Microvascular Dysfunction, Inflammation and Tissue Injury in Polymicrobial Sepsis
Bibliographic record
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 Information Collaborative 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 .
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".