Chronic muscle weakness and mitochondrial dysfunction in the absence of sustained atrophy in a preclinical sepsis model, 2019, Owen et al

[Andy]

Chronic critical illness is a global clinical issue affecting millions of sepsis survivors annually. Survivors report chronic skeletal muscle weakness and development of new functional limitations that persist for years. To delineate mechanisms of sepsis-induced chronic weakness, we first surpassed a critical barrier by establishing a murine model of sepsis with ICU-like interventions that allows for the study of survivors.

We show that sepsis survivors have profound weakness for at least 1 month, even after recovery of muscle mass. Abnormal mitochondrial ultrastructure, impaired respiration and electron transport chain activities, and persistent protein oxidative damage were evident in the muscle of survivors. Our data suggest that sustained mitochondrial dysfunction, rather than atrophy alone, underlies chronic sepsis-induced muscle weakness. This study emphasizes that conventional efforts that aim to recover muscle quantity will likely remain ineffective for regaining strength and improving quality of life after sepsis until deficiencies in muscle quality are addressed.

Open access, https://elifesciences.org/articles/49920

 

[It's M.E. Linda]

Interesting, especially as my ‘relapse’ (after a Consultant diagnosed ‘Post Viral Fatigue Syndrome’ in 2001 and ‘recovery’ to 95% by 2005) was caused by Sepsis in 2013.

Although in 2013 my GP (UK- NICE Guidelines) diagnosed ‘CFS’ and the Clinic diagnosed ‘CFS/ME’, I call myself ’disabled by M.E.’ and am a participant in one of the UK ME/CFS Biobank studies.

Both in 2001 and since 2013, I have had the classic fluctuating M.E. symptoms of delayed PEM, brain fog, sore throats, severe muscle pain, fatigue (in all, 50/58 symptoms on the Cure ME Symptom Assessment).

This Paper:

Reviewer #2 within the ’Decision Letter’ states:

” (The authors).....demonstrate reduced mitochondrial respiration, ultra-structural defects, reduced mitochondrial enzymatic activity, and evidence of oxidative damage. This suggests the proximal cause of muscle weakness is mitochondrial dysfunction. All of this is a reasonable explanation for the sustained muscle dysfunction”

and

“This is a suggestion and a hope:

6) An -omics approach of any sort – shotgun or targeted proteomics, RNAseq, etc. – could point to possible specific mechanisms dysregulating the mitochondria, would strengthen the impact and, if reported and deposited to GEO, would be a substantial contribution to the field. Such a contribution likely would enable others to query pathways of interest and thus would spark additional research using this model specifically and also more generally in the arena of sepsis-related muscle weakness/wasting.”

As a person with no Science brain, even before illness/disability, I have no idea what can be deduced from the above study but I just wanted to confirm that symptoms (muscle weakness/air hunger) mentioned in it, sound about right to me. However, this study has not investigated any humans.