Volume-pressure and morphometric observations after acute alveolar injury in the dog from N-nitroso-N-methylurethane.

Volume-pressure diagrams during inflation with air and saline were made with the lungs of 6 control dogs and 24 dogs with acute alveolar injury induced by subcutaneous injection of 6 mg of N-nitroso-N-methylurethane per kg of body weight 3 to 14 days before study. The extent of alveolar closure was estimated by measuring the mean linear intercept of the remaining open air spaces after inflation of the lung with liquid formalin at a pressure of 40 cm H2O. This alveolar closure was defined as irreversible. The volume-pressure diagrams and compliance data derived from them during the 3 to 4, 5 to 7, and 9 to 14 day periods after injection were analyzed and compared with the morphometric data. The diagrams with air inflation showed a progressive downward shift beginning with the 3 to 4 day period. This shift was at least partly independent of volume loss. The diagrams with saline inflation were unchanged during the 3 to 4 day period, but showed a downward shift, largely due to volume loss thereafter. Irreversible alveolar closure, reflected by an increased mean linear intercept, was present in the 3 to 4 day period, and its extent increased with time, correlating inversely with total lung capacity and saline compliance. The data indicate that decreased lung compliance and volume during the first 7 days of injury induced by injection of N-nitroso-N-methylurethane were due largely to increased surface tension and that tissue forces became a significant factor later. They suggest that the altered tissue forces were due principally to irreversible alveolar closure.