Respiratory Control: Central and Peripheral Mechanisms

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 Control is destined to be widely cited because of the strength of the contributors and the dearth of similar works. The four editors are affiliated with the University of Kentucky: Dexter F. Speck is associate professor of physiology and biophysics, Michael S. Dekin is assistant professor of biological sciences, W. Robert Revelette is research scientist of physiology and biophysics, and Donald T. Frazier is professor and chairman of physiology and biophysics. Experts in the field report current research and discuss novel issues facing future investigations. —SciTech Book Newshttps://uknowledge.uky.edu/upk_biology/1002/thumbnail.jp

Coordination of airway protective behaviors and swallow: effects of afferent feedback and sex.

This dissertation represents a series of studies describing mechanisms related to breathing, upper airway behaviors and their coordination in man and animal. Chapter two transformed the cough swallow aspiration protocol from the cat (previous work) to the human introducing a new strategy, volume targeting, in swallow breathing coordination. Chapter three evaluated swallow breathing coordination at increasing altitudes. As respiratory drive altered due to hypoxia and hypocapnia, swallow breathing coordination shifted toward inspiration occurring during the transition from inspiration and expiration. The collection of the two previous studies led to development of an animal model to evaluate volume targeting and mechanisms involved in this strategy. Chapter four highlights presence of vagal spinal feedback on breathing characteristics and chapter five the same for swallow behavior and swallow breathing coordination. Chapter four and five also introduce sex differences in breathing and swallow breathing coordination when vagal and spinal balance is perturbed. In conclusion, this work has furthered the knowledge of swallow breathing coordination and suggested mechanisms responsible for these behaviors. Describing basic swallow parameters in human could lead to potential detection of pathologic changes in the upper airway as well as further the understanding of pulmonary complications such as aspiration pneumonia. The influence of the thoracic cavity spinal feedback could lead to new therapeutic techniques for breathing, swallow and their coordination in spinal cord injured patients

Pathophysiology of Respiratory Failure Following Acute Organophosphate Poisoning : A Dissertation

Organophosphate (OP) poisoning is a health issue worldwide with over 200,000 deaths per year. Although not a problem in most developed countries, in some third world countries, one third of a hospital’s population could be patients with OP exposure. Even with the most aggressive therapy, 10-40% of patients admitted to an intensive care unit will die. Research into the best practice for treating OP poisoning is lacking, due somewhat to a lack of detailed understanding of the physiology of OP poisoning. Our research uses animal models of acute OP poisoning to explore the mechanism of OP-induced respiratory failure. Our research shows that animals poisoned with dichlorvos demonstrated a uniformly fatal central apnea that, if prevented, was followed immediately by a variable pulmonary dysfunction. Potential mechanisms for dichlorvos-induced central apnea can be divided into direct effects on the central respiratory oscillator (CRO) and feedback inhibition of the CRO. Two afferent pathways that can induce apnea include vagal feedback pathways and feed-forward pathways from the cerebral hemispheres. In our studies we found that vagal feedback and feed forward inhibition from the cerebral hemispheres were not required for OP-induced central apnea. The pre-Botzinger complex in the brainstem is thought to be the kernel of the CRO, but exposure of the pre-Botzinger complex to dichlorvos was not sufficient for apnea. Although OP induced central apnea was uniformly fatal, partial recovery of the CRO occurred post apnea with mechanical ventilation. Central apnea was ubiquitous in our rat poisoning model, but pulmonary dysfunction was extremely variable, with a range of pulmonary effects from fulminate pulmonary failure with prominent pulmonary secretions to no pulmonary dysfunction at all. Vagal efferent activity is involved in neural control of pulmonary tissue but the vagus was not involved in OP-induced pulmonary dysfunction. Anti-muscarinic medications are the mainstay of clinical therapy and are commonly dosed by their effects on pulmonary secretions. Our studies found that atropine (the most common therapeutic agent for OP poisoning) resulted in a ventilation-perfusion mismatch secondary to effects on the pulmonary vasculature

