Respiratory Control

Respiratory Control: Central and Peripheral Mechanisms

DEXTER F. SPECK
MICHAEL S. DEKIN
W. ROBERT REVELETTE
DONALD T. FRAZIER
Copyright Date: 1993
Pages: 248
https://www.jstor.org/stable/j.ctt130jgrq
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  • Book Info
    Respiratory Control
    Book Description:

    Understanding of the respiratory control system has been greatly improved by technological and methodological advances. This volume integrates results from many perspectives, brings together diverse approaches to the investigations, and represents important additions to the field of neural control of breathing.

    Topics include membrane properties of respiratory neurons, in vitro studies of respiratory control, chemical neuroanatomy, central integration of respiratory afferents, modulation of respiratory pattern by peripheral afferents, respiratory chemoreception, development of respiratory control, behavioral control of breathing, and human ventilatory control.

    Forty-seven experts in the field report research and discuss novel issues facing future investigations in this collection of papers from an international conference of nearly two hundred leading scientists held in October 1990. This research is of vital importance to respiratory physiologists and those in neurosciences and neurobiology who work with integrative sensory and motor systems and is pertinent to both basic and clinical investigations.

    Respiratory Controlis destined to be widely cited because of the strength of the contributors and the dearth of similar works.

    eISBN: 978-0-8131-6046-7
    Subjects: Health Sciences

Table of Contents

  1. Front Matter
    (pp. i-iv)
  2. Table of Contents
    (pp. v-viii)
  3. Preface
    (pp. ix-x)
    Dexter F. Speck, Michael S. Dekin, W. Robert Revelette and Donald T. Frazier
  4. Part I Membrane Properties of Respiratory Neurons
    • 1 Membrane Properties of Respiratory Neurons: An Overview
      (pp. 2-5)
      Michael S. Dekin

      A major goal of respiratory neurophysiologists has been to characterize the membrane properties of respiratory neurons and associate these properties with models of the respiratory central pattern generator (respiratory CPG). Much of this effort has been directed towards describing intrinsic cellular mechanisms underlying rhythm generation such as endogenous pacemaker activity and postinhibitory rebound phenomena. More recently we have also begun to appreciate the role of membrane properties in nonrhythmgenerating functions such as pattern formation. In this regard, it is now recognized that many respiratory neurons do not act as high fidelity followers of their synaptic inputs. Rather, these neurons possess...

    • 2 Properties of Brainstem Neurons: Calcium Currents in Hypoglossal Motoneurons
      (pp. 6-11)
      Albert J. Berger and Felix Viana

      The subthreshold and firing behaviors of respiratoryrelated neurons are governed both by their intrinsic membrane properties and by their synaptic inputs. Recently our interest has turned to investigating intrinsic properties of brainstem respiratory neurons, in particular voltageand time-dependent conductances that are present in hypoglossal motoneurons. At present little is known about Ca++currents in respiratory motoneurons. We hypothesize that these currents have an important role in determining the subthreshold and firing behaviors of respiratory motoneurons.

      Voltage-gated neuronal calcium currents have been categorized in two major ways. The first considers Ca++currents to consist of low-voltage-activated (LVA) and highvoltage-activated (HVA) types...

    • 3 Neuronal Membrane Properties during O₂ Deprivation: In Vitro Intracellular Studies
      (pp. 12-14)
      Gabriel Haddad and Chun Jiang

      It is well recognized that cellular and membrane properties play an important role in the repetitive firing of neurons in the central nervous system (CNS) of vertebrates as well as invertebrates (9). Although the importance of these membrane properties in respiratory neurogenesis and rhythm maintenance have not been demonstrated fully inin vivoconditions, a number of examples in vertebrates have been well documented (3, 4, 5, 10). Nowhere have these examples been more readily available than in adult hippocampal neurons (3), in cerebellar and thalamic neurons (10), and in spinal motoneurons (5). Neural oscillatory activities such as seizures, alternating...

    • 4 New Insights on Synaptic Transmission in the Nucleus Tractus Solitarius
      (pp. 15-20)
      J. Champagnat, P. Branchereau, M. Denavit-Saubié, G. Fortin, T. Jacquin and P. Schweitzer

      Most synaptic interactions in the central nervous system involve more than one messenger molecule. Functional pools of different transmitters can be co-regulated at pre- and postsynaptic sites. At presynaptic sites, neurotransmitters are co-localized and different patterns of afferent input may determine differential release of transmitters. At postsynaptic sites, multiple transmitter actions are integrated at different steps of the chain of events initiated by the agonists’ actions on receptive sites, intracellular messenger pathways, and membrane permeabilities. These synaptic influences operating in brainstem structures such as the nucleus tractus solitarius (NTS) probably contribute to central modulation of respiratory patterns.

