An oligosaccharide sialyl-Lewis(x) analogue does not reduce myocardial infarct size after ischemia and reperfusion in dogs.

BACKGROUND

Polymorphonuclear leukocytes, particularly neutrophils, are important mediators of ischemia/reperfusion-induced myocardial and coronary vascular injury. The selectin family of glycoprotein receptors mediates neutrophil "rolling," a loose, transient adhesion to the coronary endothelium that precedes the firmer adhesion associated with cardiovascular injury. The oligosaccharide sialyl-Lewis(x) (SLe(x)) is the probable neutrophil counterligand for endothelial E- and P-selectin. Administration of analogues of SLe(x) could potentially prevent neutrophil rolling by competing for the selectin-adhesion sites. We investigated the effects of treatment with an analogue of SLe(x) in a chronic canine model of ischemia/reperfusion.

METHODS AND RESULTS

Anesthetized mongrel dogs were subjected to 90 minutes of ischemia through occlusion of the left anterior descending coronary artery and 48 hours of reperfusion. Five minutes before the onset of reperfusion, dogs received either the SLe(x) analogue CY-1503 at a dose of 20 mg/kg or normal saline. Myocardial infarct size was measured through triphenyltetrazolium chloride staining, and polymorphonuclear leukocyte accumulation was evaluated through measurement of cardiac myeloperoxidase activity. After adjustment for blood flow, the mean infarct size of control dogs (44.7 +/- 4.2%) was not different from that of treated dogs (33.4 +/- 4.0%, P = .06), although there was a trend toward a slightly lower value in the treated dogs. Myeloperoxidase activity was not different in the infarcted myocardium of the treated group compared with that of the control group (2.7 +/- 0.71 treated versus 1.08 +/- 0.41 units/mg protein control, P = .06).

CONCLUSIONS

We conclude that CY-1503 does not substantially or consistently reduce myocardial infarct size or neutrophil accumulation in dogs subjected to ischemia followed by a prolonged period (48 hours) of reperfusion.