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Establishment of a saline lavage model in the isolated perfused rat lung

: Walter, Dorothee; Fischer, Monika; Pohlmann, Gerhard; Kemkowski, J.; Muynck, C. de; Dasenbrock, Clemens

The Toxicologist 54 (2015), No.1, pp.397, Abstract PS 1851
ISSN: 0731-9193
Society of Toxicology (Annual Meeting) <54, 2015, San Diego/Calif.>
Fraunhofer ITEM ()

For studies on the effectiveness of new lung surfactant formulations, the rat lung lavage (RLL) model is the method of choice. Prior to the test, the rats are anesthetized, tracheostomized and pressure-controlled ventilated. Saline lavages are performed, whereupon the rats receive aerosolized surfactant. The restoration of the lung function is indicated by the recovery of oxygenation. During the test procedure, the RLL model provides a large bandwidth within the measured parameters which is why another model for the investigation of lung surfactant formulations is desirable. In this context, the establishment of an ex vivo model such as the isolated perfused rat lung (IPL) should provide more constant measurement results, as the respiratory parameters can be adjusted individually. Furthermore, the use of the IPL contributes to the refinement and reduction of animal testing. We tested the effect of different lavage procedures and various ventilation strategies using the IPL. Sprague-Dawley rats were ventilated with 100 % oxygen at a respiratory rate of 80 breaths/min, inspiration : expiration ratio of 1 : 1, and a positive end-expiratory pressure (PEEP) of 3 cmH2O. High inspiratory pressure (Pinsp / PEEP) of 26 / 3 cmH2O led to edema formation in less than one hour. With a Pinsp of up to 15 cmH2O, the lungs survived with normal respiratory values for at least three hours. Up to 8 lavages with 0,9% NaCl-solution drop the O2 level for at least 200 units without leading to severe edema, when pressure-controlled ventilated with a Pinsp of 15 cmH2O. Our results show that an imitation of moderate Acute Respiratory Distress Syndrome (100 mmHg < PaO2 / FiO2 = 200 mmHg) in the ex vivo model IPL is possible. In the future, the development of a new test system for surfactant formulations shall replace the in vivo batch testing.