THE EFFECT OF ANTI-L-SELECTIN (EL-246) ON REMOTE LUNG INJURY AFTER INFRARENAL ISCHEMIA REPERFUSION/

The clinical concern in using neutrophil adhesion blocking agents is w hether or not neutrophil function may be down-regulated, rendering neu trophils incapable of dealing with infections that may threaten the pa tient. In a sheep model of ischemia and reperfusion, we have investiga ted the effect of anti-l-selectin (EL-246) on the pulmonary injury as well as on the neutrophil function, assessed by in vitro chemiluminesc ence (CL) of isolated neutrophils. Infrarenal ischemia (3 h) followed by reperfusion (4 h) resulted in pulmonary capillary leakage as eviden t by an increased alveolar/plasma protein ratio (.76 vs. .19 in contro l, p < .01) and also led to a significant pulmonary neutrophil accumul ation as assessed by the myeloperoxidase content in homogenized lung t issue (31.7 vs. 6.1 U, p < .01). Anti-L-selectin, infused at a dose of 1 mg/kg at the time of reperfusion, significantly reduced the pulmona ry leakage by 59% (.42 vs. .76 U) and neutrophil accumulation by 84% ( 10.2 vs. 31.7 ii). Pulmonary function improved by anti-L-selectin as r epresented by an increase of the arterio-venous oxygen ratio. CL decre ased from 1.85 x 10(6) counts (c)/min to 1.02 x 10(6) c/min at 15 min of reperfusion in the positive control followed by a subsequent return to normal, In contrast to myeloperoxidase, the significant change in CL was not affected by the use of anti-l-selectin. Based on our data, we conclude that anti-l-selectin is able to significantly reduce the p ulmonary injury in ischemia-reperfusion but in parallel does not resul t in neutrophil dysfunction regarding for example, the respiratory bur st. Thus, using neutrophil adhesion blocking agents in patients appear s to be unlikely to increase the risk of septic complications.