DOCSLIB.ORG

Mechanisms and Limits of Induced Postnatal Lung Growth This Official Workshop Report Was Approved by the ATS Board of Directors December 2003

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Mechanisms and Limits of Induced Postnatal Lung Growth This Official Workshop Report Was Approved by the ATS Board of Directors December 2003 American Thoracic Society Documents Mechanisms and Limits of Induced Postnatal Lung Growth This Official Workshop Report was approved by the ATS Board of Directors December 2003. TABLE OF CONTENTS ties of tissue remodeling, structural interaction, and physiologic function; (2) providing an update on the mechanisms and func- Introduction tional limits of induced lung growth; and (3) identifying key Postnatal Lung Development issues for further investigation. Normal Development Abnormal Development POSTNATAL LUNG DEVELOPMENT Models of Induce Postnatal Lung Growth Increased Metabolic Oxygen Demand Normal Development Increased Mechanical Lung Strain Alveolarization. Transformation of the immature saccular lung Reduced Size (Lobar) Lung Transplant with a limited gas-exchange area to a mature lung with a large Chronic Hypoxia or High-altitude Exposure internal surface area entails thinning of alveolar walls, growth Extracellular Matrix and Elastic Fibers of capillary network, and extensive subdivision of gas exchange Signals and Mediators of Induced Lung Growth units. This period is marked by interstitial fibroblast proliferation Mechanical Signals while epithelial cells flatten and decrease in number, resulting Nonmechanical Signals and Mediators in a net thinning of distal airspace walls. Concurrently, alveolar Role of Pluripotent Stem Cells capillary network becomes more complex. Alveolar septation Functional Correlates and Limits of Induced Lung Growth begins as secondary crests that extend from primary alveolar Compensatory Versus Reparative Growth walls. Development of these crests or septae occurs through Nonstructural Sources of Adaptation: Recruitment deposition of new basement membrane, outgrowth of epithelial of Reserves cells and myofibroblasts at the tips of septae, and elastin deposi- Limits Imposed by Dysanaptic Lung Growth tion (1). In humans, the process begins at approximately 36 weeks Limits Imposed by Heart–Lung–Thorax Interaction of gestation (2). At birth, only approximately 15% of alveoli Growth Induction and Carcinogenesis have formed, with the remaining subdivisions developing in the Future Directions first few postnatal years (2–5). Bronchovasculoalveolar interaction. Vascular development INTRODUCTION occurs via two processes: (1) vasculogenesis, the development The mature lung has traditionally been assumed to be nonmalle- of blood vessels from the differentiation of angioblasts in meso- able; structural changes were considered irreversible once nor- derm, and (2) angiogenesis, classically described as sprouting of mal alveolar development was completed, and treatment for blood vessels from existing vessels (6–8), but can also occur by chronic lung disease typically focuses on minimizing symptoms “intussusception” (9), formation and growth of a transcapillary and preventing further tissue destruction. This approach is being tissue pillar that eventually divides an existing capillary segment revised in light of recent findings. There is growing clinical evi- into two. The bronchial (systemic) vessels develop with preacinar dence of accelerated or “catch-up” lung growth in youngsters airways; development is complete by approximately 16-weeks whose lung disease is no longer active. Several experimental gestation with further growth in size to match lung growth (3). models have shown the possibility of accelerating the rate of lung Bronchial vessels generally are not found in the peripheral acinar growth during and beyond the period of postnatal maturation. region and thus do not normally participate in alveolar gas ex- There has been new insight into the signals, mediators, and ana- change. Preacinar pulmonary arteries, supplied by the right heart, tomic sites of postnatal lung growth as well as their interactions grow with the airways into the intra-acinar region and fuse with and physiologic correlates. Although much remains unknown, this peripheral microvasculature that has arisen from the mesen- field is poised on the verge of practical application, with potential chyme by vasculogenesis (8). It is not clear whether capillary therapeutic implications for the management of chronic lung dis- invasion stimulates alveolar septation or vice versa, but alveolar ease, lung volume reduction surgery, and transplantation. This septation