title: Physiologic responses of sheep to two different methods of papain exposure.
abstract: Human emphysema is a progressive, destructive lung disease that produces morphologic and functional heterogeneity throughout its course. Consequently, the mature form of the disease is described by a broad range of anatomic, radiological, and physiologic patterns. This report describes the development and characterization of a sheep model of emphysema that represents many of the essential features of both homogeneous and heterogeneous emphysema. Emphysema was produced by two different techniques of papain exposure: (1) aerosol (75 IU/kg) given weekly for 4 treatments (HM) or (2) aerosol (75 IU/kg) weekly for 3 treatments following subsegmental intrabronchial instillations, 75 IU (in 10 saline) per lobe in 6 lobes (HT). Dexamethasone (0.06 mg/kg iv) was administered prior intrabronchial instillations only. On computed tomography, the HM group had homogeneous emphysema, the HT group gross nonuniformity of disease and bullae formation. Both groups demonstrated a significant (p < 0.05) increase in residual volume (HM, +38%; HT, +30%). There was a significant increase (p = 0.002) in total lung capacity per kilogram for the HM group. Emphysema had no effect on active or passive chest wall compliances. Diffusion capacity was significantly (p < 0.05) reduced in both groups. Both elastic (p = 0.066) and resistive (p = 0.025) components of impedance were increased in the HT, and airway resistance increased significantly in the HM groups. The HM model demonstrated gas trapping, a characteristic feature of emphysema, but failed to replicate the alterations in lung dynamics observed in the human form of this disease. The HT model demonstrated less static hyperinflation but significant frequency dependence and hence appeared to better represent the dynamic characteristics of human emphysema.
authors.affiliation: Department of Clinical Sciences, Tufts University School of Veterinary Medicine, 200 Westboro Rd, North Grafton, MA 01536, USA. andrew.hoffman@tufts.edu
authors.forename: Andrew
authors.initials: A
authors.lastname: Hoffman
authors.forename: A Courtney
authors.initials: AC
authors.lastname: Henderson
authors.forename: Larry
authors.initials: L
authors.lastname: Tsai
authors.forename: Edward
authors.initials: E
authors.lastname: Ingenito
mesh_terms: D000280:Administration, Inhalation; D000336:Aerosols / Q000008:administration & dosage / Q000009:adverse effects; D000818:Animals; D001980:Bronchi; D002248:Carbon Monoxide; D004058:Diffusion / Q000187:drug effects; D004195:Disease Models, Animal; D004646:Emphysema / Q000139:chemically induced / Q000503:physiopathology*; D005260:Female; D005652:Functional Residual Capacity / Q000187:drug effects; D007322:Instillation, Drug; D008168:Lung / Q000000981:diagnostic imaging / Q000503:physiopathology; D009991:Oscillometry; D010206:Papain / Q000009:adverse effects*; D012756:Sheep / Q000502:physiology*; D013997:Time Factors; D014055:Tomography, Emission-Computed
chemical_list: D000336:Aerosols; D002248:Carbon Monoxide; D010206:Papain