Lung reperfusion injury is reduced by inhibiting a CD18-dependent mechanism.

CD18 designates a component of a leukocyte surface glycoprotein complex that mediates endothelial adherence. To determine whether interference with CD18-dependent leukocyte adhesion modifies reperfusion injury, we transplanted 16 canine left lungs after 4-hour preservation with modified Euro-Collins solution. Anti-canine CD18 monoclonal antibody (R15.7, 1 mg/kg, intravenously) was administered to eight lung recipients 5 minutes before reperfusion; eight control recipients were not treated. Ventilation was identical in donor-recipient pairs (tidal volume, 600 ml; fraction of inspired oxygen, 0.53; positive end-expiratory pressure, 5 cm H2O). Respiratory and inert gas exchange and hemodynamics were assessed in left lung donors one-half hour after right lung exclusion and in allograft recipients at 0.5, 1.5, 2.5, 3.5, and 6.0 hours after transplantation and right lung exclusion. Reperfusion injury was evident in both recipient groups at 6 hours after transplantation, but inert gas shunt was lower in monoclonal antibody-treated dogs (13% +/- 6%) than in controls (30% +/- 17%, p < 0.05); comparisons of arterial blood gases in monoclonal antibody recipients (PaO2, 209 +/- 83 mm Hg; PaCO2, 45 +/- 7 mm Hg) and controls (PaO2, 108 +/- 54, p < 0.05; PaCO2, 64 +/- 25, p < 0.05) at 6 hours indicated that monoclonal antibody administration distinctly improved respiratory gas transfer. Gravimetric lung water was less in monoclonal antibody recipients (5.78 +/- 1.01 ml/kg) than in controls (8.02 +/- 1.90 ml/kg, p < 0.05), but lung compliance at 6 hours was equally reduced in monoclonal antibody recipients (40 +/- 9 ml/cm H2O) and in controls (39 +/- 7 ml/cm H2O, p = not significant). Pulmonary vascular resistance doubled immediately after transplantation but was identical in monoclonal antibody-treated dogs (890 +/- 168 dynes.sec.cm-5) and in controls (874 +/- 162 dynes.sec.cm-5, p = not significant) at 6 hours. We conclude that inhibition of CD18-dependent leukocyte function attenuates the development of both shunt and abnormal respiratory gas exchange in lung reperfusion injury. Significant physiologic abnormalities occurred despite R15.7 treatment and may represent inadequate preservation or the effect of CD18-independent adhesion mechanisms.