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J. Thorac. Cardiovasc. Surg. · Jun 1999
A novel sialyl Lewis X analog attenuates cerebral injury after deep hypothermic circulatory arrest.
- T Shin'oka, M Nagashima, G Nollert, D Shum-Tim, P C Laussen, H G Lidov, A du Plessis, and R A Jonas.
- Department of Cardiovascular Surgery, Children's Hospital, Harvard Medical School, Boston, MA, USA.
- J. Thorac. Cardiovasc. Surg. 1999 Jun 1; 117 (6): 1204-11.
BackgroundThe 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.MethodsTwelve 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.ResultsTwo 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.offConclusionBlockade 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.
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