These studies investigated the mechanical, biophysical and biochemical properties of multiply lavaged excised rat lungs at 37°C to define a surfactant-deficient lung model for the evaluation of surfactant replacement mixtures and methodologies. The volume-pressure (VP) and volume-surface tension characteristics of excised lungs were determined before and after extensive washing with physiologic saline. Following a series of 15 consecutive lavages, a highly reproducible, sigmoidal deflation VP curve was observed, and recoil pressures at lung volumes below 95% of total lung capacity (TLC) were increased over baseline. The volume of trapped gas (Vtg) at 0 cm H2O transpulmonary pressure was reduced from 10.6% TLC before lavage to 2.0% TLC after. Prior to lavage, calculated alveolar surface tension decayed exponentially during lung deflation from an assumed maximum of 46.0 dynes/cm at TLC to <5.0 dynes/cm at 75% TLC and to <1.0 dyne/cm at 35% TLC. Following lavage, calculated surface tension was higher at all lung volumes and had a value of 18.0 dynes/cm at 75% TLC and 13.5 dynes/cm at 35% TLC. To determine the stability of the surfactant-deficient lavaged lung, VP properties were measured after subsequent periods of ventilation and refrigeration (for 72 hours at 4°C); VP characteristics and Vtg of lavaged lungs were found to be unaffected by these maneuvers. In a subgroup of experiments, the surfactant-deficient lung model was used to evaluate the effect of tracheal instillations of various amounts of a natural lung surfactant extract. A progressive return of normal lung mechanics was observed as the amount of instilled surfactant was increased from 0 to 74.0 µmoles of dispersed phospholipid in 2.5 ml of 0.15 M NaCl. Our results show that lavage of excised rat lungs yields a reproducible and stable state of surfactant deficiency at 37°C which is suitable for the evaluation of surfactant replacement mixtures and techniques.
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