      The NTS is...

    • 5 Modulation of Respiratory Patterns during Hypoxia
      (pp. 21-28)
      D. W. Richter, A. Bischoff, K. Anders, M. Bellingham and U. Windhorst

      Mammals react with a diphasic change in respiration when acute systemic hypoxia persists for longer than a few minutes (18, 46). This response starts with an initial increase of respiration which then turns to depression and terminates in apnea when partial oxygen pressure is below a value of 15 torr within the extracellular space of the respiratory network (1, 32, 45). When such severe hypoxia continues, inspiratory muscles are only transiently activated during gasps which are supposed to be organized by structures other than the medullary respiratory network producing the normal respiratory rhythm (40). This observation supports the hypothesis of...

  5. Part II In Vitro Studies of Respiratory Control
    • 6 In Vitro Studies of Respiratory Control: An Overview
      (pp. 30-33)
      Gordon S. Mitchell

      In vitroexperimental preparations have proven to be invaluable in many areas of contemporary neuroscience, allowing insights into the form and function of neural systems that were elusive with more traditional approaches (e.g., 31). Among the more powerful advantages ofin vitropreparations are the following: (1) direct access to neurons of interest, allowing direct visualization with modern microscopic techniques; (2) mechanical stability, thereby improving the stability of intracellular recordings with conventional or whole-cell patch techniques; and (3) improved control of the environment surrounding the neurons.

      By 1931 anin vitropreparation had already been applied to respiratory neurobiology (1),...

    • 7 Novel Approaches to the Study of Cellular Mechanisms Generating Respiratory Rhythm in Vitro
      (pp. 34-38)
      Jeffrey C. Smith, John J. Greer, Klaus Ballanyi, Jack L. Feldman and Diethelm W. Richter

      The neuronal mechanisms underlying respiratory rhythm-generation in the mammalian nervous system are unknown. Although there has been substantial progress in identifying cellular and synaptic properties of medullary respiratory neurons (11), the cellular mechanisms responsible for rhythm generation have not been elucidated. This is largely because the rhythm-generating neurons in the medulla have not been identified, due in part to technical limitations of experimental approaches applied to this problem in the nervous systemin vivo.

      Isolated preparations of the mammalian brainstem that preserve respiratory network and cellular functionin vitroallow the application of a broader range of neurobiological techniques and...

    • 8 Respiratory Rhythm Generation in the Ventral Medulla
      (pp. 39-42)
      Ikuo Homma, Akiko Arata and Hiroshi Onimaru

      Respiratory output is shaped by neurons in the dorsal and ventral respiratory groups (DRG and VRG) of the medulla. Although the shape and the amplitude of the inspiratory output are greatly altered by microlesion (19, 20) or by focal cooling (3) of these areas, respiratory rhythm remains. The exact locus and types of neurons constituting the respiratory rhythm generator are unknown. Several recent reports (4, 7) have suggested that structures localized ventral to the VRG are critical in the generation of rhythm and patterns of respiratory activity.

      In 1984, Suzue (21) used a brainstem–spinal cord preparation isolated from newborn...

    • 9 Noradrenergic Modulation of the Medullary Respiratory Rhythm Generator by the Pontine A5 Area
      (pp. 43-46)
      G. Hilaire, R. Monteau, S. Errchidi, D. Morin and J. M. Cottet-Emard

      Cardiovascular and respiratory regulation are based on intermingled mechanisms which interact peripherally and/or centrally. Therefore, it is often difficult to define the functional entirety of the central structures implicated in these regulations (11). Previous reports demonstrated that the pontine A5 area is involved in cardiovascular regulation (7). To define whether the A5 area also participates in respiratory regulation,in vitroexperiments were performed in the isolated brainstem–spinal cord preparation of newborn rats, which retains a respiratory activity after the elimination of all peripheral mechanisms. Results suggested that A5 may exert a tonic inhibitory modulation of the medullary respiratory rhythm...

    • 10 Bulbospinal Transmission of Respiratory Drive to Phrenic Motoneurons
      (pp. 47-51)
      Guosong Liu and Jack L. Feldman

      The continuous and reliable transmission of respiratory drive to spinal cord motoneurons controlling the muscles of the respiratory pump is a basic condition for life in mammals. This respiratory rhythm is generated in the brainstem and is transmitted to spinal motoneurons via bulbospinal neurons. Understanding the mechanism controlling the excitability of spinal cord respiratory motoneurons is fundamental to the understanding of neural control of respiration.

      Neuronal excitability is determined dynamically by synaptic input and intrinsic membrane properties. To study synaptic input to a neuron, the factors that control the generation and transmission of synaptic current must be determined. This requires...