Studies of lung function

This thesis outlines the candidate's contribution to the study of Respiratory Physiology in two main areas 1. The effect of lung morphometry on lung function and 2. Reflex control of pattern of breathing.The work that makes up this thesis is laid out in largely chronological order describing the evolution of the investigations.The effect of bronchial tree structure on function was investigated using a number of new techniques developed by the author. These include a method of modelling the bronchial tree to previously unobtained detail in the form of a hollow cast. This enabled gas transit times to airways of 2-3 mm diameter to be measured and the contribution made by architecture, tissue compliance and the gradient of pleural pressure to the distribution of ventilation to be apportioned. This was the first time transit times to individual airways had been measured. Using these techniques the effect of bronchial tree structure on the phenomenon of separation of gas mixtures into their components during breathing, and the effect of the beating heart on the mixing of gases during breathing was quantified. The author's contributions to the investigation of neural control of breathing follow. A fortuitous observation that SO₂ blocks pulmonary stretch receptors (PSR) in rabbits, which took place while developing an animal model of bronchitis, lead to the observation of a non PSR mechanism determining inspiratory time (ti). Investigation of the action of rapidly adapting pulmonary receptors (RAR) using SO₂ confirmed their role in provoking sighs or augmented breaths and demonstrated that they terminated expiratory duration (tn) with a constant latency. A consistent effect of RARs on inspiration proved elusive until it was discovered that after provoking an augmented breath ft is refractory to the direct effects of RAR activity for about 2 minutes. This observation lead to the development of a theoretical model of control of ft via a central linking. This explained our observation of a non-PSR effect restricting ft after SO₂ block. Further investigations confirmed a role for RAR in control of breathing in conscious dogs. The action of RAR in initiating inspiration was demonstrated using PSR block. The same technique was used to elucidate the role played by PSR in shifts in functional residual capacity during changes in posture. An interesting observation made at this time is that although cough is primarily associated with RAR activity it can not be triggered from the lungs. The results of experiments demonstrating a similar role for RAR in conscious animals are presented.The influence of high frequency ventilation, on pulmonary receptors, the reflexes they produce and on the non-Newtonian properties of bronchial mucus is described.The way in which different species control their very different frequencies of breathing is included and the way pulmonary receptor activity is changed in some models of lung disease. The effects of modern anaesthetics on receptor activity and the effect of acupuncture as a respiratory stimulant are reported. The results of some investigations of human movement and tremor are presented. The candidates contributions to books and books published are described

Swallow and breathing coordination following suprahyoid muscle injury.

Swallowing motility disorders (dysphagia) are a major complication following radiation treatment for head and neck cancer, affecting ~50% of those treated. One reason for this is that radiation causes muscle damage, provoking sensorimotor pathologies. Previous work has suggested that injury may cause discoordination between breathing and swallowing behaviors. We sought to determine if muscle injury provokes changes in this behavior. We hypothesized that acute suprahyoid muscle damage would alter cross-behavior excitability, causing destabilization of the respiratory-swallow pattern. Swallowing was evoked in anesthetized spontaneously breathing cats via injection of a 3cc bolus of water into the oropharyngeal cavity. A suprahyoid injury was induced unilaterally by applying a ~2mm cryoprobe to the belly of the mylohyoid muscle. Electromyography (EMG) activity (duration, amplitude) was measured concurrently in thyrohyoid, mylohyoid, thyropharyngeal, and diaphragm muscles. Swallow-breathing coordination (SBC) was measured by determining inspiration/expiration phase during the onset and offset of a swallowing event, based off the mylohyoid initiation and thyropharyngeal termination bursts, respectively. Results showed an injury-related effect in the mylohyoid muscle, as indicated by a significant decrease in the mean amplitude post-injury compared to pre-injury. During swallowing, the expiratory phase was found to predominate the respiratory cycle in both pre- and post-injury. No significant changes to the swallow-breathing coordination were found following injury. Results demonstrate that mylohyoid muscle injury does not appear to interfere with short-term changes in the respiratory-swallow pattern. Although deficits in muscle function were found immediately following injury, an extended time or more severe injury may be needed to adversely inhibit these behaviors. Thus, disrupting the stable coupling between respirations and swallowing, which has been found clinically, may not be apparent immediately after injury and require long-term changes in function

Aerospace medicine and biology: A continuing bibliography with indexes (supplement 403)

This bibliography lists 217 reports, articles and other documents introduced into the NASA Scientific and Technical Information System during July 1995. Subject coverage includes: aerospace medicine and physiology, life support systems and man/system technology, protective clothing, exobiology and extraterrestrial life, planetary biology, and flight crew behavior and performance

