Prevention of elastase induced experimental emphysema by oral administration of a synthetic elastase inhibitor

Experiments were undertaken to determine whether oral administration of a synthetic elastase inhibitor would prevent or diminish the severity of emphysema induced by intrapulmonary instillation of elastase into mice. Lightly anesthetized male, Swiss-Webster mice were given a transoral dose of 6 units of porcine pancreatic elastase dissolved in 50 μl of saline. These same animals also received 0.3 ml of water by stomach tube. Four weeks later, the average mean linear intercept in the lungs of these mice (94 ± 23 μm) was more than twice the normal value (43 ± 1 μm in untreated mice and 44 ± 5 μm in mice given 50 μl of saline transorally). Other mice simultaneously treated with porcine pancreatic elastase also received a single dose of 300 to 400 μg of methyoxysuccinyl-alanyl-alanyl-prolyl-valine-chloromethyl ketone (dissolved in 0.3 ml of water) by stomach tube, at times ranging from 2 h before instillation of the enzyme to 48 h after the enzyme. Mice that received chloromethyl ketone within 15 min before i...