EFFECTS OF LOW DOSE-INTRA-ARTERIAL MONOCLONAL-ANTIBODIES TO ICAM-1 AND CD11 CD18 ON LOCAL AND SYSTEMIC CONSEQUENCES OF ISCHEMIA-REPERFUSIONINJURY IN SKELETAL-MUSCLE/

The aim of this study was to investigate the effects of intra-arterial infusion of low doses of monoclonal antibodies (Mabs) against adhesio n molecules (the neutrophil CD18 integrins, and the endothelial adhesi on molecule, ICAM-1) on reperfusion injury in skeletal muscle. The rab bit rectus femoris muscle was rendered ischaemic for 2 1/2 hours. Mabs were infused (similar to 0.5 mg/kg) commencing 20 minutes before the end of ischaemia and for the first hour of reperfusion. 24 hours after reperfusion, the muscle was assessed for viability, oedema and neutro phil infiltration (myeloperoxidase (MPO) levels). The results of the v iability assessment (control-20.9 (0-47.5)% [median (range)], anti-CD1 8 - 30.5 (3.0-89.4)%, anti-ICAM-1 - 27.9 (7.8-78.1)% and anti-CD18 com bined with anti-ICAM-1 - 45.2 (15.6-92.3)%) showed no significant diff erences between groups, while analysis of MPO in the postischaemic mus cle showed that the anti-ICAM-1 Mab reduced neutrophil infiltration si gnificantly. Furthermore, in contralateral unoperated muscles MPO leve ls were elevated 24 hours after ischaemia in the contralateral muscle. This increased neutrophil infiltration was prevented by pretreatment with anti-ICAM-1. These results suggest that low doses of anti-CD18 an d anti-ICAM-1 Mabs do not reduce reperfusion injury in skeletal muscle but may help to protect against systemic effects of severe trauma. Th e evidence suggests that reperfusion injury in this skeletal muscle mo del may be largely independent of neutrophil involvement.