is always associated with capillary invasion. The impor- workshop was conducted to summarize relevant recent advances tance of vascular supply to alveolarization is demonstrated by with the objectives of (1) promoting an integrative understand- studies using antiangiogenic agents such as fumagillin, thalidomide, ing of the potential for postnatal lung growth that encompasses and Su-5416, an inhibitor of the vascular endothelial growth not just gene expression and cell division, but also the complexi- factor (VEGF) receptor; these agents disrupt vascular develop- ment, leading to reduced pulmonary arterial density and inhibi- tion of alveolar growth (10). Bronchial arteries are responsive to angiogenic stimuli throughout life. Unilateral pulmonary artery ligation augments Members of the ad hoc Statement Committee have disclosed any direct commer- growth of bronchial arteries in lambs and mice (11, 12). In chronic cial associations (financial relationships or legal obligations) related to the prepara- pulmonary hypertension, bronchial vessels grow even as periph- tion of this statement. This information is kept on file at the ATS headquarters. eral pulmonary vessels are lost (13). In lung disease, angiogenesis Am J Respir Crit Care Med Vol 170. pp 319–343, 2004 DOI: 10.1164/rccm.200209-1062ST of the bronchial circulation does not support normal gas ex- Internet address: www.atsjournals.org change, and the high pressure of these systemic vessels can lead 320 AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE VOL 170 2004 to life-threatening hemoptysis. In regions of bronchial angiogen- with a thicker septal interstitium, which contains more collagen esis, local pulmonary vessels do not show angiogenesis, sug- and elastin fibers to bear the force of lung distension (37, 38). gesting that the two vascular systems respond independently Rodents are born with the lung in the saccular stage; alveolariza- (14). There is only limited evidence supporting induced postnatal tion occurs exclusively from Days 4–14 after birth, followed by growth of intra-acinar blood vessels, as after chronic pseudo- alveolar wall thinning between Days 14–21 (39). Because rodent monas infection in rats (15) and in patients with veno-occlusive epiphyses never close (40), thoracic growth and alveolarization disease (16). persist throughout life (41). In comparison, most of the alveoli in Although the lung is extensively innervated from early fetal guinea pig lungs have already formed at birth (42, 43) containing life, postnatal denervation by cervical vagotomy and sympathec- more septal connective tissue (44) and less pulmonary vascular tomy does not significantly affect subsequent lung growth or smooth muscle (45). Guinea pigs also undergo epiphyseal closure mechanics in growing rats and rabbits (17–19); hence, pattern beginning at approximately 5 months of age (46), suggesting and extent of growth are not critically dependent on neural that older animals reach an upper limit of thoracic and hence control or communication. lung size. In rabbits, alveoli continue to form after birth into adulthood (36 weeks), but septal thinning occurs mostly before Abnormal Development birth (47). Their alveolar blood–gas barrier is thinner with a Clinical syndromes. Syndromes that alter expression of growth higher capillary wall stress compared with larger species (dog factors, cytokines, transcription factors, or extracellular matrix and horse) (48, 49); septal thickness and capillary wall strength (ECM) proteins provide models to explore mechanisms that increase with postnatal maturation (50). control alveolar development. Signals that regulate the saccular- There are no major differences between dogs and humans in to-alveolar morphologic transition are poorly understood, but the characteristics of lung structure or function during postnatal disrupting lung septation during this transition impairs alveolar maturation and aging (51). Because they are highly aerobic and formation, resulting in a loss of alveolar surface area (20, 21). easily trained, dogs are used in exercise studies to define the There are several syndromes of abnormal lung alveolarization functional correlates of lung growth. Sheep are born with well- in humans. Trisomy 21 (Down syndrome) is associated with formed alveoli; postnatal growth only modestly increases alveo- reduced lung volumes, alveolar surface area, fewer alveoli, defec- lar complexity and total alveolar number (52). Pigs are born tive elastin deposition, and vascular abnormalities (22, 23). Lep- with alveolar–capillary surface densities and air–blood tissue rechaunism, caused by a defect of the insulin/insulin-like growth barrier thickness already at adult levels (53). Airspace expansion factor-I receptor, is associated with reduced lung surface areas and septal thinning during the first postnatal week increases as well as fewer and larger alveoli (24). Oligohydramnios (25), elastic recoil, followed by vigorous septal subdivision and thick- congenital diaphragmatic hernia (CDH) (26), and intrathoracic ening (54, 55). Lung development in primates closely mimics mass lesions are all associated with pulmonary hypoplasia caused that in humans, although postnatal alveolar growth in monkeys by the
