title: Early myocardial dysfunction is not caused by mitochondrial abnormalities in a rat model of peritonitis.
abstract: BACKGROUND
  Patients with complicated intra-abdominal infections are prone to develop multiple organ failure, including myocardial dysfunction. We hypothesized that early dysfunction during sepsis is associated with inflammation, mitochondrial injury, impaired mitochondrial function, and activation of mitochondrial biogenesis.
  
  
  METHODS
  Rats received lipopolysaccharide (LPS, n = 11) intraperitoneally. Healthy rats (n = 6) served as controls. Myocardial function was measured ex vivo in an isolated Langendorff-perfused heart set-up. Myocardial vascular cell adhesion molecule-1 (VCAM-1) expression was determined by immunofluorescence microscopy. Cytochrome c release and cytochrome c oxidase (COX IV) activity were measured by immunohistochemistry and enzyme histochemistry, respectively. Protein expression of tumor necrosis factor-α (TNF-α), B-cell lymphoma (Bcl)-2, peroxisome proliferator activated receptor γ cofactor 1α (PGC-1α), and mitochondrial transcription factor A (TFAM) were analyzed by Western blot technique. Mitochondria were studied by electron microscopy.
  
  
  RESULTS
  Two hours after LPS injection, developed pressure had decreased and after 4 h myocardial contractility (+dP/dt) and relaxation (-dP/dt) also had decreased. TNF-α protein expression was increased after 2 h and returned to normal at 4 h, whereas after 4 h VCAM-1 expression was higher in LPS-treated animals. At 2 h a substrate-dependent increase in COXIV-activity was seen, but no mitochondrial damage occurred as cytochrome c release, COX IV activity and Bcl-2, PGC-1α or TFAM expression were not changed. Electron microscopy did not reveal differences in myocardial mitochondrial characteristics between LPS-treated and control rats.
  
  
  CONCLUSIONS
  Early myocardial dysfunction in sepsis is associated with myocardial inflammation but not with mitochondrial injury, impaired mitochondrial function, or activated mitochondrial biogenesis.
authors.affiliation: Department of Pediatric Intensive Care, VU University Medical Center, Amsterdam, The Netherlands. l.smeding@vumc.nl
authors.forename: Lonneke
authors.initials: L
authors.lastname: Smeding
authors.forename: Willem J
authors.initials: WJ
authors.lastname: van der Laarse
authors.forename: Toke A
authors.initials: TA
authors.lastname: van Veelen
authors.forename: Regis R
authors.initials: RR
authors.lastname: Lamberts
authors.forename: Hans W M
authors.initials: HW
authors.lastname: Niessen
authors.forename: Martin C J
authors.initials: MC
authors.lastname: Kneyber
authors.forename: A B Johan
authors.initials: AB
authors.lastname: Groeneveld
authors.forename: Frans B
authors.initials: FB
authors.lastname: Plötz
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D006321:Heart / Q000503:physiopathology*; D008070:Lipopolysaccharides / Q000009:adverse effects*; D008297:Male; D008929:Mitochondria, Heart / Q000502:physiology* / Q000648:ultrastructure; D009200:Myocardial Contraction / Q000502:physiology; D009206:Myocardium / Q000378:metabolism; D010538:Peritonitis / Q000139:chemically induced* / Q000378:metabolism / Q000503:physiopathology*; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism
chemical_list: D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1