Small bowel transplantation in the rat: ultrastructural changes during the early phases of rejection

Small bowel transplantation has great potential for the treatment of short bowel syndrome, but the poorly understood rapid rejection of the bowel has hindered progress in this field. In this study, the rat model was used to evaluate the earliest detectable changes of bowel rejection. Eleven pairs of outbred rats underwent heterotopic transplantation of 10-15 cm segments of proximal jejunum on a pedicle of superior mesenteric artery and vein, anastomosed microsurgically to recipient aorta and inferior vena cava, respectively. The bowel extremities were exteriorized. Eight successfully transplanted rats were studied with serial punch biopsies, immediately post-transplantation and daily for 7 successive days. Biopsies were evaluated by light (LM) and transmission electron microscopy (TEM). Ultrastructural changes were evident before any gross or histologic changes. Endothelial damage, detected only by TEM, was common and resulted in exposure of the thrombus-promoting subendothelial components. Activated platelets as well as platelet aggregates adhered to these damaged areas. The lumen of some vessels was filled with tightly packed erythrocytes, at times showing intravascular hemolysis, suggestive of stasis. Extravascular features included edema and small numbers of immunocompetent cells. The epithelium showed a variable morphology depending on the degree of change in the underlying vessels and submucosa. The findings suggest that vascular damage and thrombosis as well as immunologic events are important in the early phase of the rejection process. Sustaining a viable segment of transplanted intestine may depend on suppressing both the microthrombotic aspect (with anticoagulants and/or antiplatelet agents) and the ensuing immunologic process with newer modalities such as cyclosporine.