Load more

Recommended publications
  • Relative Indicators and Predicative Ability of Some Biological Variables on Cardiac Neural Activity for Volleyball Players
    Sys Rev Pharm 2020;11(9):834-840 A multifaceted review journal in the field of pharmacy Relative Indicators and Predicative Ability of Some Biological Variables on Cardiac Neural Activity for Volleyball Players Mohammed Nader Shalaby 1*, Marwa Ahmed Fadl2 1 Biological Sciences and Sports Health Department, Faculty of Physical Education, Suez Canal University, Egypt, [email protected] 2 Training and Kinematics Department, Faculty of Physical Education for Girls- Alexandria University. Egypt. Corresponding Author: Mohammed Nader Shalaby Email: [email protected] ABSTRACT The current research aims to study the relative indicators and predictive Keywords: Cardiac Neural Activity – HRV - Cardio-respiratory Fitness - ability of some biological variables for the cardiac neural activity of volleyball Volleyball players. The researchers used the descriptive approach as it is suitable for these research objectives. The researchers used the descriptive approach as it is suitable for these research objectives. Results indicated that: Correspondence: • There are positive correlations between biological variables and Heart Rate Mohammed Nader Shalaby Variability for the following variables: VC max – PEF – VC – EV – IV – HR max Associate Professor of Biological Sciences and Sports Health Department, – CO2 max. These variables are considered as indicators for evaluating the Faculty of Physical Education, Suez Canal University, Egypt, functional training status of volleyball players. Email: [email protected] • Relative contribution of biological variables was between (31.40%) as the least value fir VC max and (97.25%) as the highest value for the following nine variables: VC max + PEF + VC + EV + IV + HR max + VO2 max + CO2 max. these variables contribute collectively in HRV for volleyball players.
    [Show full text]
  • Pulmonary Haemodynamics During Exercise
    ERS OFFICIAL DOCUMENT ERS STATEMENT An official European Respiratory Society statement: pulmonary haemodynamics during exercise Gabor Kovacs1,2, Philippe Herve3, Joan Albert Barbera4,5, Ari Chaouat6,7, Denis Chemla8, Robin Condliffe9, Gilles Garcia8, Ekkehard Grünig10, Luke Howard11, Marc Humbert 8, Edmund Lau12, Pierantonio Laveneziana13,14, Gregory D. Lewis15, Robert Naeije16, Andrew Peacock17, Stephan Rosenkranz18, Rajeev Saggar19, Silvia Ulrich20, Dario Vizza 21, Anton Vonk Noordegraaf22 and Horst Olschewski1,2 @ERSpublications Pulmonary haemodynamics during exercise provides relevant information on the lung, pulmonary vessels and heart http://ow.ly/EBOF30fuHWY Cite this article as: Kovacs G, Herve P, Barbera JA, et al. An official European Respiratory Society statement: pulmonary haemodynamics during exercise. Eur Respir J 2017; 50: 1700578 [https://doi.org/ 10.1183/13993003.00578-2017]. ABSTRACT There is growing recognition of the clinical importance of pulmonary haemodynamics during exercise, but several questions remain to be elucidated. The goal of this statement is to assess the scientific evidence in this field in order to provide a basis for future recommendations. Right heart catheterisation is the gold standard method to assess pulmonary haemodynamics at rest and during exercise. Exercise echocardiography and cardiopulmonary exercise testing represent non-invasive tools with evolving clinical applications. The term “exercise pulmonary hypertension” may be the most adequate to describe an abnormal pulmonary haemodynamic response characterised by an excessive pulmonary arterial pressure (PAP) increase in relation to flow during exercise. Exercise pulmonary hypertension may be defined as the presence of resting mean PAP <25 mmHg and mean PAP >30 mmHg during exercise with total pulmonary resistance >3 Wood units. Exercise pulmonary hypertension represents the haemodynamic appearance of early pulmonary vascular disease, left heart disease, lung disease or a combination of these conditions.
