Nasal Ventilation Alters Mesenchymal Cell Turnover and Improves Alveolarization in Preterm Lambs

Reyburn, Brent; Li, Marlana; Metcalfe, Drew; Kroll, Nicholas; Alvord, Jeremy; Wint, Albert; Dahl, Mar Janna; Sun, Jiehao; Dong, Liang; Wang, Zhengke; Callaway, Christopher W.; McKnight, Robert A.; Moyer‐Mileur, Laurie J.; Yoder, Bradley A.; Null, Donald M.; Lane, Robert H.; Albertine, Kurt H.

doi:10.1164/rccm.200802-359oc

Cited by 66 publications

(91 citation statements)

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“…The data presented previously and in this report indicate that HAB-CPAP provides considerable ventilation, either through nasal prong interfaces or through endotracheal tubes. The failure of HAB-CPAP0 and HAB-CPAP90 to ventilate the paralyzed rabbits in our studies is also consistent with previous reports of others (7,8) who observed limited or insufficient ventilation using standard B-CPAP. The additional gas movement provided by the higher amplitude pressure fluctuations caused by the action at the bubbler air-water interface of the HAB-CPAP135 seems to be pivotal to the capabilities of this device.…”

Section: Discussionsupporting

confidence: 93%

Effective Gas Exchange in Paralyzed Juvenile Rabbits Using Simple, Inexpensive Respiratory Support Devices

et al. 2010

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ABSTRACT:We have developed two devices: a high-amplitude bubble continuous positive airway pressure (HAB-CPAP) and an inexpensive bubble intermittent mandatory ventilator (B-IMV) to test the hypotheses that simple, inexpensive devices can provide gas exchange similar to that of bubble CPAP (B-CPAP) and conventional mechanical ventilation (CMV). Twelve paralyzed juvenile rabbits were intubated, stabilized on CMV, and then switched to CPAP. On identical mean airway pressures (MAPs), animals were unable to maintain pulse oximeter oxygen saturation (SpO 2 ) Ͼ80% on conventional B-CPAP, but all animals oxygenated well (97.3 Ϯ 2.1%) on HAB-CPAP. In fact, arterial partial pressures of O 2 (PaO 2 ) were higher during HAB-CPAP than during CMV (p ϭ 0.01). After repeated lung lavages, arterial partial pressures of CO 2 (PaCO 2 ) were lower with B-IMV than with CMV (p Ͻ 0.0001), despite identical ventilator settings. In lavaged animals, when HAB-CPAP was compared with CMV at the same MAP and 100% O 2 , no differences were observed in PaO 2 , but PaCO 2 levels were higher with HAB-CPAP (70 Ϯ 7 versus 50 Ϯ 5 mm Hg; p Ͻ 0.05). Arterial blood pressures were not impaired by HAB-CPAP or B-IMV. The results confirm that simple inexpensive devices can provide respiratory support in the face of severe lung disease and could extend the use of respiratory support for preterm infants into severely resourcelimited settings. (Pediatr Res 68: 526-530, 2010) I nfant mortality caused by respiratory distress syndrome in the United States decreased from ϳ268 in 100,000 live births in 1971 to 98 in 100,000 live births in 1985 (1) and 17 in 100,000 live births in 2007 (2). The decrease in mortality from 1971 to 1985 was, in large part, due to the development and widespread availability of mechanical ventilators and continuous positive airway pressure (CPAP) devices designed to assist lung recruitment and gas exchange in newborn infants in respiratory distress. However, Ͼ4 million infants die throughout the world each year, with 1 million dying principally from respiratory insufficiency (3,4), largely because of the lack in resource-limited countries of the respiratory support devices and technologies that are commonly used in more affluent societies.Modern ventilators are expensive to purchase, which limits availability in resource-limited countries. Even if the devices are donated, the need for highly trained personnel to operate, maintain, and repair the ventilators effectively prevent significant use of modern ventilators in most facilities. Practical methods for respiratory support of prematurely born infants could save hundreds of thousands of newborn lives each year.In an effort to bridge the gap between the need for less expensive, simpler, more practical approaches to respiratory support and the need for greater range of simple support methods, we have developed two novel devices that can be used separately or together to provide a broad range of respiratory support for infants.One device, termed high-amplitude bubble continuous positive...

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Section: Discussionsupporting

confidence: 93%

Effective Gas Exchange in Paralyzed Juvenile Rabbits Using Simple, Inexpensive Respiratory Support Devices

et al. 2010

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“…Another difference, at least during the initial years using the preterm lamb model, is that the ductus arteriosus was surgically ligated within a few days of preterm birth (6,20,139). The protocol was subsequently changed to let the ductus close spontaneously (5,135,150). Rationale for eliminating ductal ligation was to minimize surgical trauma to the lung and postoperative edema, inflammation, infection, and atelectasis.…”

Section: Animal Models As Tools To Identify Pathogenic Mechanisms Leamentioning

confidence: 99%

“…Both models also recapitulate the pathophysiology and pathology of evolving neonatal CLD in preterm baboons (46,49,50,58,63,124,199) and preterm lambs (5,6,20,24,25,111,139,150). We use the term "evolving neonatal CLD" for the preterm baboon and preterm lamb models and reserve the term "BPD" for preterm human infants, to avoid confusion between large-animal models vs. the human disease.…”

Section: Animal Models As Tools To Identify Pathogenic Mechanisms Leamentioning

confidence: 99%

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Utility of large-animal models of BPD: chronically ventilated preterm lambs

