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


METHODS
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.


RESULTS
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.


CONCLUSIONS
The selectin antagonist TBC 1269 reduces neutrophil infiltration into the ileum without altering ileal microvascular permeability or edema associated with cardiopulmonary bypass.
Cox
C S
CS
Department of Surgery, Division of Pediatric Surgery, and the Center for Lymphatic and Microvascular Studies at the University of Texas-Houston, Medical School, Houston, Texas, USA. ccox@utsurg.med.uth.tmc.edu
Allen
S J
SJ
Sauer
H
H
Frederick
J
J
D000818:Animals; D001713:Biphenyl Compounds / Q000494:pharmacology*; D002199:Capillary Permeability; D002315:Cardiopulmonary Bypass; D004285:Dogs; D005260:Female; D007983:Lewis Blood Group Antigens; D016256:Lewis X Antigen / Q000187:drug effects*; D008297:Male; D008358:Mannose / Q000031:analogs & derivatives; D008362:Mannosides / Q000494:pharmacology*; D008833:Microcirculation; D000080506:Sialyl Lewis X Antigen
D001713:Biphenyl Compounds; D007983:Lewis Blood Group Antigens; D016256:Lewis X Antigen; D008362:Mannosides; D000080506:Sialyl Lewis X Antigen; C408402:sialyl-trimeric-Lewis X; C108700:bimosiamose disodium; D008358:Mannose