gms | German Medical Science

123. Kongress der Deutschen Gesellschaft für Chirurgie

Deutsche Gesellschaft für Chirurgie

02. bis 05.05.2006, Berlin

Burn-induced Cardiac Dysfunction: Recombinant Lipopolysaccharide-binding protein (rLBP) attenuates Cardiomyocyte Contraction Deficits

Meeting Abstract

  • corresponding author A.D. Niederbichler - University of Michigan, Dept. of Surgery, Trauma Burn Center, Ann Arbor, MI, USA
  • L.M. Hoesel - University of Michigan, Dept. of Surgery, Trauma Burn Center, Ann Arbor, MI, USA
  • K. Ipaktchi - University of Michigan, Dept. of Surgery, Trauma Burn Center, Ann Arbor, MI, USA
  • S. Arbabi - University of Michigan, Dept. of Surgery, Trauma Burn Center, Ann Arbor, MI, USA
  • M. Erdmann - Klinik f. Plastische, Hand- und Wiederherstellungschirurgie, Schwerbrandverletztenzentrum, Med. Hochschule Hannover, Deutschland
  • M.V. Westfall - University of Michigan, Dept. of Surgery, Trauma Burn Center, Ann Arbor, MI, USA
  • M.R. Hemmila - University of Michigan, Dept. of Surgery, Trauma Burn Center, Ann Arbor, MI, USA
  • P.M. Vogt - Klinik f. Plastische, Hand- und Wiederherstellungschirurgie, Schwerbrandverletztenzentrum, Med. Hochschule Hannover, Deutschland
  • S.C. Wang - University of Michigan, Dept. of Surgery, Trauma Burn Center, Ann Arbor, MI, USA

Deutsche Gesellschaft für Chirurgie. 123. Kongress der Deutschen Gesellschaft für Chirurgie. Berlin, 02.-05.05.2006. Düsseldorf, Köln: German Medical Science; 2006. Doc06dgch5496

Die elektronische Version dieses Artikels ist vollständig und ist verfügbar unter: http://www.egms.de/de/meetings/dgch2006/06dgch387.shtml

Veröffentlicht: 2. Mai 2006

© 2006 Niederbichler et al.
Dieser Artikel ist ein Open Access-Artikel und steht unter den Creative Commons Lizenzbedingungen (http://creativecommons.org/licenses/by-nc-nd/3.0/deed.de). Er darf vervielf&aauml;ltigt, verbreitet und &oauml;ffentlich zug&aauml;nglich gemacht werden, vorausgesetzt dass Autor und Quelle genannt werden.


Gliederung

Text

Einleitung: Postburn cardiac dysfunction plays a pivotal role because it is decisive of patient survival or death. Gram-negative bacterial infection can lead to further contractile deterioration via the exposure to endotoxin (lipopolysaccharide, LPS). LPS induces substantial cardiomyocyte sarcomere contraction deficits both alone and – more severely – after burn injury. Lipopolysaccharide-binding protein (LBP) is an acute phase protein capable of initiating recognition of LPS aggregates by binding to the lipid A moiety of LPS. In the present study we sought to determine the effect of LBP on single-cardiomyocyte sarcomere contraction after burn or sham injury in the presence or absence of bacterial endotoxin.

Material und Methoden: Male Sprague-Dawley rats (~300g BW) were given a III° burn injury (~30% TBSA). At t=24 hrs, cardiomyocytes were isolated and subsets of cardiomyocytes were challenged with rLBP or BVCat (control protein) ± 50 µg LPS / ml media. Mechanistically, serum (1,3 %) derived from LBP knockout (LBPko) and wildtype C57/Bl6 mice was added to myocyte subsets (± LPS challenge). Single-cell sarcomere shortening levels and functional parameters were recorded using a CCD video camera system. rLBP was produced in a baculovirus expression system. Full-length rat LBP cDNA was cloned in-frame into pBluebacHis2c (Invitrogen, Carlsbad, CA) to cotransfect SF-9 insect cells. An irrelevant control protein, chloramphenicol acetyltransferase (BVCat) was produced in a similar fashion. Statistical analysis was done using analysis of variance (ANOVA) followed by Tukey’s post-hoc tests where appropriate.

Ergebnisse: rLBP at higher concentrations (>10%) improved peak sarcomere shortening levels in the presence of 50 µg/ml LPS in burn and sham cardiomyocytes in vitro (p<0.01). LBP significantly improved the contraction velocity (1/s). Mechanistically, addition of LBPko serum revealed no functional effects, whereas C57/Bl6 serum at 3% (LBP-sufficient) significantly improved the myocyte contractile function (p<0.05).

Schlussfolgerung: 1.Recombinant LBP has a beneficial effect on cardiomyocyte sarcomere contraction in vitro. 2.This effect is LBP-specific - LBPko serum had no effect on myocyte function and LBP-sufficient serum induced contractile improvement.3.We propose a blocking effect of LBP leading to non-functional LPS-LBP aggregates that are incapable of binding to the CD14 receptor. 4.LPS interception using recombinant LBP may represent a novel therapeutic strategy for postburn cardiac dysfunction.