Hepatic function is altered in many surgery-related diseases.
Bile acid secretion is the major determinant of bile formation and an important
indicator of overall hepatic function. To investigate the cause of
intrahepatic cholestasis, which is frequently associated with
sepsis, we studied the effects of cecal
ligation and
puncture (CLP) and surgical stress on
bile acid secretion and composition. CLP or a
sham operation was performed on 20 male Sprague-Dawley rats. Bile was collected from each rat by cannulation of the common bile duct for 10-minute intervals, at 5 and 20 hours after the initial procedure.
Bile acid analysis was then performed by high performance liquid chromatography (HPLC). In CLP rats, there was a significant (P < 0.05) cholestatic effect. Bile flow was reduced to 70 +/- 13 per cent at 5 hours, and to 55 +/- 16 per cent at 20 hours (per cent of the
sham mean value). In the
sham-operated rats, there was a significant choleresis at 20 hours. Bile flow was increased to 146 +/- 13 per cent;
bile acid secretion to 245 +/- 24 per cent; and total
bile acid concentration to 175 +/- 19 per cent of the
sham 5-hour value (P < 0.05). This increased secretion was significantly greater in the metabolites of
chenodeoxycholate. However, these surgical stress-associated changes in
bile acid secretion and composition did not occur in CLP rats. These findings are consistent with surgical stress-induced induction of
7 alpha-hydroxylase, which was not found in the septic animals. These observations may provide useful insights into the early stages of the pathogenesis of
sepsis-related hepatic dysfunction and failure.