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Microvascular perfusion deficits are not a prerequisite for mucosal injury in septic rats
R R Nevière1, M L Pitt-Hyde, R D Piper
1London Health Sciences Centre Research, and the Departments of Medical Biophysics and Medicine, University of Western Ontario, London, Ontario, Canada N6A 4G5.
Abstract:
Our major objective was to investigate whether injury to the mucosa of the small intestine occurred in a normotensive model of sepsis and whether such injury was associated with microvascular perfusion deficits. Using fluorescence intravital microscopy, we show direct evidence of cell injury within the mucosa (pneumonia 12.4 +/- 2.6 cells/field, sham 2.2 +/- 0.7 cells/field), whereas use of 51Cr-labeled EDTA showed evidence of increased mucosal permeability (pneumonia 1.90 +/- 0.67 ml. min-1. 100 g-1; sham 0.24 +/- 0.04 ml. min-1. 100 g-1), 48 h following induction of pneumonia. Despite such injury the capillary density in the ileal mucosa and submucosa of pneumonic rats (1,027 +/- 77 and 1,717 +/- 86 mm2) was not significantly different compared with sham (998 +/- 63 and 1,812 +/- 101 mm2). However, a modest albeit significant decrease in capillary perfusion was measured in the muscularis layer of pneumonia (11.0 +/- 1.3 mm) compared with sham (13.9 +/- 0.63 mm) and appeared to be associated with leukocyte entrapment. Pretreatment using low doses of endotoxin to induce endotoxin tolerance not only increased muscularis capillary density but reduced the number of leukocytes trapped within the microvasculature, decreased myeloperoxidase activity within the ileum in pneumonic rats, and prevented mucosal injury. In conclusion, we have shown that pneumonia results in remote injury to the mucosa of the ileum and that such injury was not associated with concurrent mucosal perfusion deficits.
Insights
Pneumonia causes small intestine mucosal injury and increased permeability, but not reduced blood flow. Endotoxin tolerance prevented this injury by reducing leukocyte buildup in the gut.
Area of Science:
- Gastroenterology
- Microcirculation
- Sepsis Research
Background:
- Sepsis can lead to remote organ damage, including the small intestine.
- The relationship between intestinal mucosal injury and microvascular perfusion deficits during sepsis is not fully understood.
Purpose of the Study:
- To investigate small intestine mucosal injury in a normotensive sepsis model.
- To determine if this injury is linked to microvascular perfusion deficits.
Main Methods:
- Utilized fluorescence intravital microscopy to assess cell injury.
- Employed 51Cr-labeled EDTA to measure mucosal permeability.
- Examined capillary density and perfusion in the ileal mucosa and submucosa.
Main Results:
- Pneumonia induced significant cell injury and increased mucosal permeability in the ileum.
- Capillary density remained unchanged, but muscularis capillary perfusion decreased, associated with leukocyte entrapment.
- Endotoxin tolerance pretreatment prevented mucosal injury and reduced leukocyte entrapment.
Conclusions:
- Pneumonia causes remote ileal mucosal injury independent of concurrent mucosal perfusion deficits.
- Leukocyte entrapment in the muscularis layer may contribute to sepsis-induced intestinal injury.
- Endotoxin tolerance offers a protective mechanism against pneumonia-induced intestinal mucosal damage.