Establishment and validation of an isolated rat lung model for pulmonary metabolism studies

An isolated rat lung model was established and validated for use in pulmona ry metabolism studies. During the establishment phase of the study, several problems were encountered and overcome in order to maintain the lungs in p hysiological condition. In the validation phase of the study, the lungs wer e removed, ventilated and perfused from 34 male Fischer 344 rats. After an equilibration period, lungs were ventilated and perfused for up to 4 h, Mor phological, biochemical and functional parameters were evaluated to validat e the physiological condition of the lungs. Morphological parameters includ ed wet/dry lung weight ratios and gross and histological scoring for edema. Biochemical parameters included assays for tissue ATP and reduced glutathi one content, glutathione reductase activity and glucose utilization. Functi onal parameters included changes in lung tidal volume, dynamic compliance a nd airway resistance. Results indicated that edema formation was only detec ted histologically, that lungs remained nearly biochemically normal for 210 min and that pulmonary function declined to about 80-90% of normal. Overal l, these findings indicated that the isolated, perfused rat lung remained i n acceptable physiological condition for ca. 210 min. This period of time s hould be adequate for conducting pulmonary metabolism studies with a variet y of exogenous compounds. Copyright (C) 1999 John Whey & Sons, Ltd.