Monoclonal Antibody Against CD18 Reduces Intestinal and Pulmonary Injury in a Model of Ruptured Abdominal Aortic Aneurysm

Abstract

Rupture of an abdominal aortic aneurysm (RAAA) is associated with significant morbidity and mortality due to multiple organ failure after successful repair. Because neutrophils are thought to play a pivotal role in the generation of ischemia-reperfusion injury, the purpose of this study was to determine the role of neutrophils in the generation of local (intestinal) and remote (pulmonary) injury after the combined insults of shock and supramesenteric aortic clamping in a model simulating RAAA repair. Methods Sprague-Dawley rats (450 to 550 g) were hemorrhaged to a mean arterial pressure of 50 mm Hg for 1 hour, followed by 45 minutes of supramesenteric aortic clamping. Animals were given anti-CD18 (4 mg/kg) or control antibody (4 mg/kg) 55 minutes into shock and 5 minutes before clamp placement. Intestinal permeability was determined by measuring I 125 -labeled albumin loss into an isolated, perfused segment of small intestine. Pulmonary permeability (LPI) to albumin-I 125 was determined by bronchoalveolar la-vage. Intestinal and pulmonary myeloperoxidase (MPO) activity and F2-isoprostane levels were measured as indexes of neutrophil sequestration and oxidative stress, respectively. Results In shock plus clamp (S + C) animals there was a significant increase in intestinal plasma protein loss from 7.36 ± 2.14 to 33.66 ± 5.90 mg/g dry intestine ( p p p p p p p p p Conclusions The combination of shock and supramesenteric aortic clamping caused a significant intestinal and pulmonary injury characterized by increased capillary permeability, oxidative stress, and neutrophil sequestration. The administration of anti-CD18 antibody significantly decreased organ injury; however, the results suggest that different neutrophil-mediated mechanisms are responsible for the local intestinal and remote pulmonary injury in this RAAA model.