EFFECTS OF A MONOCLONAL-ANTIBODY TO P-SELECTIN ON RECOVERY OF NEONATAL LAMB HEARTS AFTER COLD CARDIOPLEGIC ISCHEMIA

Background-The interaction between endothelium and leukocytes plays a crucial role in ischemia-reperfusion injury. P-selectin, which is expr essed on activated endothelium, mediates the first step in leukocyte a dherence to the endothelium. This study examined the effects of a mono clonal antibody (mAb) against P-selectin on the recovery of cardiac fu nction and myocardial neutrophil infiltration after ischemia. Methods and Results-Thirteen blood-perfused, isolated neonatal lamb hearts und erwent 2 hours of hypothermic cardioplegic at-rest and 2 hours of repe rfusion. Immediately before reperfusion, mAb to P-selectin was adminis tered to the perfusate (15 mu g/mL) in 6 hearts (group P-sel). In cont rol (n = 7), the same volume of saline was added. Isovolumic left vent ricular function and coronary blood flow were measured. At 2 hours aft er reperfusion, myocardial myeloperoxidase activity, an index of neutr ophil accumulation, was assayed. At 30 minutes of reperfusion, hearts treated with mAb to P-selectin achieved significantly greater recovery of maximum developed pressure (70+/-4% in control versus 77+/-2% in g roup P-sel, P<0.01), maximum positive first derivative of pressure (dP /dt) (64+/-7% in control versus 73+/-5% in group P-sel, P<0.05), and m aximum negative dP/dt (61+/-6% in control versus 70+/-6% in group P-se l, P<0.05) compared with control. Percent baseline of coronary blood f low was also significantly increased in group P-sel (135+/-40% in cont rol versus 205+/-43% in group P-sel, P<0.05). Myocardial myeloperoxida se activity was significantly lower (P<0.05) in group P-sel (4.7+/-3.2 ) versus control (16.0+/-10.1). (Units are change in absorbance/min/g tissue.) Conclusions-The functional blockade of P-selectin resulted in better recovery of cardiac function and attenuated neutrophil accumul ation during early reperfusion. Strategies to block P-selectin mediate d neutrophil adherence may have clinical application in improving myoc ardial function at early reperfusion.