    • 11 Comparative Approach to Neural Control of Respiration
      (pp. 52-58)
      Allan I. Pack, Raymond J. Galante, Robert E. Walker, Leszek K. Kubin and Alfred P. Fishman

      Most studies to elucidate the neural basis of respiratory rhythmogenesis have been done in mammals. Less investigation has been done in nonmammalian species. Although studies inAplysia(5), mollusk (41), lamprey (21, 22, 35, 36, 42), and teleost fish (1, 2) have provided certain interesting insights, they have shed little light on the evolution of the respiratory pattern generator. A comparative approach to neural systems can provide important insights (for discussion of this approach, see 4) by relating evolutionary changes in behavior to the neural basis of the behavior. With evolution there have been major changes in the mechanical act...

  6. Part III Chemical Neuroanatomy
    • 12 Chemical Neuroanatomy: An Overview
      (pp. 60-61)
      Albert J. Berger

      Chemical neuroanatomy deals with the localization of neurotransmitter substances within neural structures or path-ways. The purpose of chemical neuroanatomical studies is to learn more about the associations of neurotransmitters, their synthetic machinery, and receptors with certain functionally defined structures. This is particularly important for chemical neuroanatomical studies that are designed to advance our understanding of the neural control of respiration. Although much is known about neural structures that have a role in respiration, many of these structures lie within portions of the nervous system that have diverse functions, such as control of circulation. It is imperative, therefore, that chemical neuroanatomical...

    • 13 Neurotransmitter Content of Respiratory Neurons and Their Inputs: Double-Labeling Studies Using Intracellular Tracers and Immunohistochemistry
      (pp. 62-65)
      J. Lipski, C. Barton, D. de Castro, C. Jiang, I. Llewellyn-Smith, G. S. Mitchell, P.M. Pilowsky, M. D. Voss and H. J. Waldvogel

      Studies of respiratory neurons using a combination of intracellular recording and labeling with horseradish peroxidase (HRP) have greatly extended our knowledge of the relationship between the function and structure of brain-stem and spinal cord neurons involved in the control of respiratory motor output (e.g., 1, 2, 15, 23). Other studies utilizing the techniques of simultaneous extra-and intracellular recording from pairs of respiratory neurons and spike-triggered averaging have demonstrated monosynaptic connections between various subpopulations of respiratory neurons (e.g., 4, 6, 11, 14, 19). Although the latter studies show the direction of the synaptic influence (excitation or inhibition), they provide no information...

    • [Illustrations]
      (pp. None)
    • 14 Induction of Tyrosine Hydroxylase Gene in Carotid Body by Hypoxia
      (pp. 66-70)
      Maria F. Czyzyk-Krzeska, Douglas A. Bayliss and David E. Millhorn

      The carotid body (glomus caroticum) is a chemosensitive organ located at the bifurcation of the common carotid artery. The mammalian carotid body detects alterations in the partial pressures of oxygen (PO₂), carbon dioxide (PCO₂) and pH in arterial blood and transduces these signals into electrical impulses in primary sensory fibers of the carotid sinus nerve. Although the actual mechanism by which changes in blood gases are detected by the carotid body remains unknown, it is now generally believed that chemosensory signals are transmitted from Type I (glomus) cells to closely apposed sensory terminals (15) by release of a chemical transmitter...

    • 15 Expression and Development of Transmitter Properties in Carotid Body Afferent Neurons
      (pp. 71-74)
      David M. Katz

      Physiologic studies have demonstrated that peripheral chemoreflexes change markedly during development, profoundly altering respiratory responses to hypoxia (5, 9, 14, 15, 18, 19, 35). In the fetus, for example, the carotid chemoreceptors are relatively ineffective in increasing respiration during hypoxia (5, 7, 19, 35) and hypoxic stimulation leads to depression of respiratory movements (5). In neonates, on the other hand, hypoxia produces a transient hyperventilation, followed by a prolonged hypoventilation (5, 7, 9, 14, 15, 32, 35). In adults, however, hypoxia evokes a relatively sustained increase in ventilation, primarily by acting on the carotid bodies (10). Mechanisms that underlie these...

    • 16 Intrinsic Organization and Pontomedullary Connections of Rat Ventral Respiratory Group
      (pp. 75-80)
      Howard H. Ellenberger and Jack L. Feldman

      The medullary lateral tegmental field (LTF) is critically important for neural control of respiration. Our knowledge of the remarkably complex intrinsic organization of this region and its network connections with other respiratory neuron populations has been increasingly elaborated over the past decade. Recognition of these complexities is essential in order to understand the functional role of this region and for designing and appropriately interpreting experiments. A major focus of our recent research has been to determine the organization of cell columns within the medullary lateral tegmental field that are involved in the control of breathing. We briefly summarize the most...

