[Clinically relevant sepsis model in minipigs]

Abstract

Objective: Our aim was to develop a large animal model of sepsis induced by fecal peritonitis, which reproduces the characteristic macrohemodynamic, microcirculatory and inflammatory changes seen in human sepsis.

Materials and methods: Anesthetized minipigs were subjected to fecal peritonitis (n = 9; 0.5 g/kg i.p. autofeces) or sham-operation (i.p. saline, n = 6). Invasive hemodynamic monitoring was started with regular blood gas analyses between the 15-24 hr of the insult. Sublingual microcirculation was characterized by red blood cell velocity changes (with orthogonal polarization spectral imaging), and the extravascular lung water index (EVLWI) was measured. The plasma levels of big-endothelin (big-ET) and high-mobility group box protein-1 (HMGB1) were determined from venous blood samples.

Results: The mean arterial pressure gradually decreased below 70 mmHg in septic animals, while the heart rate and cardiac output increased constantly. In spite of the hyperdynamic reaction, significant elevation of the EVLWI was observed, while the sublingual microcirculation deteriorated, as compared with the control group. The big-ET and HMGB1 plasma concentrations were significantly elevated between 6-24 hr of peritonitis.

Conclusion: The in vivo data suggest that our fecal peritonitis-induced experimental sepsis model is of clinical relevance, and may play useful roles in the development of novel, sepsis-related therapies.