SLEEP-RELATED BREATHING DISORDERS EXPERIMENTAL MODELS AND THERAPEUTIC POTENTIAL Edited by David W Carley Miodrag Radulovacki University of Illinois Chicago, Illinois, U.S.A MARCEL MARCEL DEKKER, INC DEKKER NEWYORK BASEL Library of Congress Cataloging-in-Publication Data A catalog record for this book is available from the Library of Congress ISBN: 0-8247-0877-6 This book is printed on acid-free paper Headquarters Marcel Dekker, Inc 270 Madison Avenue, New York, NY 10016 tel: 212-696-9000; fax: 212-685-4540 Eastern Hemisphere Distribution Marcel Dekker AG Hutgasse 4, Postfach 812, CH-4001 Basel, Switzerland tel: 41-61-260-6300; fax: 41-61-260-6333 World Wide Web http://www.dekker.com The publisher offers discounts on this book when ordered in bulk quantities For more information, write to Special Sales/Professional Marketing at the headquarters address above Copyright # 2003 by Marcel Dekker, Inc All Rights Reserved Neither this book nor any part may be reproduced or transmitted in any form or by any means, electronic or mechanical, including photocopying, microfilming, and recording, or by any information storage and retrieval system, without permission in writing from the publisher Current printing (last digit): 10 PRINTED IN THE UNITED STATES OF AMERICA LUNG BIOLOGY IN HEALTH AND DISEASE Executive Editor Claude Lenfant Director, National Heart, Lung, and Blood Institute National Institutes of Health Bethesda, Maryland Immunologic and Infectious Reactions in the Lung, edited by C H Kirkpatrick and H Y Reynolds The Biochemical Basis of Pulmonary Function, edited by R G Crystal Bioengineering Aspects of the Lung, edited by J B West Metabolic Functions of the Lung, edited by Y S Bakhle and J R Vane Respiratory Defense Mechanisms (in two parts), edited by J D Brain, D F Proctor, and L M Reid Development of the Lung, edited by W A Hodson Lung Water and Solute Exchange, edited by N C Staub Extrapulmonary Manifestations of Respiratory Disease, edited by E D Robin Chronic Obstructive Pulmonary Disease, edited by T L Petty 10 Pathogenesis and Therapy of Lung Cancer, edited by C C Harris 11 Genetic Determinants of Pulmonary Disease, edited by S D Litwin 12 The Lung in the Transition Between Health and Disease, edited by P T Macklem and S Permutt 13 Evolution of Respiratory Processes: A Comparative Approach, edited by S C Wood and C Lenfant 14 Pulmonary Vascular Diseases, edited by K M Moser 15 Physiology and Pharmacology of the Airways, edited by J A Nadel 16 Diagnostic Techniques in Pulmonary Disease (in two parts), edited by M A Sackner 17 Regulation of Breathing (in two parts), edited by T F Hornbein 18 Occupational Lung Diseases: Research Approaches and Methods, edited by H Weill and M Turner-Warwick 19 Immunopharmacology of the Lung, edited by H H Newball 20 Sarcoidosis and Other Granulomatous Diseases of the Lung, edited by B L Fanburg 21 Sleep and Breathing, edited by N A Saunders and C E Sullivan 22 Pneumocystis carinii Pneumonia: Pathogenesis, Diagnosis, and Treatment, edited by L S Young 23 Pulmonary Nuclear Medicine: Techniques in Diagnosis of Lung Disease, edited by H L Atkins 24 Acute Respiratory Failure, edited by W M Zapol and K J Falke 25 Gas Mixing and Distribution in the Lung, edited by L A Engel and M Paiva 26 High-Frequency Ventilation in Intensive Care and During Surgery, edited by G Carlon and W S Howland 27 Pulmonary Development: Transition from Intrauterine to Extrauterine Life, edited by G H Nelson 28 Chronic Obstructive Pulmonary Disease: Second Edition, edited by T L Petty 29 The Thorax (in two parts), edited