Sustained hypermetabolic sepsis in rats: characterization of the model

This paper describes the development of a sustained sepsis model, using chronically catheterized conscious unrestrained rats, which simulates the progression of septicemia in man, including a sustained hypermetabolic phase. Following chronic arterial catheterization, sepsis was induced in rats by intraperitoneal administration of 0.5 ml of a pooled fecal inoculum. The pooled inoculum, which was used to ensure a uniform inoculation of microorganisms to all animals, produced a septicemia which was progressively lethal. The resultant peritonitis was characterized as polymicrobial, with gram-negative bacteria being continuously present in both peritoneal fluid and blood. Septic animals were normotensive but tachycardic, compared to time-matched controls, throughout the observation period. In contrast to the stable colonic temperature of control animals, septic rats showed a significant febrile response on the first 3 days following inoculation. The hypermetabolic response in septic rats was also manifested by a 25, 38, and 28% increase in oxygen consumption on Days 1, 2, and 3 postinoculation. Animals responded to sepsis with a fall in blood glucose (on Day 2) which remained 15--20% below control levels. Mild hyperlactacidemia (2 mM) and reduced alanine concentrations (14--33%) were also seen in the septic group on Days 2 through 5. Despite the increased lactate levels, septic animals were mildly alkalotic (pH 7.51) which probably reflected the increased (32%) respiratory rate. Light microscopic findings in the septic animals revealed a spectrum of morphologic lesions including an extensive fibrinopurulent exudate, bacterial colonies, and abscesses, which involved most of the abdominal viscera. This investigation characterizes an experimental model of sustained sepsis in rats which exhibits hemodynamics, metabolic and pathologic alterations similar to those seen in human peritonitis.