Volume 2 Supplement 1
0033. Hypothermia protects brain mitochondrial function from hypoxia in sepsis
© Chisholm et al; licensee Springer. 2014
Published: 26 September 2014
Hypothermia reduces metabolic requirements and thereby the oxygen supply-demand imbalance arising from hypoxia. Hypothermia has been an effective treatment in several critical care conditions, but the effects of hypothermia on brain mitochondrial dysfunction in sepsis are poorly understood.
To examine the relationship between spontaneous hypothermia in a murine model of sepsis, and changes in inspired oxygen, systemic oxygenation and mitochondrial function in the cerebral cortex.
Mice (C57/bl6) were injected intraperitoneally with lipopolysaccharide (LPS) (5 mg/kg; n = 15) or saline (0.01 ml/g; n = 6). Six hours later, the cerebral cortex was exposed and mitochondrial function assessed using the inherent fluorescence of flavin adenine dinucleotide (FAD). The mice spontaneously breathed a sequence of 21% oxygen (room air), 100%, 21%, 15%, 21% and 10% for 5 minutes each. Seven of the endotoxic mice were maintained at their original body temperature post-LPS injection, while eight were maintained at 37°C using a homeothermic heating mat. Systemic oxygenation was assessed using pulse oximetry. Statistical analysis was performed by selecting areas around the veins and arteries in order to ratio the fluorescence intensity of arteries over veins. The difference in the ratio between groups was compared using a one way ANOVA followed by independent sample t-tests on IBM SPSS 22.
Systemic administration of LPS increases the vulnerability of cortical mitochondrial function to reductions in inspired oxygen, despite maintenance of arterial oxygen saturation. This vulnerability was reversed by spontaneous hypothermia.
UK MS Society, National MS Society, MRC, UCL Grand Challenge Studentship
This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.