Monoclonal antibody to P-selectin (PB1.3) protects against myocardial reperfusion injury in the dog

Abstract

The aim was to determine whether a monoclonal antibody directed at P-selectin (PB1.3) would diminish neutrophil accumulation and protect against decrease in coronary flow reserve and myocardial function after coronary occlusion-reperfusion. Sixteen open chest anaesthetised dogs were randomly given PB1.3 (2 mg.kg-1) or buffer intravenously after 50 min of total left anterior descending coronary artery occlusion. Ten minutes later, the artery was reperfused for 1 h. Coronary flow reserve was measured as peak reactive hyperaemic flow and as increase in coronary flow in response to acetylcholine and glyceryl trinitrate. Myocardial contractile fraction was measured by ultrasonic crystals. Neutrophil infiltration and oxidative burst in the reperfused area were also measured. Coronary flow reserve and myocardial contractile function were markedly impaired in the supply region following left anterior descending coronary artery occlusion-reperfusion in the buffer treated dogs. In contrast, both coronary flow reserve and contractile fraction were preserved in PB1.3 treated dogs despite coronary occlusion-reperfusion. Myeloperoxidase, an index of neutrophil infiltration, was increased in the reperfused region in buffer treated dogs, but not in the PB1.3 treated dogs. Myocardial histology confirmed the reduction in neutrophil accumulation in the reperfused regions in PB1.3 treated dogs. Flow cytometry of the regions supplied by the left anterior descending coronary artery showed a marked decrease in neutrophil oxidative burst in the reperfused region in these dogs. Antibody to P-selectin (PB1.3) protects against attenuation of coronary flow reserve and myocardial contractile function after coronary occlusion-reperfusion, and decreases neutrophil deposition and activation in the reperfused region.