Atrophy and impaired muscle protein synthesis during prolonged inactivity and stress.
BACKGROUND
We recently demonstrated that 28-d bed rest in healthy volunteers results in a moderate loss of lean leg mass and strength.


OBJECTIVE
The objective of this study was to quantify changes in muscle protein kinetics, body composition, and strength during a clinical bed rest model reflecting both physical inactivity and the hormonal stress response to injury or illness.


METHODS
Muscle protein kinetics were calculated during a primed, continuous infusion (0.08 micromol/kg.min) of 13C6-phenylalanine on d 1 and 28 of bed rest.


METHODS
The setting for this study was the General Clinical Research Center at the University of Texas Medical Branch.


METHODS
Participants were healthy male volunteers (n = 6, 28 +/- 2 yr, 84 +/- 4 kg, 178 +/- 3 cm).


METHODS
During bed rest, hydrocortisone sodium succinate was administered iv (d 1 and 28) and orally (d 2-27) to reproduce plasma cortisol concentrations consistent with trauma or illness (approximately 22 microg/dl).


METHODS
We hypothesized that inactivity and hypercortisolemia would reduce lean muscle mass, leg extension strength, and muscle protein synthesis.


RESULTS
Volunteers experienced a 28.4 +/- 4.4% loss of leg extension strength (P = 0.012) and a 3-fold greater loss of lean leg mass (1.4 +/- 0.1 kg) (P = 0.004) compared with our previous bed rest-only model. Net protein catabolism was primarily due to a reduction in muscle protein synthesis [fractional synthesis rate, 0.081 +/- 0.004 (d 1) vs. 0.054 +/- 0.007%/h (d 28); P = 0.023]. There was no change in muscle protein breakdown.


CONCLUSIONS
Prolonged inactivity and hypercortisolemia represents a persistent catabolic stimulus that exacerbates strength and lean muscle loss via a chronic reduction in muscle protein synthesis.
Paddon-Jones
Douglas
D
Department of Surgery, The University of Texas Medical Branch, 301 University Boulevard, Galveston, Texas 77550, USA. djpaddon@utmb.edu
Sheffield-Moore
Melinda
M
Cree
Melanie G
MG
Hewlings
Susan J
SJ
Aarsland
Asle
A
Wolfe
Robert R
RR
Ferrando
Arny A
AA
D000328:Adult; D001510:Bed Rest / Q000009:adverse effects*; D001823:Body Composition; D006801:Humans; D006854:Hydrocortisone / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood; D007328:Insulin / Q000097:blood; D008297:Male; D009043:Motor Activity / Q000502:physiology; D009124:Muscle Proteins / Q000096:biosynthesis*; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D009133:Muscular Atrophy / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D010649:Phenylalanine / Q000097:blood; D013312:Stress, Physiological / Q000150:complications / Q000378:metabolism*
D007328:Insulin; D009124:Muscle Proteins; D010649:Phenylalanine; D006854:Hydrocortisone