Sheep lung airway

BACKGROUND: Surgical stabilization of the airway through tracheobronchoplasty (TBP) is the current treatment modality for patients with severe symptomatic excessive dynamic airway collapse. However, TBP is associated with increased morbidity and mortality. Bronchoscopic treatment of the posterior membrane using argon plasma coagulation (APC) may be a safer alternative to TBP in highly selected patients. This study aimed to evaluate the effect of APC in the tracheobronchial tree of a sheep animal model...

BACKGROUND: In the fetus, the appropriate balance of prooxidants and antioxidants is essential to negate the detrimental effects of oxidative stress on lung maturation. Antioxidants improve respiratory function in postnatal life and adulthood. However, the outcomes and biological mechanisms of antioxidant action in the fetal lung are unknown. METHODS: We investigated the effect of maternal daily vitamin C treatment (200 mg/kg, intravenously) for a month in late gestation (105-138 days gestation, term ~145 days) on molecular regulation of fetal lung maturation in sheep...

BACKGROUND: Epithelial sodium channel (ENaC) is an important regulator of airway surface liquid volume; ENaC is hyperactivated in cystic fibrosis (CF). ENaC inhibition is a potential therapeutic target for CF. Here, we report in vitro and in vivo results for BI 1265162, an inhaled ENaC inhibitor currently in Phase II clinical development, administered via the Respimat® Soft Mist™ inhaler. METHODS: In vitro inhibition of sodium ion (Na+ ) transport by BI 1265162 was tested in mouse renal collecting duct cells (M1) and human bronchial epithelial cells (NCI-H441); inhibition of water transport was measured using M1 cells...

Jaagsiekte sheep retrovirus (JSRV) induces tumors in the distal airways of sheep and goats. A putative intragenic enhancer, termed JE, localized to the 3' end of the JSRV env gene, has been previously described. Herein we provide further evidence that the JE functions as a transcriptional enhancer, as it was able to enhance gene expression when placed in either forward or reverse orientation when combined with a heterologous chicken beta actin promoter. We then generated novel composite promoters designed to improve transgene expression from adeno-associated virus (AAV) gene therapy vectors...

BACKGROUND: Non-invasive and lung-protective ventilation techniques may improve outcomes for patients with an acute exacerbation of chronic obstructive pulmonary disease or moderate acute respiratory distress syndrome by reducing airway pressures. These less invasive techniques can fail due to hypercapnia and require transitioning patients to invasive mechanical ventilation. Extracorporeal CO2 removal devices remove CO2 independent of the lungs thereby controlling the hypercapnia and permitting non-invasive or lung-protective ventilation techniques...

The severity of burn and smoke inhalation-induced acute lung injury (BSI-ALI) is associated with alveolar and interstitial edema, bronchospasm, and airway mucosal hyperemia. Previously, we have reported beneficial effects of epinephrine nebulization on BSI-ALI. However, the underlying mechanisms of salutary effects of nebulized epinephrine remain unclear. The present study compared the effects of epinephrine, phenylephrine, and albuterol on a model of BSI-ALI. We tested the hypothesis that both α1- and β2-agonist effects are required for ameliorating more efficiently the BSI-ALI...

BACKGROUND: Targeted lung denervation (TLD), a novel bronchoscopic procedure which attenuates pulmonary nerve input to the lung to reduce the clinical consequences of neural hyperactivity, may be an important emerging treatment for COPD. While procedural safety and impact on clinical outcomes have recently been reported, the mechanism of action has not been reported. We explored the long-term pathologic and histopathologic effects in a sheep model of ablation of bronchial branches of the vagus nerve using a novel dual-cooled radiofrequency ablation catheter...

OBJECTIVE: To compare the effects of freshwater and seawater drowning on sheep's pulmonary circulation hemodynamics and respiratory mechanics. METHODS: According to the random number table method, healthy crossbred sheep were divided into freshwater drowning group (n = 12) and seawater drowning group (n = 12). 30 mL/kg of freshwater or seawater was infused respectively through trachea for approximately 5 minutes. Before the drowning, immediately after drowning, and 30, 60, 120 minutes after drowning, the systemic circulation hemodynamic parameters [heart rate (HR), mean arterial pressure (MAP), cardiac output (CO)] were monitored by pulse indicator continuous cardiac output (PiCCO); the respiratory parameters were obtained through the ventilator, including tidal volume (VT), lung compliance (Cdyn), oxygenation index (PaO2 /FiO2 ), peak airway pressure (Ppeak)]; PiCCO and the right heart floating catheter (Swan-Ganz catheter) was used to measure pulmonary hemodynamic parameters [pulmonary systolic pressure (PAS), pulmonary diastolic pressure (PAD), pulmonary artery wedge pressure (PAWP), and extravascular lung water (EVLW)]...

BACKGROUND AND OBJECTIVE: Targeted lung denervation (TLD) is a pulmonary interventional procedure for COPD that aims to disrupt parasympathetic nerve input to the lung to reduce the clinical consequences of cholinergic hyperactivity. TLD has been proven to be a safe procedure and effectively alleviate symptoms and reduce the onset of exacerbation. In the present study, we developed a novel cryo-balloon TLD system and evaluated its feasibility, safety, and effectiveness. METHODS: A preclinical study was performed on twelve sheep, four were tested for airway resistance alterations before and after TLD, two were tested for the Hering-Breuer reflex (HBR) and the remaining six sheep were evaluated for 28 days to assess the safety and effectiveness of the procedure...

