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J Korean Soc Emerg Med > Volume 19(2); 2008 > Article
Journal of The Korean Society of Emergency Medicine 2008;19(2): 178-184.
The Effect of Hypothermia on the Gene Expression of Inducible NOS and NF-kappaB in the Lung in Hemorrhagic Shock in Rats
Kyu Seok Kim, Jae Hyuk Lee, You Hwan Jo, Kyung Su Kim, Joong Eui Rhee, Woo Jeong Kim, Gil Joon Suh, Jung Bin Lee
1Department of Emergency Medicine, Seoul National University Bundang Hospital, Gyeonggi-do, Korea.
2Department of Emergency Medicine, Seoul National University College of Medicine, Seoul, Korea. suhgil@snu.ac.kr
3Department of Emergency Medicine, Cheju National University Hospital, Jeju-do, Korea.
4Department of Forensic Medicine, Seoul National University College of Medicine, Seoul, Korea.
ABSTRACT
PURPOSE:
In previous studies, therapeutic hypothermia (HT) in hemorrhagic shock (HS) had beneficial effects on the hemodynamic and metabolic parameters, and on the survival. The mechanism is uncertain. We hypothesized that the suppression of inducible nitric oxide synthase (iNOS) and NF-kappaB could be associated with the beneficial effects of therapeutic HT in HS.
METHODS:
Sixteen male Sprague-Dawley rats were randomized to normothermia (36~37degrees C, NT group) or moderate hypothermia (27~30degrees C, HT group). They underwent volumecontrolled (2 ml/100 g weight) HS (90 minutes) and partial resuscitation with shed blood (1 ml/100 g).
RESULTS:
In the HS and post-resuscitation phase, the mean arterial pressures were higher in the HT group than in the NT group and PaO2 was higher in the HT group than in the NT group. The lactate level was lower in the HT group than in the NT group (1.1+/-1.1 nmol/L vs 6.4+/-5.0 nmol/L, p=0.021). Serum concentrations of IL-1 beta and IL-6 and activated p65 NF-kappaB levels in the lung tissue were higher in NT group than in the HT group (p<0.05). Lung malondialdehyde contents and the expression of iNOS mRNA were significantly decreased in the HT group compared to the NT group (63.8+/-6.2 nmol/g vs 44.6+/-4.5 nmol/g, p<0.001; 1313.0+/-924.4 vs 9088.4+/-3984.0 arbitrary units, p<0.001, respectively).
CONCLUSION:
These data suggest that in HS, therapeutic HT inhibits lipid peroxidation, activation of NF-kappaB, and gene expression of iNOS in the lung. These factors might be the mechanism of the beneficial effects of HT in HS.
Key words: Hypothermia, Hemorrhagic shock, Nitric Oxide Synthase Type II, NF-kappa B, Cytokines
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