Inflammation and lung injury in an ovine model of fluid resuscitated endotoxemic shock

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.

An Ovine Model of Hemorrhagic Shock and Resuscitation, to Assess Recovery of Tissue Oxygen Delivery and Oxygen Debt, and Inform Patient Blood Management

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“…The lung histopathology score was calculated according to the histopathological severity of the analyzed sections of each lung (six separate random fields per tissue section). The scores were assigned as follows: normal = 0; minor = 1; mild= 2; intermediate = 3; and severe = 4 ( 22 , 23 ).…”

Palmatine Attenuates Metastatic Lung Colonization of Triple Negative Breast Cancer Cells

“…4 µm thick deparaffinized sections were stained with hematoxylin and eosin (H&E) and analyzed at 10 × magnification. The histology sections were evaluated for metastatic lesions, morphological changes and necroinflammation according to a modified histology activity index ( Gibson-Corley et al, 2013 ; Passmore et al, 2018 ). The sections were scored by a cumulative quantitative score of 0–4 representing; 0—Normal histological alterations, 1–3—Mild/moderate/severe and 4- Extreme histological alterations ( Tables 1 and 2 ).…”