Lung fluid absorption is induced in preterm guinea pigs ventilated with low tidal volumes

Koshy, Shyny; Beard, LaMonta L.; Kuzenko, Stephanie R.; Li, Tianbo; Folkesson, Hans G.

doi:10.3109/01902148.2010.514024

Cited by 6 publications

(2 citation statements)

References 38 publications

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“…This injury is exacerbated when preterm animals are exposed to high oxygen concentration (95% O 2 ), and/or high tidal volume ventilation strategies as frequently experienced by neonates being resuscitated and receiving respiratory support in the NICU (Koshy et al . ). Together with similar timing of lung maturation between guinea pigs and humans (Sosenko & Frank, ; Kelly et al .…”

Section: Introductionmentioning

confidence: 97%

Guinea pig models for translation of the developmental origins of health and disease hypothesis into the clinic

Morrison

Botting

Darby

et al. 2018

The Journal of Physiology

125

108

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Over 30 years ago Professor David Barker first proposed the theory that events in early life could explain an individual's risk of non-communicable disease in later life: the developmental origins of health and disease (DOHaD) hypothesis. During the 1990s the validity of the DOHaD hypothesis was extensively tested in a number of human populations and the mechanisms underpinning it characterised in a range of experimental animal models. Over the past decade, researchers have sought to use this mechanistic understanding of DOHaD to develop therapeutic interventions during pregnancy and early life to improve adult health. A variety of animal models have been used to develop and evaluate interventions, each with strengths and limitations. It is becoming apparent that effective translational research requires that the animal paradigm selected mirrors the tempo of human fetal growth and development as closely as possible so that the effect of a perinatal insult and/or therapeutic intervention can be fully assessed. The guinea pig is one such animal model that over the past two decades has demonstrated itself to be a very useful platform for these important reproductive studies. This review highlights similarities in the in utero development between humans and guinea pigs, the strengths and limitations of the guinea pig as an experimental model of DOHaD and the guinea pig's potential to enhance clinical therapeutic innovation to improve human health.

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Section: Introductionmentioning

confidence: 97%

Guinea pig models for translation of the developmental origins of health and disease hypothesis into the clinic

Morrison

Botting

Darby

et al. 2018

The Journal of Physiology

125

108

View full text Add to dashboard Cite

show abstract

“…ENaC plays a central role in ARDS pathogenesis as a key regulator of alveolar fluid clearance, as required during the exudative phase of ARDS (5,6,69,110). Furthermore, in the developing lung stretch increases epithelial ENaC expression via p38, MAPK, and JNK pathways and improves alveolar fluid clearance (14,102,133), which could accelerate recovery from the exudative phase of ARDS. In contrast, elevated serotonin levels, as commonly observed in ARDS lungs, inhibit ENaC activity and correlate with worsening pulmonary edema and ARDS outcomes (72,128).…”

Section: Stretch-activated Na ϩ Channelsmentioning

confidence: 99%

The role of stretch-activated ion channels in acute respiratory distress syndrome: finally a new target?

Schwingshackl

2016

American Journal of Physiology-Lung Cellular and Molecular Phys

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Mechanical ventilation (MV) and oxygen therapy (hyperoxia; HO) comprise the cornerstones of life-saving interventions for patients with acute respiratory distress syndrome (ARDS). Unfortunately, the side effects of MV and HO include exacerbation of lung injury by barotrauma, volutrauma, and propagation of lung inflammation. Despite significant improvements in ventilator technologies and a heightened awareness of oxygen toxicity, besides low tidal volume ventilation few if any medical interventions have improved ARDS outcomes over the past two decades. We are lacking a comprehensive understanding of mechanotransduction processes in the healthy lung and know little about the interactions between simultaneously activated stretch-, HO-, and cytokine-induced signaling cascades in ARDS. Nevertheless, as we are unraveling these mechanisms we are gathering increasing evidence for the importance of stretch-activated ion channels (SACs) in the activation of lung-resident and inflammatory cells. In addition to the discovery of new SAC families in the lung, e.g., two-pore domain potassium channels, we are increasingly assigning mechanosensing properties to already known Na(+), Ca(2+), K(+), and Cl(-) channels. Better insights into the mechanotransduction mechanisms of SACs will improve our understanding of the pathways leading to ventilator-induced lung injury and lead to much needed novel therapeutic approaches against ARDS by specifically targeting SACs. This review 1) summarizes the reasons why the time has come to seriously consider SACs as new therapeutic targets against ARDS, 2) critically analyzes the physiological and experimental factors that currently limit our knowledge about SACs, and 3) outlines the most important questions future research studies need to address.

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Fetal Lung Epithelial Ion Channels Relocate in the Cell Membrane During Late Gestation

Beard¹,

Li²,

Hu³

et al. 2011

The Anatomical Record

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Near the end of gestation, the direction of ion and fluid flow across the alveolar epithelium rapidly changes from secretion to absorption. Thus, the relative cell membrane location of epithelial Na channels (ENaCs) and cystic fibrosis transmembrane regulator (CFTR) Cl channels during late fetal lung development and after maternal interleukin-1b (IL1b) pretreatment was the focus of our study. Western blot analysis after sucrose gradient separation of caveolin-1-(Cav-1)-rich membrane regions (CRR) and Cav-1-poor membrane (non-CRR) revealed primary CRR ENaC localization at gestation day (GD) 61 in guinea pigs. Correlating with the natural induction of distal lung fluid absorption, ENaC appeared in the non-CRR cell membrane regions at GD68. Conversely, CFTR was present in the non-CRR cell membrane regions at GD61 and in the CRRs at GD68. IL-1b-induced conversion to distal lung fluid absorption at GD61 was associated with ENaC non-CRR presence and CFTR CRR presence, suggesting that relative ENaC and CFTR locations induced distal lung fluid absorption and decreased fluid secretion. Instilling fetal lungs with the CRR-disrupting agent methyl-b-cyclodextrin resulted in the conversion from lung fluid secretion to absorption and ENaC non-CRR presence at GD61. Coimmunoprecipitation of Cav-1 with a-and b-ENaC demonstrated reduced coimmunoprecipitation with increased GD and after IL-1b pretreatment. On the other hand, coimmunoprecipitation of Cav-1 with CFTR demonstrated increased coimmunoprecipitation with increasing GD and after IL-1b pretreatment. This concept may provide novel molecular mechanisms for the rapid transition from fetal distal lung fluid secretion to absorption in near-term lungs.

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Lung fluid absorption is induced in preterm guinea pigs ventilated with low tidal volumes

Cited by 6 publications

References 38 publications

Guinea pig models for translation of the developmental origins of health and disease hypothesis into the clinic

Guinea pig models for translation of the developmental origins of health and disease hypothesis into the clinic

The role of stretch-activated ion channels in acute respiratory distress syndrome: finally a new target?

Fetal Lung Epithelial Ion Channels Relocate in the Cell Membrane During Late Gestation

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