  7. Part IV Central Integration of Respiratory Afferents
    • 17 Central Integration of Respiratory Afferents: An Overview
      (pp. 82-85)
      K. M. Spyer

      A large body of information is available on the range of afferent inputs that modify moment by moment the pattern of respiratory activity. Several chapters of this volume have been devoted to this issue and there are a number of excellent reviews on this topic (32, and others). It is, however, important to recognize that these same afferents influence other systems and that their major physiological role is the maintenance of cardio-respiratory homeostasis (9, 28). Given the importance of their role it is perhaps surprising that much less is known of the central processing of these inputs in achieving their...

    • 18 The Breuer-Hering Reflex Requires Excitatory Amino Acid Neurotransmission in a Discrete Region of the Nucleus Tractus Solitarius
      (pp. 86-90)
      Donald R. McCrimmon, Ann C. Bonham and Sharon K. Coles

      In most mammalian species lung inflation during eupneic breathing activates slowly adapting pulmonary stretch receptors (SAR) thereby shortening inspiration and prolonging expiration. Although these reflex effects are often collectively referred to as the Breuer-Hering reflex, it is not clear that the central nervous system pathways giving rise to inspiratory termination are necessarily the same as those lengthening expiration (cf. 12). The focus of this discussion will be on the identity and synaptic pharmacology of interneurons mediating the expiratory lengthening response, which, for simplicity, we will refer to as the Breuer-Hering reflex.

      Large myelinated afferent fibers arising from SAR course in...

    • 19 Connectivity of Rostral Pontine Inspiratory-Modulated Neurons as Revealed by Responses to Vagal and Superior Laryngeal Afferent Stimulation
      (pp. 91-94)
      Morton I. Cohen, Chen-Fu Shaw and Russell Barnhardt

      The classical experiments of Lumsden (15), in which transections at the level of the rostral pons produced apneusis (maintained inspiratory discharge), led to the concept that the region was the site of a “pneumotaxic center” that controls respiratory pattern. More modern hypotheses suggested that the pneumotaxic center facilitates the inspiratory off-switch (5). Subsequent lesion studies (20) resulted in a more precise localization of the pneumotaxic center to the region of the nucleus parabrachialis (NPBM) and the Kolliker-Fuse nucleus (KFN).

      To further elucidate pneumotaxic center function, microelectrode explorations were done by several groups of investigators. The early study by Cohen and...

    • 20 Respiratory Modulation of Afferent Transmission to the Cerebellum
      (pp. 95-99)
      S. Baker, C. Seers and T. A. Sears

      The diaphragm, intercostal, and abdominal muscles form the boundary of the thorax and abdomen. Their coordinated activities power lung ventilation and contribute mechanical stability to the spine in posture and locomotion. In eupnea (effortless breathing) the respiratory movements satisfying metabolic demands normally occur automatically and without the need for conscious intervention even during changes in posture. Yet the slightest unexpected hindrance to breathing, such as an increase in elastic loading, is readily perceived (12). Breathing then shifts from the realm of “automatic” to “voluntary” and remains thus until the load is removed or, following habituation again becomes automatic and “eupneic”....

    • 21 Respiratory Afferents and the Inhibition of Inspiration
      (pp. 100-104)
      Dexter F. Speck, Diane R. Karius and Liming Ling

      Although many studies have examined the phenomena of inspiratory inhibitory reflexes, there is very little information available concerning the neural circuits and neurotransmitters utilized in mediating these inhibitions. There are at least two distinct types of inhibitory (or disfacilitatory) effects evident in the response of the respiratory motor output to perturbations elicited through respiratory-related afferents. The first type of inhibition involves a transient reduction of inspiratory motor output and may be observed after a single electrical shock delivered to either the superior laryngeal nerve (SLN; 2, 3, 15), the intercostal nerve (ICN; 8, 21) or the phrenic nerve (PN; 16,...

  8. Part V Modulation of Respiratory Pattern by Peripheral Afferents
    • 22 Modulation of Respiratory Pattern by Peripheral Afferents: An Overview
      (pp. 106-109)
      Hazel M. Coleridge

      Respiratory patterns are modulated by peripheral neural feedback to the central respiratory networks. The inputs discussed in the following chapters include a description of input from the larynx, diaphragm, and exercising muscle, and an account of the special properties of chemosensitive C fibers in the bronchial branches of the vagus nerve. By way of introduction, I will discuss the functional significance of these peripheral inputs and give a brief description of input from the lower respiratory tract.

      The papers in this session emphasize that the afferent fibers comprising anatomically defined peripheral inputs that modulate breathing are not homogeneous. Afferent fibers...

