Sialyl Lewis(x) oligosaccharide preserves cardiopulmonary and endothelial function after hypothermic circulatory arrest in lambs

Objective: Neutrophil adhesion to endothelium contributes to cardiopulmonar y dysfunction after cardiac surgical procedures. Initial neutrophil-endothe lial interactions involve selectins, which bind carbohydrate ligands, such as sialyl-Lewis(x). Blockade of selectin-mediated neutrophil interactions w ith CY1503, a synthetic oligosaccharide analog of sialyl-Lewis(x), could li mit neutrophil-mediated injury after cardiopulmonary bypass. Methods: The efficacy of CY1503 treatment was tested in a lamb model of car diopulmonary bypass with hypothermic circulatory arrest. Neonatal lambs rec eived CY1503 (n = 6, CPB-CY1503) or saline solution vehicle (n = 7, CPB-sal ine) into the pump prime before bypass and as a continuous infusion through out reperfusion. Five lambs served as control animals for in vitro microves sel studies. Indexes of myocardial function (preload recruitable stroke wor k index, and rate of pressure rise) and pulmonary function (compliance, air way resistance, and arterial Po-2) were measured before bypass and during r eperfusion, The effect of CY1503 on endothelium-dependent vascular reactivi ty was assessed by means of in vitro pulmonary and coronary microvessel stu dies. Results: Myocardial function was depressed after circulatory arrest, but CY 1503 preserved function near baseline (36% +/- 25% vs 99% +/- 19% of baseli ne at 3 hours of reperfusion), CY1503-treated animals also demonstrated imp roved pulmonary function during reperfusion, In vitro microvessel analysis of vascular reactivity revealed endothelial dysfunction after circulatory a rrest compared with control lambs, CY1503-treated lambs (CPB-CY1503) had in tact endothelial function, as demonstrated by normal vasodilatory responses to endothelium-dependent vasodilators, Conclusions: CY1503 preserves cardiopulmonary and endothelial function afte r cardiopulmonary bypass and hypothermic circulatory arrest in neonatal lam bs. This suggests a role for selectin-mediated, neutrophil-endothelial inte ractions in the inflammatory response after cardiac operations.