title: Bioenergetic adaptation of individual human diaphragmatic myofibers to severe COPD.
abstract: To assess the effect of severe chronic obstructive pulmonary disease (COPD) on the ability of human diaphragmatic myofibers to aerobically generate ATP relative to ATP utilization, we obtained biopsy specimens of the costal diaphragm from seven patients with severe COPD (mean +/- SE; age 56 +/- 1 yr; forced expiratory volume in 1 s 23 +/- 2% predicted; residual volume 267 +/- 30% predicted) and seven age-matched control subjects. We categorized all fibers in these biopsies by using standard techniques, and we carried out the following quantitative histochemical measurements by microdensitometry: 1) succinate dehydrogenase (SDH) activity as an indicator of mitochondrial oxidative capacity and 2) calcium-activated myosin ATPase (mATPase) activity, the ATPase that represents a major portion of ATP consumption by contracting muscle. We noted the following: 1) COPD diaphragms had a larger proportion of type I fibers, a lesser proportion of type IIax fibers, and the same proportion of type IIa fibers as controls. 2) SDH activities of each of the fiber types were higher in COPD than control diaphragms (P < 0.0001); the mean increases (expressed as percent of control values) in types I, IIa, and IIax were 84, 114, and 130%, respectively. 3) COPD elicited no change in mATPase activity of type I and IIa fibers, but mATPase decreased in type IIax fibers (P = 0.02). 4) Mitochondrial oxidative capacity relative to ATP demand (i.e., SDH/mATPase) was higher (P = 0.03) in each of the fiber types in COPD diaphragms than in controls. These results demonstrate that severe COPD elicits an increase in aerobic ATP generating capacity relative to ATP utilization in all diaphragmatic fiber types as well as the previously described fast-to-slow fiber type transformation (Levine S, Kaiser L, Leferovich J, and Tikunov B, N Engl J Med 337: 1799-1806, 1997).
authors.affiliation: Medical, Surgical, and Research Services, Philadelphia Veterans Affairs Medical Center, Pennsylvania 19104, USA. sdlevine@mail.med.upenn.edu
authors.forename: Sanford
authors.initials: S
authors.lastname: Levine
authors.forename: Chris
authors.initials: C
authors.lastname: Gregory
authors.forename: Taitan
authors.initials: T
authors.lastname: Nguyen
authors.forename: Joseph
authors.initials: J
authors.lastname: Shrager
authors.forename: Larry
authors.initials: L
authors.lastname: Kaiser
authors.forename: Neal
authors.initials: N
authors.lastname: Rubinstein
authors.forename: Gary
authors.initials: G
authors.lastname: Dudley
mesh_terms: D000222:Adaptation, Physiological; D003964:Diaphragm / Q000473:pathology / Q000503:physiopathology*; D004734:Energy Metabolism / Q000502:physiology*; D005260:Female; D006801:Humans; D008176:Lung Volume Measurements; D008297:Male; D008875:Middle Aged; D018656:Muscle Fibers, Fast-Twitch / Q000473:pathology / Q000502:physiology; D018485:Muscle Fibers, Skeletal / Q000473:pathology / Q000502:physiology*; D018657:Muscle Fibers, Slow-Twitch / Q000473:pathology / Q000502:physiology; D009218:Myosins / Q000378:metabolism; D029424:Pulmonary Disease, Chronic Obstructive / Q000473:pathology / Q000503:physiopathology*; D012720:Severity of Illness Index; D013385:Succinate Dehydrogenase / Q000378:metabolism
chemical_list: D013385:Succinate Dehydrogenase; D009218:Myosins