Hypoxemic resuscitation from hemorrhagic shock prevents lung injury and attenuates oxidative response and IL-8 overexpression.
We investigated whether hypoxemic resuscitation from hemorrhagic shock prevents lung injury and explored the mechanisms involved. We subjected rabbits to hemorrhagic shock for 60 min by exsanguination to a mean arterial pressure of 40 mm Hg. By modifying the fraction of the inspired oxygen, we performed resuscitation under normoxemia (group NormoxRes, P(a)O(2)=95-105 mm Hg) or hypoxemia (group HypoxRes, P(a)O(2)=35-40 mm Hg). Animals not subjected to shock constituted the sham group (P(a)O(2)=95-105 mm Hg). We performed bronchoalveolar lavage (BAL) fluid, lung wet-to-dry weight ratio, and morphological studies. U937 monocyte-like cells were incubated with BAL fluid from each group. Cell peroxides, malondialdehyde, proteins, and cytokines in the BAL fluid were lower in sham than in shocked animals and in HypoxRes than in NormoxRes animals. The inverse was true for ascorbic acid and reduced glutathione. Lung edema, lung neutrophil infiltration, myeloperoxidase, and interleukin (IL)-8 gene expression were reduced in lungs of HypoxRes compared with NormoxRes animals. A colocalized higher expression of IL-8 and nitrotyrosine was found in lungs of NormoxRes animals compared to HypoxRes animals. The BAL fluid of NormoxRes animals compared with HypoxRes animals exerted a greater stimulation of U937 monocyte-like cells for proinflammatory cytokine release, particularly for IL-8. In the presence of p38-MAPK and Syk inhibitors and monosodium urate crystals, IL-8 release was reduced. We conclude that hypoxemic resuscitation from hemorrhagic shock ameliorates lung injury and reduces oxygen radical generation and lung IL-8 expression.
Third Department of Critical Care Medicine, University of Athens Medical School, Evgenidio Hospital, Athens 115 28, Greece. edouzin@med.uoa.gr
Emmanuel E
EE
Douzinas
Alex
A
Betrosian
Evangelos J
EJ
Giamarellos-Bourboulis
Marios-Konstantinos
MK
Tasoulis
Panagiotis
P
Prigouris
Olga
O
Livaditi
Ilias
I
Andrianakis
Nikolaos
N
Goutas
Dimitrios
D
Vlachodimitropoulos
Aimilia
A
Pelekanou
Vassiliki
V
Villiotou
Ioannis
I
Legakis
George P
GP
Chrousos
D000818:Animals; D001992:Bronchoalveolar Lavage Fluid; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D006801:Humans; D000860:Hypoxia; D007124:Immunoenzyme Techniques; D016209:Interleukin-8 / Q000378:metabolism*; D055370:Lung Injury / Q000378:metabolism / Q000517:prevention & control*; D008297:Male; D009504:Neutrophils / Q000378:metabolism; D009195:Peroxidase / Q000378:metabolism; D011817:Rabbits; D017382:Reactive Oxygen Species / Q000378:metabolism; D012151:Resuscitation; D012771:Shock, Hemorrhagic / Q000503:physiopathology*; D020298:U937 Cells
D016207:Cytokines; D016209:Interleukin-8; D017382:Reactive Oxygen Species; D009195:Peroxidase