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126. Kongress der Deutschen Gesellschaft für Chirurgie

Deutsche Gesellschaft für Chirurgie

28.04. - 01.05.2009, München

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Pharmacological inhibition of p38MAPK in macrophages ameliorates ischemia reperfusion injury after small bowel transplantation (SBTx)

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  • corresponding author T. Pech - Klinik und Poliklinik für Allgemein-, Viszeral-, Thorax-, Gefäßchirurgie, Universitätsklinikum Bonn, Bonn, Deutschland
  • M. Praktiknjo - Klinik und Poliklinik für Allgemein-, Viszeral-, Thorax-, Gefäßchirurgie, Universitätsklinikum Bonn, Bonn, Deutschland
  • J. Fujishiro - Klinik und Poliklinik für Allgemein-, Viszeral-, Thorax-, Gefäßchirurgie, Universitätsklinikum Bonn, Bonn, Deutschland
  • K. Abu-Elmagd - Thomas E. Starzl Transplantation Institute, University of Pittsburgh, Pittsburgh, PA, USA
  • A. Hirner - Klinik und Poliklinik für Allgemein-, Viszeral-, Thorax-, Gefäßchirurgie, Universitätsklinikum Bonn, Bonn, Deutschland
  • J.C. Kalff - Klinik und Poliklinik für Allgemein-, Viszeral-, Thorax-, Gefäßchirurgie, Universitätsklinikum Bonn, Bonn, Deutschland
  • A. Tuerler - Klinik und Poliklinik für Allgemein-, Viszeral-, Thorax-, Gefäßchirurgie, Universitätsklinikum Bonn, Bonn, Deutschland
  • N. Schaefer - Klinik und Poliklinik für Allgemein-, Viszeral-, Thorax-, Gefäßchirurgie, Universitätsklinikum Bonn, Bonn, Deutschland

Deutsche Gesellschaft für Chirurgie. 126. Kongress der Deutschen Gesellschaft für Chirurgie. München, 28.04.-01.05.2009. Düsseldorf: German Medical Science GMS Publishing House; 2009. Doc09dgch11327

doi: 10.3205/09dgch292, urn:nbn:de:0183-09dgch2922

Published: April 23, 2009

© 2009 Pech et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by-nc-nd/3.0/deed.en). You are free: to Share – to copy, distribute and transmit the work, provided the original author and source are credited.

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Introduction: Resident macrophages within the tunica muscularis are known to play a crucial role in initiating ischemia reperfusion injury (IRI) after SBTx contributing to graft dysmotility and bacterial translocation. Therefore we investigated the effects of inhibition of macrophages cytokine releasing pathway on IRI in SBTx by pharmacological inhibition of p38MAPK a key player in cytokine synthesis.

Material and methods: Orthotopic isogenic SBTx was performed in rats (Lewis-Lewis). Recipient and donor animals were treated perioperatively with a macrophage specific p38MAPK inhibitor (1mg/kg, i.v.). Non-transplanted native animals and vehicle treated animals served as control groups (n=8). Animals were sacrificed 3h and 18h after reperfusion. Park’s score was used for histological grading. Leukocyte infiltration was investigated by immunohistochemistry and histochemistry, apoptosis by TUNEL-staining and mediator expression by Real-Time-RT-PCR, ELISA and Griess reaction. Smooth muscle contractility was assessed in a standard organ bath under bethanechol stimulation. Statistics consisted of analysis of variance (ANOVA).

Results: Inhibition of p38MAPK in macrophages results in significant less leukocyte (ED1, MPO) infiltration and amelioration of graft dysmotility 18h after reperfusion compared to vehicle treated group. Proinflammatory cytokines and kinetic active mediators were significantly decreased 3h after reperfusion whereas no significant differences were detectable after 18h. Histologic evaluation revealed protective effects of p38MAPK inhibition at all timepoints.

Conclusion: Early inflammatory processes in the tunica muscularis in SBTx due to ischemia reperfusion injury initiated by activated macrophages are leading to impaired graft motor function. Preoperative treatment with a macrophage specific p38MAPK inhibitor provides protection from IRI with reduced inflammation and graft dysmotility after isogenic SBTx.