and Specific Aims.) In emphysema (EMP), significant increases in lung volume, particularly when accompanied by dynamic hyperinflation, impose a chronic persistent load on the diaphragm (DIA) (122) which results in a number of adaptations in the DIA muscle. Corticosteroids are commonly used in patients with chronic obstructive pulmonary disease (COPD) either during exacerbations of the condition or as maintenance therapy in a subset of these patients. While it is well known that corticosteroids in and of themselves can affect muscle structure and function, there is little objective data on the interactive influences of corticosteroids and EMP on DIA performance. Growth factors such as anabolic steroids, growth hormone (GH) or insulin-like growth factor-I (IGF-I) may exert a positive influence on muscle function, but have only been used experimentally in patients with COPD. The overall objective is therefore to examine the interaction between EMP and currently used (corticosteroids) and possible (growth factors) therapeutic agents on DIA structure and function.
The Specific Aims are: 1) to examine independently the impact of EMP, corticosteroids, anabolic steroids and IGF-I on: a) mechanical properties of the DIA - a) DIA specific force (i,e., force/unit/cross- sectional area), b) maximum velocity of shortening; and c) fatigue resistance; b) Fiber type proportions and fiber cross-sectional areas; c) Myosin heavy chain composition; and d) Oxidative enzyme capacity; and 2) to examine the interactions between EMP and either corticosteroids, anabolic steroids or IGF- I on the DIA structure and function, as outlined above.It is hypothesized that EMP, corticosteroids, anabolic steroids and IGF-I influence myosin heavy chain isoform expression and/or oxidative enzyme activity and, therefore, alter the contractile and fatigue properties of the DIA muscle. It is further hypothesized that the effects of corticosteroids, anabolic steroids, and IGF-I are interactive with those of EMP.
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