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  1. Article ; Online: Tissue Perfusion and Diffusion and Cellular Respiration: Transport and Utilization of Oxygen.

    Hsia, Connie C W

    Seminars in respiratory and critical care medicine

    2023  Volume 44, Issue 5, Page(s) 594–611

    Abstract: This article provides an overview of the journey of inspired oxygen after its uptake across the alveolar-capillary interface, and the interplay among tissue perfusion, diffusion, and cellular respiration in the transport and utilization of oxygen. The ... ...

    Abstract This article provides an overview of the journey of inspired oxygen after its uptake across the alveolar-capillary interface, and the interplay among tissue perfusion, diffusion, and cellular respiration in the transport and utilization of oxygen. The critical interactions between oxygen and its facilitative carriers (hemoglobin in red blood cells and myoglobin in muscle cells), and with other respiratory and vasoactive molecules (carbon dioxide, nitric oxide, and carbon monoxide), are emphasized to illustrate how this versatile system dynamically optimizes regional convective transport and diffusive gas exchange. The rates of reciprocal gas exchange in the lung and the periphery must be well-matched and sufficient for meeting the range of energy demands from rest to maximal stress but not excessive as to become toxic. The mobile red blood cells play a vital role in matching tissue perfusion and gas exchange by dynamically regulating the controlled uptake of oxygen and communicating regional metabolic signals across different organs. Intracellular oxygen diffusion and facilitation via myoglobin into the mitochondria, and utilization via electron transport chain and oxidative phosphorylation, are summarized. Physiological and pathophysiological adaptations are briefly described. Dysfunction of any component across this integrated system affects all other components and elicits corresponding structural and functional adaptation aimed at matching the capacities across the entire system and restoring equilibrium under normal and pathological conditions.
    MeSH term(s) Humans ; Oxygen ; Myoglobin ; Lung ; Cell Respiration ; Perfusion ; Oxygen Consumption/physiology
    Chemical Substances Oxygen (S88TT14065) ; Myoglobin
    Language English
    Publishing date 2023-08-04
    Publishing country United States
    Document type Journal Article
    ZDB-ID 1183617-9
    ISSN 1098-9048 ; 1069-3424
    ISSN (online) 1098-9048
    ISSN 1069-3424
    DOI 10.1055/s-0043-1770061
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  2. Article: Tissue Perfusion and Diffusion and Cellular Respiration: Transport and Utilization of Oxygen

    Hsia, Connie C. W.

    Seminars in Respiratory and Critical Care Medicine

    (Pulmonary Physiology)

    2023  Volume 44, Issue 05, Page(s) 594–611

    Abstract: This article provides an overview of the journey of inspired oxygen after its uptake across the alveolar–capillary interface, and the interplay among tissue perfusion, diffusion, and cellular respiration in the transport and utilization of oxygen. The ... ...

    Series title Pulmonary Physiology
    Abstract This article provides an overview of the journey of inspired oxygen after its uptake across the alveolar–capillary interface, and the interplay among tissue perfusion, diffusion, and cellular respiration in the transport and utilization of oxygen. The critical interactions between oxygen and its facilitative carriers (hemoglobin in red blood cells and myoglobin in muscle cells), and with other respiratory and vasoactive molecules (carbon dioxide, nitric oxide, and carbon monoxide), are emphasized to illustrate how this versatile system dynamically optimizes regional convective transport and diffusive gas exchange. The rates of reciprocal gas exchange in the lung and the periphery must be well-matched and sufficient for meeting the range of energy demands from rest to maximal stress but not excessive as to become toxic. The mobile red blood cells play a vital role in matching tissue perfusion and gas exchange by dynamically regulating the controlled uptake of oxygen and communicating regional metabolic signals across different organs. Intracellular oxygen diffusion and facilitation via myoglobin into the mitochondria, and utilization via electron transport chain and oxidative phosphorylation, are summarized. Physiological and pathophysiological adaptations are briefly described. Dysfunction of any component across this integrated system affects all other components and elicits corresponding structural and functional adaptation aimed at matching the capacities across the entire system and restoring equilibrium under normal and pathological conditions.
    Keywords oxygen ; hemoglobin ; allosterism ; myoglobin ; electron transport ; oxidative phosphorylation ; mitochondrial coupling
    Language English
    Publishing date 2023-08-04
    Publisher Thieme Medical Publishers, Inc.
    Publishing place Stuttgart ; New York
    Document type Article
    ZDB-ID 1183617-9
    ISSN 1098-9048 ; 1069-3424
    ISSN (online) 1098-9048
    ISSN 1069-3424
    DOI 10.1055/s-0043-1770061
    Database Thieme publisher's database

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  3. Article ; Online: Drowning in a river with an average depth of 3 ft: interpreting athletic performance gains.

