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Sheep lung airway

T Brett Kothe, Emily Royse, Matthew W Kemp, Augusto F Schmidt, Fabrizio Salomone, Masatoshi Saito, Haruo Usuda, Shimpei Watanabe, Gabrielle C Musk, Alan H Jobe, Noah H Hillman
BACKGROUND: 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. OBJECTIVE: Determine the effects of budesonide and surfactant on injury from high tidal volume (VT) ventilation in preterm lambs. METHODS: Ewes at 125 {plus minus} 1 day GA had fetal surgery to expose fetal head and chest with placental circulation intact...
April 19, 2018: American Journal of Physiology. Lung Cellular and Molecular Physiology
Junfei Wang, Alen Faiz, Qi Ge, Cornelis J Vermeulen, Joanne Van der Velden, Kenneth J Snibson, Rob van de Velde, Sonia Sawant, Dikaia Xenaki, Brian Oliver, Wim Timens, Nick Ten Hacken, Maarten van den Berge, Alan James, John G Elliot, Liang Dong, Janette K Burgess, Anthony W Ashton
Neovascularization, increased basal membrane thickness and increased airway smooth muscle (ASM) bulk are hallmarks of airway remodelling in asthma. In this study, we examined connective tissue growth factor (CTGF) dysregulation in human lung tissue and animal models of allergic airway disease. Immunohistochemistry revealed that ASM cells from patients with severe asthma (A) exhibited high expression of CTGF, compared to mild and non-asthmatic (NA) tissues. This finding was replicated in a sheep model of allergic airways disease...
May 2018: Journal of Cellular and Molecular Medicine
Ishmael M Inocencio, Robert J Bischof, Sue D Xiang, Valerie A Zahra, Vy Nguyen, Tammy Lim, Domenic LaRosa, Jade Barbuto, Mary Tolcos, Magdalena Plebanski, Graeme R Polglase, Timothy J Moss
Mechanical ventilation of preterm neonates causes lung inflammation and injury, with potential life-long consequences. Inert 50-nm polystyrene nanoparticles (PS50G) reduce allergic inflammation in the lungs of adult mice. We aimed to confirm the anti-inflammatory effects of PS50G in a sheep asthma model, and investigate the effects of prophylactic administration of PS50G on ventilation-induced lung injury (VILI) in preterm lambs. We assessed lung inflammatory cell infiltration, with and without PS50G, after airway allergen challenge in ewes sensitised to house dust mite...
October 31, 2017: Scientific Reports
Shawn T Terryah, Robert C Fellner, Saira Ahmad, Patrick J Moore, Boris Reidel, Juliana I Sesma, Christine S Kim, Alaina L Garland, David W Scott, Juan R Sabater, Jerome Carpenter, Scott H Randell, Mehmet Kesimer, William M Abraham, William J Arendshorst, Robert Tarran
In cystic fibrosis (CF) lungs, epithelial Na+ channel (ENaC) hyperactivity causes a reduction in airway surface liquid volume, leading to decreased mucocilliary clearance, chronic bacterial infection, and lung damage. Inhibition of ENaC is an attractive therapeutic option. However, ENaC antagonists have failed clinically because of off-target effects in the kidney. The S18 peptide is a naturally occurring short palate lung and nasal epithelial clone 1 (SPLUNC1)-derived ENaC antagonist that restores airway surface liquid height for up to 24 h in CF human bronchial epithelial cultures...
January 1, 2018: American Journal of Physiology. Lung Cellular and Molecular Physiology
Graeme R Polglase, Jade Barbuto, Beth J Allison, Tamara Yawno, Amy E Sutherland, Atul Malhotra, Keith E Schulze, Euan M Wallace, Graham Jenkin, Sharon D Ricardo, Suzanne L Miller
Oxidative stress arising from suboptimal placental function contributes to a multitude of pathologies in infants compromised by fetal growth restriction (FGR). FGR infants are at high risk for respiratory dysfunction after birth and poor long-term lung function. Our objective was to investigate the contribution of oxidative stress to adverse lung development and the effects of melatonin administration, a powerful antioxidant, on lung structure in FGR lambs. Placental insufficiency and FGR was surgically induced in 13 fetal sheep at ∼105 days of gestation by ligation of a single umbilical artery...
November 1, 2017: Journal of Applied Physiology
Martin Donnelley, Kaye S Morgan, Maged Awadalla, Nigel R Farrow, Chris Hall, David W Parsons
BACKGROUND: The Australian Synchrotron Imaging and Medical Beamline (IMBL) was designed as the world's widest synchrotron X-ray beam, enabling both clinical imaging and therapeutic applications for humans as well as the imaging of large animal models. Our group is developing methods for imaging the airways of newly developed CF animal models that display human-like lung disease, such as the CF pig, and we expect that the IMBL can be utilised to image airways in animals of this size. METHODS: This study utilised samples of excised tracheal tissue to assess the feasibility, logistics and protocols required for airway imaging in large animal models such as pigs and sheep at the IMBL...
