A novel Sialyl Lewis X analog attenuates cerebral injury after deep hypothermic circulatory arrest

Background: The initial step in the inflammatory process, which can be init iated by cardiopulmonary bypass and by ischemia/reperfusion, is mediated by interactions between selectins on endothelial cells and on neutrophils, We studied the effects of selectin blockade using a novel Sialyl Lewis X anal og (CY-1503) on recovery after deep hypothermic circulatory arrest in a pig let model. Methods: Twelve Yorkshire piglets were subjected to cardiopulmon ary bypass, 30 minutes of cooling, 100 minutes of circulatory arrest at 15 degrees C, and 40 minutes of rewarming, Five animals received a bolus of 60 mg/kg of CY-1503 and an infusion (3 mg/kg per hour) for 24 hours from repe rfusion (group O), and 7 randomly selected control piglets received saline solution (group C). Body weight and total body water content were evaluated 3 hours and 24 hours after reperfusion by a bio-impedance technique. Neuro logic recovery of animals was evaluated daily by neurologic deficit score ( 0 = normal, 500 = brain death) and overall performance categories (1 = norm al, 5 = brain death), The brain was fixed in situ on the fourth postoperati ve day and examined by histologic score (0 = normal, 5+ = necrosis) in a bl inded fashion, Results: Two of 7 animals in group C died, The neurologic de ficit score was significantly lower in group O than in group C (postoperati ve day 1, P < .001; postoperative day 2, P = .02), The overall performance category was significantly lower in group O than in group C on postoperativ e day 2 (P = .01), Percentage total body water after cardiopulmonary bypass was significantly higher in group C than in group O (P = .03), Histologic score tended to be higher in group C than in group 0, but this difference d id not reach statistical significance (group O = 0.5 +/- 0.7; group C = 1.3 +/- 1,9), Conclusion: Blockade of selectin adhesion molecules by saturatio n with a Sialyl Lewis(x) analog accelerates recovery after 100 minutes of d eep hypothermic circulatory arrest in a piglet survival model.