    • 23 Laryngeal Sensory Modalities and Their Functional Significance
      (pp. 110-114)
      Giuseppe Sant’Ambrogio, James W. Anderson and Franca B. Sant’Ambrogio

      The larynx has a very rich sensory supply (1, 4), which plays an important role in defensive reflexes as well as the regulation of breathing. On the basis of their activation during upper airway breathing, tracheostomy breathing, upper airway occlusion, and tracheal occlusion, respiratory modulated laryngeal endings have been classified as cold, pressure, and “drive” receptors (16).

      Cold receptors are activated during upper airway breathing and remain silent during tracheal breathing, upper airway occlusion, and tracheal occlusion (fig. 23.1). These receptors are silent at body temperature and are activated during inspiration when temperature in the laryngeal lumen decreases (17). They...

    • 24 Diaphragmatic Afferents
      (pp. 115-119)
      Yves Jammes and Emmanuel Balzamo

      Dogiel (5) first identified muscle spindles and Golgi tendon organs in the diaphragmatic cupolae in humans, monkeys, dogs, cats, and rabbits. From these initial histological observations, the existence of a sensory component in the phrenic nerve has been accepted. This gave rise to numerous structural and neurophysiological investigations. Few histological studies on diaphragmatic receptors have been performed, and they were mostly done in cats, in which Duron (7) has identified only muscle spindles in the crural portion of this muscle. However, Winckler and Delaloye (30) and Winckler (31) reported the existence of muscle spindles in the diaphragmatic cupolae in humans....

    • 25 Responses of Group III and IV Muscle Afferents to Mechanical and Metabolic Stimuli Likely to Occur during Exercise
      (pp. 120-124)
      Marc P. Kaufman, Janeen M. Hill, Joel G. Pickar and Diane M. Rotto

      Static exercise has been firmly established to increase arterial pressure, myocardial contractility, heart rate, and ventilation. The mechanism causing these increases is not known. Three theories have been postulated to explain the increases in cardiovascular and ventilatory function evoked by exercise. The first theory proposes that the increases are due to a reflex originating in the contracting skeletal muscle (2), while the second theory, called “central command,” proposes that the increases are caused by direct action of central locomotor circuits on the medullary and spinal neuronal pools controlling ventilatory and cardiovascular function (5, 7). The third theory proposes that the...

    • 26 Neurotransmitter Mechanisms in the Periphery of Respiratory Afferents
      (pp. 125-128)
      Jan M. Lundberg and Kjell Alving

      The sensory nerves in the airways represent a first line of defense and alarm system. It is well known that the acute allergic reaction is associated with rapid sensory nerve activation as revealed by irritant sensations in the airway mucosa. Furthermore, additional central protective neural reflexes (sneezing and coughing) contribute to the initial phase of the allergen reaction in the airways. There is now evidence for a close anatomical association between mast cells and peptide containing sensory nerves in the airway mucosa (3, 24). Some of these nerve fibers close to mast cells contain tachykinins (neurokinin A [NKA] and substance...

  9. Part VI Respiratory Chemoreception:: Peripheral and Central
    • 27 Respiratory Chemoreception: Peripheral and Central: An Overview
      (pp. 130-131)
      Robert S. Fitzgerald and Machiko Shirahata

      Fundamental to the existence of an organism is oxygen. This most essential nutrient must be captured from the environment. Whereas for most mammalian species carbohydrate, protein, fat, minerals, and even water can be environmentally unavailable for days, perhaps weeks, the absence of oxygen from the environment for more than a few minutes is lethal. In the course of evolutionary development, organisms ranging in complexity from single to multicell animals have developed highly interactive systems and strategies for capturing oxygen. Simplest, of course, is the diffusion of oxygen from the environment across a membrane into the cytosol of the cell and...

    • 28 Carbonic Anhydrase, CI–-HCO₃– Exchanger, and Cellular pH in O₂ and CO₂ Chemoreception in the Cat Carotid Body in Vitro
      (pp. 132-137)
      S. Lahiri, R. Iturriaga, W. L. Rumsey, D. F. Wilson and D. Spergel

      Glomus cells in the carotid body (CB) serve as the sensor for the neuron in the petrosal ganglion. The levels of PO₂, PCO2₂ and pH of the arterial blood are detected by the glomus cells and the chemoreception is expressed as neurotransmitter release and sensory discharge (4). Carbonic anhydrase (CA) is present in the glomus cells of the CB (for review see 9). Knowledge of its subcellular distribution and isoenzyme types would help to understand the role that CA might play in the mechanisms and modulations of chemoreception of CO₂ and O₂. For the purpose of this presentation we will...