by C Roussos and P T Macklem 30 The Pleura in Health and Disease, edited by J Chrétien, J Bignon, and A Hirsch 31 Drug Therapy for Asthma: Research and Clinical Practice, edited by J W Jenne and S Murphy 32 Pulmonary Endothelium in Health and Disease, edited by U S Ryan 33 The Airways: Neural Control in Health and Disease, edited by M A Kaliner and P J Barnes 34 Pathophysiology and Treatment of Inhalation Injuries, edited by J Loke 35 Respiratory Function of the Upper Airway, edited by O P Mathew and G Sant'Ambrogio 36 Chronic Obstructive Pulmonary Disease: A Behavioral Perspective, edited by A J McSweeny and I Grant 37 Biology of Lung Cancer: Diagnosis and Treatment, edited by S T Rosen, J L Mulshine, F Cuttitta, and P G Abrams 38 Pulmonary Vascular Physiology and Pathophysiology, edited by E K Weir and J T Reeves 39 Comparative Pulmonary Physiology: Current Concepts, edited by S C Wood 40 Respiratory Physiology: An Analytical Approach, edited by H K Chang and M Paiva 41 Lung Cell Biology, edited by D Massaro 42 Heart–Lung Interactions in Health and Disease, edited by S M Scharf and S S Cassidy 43 Clinical Epidemiology of Chronic Obstructive Pulmonary Disease, edited by M J Hensley and N A Saunders 44 Surgical Pathology of Lung Neoplasms, edited by A M Marchevsky 45 The Lung in Rheumatic Diseases, edited by G W Cannon and G A Zimmerman 46 Diagnostic Imaging of the Lung, edited by C E Putman 47 Models of Lung Disease: Microscopy and Structural Methods, edited by J Gil 48 Electron Microscopy of the Lung, edited by D E Schraufnagel 49 Asthma: Its Pathology and Treatment, edited by M A Kaliner, P J Barnes, and C G A Persson 50 Acute Respiratory Failure: Second Edition, edited by W M Zapol and F Lemaire 51 Lung Disease in the Tropics, edited by O P Sharma 52 Exercise: Pulmonary Physiology and Pathophysiology, edited by B J Whipp and K Wasserman 53 Developmental Neurobiology of Breathing, edited by G G Haddad and J P Farber 54 Mediators of Pulmonary Inflammation, edited by M A Bray and W H Anderson 55 The Airway Epithelium, edited by S G Farmer and D Hay 56 Physiological Adaptations in Vertebrates: Respiration, Circulation, and Metabolism, edited by S C Wood, R E Weber, A R Hargens, and R W Millard 57 The Bronchial Circulation, edited by J Butler 58 Lung Cancer Differentiation: Implications for Diagnosis and Treatment, edited by S D Bernal and P J Hesketh 59 Pulmonary Complications of Systemic Disease, edited by J F Murray 60 Lung Vascular Injury: Molecular and Cellular Response, edited by A Johnson and T J Ferro 61 Cytokines of the Lung, edited by J Kelley 62 The Mast Cell in Health and Disease, edited by M A Kaliner and D D Metcalfe 63 Pulmonary Disease in the Elderly Patient, edited by D A Mahler 64 Cystic Fibrosis, edited by P B Davis 65 Signal Transduction in Lung Cells, edited by J S Brody, D M Center, and V A Tkachuk 66 Tuberculosis: A Comprehensive International Approach, edited by L B Reichman and E S Hershfield 67 Pharmacology of the Respiratory Tract: Experimental and Clinical Research, edited by K F Chung and P J Barnes 68 Prevention of Respiratory Diseases, edited by A Hirsch, M Goldberg, J.-P Martin, and R Masse 69 Pneumocystis carinii Pneumonia: Second Edition, edited by P D Walzer 70 Fluid and Solute Transport in the Airspaces of the Lungs, edited by R M Effros and H K Chang 71 Sleep and Breathing: Second Edition, edited by N A Saunders and C E Sullivan 72 Airway Secretion: Physiological Bases for the Control of Mucous Hypersecretion, edited by T Takishima and S Shimura 73 Sarcoidosis and Other Granulomatous Disorders, edited by D G James 74 Epidemiology of Lung Cancer, edited by J M Samet 75 Pulmonary Embolism, edited by M Morpurgo 76 Sports and Exercise Medicine, edited by S C Wood and R C Roach 77 Endotoxin and the Lungs, edited by K L Brigham 78 The Mesothelial Cell and Mesothelioma, edited by M.