Universität zu Köln

Thot, Georgina Katharina ORCID: 0000-0003-4015-7339 (2023). Effects of immobilization by 60 days of experimental bed rest on endomysium of the soleus muscle in humans. PhD thesis, Universität zu Köln.

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Abstract

Movements result from contracting skeletal muscles. Muscles adapt to changing loads through hypertrophy (enlargement of muscle mass due to increased load) and atrophy (loss of muscle mass due to decreased load). Muscles are known to atrophy during immobilization and disuse. The two primary components of muscle are the muscle fibers (muscle cells) and intramuscular connective tissue. Intramuscular connective tissue can be categorized into endomysium (the smallest component which engulfs each individual muscle fiber), perimysium (which engulfs muscle bundles), and epimysium (which engulfs the muscle as a whole). It has been suggested that endomysium plays a key role for intramuscular force transmission. Animal data suggests that long-term immobilization results in increased endomysium content in the muscle while the muscle fibers themselves atrophy. This result has to date not been demonstrated in humans. Our objective was therefore to examine the endomysium content of the human soleus muscle during 60 days of bed rest. Bed rest is an established model to investigate changes occurring in microgravity conditions. For muscle, these changes include, muscle fiber atrophy and a loss of muscle strength. A 6° head down tilt is commonly applied to simulate the altered fluid distribution which occurs in microgravity. The 60-day 6° head-down tilt AGBRESA bed rest study, on which this work is based, sought to examine short duration continuous and intermittent centrifugation, i.e., artificial gravity, as a countermeasure to the adverse effects of microgravity on the human body. A short-arm centrifuge at the :envihab in Cologne, Germany, was used to simulate gravity by pulling blood towards the lower extremities. Muscle biopsies of the soleus muscle, a muscle which bears significant loads during daily tasks such as walking and standing, were extracted from 21 healthy volunteers (14 men and 7 women) at three timepoints: at baseline before bed rest (BDC), and during day 6 and day 55 (HDT6 and HDT55) of the head-down tilt bed rest. The biopsies were frozen, sectioned, and stained for laminin γ-1, a protein of the muscle basement membrane, which surrounds each cell. Laminin γ-1 can be used to determine the intramuscular connective tissue area located in between the individual fibers. Two parameters were calculated: the endomysium-to-fiber-area ratio (EFAr, in %) and the endomysium-to-fiber number ratio (EFNr). EFAr can show an increase in endomysium while EFNr can differentiate between a relative increase, attributed to muscle fiber atrophy, and an absolute endomysium increase. Muscle fibers atrophied by 16.6 % (SD 28.2 %) at HDT55 (p=0.0031) during bed rest. EFAr increased on day 55 (p<0.001), while EFNr showed no significant effect of bed rest (p=0.62). Neither intervention group showed significant effects in response to the use of short-arm centrifugation as a countermeasure to the adverse effects of microgravity on muscle fiber atrophy. The results of an EFAr increase and EFNr stability are explainable by immobilization-induced muscle fiber atrophy. Assuming that the number of fibers remains constant during long-term immobilization, these results suggest an unchanged amount of endomysial connective tissue content coupled with an increase in the relative amount of connective tissue per muscle fiber. This change is likely to affect muscle stiffness and thus muscle function.

Item Type:	Thesis (PhD thesis)
Creators:	Creators Email ORCID ORCID Put Code Thot, Georgina Katharina ginathot@gmail.com orcid.org/0000-0003-4015-7339 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-647507
Date:	2 February 2023
Language:	English
Faculty:	Faculty of Medicine
Divisions:	Faculty of Medicine > Kinder- und Jugendmedizin > Klinik und Poliklinik für Kinder- und Jugendmedizin
Subjects:	Medical sciences Medicine
Uncontrolled Keywords:	Keywords Language connective tissue English endomysium English immobilisation English
Date of oral exam:	12 December 2022
Referee:	Name Academic Title Rittweger, Jörn Universitätsprofessor Dr. med. Niehoff, Anja Professorin Dr. Sportwiss.
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/64750