Large-Animal Models of Acute Respiratory Distress Syndrome

Ballard-Croft, Cherry; Wang, Dongfang; Sumpter, L. Ryan; Zhou, Xuguo; Zwischenberger, Joseph B.

doi:10.1016/j.athoracsur.2011.06.107

Cited by 100 publications

(105 citation statements)

References 69 publications

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“…However, addressing open questions by using a large animal model can offer greater clinical translational potential [8] and benefits both, human and veterinary medicine [9]. In this particular model, the respiratory tract as the target organ was chosen because there is still a lack of knowledge regarding the pathophysiology of pulmonary disorders induced by C. psittaci .…”

Section: Introductionmentioning

confidence: 99%

Evaluation of pulmonary dysfunctions and acid–base imbalances induced by Chlamydia psittaci in a bovine model of respiratory infection

Ostermann

Linde

Siegling-Vlitakis

et al. 2014

Multidisciplinary Respiratory Medicine

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BackgroundChlamydia psittaci (Cp) is a respiratory pathogen capable of inducing acute pulmonary zoonotic disease (psittacosis) or persistent infection. To elucidate the pathogenesis of this infection, a translational large animal model was recently introduced by our group. This study aims at quantifying and differentiating pulmonary dysfunction and acid–base imbalances induced by Cp.MethodsForty-two calves were grouped in (i) animals inoculated with Cp (n = 21) and (ii) controls sham-inoculated with uninfected cell culture (n = 21). For pulmonary function testing, impulse oscillometry, capnography, and FRC (functional residual capacity) measurement were applied to spontaneously breathing animals. Variables of acid–base status were assessed in venous blood using both (i) traditional Henderson-Hasselbalch and (ii) strong ion approach.ResultsBoth obstructive and restrictive pulmonary disorders were induced in calves experimentally inoculated with Cp. Although disorders in respiratory mechanics lasted for 8–11 days, the pattern of spontaneous breathing was mainly altered in the period of acute illness (until 4 days post inoculation, dpi). Expiration was more impaired than inspiration, resulting in elevated FRC. Ventilation was characterised by a reduction in tidal volume (−25%) combined with an increased percentage of dead space volume and a significant reduction of alveolar volume by 10%. Minute ventilation increased significantly (+50%) due to a compensatory doubling of respiratory rate. Hyperventilatory hypocapnia at 2–3 dpi resulted in slightly increased blood pH at 2 dpi. However, the acid–base equilibrium was additionally influenced by metabolic components, i.e. the systemic inflammatory response, all of which were detected with help of the strong ion theory. Decreased concentrations of albumin (2–10 dpi), a negative acute-phase marker, resulted in a decrease in the sum of non-volatile weak acids (Atot), revealing an alkalotic effect. This was counterbalanced by acidic effects of decreased strong ion difference (SID), mediated by the interplay between hypochloraemia (alkalotic effect) and hyponatraemia (acidic effect).ConclusionsThis bovine model was found to be suitable for studying pathophysiology of respiratory Cp infection and may help elucidating functional host-pathogen interactions in the mammalian lung.

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Section: Introductionmentioning

confidence: 99%

Evaluation of pulmonary dysfunctions and acid–base imbalances induced by Chlamydia psittaci in a bovine model of respiratory infection

Ostermann

Linde

Siegling-Vlitakis

et al. 2014

Multidisciplinary Respiratory Medicine

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“…The declining effect with further increase in PEEP and EELV on the other hand should be related to a shift from normal to high V A /Q areas and impaired perfusion. The complex combination of several pathomechanisms in ARDS can hardly by mimicked in full extent by experimental models [23]. Assessment of lung recruitability is crucial in ARDS patients: the individual recruitability may influence the ventilatory management, PEEP requirement, and even survival [24].…”

