Further Evidence that Accelerated Muscle Protein Breakdown During Sepsis Is Not Mediated by Prostaglandin E2

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Abstract
Prostaglandin E2 (PGE2) reportedly increases protein breakdown in skeletal muscle. The role of PGE2 for accelerated muscle proteolysis during sepsis, however, is controversial. In this study, the effect of the prostaglandin synthesis inhibitor indomcthacin on PGE2 release and protein breakdown in skeletal muscle from nonscptic and septic rats was evaluated. Sepsis was induced in male Sprague-Dawley rats (40–60 g) by cecal ligation and puncture (CLP). After 16 hours the extensor digitorum longus (EDL) and soleus (SOL) muscles were dissected with intact tendons and incubated in an oxygenated medium, and the release of tyrosine (protein breakdown) and PGE2 into the incubation medium was determined. Paired muscles were incubated in the absence or presence of indomcthacin (3 $mUmol/L or 6 $mUmol/L). In some experiments the effect of indomethacin was investigated in the presence of different concentrations of insulin (1, 10, or 100 mU/mL) since previous reports suggested an interaction between insulin and prostaglnndins on protein turnover in skeletal muscle. In other experiments muscles were incubated in a flaccid or stretched state, which is known to influence the metabolic response to different substances. Protein breakdown rate was 0.210 ± 0.013 and 0.492 ± 0.025 $mUmol Tyr/g χ 2 hours in EDL from nonscptic and septic rats, respectively (p < 0.01). The corresponding values for SOL were 0.480 ± 0.037 and 0.712 ± 0.039 $mUmol Tyr/g χ 2 hours (p < 0.01). Addition of indomcthacin to the incubation medium reduced PGE2 release from 29.1 ± 3.1 to 6.8 ± 0.7 ng/g χ 2 hours in nonseptic SOL and from 50.6 ± 10.4 to 5.6 ± 0.7 ng/g χ 2 hours in septic SOL. Protein breakdown rate in SOL and EDL from sham-operated or septic rats was unaffected by indomethacin, both when muscles were incubated in a flaccid or stretched state, and when they were incubated in the presence or absence of insulin. The present results do not suggest a role of PGE2 for accelerated muscle proteolysis in the present experimental septic model.