lewis-x-antigen and bimosiamose-disodium

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.

Topics: Animals; Biphenyl Compounds; Capillary Permeability; Cardiopulmonary Bypass; Dogs; Female; Lewis Blood Group Antigens; Lewis X Antigen; Male; Mannose; Mannosides; Microcirculation; Sialyl Lewis X Antigen

Neonatal hearts have altered adhesion molecule interactions in response to ischemia-reperfusion. How this affects myocardial function is unknown.. Isolated, buffer perfused 0- to 2-day (newborn) and 2-week piglet hearts were first subjected to 20-minute global, normothermic ischemia, followed by 45 minutes of reperfusion during which 150 x 10(6) newborn or 2-week neutrophils were infused. In some hearts, an antibody to SLe(x) (CSLEX-1) was infused with neutrophils during reperfusion. Hemodynamic variables, including left ventricular developed pressure (LVDP), were recorded at timed intervals. Neutrophil CD-18, L-selectin, and SLe(x) contents were measured by flow cytometry.. Full recovery of LVDP was observed in newborn hearts receiving newborn or 2-week-old neutrophils. Recovery of LVDP was depressed (p < 0.01, ANOVA) in 2-week-old hearts receiving 2-week old, not newborn, neutrophils. Infusion of CSLEX-1 in 2-week-old hearts restored LVDP to baseline. Whereas flow cytometry showed higher (p < 0.01, Student's t test) CD-18 and L-selectin expression on newborn versus 2-week-old neutrophils, newborn neutrophils expressed lower (p < 0.01) SLe(x) levels.. Initial "loose" neutrophil-endothelial selectin interactions are a necessary prelude to "firm" adhesion and reperfusion injury. Operations performed soon after birth may be better tolerated than when surgery is delayed; anti-SLe(x) preparations may prove beneficial when performing cardiac procedures on older infants.

Topics: Animals; Animals, Newborn; Antibodies, Monoclonal; Biphenyl Compounds; CD18 Antigens; Chemotaxis, Leukocyte; Coronary Circulation; Heart Rate; Hemodynamics; L-Selectin; Lewis X Antigen; Mannose; Mannosides; Neutrophils; Reperfusion Injury; Swine