Sepsis-induced myofibrillar protein catabolism in rat skeletal muscle.

This study evaluated sepsis-induced changes in myosin heavy chain (Mhc) protein breakdown and synthesis in rat soleus muscles. Rats were anesthetized and their external jugular veins were cannulated. After 12-16 h, rats were implanted intraabdominally with a sterile fecal pellet, or a pellet containing bacteria (Escherichia coli, 150 CFU and Bacteroides fragilis 10(4) CFU). Thirty hours after implantations, rats were infused with 14C-Leu (60 x 10(3) Bq/h) through the jugular cannula for 4 h. Protein fractional synthetic rate coefficient (FSRC) was determined in muscles of different rat groups. In separate experiments, intact soleus muscles were removed from the three rat groups on days 1 and 2 after implantations, and processed for their wet weight, total protein and Mhc contents. No mortality occurred in sterile-implanted rats. Approximately 40-45% of all septic-implanted rats died on days 1-3, post-implantation. Whereas an approximately 15% (P < 0.01, days 1 or 2) decrease occurred in Mhc content in sterile-implanted rats compared to unoperated controls, septic insult resulted in a greater Mhc loss (a 27% decrease, P < 0.001). Rats' body weight, soleus wet weight and tolat muscle protein changes with sepsis relative to controls were also greater than in the sterile groups. The FSRC value in the septic-implanted rats was significantly lower (P < 0.05) than in non-septic rat muscle. TNF-alpha administration to the septic animals or their treatment with diltiazem did not have a significant effect on FSRC. Overall, these results indicate myosin as a major muscle protein subjected to net catabolism during sepsis, and that the net catabolic response was related to a more pronounced increased in Mhc degradation than the decrease in Mhc synthesis.