SIALYL LEWIS(X)-CONTAINING OLIGOSACCHARIDE ATTENUATES MYOCARDIAL REPERFUSION INJURY IN CATS

Neutrophil(PMN) adhesion to the vascular endothelium is an important mechanism of myocardial reperfusion injury. The adhesion process is initially mediated by selectins (e.g., P- and L-selectin), and monoclonal antibodies directed against these adhesion molecules exert cardioprotective activity in ischemia/reperfusion models. The counterreceptors for these selectins are thought to be carbohydrate-containing moieties. In this connection, we studied the effect of a soluble sialyl Lewis(x)-containing oligosaccharide (SLe(x)-OS) on PMN-endothelial interactions in a feline model of myocardial ischemia/reperfusion (MI/R). SLe(x)-OS (10 mg/kg), administered 10 min before R, significantly reduced myocardial necrosis compared with its vehicle 270 min after reperfusion (6 +/- 1% vs. 35 +/- 4% of area at risk, P < 0.01). The cardioprotection was confirmed by significantly lower plasma creatine kinase activities in SLe(x)-OS vs. vehicle-treated cats (P < 0.01). Cardiac contractility (dP/dt max) of cats receiving SLe(x)-OS was significantly preserved after 270 min of R (97 +/- 2% vs. 78 +/- 5% of initial, P < 0.01). Furthermore, endothelium-dependent relaxation to acetylcholine in coronary artery rings isolated from MI/R cats treated with SLe(x)-OS was significantly preserved (73 +/- 7% vs. 22 +/- 6% vasorelaxation, P < 0.01). In vitro PR adherence to coronary vascular endothelium after 270 min of R was significantly attenuated in the SLe(x)-OS-treated group compared with the vehicle group (14 +/- 5 vs. 91 +/- 12 PMN/mm(2), P < 0.01). Our results indicate that a SLe(x)-OS is cardioprotective and preserves coronary endothelial function after MI/R, indicating an important role of sialyl Lewis(x) in PR-IN accumulation, endothelial dysfunction, and myocardial injury in myocardial ischemia/reperfusion.