Induced hypothermia attenuates the acute lung injury in hemorrhagic shock.
BACKGROUND
In previous animal studies, induction of therapeutic hypothermia (HT) in hemorrhagic shock (HS) had beneficial effects on the hemodynamic and metabolic parameters and on the survival. However, the effect of induced HT on acute lung injury (ALI) in HS has not been investigated. We sought to determine the effects of HT on ALI in HS.


METHODS
Male Sprague-Dawley rats (350-390 g; n = 8 per group) were randomized to the normothermia (NT; 36-37 degrees C) group or the moderate HT (27-30 degrees C) group and were subjected to volume-controlled (2 mL/100 g weight) HS (90 minutes) followed by 90 minutes of resuscitation. ALI score, lung malondialdehyde content, and myeloperoxidase activity were measured. The expression of glycogen synthase kinase 3beta (GSK-3beta), phosphorylated GSK-3beta, inducible nitric oxide synthase (iNOS), heat shock protein (HSP) 72, and nuclear factor-kappaB (NF-kappaB) in the lung were compared.


RESULTS
ALI score, lung malondialdehyde content, and myeloperoxidase were lower in the HT group. GSK-3beta and iNOS gene expressions in lung tissue were significantly decreased in the HT group (p < 0.05). On the contrary, the expression of phosphorylated GSK-3beta was increased in the HT group (p < 0.001). HSP 72 was expressed in the HT group but not in the NT group. The activated p65 NF-kappaB levels in lung nuclear extract were significantly lower in the NT group (p = 0.03).


CONCLUSIONS
HT attenuates HS-induced ALI in rats by the modulation of GSK, HSP 72, iNOS, and NF-kappaB.
Kim
Kyuseok
K
Department of Emergency Medicine, Seoul National University College of Medicine, South Korea. dremkks@snubh.org
Kim
Woojeong
W
Rhee
Joong Eui
JE
Jo
You Hwan
YH
Lee
Jae Hyuk
JH
Kim
Kyung Su
KS
Kwon
Woon Yong
WY
Suh
Gil Joon
GJ
Lee
Christopher C
CC
Singer
Adam J
AJ
D055371:Acute Lung Injury / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control*; D000818:Animals; D038362:Glycogen Synthase Kinase 3 / Q000032:analysis; D050884:HSP72 Heat-Shock Proteins / Q000032:analysis; D007036:Hypothermia, Induced; D016753:Interleukin-10 / Q000032:analysis; D015850:Interleukin-6 / Q000032:analysis; D008168:Lung / Q000737:chemistry; D008297:Male; D008315:Malondialdehyde / Q000032:analysis; D016328:NF-kappa B / Q000032:analysis; D052247:Nitric Oxide Synthase Type II / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D012771:Shock, Hemorrhagic / Q000150:complications* / Q000503:physiopathology
D050884:HSP72 Heat-Shock Proteins; D015850:Interleukin-6; D016328:NF-kappa B; D016753:Interleukin-10; D008315:Malondialdehyde; D052247:Nitric Oxide Synthase Type II; D038362:Glycogen Synthase Kinase 3