ENDOTHELIN CONCENTRATIONS IN EXPERIMENTAL SEPSIS - PROFILES OF BIG ENDOTHELIN AND ENDOTHELIN-1-21 IN LETHAL PERITONITIS IN RATS

Objective: To define the profiles of endothelin (ET), both big ET and active 21 amino acid ET (ET 1-21) in the plasma and peritoneal cavity of rats with peritonitis. Design: Open laboratory study. Setting. Univ ersity hospital, Norway. Material: 170 adult male Wistar rats. Interve ntions: Lethal peritonitis was induced by making a 4 mm caecal perfora tion. Main outcome measures: Mortality, together with concentrations o f total ET, ET 1-21 (measured by two radioimmunoassays), bacteria, end otoxin, tumor necrosis factor (TNF), interleukin 6 (IL-6), and lactate at baseline, two hours, and then four-hourly intervals for 24 hours. Results: ET reached its maximum at 8 hours, and had returned to baseli ne after 24 hours. In the first phase of septicaemia there was more bi g ET than ET 1-21, but the proportions had equalised by 8 hours. There were higher concentrations of both big ET and ET 1-21 in peritoneal f luid than in plasma. Conclusions: In rats with peritonitis the profile s of big ET and ET 1-21 closely followed mortality, and blood concentr ations of bacteria, endotoxin, TNF, IL-6, and lactate.