Microvascular Dysfunction, Inflammation and Tissue Injury in Polymicrobial Sepsis

Abstract

Sepsis is an overwhelming systemic inflammatory response to infection that may lead to multiple organ failure and shock. One of the characteristics of sepsis is early microvascular dysfunction. In our rat model of polymicrobial sepsis, microvascular dysfunction is detected as early as 3 hours after infection (Bateman et al., Am J Physiol Heart Circ Physiol, 2001). The objective of this study was to examine the timing of microvascular dysfunction in the context of tissue injury and inflammation. Sepsis was induced in male Sprague‐Dawley rats with an intraperitoneal injection of a fecal slurry. Control animals were injected with normal saline. The septic and control animals were then prepared for intravital video microscopy (IVVM) of the right extensor digitorum longus (EDL) muscle. The microvasculature was examined for changes in hemodynamics and erythrocyte oxygen saturation using dual wavelength IVVM for a period of 4 or 6 hours after the injection of the fecal slurry. The data were set aside for future analysis and comparisons were made to our existing hemodynamic data in order to further characterize our sepsis model. Completion of IVVM observations was followed by perfusion fixation and organ collection. Hematoxylin and eosin‐stained sections were graded for pathological and inflammatory changes normalized to tissues collected from naïve control animals. Livers from septic and control animals were both marked by mild leukocyte infiltration in the 4‐hour and 6‐ hour groups, while erythrocyte trapping within the microvasculature did not rise above naïve levels and parenchymal cell architecture was not altered. The EDL muscles from septic animals did not exhibit increased inflammatory cell infiltration. Immunohistochemical labelling of brain sections for rat MHC class II did not show signs of inflammatory microglial activation in coronal slices spanning the entire brain in the septic animals from the 4‐hour and 6‐hour groups. Intravenous injection of Evans Blue prior to perfusion fixation also indicated that the blood‐brain barrier was not broken. On the other hand, septic rats had evidence of increased dye leakage in the liver and kidneys, which was not observed in the saline‐injected animals. Evans Blue leakage was not observed in the intact EDL muscles of either group. The findings of this study suggest that microvascular dysfunction occurs before detectable organ injury in our rat fecal‐induced peritonitis model of sepsis.Support or Funding InformationCollaborative Health Research Projects ( CHRP )This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.