Open Access Research

Extracorporeal immune therapy with immobilized agonistic anti-Fas antibodies leads to transient reduction of circulating neutrophil numbers and limits tissue damage after hemorrhagic shock/resuscitation in a porcine model

Tim T Lögters12*, Jens Altrichter1, Adnana Paunel-Görgülü1, Martin Sager1, Ingo Witte1, Annina Ott1, Sarah Sadek1, Jessica Baltes1, José Bitu-Moreno3, Alberto Schek1, Wolfram Müller4, Teresa Jeri1, Joachim Windolf1 and Martin Scholz1

Author Affiliations

1 Department of Trauma and Hand Surgery, University Hospital, Düsseldorf, Germany

2 Department of Thoracic and Cardiovascular Surgery, University Hospital, Frankfurt am Main, Germany

3 Department of Vascular Surgery, Faculdade Medicina Marilia (FAMEMA), Marilia, Brasil

4 Pathology Group Starnberg, Starnberg, Germany

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Journal of Inflammation 2010, 7:18  doi:10.1186/1476-9255-7-18

Published: 20 April 2010

Abstract

Background

Hemorrhagic shock/resuscitation is associated with aberrant neutrophil activation and organ failure. This experimental porcine study was done to evaluate the effects of Fas-directed extracorporeal immune therapy with a leukocyte inhibition module (LIM) on hemodynamics, neutrophil tissue infiltration, and tissue damage after hemorrhagic shock/resuscitation.

Methods

In a prospective controlled double-armed animal trial 24 Munich Mini Pigs (30.3 ± 3.3 kg) were rapidly haemorrhaged to reach a mean arterial pressure (MAP) of 35 ± 5 mmHg, maintained hypotensive for 45 minutes, and then were resuscitated with Ringer' solution to baseline MAP. With beginning of resuscitation 12 pigs underwent extracorporeal immune therapy for 3 hours (LIM group) and 12 pigs were resuscitated according to standard medical care (SMC). Haemodynamics, haematologic, metabolic, and organ specific damage parameters were monitored. Neutrophil infiltration was analyzed histologically after 48 and 72 hours. Lipid peroxidation and apoptosis were specifically determined in lung, bowel, and liver.

Results

In the LIM group, neutrophil counts were reduced versus SMC during extracorporeal immune therapy. After 72 hours, the haemodynamic parameters MAP and cardiac output (CO) were significantly better in the LIM group. Histological analyses showed reduction of shock-related neutrophil tissue infiltration in the LIM group, especially in the lungs. Lower amounts of apoptotic cells and lipid peroxidation were found in organs after LIM treatment.

Conclusions

Transient Fas-directed extracorporeal immune therapy may protect from posthemorrhagic neutrophil tissue infiltration and tissue damage.