Murine models in critical care research.

INTRODUCTION: Access to genetically engineered mice has opened many new opportunities to address questions relevant to the pathophysiology and treatment of patients in critical conditions. However, the results of studies in mice cannot disregard the unique ability of small rodents to adjust their temperature and high metabolic rate and the corresponding respiratory and circulatory requirements in response to hypoxia. POINT OF VIEW: Studies performed in mice on questions related to metabolic, circulatory, and respiratory regulation should always be considered in light of the ability of mice to rapidly drop their nonshivering thermogenesis-related metabolism. As an example, it has been recently argued that a moderate level of inhaled hydrogen sulfide may have a potential benefit in patients in coma or shock or during an anoxic or ischemic insult, as this toxic gas dramatically reduces the metabolic rate in resting mice. However, acute hypometabolism has long been described in small mammals in response to hypoxia and is not specific to hydrogen sulfide. More importantly, mice have a specific metabolic rate that is 15-20 times higher than the specific metabolic level of a resting human. This difference can be accounted for by the large amount of heat produced by mice through nonshivering thermogenesis, related to the activity of uncoupling proteins. This mechanism, which is essential for maintaining homeothermia in small mammals, is virtually absent in larger animals, including in adult humans. Accordingly, no direct metabolic effect of hydrogen sulfide is observed in large mammals. We present the view that similar reasoning should be applied when the circulatory or respiratory response to hypoxic exposure is considered. This leads us to question whether a similar strategy could occur in mice in critical conditions other than hypoxia, such as in hypovolemic, septic, or cardiogenic shock.
CONCLUSION: Mouse models developed to understand the mechanisms of protection against hypoxia or ischemia or to propose new therapeutic approaches applicable in critical care patients should be understood in light of the specificity of the metabolic, respiratory, and circulatory responses of mice to a hypoxic insult, since many of these adaptations have no clear equivalent in humans.