-C Jaurand and J Bignon 79 Regulation of Breathing: Second Edition, edited by J A Dempsey and A I Pack 80 Pulmonary Fibrosis, edited by S Hin Phan and R S Thrall 81 Long-Term Oxygen Therapy: Scientific Basis and Clinical Application, edited by W J O'Donohue, Jr 82 Ventral Brainstem Mechanisms and Control of Respiration and Blood Pressure, edited by C O Trouth, R M Millis, H F Kiwull-Schöne, and M E Schläfke 83 A History of Breathing Physiology, edited by D F Proctor 84 Surfactant Therapy for Lung Disease, edited by B Robertson and H W Taeusch 85 The Thorax: Second Edition, Revised and Expanded (in three parts), edited by C Roussos 86 Severe Asthma: Pathogenesis and Clinical Management, edited by S J Szefler and D Y M Leung 87 Mycobacterium avium–Complex Infection: Progress in Research and Treatment, edited by J A Korvick and C A Benson 88 Alpha 1–Antitrypsin Deficiency: Biology · Pathogenesis · Clinical Manifestations · Therapy, edited by R G Crystal 89 Adhesion Molecules and the Lung, edited by P A Ward and J C Fantone 90 Respiratory Sensation, edited by L Adams and A Guz 91 Pulmonary Rehabilitation, edited by A P Fishman 92 Acute Respiratory Failure in Chronic Obstructive Pulmonary Disease, edited by J.-P Derenne, W A Whitelaw, and T Similowski 93 Environmental Impact on the Airways: From Injury to Repair, edited by J Chrétien and D Dusser 94 Inhalation Aerosols: Physical and Biological Basis for Therapy, edited by A J Hickey 95 Tissue Oxygen Deprivation: From Molecular to Integrated Function, edited by G G Haddad and G Lister 96 The Genetics of Asthma, edited by S B Liggett and D A Meyers 97 Inhaled Glucocorticoids in Asthma: Mechanisms and Clinical Actions, edited by R P Schleimer, W W Busse, and P M O’Byrne 98 Nitric Oxide and the Lung, edited by W M Zapol and K D Bloch 99 Primary Pulmonary Hypertension, edited by L J Rubin and S Rich 100 Lung Growth and Development, edited by J A McDonald 101 Parasitic Lung Diseases, edited by A A F Mahmoud 102 Lung Macrophages and Dendritic Cells in Health and Disease, edited by M F Lipscomb and S W Russell 103 Pulmonary and Cardiac Imaging, edited by C Chiles and C E Putman 104 Gene Therapy for Diseases of the Lung, edited by K L Brigham 105 Oxygen, Gene Expression, and Cellular Function, edited by L Biadasz Clerch and D J Massaro 106 Beta2-Agonists in Asthma Treatment, edited by R Pauwels and P M O’Byrne 107 Inhalation Delivery of Therapeutic Peptides and Proteins, edited by A L Adjei and P K Gupta 108 Asthma in the Elderly, edited by R A Barbee and J W Bloom 109 Treatment of the Hospitalized Cystic Fibrosis Patient, edited by D M Orenstein and R C Stern 110 Asthma and Immunological Diseases in Pregnancy and Early Infancy, edited by M Schatz, R S Zeiger, and H N Claman 111 Dyspnea, edited by D A Mahler 112 Proinflammatory and Antiinflammatory Peptides, edited by S I Said 113 Self-Management of Asthma, edited by H Kotses and A Harver 114 Eicosanoids, Aspirin, and Asthma, edited by A Szczeklik, R J Gryglewski, and J R Vane 115 Fatal Asthma, edited by A L Sheffer 116 Pulmonary Edema, edited by M A Matthay and D H Ingbar 117 Inflammatory Mechanisms in Asthma, edited by S T Holgate and W W Busse 118 Physiological Basis of Ventilatory Support, edited by J J Marini and A S Slutsky 119 Human Immunodeficiency Virus and the Lung, edited by M J Rosen and J M Beck 120 Five-Lipoxygenase Products in Asthma, edited by J M Drazen, S.