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J Thorac Cardiovasc Surg 1996;111:941-947
© 1996 Mosby, Inc.

GENERAL THORACIC SURGERY

ENHANCED ISOLATED LUNG FUNCTION AFTER ISCHEMIA WITH ANTININTERCELLULAR ADHESION MOLECULE ANTIBODY

From the Thoracic and Cardiovascular Research Laboratory, Department of Surgery, University of Virginia Health Sciences Center, Charlottesville, Va.

Received for publication June 21, 1995 Revisions requested Oct. 3, 1995; revisions received Oct. 20, 1995 Accepted for publication Dec. 21, 1995. Address for reprints: Curtis G. Tribble, MD, Professor, Thoracic and Cardiovascular Surgery, Box 310, Department of Surgery, University of Virginia Health Sciences Center, Charlottesville, VA 22908.

Abstract

The binding of leukocytes to intercellular adhesion molecules expressed on endothelial surfaces during ischemia and subsequent reperfusion initiates leukocyte-mediated reperfusion injury. Interruption of this leukocyte-endothelium interaction may therefore prevent reperfusion injury. In an isolated, ventilated, blood-perfused rabbit lung preparation, we studied the effect of a monoclonal anti–intercellular adhesion molecule antibody on lung function during reperfusion. Lungs were harvested with 50 ml/kg cold Euro-Collins flush and 30 µg prostaglandin E₁ before storage for 18 hours at 4º C. Experimental groups received low-dose (100 µg) or high-dose (200 µg) anti–intercellular adhesion molecule antibody added to the pulmonary flush at harvest and to the initial reperfusate. Eighteen-hour control preparations were preserved for 18 hours and received saline solution vehicle. Immediate control preparations were harvested and immediately reperfused. The oxygen tension in the recirculated pulmonary venous effluent was measured 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 mean) were 138.29 ± 6.23, 58.86 ± 9.14, 86.87 ± 11.32, and 139.33 ± 16.15 mm Hg in immediate control preparations, 18-hour control preparations, low-dose antibody group, and high-dose antibody group, respectively (p = 0.0001). The leukocyte grades (mean ± standard error of the mean) 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–intercellular adhesion molecule antibody added to the pulmonary flush and 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. (J THORAC CARDIOVASC SURG 1996;111:941-7)

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