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.


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.
Ueyama
T
T
Third Department of Internal Medicine, Kurume University School of Medicine, Japan.
Ikeda
H
H
Haramaki
N
N
Kuwano
K
K
Imaizumi
T
T
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D003326:Coronary Circulation / Q000187:drug effects*; D003327:Coronary Disease / Q000503:physiopathology*; D004285:Dogs; D004338:Drug Combinations; D004730:Endothelium, Vascular / Q000293:injuries*; D009844:Oligosaccharides / Q000494:pharmacology*; D019007:P-Selectin / Q000276:immunology*; D000080506:Sialyl Lewis X Antigen; D014947:Wounds and Injuries / Q000503:physiopathology*
D000911:Antibodies, Monoclonal; D004338:Drug Combinations; D009844:Oligosaccharides; D019007:P-Selectin; D000080506:Sialyl Lewis X Antigen