-E Dahlén, and T H Lee 121 Complexity in Structure and Function of the Lung, edited by M P Hlastala and H T Robertson 122 Biology of Lung Cancer, edited by M A Kane and P A Bunn, Jr 123 Rhinitis: Mechanisms and Management, edited by R M Naclerio, S R Durham, and N Mygind 124 Lung Tumors: Fundamental Biology and Clinical Management, edited by C Brambilla and E Brambilla 125 Interleukin-5: From Molecule to Drug Target for Asthma, edited by C J Sanderson 126 Pediatric Asthma, edited by S Murphy and H W Kelly 127 Viral Infections of the Respiratory Tract, edited by R Dolin and P F Wright 128 Air Pollutants and the Respiratory Tract, edited by D L Swift and W M Foster 129 Gastroesophageal Reflux Disease and Airway Disease, edited by M R Stein 130 Exercise-Induced Asthma, edited by E R McFadden, Jr 131 LAM and Other Diseases Characterized by Smooth Muscle Proliferation, edited by J Moss 132 The Lung at Depth, edited by C E G Lundgren and J N Miller 133 Regulation of Sleep and Circadian Rhythms, edited by F W Turek and P C Zee 134 Anticholinergic Agents in the Upper and Lower Airways, edited by S L Spector 135 Control of Breathing in Health and Disease, edited by M D Altose and Y Kawakami 136 Immunotherapy in Asthma, edited by J Bousquet and H Yssel 137 Chronic Lung Disease in Early Infancy, edited by R D Bland and J J Coalson 138 Asthma's Impact on Society: The Social and Economic Burden, edited by K B Weiss, A S Buist, and S D Sullivan 139 New and Exploratory Therapeutic Agents for Asthma, edited by M Yeadon and Z Diamant 140 Multimodality Treatment of Lung Cancer, edited by A T Skarin 141 Cytokines in Pulmonary Disease: Infection and Inflammation, edited by S Nelson and T R Martin 142 Diagnostic Pulmonary Pathology, edited by P T Cagle 143 Particle–Lung Interactions, edited by P Gehr and J Heyder 144 Tuberculosis: A Comprehensive International Approach, Second Edition, Revised and Expanded, edited by L B Reichman and E S Hershfield 145 Combination Therapy for Asthma and Chronic Obstructive Pulmonary Disease, edited by R J Martin and M Kraft 146 Sleep Apnea: Implications in Cardiovascular and Cerebrovascular Disease, edited by T D Bradley and J S Floras 147 Sleep and Breathing in Children: A Developmental Approach, edited by G M Loughlin, J L Carroll, and C L Marcus 148 Pulmonary and Peripheral Gas Exchange in Health and Disease, edited by J Roca, R Rodriguez-Roisen, and P D Wagner 149 Lung Surfactants: Basic Science and Clinical Applications, R H Notter 150 Nosocomial Pneumonia, edited by W R Jarvis 151 Fetal Origins of Cardiovascular and Lung Disease, edited by David J P Barker 152 Long-Term Mechanical Ventilation, edited by N S Hill 153 Environmental Asthma, edited by R K Bush 154 Asthma and Respiratory Infections, edited by D P Skoner 155 Airway Remodeling, edited by P H Howarth, J W Wilson, J Bousquet, S Rak, and R A Pauwels 156 Genetic Models in Cardiorespiratory Biology, edited by G G Haddad and T Xu 157 Respiratory-Circulatory Interactions in Health and Disease, edited by S M Scharf, M R Pinsky, and S Magder 158 Ventilator Management Strategies for Critical Care, edited by N S Hill and M M Levy 159 Severe Asthma: Pathogenesis and Clinical Management, Second Edition, Revised and Expanded, edited by S J Szefler and D Y M Leung 160 Gravity and the Lung: Lessons from Microgravity, edited by G K Prisk, M Paiva, and J B West 161 High Altitude: An Exploration of Human Adaptation, edited by T F Hornbein and R B Schoene 162 Drug Delivery to the Lung, edited by H Bisgaard, C O’Callaghan, and G C Smaldone 163 Inhaled Steroids in Asthma: Optimizing Effects in the Airways, edited by R P Schleimer, P M O’Byrne, S J Szefler, and R Brattsand 164 IgE and Anti-IgE Therapy in Asthma and Allergic Disease, edited by R B Fick, Jr., and P M Jardieu 165 Clinical Management of Chronic Obstructive Pulmonary Disease, edited by T Similowski, W A Whitelaw, and J.