    • 29 Physiological Roles of the Central Chemoreceptors
      (pp. 138-146)
      Neil S. Cherniack

      A key feature of the respiratory system is its ability to significantly limit the changes in arterial PCO₂ (PaCO₂) caused by varying activity or residence at different altitudes (15, 37). This near copstancy of PaCO₂ together with the impressive ventilatory effects produced by inhaled CO₂ demonstrates the presence in the body of important receptors that respond either directly to PCO₂ changes or the acid-base alterations induced by CO₂ (6, 10, 11, 34, 36, 39).

      Several types of CO₂-sensitive receptors have been identified. The arterial chemoreceptors (the carotid body and to a lesser extent the aortic body) increase their discharge...

    • 30 Studies on Chemosensory Mechanisms in Rat Carotid Body Using Dissociated Cell Cultures
      (pp. 147-151)
      C. A. Nurse, A. Stea and C. Vollmer

      The mammalian carotid body is an arterial chemosensory organ located near the carotid bifurcation and is intimately associated with the pulmonary and cardiovascular systems (1, 4, 11). It is sensitive to natural changes in the chemical composition of arterial blood. Low PO₂ (hypoxia), elevated PCO₂ (hypercapnia), and low pH (acidity) excite the organ and reflexly stimulate respiration. The biophysical and neural mechanisms by which this single sensory organ responds to such varied stimuli have remained elusive for many years (4) and only recently did clues on possible transduction mechanisms emerge (2, 7, 10). Progress this area was hampered by difficul...

    • 31 Cellular Mechanisms of Central Chemosensitivity
      (pp. 152-156)
      Judith A. Neubauer

      The majority of central nervous system neurons respond to extracellular acidosis with membrane hyperpolarization and a reduction in excitability (14, 19, 21). Classical respiratory physiology has shown, however, that there exists a unique subset of neurons which are excited by hypercapnia and which participate in exciting the central respiratory neurons. These chemosensitive cells are located bilaterally in superficial regions of the ventrolateral medulla. Relatively little is understood regarding the mechanisms involved in the CO₂ transduction process.In vivostudies indicate that CO₂ is a much better stimulus of chemosensitive cells than fixed acid (9, 30, 33) suggesting that signal transduction...

  10. Part VII Development of Respiratory Control
    • 32 Development of Respiratory Control: An Overview
      (pp. 158-162)
      William E. Cameron

      This introduction provides an overview of some issues regarding the development of the neural control of respiration in mammals. This chapter will divide the discussion of the development of respiratory control into three parts: (1) the maturation of sensory inputs that influence respiration, (2) the evolution of the central circuits that generate the breath and (3) the alterations of the efferent outputs that transmit this rhythm to the respiratory muscles. More specifically, the changes occurring in the sensory transduction of some respiratory afferents, the synaptic efficacy of their central projections, and the changes in the properties of central neurons or...

    • 33 Central Effect of Hypoxia in the Neonate
      (pp. 163-166)
      Sandra J. England

      In both adult (9, 29) and newborn (4, 6, 14) animals, the ventilatory response to hypoxia is characterized by a biphasic pattern. Ventilation initially increases due to stimulation of peripheral chemoreceptors but this hyperventilation is not sustained. The secondary decline in ventilation is most prominent in newborn animals in which ventilation can fall below normoxic levels within minutes after the initiation of the hypoxic exposure. Several mechanisms for the secondary ventilatory depression have been proposed and investigated (14, 19).

      Adaptation of the afferent output of peripheral chemoreceptors during hypoxia has been demonstrated in some (4, 24) but not all investigations...

    • 34 Mechanisms of Apnea in the Newborn
      (pp. 167-171)
      Edward E. Lawson, Maria F. Czyzyk-Krzeska and Roger C. Rudesill

      In various animal species the respiratory central pattern generator of adults as well as newborns consists of three phases identified as inspiration and two distinctly different periods of expiration (15, 22, 31). The two phases of expiration are termed postinspiration (passive expiration) and stage II (active) expiration. The postinspiratory phase appears to mediate cessation of inspiration and to provide a transition to active stage II expiration (24) and, therefore, postinspiration might be the phase most sensitively affecting the respiratory rhythm.

      Introduction of smoke or water into the larynx activates medullary post-inspiratory mechanisms resulting in slowing of the respiratory rhythm or...

    • 35 Developmental Influences on Breathing Pattern by the Vagus Nerve: Some Correlations with Activities of Medullary Respiratory Neurons and Lung Mechanoreceptors
      (pp. 172-175)
      Jay P. Farber

      The role of vagally mediated pulmonary afferents in the generation and maintenance of breathing rhythm has been studied extensively. Of interest has been not only the breath by breath regulation of inspiration and expiration, but also maintenance of an adequate minute ventilation through vagal input. Thus, Sullivan et al. (23) noted that vagal blockade greatly decreased breathing rate in sleeping dogs. With respect to development, it has been shown that some anesthetized and/or unanesthetized neonatal mammals (e.g., the rat [14], the cat [6, 22], and the monkey [20]) have difficulty maintaining an adequate level of ventilation after bilateral vagotomy, due...

