A CD18 monoclonal antibody reduces multiple organ injury in a model of ruptured abdominal aortic aneurysm

Abstract

The role of CD18 antibody (anti-CD18) in remote and local injury in a model of ruptured abdominal aortic aneurysm repair was investigated. Rats were divided into sham, shock, clamp, and shock + clamp groups. Shock + clamp animals received anti-CD18 or a control monoclonal antibody. One hour of hemorrhagic shock was followed by 45 min of supramesenteric aortic clamping. Intestinal and pulmonary permeability to125I-labeled albumin was determined. Myeloperoxidase (MPO) activity, F2-isoprostane levels, and transaminases were also measured. Only shock + clamp resulted in statistically significant increases in pulmonary and intestinal permeability, which were associated with significant increases in MPO activity and F2-isoprostane levels. Treatment with anti-CD18 significantly decreased intestinal and pulmonary permeability in shock + clamp animals. These reductions were associated with significantly reduced intestinal and hepatic MPO activity and pulmonary F2-isoprostane levels and reduced alanine and aspartate aminotransferase levels; however, anti-CD18 had no effect on intestinal or hepatic F2-isoprostane levels or on pulmonary MPO activity. These results suggest CD18-dependent and -independent mechanisms of local and remote organ injury in this model of ruptured abdominal aortic aneurysm.

Selective inducible nitric oxide synthase (iNOS) inhibition attenuates remote acute lung injury in a model of ruptured abdominal aortic aneurysm1

“…Treatment with the selective iNOS inhibitor, L-NIL, early in the reperfusion period significantly prevented the increased pulmonary permeability and neutrophil sequestration. The mechanism whereby lung injury in this model is primarily caused by neutrophil adherence, sequestration, and subsequent respiratory burst-induced oxidative injury is supported by the observation that lung injury can be attenuated with anti-CD18 monoclonal antibodies [12]. In this model, the combination of the systemic hemorrhagic shock injury compounded by lower torso ischemia-reperfusion produces a severe acute lung injury.…”

“…Intestinal permeability, which was used as an index of intestinal injury, was measured as previously described [12]. A 5-cm segment of jejunum, approximately 10 cm from the ligament of Treitz, was isolated and cannulated at its proximal end with an input cannula and at its distal end with an output cannula.…”

“…Tissues were assayed for MPO, an index of neutrophil sequestration, as previously described [12]. In short, MPO activity was assessed at 37°C by monitoring the change in absorbance at 655 nm over a 3-min period in a Cobas FARA II centrifugal analyzer (Roche Diagnostic Systems, Montclair, NJ).…”

“…Pulmonary sequestration of activated neutrophils is followed by acute pulmonary microvascular injury [7][8][9][10], acute respiratory distress syndrome (ARDS) [11], and a high subsequent mortality. We have previously shown, in a rat model of RAAA, that hemorrhagic shock paired with supramesenteric aortic clamping results in local intestinal and remote lung injury, and that this remote lung injury is mainly neutrophil mediated and can be attenuated by reducing neutrophil adherence [12].…”

Protective Strategies of High-Frequency Oscillatory Ventilation in a Rabbit Model

“…MPO activity assays of frozen tissue samples used in experimental models as an index of neutrophil sequestration are well described (12)(13)(14). MPO activity was assessed using a spectrophotometric technique with tetramethylbenzidine as substrate (15,16).…”