-P Derenne 166 Sleep Apnea: Pathogenesis, Diagnosis, and Treatment, edited by A I Pack 167 Biotherapeutic Approaches to Asthma, edited by J Agosti and A L Sheffer 168 Proteoglycans in Lung Disease, edited by H G Garg, P J Roughley, and C A Hales 169 Gene Therapy in Lung Disease, edited by S M Albelda 170 Disease Markers in Exhaled Breath, edited by N Marczin, S A Kharitonov, M H Yacoub, and P J Barnes 171 Sleep-Related Breathing Disorders: Experimental Models and Therapeutic Potential, edited by D W Carley and M Radulovacki 172 Chemokines in the Lung, edited by R M Strieter, S L Kunkel, and T J Standiford 173 Respiratory Control and Disorders in the Newborn, edited by O P Mathew 174 The Immunological Basis of Asthma, edited by B N Lambrecht, H C Hoogsteden, and Z Diamant 175 Oxygen Sensing: Responses and Adaptation to Hypoxia, edited by S Lahiri, G L Semenza, and N R Prabhakar 176 Non-Neoplastic Advanced Lung Disease, edited by J Maurer ADDITIONAL VOLUMES IN PREPARATION Therapeutic Targets in Airway Inflammation, edited by N T Eissa and D Huston Respiratory Infections in Asthma and Allergy, edited by S Johnston and N Papadopoulos Acute Respiratory Distress Syndrome, edited by M A Matthay Upper and Lower Respiratory Disease, edited by J Corren, A Togias, and J Bousquet Venous Thromboembolism, edited by J E Dalen Acute Exacerbations of Chronic Obstructive Pulmonary Disease, edited by N Siafakas, N Anthonisen, and D Georgopolous Lung Volume Reduction Surgery for Emphysema, edited by H E Fessler, J J Reilly, Jr., and D J Sugarbaker The opinions expressed in these volumes not necessarily represent the views of the National Institutes of Health SUBJECT INDEX A Acetylcholine (ACh) dose-response curve, 194 transporter, 76 protein, 72 Acetylcholinesterase (AChE) inhibitor, 59 Acoustic-induced sleep fragmentation, 204–205 Acquired abnormalities, craniofacial structure, 10 Actinomycin D, 150 Active glottal closure, spontaneous apnea, preterm lamb, 230 Active REM/paradoxical sleep, cholinergic modulation, Koch’s postulates, 60–62 Active sleep neural system behavior, 246–247 [Active sleep] perinatal period, 241–243 suppression, 250–251 Acute blood pressure elevation episodic eucapnic hypoxia versus episodic hypocapnic hypoxia, 187–188 Adenosine agonists, apnea, 274–276 Adenovirus EIA-associated 300 kDa protein, 137–138 Adrenal medulla cells, 129 Adult behavior, neonatal modulation, 243–246 Adult ventilatory consequences, neonatal interventions, 252–254 Adult ventilatory phenotypes neonatal experience, 254–257 neonatal perturbations, 247–248 371 372 Age-related changes, English bulldog model, SDB, 307–309 Age-related influences, 7–9 developmental aspects, 7–8 Airway obstruction, tongue, 68–72 Airway occlusion arousal responses, 209 obstructive sleep apnea chronic canine model, 212 Airway occlusion system tracing, 202 Amazonian dolphins (Inia geoffrensis), EEG symmetry patterns, 329 Amazonian manatee (Trichechus inunguis), 331 Aminergic receptor mRNA, upper airway motoneurons, 123–128 Aminobenzovesamicol, 75 Anatomical defects, Apnea adenosine agonists, 274–276 benzodiazepines, 286–288 blood