Lavage-induced Surfactant Depletion in Pigs As a Model of the Acute Respiratory Distress Syndrome (ARDS)

Ruß, Martin; Kronfeldt, Sebastian; Boemke, Willehad; Busch, Thilo; Francis, Roland C. E.; Pickerodt, Philipp A.

doi:10.3791/53610

Cited by 19 publications

(19 citation statements)

References 10 publications

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“…Our novel model offers advantages over both small animal (rodent) models as well as existing swine models that rely on clinically unrepresentative single-hit exposures (e.g. oleic acid infusion (18,19), surfactant washout (20)). Additionally, in alignment with NHLBI clinical research priorities, our novel preclinical model 1) uses a biologically-relevant infectious exposure (inoculation of viable E. coli) (23), 2) allows for the study of organ dysfunction and organ support, and 3) permits cointerventions (e.g.…”

Section: Discussionmentioning

confidence: 99%

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A Novel Swine Model of the Acute Respiratory Distress Syndrome Using Clinically-Relevant Injury Exposures

Tiba

McCracken

Leander

et al. 2021

Preprint

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To date, existing animal models of the acute respiratory distress syndrome (ARDS) have failed to translate preclinical discoveries into effective pharmacotherapy or diagnostic biomarkers. To address this translational gap, we developed a high-fidelity swine model of ARDS utilizing clinically-relevant lung injury exposures. Fourteen male swine were anesthetized, mechanically ventilated, and surgically instrumented for hemodynamic monitoring, blood, and tissue sampling. Animals were allocated to one of three groups: 1) Indirect lung injury only: animals were inoculated by direct injection of E. coli into the kidney parenchyma, provoking systemic inflammation and distributive shock physiology; 2) Direct lung injury only: animals received volutrauma, hyperoxia, and bronchoscope-delivered gastric particles; 3) Combined indirect and direct lung injury: animals were administered both above-described indirect and direct lung injury exposures. Animals were monitored for up to 12 hours, with serial collection of physiologic data, blood samples, and radiographic imaging. Lung tissue was acquired post-mortem for pathological examination. In contrast to indirect lung injury only and direct lung injury only groups, animals in the combined indirect and direct lung injury group exhibited all of the physiological, radiographic, and histopathologic hallmarks of human ARDS: impaired gas exchange (mean PaO2/FiO2 ratio 124.8 ± 63.8), diffuse bilateral opacities on chest radiographs, and extensive pathologic evidence of diffuse alveolar damage. Our novel porcine model of ARDS, built on clinically-relevant lung injury exposures, faithfully recapitulates the physiologic, radiographic, and histopathologic features of human ARDS, and fills a crucial gap in the translational study of human lung injury.

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Section: Discussionmentioning

confidence: 99%

“…Several swine models of ARDS exist, yet these rely on clinically unrepresentative single exposures (e.g. oleic acid infusion (18,19), surfactant washout (20)). To our knowledge, no existing swine model recapitulates the core features of human ARDS using clinically-relevant exposures.…”

Section: Introductionmentioning

confidence: 99%

A Novel Swine Model of the Acute Respiratory Distress Syndrome Using Clinically-Relevant Injury Exposures

Tiba

McCracken

Leander

et al. 2021

Preprint

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“…The mechanism underlying the occurrence of DD after BAL is still unclear, but an active inflammation status may be a crucial trigger. In addition to active inflammation, the spread of infection caused by the BAL procedure, atelectasis, and pulmonary injury induced by the washout of pulmonary surfactant (Lachmann, Robertson & Vogel, 1980;Russ et al, 2016) and the elevation of inflammatory cytokines, such as IL-6 and TNF α, in the blood and BAL fluid (Krause et al, 1997;Terashima et al, 2001) may be involved in the occurrence of BAL-DDs. The BAL-DD group in our study included four patients (26.7%) who had been diagnosed with eosinophilic pneumonia, which was consistent with the finding that the eosinophil percentage in the BAL fluid of the BAL-DD group was significantly higher than that of the non-BAL-DD group.…”

Section: Discussionmentioning

confidence: 99%

Risk factors for disease-related deterioration following diagnostic bronchoalveolar lavage procedures in diffuse lung disease: a case-control study