    • 36 Adaptation and Acclimatization in the Hypoxic Newborn Mammal
      (pp. 176-180)
      Jacopo P. Mortola, Robin D. Gleed and Chikako Saiki

      For any given inspired O₂ concentration, the alveolar and arterial O₂ pressures are mainly determined by the ratio between oxygen consumption (VO₂) and alveolar ventilation (VA). This suggests that the general mechanisms for protection of arterial PO₂ against hypoxia could consist of a reduction in VO₂ (metabolic adaptation), an increase in VA(respiratory acclimatization), or a combination of the two. This paper is a brief analysis of how the newborn mammal combines metabolic adaptation and ventilatory acclimatization to cope with acute and chronic hypoxia. It also discusses some of the short- and long-term effects of these strategies.

      In adult mammals,...

    • 37 Birth-Related Activation of the “Substance P Gene” in Central Respiratory Neurons and Dopaminergic Disinhibition of Carotid Bodies at Birth
      (pp. 181-184)
      Hugo Lagercrantz, Torbjörn Hertzberg, Håkan Persson, Meera Srinivasan and Yuji Yamamoto

      Breathing movements are episodic and partially inhibited before birth (3). The peripheral chemoreceptors are active, but their sensitivity is set at the low-PO2 level of the fetus, and they do not seem to contribute to the ventilatory drive before birth (2). The prenatal inhibition of breathing can be assumed to be due to the possibility that excitatory neurotransmitters stimulating breathing are not sufficiently expressed before birth and/or inhibitory neuroactive agents dominate in the fetus (9). To save oxygen consumption it might be appropriate to decrease breathing movements as well as general motor activity, particularly during asphyxia when the fetus reacts...

  11. Part VIII Behavioral Control of Breathing
    • 38 Behavioral Control of Breathing: An Overview
      (pp. 186-190)
      John Orem

      Behavioral control of breathing may be reflexive, as in sneezing, coughing, vomiting, and eructation, or voluntary (or learned), as during speaking, breathholding, and playing a wind instrument. These behavioral acts involve integration of large amounts of information in the brainstem and spinal circuits that produce automatic breathing. This information is nonrespiratory in form. It is not known for any of the acts of behavioral control listed above exactly how the control occurs.

      The list of structures that can control brainstem and spinal respiratory neurons is long and includes structures from all levels of the neuraxis. For example, hypothalamic control occurs...

    • 39 Respiratory Responses to Prolonged Central or Peripheral Hypoxia
      (pp. 191-194)
      G. E. Bisgard, M. J. A. Engwall, W. Z. Niu, L. Daristotle and J. Pizarro

      Prolonged hypoxic exposure results in a time-dependent ventilatory increase that is termed ventilatory acclimatization to hypoxia (VAH). This process requires up to one week to complete in humans and a much shorter period in animals (7). The process is completed sufficiently in four hours in the goat to make the goat a convenient animal model to investigate mechanisms of ventilatory control in hypoxic states including VAH (2, 4, 11, 18).

      We have examined the separate roles of carotid body (CB) and central nervous system (CNS) hypoxia on ventilatory control in the awake goat using isolated perfusion of the CB (1,...

    • 40 Forebrain-Brainstem Interactions Modulating Respiratory Patterning
      (pp. 195-198)
      Ronald M. Harper, C. A. Richard, H. Ni, J. X. Zhang and R. K. Harper

      Although it is essential to consider the microenvironment of the local brainstem and spinal cord circuitry which allows for cyclic activation of respiratory musculature, the reality of moment-by-moment respiratory control in behaving animals is that a large number of external forces modify respiratory patterning. The “external influences” include mechanisms which can affect breathing on a breathby-breath or an overall basis, and are brought into play when the organism encounters particular needs. These needs include such actions as dissipation of excess heat through air exchange, or enhancing oxygen capacity in anticipation of exercise.

      On occasion, organisms need to recruit respiratory musculature...

    • 41 State-Dependent Variations in Medullary Respiratory-Related Discharge Patterns
      (pp. 199-206)
      Fat-Chun T. Chang

      Modifications of brainstem respiratory neuronal activities by physiological and behavioral changes have been investigated in unanesthetized preparations by several laboratories. These studies showed that brainstem respiratory neuronal activities can undergo marked variations not only with sleep/wakefulness cycles (22, 28, 30, 31, 35, 38, 40), but also with changes in cardiovascular activities (14, 36), and during the execution of a conditioned inspiratory inhibition response (23–25, 29). More recently, a freely behaving guinea pig model system has been developed in my laboratory (8, 9). This model system permits hours of stable recording from single medullary respiratory neurons in freely behaving animals...

