Rapid Disuse Atrophy of Diaphragm Fibers in Mechanically Ventilated Humans

• Published in: The New England journal of medicine Vol. 358; no. 13; pp. 1327 - 1335
• Main Authors: Levine, Sanford, Nguyen, Taitan, Taylor, Nyali, Friscia, Michael E, Budak, Murat T, Rothenberg, Pamela, Zhu, Jianliang, Sachdeva, Rajeev, Sonnad, Seema, Kaiser, Larry R, Rubinstein, Neal A, Powers, Scott K, Shrager, Joseph B
• Format: Journal Article
• Language: English
• Published: Boston, MA Massachusetts Medical Society 27.03.2008
• Subjects: Adolescent; Adult; Aged; Biological and medical sciences; Biopsy; Brain Death; Case-Control Studies; Diaphragm - anatomy & histology; Diaphragm - metabolism; Diaphragm - pathology; Female; Gene Expression; General aspects; Humans; Male; Medical research; Medical sciences; Metabolic diseases; Methods; Middle Aged; Muscle Fibers, Skeletal - cytology; Muscle Fibers, Skeletal - pathology; Muscle Proteins - genetics; Muscle Proteins - metabolism; Muscular Atrophy - etiology; Muscular Atrophy - pathology; Pectoralis Muscles - anatomy & histology; Respiration, Artificial - adverse effects; RNA, Messenger - metabolism; SKP Cullin F-Box Protein Ligases - genetics; SKP Cullin F-Box Protein Ligases - metabolism; Tissue Donors; Tripartite Motif Proteins; Ubiquitin-Protein Ligases - genetics; Ubiquitin-Protein Ligases - metabolism; Ventilation; Atrophy; Human; Medicine; Nutrition; Diet; Fiber; Diaphragm
• ISSN: 0028-4793; 1533-4406
• DOI: 10.1056/NEJMoa070447

Weaning patients from mechanical ventilation after modest periods of diaphragmatic inactivity can be difficult. In this study, changes in the cross-sectional area and biochemical composition of biopsy specimens from brain-dead patients with inactive diaphragms at the time of organ donation were compared with similar measurements from patients undergoing thoracic surgery. The data were consistent with atrophy of the diaphragm after periods of inactivity on the order of a day. Changes in biopsy specimens from brain-dead patients with inactive diaphragms at the time of organ donation were compared with similar measurements from patients undergoing thoracic surgery. The data were consistent with atrophy of the diaphragm after periods of inactivity on the order of a day. Mechanical ventilation is a critical component of modern intensive care medicine, but the process of discontinuing mechanical ventilation can be difficult. 1 , 2 Laboratory studies have shown that the combination of diaphragmatic inactivity and mechanical ventilation for prolonged periods (more than 18 hours) is associated with atrophy of myofibers in the rat diaphragm. 3 – 5 We hypothesized that similar changes occur in the human diaphragm and that disuse atrophy of human diaphragm myofibers could be a major contributor to the weaning problems that occur in some of our patients. We evaluated the diaphragms of brain-dead organ donors, who show respiratory-muscle inactivity and . . .