Early mucosal and microvascular changes in feline intestinal transplants

Bowel transplantation in humans is being performed with increasing success, but little is known about the early physiological alterations occurring in the graft. The objectives of this study were to characterize the mucosal and microvascular alterations that occur in the early stages of reperfusion of small intestinal allografts after varying intervals of hypothermic preservation and to assess the role of reactive oxygen metabolites and leukocyte adhesion glycoproteins in mediating these alterations.

A feline model of small intestinal transplantation was developed in which ileal grafts underwent 0-24 hours of cold ischemia before reperfusion. Some allografts, which underwent 6 hours of cold ischemia, were treated with monoclonal antibodies directed against either leukocyte (CD11/CD18) or endothelial cell (ICAM-1 or P-selectin) adhesion molecules or with a combination of superoxide dismutase and catalase.

Cold preservation for 6 hours resulted in significant increases in intestinal microvascular fluid and protein exchange, and mucosal function was compromised. These alterations were not affected by treatment with either superoxide dismutase and catalase or monoclonal antibodies against ICAM-1 or P-selectin; however, the microvascular dysfunction was largely prevented by immunoneutralization of CD11/CD18 on leukocytes.

CD11/CD18 antibodies may be useful in preserving microvascular function in allografts after prolonged hypothermic ischemia.