May 16, 2017: Respiratory Research
David W Scott, Matthew P Walker, Juliana Sesma, Bryant Wu, Timothy J Stuhlmiller, Juan R Sabater, William M Abraham, Timothy M Crowder, Dale J Christensen, Robert Tarran
RATIONALE: Cystic fibrosis (CF) lung disease is caused by the loss of function of the cystic fibrosis transmembrane conductance regulator (CFTR) combined with hyperactivation of the epithelial sodium channel (ENaC). In the lung, ENaC is responsible for movement of sodium. Hyperactivation of ENaC, which creates an osmotic gradient that pulls fluid out of the airway, contributes to reduced airway hydration, causing mucus dehydration, decreased mucociliary clearance, and recurrent acute bacterial infections...
September 15, 2017: American Journal of Respiratory and Critical Care Medicine
Jens Bräunlich, Friederike Goldner, Hubert Wirtz
INTRODUCTION: Nasal highflow (NHF) has a growing evidence in treatment of hypoxemic respiratory failure. There are preliminary data available about use in acute and chronic type-II-respiratory failure. Unfortunately underlying mechanisms of NHF are not well understood. Increase in airway pressure seems too small to explain the observed reduction in hypercapnia. Most interesting effects are wash-out of upper airways and reduction of functional dead space. There are no data available about a wash-out of lower airways...
April 7, 2017: Respiratory Physiology & Neurobiology
Ravi Alluri, Hilliard L Kutscher, Barbara A Mullan, Bruce A Davidson, Paul R Knight
Acid pneumonitis is a major cause of sterile acute lung injury (ALI) in humans. Acid pneumonitis spans the clinical spectrum from asymptomatic to acute respiratory distress syndrome (ARDS), characterized by neutrophilic alveolitis, and injury to both alveolar epithelium and vascular endothelium. Clinically, ARDS is defined by acute onset of hypoxemia, bilateral patchy pulmonary infiltrates and non-cardiogenic pulmonary edema. Human studies have provided us with valuable information about the physiological and inflammatory changes in the lung caused by ARDS, which has led to various hypotheses about the underling mechanisms...
February 26, 2017: Journal of Visualized Experiments: JoVE
Aida I Vientós-Plotts, Aaron C Ericsson, Hansjorg Rindt, Megan E Grobman, Amber Graham, Kaitlin Bishop, Leah A Cohn, Carol R Reinero
Advances in the field of metagenomics using culture-independent methods of microbial identification have allowed characterization of rich and diverse communities of bacteria in the lungs of healthy humans, mice, dogs, sheep and pigs. These data challenge the long held belief that the lungs are sterile and microbial colonization is synonymous with pathology. Studies in humans and animals demonstrate differences in the composition of airway microbiota in health versus disease suggesting respiratory dysbiosis occurs...
2017: PloS One
Emanuele Rezoagli, Alberto Zanella, Massimo Cressoni, Lorenzo De Marchi, Theodor Kolobow, Lorenzo Berra
BACKGROUND: The presence of an endotracheal tube is the main cause for developing ventilator-associated pneumonia (VAP), but pneumonia can still develop in hospitalized patients after endotracheal tube removal (postextubation pneumonia [PEP]). We hypothesized that short-term intubation (24 hours) can play a role in the pathogenesis of PEP. To test such hypothesis, we initially evaluated the occurrence of lung colonization and VAP in sheep that were intubated and mechanically ventilated for 24 hours...
April 2017: Anesthesia and Analgesia
William D Wong, Lu Wang, Peter D Paré, Chun Y Seow
Taking a big breath is known to reverse bronchoconstriction induced by bronchochallenge in healthy subjects; this bronchodilatory effect of deep inspiration (DI) is diminished in asthmatics. The mechanism underlying the DI effect is not clear. Observations from experiments using isolated airway smooth muscle (ASM) preparations and airway segments suggest that straining of ASM due to DI could lead to bronchodilation, possibly due to strain-induced reduction in ASM contractility. However, factors external to the lung cannot be excluded as potential causes for the DI effect...
February 1, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
Yanan Li, Zhongjia Jiang, Di Xue, Guangcun Deng, Min Li, Xiaoming Liu, Yujiong Wang
BACKGROUND: Mycoplasma ovipneumoniae (M. ovipneumoniae) is a species of Mycoplasma bacteria that specifically infects sheep and goat, causing ovine infectious pleuropneumonia. However, the mechanism underlying the pathogen-host interaction between M. ovipneumoniae and airway epithelial cells is unknown. METHODS: A primary air-liquid interface (ALI) epithelial culture model generated from the bronchial epithelial cells of Ningxia Tan sheep (ovis aries) was employed to explore the potential mechanism of M...
