The Effect of Enzyme-Induced Pulmonary Emphysema in Syrian Hamsters on the Deposition and Long-Term Retention of Inhaled Particles

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Abstract
Experimental emphysema was induced in Syrian hamsters by: (a) intratracheal instillation of elastase; or (b) inhalation of paparin aerosols. Additional hamsters served as controls and were either instilled with a sterile saline solution or exposed to an aerosol of enzyme diluent. After 3 wk, treated and control groups were simultaneously exposed to an aerosol of relatively insoluble 137 Cs-labeled, heat-treated aluminosilicate particles with an aerodynamic diameter of 1.4 or 1.6 ixm. The lung deposition of particles measured 3 hr after inhalation exposure was significantly lower in hamsters exposed to elastase or papain (45% and 65%, respectively of the amounts deposited in control hamsters). The mean whole-body retention data for each group were fitted with three-component exponential equations. The first component, which represented early clearance and constituted 78% to 83% of the initial body burden in all groups, occurred rapidly with a half-time of 0.6 to 0.8 days, and probably represented particles deposited in the nasopharynx and ciliated airways. The second component represented an intermediate clearance phase and was much faster in animals with emphysema than in controls. There were 6 and 11 day half-times in elastase- and papain-treated hamsters respectively, compared with 21 and 32 day half-times in controls. The long-term clearance component represented 4% and 5% of the initial body burden in enzymetreated groups and 8% and 9% of the initial body burden in control groups. The enzyme treatments resulted in a prolonged half-time in the long-term clearance component of 128 and 169 days compared to 98 and 110 days for the controls. The effect of both enzyme treatments on the retention of particles was similar although the patterns of emphysema produced differed. Elastase instilled intratracheally caused diffuse destruction and enlargement of alveoli with a loss of pulmonary elastic recoil. Papain aerosols caused focal destruction and enlargement of alveoli around terminal bronchioles with no loss of elastic recoil. A common feature of both enzyme-treated groups was an increased number of alveolar macrophages, which may account for the increased, early clearance of particles. The prolonged retention of a small fraction of particles may be due to focal accumulations of particle-laden macrophages which were prominent in distal alveoli of the papainexposed hamsters and, to a lesser degree, in the elastasetreated hamsters.