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Infection and Immunity, March 1999, p. 1079-1085, Vol. 67, No. 3
0019-9567/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

A Sustained Rat Model for Studying the Long-Lasting Catabolic State of Sepsis

Denis Breuille,1,* Laure Voisin,2 Michel Contrepois,3 Maurice Arnal,2 Francis Rose,1 and Christiane Obled2

Clintec Technologies, 78140 Vélizy-Villacoublay,1 and Laboratoire d'Etude du Métabolisme Azoté,2 and Laboratoire de Microbiologie,3 INRA Theix, 63122 Ceyrat, France

Received 29 June 1998/Returned for modification 2 November 1998/Accepted 1 December 1998

Most animal models of sepsis induced high mortality or early recovery and do not mimic the long-lasting catabolic state observed in patients. The purpose of this study is to develop a model of sepsis which reproduces these disorders, especially the long-lasting muscle wasting. This report summarizes our observations in a series of seven experiments using this model with rats to study the route of live Escherichia coli administration, dose of bacteria, reproducibility of the model, bacterial count in tissues, comparison of injection of live or dead bacteria, metabolic perturbations linked to infection, and potential role of tumor necrosis factor alpha (TNF-alpha ) in muscle wasting. After intravenous infection, animals were anorexic and the catabolic state was long-lasting: body weight loss for 2 to 3 days followed by a chronic wasting state for several days. Liver, spleen, lung protein content, and plasma concentration of alpha 2-macroglobulin were increased 2 and 6 days after infection. At 6 days, muscle protein content was substantially (-40%) reduced. The plasma TNF-alpha level measured 1.5 h after infection correlated with body weight loss observed 9 days later. The inhibition of TNF-alpha secretion by administration of pentoxifylline 1 h before infection reduced muscle wasting and activation of proteolysis at day 2 and abolished them at day 6. This septic model mimics in rats the prolonged protein metabolism alterations and muscle atrophy characteristics of infected patients and thus is useful for studying the impact of nutritional support on outcome.

* Corresponding author. Mailing address: Laboratoire d'Etude du Métabolisme Azoté, INRA Theix, 63122 Ceyrat, France. Phone: (33) 04 73 62 42 10. Fax: (33) 04 73 62 47 55. E-mail: Breuille{at}Clermont.inra.fr.

Infection and Immunity, March 1999, p. 1079-1085, Vol. 67, No. 3
0019-9567/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


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