Chronic hyperdynamic sepsis in the rat: I. Characterization of the animal model

We describe a new rat model of chronic hyperdynamic sepsis. After control values for weight gain, and food and water intake of each animal were obtained over a 5-day period, male Sprague-Dawley rats weighing 370-425 g were anesthetized, catheterized to allow chronic cardiac-output measurements, and a sterile subcutaneous cavity was formed over the flank area. The animals were allowed a 3-4 day postoperative recovery period. Body weight, food and water intake, and cardiac output were measured daily. Frequent blood samples were withdrawn for bacterial cultures and white cell counts (WBC). On the third and, in some cases, the fourth postoperative day, the subcutaneous cavity was inoculated with 10(9) colony-forming units of Escherichia coli and Bacteroides fragilis. The resulting sepsis was characterized by loss of body weight in spite of normal food and water intake, increased cardiac output, increased WBC, intermittent bacteremia, decreased muscle mass, and decreased cross-sectional area of skeletal muscle myofibrils. Two levels of septic response emerged--moderate and severe. Based on the above-mentioned measurements, it was possible to categorize all long-term septic animals into these two groups. Both groups exhibited cardiac-output, body-weight, and WBC data significantly different from sham controls. Repeated inoculations of the subcutaneous abscess initiated on the third postoperative day resulted in moderate sepsis with no long-term mortality, severe sepsis with 23% mortality over a 3-week period, or a 100% mortality within 4 days, depending on the virulence of the E. coli organisms used. The new model is ideally suited for pathophysiologic studies of sustained, hyperdynamic sepsis.