Sialyl Lewis(x) oligosaccharide preserves myocardial and endothelial function during cardioplegic ischemia

Background. Neutrophil adhesion to endothelium contributes to myocardial re perfusion injury after cardiac operation. Initial neutrophil-endothelial in teractions involve selectins, which bind Sialyl-Lewis(X) on neutrophils. Bl ockade of selectin-mediated neutrophil-endothelial interactions with CY-150 3, a synthetic analogue of Sialyl-Lewis(X), might reduce reperfusion injury after myocardial ischemia. Methods. The efficacy of CY-1503 to attenuate global myocardial reperfusion injury was assessed in isolated blood-perfused neonatal lamb hearts that h ad 2 hours of cold cardioplegic ischemia. CY-1503 (40 mg/L) or saline vehic le was added to blood perfusate before ischemia. Contractile function (deve loped pressure, dP/dt) and coronary vascular endothelial function (acetylch oline response) were assessed at base line and during reperfusion. Myocardi al neutrophil accumulation was assessed by myeloperoxidase quantification. Results. Compared to controls, treatment with CY-1503 improved recovery of all indices of contractile function, preserved coronary vascular endothelia l function, and reduced myocardial neutrophil accumulation. Conclusions. In isolated neonatal lamb hearts that underwent hypothermic ca rdioplegic ischemia, CY-1503 administration reduced myocardial neutrophil a ccumulation and preserved endothelial and contractile function. Selectin bl ockade of leukocyte-endothelial interactions might attenuate reperfusion in jury and enhance myocardial protection during cardiac surgical procedures. (Ann Thorac Surg 2000;70:890-4) (C) 2000 by The Society of Thoracic Surgeon s.