Effects of selectin-sialyl Lewis(x) blockade on mesenteric microvascular permeability associated with cardiopulmonary bypass

Objectives: Cardiopulmonary bypass is associated with an inflammatory respo nse that is associated with a neutrophil-mediated microvascular barrier inj ury. We studied the effects of blocking neutrophil-endothelial tethering on microvascular permeability and edema formation during cardiopulmonary bypa ss. Using a selectin antagonist that prevents interactions with their ligan ds, we hypothesized that there would be less neutrophil infiltration into t he tissue and a reduction in microvascular permeability and edema formation . Methods: A canine mesenteric lymphatic fistula was created to measure Starl ing forces and to determine microvascular permeability. Normothermic, atria l-femoral cardiopulmonary bypass was initiated (70-90 mL . kg(-1) . min(-1) ). Intestinal tissue water was determined with microgravimetry. Ileal tissu e myeloperoxidase was measured as an index of neutrophil tissue infiltratio n. One experimental group received the selectin antagonist TBC 1269 before the initiation of bypass, and the control group received saline solution. Results: There was a modest increase in microvascular permeability in both groups, as evidenced by significantly increased transvascular protein clear ance and a trend toward a decrease in reflection coefficient. There were no differences in the experimental group compared with the control group. Ile al tissue myeloperoxidase levels were lower in the experimental group than in the control group. Conclusions: The selectin antagonist TBC 1269 reduces neutrophil infiltrati on into the ileum without altering ileal microvascular permeability or edem a associated with cardiopulmonary bypass.