The effect of CY1503, a sialyl Lewisx analog blocker of the selectin adhesion molecules, on infarct size and "no-reflow" in the rabbit model of acute myocardial infarction/reperfusion.

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+/-0.33 v 2. 34+/-0.34 ml/g/min in CY1503 and controls at 30 min (P=0.75), and 0. 43+/-0.07 v 0.41+/-0.08 at 4 h of reperfusion (P=0.85). The corresponding results for protocol 2 were 1.77+/-0.29 v 1.53+/-0.34 at 30 min (P=0.61) and 0.53+/-0.16 v 0.91+/-0.55 at 4 h (P=0.53). RMBF in RZ in protocol 3 were 1.52+/-0.25 v 1.32+/-0.20 at 30 min (P=0.56) and 0.30+/-0.05 v 0.29+/-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+/-0.04 v 0.37+/-0.06, 0.37+/-0.08 v 0.33+/-0. 07, and 0.51+/-0.05 v 0.38+/-0.05 in protocols 1, 2, and 3, respectively). CY1503 did not limit infarct size or prevent the "no-reflow" phenomenon in the rabbit.