The purpose of this investigation was to ascertain whether nitric oxide (NO) released into the circulation by a noninvasive technology called whole body periodic acceleration (WBPA) could increase mucociliary clearance (MCC). It was based on observations by others that nitric oxide donor drugs increase ciliary beat frequency of nasal epithelium without increasing mucociliary clearance. Tracheal mucous velocity (TMV), a reflection of MCC, was measured in sheep after 1-hour treatment of WBPA and repeated after pretreatment with the NO synthase inhibitor, L-NAME to demonstrated action of NO...

KEY POINTS: Experimental maternal allergic asthma in sheep provides an experimental model in which to test impacts on progeny. Fetuses from allergic asthmatic ewes had fewer surfactant-producing cells in lungs. A greater proportion of lymphocytes from thymus were CD44 positive in fetuses from allergic asthmatic ewes than in controls. These changes to fetal development might contribute to poor neonatal lung function and increased risk of allergy seen in offspring of pregnancies complicated by asthma...

OBJECTIVES: To evaluate the dose effects of Recombinant human Club cell 10-kDa protein (rhCC10) on lung function in a well-characterized ovine model of acute respiratory distress syndrome (ARDS) induced by smoke inhalation injury (SII); specifically, the potential of rhCC10 protein to control the inflammatory response and protect pulmonary tissue and function following SII. DESIGN: Randomized, controlled, prospective, and large animal translational studies. SETTING: University large animal intensive care unit...

Lung cancer patients often suffer from severe airway stenosis, the symptoms of which can be relieved by the implantation of stents. Different respiratory stents are commercially available, but the impact of their mechanical performance on tissue responses is not well understood. Two novel laser-cut and hand-braided nitinol stents, partially covered with polycarbonate urethane, were bench tested and implanted in Rhön sheep for 6 weeks. Bench testing highlighted differences in mechanical behavior: the laser-cut stent showed little foreshortening when crimped to a target diameter of 7...

Mechanical ventilation with normal tidal volumes (VT ) causes lung and systemic inflammation in preterm sheep. Mechanical ventilation is associated with bronchopulmonary dysplasia (BPD) in preterm infants, and the addition of budesonide to surfactant decreases BPD in clinical trials. Budesonide with surfactant will decrease the lung injury from mechanical ventilation for 24 h in preterm sheep. Lambs at 126 ± 1 day gestational age were delivered and randomized to either: 1 ) surfactant (200 mg/kg) or 2 ) surfactant mixed with budesonide (0...

Acquisition of high-resolution images from within internal organs using endoscopic optical imaging has numerous clinical applications. However, difficulties associated with optical aberrations and the trade-off between transverse resolution and depth-of-focus significantly limit the scope of applications. Here, we integrate a metalens, with the ability to modify the phase of incident light at sub-wavelength level, into the design of an endoscopic optical coherence tomography catheter (termed nano-optic endoscope) to achieve near diffraction-limited imaging through negating non-chromatic aberrations...

The Australian Synchrotron Imaging and Medical Beamline (IMBL) was designed to be the world's widest synchrotron X-ray beam, partly to enable clinical imaging and therapeutic applications for humans, as well as for imaging large-animal models. Our group is currently interested in imaging the airways of newly developed cystic fibrosis (CF) animal models that display human-like lung disease, such as the CF pig. One key outcome measure for assessing the effectiveness of CF airway therapies is the ability of the lung to clear inhaled particulates by mucociliary transit (MCT)...

Parasympathetic efferent innervation of the lung is the primary source of lung acetylcholine. Inhaled long-acting anticholinergics improve lung function and symptoms in patients with chronic obstructive pulmonary disease. Targeted lung denervation (TLD), a bronchoscopic procedure intended to disrupt pulmonary parasympathetic inputs, is an experimental treatment for chronic obstructive pulmonary disease. The physiologic and histologic effects of TLD have not previously been assessed. Eleven sheep and two dogs underwent circumferential ablation of the main bronchi with simultaneous balloon surface cooling using a lung denervation system (Nuvaira, Inc...

BACKGROUND: Epidermal growth factor receptor (EGFR) is important for airway branching and lung maturation. Mechanical ventilation of preterm lambs causes increases in EGFR and EGFR ligand mRNA in the lung. Abnormal EGFR signaling may contribute to the development of bronchopulmonary dysplasia. HYPOTHESIS: Inhibition of EGFR signaling will decrease airway epithelial cell proliferation and lung inflammation caused by mechanical ventilation in preterm, fetal sheep...

BACKGROUND: Airway fibrin casts are clinically important complications of severe inhalational smoke-induced acute lung injury (ISIALI) for which reliable evidence-based therapy is lacking. Nebulized anticoagulants or a tissue plasminogen activator; tPA, has been advocated, but airway bleeding is a known and lethal potential complication. We posited that nebulized delivery of single chain urokinase plasminogen activator, scuPA, is well-tolerated and improves physiologic outcomes in ISIALI...

Mechanical ventilation causes lung injury and systemic inflammatory responses in preterm sheep and is associated with bronchopulmonary dysplasia (BPD) in preterm infants. Budesonide added to surfactant decreased BPD by 20% in infants. We wanted to determine the effects of budesonide and surfactant on injury from high tidal volume (VT ) ventilation in preterm lambs. Ewes at 125 ± 1 days gestational age had fetal surgery to expose fetal head and chest with placental circulation intact. Lambs were randomized to 1) mechanical ventilation with escalating VT to target 15 ml/kg by 15 min or 2) continuous positive airway pressure (CPAP) of 5 cmH2 O...