Abstract

BackgroundSepsis 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.MethodsEndotoxemic 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.ResultsEndotoxemia 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.ConclusionsThis 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.

Highlights

  • Sepsis represents a serious global health issue, accounting for more than USD $20 billion of total US hospital costs in 2011 [1]

  • It is unclear if the observed incidence of acute respiratory distress syndrome (ARDS) in sepsis is wholly attributable to the response to infection, or partially due to iatrogenic injury from fluid resuscitation

  • This study aims to investigate if a resuscitation strategy utilizing fluid resuscitation independently contributes to inflammation, lung injury and the development of ARDS in sepsis

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Summary

Introduction

Sepsis represents a serious global health issue, accounting for more than USD $20 billion of total US hospital costs in 2011 [1]. Acute lung injury and acute respiratory distress syndrome (ARDS) are common complications of sepsis. Sepsis is characterized by pulmonary inflammation, neutrophil recruitment, oedema and tissue fibrosis, all leading to decreased pulmonary function [9]. It is unclear if the observed incidence of ARDS in sepsis is wholly attributable to the response to infection, or partially due to iatrogenic injury from fluid resuscitation. 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

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