Urethan anesthesia protects rats against lethal endotoxemia and reduces TNF-alpha release

Anastasia Kotanidou, Augustine M. K. Choi, Richard A. Winchurch, Leo Otterbein, and Henry E. Fessler Division of Pulmonary and Critical Care Medicine and Department of Surgery, The Johns Hopkins Medical Institutions, Baltimore, Maryland 21205-2196; and Department of Critical Care, Medical School of Athens University, Evangelismos Hospital, Athens, Greece GR106 76 Received 21 December 1995; accepted in final form 17 June 1996. Kotanidou, Anastasia, Augustine M. K. Choi, Richard A. Winchurch, Leo Otterbein, and Henry E. Fessler. Urethan anesthesia protects rats against lethal endotoxemia and reduces TNF- release. J. Appl. Physiol. 81(5): 2304-2311, 1996. Urethan is a commonly used animal anesthetic for nonrecovery laboratory surgery. However, urethan has diverse biological effects that may complicate the interpretation of experimental findings. This study examined the effect of urethan on the response to an intravenous bolus of lipopolysaccharide (LPS; 30 mg/kg) in rats. In instrumented rats, urethan (1.2 gm/kg ip) completely prevented the fall in arterial pressure immediately after LPS administration but did not prevent late cardiovascular collapse. In uninstrumented rats, urethan also attenuated indexes of organ injury measured 4 h after LPS administration, including mural bowel hemorrhage, hemoconcentration, hypoglycemia, metabolic acidosis, and lung myeloperoxidase activity, a measure of neutrophil sequestration. The peak increase in tumor necrosis factor- (TNF- ) 90 min after LPS administration was reduced 88% by urethan (2,060 ± 316 vs. 16,934 ± 847 pg/ml; P