Ischemia at 4 degrees C: a novel mouse model to investigate the effect of hypothermia on postischemic hepatic microcirculatory injury

Hypothermia of the ischemic organ at 4 degreesC protects hepatic microcircu lation from ischemia-reperfusion (IR) injury. The effect of hypothermia dur ing ischemia was investigated in animal models using liver transplantation and storage of the harvested organ in cold preservation solutions. No inves tigation of the isolated influence of hypothermia at 4 degreesC of the isch emic organ on hepatic IR injury exists, due to the lack of an appropriate a nimal model. Therefore. the aim of our present study was to develop such a model using intravital video fluorescence microscopy (IVM). In C57BL/6 mice , a reversible isolated ischemia of the left liver lobe was induced for 90 min, followed by 240 min of reperfusion. The temperature of the ischemic or gan was adjusted to either 4 degreesC or 37 degreesC by superfusion with 0. 9% NaCl. Sham-operated animals without IR served as controls. The hepatic m icrocirculation was analyzed using IVM at 30 min and 240 min after reperfus ion by quantifying sinusoidal perfusion and leukocyte-endothelial cell inte raction in postsinusoidal venules. At the end of the experiment, blood and tissue samples were taken for measurement of liver enzyme activities and li ght and electron microscopy. Mean arterial pressure and body temperature we re kept constant throughout the experiment, while the temperature of the is chemic liver lobe was adjusted to predefined levels. After normothermic isc hemia. hepatic microvascular perfusion was significantly impaired compared with sham-operated animals. Perfusion failure was significantly reduced in hypothermic livers and did not differ from livers of the sham-group. Liver enzyme activities in the normothermic group were significantly higher than in the sham and hypothermic groups. Light and electron microscopy revealed severe histological alterations at 37 degreesC ischemia. whereas at 4 degre esC ischemia only minimal lesions were encountered. Our novel model allows for isolated adjustment of ischemic liver lobe temperature without changing body temperature and systemic macrohemodynamic parameters. Hypothermia at 4 degreesC largely attenuates postischemic microvascular perfusion injury o f the liver.