Unilateral acute lung injury in pig: a promising animal model

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.

Lung regeneration: diverse cell types and the therapeutic potential

“…173 Some studies have shown a pioneering model of unilateral ALI, induced by cyclic rinsing with 0.9% saline and 0.3% Triton X-100 in mechanically ventilated pigs. 174 Genome-wide association analysis has allowed researchers to recognize the contribution of genetic background to IPF, leading to the development of some genetically engineered mice to mimic the process of spontaneous pulmonary fibrosis. AT2 cell targeted knockout telomeric repeat binding factor 1 mice exhibit spontaneous pulmonary fibrosis characteristics through telomere damage.…”

“…For vascular ECs, there are different injury modes such as intravenous injection of oleic acid, LPS, and endotoxin 173 . Some studies have shown a pioneering model of unilateral ALI, induced by cyclic rinsing with 0.9% saline and 0.3% Triton X‐100 in mechanically ventilated pigs 174 …”

Animal models of acute exacerbation of pulmonary fibrosis

“…Pigs, due to their anatomical size and structure, physiology, immunology, and genome similarity to humans, have been utilized in the investigation of various lung diseases [131,132]. A model of unilateral acute lung injury in pigs has been established, validated by histopathology and an inflammatory response [133]. This model can serve as a basis for comparing the pathophysiological changes in both the injured and uninjured lungs within the same animal [133], and holds potential for the study of AE-IPF in the future.…”

“…A model of unilateral acute lung injury in pigs has been established, validated by histopathology and an inflammatory response [133]. This model can serve as a basis for comparing the pathophysiological changes in both the injured and uninjured lungs within the same animal [133], and holds potential for the study of AE-IPF in the future. Numerous studies have explored the utilization of sheep as an animal model for pulmonary fibrosis.…”

P21 facilitates macrophage chemotaxis by promoting CCL7 in the lung epithelial cell lines treated with radiation and bleomycin

“…In order to better understand the development mechanism of lung pathology, numerous animal models of lung injury have been established [ 2 , 3 ]. The disease models of bleomycin (BLM)-induced pulmonary fibrosis (BIPF) and radiation-induced lung injury (RILI) are commonly used in oncology since they can better mimic the successive progression of pneumonitis and lung fibrosis after drug treatment or radiotherapy [ 4 ].…”