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

Abstract

The initial step in the inflammatory process, which can be initiated 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 analog (CY-1503) on recovery after deep hypothermic circulatory arrest in a piglet model. Twelve Yorkshire piglets were subjected to cardiopulmonary 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 reperfusion (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. Neurologic recovery of animals was evaluated daily by neurologic deficit score (0 = normal, 500 = brain death) and overall performance categories (1 = normal, 5 = brain death). The brain was fixed in situ on the fourth postoperative day and examined by histologic score (0 = normal, 5+ = necrosis) in a blinded fashion. Two of 7 animals in group C died. The neurologic deficit score was significantly lower in group O than in group C (postoperative day 1, P <.001; postoperative day 2, P =.02). The overall performance category was significantly lower in group O than in group C on postoperative 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 O, but this difference did not reach statistical significance (group O = 0.5 +/- 0.7; group C = 1.3 +/- 1.off Blockade of selectin adhesion molecules by saturation with a Sialyl Lewisx analog accelerates recovery after 100 minutes of deep hypothermic circulatory arrest in a piglet survival model.