Unilateral acute lung injury in pig: a promising animal model

Abstract

Abstract Background Acute lung injury (ALI) occurs in 23% unilateral. Models of unilateral ALI were developed and used previously without clearly demonstrating the strictly unilateral nature and severity of lung injury by the key parameters characterizing ALI as defined by the American Thoracic Society (ATS). Thus, the use of unilateral ALI remained rare despite the innovative approach. Therefore, we developed a unilateral model of ALI and focused on the crucial parameters characterizing ALI. This model can serve for direct comparisons between the injured and intact lungs within single animals, thus, reducing the number of animals required for valid experimental conclusions. Methods We established the model in nine pigs, followed by an evaluation of key parameters in six pigs (main study). Pigs were ventilated using an adapted left double-lumen tube for lung separation and two ventilators. ALI was induced in the left lung with cyclic rinsing (NaCl 0.9% + Triton® X-100), after which pigs were ventilated for different time spans to test for the timing of ALI onset. Ventilatory and metabolic parameters were evaluated, and bronchoalveolar lavage (BAL) was performed for measurements of inflammatory mediators. Finally, histopathological specimens were collected and examined in respect of characteristics defining the lung injury score (LIS) as suggested by the ATS. Results After adjustments of the model (n = 9) we were able to induce strictly left unilateral ALI in all six pigs of the evaluation study. The median lung injury score was 0.72 (IQR 0.62–0.79) in the left lung vs 0.14 (IQR 0.14–0.16; p < 0.05) in the right lung, confirming unilateral ALI. A significant and sustained drop in pulmonary compliance (Cdyn) of the left lung occurred immediately, whereas Cdyn of the right lung remained unchanged (p < 0.05). BAL fluid concentrations of interleukin-6 and -8 were increased in both lungs. Conclusions We established a model of unilateral ALI in pigs, confirmed by histopathology, and typical changes in respiratory mechanics and an inflammatory response. This thoroughly evaluated model could serve as a basis for future studies and for comparing pathophysiological and pharmacological changes in the uninjured and injured lung within the same animal.

Keywords

• Acute lung injury
• Large animal model
• Unilateral mechanical ventilation