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Short-term Influences of Lung Volume Reduction Surgery on the Diaphragm in Emphysematous Hamsters

Divisions of Pulmonary/Critical Care Medicine and Thoracic Surgery, Department of Pathology and Laboratory Medicine, Burns & Allen Research Institute, Cedars-Sinai Medical Center, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, California

Correspondence and requests for reprints should be addressed to Michael I. Lewis, M.D., Cedars-Sinai Medical Center, Division of Pulmonary/Critical Care Medicine, 8700 Beverly Boulevard, Room 6732, Los Angeles, CA 90048. E-mail: lewism{at}cshs.org

With emphysema, diaphragm length adaptation results in shortened fibers. We hypothesize that passive diaphragm stretch occurring acutely after lung volume reduction surgery (LVRS) results in fiber injury. Bilateral LVRS was performed in emphysematous hamsters. Studies were performed 1 (D1) and 4 (D4) days after LVRS, and compared with sham-treated groups. Sarcolemmal rupture was evident in 10.9% of fibers in LVRS-D1 and reduced to 1.6% in LVRS-D4. Ultrastructural analysis revealed focal abnormalities in both LVRS-D1 and LVRS-D4 animals in over one-third of fibers. Myofibrillar disruption was not observed in sham-treated animals. Diaphragm insulin-like growth factor-I (IGF-I) was increased in LVRS-D4 compared with other emphysematous groups. Increased IGF-I immunoreactivity was localized to types IIA and I fibers. The abundance of the splice variant of IGF-I mRNA sensitive to muscle stretch (IGF-IEb) increased 3.2-fold in LVRS D-4 diaphragms, compared with emphysema-sham animals. The main form of IGF-I mRNA was unchanged. Marked force deficit was observed in the LVRS-D1 diaphragm, compared with emphysema-sham and emphysema (no surgery) animals. These data highlight a markedly compromised ventilatory pump acutely after LVRS. Acute fiber stretch predisposes to muscle fiber injury and may also be a necessary mechanotransductive stimulus for fiber remodeling as the diaphragm adapts to reduced lung volume.

Key Words: diaphragm contractility • insulin-like growth factor-I • muscle fiber injury and remodeling • muscle stretch

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