Prevention of Emphysema‐Induced Reductions in Diaphragm Muscle Mass

Chronic hypercapnic COPD patients have an unfavorable prognosis. Respiratory muscle atrophy and weakness may lead to CO 2 retention and ultimately respiratory failure. Therefore, the purpose of this investigation was to determine whether PG‐873637, a corticotrophin‐releasing factor 2 receptor‐selective agonist, would ameliorate diaphragm atrophy and/or induce hypertrophy. To establish the time course of emphysema induced diaphragmatic atrophy, costal diaphragm mass was measured at 4 and 8 months following saline (control) or elastase (emphysema) instillation in hamsters. Subsequently, after demonstration of atrophy, control and emphysema hamsters were treated with either saline (vehicle) or PG‐873637 (treatment) for 1 or 5 months prior to sacrifice. Excised lung volume increased (>140%) with emphysema at all time points. PG‐873637 treatment increased diaphragm muscle mass at both time points in emphysema animals (1‐month = 13% and 5‐month = 12%). These data demonstrate that PG‐873637 is efficacious as a treatment to preserve mass or induce hypertrophy in the emphysematous diaphragm.