0027. Kinetic of muscle mass regulation during experimental sepsis
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0027. Kinetic of muscle mass regulation during experimental sepsis J-C Palao1,2*, J Morel1,2, A-C Durieux2, J Castells2, S Molliex1, D Freyssenet2 From ESICM LIVES 2014 Barcelona, Spain. 27 September - 1 October 2014 Introduction Sepsis induced muscle weakness (SIMW) is associated with an important morbidity of critical care patients. Moreover, respiratory muscles weakness delays weaning from mechanical ventilation. The down-regulation of Akt pathway and the activation of proteolytic pathways, such as ubiquitin-proteasome or autophagy-lysosome pathways, could play a key role in the pathogenesis of SIMW. However, the kinetic response of these pathways is currently unknown. Objectives The aim of this study was to describe the kinetic response of anabolic and proteolytic pathways in a murine model of sepsis. A clear picture of mechanisms involved in SIMW could help to develop strategies to prevent muscle casting. Methods Sixteen week-old male mice were divided in a septic group (peritonitis induced by cecal ligature and puncture, CLP) and a sham group (laparotomy without cecal ligature or puncture). Sham-operated mice were pair-fed to septic mice. Following surgery, mice were daily hydrated subcutaneously. Mice were weighed daily and muscle strength assessed by grip test. Animals were sacrificed at day 1, 4 or 7 after surgery (n = 8/group). Tibialis anterior, gastrocnemius, quadriceps, soleus, extensor digitorum longus and
diaphragm muscles were removed to perform molecular (enzymology, RT-qPCR and western blotting) and histological analyses.
Results Loss of muscle mass and strength was observed as soon as day 1 following CLP and was maximum at day 4 for all skeletal muscles (Fig 1). In the gastrocnemius muscle, chymotrypsin-like activity of the proteasome was also higher at day 4 (Fig 2), whereas activity of cathepsin B+L, proteins involved in autophagy-lysosomal pathway, was maximum at day 7 (Fig 2). In the diaphragm muscle, chymoptrysin-like and cathespin B+L activities peaked at day 4. Citrate synthase activity, a marker of mitochondrial content, was minimal at day 4 both in gastrocnemius and diaphragm muscles. Conclusions Our results confirm a major role for the proteasome in muscle wasting during sepsis. Interestingly, the increase in cathepsin B+L activity at day 7 in gastrocnemius muscle, when muscle mass had already started to recover, suggests that the autophagy pathway could participate to the recovery of skeletal muscle by inducing the clearance of damaged proteins and organelles. Such a late increase in cathepsin B+L activity was not observed in diaphragm muscle. The decrease in citrate synthase activity observed in both muscles may reflect mitochondrial impairment. These results should be
1 Centre Hospitalier Universitaire de Saint-Etienne, Service d’AnesthésieRéanimation, Saint-Priest en Jarez, France Full list of author information is available at the end of the article
© 2014 Palao et al; licensee Springer. This is an Open Access article distributed under the terms
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