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A saline lavage model in the isolated perfused rat lung

: Walter, Dorothee; Fischer, Monika; Steinberg, Pablo; Dasenbrock, Clemens

Naunyn-Schmiedebergs archives of pharmacology 388 (2015), Supplement 1, S.S85, Abstract 342
ISSN: 0028-1298
ISSN: 1432-1912
Deutsche Gesellschaft für Experimentelle und Klinische Pharmakologie und Toxikologie (Annual Meeting) <81, 2015, Kiel>
Fraunhofer ITEM ()

The rat lung lavage (RLL) model is often used to test the effectiveness of new lung surfactant formulations.
In this secondary surfactant deficiency model, repetitive lung lavages are performed in anesthetized, tracheostomized and pressure-controlled ventilated animals. This procedure leads to dramatically reduced gas exchange with similarities to acute respiratory distress syndrome (ARDS). After the administration of aerosolized surfactant, the restoration of lung function is indicated by the recovery of oxygenation. For the refinement and reduction of the RLL animal tests, the establishment of an ex vivo model such as the isolated perfused rat lung (IPL) is desirable. We tested the effect of saline lavage procedures using IPL. Sprague-Dawley rats were ventilated under negative conditions (end-inspiratory pressure (Pinsp) / end-expiratory pressure of -15 / -3 cm H2O), an inspiration : expiration ratio of 1 : 1 and 100% oxygen at a respiratory rate of 80 breaths / min. Every 5 min one deep breath with a Pinsp of 20 cm H2O was performed to reduce atelectasis formation. Up to 6 lavages with 0,9 % NaCl-solution caused a decreasing O2 level of at least 200 mm Hg. LDH and total protein were measured in single lavages from IPL and RLL trials. Both biochemical parameters did not differ significantly between lavages. Furthermore, LDH and total protein in lavages from IPL and RLL experiments were in equal ranges. Our data show that a high Pinsp of 15 cm H2O, combined with repeated saline lavages, does not severely damage lung tissue in the IPL model. With this procedure we are able to imitate the oxygenation status of moderate ARDS (100 mm Hg < PaO2 / FiO2 = 200 mm Hg) in the IPL. In addition, lavaged lung tissue in the IPL model is equally affected as lungs in RLL trials. In the future, the development of a new test system for surfactant formulations shall replace the in vivo surfactant formulation testing.