2016: BMC Microbiology
Rebecca Y Petersen, Emily Royse, Matthew W Kemp, Yuichiro Miura, Andres Noe, Alan H Jobe, Noah H Hillman
BACKGROUND: Mechanical ventilation at birth causes airway injury and lung inflammation in preterm sheep. Continuous positive airway pressure (CPAP) is being increasingly used clinically to transition preterm infants at birth. OBJECTIVE: To test if distending pressures will activate acute phase reactants and inflammatory changes in the airways of fetal, preterm lambs. METHODS: The head and chest of fetal lambs at 128±1 day GA were surgically exteriorized...
2016: PloS One
Nicole Deptula, Emily Royse, Matthew W Kemp, Yuichiro Miura, Suhas G Kallapur, Alan H Jobe, Noah H Hillman
Mechanical ventilation of preterm lambs causes lung inflammation and injury to the airway epithelium, which is repaired by 15 days after ventilation. In mice, activated basal cells (p63+, KRT14+, KRT8+) initiate injury repair to the trachea, whereas club cells coordinate distal airway repair. In both human and sheep, basal cells line the pseudostratified airways to the distal bronchioles with club cells only present in terminal bronchioles. Mechanical ventilation causes airway epithelial injury that is repaired through basal cell activation in the fetal lung...
August 1, 2016: American Journal of Physiology. Lung Cellular and Molecular Physiology
Joanne Van der Velden, Louise M Harkness, Donna M Barker, Garry J Barcham, Cathryn L Ugalde, Emmanuel Koumoundouros, Heidi Bao, Louise A Organ, Ana Tokanovic, Janette K Burgess, Kenneth J Snibson
Tumstatin, a protein fragment of the alpha-3 chain of Collagen IV, is known to be significantly reduced in the airways of asthmatics. Further, there is evidence that suggests a link between the relatively low level of tumstatin and the induction of angiogenesis and inflammation in allergic airway disease. Here, we show that the intra-segmental administration of tumstatin can impede the development of vascular remodelling and allergic inflammatory responses that are induced in a segmental challenge model of experimental asthma in sheep...
2016: Scientific Reports
Lauren E McClain, Marcus G Davey, Phillip W Zoltick, Maria P Limberis, Alan W Flake, William H Peranteau
PURPOSE: Successful in utero or perinatal gene therapy for congenital lung diseases, such as cystic fibrosis and surfactant protein deficiency, requires identifying clinically relevant viral vectors that efficiently transduce airway epithelial cells. The purpose of the current preclinical large animal study was to evaluate lung epithelium transduction of adeno-associated viral (AAV) vector serotypes following intratracheal delivery. METHODS: Six different AAV vector serotypes (AAV1, AAV5, AAV6, AAV8, AAV9, and AAVrh10) expressing the green fluorescent protein (GFP) as the transgene were injected into the right upper lobe of perinatal sheep via bronchoscopy...
June 2016: Journal of Pediatric Surgery
Laura Glendinning, Steven Wright, Jolinda Pollock, Peter Tennant, David Collie, Gerry McLachlan
UNLABELLED: Sequencing technologies have recently facilitated the characterization of bacterial communities present in lungs during health and disease. However, there is currently a dearth of information concerning the variability of such data in health both between and within subjects. This study seeks to examine such variability using healthy adult sheep as our model system. Protected specimen brush samples were collected from three spatially disparate segmental bronchi of six adult sheep (age, 20 months) on three occasions (day 0, 1 month, and 3 months)...
June 1, 2016: Applied and Environmental Microbiology
Erin V McGillick, Sandra Orgeig, Janna L Morrison
Inhibition of hypoxia signalling leads to respiratory distress syndrome (RDS), whereas administration of vascular endothelial growth factor (VEGF), the most widely characterized hypoxia responsive factor, protects from RDS. In the lung of the chronically hypoxaemic placentally restricted (PR) fetus, there is altered regulation of hypoxia signalling. This leads to reduced surfactant maturation in late gestation and provides evidence for the increased risk of RDS in growth restricted neonates at birth. We evaluated the effect of recombinant human VEGF administration with respect to bypassing the endogenous regulation of hypoxia signalling in the lung of the normally grown and PR sheep fetus...
March 1, 2016: Journal of Physiology
Bahar Liravi, David Piedrafita, Gary Nguyen, Robert J Bischof
BACKGROUND: IL-4 and IL-13 play a critical yet poorly understood role in orchestrating the recruitment and activation of effector cells of the asthmatic response and driving the pathophysiology of allergic asthma. The house dust mite (HDM) sheep asthma model displays many features of the human condition and is an ideal model to further elucidate the involvement of these critical Th2 cytokines. We hypothesized that airway exposure to HDM allergen would induce or elevate the expression profile of IL-4 and IL-13 during the allergic airway response in this large animal model of asthma...
2015: BMC Pulmonary Medicine
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