    Hsia, Connie C W

    Journal of applied physiology (Bethesda, Md. : 1985)

    2017  Volume 123, Issue 5, Page(s) 1256–1257

    MeSH term(s) Altitude ; Athletic Performance ; Drowning ; Humans ; Rivers
    Language English
    Publishing date 2017-08-24
    Publishing country United States
    Document type Editorial ; Comment
    ZDB-ID 219139-8
    ISSN 1522-1601 ; 0021-8987 ; 0161-7567 ; 8750-7587
    ISSN (online) 1522-1601
    ISSN 0021-8987 ; 0161-7567 ; 8750-7587
    DOI 10.1152/japplphysiol.00733.2017
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  4. Article ; Online: Comparative analysis of the mechanical signals in lung development and compensatory growth.

    Hsia, Connie C W

    Cell and tissue research

    2017  Volume 367, Issue 3, Page(s) 687–705

    Abstract: This review compares the manner in which physical stress imposed on the parenchyma, vasculature and thorax and the thoraco-pulmonary interactions, drive both developmental and compensatory lung growth. Re-initiation of anatomical lung growth in the ... ...

    Abstract This review compares the manner in which physical stress imposed on the parenchyma, vasculature and thorax and the thoraco-pulmonary interactions, drive both developmental and compensatory lung growth. Re-initiation of anatomical lung growth in the mature lung is possible when the loss of functioning lung units renders the existing physiologic-structural reserves insufficient for maintaining adequate function and physical stress on the remaining units exceeds a critical threshold. The appropriate spatial and temporal mechanical interrelationships and the availability of intra-thoracic space, are crucial to growth initiation, follow-on remodeling and physiological outcome. While the endogenous potential for compensatory lung growth is retained and may be pharmacologically augmented, supra-optimal mechanical stimulation, unbalanced structural growth, or inadequate remodeling may limit functional gain. Finding ways to optimize the signal-response relationships and resolve structure-function discrepancies are major challenges that must be overcome before the innate compensatory ability could be fully realized. Partial pneumonectomy reproducibly removes a known fraction of functioning lung units and remains the most robust model for examining the adaptive mechanisms, structure-function consequences and plasticity of the remaining functioning lung units capable of regeneration. Fundamental mechanical stimulus-response relationships established in the pneumonectomy model directly inform the exploration of effective approaches to maximize compensatory growth and function in chronic destructive lung diseases, transplantation and bioengineered lungs.
    MeSH term(s) Animals ; Lung/growth & development ; Lung/metabolism ; Mechanotransduction, Cellular ; Regeneration ; Signal Transduction ; Translational Research, Biomedical
    Language English
    Publishing date 2017-01-13
    Publishing country Germany
    Document type Comparative Study ; Journal Article ; Review
    ZDB-ID 125067-x
    ISSN 1432-0878 ; 0302-766X
    ISSN (online) 1432-0878
    ISSN 0302-766X
    DOI 10.1007/s00441-016-2558-8
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  5. Article ; Online: Alveolo-capillary diffusion of hyperpolarized 129Xe as a marker of pulmonary fibrosis.

    Hsia, Connie C W

    Journal of applied physiology (Bethesda, Md. : 1985)

    2014  Volume 117, Issue 6, Page(s) 573–574

    MeSH term(s) Female ; Humans ; Male ; Pulmonary Fibrosis/pathology ; Xenon Isotopes
    Chemical Substances Xenon Isotopes
    Language English
    Publishing date 2014-08-07
    Publishing country United States
    Document type Editorial ; Comment
    ZDB-ID 219139-8
    ISSN 1522-1601 ; 0021-8987 ; 0161-7567 ; 8750-7587
    ISSN (online) 1522-1601
    ISSN 0021-8987 ; 0161-7567 ; 8750-7587
    DOI 10.1152/japplphysiol.00688.2014
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  6. Article ; Online: Call for Papers: "Morphology is the link between genetics and function": a tribute to Ewald R. Weibel.

