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Reduction of Myocardial Infarct Size in the Rabbit by a Carbohydrate Analog of Sialyl Lewisx

Department of Pathology, University of Michigan Medical School, Ann Arbor, Michigan

James L. Park

Department of Pharmacology, University of Michigan Medical School, Ann Arbor, Michigan

Liguo Chi

Department of Pharmacology, University of Michigan Medical School, Ann Arbor, Michigan

John H. Musser

Glycomed, Inc., Alameda, California

Vandana Date

Glycomed, Inc., Alameda, California

Saeed Abbas

Glycomed, Inc., Alameda, California

Benedict R. Lucchesi

Department of Pharmacology, University of Michigan Medical School, Ann Arbor, Michigan

Background: Available data suggest that the accumulation of neutrophils within the myocardium following an ischemic event plays an important role in the pathogenesis of myocardial ischemia/reperfusion injury. It is of interest, therefore, to develop pharmacologic agents designed to inhibit neutrophil adhesion to the endothelium.

Methods and Results: A synthetic carbohydrate analog to the P-selectin ligand sialyl Lewis ^x (sLe^x) was evaluated for its ability to protect the myocardium from ischemia/reperfusion injury. Open chest anesthetized rabbits were subjected to 30 minutes occlusion of the left cir cumflex artery followed by 5 hours of reperfusion. Vehicle or sLe ^x analog (10 mg/kg) was administered intravenously before the onset of reperfusion and every hour during the reper fusion period. Myocardial infarct size in rabbits treated with the sLe^x analog was significantly reduced when compared to rabbits treated with vehicle (28 ± 9% vs 57 ± 10% of the area at risk, P < .05). The compound did not alter circulating neutrophil counts or myocardial oxy gen demand as determined by the rate-pressure product. Furthermore, neutrophil accumula tion within the ischemic region was decreased by 44% (P < .05) in the hearts of animals receiving sLe^x analog as compared to vehicle.

Conclusions: Carbohydrate derivatives of sLe^x may be effective in reducing the degree of myocardial injury after ischemia/reperfusion.

Key Words: selectins • reperfusion injury • neutrophils.

Journal of Cardiovascular Pharmacology and Therapeutics, Vol. 1, No. 1, 49-56 (1996)
DOI: 10.1177/107424849600100108


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