Comparison of urethane/chloralose and pentobarbitone anaesthesia for examining effects of bacterial lipopolysaccharide in mice

Although anaesthetics are widely used to alleviate stress in endotoxaemic animals, these drugs themselves may interfere with the effects of lipopolysaccharide (LPS). The effects of LPS on serum glucose, biochemical markers of hepatic, renal and pancreatic exocrine function, and lung myeloperoxidase (MPO) activity were compared using anaesthesia with either urethane/chloralose or pentobarbitone. Groups of 10-13 of C57B1/6 mice (22.3 +/- 0.18 g) were treated with 40 mg/kg LPS or the same volume of saline (10 mL/kg, i.p.) at time 0, Animals were anaesthetized either with urethane (1000 mg/kg) and chloralose (50 mg/kg) or with pentobarbitone (90 mg/kg, i.p.) after 2 h and blood and lung samples obtained after 6 h. In pentobarbitone-anaesthetized mice, LPS caused hypoglycaemia and increased serum levels of alanine aminotransferase (ALT), lipase and creatinine suggesting damage/dysfunction of liver, exocrine pancreas and kidney respectively. Lung tissue MPO activity, an indicator of neutrophil infiltration, was also increased. Urethane/chloralose-treated mice demonstrated hypoglycaemia and enhanced serum levels of ALT and creatinine in response to LPS, but failed to show LPS-induced increases in serum lipase and lung MPO activity. It is concluded that while pentobarbitone may be successfully used in experimental models of endotoxaemia in mice, anaesthesia with urethane and chloralose may protect mice against LPS-mediated damage/dysfunction in the exocrine pancreas and in the lung, and therefore, is not recommended in studies on endotoxaemic mice.