Effects of Monoclonal Antibody to P-Selectin and Analogue of Sialyl Lewis X on Cyclic Flow Variations in Stenosed and Endothelium-Injured Canine Coronary Arteries

BACKGROUND: A fundamental role of cell adhesion molecules is implicated in the disease processes of acute coronary syndromes. We have shown an increase in the soluble form of P-selectin in these syndromes, suggesting the important interaction between P-selectin and sialyl Lewis X (SLe(x)) for the pathophysiology of these syndromes. To further test this, we examined the effects of a monoclonal antibody against P-selectin (PB1.3) and a carbohydrate analogue of SLe(x) (SLe(x)-OS) on cyclic flow variations (CFVs) in stenosed and endothelium-injured canine coronary arteries. METHODS AND RESULTS: Anesthetized, open-chest dogs (n = 48) were divided into six groups after CFVs were established. Dogs received intravenous normal saline, PB1.3 (1 mg/kg bolus), a low dose (5 mg/kg bolus) or a high dose (40 mg/kg bolus) of SLe(x)-OS followed by an infusion (5 mg.kg-1.h-1) for 60 minutes, a combination of PB1.3 and SLe(x)-OS (low dose), or a combination of a nonblocking antibody against P-selectin (PNB1.6, 1 mg/kg) and SLe(x)-OS (low dose). Although saline, PB1.3, SLe(x)-OS (low dose), and the combination of PNB1.6 and SLe(x)-OS (low dose) did not affect CFVs, the high dose of SLe(x)-OS and the combination of PB1.3 and SLe(x)-OS (low dose) significantly reduced CFVs. CONCLUSIONS: These findings indicate that the high dose of SLe(x)-OS and the combination of PB1.3 and the low dose of SLe(x)-OS provide protection against CFVs. Thus, the adhesive interaction between P-selectin and SLe(x) may play an important role in mediating CFVs in this model.