Comparative safety respiratory pharmacology : validation of a head-out plethysmograph – pneumotachometer testing device in male Sprague–Dawley rats, Beagle dogs and Cynomolgus monkeys

Le but de cette étude était d’évaluer les qualifications de performance du système FlexiWare® chez le rat male Sprague Dawley et le singe Cynomolgus éveillés, ainsi que chez le chien Beagle éveillé et anesthésié, suite à l’administration de produits ayant une activité pharmacologique connue. Les produits utilisés incluaient l’albutérol administré par inhalation, la méthacholine, et le rémifentanil administrés par voie intraveineuse. Une solution saline administré par voie intraveneuse, a été utilisée comme substance témoin. Différentes variables ont servi à évaluer la réponse des animaux (rats, chien, singe). Ces dernières comprenaient la fréquence respiratoire (RR), le volume courant (TV), la ventilation minute (MV). Des paramètres additionnels ont été évalués chez le rat, soit les temps d’inspiration (IT) et d’expiration (ET), le temps du pic de débit expiratoire, les pics de débits inspiratoire et expiratoire, le ratio inspiratoire:expiratoire (I:E), le ratio inspiratoire sur respiration totale (I:TB), et l’écoulement expiratoire moyen (EF50). Les résultats obtenus ont démontré que le système FlexiWare® était suffisamment sensible et spécifique pour dépister, chez les espèces animales utilisées, les effets bronchodilateur, bronchoconstricteur et dépresseur central des substances testées. Il pourrait faire partie des méthodes (ICH 2000) utilisées en pharmacologie de sécurité lors de l’évaluation de substances pharmacologiques sur le système respiratoire des animaux de laboratoire. Les espèces animales utilisées ont semblé s’adapter aisément aux procédures de contention. Les paramètres évalués, RR, TV et MV ont permis de caractériser la réponse des animaux suite à l’administration de produits pharmacologiques à effets connus, judicieusement complétés par les variables de débit. L’ajout de paramètres du temps n’était pas primordiale pour détecter les effets des drogues, mais offre des outils complémentaires d’interpréter les changements physiologiques. Cependant, chez le rat conscient, la période d’évaluation ne devrait pas s’étendre au-delà d’une période de deux heures post traitement. Ces études constituent une évaluation des qualifications de performance de cet appareil et ont démontré de manière originale, la validation concurrentielle, en terme de précision (sensibilité et spécificité) et fiabilité pour différentes variables et sur différentes espèces.The aim of this study was to evaluate the performance qualifications of the FlexiWare® system in conscious Sprague-Dawley rats, Cynomolgus monkeys, as well as awake and anesthetized Beagle dogs following the administration of pharmacological substances with known effects on the respiratory system. The pharmacological substances included albuterol administered by inhalation; methacholine and remifentanil, both administered intravenously. A preparation of saline solution administered intravenously was used as control. Respiratory monitoring included: respiratory rate (RR), tidal volume (TV), minute ventilation (MV), in rats, dogs and monkeys. Additional time-, flow-, and ratio-derived variables were used in the rat model. Those variables included inspiratory (IT) and expiratory (ET) times, time to peak expiratory flow, peak inspiratory and expiratory flows, mid-tidal expiratory flow (EF50), inspiratory:expiratory (I:E) and inspiratory to total breath (I:TB) ratios. The results of this study have proven that the FlexiWare® was a reliable method and should be considered in the core battery recommended in safety pharmacology studies (ICH 2000) to assess the broncho-dilative, -constrictive, and central depressant effects of drugs on the respiratory system of the common laboratory animal specie. The animals appeared to adapt well to the restraint unit. The variables evaluated, particularly RR, TV and MV, were adequate and allowed to characterize the response of the animals following the administration of the pharmacological substances. They are judiciously completed with flowderived variables. The addition of within-breath time parameters was not primordial to detect drug effects but offered complementary tools to interpret physiological changes. However the evaluation period should be limited to the first 2 hours post treatment. These studies represent a performance qualifications evaluation of the system and have originally demonstrated the precision (sensitivity and specificity) as well as repeatability for different variables and on different specie of interest