Does endotoxin-activated complement alter myocellular sodium homeostasis during sepsis?

Area of Science:

• Physiology
• Immunology
• Biochemistry

Background:

• Inappropriate complement activation contributes to tissue injury in systemic infections.
• The role of endotoxin-induced complement activation in sepsis-related myocellular sodium imbalance remains unclear.

Purpose of the Study:

• To investigate the impact of polymicrobial sepsis on myocellular sodium homeostasis in rats.
• To determine if endotoxin-induced complement activation mediates sepsis-induced changes in muscle sodium balance.

Main Methods:

• Rats underwent cecal ligation and puncture (CLP) or sham operation to induce sepsis.
• Isolated extensor digitorum longus (EDL) muscles were analyzed for intracellular sodium ([Na+]i) and potassium ([K+]i) content.
• Muscles were incubated with zymosan-activated sera, lipopolysaccharide (LPS)-activated sera, or septic sera to assess complement activation effects.

Main Results:

• CLP-induced sepsis significantly increased myocellular [Na+]i and [Na+]i/[K+]i ratios, correlating with decreased complement activity and elevated endotoxin levels.
• Zymosan-activated sera increased myocellular [Na+]i and [Na+]i/[K+]i ratios, while LPS-activated sera did not.
• Septic sera, even when treated with complement inhibitor, did not alter myocellular sodium and potassium levels.

Conclusions:

• Polymicrobial sepsis alters sodium homeostasis in fast-twitch skeletal muscles.
• Changes in muscle sodium balance are associated with systemic complement activation and endotoxin levels.
• Endotoxin-induced complement activation is not responsible for the observed myocellular sodium dysregulation in sepsis.