PLETHYSMOGRAPHIC METHOD FOR MEASURING FUNCTION IN LOCALLY IRRADIATED MOUSE LUNG

A plethysmograph has been developed to measure pulmonary function in mice after single doses of X-rays to both lungs. The apparatus consists of a whole-body airtight chamber fitted with a Lavalier microphone. The microphone acts as a sensitive electrical capacitance manometer converting pressure changes in the chamber into an electrical signal which is electronically processed and recorded on a pen recorder. Two parameters of lung function were simultaneously monitored, breathing rate and amplitude. Lung function has been tested in male CBA mice aged two to six months and in animals which have received graded X-rays doses to both lungs. No diurnal rhythm or age-related increase has been observed up to six months in control mice. The two lung-function parameters exhibited a dose-dependent response in irradiated lungs tested 16 weeks after irradiation; the response was reproducible in successive experiments. Respiration rate was increased above a threshold dose of 11 Gy (1100 rad) while amplitude decreased, also with a threshold at 11 Gy. These changes were observed before histological evidence of fibrosis became apparent and before pulmonary insufficiency led to deaths in the higher dose groups. The measurement of lung function by plethysmography is an alternative to lethality for assessing radiation damage in the lungs of small animals. The technique is non-destructive, responding to lower doses than LD50, and allows quantitative assessment of sequential changes in the lungs in each mouse over long post-irradiation times.