Sepsis-induced inflammation of the lung leads to acute respiratory distress syndrome (ARDS), which may trigger persistent fibrosis. The pathology of ARDS is complex and poorly understood, and the therapeutic approaches are limited. We used a baboon model of Escherichia coli sepsis that mimics the complexity of human disease to study the pathophysiology of ARDS. We performed extensive biochemical, histological, and functional analyses to characterize the disease progression and the long-term effects of sepsis on the lung structure and function. Similar to humans, sepsis-induced ARDS in baboons displays an early inflammatory exudative phase, with extensive necrosis. This is followed by a regenerative phase dominated by proliferation of type 2 epithelial cells, expression of epithelial-to-mesenchymal transition markers, myofibroblast migration and proliferation, and collagen synthesis. Baboons that survived sepsis showed persistent inflammation and collagen deposition 6-27 months after the acute episodes. Long-term survivors had almost double the amount of collagen in the lung as compared with age-matched control animals. Immunostaining for procollagens showed persistent active collagen synthesis within the fibroblastic foci and interalveolar septa. Fibroblasts expressed markers of transforming growth factor-b and platelet-derived growth factor signaling, suggesting their potential role as mediators of myofibroblast migration and proliferation, and collagen deposition. In parallel, up-regulation of the inhibitors of extracellular proteases supports a deregulated matrix remodeling that may contribute to fibrosis. The primate model of sepsisinduced ARDS mimics the disease progression in humans, including chronic inflammation and long-lasting fibrosis. This model helps our understanding of the pathophysiology of fibrosis and the testing of new therapies.Keywords: lung; acute respiratory distress syndrome; sepsis; organ failure; fibrosis Clinical RelevanceSepsis-induced acute lung injury and subsequent persistent inflammation are potential triggers of the fibrotic response. We developed a baboon model of sepsis-induced acute respiratory distress syndrome that leads to long-term inflammation and fibrosis and thus recapitulates the pathophysiology of the human disease.

A young female Boxer had a history of chronic soft stool. Survey abdominal radiographs were unremarkable. A duodenal diverticulum was identified in abdominal ultrasound and barium upper-gastrointestinal contrast examinations. Before surgery a 99mTc-pertechnetate study was performed to evaluate for ectopic gastric mucosa in the duodenal diverticulum. Focal abnormal increased radioactivity was identified in the right caudal abdominal quadrant. The diverticulum was excised. Upon histopathologic examination of the duodenal diverticulum, ectopic gastric mucosa was not identified but ectopic pancreatic tissue was found. Mild eosinophilic inflammation within the diverticulum was suspected to be the cause of the mild 99mTc uptake seen in this dog.

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