Albertine

2015

American Journal of Physiology-Lung Cellular and Molecular Phys

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Albertine KH. Utility of large-animal models of BPD: chronically ventilated preterm lambs. Am J Physiol Lung Cell Mol Physiol 308: L983-L1001, 2015. First published March 13, 2015; doi:10.1152/ajplung.00178.2014.-This paper is focused on unique insights provided by the preterm lamb physiological model of bronchopulmonary dysplasia (BPD). Connections are also made to insights provided by the former preterm baboon model of BPD, as well as to rodent models of lung injury to the immature, postnatal lung. The preterm lamb and baboon models recapitulate the clinical setting of preterm birth and respiratory failure that require prolonged ventilation support for days or weeks with oxygen-rich gas. An advantage of the preterm lamb model is the large size of preterm lambs, which facilitates physiological studies for days or weeks during the evolution of neonatal chronic lung disease (CLD). To this advantage is linked an integrated array of morphological, biochemical, and molecular analyses that are identifying the role of individual genes in the pathogenesis of neonatal CLD. Results indicate that the mode of ventilation, invasive mechanical ventilation vs. less invasive high-frequency nasal ventilation, is related to outcomes. Our approach also includes pharmacological interventions that test causality of specific molecular players, such as vitamin A supplementation in the pathogenesis of neonatal CLD. The new insights that are being gained from our preterm lamb model may have important translational implications about the pathogenesis and treatment of BPD in preterm human infants.neonatal chronic lung disease; alveolarization; alveolar simplification; pulmonary hypertension; airway expiratory resistance; nitric oxide; vitamin A; endothelial nitric oxide synthase; nasal CPAP; insulin-like growth factor-1; epigenetics ACUTE RESPIRATORY FAILURE of preterm human infants reflects immaturity of the lung following preterm birth, disrupted developmental processes, and dysregulated repair responses. This reflection occurs in the neonatal intensive care setting of continuous invasive mechanical ventilation support with oxygen-rich gas that is necessary to keep many preterm human infants alive. Among survivors of preterm birth and initial days of ventilation support with oxygen-rich gas, human infants who require prolonged invasive ventilation support with oxygen-rich gas frequently develop bronchopulmonary dysplasia (BPD). BPD is a significant pediatric health problem because, almost four decades after its initial description (134), this disease of preterm infants remains the most common cause of long-term pour outcomes, including postnatal growth failure, recurrent hospitalization for respiratory tract infections, and intraventricular hemorrhage (53, 178). In the United States, since 2006, the overall rate of prematurity is 1 in 8 births, or ϳ12% (74, 118). However, the underlying pathogenic mechanisms are incompletely understood.Gaps in knowledge about the underlying pathogenic mechanisms that contribute to BPD are related, in p...

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“…Dysregulated apoptosis may contribute to the structural aberrations associated with acute and chronic lung diseases, including BPD (36)(37)(38). On the other hand, enhanced apoptosis of mesenchymal cells has been associated with improved alveolarization and thinning of airspace walls (51). At PN7, apoptosis was enhanced in the alveolar septa of IL-1b/b6 2/2 mice compared with IL-1b/b6 1/1 mice.…”

Section: Apoptosis and Proliferation In The Lungsmentioning

confidence: 99%

β6 Integrin Subunit Deficiency Alleviates Lung Injury in a Mouse Model of Bronchopulmonary Dysplasia

Hogmalm¹,

Sheppard²,

Lappalainen³

et al. 2010

Am J Respir Cell Mol Biol

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Pulmonary inflammation is associated with the development of bronchopulmonary dysplasia in premature infants. We have previously shown that perinatal pulmonary expression of human IL-1b is sufficient to cause a lung disease similar to bronchopulmonary dysplasia, characterized by inflammation, impaired alveolarization, poor postnatal growth, and increased mortality in infant mice. The avb6 integrin plays a critical role in regulating inflammation in the adult lung. To study the role of the b6 integrin subunit in neonatal inflammatory lung disease, we compared the pulmonary development in IL-1b-expressing infant mice with wild-type or null b6 integrin loci. Absence of the b6 integrin subunit decreased the mortality and improved the postnatal growth of IL-1b-expressing pups. The disrupted alveolar development of IL-1b-expressing mice was improved by b6 integrin deficiency. IL-1b-expressing b6 2/2 pups had shorter alveolar chord length and thinner alveolar walls than IL-1b-expressing b6 1/1 pups. In addition, the absence of the b6 integrin subunit reduced IL-1b-induced neutrophil and macrophage infiltration into the alveolar spaces. b6 integrin subunit deficiency suppressed inflammation and goblet cell hyperplasia in the airways and alleviated airway remodeling in IL-1b-expressing mice. The expression of the chemoattractant proteins, keratinocyte-derived chemokine, macrophage-inflammatory protein-2, calgranulin A, and calgranulin B, of osteopontin, and of the chitinase-like lectins, Ym1 and Ym2, was lower in IL-1b-expressing b6 2/2 than in IL-1b-expressing b6 1/1 mice. We conclude that absence of the b6 integrin subunit protects the infant murine lung against IL-1b-induced inflammation and injury.

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Nasal Ventilation Alters Mesenchymal Cell Turnover and Improves Alveolarization in Preterm Lambs

Cited by 66 publications

References 66 publications

Effective Gas Exchange in Paralyzed Juvenile Rabbits Using Simple, Inexpensive Respiratory Support Devices

Effective Gas Exchange in Paralyzed Juvenile Rabbits Using Simple, Inexpensive Respiratory Support Devices

Utility of large-animal models of BPD: chronically ventilated preterm lambs

β6 Integrin Subunit Deficiency Alleviates Lung Injury in a Mouse Model of Bronchopulmonary Dysplasia

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