Hepatic protein synthesis in a modified septic rat model

Abstract

The aim of this study was to develop a reproducible and sustained sepsis model in rats, lasting 3–4 days and characterized by appropriate metabolic changes, including increased hepatic protein synthesis, consistent with an acute-phase response. The rat cecal ligation and puncture (CLP) model was modified by decreasing the size and number of cecal punctures and increasing fluid resuscitation, which resulted in a 60% survival rate at 96 hr compared to 20% for standard CLP. Cultures of blood and peritoneal fluid 96 hr following induction of sepsis were positive in all septic animals with a mixed aerobic and anaerobic flora but with predominant growth of Escherichia coli. Septic rats demonstrated increased serum lactate levels and leukocytosis, while serum glucose and resting energy expenditure were not different from controls. Hepatic protein synthesis, measured in vivo by flooding dose technique, was increased by 74% in septic animals. Synthesis of the acute-phase proteins α 1-acid glycoprotein, complement component C3, and transferrin, measured by incorporation of [ 14C]leucine into proteins during a 120-min isolated liver perfusion, was increased twofold in septic animals. The present modified CLP model in rats may be useful in studies on the regulation of acute-phase protein synthesis during prolonged sepsis and in experiments aimed at modulating the septic response in liver by different treatments.