    [Show full text]
  • Xerox University Microfilms
    INFORMATION TO USERS This material was produced from a microfilm copy of the original document. While the most advanced technological means to photograph and reproduce this document have been used, the quality is heavily dependent upon the quality of the original submitted. The following explanation of techniques is provided to help you understand markings or patterns which may appear on this reproduction. 1. The sign ur "target" for pages apparently lacking from the document photographed is "Missing Page(s)". If it was possible to obtain the missing page(s) or section, they are spliced into the film along with adjacent pages. This may have necessitated cutting thru an image and duplicating adjacent pages to insure you complete continuity. 2. When an image on the film is obliterated with a large round black mark, it is an indication that the photographer suspected that the copy may have moved during exposure and thus cause a blurred image. You will find a good image of the page in the adjacent frame. 3. When a map, drawing or chart, etc., was part of the material being photographed the photographer followed a definite method in "sectioning" the material. It is customary to begin photoing at the upper left hand corner of a large sheet and to continue photoing from left to right in equal sections with a small overlap. If necessary, sectioning is continued again — beginning below the first row and continuing on until complete. 4. The majority of users indicate that the textual content is of greatest value, however, a somewhat higher quality reproduction could be made from "photographs" if essential to the understanding of the dissertation.
    [Show full text]
  • HHP 430 Exercise Physiology
    HHP 430 Exercise Physiology Image from: http://www.dsu.edu/majors-programs/exercise-science.aspx taught by: Kathe A. Gabel, PhD, RD, CSSD Department of Health and Human Performance Image from: http://fhs-bio-wiki.pbworks.com/w/page/12145766/ETC Spring Semester, 2012 College of Allied Health Professions Montana State University – Billings MSU – Billings College of Allied Health Professions Department of Health and Human Performance Spring, 2012 Course Rubric & Title: HHP 430 Exercise Physiology Instructor: Kathe A. Gabel, PhD, RD, CSSD Office/Hours: PE 117, MW 9:00 – 10:00 a.m., by apptmt Phone: 406-657-2927 E-mail: [email protected] Class Times: TR 8:40 – 10:10 a.m. Location: PE 121 Required Text: Plowman, S.A., Smith, D.L. (2011). Exercise Physiology for Health, Fitness, and Performance, 3rd Ed. Philadelphia: Wolters Kuwer/Lippincott Williams & Wilkins. Required Course Packet: Gabel, K.A., (Spring, 2012) Course Materials for HHP 430. MSU-Billings Bookstore. Catalog Description: HHP 430 Exercise Physiology, 3 cr. Prerequisite: HHP 100 – Foundations in Exercise Science Highly recommended prerequisite: Anatomy and Physiology The course provides students the opportunity to study the physiological fundamentals needed to understand skilled movement. The course focuses on the responses of the human body to exercise with emphasis on professional interventions in various education, health promotion, and human performance settings. Various body systems (i.e. respiratory, circulatory, musculoskeletal, endocrine) are studied to understand the adaptations associated with involvement in physical fitness, sport, and healthy lifestyle activities. Course Goals: Upon successful course completion, you will be able to: 1. demonstrate knowledge & comprehension of physiological principles of human movement.
    [Show full text]
  • Tibetan and Andean Patterns of Adaptation to High-Altitude Hypoxia
    Tibetan and Andean Patterns of Adaptation to High-Altitude Hypoxia 1 CYNTHIA M. BEALL Abstract Understanding the workings of the evolutionary process in contemporary humans requires linking the evolutionary history of traits with their current genetics and biology. Unusual environments provide natural experimental settings to investigate evolution and adaptation. The example of high-altitude hypoxia illustrates some of the progress and many of the remaining challenges for studies of evolution in contem- porary populations. Current studies exemplify the frequently encountered problem of determining whether large, consistent population differences in mean values of a trait reflect genetic differences. In this review I de- scribe 4 quantitative traits that provide evidence that indigenous popu- lations of the Tibetan and Andean plateaus differ in their phenotypic adaptive responses to high-altitude hypoxia. These 4 traits are resting ventilation, hypoxic ventilatory response, oxygen saturation, and hemo- globin concentration. The Tibetan means of the first 2 traits were more than 0.5 standard deviation higher than the Aymara means, whereas the Tibetan means were more than 1 standard deviation lower than the Ay- mara means for the last 2 traits. Quantitative genetic analyses of within- population variance revealed significant genetic variance in all 4 traits in the Tibetan population but only in hypoxic ventilatory response and he- moglobin concentration in the Aymara population. A major gene for oxygen saturation was detected among the Tibetans. These findings are interpreted as indirect evidence of population genetic differences. It ap- pears that the biological characteristics of sea-level humans did not con- strain high-altitude colonists of the 2 plateaus to a single adaptive re- sponse.
