Herminghaus 2014 Abstract MiP2014
|Severity of polymicrobial sepsis modulates mitochondrial function in rat liver.|
Microcirculatory and mitochondrial dysfunction are considered as the main pathophysiological mechanisms in septic shock and multiorgan failure . However, results concerning mitochondrial function in the liver are controversial [2-4]. One possible reason for this heterogeneity could be a wide spectrum of septic models used, with varying degrees of sepsis severity. The aim of the present study was to analyze hepatic mitochondrial function during polymicrobial sepsis with abdominal focus, depending on severity of the septic process.
31 Wistar rats were divided into four groups: control, sham (laparotomy only) and two septic groups (colon ascendens stent peritonitis, CASP, using 16G or 14G stent). 24 h after sham or CASP operation, liver mitochondria were isolated. Mitochondrial oxygen consumption was determined using a Clark type electrode in the presence of glutamate+malate (GM) or succinate (S), to examine Complex I- or Complex II- (CI- or CII-) linked respiration, respectively. LEAK (LN, presence of substrates, no adenylates) and OXPHOS (ADP stimulated) respiration were assessed. The respiratory acceptor control ratio (RCR, OXPHOS/LEAK) and ADP/O ratio (ADP added/oxygen consumed) for both substrate states were calculated. Data are presented as means±SD, 1-way ANOVA followed by Tukey's post hoc-test.
RCR (CII) was higher after laparotomy compared to control. In septic animals with the smaller stent (16G) RCR (CI and CII) was higher compared to controls. In contrast, in septic animals with a larger stent size (14G) RCR was similar to controls. ADP/O ratios were comparable in all groups (Table 1).
Operative stress induced by laparotomy and, to a greater extent, moderate sepsis (CASP 16G) lead to a higher energy coupling without affecting the efficacy of oxidative phosphorylation. More severe sepsis (CASP 14G) does not affect hepatic mitochondrial function. Thus, the severity of sepsis might explain the heterogeneity of mitochondrial function reported in the literature.
This study was performed with approval of the local animal care and use committee.
Labels: MiParea: Respiration, mt-Medicine Pathology: Sepsis
Organism: Rat Tissue;cell: Liver Preparation: Isolated mitochondria
Regulation: Coupling efficiency;uncoupling Coupling state: LEAK, OXPHOS Pathway: N, S
Event: A4, Poster MiP2014
Dep Anesthesiology, Univ Hospital Duesseldorf, Germany. - [email protected]
|Mean±SD||RCR (GM)||RCR (S)||ADP/O (GM)||ADP/O (S)|
(*P<0.05 vs control, #P<0.05 vs 16G)
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