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Parasternal intercostal muscle remodeling in severe chronic obstructive pulmonary disease

Departments of ¹Surgery and ²Cell and Developmental Biology, University of Pennsylvania School of Medicine; ³Department of Biology, University of Pennsylvania; and ⁴Surgical and Research Services, Philadelphia Veterans Affairs Medical Center, Philadelphia, Pennsylvania

Submitted 22 December 2005 ; accepted in final form 31 May 2006

Studies in experimental animals indicate that chronic increases in neural drive to limb muscles elicit a fast-to-slow transformation of fiber-type proportions and myofibrillar proteins. Since neural drive to the parasternal intercostal muscles (parasternals) is chronically increased in patients with severe chronic obstructive pulmonary diseases (COPDs), we carried out the present study to test the hypothesis that the parasternals of COPD patients exhibit an increase in the proportions of both slow fibers and slow myosin heavy chains (MHCs). Accordingly, we obtained full thickness parasternal muscle biopsies from the third interspace of seven COPD patients (mean ± SE age: 59 ± 4 yr) and seven age-matched controls (AMCs). Fiber typing was done by immunohistochemistry, and MHC proportions were determined by SDS-PAGE followed by densitometry. COPD patients exhibited higher proportions of slow fibers than AMCs (73 ± 4 vs. 51 ± 3%; P < 0.01). Additionally, COPD patients exhibited higher proportions of slow MHC than AMCs (56 ± 4 vs. 46 ± 4%, P < 0.04). We conclude that the parasternal muscles of patients with severe COPD exhibit a fast-to-slow transformation in both fiber-type and MHC proportions. Previous workers have demonstrated that remodeling of the external intercostals, another rib cage inspiratory muscle, elicited by severe COPD is characterized by a slow-to-fast transformation in both fiber types and MHC isoform proportions. The physiological significance of this difference in remodeling between these two inspiratory rib cage muscles remains to be elucidated.

muscle fiber types; myosin heavy chain isoform expression; diaphragm

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