    [Show full text]
  • Evidence-Based Role of Hypercapnia and Exhalation Phase in Vagus
    P a & hys Singh, J Yoga Phys Ther 2017, 7:3 og ic Y a f l o T DOI: 10.4172/2157-7595.1000276 l h a e n r a r p u y o J Journal of Yoga & Physical Therapy ISSN: 2157-7595 ReviewResearch Article Article Open Access Evidence-Based Role of Hypercapnia and Exhalation Phase in Vagus Nerve Stimulation: Insights into Hypercapnic Yoga Breathing Exercises Umesh Pal Singh* Subharti Medical College, Meerut, Uttar Pradesh India Abstract Being a yoga practitioner, Dr. Singh has always been curious to know of how yoga works. First, after going through the book—Nature and Health, he could find that carbon dioxide stimulates vagus nerve. Thereafter he could also find a study that shows of how increased blood concentration of carbon dioxide (hypercapnia) in conscious humans can stimulate the vagus nerve that in turn, manifests as respiratory sinus arrhythmia (RSA). Even more important, the results of this study also prove that when hypercapnia is coupled with exhalation phase, a synergistic effect occurs that compounds the cardio-inhibitory response of vagus nerve. In some review articles, it was stated that increased blood CO2 concentration is the most porobable mechanism that determines an enhanced effect on the cardio-inhibitory response of vagus nerve during exhalation phase of the breathing rhythm. In another very interesting study, the importance of exhalation phase of the breathing rhythm in superficial acupuncture stimulation was revealed. As the effect is comparatively pronounced when acupuncture stimulation is applied only during exhalation versus continuous stimulation during both inhalation as well as inhalation phase.
    [Show full text]
  • INQUIRY QUESTION What Would Be the Chronic Adaptations That Would
    INQUIRY QUESTION What would be the chronic adaptations that would allow Jared Tallent to perform at his best for the 50 km walk? CHAPTER Chronic adaptations to 12 training Chronic adaptations are the long-term physiological changes that occur as a result of participating in a training program. The types of adaptations that lead to improved performance are dependent on the specific type of training that is undertaken. KEY KNOWLEDGE İ Chronic adaptations of the cardiovascular, respiratory and muscular systems to aerobic, anaerobic and resistance training KEY SKILL İ Explain how the cardiovascular, respiratory and muscular systems’ chronic adaptations to training lead to improved performance CHAPTER PREVIEW Chronic adaptations to training Aerobic Anaerobic Resistance training training training adaptations adaptations adaptations Cardiovascular Respiratory Muscular Muscular Neuromuscular Heart size Pulmonary O2 utilisation Muscle Muscle size and Heart ventilation a-VO2 difference hypertrophy structure capillarisation Tidal volume Mitochondria Fuel stores Muscle bre type Stroke volume Respiratory rate Myoglobin Enzymes adaptation Heart rate Pulmonary Fuel stores Motor unit Neural control Cardiac output diffusion Oxidative recruitment Synchronisation Blood pressure enzymes Lactate tolerance of motor units Muscle Fibre type Firing rate of capillarisation adaptation motor units Blood volume Inhibitory signals VO2 maximum Lactate inection point 12.1 Chronic training adaptations KEY CONCEPT Chronic adaptations of the cardiovascular, respiratory and muscular systems occur as a result of long-term participation in a training program. These responses depend on the type, frequency, duration/time and intensity of the training undertaken. Exercise or training undertaken regularly over an extended period of time (usually at least three times per week for a minimum of 6–8 weeks) leads to the development Chronic adaptations are the of long-term or chronic adaptations to training.
