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(Circulation. 1997;95:1554-1559.)
© 1997 American Heart Association, Inc.

Articles

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

Takahisa Ueyama, MD; Hisao Ikeda, MD, PhD; Nobuya Haramaki, MD, PhD; Kazunori Kuwano, MD, PhD; Tsutomu Imaizumi, MD, PhD

From the Third Department of Internal Medicine and the Institute of Cardiovascular Diseases, Kurume (Japan) University School of Medicine.

Correspondence to Hisao Ikeda, MD, PhD, The Third Department of Internal Medicine, Kurume University School of Medicine, 67 Asahi-machi, Kurume, 830 Japan.

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.

Key Words: selectins • platelets • sialyl Lewis X • leukocytes • thrombosis

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