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Changes in Diaphragm Linked to Inactivity, Ventilation

Specimens taken after lengthy mechanical ventilation show atrophy, other differences

WEDNESDAY, March 26 (HealthDay News) -- Both fast- and slow-twitch fibers in the diaphragm atrophy markedly after extended periods of diaphragmatic inactivity and mechanical ventilation, according to research published in the March 27 issue of the New England Journal of Medicine.

Sanford Levine, M.D., of the University of Pennsylvania in Philadelphia, and colleagues compared biopsy specimens from the costal diaphragm in 14 brain-dead organ donors, representing cases, with those from eight patients undergoing surgery, representing controls. The cases had diaphragmatic inactivity and had been on mechanical ventilation for 18 to 69 hours, compared to two to three hours in controls. The researchers assessed histological, biochemical and gene-expression measurements on the specimens.

The cross-sectional area of slow-twitch fibers decreased in case specimens 57 percent compared to controls, and 53 percent for fast-twitch fibers, the investigators found. In addition, glutathione concentration in case specimens was lower than in controls (consistent with oxidative stress), and active caspase-3 expression was higher (active caspase plays a role in muscle proteolysis).

"The results reported by Levine et al. certainly argue against the use of controlled mechanical ventilation as a protective, fatigue-reversing intervention for patients requiring ventilatory assistance in intensive care settings. Whether patients undergoing shorter-term procedures (e.g., surgical anesthesia) should also be considered at risk of ventilator-induced diaphragmatic dysfunction remains to be explored, but it is likely that alternative ventilatory strategies will be necessary, especially for patients with decreased energy capacity at baseline," write Gary C. Sieck, Ph.D., and Carlos B. Mantilla, M.D., Ph.D., of the Mayo Clinic in Rochester, Minn., in an accompanying editorial.

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