Abstract
Reperfusion injury is related closely to inflammatory reactions such as the activation and accumulation of neutrophils. We investigated the efficacy of a novel small molecule selectin antagonist (bimosiamose) in a rat model of transient left coronary artery occlusion (30 min) and reperfusion (24 h). Treatment with bimosiamose (25 mg/kg, intravenously at reperfusion) showed a significant reduction in infarction area/area at risk of approximately 41% compared to vehicle control ( P=0.01) and preserved the left ventricular function. The accumulation of polymorphonuclear neutrophils at the site of area at risk was decreased significantly, accompanied by 78% reduction of the myeloperoxidase activity. Parallel-plate flow chamber analysis revealed that bimosiamose showed a significant inhibition in rolling (62%, P<0.001) and adhesion (38%, P<0.05) of HL-60 cells to activated human umbilical vein endothelial cells compared with vehicle control. This study demonstrates for the first time that bimosiamose, a novel small molecule selectin antagonist, attenuates significantly ischemia/reperfusion injury.
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