Section: Discussionmentioning

confidence: 99%

Endexpiratory lung volume measurement correlates with the ventilation/perfusion mismatch in lung injured pigs

et al. 2017

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BackgroundIn acute respiratory respiratory distress syndrome (ARDS) a sustained mismatch of alveolar ventilation and perfusion (VA/Q) impairs the pulmonary gas exchange. Measurement of endexpiratory lung volume (EELV) by multiple breath-nitrogen washout/washin is a non-invasive, bedside technology to assess pulmonary function in mechanically ventilated patients. The present study examines the association between EELV changes and VA/Q distribution and the possibility to predict VA/Q normalization by means of EELV in a porcine model.MethodsAfter approval of the state and institutional animal care committee 12 anesthetized pigs were randomized to ARDS either by bronchoalveolar lavage (n = 6) or oleic acid injection (n = 6). EELV, VA/Q ratios by multiple inert gas elimination and ventilation distribution by electrical impedance tomography were assessed at healthy state and at five different positive endexpiratory pressure (PEEP) steps in ARDS (0, 20, 15, 10, 5 cmH2O; each maintained for 30 min).ResultsVA/Q, EELV and tidal volume distribution all displayed the PEEP-induced recruitment in ARDS. We found a close correlation between VA/Q < 0.1 (representing shunt and low VA/Q units) and changes in EELV (spearman correlation coefficient −0.79). Logistic regression reveals the potential to predict VA/Q normalization (VA/Q < 0.1 less than 5%) from changes in EELV with an area under the curve of 0.89 with a 95%-CI of 0.81–0.96 in the receiver operating characteristic. Different lung injury models and recruitment characteristics did not influence these findings.ConclusionIn a porcine ARDS model EELV measurement depicts PEEP-induced lung recruitment and is strongly associated with normalization of the VA/Q distribution in a model-independent fashion. Determination of EELV could be an intriguing addition in the context of lung protection strategies.

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“…Repetitive lavage alone hardly mimics the full pattern of ARDS. The combination with an injurious ventilation mode, however, should induce ongoing epithelial barrier damage and is propagated to be more similar to human ARDS [20,23]. However, standardized protocols to achieve this are lacking.…”

Section: Discussionmentioning

confidence: 99%

TIP peptide inhalation in experimental acute lung injury: effect of repetitive dosage and different synthetic variants

et al. 2014

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BackgroundInhalation of TIP peptides that mimic the lectin-like domain of TNF-α is a novel approach to attenuate pulmonary oedema on the threshold to clinical application. A placebo-controlled porcine model of acute respiratory distress syndrome (ARDS) demonstrated a reduced thermodilution-derived extravascular lung water index (EVLWI) and improved gas exchange through TIP peptide inhalation within three hours. Based on these findings, the present study compares a single versus a repetitive inhalation of a TIP peptide (TIP-A) and two alternate peptide versions (TIP-A, TIP-B).MethodsFollowing animal care committee approval ARDS was induced by bronchoalveolar lavage followed by injurious ventilation in 21 anaesthetized pigs. A randomised-blinded three-group setting compared the single-dosed peptide variants TIP-A and TIP-B as well as single versus repetitive inhalation of TIP-A (n = 7 per group). Over two three-hour intervals parameters of gas exchange, transpulmonary thermodilution, calculated alveolar fluid clearance, and ventilation/perfusion-distribution were assessed. Post-mortem measurements included pulmonary wet/dry ratio and haemorrhage/congestion scoring.ResultsThe repetitive TIP-A inhalation led to a significantly lower wet/dry ratio than a single dose and a small but significantly lower EVLWI. However, EVLWI changes over time and the derived alveolar fluid clearance did not differ significantly. The comparison of TIP-A and B showed no relevant differences. Gas exchange and ventilation/perfusion-distribution significantly improved in all groups without intergroup differences. No differences were found in haemorrhage/congestion scoring.ConclusionsIn comparison to a single application the repetitive inhalation of a TIP peptide in three-hour intervals may lead to a small additional reduction the lung water content. Two alternate TIP peptide versions showed interchangeable characteristics.

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Large-Animal Models of Acute Respiratory Distress Syndrome

Cited by 100 publications

References 69 publications

Evaluation of pulmonary dysfunctions and acid–base imbalances induced by Chlamydia psittaci in a bovine model of respiratory infection

Evaluation of pulmonary dysfunctions and acid–base imbalances induced by Chlamydia psittaci in a bovine model of respiratory infection

Endexpiratory lung volume measurement correlates with the ventilation/perfusion mismatch in lung injured pigs

TIP peptide inhalation in experimental acute lung injury: effect of repetitive dosage and different synthetic variants

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