MONOCLONAL-ANTIBODY TO P-SELECTIN (PB1.3) PROTECTS AGAINST MYOCARDIALREPERFUSION INJURY IN THE DOG

Objective: The aim was to determine whether a monoclonal antibody dire cted at P-selectin (PB1.3) would diminish neutrophil accumulation and protect against decrease in coronary dow reserve and myocardial functi on after coronary occlusion-reperfusion. Methods: Sixteen open chest a naesthetised dogs were randomly given PB1.3 (2 mg.kg(-1)) or buffer in travenously after 50 min of total left anterior descending coronary ar tery occlusion. Ten minutes later, the artery was reperfused for 1 h. Coronary flow reserve was measured as peak reactive hyperaemic flow an d as increase in coronary flow in response to acetylcholine and glycer yl trinitrate. Myocardial contractile fraction was measured by ultraso nic crystals. Neutrophil infiltration and oxidative burst in the reper fused area were also measured. Results: Coronary flow reserve and myoc ardial contractile function were markedly impaired in the supply regio n following left anterior descending coronary artery occlusion-reperfu sion in the buffer treated dogs. In contrast, both coronary flow reser ve and contractile fraction were preserved in PB1.3 treated dogs despi te coronary occlusion-reperfusion. Myeloperoxidase, an index of neutro phil infiltration, was increased in the reperfused region in buffer tr eated dogs, but not in the PB1.3 treated dogs. Myocardial histology co nfirmed the reduction in neutrophil accumulation in the reperfused reg ions 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. Conclusions: Antibody to P-selectin (PB 1.3) protects against attenuat ion of coronary flow reserve and myocardial contractile function after coronary occlusion-reperfusion, and decreases neutrophil deposition a nd activation in the reperfused region.