    • 42 Vomiting: Its Respiratory Components
      (pp. 207-210)
      Alan D. Miller

      Vomiting is produced primarily by changes in intrathoracic and intraabdominal pressures that are generated by the coordinated action of the major respiratory muscles (25, 26). This article reviews the pattern of activation and current state of knowledge concerning the control of these muscles during the retching and expulsion phases of vomiting. The reader is referred to other recent reviews for more general considerations regarding vomiting (4, 9, 10), the gastrointestinal correlates of vomiting (21), motion and space sickness (7), pregnancy sickness (1), and vomiting associated with cancer chemotherapy and radiation (9, 10).

      Respiratory muscle control is likely to be complex...

  12. Part IX Ventilatory Control in Humans
    • 43 Ventilatory Control in Humans: An Overview
      (pp. 212-215)
      Jerome A. Dempsey, N. Omar Suwarno and Douglas R. Seals

      The study of the control of breathing in the human has an illustrious and rich history. Many of the fundamental characteristics of ventilatory control such as chemoresponsiveness, the effects of state, and the regulation of exercise hyperpnea are attributable to the pioneering efforts of Krogh, Haldane, Asmussen, and others through their study of humans. Other work utilizing carefully documented lesions of specific neural pathways in human patients provided invaluable insights into mechanisms of load perception and compensation (Campbell), voluntary control of breathing via corticospinal tracts (Plum), and lengthcompensating reflexes arising from the diaphragm (Mead). There are many excellent reasons to...

    • 44 The Effect of Increased Inspiratory Drive on the Sensory Activation of the Cerebral Cortex by Inspiratory Occlusion
      (pp. 216-221)
      Paul W. Davenport, Gregory A. Holt and Paul McN. Hill

      Respiratory sensations are common experiences that allow humans and animals to become aware of their breathing. Sensations elicited by increased inspiratory mechanical loads have been studied previously using psychophysical techniques. Yet very little is known about the sensory neural mechanisms mediating the sensation of mechanical loads. A prerequisite for understanding the mechanisms of respiratory sensations is identification of cerebral cortical activation by respiratory related stimuli. Sensory activation of the cerebral cortex in humans has been studied extensively in the auditory, visual, and somatosensory systems. Event-related potentials elicited by stimulation of afferents from these sensory modalities have been found using computer...

    • 45 Control of Respiratory Cycle Timing in Newborn Infants
      (pp. 222-225)
      Ann R. Stark

      This chapter discusses several aspects of our work on respiratory cycle timing in infants and focuses on developmental differences that occur between infants and adults. First, infants differ from adults in the control of endexpiratory lung volume (EEV) and in the response to changes in lung volume. Second, infants have potent volume-sensitive timing reflexes similar to those described in animals. Third, infants have frequent disruptions in the expected sequential activation of the upper airway and inspiratory pump muscles. Some of these observations may be of clinical significance.

      Compared to adults, infants have a mechanical disadvantage in breathing due to their...

    • 46 Modulation of Respiratory Pattern during NREM Sleep
      (pp. 226-230)
      James B. Skatrud, M. Safwan Badr and Jerome A. Dempsey

      During wakefulness, the ventilatory control system provides effective control of the overall level of alveolar ventilation and the relative stability of breathing pattern. Ventilatory compensation to mechanical loads or to low levels of chemical stimuli occurs quickly causing only transient changes in respiratory pattern. In contrast, withdrawal of wakefulness is associated with changes in mechanical and chemical influences which can result in periodic breathing, apnea, and upper airway obstruction. First, the sleeping state is directly linked to an increase in upper airway resistance. Lack of immediate compensation for this increased impedance can accentuate episodes of hypoventilation during fluctuating sleep states....

    • 47 Exercise and the Respiratory Mechanical Load
      (pp. 231-234)
      Magdy Younes

      The respiratory mechanical load can affect exercise performance in a variety of ways. Two of these will be reviewed here: the respiratory load and exercise ventilation and breathing pattern.

      Respiratory elastance and resistance determine the level of ventilation and tidal volume for a given pattern of respiratory muscle activation. Ventilation and tidal volume, in turn, determine arterial blood gas tensions and, to some extent, pH at a given level of exercise. These are clearly of some importance to the exercising muscles. It is, therefore, reasonable to ask whether the respiratory load constrains exercise ventilation, thereby possibly contributing to fatigue of...

  13. Contributing Laboratories
    (pp. 235-236)
  14. Index
    (pp. 237-238)