Effects of selectin-sialyl Lewis blockade on mesenteric microvascular permeability associated with cardiopulmonary bypass.

Abstract

Cardiopulmonary bypass is associated with an inflammatory response that is associated with a neutrophil-mediated microvascular barrier injury. We studied the effects of blocking neutrophil-endothelial tethering on microvascular permeability and edema formation during cardiopulmonary bypass. Using a selectin antagonist that prevents interactions with their ligands, we hypothesized that there would be less neutrophil infiltration into the tissue and a reduction in microvascular permeability and edema formation. A canine mesenteric lymphatic fistula was created to measure Starling forces and to determine microvascular permeability. Normothermic, atrial-femoral cardiopulmonary bypass was initiated (70-90 mL. kg(-1). min(-1)). Intestinal tissue water was determined with microgravimetry. Ileal tissue myeloperoxidase was measured as an index of neutrophil tissue infiltration. One experimental group received the selectin antagonist TBC 1269 before the initiation of bypass, and the control group received saline solution. There was a modest increase in microvascular permeability in both groups, as evidenced by significantly increased transvascular protein clearance and a trend toward a decrease in reflection coefficient. There were no differences in the experimental group compared with the control group. Ileal tissue myeloperoxidase levels were lower in the experimental group than in the control group. The selectin antagonist TBC 1269 reduces neutrophil infiltration into the ileum without altering ileal microvascular permeability or edema associated with cardiopulmonary bypass.