Sialyl LewisX oligosaccharide preserves myocardial and endothelial function during cardioplegic ischemia.
BACKGROUND
Neutrophil adhesion to endothelium contributes to myocardial reperfusion injury after cardiac operation. Initial neutrophil-endothelial interactions involve selectins, which bind Sialyl-LewisX on neutrophils. Blockade of selectin-mediated neutrophil-endothelial interactions with CY-1503, a synthetic analogue of Sialyl-LewisX, 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 had 2 hours of cold cardioplegic ischemia. CY-1503 (40 mg/L) or saline vehicle was added to blood perfusate before ischemia. Contractile function (developed pressure, dP/dt) and coronary vascular endothelial function (acetylcholine response) were assessed at base line and during reperfusion. Myocardial 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 endothelial function, and reduced myocardial neutrophil accumulation.


CONCLUSIONS
In isolated neonatal lamb hearts that underwent hypothermic cardioplegic ischemia, CY-1503 administration reduced myocardial neutrophil accumulation and preserved endothelial and contractile function. Selectin blockade of leukocyte-endothelial interactions might attenuate reperfusion injury and enhance myocardial protection during cardiac surgical procedures.
Schermerhorn
M L
ML
Department of Cardiac Surgery, The Children's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.
Nelson
D P
DP
Blume
E D
ED
Phillips
L
L
Mayer
J E
JE
D000818:Animals; D000831:Animals, Newborn; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000502:physiology; D006321:Heart / Q000187:drug effects* / Q000502:physiology; D066298:In Vitro Techniques; D007983:Lewis Blood Group Antigens; D009200:Myocardial Contraction / Q000187:drug effects; D015428:Myocardial Reperfusion Injury / Q000517:prevention & control*; D009504:Neutrophils / Q000166:cytology; D009844:Oligosaccharides / Q000494:pharmacology* / Q000627:therapeutic use; D009195:Peroxidase / Q000032:analysis; D012756:Sheep; D014664:Vasodilation / Q000187:drug effects*
C090410:CY 1503; D007983:Lewis Blood Group Antigens; D009844:Oligosaccharides; D009195:Peroxidase