Usagawa

Komiya

Yamasue

et al. 2020

PeerJ

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Background Although the risk factors for diagnostic bronchoalveolar lavage (BAL)-induced acute exacerbations in patients with idiopathic pulmonary fibrosis (IPF) have been previously reported, no study has assessed these in patients with non-IPF. We aimed to identify the risk factors for BAL-induced disease deterioration (BAL-DD) in all types of diffuse lung disease. Methods Patients with diffuse lung disease who underwent BAL at our hospital from April 2012 to November 2017 were retrospectively analyzed. The patient information, laboratory data, radiological findings, and BAL fluid analysis results in patients who developed BAL-DDs were compared with those in patients who did not. Results BAL-DDs occurred in 14 (3.3%) of the 429 patients included the study. The BAL-DD group had a significantly poorer performance status, higher C-reactive protein level, lower partial pressure of oxygen in the arterial blood at rest, greater proportion of desaturation on exertion and cases having followed a progressive clinical course before BAL, and more extensive consolidation and ground-glass opacity on chest high-resolution computed tomography (HRCT) than the non-BAL-DD group. A high total cell concentration and an increased number of eosinophils in the BAL fluid were more frequently found in patients with BAL-DD than in those without. Conclusions Patients with decreased physical activity level, increased level of inflammatory markers, low oxygenation status, and extensive lung involvements on chest HRCT and following a progressive clinical course before BAL may be warned of the BAL-DD risk. Elevated eosinophil counts in the BAL fluid could be associated with the triggering of BAL-DDs.

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“…In contrast, the well-established lavage model is characterized by surfactant depletion, which leads to an increase in alveolar surface tension. As a result, atelectasis and edema frequently occur, leading to impaired gas exchange [5,24]. The pathophysiological changes of this ARDS model also demonstrate some similarities with human ARDS, but the model fails to reproduce human ARDS completely.…”

Section: Discussionmentioning

confidence: 99%

Comparison of two experimental ARDS models in pigs using electrical impedance tomography

et al. 2019

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BackgroundAnimal trials contribute to major achievements in medical science. The so-called lavage model is frequently used to evaluate ventilation strategies in acute respiratory distress syndrome (ARDS) using electrical impedance tomography (EIT). But, the lavage model itself might have systematic impacts on EIT parameters. Therefore, we established an additional experimental model, in which ARDS is caused by intravenously administered lipopolysaccharide (LPS). In this study, we want to examine if EIT measurements provide consistent results in both experimental models or whether the pathophysiology of the model influences the findings. Overall, we want to compare both experimental models regarding clinical parameters and EIT-derived indices, namely the global inhomogeneity (GI) index and the regional ventilation delay (RVD) index.MethodsNineteen pigs were included in this study, allocated to the control group (CO; n = 5), lavage group (LAV; n = 7) and LPS group (LPS; n = 7). After baseline measurements and the establishment of ARDS, assessment of respiratory mechanics, hemodynamics, gas exchange and EIT recordings were performed hourly over eight hours.ResultsIn both experimental ARDS models, EIT measurements provided reliable results. But, the GI and the RVD index did not show consistent results as compared to the CO group. Initially, GI and RVD index were higher in the LAV group but not in the LPS group as compared to the CO group. This effect disappeared during the study. Furthermore, the GI index and the RVD index were higher in the LAV group compared to the LPS group in the beginning as well. This, once again, disappeared. Clinical lung injury parameters remained more stable when using LPS.ConclusionThe two models showed quite different influences on the GI and RVD index. This implies, that the underlying pathophysiology affects EIT parameters and thus the findings. Hence, translation to EIT-guided clinical therapy in humans suffering from ARDS might be limited.

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Lavage-induced Surfactant Depletion in Pigs As a Model of the Acute Respiratory Distress Syndrome (ARDS)

Cited by 19 publications

References 10 publications

A Novel Swine Model of the Acute Respiratory Distress Syndrome Using Clinically-Relevant Injury Exposures

A Novel Swine Model of the Acute Respiratory Distress Syndrome Using Clinically-Relevant Injury Exposures

Risk factors for disease-related deterioration following diagnostic bronchoalveolar lavage procedures in diffuse lung disease: a case-control study

Comparison of two experimental ARDS models in pigs using electrical impedance tomography

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