Molecular and functional observations on the donor intestinal muscularis during human small bowel transplantation

Background & Aims: Ischemia-reperfusion injury or intestinal manipulation evokes an Inflammatory response within the intestinal muscularis that Is associated with intestinal dysmotility. We hypothesize that human small intestinal transplantation Induces an analogous response. Methods: Human intestinal graft specimens were obtained during transplantation and compared with specimens removed early during elective bowel resections. Inflammatory gene expression was quantified by real-time reverse-transcription polymerase chain reaction. Histochemistry and Immunohistochemistry were used to characterize leukocyte Infiltration and macrophage activation. In vitro circular muscle contractility and intracellular electric neuromuscular transmission in response to electric field stimulation (EFS) were measured. Results: Messenger RNA (mRNA) values were significantly elevated before reperfusion and further increased during reperfusion (4 hour reperfusion: interleukin [IL]-6, 311-fold; monocyte chemoattractant protein [MCP]-1, 122-fold; IL-8, 338-fold; epithelial neutrophil-activating peptide-78 [ENA-78], 56-fold; intercellular adhesion molecule-1 [ICAM-1], 9-fold; and cyclooxygenase-2 [COX2], 37-fold) over elective specimens. Neutrophils and monocytes extravasated In Increased numbers In whole mounts before and after reperfusion over the elective specimens. Activated resident macrophages were identified as a major source of inflammatory mediators. Muscle contractions and neuromuscular transmission were markedly attenuated In the grafts. Conclusions: The data suggest that manipulation during organ harvesting initiates a functionally relevant molecular and cellular inflammatory response within the graft muscularis that is potentiated during the reperfusion period. Significant mechanical and neuromuscular functional alterations occurred during the transplant process.