The effect of CY1503, a Sialyl Lewis(x) 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-Lewis(x), 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 mill 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 al 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. (C) 1997 Academic Press Limited.