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-v

Cited by 3 publications

(3 citation statements)

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“…Premedication, general anesthesia, general cannulation techniques and induction of lung injury were performed as previously described. 7…”

Section: Methodsmentioning

confidence: 99%

“…After performing all measurements in healthy pigs, acute lung injury (ALI) was induced using the surfactant washout model (2–5 lavages, 0.9% saline, 37°C, 50 ml/kg body weight). 7 For baseline measurements after lavages, trueQ˙EC was set to 1 L/min and sweep gas flow was paused. Thus, the extent of lung injury was evaluated against only minimal oxygenation provided by the ECMO and no relevant extracorporeal carbon dioxide removal.…”

Section: Methodsmentioning

confidence: 99%

“…Premedication, general anesthesia, general cannulation techniques and induction of lung injury were performed as previously described. 7 In brief, animals were orally intubated (endotracheal tube, ID 8.5 mm; Mallinckrodt Hi-Contour Oral/Nasal Tracheal Tube Cuffed; Covidien), mechanical ventilated (Evita Infinity V500; Dräger, Lübeck, Germany) with a fraction of inspired oxygen (F I O 2 ) of 1.0, a tidal volume (V T ) of 6 ml/kg body weight, a positive end-expiratory pressure (PEEP) of 7 cm H 2 O, inspiratory to expiratory time ratio (I:E) of 1:1.5 and with a respiratory frequency adjusted to achieve an end-expiratory partial pressure of carbon dioxide (P et CO 2 ) of 35-40 mm Hg. Next, an introducer sheath, a central venous catheter (both left jugular vein) and an arterial catheter (femoral artery) were placed.…”

Section: General Proceduresmentioning

confidence: 99%

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Extracorporeal Membrane Oxygenation Blood Flow and Blood Recirculation Compromise Thermodilution-Based Measurements of Cardiac Output

et al. 2021

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The contribution of veno-venous (VV) extracorporeal membrane oxygenation (ECMO) to systemic oxygen delivery is determined by the ratio of total extracorporeal blood flow (trueQ˙EC) to cardiac output (trueQ˙). Thermodilution-based measurements of trueQ˙ may be compromised by blood recirculating through the ECMO (recirculation fraction; Rf). We measured the effects of trueQ˙EC and Rf on classic thermodilution-based measurements of trueQ˙ in six anesthetized pigs. An ultrasound flow probe measured total aortic blood flow (trueQ˙A0) at the aortic root. Rf was quantified with the ultrasound dilution technique. trueQ˙EC was set to 0–125% of trueQ˙A0 and trueQ˙ was measured using a pulmonary artery catheter (PAC) in healthy and lung injured animals. PAC overestimated trueQ˙ (trueQ˙Pa) at all trueQ˙EC settings compared to trueQ˙A0. The mean bias between both methods was 2.1 L/min in healthy animals and 2.7 L/min after lung injury. The difference between trueQ˙Pa and trueQ˙A0 increased with an trueQ˙EC of 75–125%/trueQ˙A0 compared to QEC <50%/trueQ˙A0. Overestimation of trueQ˙Pa was highest when trueQ˙EC resulted in a high Rf. Thus, thermodilution-based measurements can overestimate cardiac output during VV ECMO. The degree of overestimation of trueQ˙Pa depends on the trueQ˙EC/trueQ˙A0 ratio and the recirculation fraction.

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“…Premedication, general anesthesia, general cannulation techniques and induction of lung injury were performed as previously described. 7…”

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: General Proceduresmentioning

confidence: 99%

See 1 more Smart Citation

Extracorporeal Membrane Oxygenation Blood Flow and Blood Recirculation Compromise Thermodilution-Based Measurements of Cardiac Output

et al. 2021

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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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Inhalationally Administered Semifluorinated Alkanes (SFAs) as Drug Carriers in an Experimental Model of Acute Respiratory Distress Syndrome

et al. 2021

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Aerosol therapy in patients suffering from acute respiratory distress syndrome (ARDS) has so far failed in improving patients’ outcomes. This might be because dependent lung areas cannot be reached by conventional aerosols. Due to their physicochemical properties, semifluorinated alkanes (SFAs) could address this problem. After induction of ARDS, 26 pigs were randomized into three groups: (1) control (Sham), (2) perfluorohexyloctane (F6H8), and (3) F6H8-ibuprofen. Using a nebulization catheter, (2) received 1 mL/kg F6H8 while (3) received 1 mL/kg F6H8 with 6 mg/mL ibuprofen. Ibuprofen plasma and lung tissue concentration, bronchoalveolar lavage (BAL) fluid concentration of TNF-α, IL-8, and IL-6, and lung mechanics were measured. The ibuprofen concentration was equally distributed to the dependent parts of the right lungs. Pharmacokinetic data demonstrated systemic absorption of ibuprofen proofing a transport across the alveolo-capillary membrane. A significantly lower TNF-α concentration was observed in (2) and (3) when compared to the control group (1). There were no significant differences in IL-8 and IL-6 concentrations and lung mechanics. F6H8 aerosol seemed to be a suitable carrier for pulmonary drug delivery to dependent ARDS lung regions without having negative effects on lung mechanics.

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

Cited by 3 publications

References 1 publication

Extracorporeal Membrane Oxygenation Blood Flow and Blood Recirculation Compromise Thermodilution-Based Measurements of Cardiac Output

Extracorporeal Membrane Oxygenation Blood Flow and Blood Recirculation Compromise Thermodilution-Based Measurements of Cardiac Output

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

Inhalationally Administered Semifluorinated Alkanes (SFAs) as Drug Carriers in an Experimental Model of Acute Respiratory Distress Syndrome

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