Abstract:
Background: Sepsis is a multi-system syndrome that remains the leading cause of
mortality and critical illness worldwide, with hemodynamic support being one of the
cornerstones of the acute management of sepsis. We used an ovine model of
endotoxemic shock to determine if 0.9% saline resuscitation contributes to lung
inflammation and injury in acute respiratory distress syndrome, which is a common
complication of sepsis, and investigated the potential role of matrix metalloproteinases in
this process.
Methods: Endotoxemic shock was induced in sheep by administration of an escalating
dose of lipopolysaccharide, after which they subsequently received either no fluid bolus
resuscitation or a 0.9% saline bolus. Lung tissue, bronchoalveolar fluid (BAL) and
plasma were analysed by real-time PCR, ELISA, flow cytometry and
immunohistochemical staining to assess inflammatory cells, cytokines, hyaluronan and
matrix metalloproteinases.
Results: Endotoxemia was associated with decreased serum albumin and total protein
levels, with activated neutrophils, while the glycocalyx glycosaminoglycan hyaluronan
was significantly increased in BAL. Quantitative real-time PCR studies showed higher
expression of IL-6 and IL-8 with saline resuscitation but no difference in matrix
metalloproteinase expression. BAL and tissue homogenate levels of IL-6, IL-8 and IL-1β
were elevated.
Conclusions: This data shows that the inflammatory response is enhanced when a host
with endotoxemia is resuscitated with saline, with a comparatively higher release of
inflammatory cytokines and endothelial/glycocalyx damage, but no change in matrix
metalloproteinase levels.