The Effect of Hypothermia on the Gene Expression of Inducible NOS and NF-kappaB in the Lung in Hemorrhagic Shock in Rats

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.