    Mühlfeld, Christian / Hsia, Connie C W / Leikauf, George D / Orgeig, Sandra / Wain, Louise V / Ochs, Matthias

    American journal of physiology. Lung cellular and molecular physiology

    2020  Volume 320, Issue 2, Page(s) L254–L256

    MeSH term(s) Animals ; Humans ; Lung ; Lung Diseases/genetics ; Lung Diseases/metabolism ; Lung Diseases/pathology ; Periodicals as Topic
    Language English
    Publishing date 2020-11-25
    Publishing country United States
    Document type Editorial ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
    ZDB-ID 1013184-x
    ISSN 1522-1504 ; 1040-0605
    ISSN (online) 1522-1504
    ISSN 1040-0605
    DOI 10.1152/ajplung.00561.2020
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  7. Article: Lung diffusing capacity for nitric oxide measured by two commercial devices: a randomised crossover comparison in healthy adults.

    Radtke, Thomas / de Groot, Quintin / Haile, Sarah R / Maggi, Marion / Hsia, Connie C W / Dressel, Holger

    ERJ open research

    2021  Volume 7, Issue 3

    Abstract: In Europe, two commercial devices are available to measure combined single-breath diffusing capacity of the lung for nitric oxide ( ...

    Abstract In Europe, two commercial devices are available to measure combined single-breath diffusing capacity of the lung for nitric oxide (
    Language English
    Publishing date 2021-08-23
    Publishing country England
    Document type Journal Article
    ZDB-ID 2827830-6
    ISSN 2312-0541
    ISSN 2312-0541
    DOI 10.1183/23120541.00193-2021
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  8. Article: Comparative analysis of the mechanical signals in lung development and compensatory growth

    Hsia, Connie C. W

    Cell and tissue research. 2017 Mar., v. 367, no. 3

    2017  

    Abstract: This review compares the manner in which physical stress imposed on the parenchyma, vasculature and thorax and the thoraco-pulmonary interactions, drive both developmental and compensatory lung growth. Re-initiation of anatomical lung growth in the ... ...

    Abstract This review compares the manner in which physical stress imposed on the parenchyma, vasculature and thorax and the thoraco-pulmonary interactions, drive both developmental and compensatory lung growth. Re-initiation of anatomical lung growth in the mature lung is possible when the loss of functioning lung units renders the existing physiologic-structural reserves insufficient for maintaining adequate function and physical stress on the remaining units exceeds a critical threshold. The appropriate spatial and temporal mechanical interrelationships and the availability of intra-thoracic space, are crucial to growth initiation, follow-on remodeling and physiological outcome. While the endogenous potential for compensatory lung growth is retained and may be pharmacologically augmented, supra-optimal mechanical stimulation, unbalanced structural growth, or inadequate remodeling may limit functional gain. Finding ways to optimize the signal–response relationships and resolve structure-function discrepancies are major challenges that must be overcome before the innate compensatory ability could be fully realized. Partial pneumonectomy reproducibly removes a known fraction of functioning lung units and remains the most robust model for examining the adaptive mechanisms, structure–function consequences and plasticity of the remaining functioning lung units capable of regeneration. Fundamental mechanical stimulus–response relationships established in the pneumonectomy model directly inform the exploration of effective approaches to maximize compensatory growth and function in chronic destructive lung diseases, transplantation and bioengineered lungs.
    Keywords compensatory growth ; lungs ; models ; respiratory tract diseases ; thorax
    Language English
    Dates of publication 2017-03
    Size p. 687-705.
    Publishing place Springer Berlin Heidelberg
    Document type Article
    Note Review
    ZDB-ID 125067-x
    ISSN 1432-0878 ; 0302-766X
    ISSN (online) 1432-0878
    ISSN 0302-766X
    DOI 10.1007/s00441-016-2558-8
    Database NAL-Catalogue (AGRICOLA)

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  9. Article ; Online: Constitutive transgenic α-Klotho overexpression enhances resilience to and recovery from murine acute lung injury.

