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Effects of temperature and H2S inhalation on glucose metabolism in murine resuscitated septic shock
© BioMed Central Ltd. 2010
Published: 1 March 2010
In awake, spontaneously breathing mice, inhaling hydrogen sulfide (H2S) induced a hibernation-like metabolic state characterised by reduced energy expenditure and hypothermia , which protected against otherwise lethal hypoxia  and hemorrhage  as a result of impaired cellular energy metabolism . Therefore, we investigated the metabolic effects of inhaled H2S in our model of resuscitated murine septic shock.
Sixteen hours after induction of sepsis by cecal ligation and puncture (CLP) or sham operation, anesthetized and mechanically ventilated mice received 100 ppm H2S or vehicle over 5 hours at body temperatures of 38 and 27°C, respectively. During the observation period, hyperdynamic hemodynamics were maintained by colloid resuscitation and noradrenaline infusion . Endogenous glucose production was calculated from blood 13C6-glucose isotope enrichment derived from the rate of appearance of stable, non-radioactive labeled 1,2,3,4,5,6-13C6 glucose during continuous isotope infusion . Whole-body glucose oxidation rate was derived from the total CO2-production rate, the mixed expiratory 13CO2/12CO2 isotope ratio and the 13C6-glucose infusion rate after the steady state was achieved.
While endogenous glucose production was not affected by hypothermia, it was significantly higher in the septic animals when compared with the corresponding sham operated groups, most likely due to the ongoing noradrenaline infusion. In contrast, despite the catecholamine infusion and higher glucose release, whole body glucose oxidation was significantly reduced in normothermic septic animals. During hypothermia, H2S shifted substrate towards preferential glucose utilisation, but this effect disappeared in the septic mice.
H2S inhalation alone does not influence glucose metabolism once temperature is maintained at normothermic levels in anesthetized and mechanically ventilated mice. The H2S-related shift of energy metabolism towards preferential carbohydrate oxidation present during hypothermia is blunted during sepsis, possibly as a result of the ongoing catecholamine treatment.
Supported by the Deutsche Sepsis Gesellschaft, the DFG KFO 200, and Ikaria Inc., Seattle, WA, USA.
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