ENHANCED ISOLATED LUNG-FUNCTION AFTER ISCHEMIA WITH ANTI-INTERCELLULAR ADHESION MOLECULE ANTIBODY

The binding of leukocytes to intercellular adhesion molecules expresse d on endothelial surfaces during ischemia and subsequent reperfusion i nitiates leukocyte-mediated reperfusion injury. Interruption of this l eukocyte-endothelium interaction may therefore prevent reperfusion inj ury. In an isolated, ventilated, blood-perfused rabbit lung preparatio n, we studied the effect of a monoclonal anti-intercellular adhesion m olecule antibody on lung function during reperfusion. Lungs were harve sted with 50 ml/kg cold Euro-Collins flush add 30 mu g prostaglandin E (1) before storage for 18 hours at 4 degrees C. Experimental groups re ceived low-dose (100 mu g) or high-dose (200 mu g) anti-intercellular adhesion molecule antibody added to the pulmonary flush at harvest and to the initial reperfusate. Eighteen-hour control preparations were p reserved for 18 hours and received saline solution vehicle. Immediate control preparations were harvested and immediately reperfused. The ox ygen tension in the recirculated pulmonary venous effluent was measure d after 30 minutes of reperfusion. Histologic specimens were graded by blinded observers for degree of leukocyte infiltration (0, normal, to 4, severe infiltration). The mean oxygen tensions (+/-standard error of the mead) were 138.29 +/- 6.23, 58.86 +/- 9.14, 86.87 +/- 11.32, an d 139.33 +/- 16.15 mm Hg in immediate control preparations, 18-hour co ntrol preparations, low-dose antibody group, and high-dose antibody gr oup, respectively (p = 0.0001). The leukocyte grades (mean +/- standar d error of the mead) were 1.5 +/- 0.723, 3.0 +/- 0.955, 1.9 +/- 0.899, and 1.2 +/- 0.834, respectively (p = 0.0002). We conclude that anti-i ntercellular adhesion molecule antibody added to the pulmonary flush a nd initial reperfusate results in a dose-dependent enhancement of the reperfused lung's ability to oxygenate blood, possibly as a result of decreased leukocyte sequestration.