The Effect of CY1503, a Sialyl LewisxAnalog Blocker of the Selectin Adhesion Molecules, on Infarct Size and “No-Reflow” in the Rabbit Model of Acute Myocardial Infarction/Reperfusion

Abstract

CY1503, an analogue of sialyl-Lewisx, is an inhibitor of the selectin adhesion molecules. CY1503 has been found to limit myocardial infarct size in canine and feline models. However, the effect of CY1503 on the “no-reflow” phenomenon is still unknown. Anesthetised rabbits were subjected to 30 min of coronary artery occlusion and 4 h of reperfusion. Protocol 1: after 27 min of ischemia, rabbits were randomised to an iv bolus of either CY1503 (30 mg/kg) (n=9) or saline (n=9). Protocol 2: rabbits were randomly given two iv boluses of CY1503 (30 mg/kg) (n=6) or saline (n=6), administered after 10 and 25 min of ischemia. Protocol 3: after 27 min of ischemia rabbits were randomly given an iv bolus of CY1503 (30 mg/kg) (n=6) and infusion of 20 mg/kg over 4 h or saline bolus+infusion (n=6). Regional myocardial blood flow (RMBF) was assessed after 30 min and 4 h of reperfusion. The risk zone (RZ) was assessed by blue dye and the necrotic zone (NZ) by tetrazolium staining. RMBF: protocol 1: RMBF in the RZ was 2.19±0.33v2.34±0.34 ml/g/min in CY1503 and controls at 30 min (P=0.75), and 0.43±0.07v0.41±0.08 at 4 h of reperfusion (P=0.85). The corresponding results for protocol 2 were 1.77±0.29v1.53±0.34 at 30 min (P=0.61) and 0.53±0.16v0.91±0.55 at 4 h (P=0.53). RMBF in RZ in protocol 3 were 1.52±0.25v1.32±0.20 at 30 min (P=0.56) and 0.30±0.05v0.29±0.09 (P=0.90) after 4 h of reperfusion. The RZ was similar in both groups in all protocols. The NZ/RZ ratio was comparable in the CY1503 and control group in all three protocols (0.32±0.04v0.37±0.06, 0.37±0.08v0.33±0.07, and 0.51±0.05v0.38±0.05 in protocols 1, 2, and 3, respectively). CY1503 did not limit infarct size or prevent the “no-reflow” phenomenon in the rabbit.