This study evaluated sepsis-induced changes in myosin heavy chain (Mhc
) protein breakdown and synthesis in rat soleus muscles. Rats were ane
sthetized and their external jugular veins were cannulated. After 12-1
6 h, rats were implanted intraabdominally with a sterile fecal pellet,
or a pellet containing bacteria (Escherichia coli, 150 CFU and Bacter
oides fragilis 10(4) CFU). Thirty hours after implantations, rats were
infused with C-14- Leu (60 x 10(3) Bq/h) through the jugular cannula
for 4 h. Protein fractional synthetic rate coefficient (FSRC) was dete
rmined in muscles of different rat groups. In separate experiments, in
tact soleus muscles were removed from the three rat groups on days 1 a
nd 2 after implantations, and processed for their wet weight, total pr
otein and Mhc contents. No mortality occurred in sterile-implanted rat
s. 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 t
o unoperated controls, septic insult resulted in a greater Mhc loss (a
27% decrease, P<0.001). Rats' body weight, soleus wet weight and tola
t muscle protein changes with sepsis relative to controls were also gr
eater than in the sterile groups. The FSRC value in the septic-implant
ed rats was significantly lower (P<0.05) than in non-septic rat muscle
. TNF-alpha administration to the septic animals or their treatment wi
th diltiazem did not have a significant effect on FSRC. Overall, these
results indicate myosin as a major muscle protein subjected to net ca
tabolism during sepsis, and that the net catabolic response was relate
d to a more pronounced increase in Mhc degradation than the decrease i
n Mhc synthesis.