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J Thorac Cardiovasc Surg 1999;117:1204-1211
© 1999 Mosby, Inc.
SURGERY FOR CONGENITAL HEART DISEASE |
From the Department of Cardiovascular Surgery, Children's Hospital, and Department of Surgery, Harvard Medical Schoola; the Department of Anesthesia and Intensive Care, Children's Hospital, and Department of Anesthesia, Harvard Medical Schoolb; the Department of Pathology, Children's Hospital, and Department of Pathology, Harvard Medical Schoolc; and the Department of Neurology, Children's Hospital, and Department of Neurology, Harvard Medical School,d Boston, Mass.
Received for publication Dec 4, 1998. Revisions requested Jan 5, 1999. Revisions received Feb 2, 1999. Accepted for publication Feb 9, 1999. Address for reprints: Richard A. Jonas, MD, Department of Cardiovascular Surgery, Children's Hospital, 300 Longwood Ave, Boston, MA 02115.
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°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 ± 1.9).
Conclusion: Blockade of selectin adhesion molecules by saturation with a Sialyl Lewisxanalog accelerates recovery after 100 minutes of deep hypothermic circulatory arrest in a piglet survival model.
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