Boyle 2017 MiP2017
We assessed the hypothesis that CHF+DM patients are characterised by systemic skeletal muscle mitochondrial dysfunction by taking biopsies from two muscles.
Skeletal muscle biopsies were sampled consecutively from vastus lateralis and pectoralis major from age-matched healthy controls (n=6), CHF (n=12), and CHF+DM patients (n=7). Mitochondrial oxygen flux of permeabilized fibres was subsequently assessed using a standard substrate, uncoupler and inhibitor titration protocol to selectively measure isolated components of the electron transfer chain.
After correcting for mitochondrial content, we found a significant main effect for group for complex I oxygen flux, F (2, 22) = 4.16, p = 0.029, with a significant difference between CHF+DM and healthy controls in both muscles (Figure 1). In contrast, CHF patients alone were not different to controls.
In conclusion, CHF+DM patients present with a systemic skeletal muscle mitochondrial dysfunction, which is not apparent in CHF patients. These findings provide an initial rationale for why exercise intolerance is exacerbated in CHF+DM.
Labels: MiParea: Respiration Pathology: Cardiovascular, Diabetes
Organism: Human Tissue;cell: Skeletal muscle Preparation: Permeabilized tissue
Pathway: N, S HRR: Oxygraph-2k
Figure 1: Skeletal muscle oxygen flux corrected for mitochondrial content (A.U.) measured in 3 different respiratory states from age-matched healthy controls (red), CHF patients (green), and CHF+DM patients (blue). Filled bars indicate pectoralis major samples. Striped bars indicate vastus lateralis samples. Data are expressed as mean ± SEM. Between group differences were assessed using a 2-way mixed analysis of variance (ANOVA) and Bonferroni post hoc analyses.
Division Cardiovascular Diabetes Research, Leeds Inst Cardiovascular Metabolic Medicine, Fac Medicine Health, Univ Leeds, UK. - [email protected]