    Gagan, Joshuah M / Cao, Khoa / Zhang, Yu-An / Zhang, Jianning / Davidson, Taylor L / Pastor, Johanne V / Moe, Orson W / Hsia, Connie C W

    American journal of physiology. Lung cellular and molecular physiology

    2021  Volume 321, Issue 4, Page(s) L736–L749

    Abstract: Normal lungs do not express α-Klotho (Klotho) protein but derive cytoprotection from circulating soluble Klotho. It is unclear whether chronic supranormal Klotho levels confer additional benefit. To address this, we tested the age-related effects of ... ...

    Abstract Normal lungs do not express α-Klotho (Klotho) protein but derive cytoprotection from circulating soluble Klotho. It is unclear whether chronic supranormal Klotho levels confer additional benefit. To address this, we tested the age-related effects of modest Klotho overexpression on acute lung injury (ALI) and recovery. Transgenic Klotho-overexpressing (
    MeSH term(s) Acute Lung Injury/pathology ; Acute Lung Injury/prevention & control ; Animals ; Cell Line ; Cytoprotection/genetics ; Cytoprotection/physiology ; DNA Breaks, Double-Stranded ; DNA Damage/genetics ; Female ; Glucuronidase/blood ; Glucuronidase/genetics ; Glucuronidase/metabolism ; HEK293 Cells ; Humans ; Hyperoxia ; Klotho Proteins ; L-Lactate Dehydrogenase/analysis ; Lung/metabolism ; Male ; Mice ; Mice, Transgenic ; Smoke/adverse effects
    Chemical Substances Smoke ; L-Lactate Dehydrogenase (EC 1.1.1.27) ; Glucuronidase (EC 3.2.1.31) ; Klotho Proteins (EC 3.2.1.31)
    Language English
    Publishing date 2021-08-04
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 1013184-x
    ISSN 1522-1504 ; 1040-0605
    ISSN (online) 1522-1504
    ISSN 1040-0605
    DOI 10.1152/ajplung.00629.2020
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  10. Article ; Online: Acute lung injury complicating acute kidney injury: A model of endogenous αKlotho deficiency and distant organ dysfunction.

    Hsia, Connie C W / Ravikumar, Priya / Ye, Jianfeng

    Bone

    2017  Volume 100, Page(s) 100–109

    Abstract: The lung interfaces with atmospheric oxygen via a large surface area and is perfused by the entire venous return bearing waste products collected from the whole body. It is logical that the lung is endowed with generous anti-oxidative capacity derived ... ...

    Abstract The lung interfaces with atmospheric oxygen via a large surface area and is perfused by the entire venous return bearing waste products collected from the whole body. It is logical that the lung is endowed with generous anti-oxidative capacity derived both locally and from the circulation. The single-pass pleiotropic alpha-Klotho (αKlotho) protein was discovered when its genetic disruption led to premature multi-organ degeneration and early death. The extracellular domain of αKlotho is cleaved by secretases and released into circulation as endocrine soluble αKlotho protein, exerting wide-ranging cytoprotective effects including anti-oxidation on distant organs including the lung, which exhibits high sensitivity to circulating αKlotho insufficiency. Because circulating αKlotho is derived mainly from the kidney, acute kidney injury (AKI) leads to systemic αKlotho deficiency that in turn increases the risks of pulmonary complications, i.e., edema and inflammation, culminating in the acute respiratory distress syndrome. Exogenous αKlotho increases endogenous anti-oxidative capacity partly via activation of the Nrf2 pathway to protect lungs against injury caused by direct hyperoxia exposure or AKI. This article reviews the current knowledge of αKlotho antioxidation in the lung in the setting of AKI as a model of circulating αKlotho deficiency, an under-recognized condition that weakens innate cytoprotective defenses and contributes to the dysfunction in distant organs.
    MeSH term(s) Acute Kidney Injury/metabolism ; Acute Lung Injury/metabolism ; Animals ; Antioxidants/metabolism ; Humans ; Kidney/metabolism ; Renal Insufficiency, Chronic/metabolism ; Respiratory Distress Syndrome, Adult/metabolism
    Chemical Substances Antioxidants
    Language English
    Publishing date 2017-07
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 632515-4
    ISSN 1873-2763 ; 8756-3282
    ISSN (online) 1873-2763
    ISSN 8756-3282
    DOI 10.1016/j.bone.2017.03.047
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