title: Does endotoxin-activated complement alter myocellular sodium homeostasis during sepsis?
abstract: BACKGROUND
  Inappropriate complement activation is closely related to tissue injury and organ dysfunction during systemic infection. It is not clear, however, if endotoxin-induced complement activation is responsible for changes in myocellular sodium homeostasis during sepsis.
  
  
  METHODS
  Rats underwent cecal ligation and puncture (CLP) or sham operation. Twenty-four hours after operation, fast-twitch extensor digitorum longus (EDL) muscles were isolated, incubated at 30 degrees C for 1 hour in Krebs-Henseleit buffer (KHB) (pH 7.4), and used to measure intracellular Na+ and K+ contents. Blood samples were collected to measure serum hemolytic complement activity and endotoxin levels. In addition, EDL muscles isolated from normal animals were incubated at 30 degrees C for 1 hour with zymosan-activated (10 mg/mL at 37 degrees C for 1 hour) rat sera, with lipopolysaccharide (LPS)-activated (LPS from Escherichia coli 055:B5, 10 or 200 microg/mL at 37 degrees C for 30 minutes) rat sera, with heat-inactivated (56 degrees C for 30 minutes) rat sera, with LPS (1 or 20 microg/mL), or in KHB. EDL muscles isolated from normal animals were also incubated with septic sera collected 6 or 24 hours after CLP with or without administration of soluble complement receptor type 1 (20 mg/kg, intraperitoneally). Myocellular Na+ and K+ contents ([Na+]i and [K+]i) were assayed using "washout" technique. Soluble C5b-9 complex levels in zymosan-activated or LPS-activated human sera were determined by enzyme-linked immunosorbent assay to evaluate the degree of complement activation induced by zymosan or LPS.
  
  
  RESULTS
  Myocellular [Na+]i and [Na+]i/[K+]i ratios increased significantly 24 hours after CLP as compared with sham operation and were associated with decreased serum hemolytic complement activity and increased serum endotoxin levels. Zymosan-activated rat sera at sublytic concentrations markedly increased [Na+]i and [Na+]i/[K+]i ratios in isolated EDL muscles relative to heat-inactivated rat sera. LPS-activated rat sera, however, did not alter these two indices. In addition, myocellular [Na+]i and [Na+]i/[K+]i ratios were equivalent among normal EDL muscles incubated with septic sera, soluble complement receptor type 1-treated septic sera, or KHB.
  
  
  CONCLUSIONS
  These results collectively suggest that polymicrobial sepsis, as produced by CLP, alters sodium homeostasis in fast-twitch skeletal muscles in association with changes in systemic complement activation and circulating endotoxin levels. Although endotoxin can activate the complement cascade, endotoxin-induced complement activation does not appear to be responsible for changes in myocellular sodium homeostasis observed during sepsis in rats.
authors: Department of Surgery, Creighton University Medical Center, Omaha, Nebraska 68131, USA.
authors: Weiyang
authors: W
authors: Wang
authors: Ken
authors: K
authors: Okamoto
authors: Danny O
authors: DO
authors: Jacobs
mesh_terms: D000818:Animals; D002432:Cecum / Q000293:injuries / Q000503:physiopathology; D003167:Complement Activation / Q000187:drug effects* / Q000502:physiology*; D004195:Disease Models, Animal; D004731:Endotoxins / Q000494:pharmacology*; D007424:Intracellular Fluid / Q000737:chemistry / Q000187:drug effects / Q000502:physiology; D008026:Ligation / Q000009:adverse effects; D008297:Male; D018656:Muscle Fibers, Fast-Twitch / Q000187:drug effects* / Q000502:physiology*; D011677:Punctures / Q000009:adverse effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D018805:Sepsis / Q000209:etiology / Q000503:physiopathology*; D012964:Sodium / Q000032:analysis*; D014882:Water-Electrolyte Balance / Q000187:drug effects* / Q000502:physiology*
chemical_list: D004731:Endotoxins; D012964:Sodium