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 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. METHODS: 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. RESULTS: 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 CONCLUSION: 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.[1]References
- A novel sialyl Lewis X analog attenuates cerebral injury after deep hypothermic circulatory arrest. Shin'oka, T., Nagashima, M., Nollert, G., Shum-Tim, D., Laussen, P.C., Lidov, H.G., du Plessis, A., Jonas, R.A. J. Thorac. Cardiovasc. Surg. (1999) [Pubmed]
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