    [Show full text]
  • The Training Type Influence on Male Elite Athletes' Ventilatory Function
    BMJ Open Sport Exerc Med: first published as 10.1136/bmjsem-2017-000240 on 28 July 2017. Downloaded from Open Access Original article The training type influence on male elite athletes’ ventilatory function Tijana Durmic,1 Biljana Lazovic Popovic,2,3 Mirjana Zlatkovic Svenda,3,4 Marina Djelic,5 Vladimir Zugic,3,6 Tamara Gavrilovic,7 Zoran Mihailovic,1 Marija Zdravkovic,3,8 Roman Leischik9 To cite: Durmic T, Lazovic ABSTRACT What are the new findings? Popovic B, Zlatkovic Background/aim To assess and compare measured Svenda M, et al. The training ventilatory volumes (forced expiratory volume in 1 s type influence on male elite " This is a large pioneering cross-sectional study (FEV ), peak expirium flow (PEF) and maximal athletes’ ventilatory function. 1 that included 470 male elite athletes and exam- voluntary ventilation (MVV)), ventilatory function BMJ Open Sport Exerc Med ined and compared measured ventilatory 2017;3:e000240. capacities (forced vital capacity (FVC) and vital capacity volumes (forced expiratory volume in 1 s (FEV1), doi:10.1136/bmjsem-2017- (VC)) and FEV1/VC ratio in a sample of power and peak expirium flow and maximal voluntary venti- 000240 endurance elite athletes and their age-matched and lation), ventilatory function capacities (forced sex-matched sedentary control group. vital capacity (FVC) and vital capacity (VC)) and Accepted 20 June 2017 Methods A cross-sectional study was applied on male FEV1/VC ratio in a sample of power and endur- elite athletes (n=470) who were classified according to ance elite athletes and their age-matched and the type of the predominantly performed exercise in sex-matched sedentary control group.
    [Show full text]
  • Facts and Challenges in Respiratory Neurobiology
    G Model RESPNB-2465; No. of Pages 4 ARTICLE IN PRESS Respiratory Physiology & Neurobiology xxx (2015) xxx–xxx Contents lists available at ScienceDirect Respiratory Physiology & Neurobiology jou rnal homepage: www.elsevier.com/locate/resphysiol Frontiers review ଝ Facts and challenges in respiratory neurobiology a,b c,∗ d e f g T.E. Dick , M. Dutschmann , J.L. Feldman , A.Y. Fong , S. Hülsmann , K.M. Morris , h,i j J.M. Ramirez , J.C. Smith , The Respiratory Neurobiology Consortium a Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, Case Western Reserve University, Cleveland, OH, USA b Department of Neurosciences, Case Western Reserve University, Cleveland, OH, USA c Florey Institute of Neuroscience and Mental Health, University of Melbourne, Gate 11 Royal Parade, Melbourne 3052, VIC, Australia d Systems Neurobiology Laboratory, Department of Neurobiology, David Geffen School of Medicine at the University of California Los Angeles, Box 951763, Los Angeles, CA 90095-1763, USA e Department of Physiology, University of Melbourne, Melbourne 3010, VIC Australia f Clinic for Anesthesiology, RG experimental Neuroanesthesiology, Georg-August-University Göttingen, Humboldtallee 23, 37073 Göttingen, Germany g Department of Molecular Pharmacology and Physiology, University of South Florida, Tampa, FL, USA h Center for Integrative Brain Research, Seattle Children’s Research Institute, Seattle, WA 98101, USA i Department of Neurological Surgery, University of Washington, Seattle, WA 98104, USA j Cellular and Systems Neurobiology Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA a r t a b i c l e i n f o s t r a c t Article history: Respiratory neurobiology has been a lead discipline in the field of neuroscience for almost a century.
