A sustained rat model for studying the long-lasting catabolic state of sepsis

Most animal models of sepsis induced high mortality or early recovery and d o not mimic the long-lasting catabolic state observed in patients. The purp ose of this study is to develop a model of sepsis which reproduces these di sorders, especially the long-lasting muscle wasting. This report summarizes our observations in a series of seven experiments using this model with ra ts to study the route of live Escherichia coli administration, dose of bact eria, reproducibility of the model, bacterial count in tissues, comparison of injection of live or dead bacteria, metabolic perturbations linked to in fection, and potential role of tumor necrosis factor alpha (TNF-alpha) in m uscle wasting. After intravenous infection, animals were anorexic and the c atabolic 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 co ntent, and plasma concentration of alpha(2)-macroglobulin were increased 2 and 6 days after infection. At 6 days, muscle protein content was substanti ally (-40%) reduced. The plasma TNF-alpha level measured 1.5 h after infect ion correlated with body weight loss observed 9 days later. The inhibition of TNF-alpha secretion by administration of pentoxifyilline 1 h before infe ction reduced muscle wasting and activation of proteolysis at day 2 and abo lished them at day 6, This septic model mimics in rats the prolonged protei n metabolism alterations and muscle atrophy characteristics of infected pat ients and thus is useful for studying the impact of nutritional support on outcome.