The role of mast cell degranulation in ischaemia-reperfusion-induced mucosal injury in the small intestine.

The role of the intestinal mast cell system in the pathophysiology of postischaemic mucosal lesions is not understood. The present goals were to investigate the contributions of mast cells and mast cell-derived vasoactive mediators to mucosal injury caused by arterial occlusion. We evaluated the intestinal ischaemia-reperfusion-induced local morphological changes in mast cell-depleted anesthetized dogs. Animals subjected to complete segmental intestinal ischaemia and reperfusion served as controls. The selective mucosal-type mast cell degranulator Cremophor-El and the nonselective mast cell depleter Compound 48/80 were used to investigate the involvement of mast cells in reperfusion-induced tissue reactions. Ileal biopsies taken at the end of 120 min of ischaemia and after 120 min of reperfusion were evaluated histologically. The number of mast cells was determined and the degree of mucosal damage was evaluated according to the 0 to 5-grade Chiu scale. Mucosal histidine decarboxylase activity was measured in tissue biopsies and the rate of release of histamine was determined from the venous effluent of the segment. In the control group, 120 min reperfusion induced a severe tissue injury. In the Compound 48/80 and Cremophor-El-pretreated groups, the reduction in the baseline number of mast cells was 37% and 53%, respectively, and the basal mucosal histidine decarboxylase activity was significantly increased. In these groups, the ischaemia-reperfusion-induced release of histamine was significantly decreased, and the degree of damage of the intestinal mucosa was significantly reduced. Mucosal mast cell degranulation plays an important role in the initiation of tissue injury after intestinal ischaemia-reperfusion. Depletion of mast cells prior to ischaemia decreases the severity of mucosal damage, probably in consequence of the stimulation of mucosal histidine decarboxylase activity.

Mast cell degranulation prior to ischemia decreases ischemia-reperfusion injury in the canine small intestine.

OBJECTIVE: To determine the impact of previous mast cell degranulation on intestinal ischemia-reperfusion-induced mucosal damaged. MATERIALS: The hemodynamic and morphological consequences of complete arterial occlusion were evaluated in anesthetized dogs. The mast cell degranulator Cremophor-E1 (n = 5) and Compound 48/80 (n = 5) were used to investigate the involvement of gastrointestinal mast cells in ischemia-reperfusion-induced tissue reactions. Seven dogs subjected to complete segmental arterial occlusion served as controls. Intestinal biopsies taken at the end of 120-min ischemia and after 120 min of reperfusion were evaluated histologically. METHODS: The number of mast cells was determined and the degree of mucosal damage was evaluated according to the 5 grade Chiu scale. Mucosal histidine decarboxylase activity was measured in tissue samples and the rate of release of histamine was determined from the venous effluent of the ileal segment. RESULTS: In the control group, 120-min reperfusion significantly increased the plasma histamine level, and induced a severe tissue injury. In the compound 48/80 and Cremophor-E1-pretreated groups, the reduction in the baseline number of mast cells in the villi was 37% and 53%, respectively, and the ischemia-reperfusion-induced release of histamine was significantly decreased. In these groups, the basal mucosal histidine decarboxylase activity was significantly increased and the degree of damage of the intestinal mucosa was significantly reduced. CONCLUSION: It is proposed that mast cell degranulation prior to ischemia may induce a potentially protective mechanism in the small bowel mucosa and decreases ischemia-reperfusion injury in the dog.

Intramucosal pH changes following complete segmental small intestinal ischemia, as compared with the effects of superior mesenteric artery occlusion.

Microcirculatory nonperfusion of the intestinal mucosa may result in a subsequent prolongation of tissue ischemia, even after restoration of the mesenteric blood flow. It was hypothesized that there is a relationship between mucosal no-reflow and the amount of previously ischemic tissues during intestinal ischemia reperfusion. Accordingly, an examination was made of the changes in intestinal and gastric intramucosal pH (pHi) in dogs after a 120-min complete occlusion of the superior mesenteric artery (SMA) and those observed following ischemia of an ileal segment only. pHi, as an indicator of the adequacy of mucosal microcirculatory perfusion, was calculated by the tonometer technique. Baseline values of intestinal pHi (mean 7.25 +/- 0.12) and gastric pHi (mean 7.23 +/- 0.27) were determined in sham-operated animals. The 120-min intestinal ischemia caused a progressive fall in intestinal pHi to a mean value of approximately 6.8. Reperfusion resulted in a slow return to nearly normal pHi levels in the ileal segment, but essentially no intestinal pHi elevation was observed during the 90-min period following occlusion of the SMA. The gastric pHi remained at the control level during segmental intestinal ischemia reperfusion, but declined below the normal range following release of the occlusion of the SMA. It is proposed that continuing microcirculatory nonperfusion could explain the failure to demonstrate a postreperfusion elevation of pHi following complete occlusion of the SMA.

Tracheal substitution in dogs with reinforced Gore-Tex prosthesis.

Reinforced Gore-Tex prostheses were implanted into the trachea, above the bifurcation, in 11 dogs. The first 3 animals died within a few days, due to an inappropriate surgical technique. The remaining animals were subjected to an adequate surgical procedure and all survived for a period of at least several months, except one which died of an esophago-tracheal fistula after 6 weeks. Ingrowth of respiratory epithelium into the prostheses was observed 5 to 7 weeks postoperatively.