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Effect of HA330 resin-directed hemoadsorption on a porcine acute respiratory distress syndrome model.

ABSTRACT: BACKGROUND:Blood purification is an emerging approach to dampening the cytokine storm. This study aims to assess the efficacy of HA330 resin-directed hemoadsorption (HA) on endotoxin-induced porcine acute respiratory distress syndrome (ARDS) model. METHODS:Twenty-four Chinese domestic pigs were allocated into saline group receiving intravenous infusion of saline (N = 6) and endotoxin group receiving intravenous infusion of LPS (N = 18). When ALI model was initially diagnosed, six pigs in the LPS and saline group were killed for BALF and histopathological analysis. The remaining 12 pigs in LPS group received 3-h HA (N = 6) or HA-sham (N = 6) treatment, respectively. Following another 5-h observation, animals were killed. Variables on hemodynamics, blood gases and lung mechanics were recorded at a series of time points. Differentially expressed cytokines and proteins were determined by ELISA and proteomics. RESULTS:HA treatment significantly improved injured oxygenation induced by LPS. HA also partially improved the barrier permeability and reduced lung edema and inflammation/injury induced by LPS infusion. Proteomic analysis showed the differentially expressed proteins between HA- and HA-sham-treated groups mostly belonged to the categories of acute inflammation/immune response, and proteolysis. CONCLUSIONS:Hemoadsorption improved ARDS possibly by blunting the cytokine storm and by restoring homeostasis of the disordered proteome milieu in the exudative phase.

SUBMITTER: Xu X

PROVIDER: S-EPMC5555961 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature

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Effect of HA330 resin-directed hemoadsorption on a porcine acute respiratory distress syndrome model.

Xu Xuefeng X Jia Chune C Luo Sa S Li Yanming Y Xiao Fei F Dai Huaping H Wang Chen C

Annals of intensive care 20170814 1

<h4>Background</h4>Blood purification is an emerging approach to dampening the cytokine storm. This study aims to assess the efficacy of HA330 resin-directed hemoadsorption (HA) on endotoxin-induced porcine acute respiratory distress syndrome (ARDS) model.<h4>Methods</h4>Twenty-four Chinese domestic pigs were allocated into saline group receiving intravenous infusion of saline (N = 6) and endotoxin group receiving intravenous infusion of LPS (N = 18). When ALI model was initially diagnosed, six ...[more]

PMID: 28808944

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Project description:ObjectivesEffective treatment options for surfactant therapy in acute respiratory distress syndrome and coronavirus disease 2019 have not been established. To conduct preclinical studies in vitro and in vivo to evaluate efficiency, particle size, dosing, safety, and efficacy of inhaled surfactant using a breath-synchronized, nebulized delivery system in an established acute respiratory distress syndrome model.DesignPreclinical study.SettingResearch laboratory.SubjectsAnesthetized pigs.InterventionIn vitro analysis included particle size distribution and inhaled dose during simulated ventilation using a novel breath-synchronized nebulizer. Physiologic effects of inhaled aerosolized surfactant (treatment) were compared with aerosolized normal saline (control) in an adult porcine model (weight of 34.3 ± 0.6 kg) of severe acute respiratory distress syndrome (Pao2/Fio2 <100) with lung lavages and ventilator-induced lung injury during invasive ventilation.Measurements and main resultsMass median aerosol diameter was 2.8 µm. In vitro dose delivered distal to the endotracheal tube during mechanical ventilation was 85% ± 5%. Nebulizers were functional up to 20 doses of 108 mg of surfactant. Surfactant-treated animals (n = 4) exhibited rapid improvement in oxygenation with nearly full recovery of Pao2/Fio2 (~300) and end-expiratory lung volumes with nominal dose less than 30 mg/kg of surfactant, whereas control subjects (n = 3) maintained Pao2/Fio2 less than 100 over 4.5 hours with reduced end-expiratory lung volume. There was notably greater surfactant phospholipid content and lower indicators of lung inflammation and pathologic lung injury in surfactant-treated pigs than controls. There were no peridosing complications associated with nebulized surfactant, but surfactant-treated animals had progressively higher airway resistance post treatment than controls with no differences in ventilation effects between the two groups.ConclusionsBreath-synchronized, nebulized bovine surfactant appears to be a safe and feasible treatment option for use in coronavirus disease 2019 and other severe forms of acute respiratory distress syndrome.

Project description:BackgroundA continuous gas flow provided by flow-controlled ventilation (FCV) facilitates accurate dynamic compliance measurement and allows the clinician to individually optimise positive end-expiratory and peak pressure settings accordingly.ObjectiveThe aim of this study was to compare the efficiency of gas exchange and impact on haemodynamics between individualised FCV and pressure-controlled ventilation (PCV) in a porcine model of oleic acid-induced acute respiratory distress syndrome (ARDS).DesignRandomised controlled interventional trial conducted on 16 pigs.SettingAnimal operating facility at the Medical University Innsbruck.InterventionsARDS was induced in lung healthy pigs by intravenous infusion of oleic acid until moderate-to-severe ARDS at a stable Horowitz quotient (PaO 2 FiO 2-1 ) of 80 to 120 over a period of 30 min was obtained. Ventilation was then either performed with individualised FCV ( n = 8) established by compliance-guided pressure titration or PCV ( n = 8) with compliance-guided titration of the positive end-expiratory pressure and peak pressure set to achieve a tidal volume of 6 ml kg -1 over a period of 2 h.Main outcome measuresGas exchange parameters were assessed by the PaO 2 FiO 2-1 quotient and CO 2 removal by the PaCO 2 value in relation to required respiratory minute volume. Required catecholamine support for haemodynamic stabilisation was measured.ResultsThe FCV group showed significantly improved oxygenation [149.2 vs. 110.4, median difference (MD) 38.7 (8.0 to 69.5) PaO 2 FiO 2-1 ; P = 0.027] and CO 2 removal [PaCO 2 7.25 vs. 9.05, MD -1.8 (-2.87 to -0.72) kPa; P = 0.006] at a significantly lower respiratory minute volume [8.4 vs. 11.9, MD -3.6 (-5.6 to -1.5) l min -1 ; P = 0.005] compared with PCV. In addition, in FCV-pigs, haemodynamic stabilisation occurred with a significant reduction of required catecholamine support [norepinephrine 0.26 vs. 0.86, MD -0.61 (-1.12 to -0.09) μg kg -1 min -1 ; P = 0.037] during 2 ventilation hours.ConclusionIn this oleic acid-induced porcine ARDS model, individualised FCV significantly improved gas exchange and haemodynamic stability compared with PCV.Trial registrationProtocol no.: BMBWF-66.011/0105-V/3b/2019).

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Effect of HA330 resin-directed hemoadsorption on a porcine acute respiratory distress syndrome model.

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Effect of HA330 resin-directed hemoadsorption on a porcine acute respiratory distress syndrome model.

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