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.
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/H exchange and epithelial Na channels, and resuscitation with hypertonic saline.


METHODS
Prospective animal study with concurrent control.


METHODS
Small animal laboratory.


METHODS
Adult male Sprague-Dawley rats.


METHODS
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.


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.
Fujiyoshi
Naohiko
N
Department of Surgery, UMDNJ-New Jersey Medical School, Newark, NJ 07103-1709, USA.
Deitch
Edwin A
EA
Feketeova
Eleonora
E
Lu
Qi
Q
Berezina
Tamara L
TL
Zaets
Sergey B
SB
Machiedo
George W
GW
Xu
Da-Zhong
DZ
Haskó
György
G
D000584:Amiloride / Q000627:therapeutic use*; D000818:Animals; D004359:Drug Therapy, Combination; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012128:Respiratory Distress Syndrome / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D012151:Resuscitation / Q000379:methods*; D012462:Saline Solution, Hypertonic / Q000627:therapeutic use*; D012771:Shock, Hemorrhagic / Q000150:complications / Q000188:drug therapy*; D026941:Sodium Channel Blockers / Q000627:therapeutic use*
D012462:Saline Solution, Hypertonic; D026941:Sodium Channel Blockers; D000584:Amiloride