternative resuscitation strategies that might better prevent the development of trauma-hemorrhage-induced organ dysfunction and systemic inflammation. Thus, the goal of this study was to compare the effects of two resuscitation strategies alone and in combination with that of standard resuscitation with Ringer's lactate. These two strategies were intravenous injection of amiloride, an inhibitor of Na+/VH + exchange and epithelial Na+ channels, and resuscitation with hypertonic saline. Design: Prospective animal study with concurrent control. Setting: Small animal laboratory. Subjects: Adult male Sprague-Dawley rats. Interventions: Rats injected with amiloride or its vehicle were subjected to trauma-hemorrhagic shock (T/HS) or trauma sham-shock (T/SS) and resuscitated with Ringer's lactate or hypertonic saline. The T/HS model consisted of a laparotomy plus 90 mins of shock (mean arterial pressure 30 mm Hg). Three hours after the end of the shock or sham-shock period, lung permeability, lung histology, pulmonary neutrophil sequestration, neutrophil CD11b expression, gut injury, and red blood cell rigidification were assessed. Measurements and Main Results: Both amiloride and hypertonic saline reduced T/HS-induced pulmonary permeability and neutrophil sequestration, and coadministration of these two agents was more efficacious than administration of the individual agents. In contrast, whereas gut injury was attenuated by both amiloride and hypertonic saline, combined administration of amiloride and hypertonic saline failed to further protect the gut. Additionally, hypertonic saline reduced both neutrophil CD11b expression and red blood cell rigidification, whereas amiloride was without effect. Conclusions: Combined administration of amiloride and small-volume resuscitation with hypertonic saline may be a strategy worthy of further evaluation in the therapy of shock-induced distant organ injury.",
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AU - Fujiyoshi, Naohiko

AU - Deitch, Edwin A.

AU - Feketeova, Eleonora

AU - Lu, Qi

AU - Berezina, Tamara L.

AU - Zaets, Sergey B.

AU - Machiedo, George W.

AU - Xu, Da Zhong

AU - Haskó, G.

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N2 - Objective: Recognition of the limitations of standard crystalloid resuscitation has led to exploration for alternative resuscitation strategies that might better prevent the development of trauma-hemorrhage-induced organ dysfunction and systemic inflammation. Thus, the goal of this study was to compare the effects of two resuscitation strategies alone and in combination with that of standard resuscitation with Ringer's lactate. These two strategies were intravenous injection of amiloride, an inhibitor of Na+/VH + exchange and epithelial Na+ channels, and resuscitation with hypertonic saline. Design: Prospective animal study with concurrent control. Setting: Small animal laboratory. Subjects: Adult male Sprague-Dawley rats. Interventions: Rats injected with amiloride or its vehicle were subjected to trauma-hemorrhagic shock (T/HS) or trauma sham-shock (T/SS) and resuscitated with Ringer's lactate or hypertonic saline. The T/HS model consisted of a laparotomy plus 90 mins of shock (mean arterial pressure 30 mm Hg). Three hours after the end of the shock or sham-shock period, lung permeability, lung histology, pulmonary neutrophil sequestration, neutrophil CD11b expression, gut injury, and red blood cell rigidification were assessed. Measurements and Main Results: Both amiloride and hypertonic saline reduced T/HS-induced pulmonary permeability and neutrophil sequestration, and coadministration of these two agents was more efficacious than administration of the individual agents. In contrast, whereas gut injury was attenuated by both amiloride and hypertonic saline, combined administration of amiloride and hypertonic saline failed to further protect the gut. Additionally, hypertonic saline reduced both neutrophil CD11b expression and red blood cell rigidification, whereas amiloride was without effect. Conclusions: Combined administration of amiloride and small-volume resuscitation with hypertonic saline may be a strategy worthy of further evaluation in the therapy of shock-induced distant organ injury.

AB - Objective: Recognition of the limitations of standard crystalloid resuscitation has led to exploration for alternative resuscitation strategies that might better prevent the development of trauma-hemorrhage-induced organ dysfunction and systemic inflammation. Thus, the goal of this study was to compare the effects of two resuscitation strategies alone and in combination with that of standard resuscitation with Ringer's lactate. These two strategies were intravenous injection of amiloride, an inhibitor of Na+/VH + exchange and epithelial Na+ channels, and resuscitation with hypertonic saline. Design: Prospective animal study with concurrent control. Setting: Small animal laboratory. Subjects: Adult male Sprague-Dawley rats. Interventions: Rats injected with amiloride or its vehicle were subjected to trauma-hemorrhagic shock (T/HS) or trauma sham-shock (T/SS) and resuscitated with Ringer's lactate or hypertonic saline. The T/HS model consisted of a laparotomy plus 90 mins of shock (mean arterial pressure 30 mm Hg). Three hours after the end of the shock or sham-shock period, lung permeability, lung histology, pulmonary neutrophil sequestration, neutrophil CD11b expression, gut injury, and red blood cell rigidification were assessed. Measurements and Main Results: Both amiloride and hypertonic saline reduced T/HS-induced pulmonary permeability and neutrophil sequestration, and coadministration of these two agents was more efficacious than administration of the individual agents. In contrast, whereas gut injury was attenuated by both amiloride and hypertonic saline, combined administration of amiloride and hypertonic saline failed to further protect the gut. Additionally, hypertonic saline reduced both neutrophil CD11b expression and red blood cell rigidification, whereas amiloride was without effect. Conclusions: Combined administration of amiloride and small-volume resuscitation with hypertonic saline may be a strategy worthy of further evaluation in the therapy of shock-induced distant organ injury.

KW - Hyperosmolarity

KW - Hypertonic saline

KW - Lung injury

KW - Neutrophil activation

KW - Red blood cell deformability

KW - Resuscitation

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