Rapid Disuse Atrophy of Diaphragm Fibers in Mechanically Ventilated Humans
A very interesting study published in The New England Journal of Medicine this week.
Background: The combination of complete diaphragm inactivity and mechanical ventilation (for more than 18 hours) elicits disuse atrophy of myofibers in animals. It was hypothesized that the same may also occur in the human diaphragm.
Methods: Biopsy specimens obtained from 2 groups
Case subjects - the costal diaphragms of 14 brain-dead organ donors before organ harvest (case subjects). Case subjects had diaphragmatic inactivity and underwent mechanical ventilation for 18 to 69 hours
(compared them with)
control subjects - intraoperative biopsy specimens from the diaphragms of 8 patients who were undergoing surgery for either benign lesions or localized lung cancer (control subjects). control subjects diaphragmatic inactivity and mechanical ventilation were limited to 2 to 3 hours
Histologic, biochemical, and gene-expression studies were carried on these specimens.
Results: As compared with diaphragm-biopsy specimens from controls, specimens from case subjects showed
- decreased cross-sectional areas of slow-twitch and fast-twitch fibers of 57% (P=0.001) and 53% (P=0.01), respectively,
- decreased glutathione concentration of 23% (P=0.01),
- increased active caspase-3 expression of 100% (P=0.05),
- a 200% higher ratio of atrogin-1 messenger RNA (mRNA) transcripts to MBD4 (a housekeeping gene) (P=0.002), and
- a 590% higher ratio of MuRF-1 mRNA transcripts to MBD4 (P=0.001).
Conclusions: The combination of 18 to 69 hours of complete diaphragmatic inactivity and mechanical ventilation results in marked atrophy of human diaphragm myofibers. These findings are consistent with increased diaphragmatic proteolysis during inactivity.
References:
1. Rapid Disuse Atrophy of Diaphragm Fibers in Mechanically Ventilated Humans - The New England Journal of Medicine, Volume 358:1327-1335, Number 13, March 27 2008
