Pathophysiologic and Immunologic Changes in a Canine Endotoxemia Over a Period of 24 Hours

Abstract

In this study, the pathophysiologic and immunologic parameters from a 24-hr of canine endotoxemia model by lipopolysaccharide (LPS) infusion were evaluated. For that, twelve healthy beagles received a continuous 24-hr IV infusion of low dose LPS (10 μg/kg/hr, from Escherichia coli serotype O111:B4) dissolved in saline. Complete blood counts and serum biochemical analysis as well as histopathologic examination were performed to assess pathophysiologic changes such as neutrophil migration and organ injury. To evaluate immunologic parameters, the concentrations of plasma tumor necrosis factor (TNF)-α, interleukin (IL)-6 and IL-10 were determined, and neutrophil activation was also evaluated based on cell surface expression of CD11b using flow cytometry analysis. As results, systemic signs of endotoxemia including fever, vomiting, and hemorrhagic diarrhea were observed within short time after LPS infusion. Severe leukopenia and increased fluorescent intensity of CD11b on neutrophils were observed at 3 hr while percent positive of CD11b was the maximum at 12 hr during the experiment. Plasma alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), lactate dehydrogenase (LDH) and creatinine phosphokinase (CPK) concentrations increased markedly, and organ damage was confirmed on histopathologic examination. Plasma TNF-α peaked at 3 hr and decreased rapidly, while the concentrations of IL-6 and IL-10 increased gradually until 6 hr and decreased thereafter. Using this canine endotoxemia model, we were able to determine the kinetics of pathophysiologic and immunologic parameters over a period of 24 hr. This study will enhance our understanding of their mechanisms underlying canine sepsis.