    [Show full text]
  • NCS-1 Protein Upregulation Facilitates Chronic Hypoxia- Induced Respiratory Adaptation in Lymnaea Stagnalis
    NCS-1 protein upregulation facilitates chronic hypoxia- induced respiratory adaptation in Lymnaea stagnalis by Yi Quan A thesis submitted in conformity with the requirements for the degree of Master of Science Graduate Department of Physiology University of Toronto © Copyright by Yi Quan 2012 NCS-1 protein upregulation facilitates chronic hypoxia-induced respiratory adaptation in Lymnaea stagnalis Yi Quan Master of Science Graduate Department of Physiology University of Toronto 2012 Abstract Chronic hypoxia is a consequence of many common diseases, including sleep apnea and chronic lung disease. As there is no cure for many of these diseases, managing the symptoms of these diseases, including hypoxia is of great clinical importance. Preliminary data from the Feng lab show that the calcium binding protein neuronal calcium sensor-1 (NCS-1) is upregulated in the central nervous system of the freshwater pond snail Lymnaea stagnalis following chronic hypoxia treatment. This upregulation coincides with increased aerial respiratory activity. Furthermore, knockdown of NCS-1 attenuates hypoxia-induced facilitation of aerial respiration. Since this aerial respiratory activity is controlled by a respiratory central pattern generator (rCPG), it is hypothesized that hypoxia-induced upregulation of NCS-1 may regulate rCPG activity. Using intercellular sharp electrode recording, I show that in response to chronic hypoxia treatment, there is increased bursting activity and altered action potential profile in the pacemaker neuron of the rCPG, RPeD1. Knockdown of NCS-1 partially prevents these hypoxia- induced changes. Our findings suggest that NCS-1 upregulation is necessary for chronic hypoxia-induced respiratory adaptation. ii Acknowledgments I would like to thank my supervisor – Dr.
    [Show full text]
  • Onset of Respiration at Birth* M
    Arch Dis Child: first published as 10.1136/adc.49.5.333 on 1 May 1974. Downloaded from Review article Archives of Disease in Childhood, 1974, 49, 333. Onset of respiration at birth* M. J. PURVES From the Department of Physiology, The Medical School, University of Bristol The mechanisms which underly the onset of Barron and himself in the 1930s (Barcroft and respiration at birth are of common interest to the Barron, 1937a, b) in which the pattern of stimulation paediatrician, the obstetrician, and the physiologist. necessary to provoke respiration had been traced If respiration does not start shortly after birth, then throughout gestation. It was Barcroft's view that the newborn is in a precarious position with a respiration was actively inhibited in the mature fetus rapidly falling placental gas exchange and a not yet and that in some way this inhibition was lifted at developed pulmonary gas exchange. And if this birth and so the fetus was 'allowed' to breathe. It insult is added to that of a difficult labour and may be remarked in passing that this concept rests delivery, it is scarcely surprising that if the fetus heavily on evidence that breathing was easily survives, it does so with some form of neurological induced in the young fetus and not only has this not deficit. Thus the discovery of how the fetus resists been confirmed (Dawes et al., 1972), but many hypoxia and of how breathing starts at birth is not observers have commented on the difficulty of simply a problem of interest to physiologists; rather, distinguishing respiratory from nonspecific move- it can be considered a part of a wider strategy of ments at this age, a point which will be discussed in research aimed at reducing the incidence ofcrippling a later section.
    [Show full text]
  • Aging of the Respiratory System: Impact on Pulmonary Function Tests and Adaptation to Exertion Jean-Paul Janssens, MD
    Clin Chest Med 26 (2005) 469 – 484 Aging of the Respiratory System: Impact on Pulmonary Function Tests and Adaptation to Exertion Jean-Paul Janssens, MD Outpatient Section of the Division of Pulmonary Diseases, Geneva University Hospital, 1211 Geneva 14, Switzerland Life expectancy has risen sharply during the past chest wall, in static elastic recoil of the lung (Fig. 1), century and is expected to continue to rise in virtually and in strength of respiratory muscles. all populations throughout the world. In the United States population, life expectancy has risen from Age-associated changes in the chest wall 47 years in 1900 to 77 in 2001 (74.4 for the male and 79.8 for the female population) [1]. The proportion of Estenne and colleagues measured age-related the population over 65 years of age currently is more changes in chest wall compliance in 50 healthy than 15% in most developed countries and is ex- subjects ages 24 to 75: aging was associated with a pected to reach 20% by the year 2020. Healthy life significant decrease (À31%) in chest wall compli- expectancy, at the age of 60, is at present 15.3 years ance, involving rib cage (upper thorax) compliance for the male population and 17.9 years for the female and compliance of the diaphragm-abdomen compart- population [2]. These demographic changes have a ment (lower thorax) [5]. Calcifications of the costal major impact on health care, financially and clini- cartilages and chondrosternal junctions and degenera- cally. Awareness of the basic changes in respiratory tive joint disease of the dorsal spine are common physiology associated with aging and their clinical radiologic observations in older subjects and contrib- implication is important for clinicians.
    [Show full text]