pressure, 189 brainstem phasic events, 283–285 cranial nerves, 268–282 diazepam, 287–288 larynx during preterm lamb, 228–229 pattern marine animals, 321–322 reflex serotonin, 268 REM sleep, 282–283 sleep deprivation, 286 triazolam, 287 vagus nerve, 268–272 Apnea of prematurity, defined, 223 Apneic lung volume, maintenance, 233 Apparent sleep, defined, 318 AP1 transcription factors, 135–136 Aquatic mammals (see Marine mammals) Arctocephalus pusillus, EEG symmetry patterns, 331 Subject Index Arousal responses airway occlusion, 209 respiratory stimuli, 208–210 Arterial blood oxygen partial pressure, diving, 320 Arterial blood pressure elevated, 109 episodic hypoxia, 185–186, 191 losartan, 191–192 high-salt diet–episodic hypoxia exposed rats, 193 telemetry, 31 Arterial hypertension, obstructive sleep apnea, 109–110 Asymmetric EEG patterns, sleep, marine animals, 328–332 Atropine, 187–188 hypoxia-associated bradycardia, 188 Autonomic behavior, learning, 244 B Barbiturates, 249 Barometric plethysmography, 36 Baroreceptor obstructive sleep apnea chronic canine model, 212–213 stimulation sleep apnea, 281–282 Basic helix-loop-helix (bHLH), 135– 136 BDNF, 118 Behavioral changes, hypoxia, 143–144 Behavioral risk factors, Benzodiazepines, apnea, 286–288 bHLH, 135–136 Biometric risk factors, 9–10 Blood pressure apnea, 189 elevation, 187–188 episodic hypoxia, 187–188 rats, 30–31 yohimbine, 188 Body fat, distribution and metabolism, 112 Subject Index 373 Bottlenose dolphins (Tursiops truncatus) (see also Dolphins) EEG symmetry patterns, 329–331 Bradycardia diving seals, 326–327 hypoxia-associated atropine, 188 Brain-derived neurotrophic factor (BDNF), 118 Brain hypoxia, protein expression, 149–155 Brainstem phasic events, apnea, 283–285 Brain structure and function, maternal care, 244 Breathing cholinergic modulation, 57–79 experimental models mechanistic studies, 58–59 patterns preterm lamb, 227–232 rodents chronic studies, 19–48 C Canine model, obstructive sleep apnea, 199–217 Cape fur seals (Arctocephalus pusillus) EEG symmetry patterns, 331 Captopril, 279 Carbachol, 71, 76 Carbachol model, REM sleep, 309–310 Carboxyethylphenethylamino-50 -Nethylcarboxamido-adenosine hydrochloride (CGS 21680), 274–276 Cardiomyopathy, English bulldog, OSDB, 301–302 Cardiorespiratory response, 112 Cardiovascular effects, intermittent hypoxia, rat, 183–195 Carotid body, hypoxia, 131 Caspian seals (Phoca caspica) sleep state, 323 Cat, sleep cycle, 58–59 Catecholaminergic cells, hypoxia, 129– 131 Catecholamines, biosynthetic pathway, 130 CBP (CREB-binding protein), 137–138 Central apneas children, 7–8 infants, 7–8 Central cholinergic synapse, 72 Central nervous system (CNS) gene expression assessment, 113–116 medications, 242 sleep apnea, 282–288 Cetaceans, 319 EEG symmetry patterns, 329–331 C-fos gene, 116, 117 galanin-containing neurons, 119 REM sleep, 119 C-fos proteins environmental hypoxia, 135 CGS 21680, 274–276 ChAT, 70 Children central apneas, 7–8 obstructive SRBD, 7–8 Choline acetyltransferase (ChAT), 70 Cholinergic model, REM sleep generation, 59 Cholinergic modulation active REM/paradoxical sleep Koch’s postulates, 60–62 hypoglossal nucleus, 68–72 sleep and breathing, 57–79 Cholinergic pontine mechanisms sleep-dependent declines upper airway muscle activity, 62– 65 sleep-dependent decrements respiratory neuron excitability, 66–68 374 Cholinergic synapse, 74 Chronic blood pressure, episodic hypoxia, 187–188 Chronic canine model, obstructive sleep apnea, 199–217 Chronic EEG and EMG recordings, rats, 24 Chronic episodic hypoxia, 184–186 renin angiotensin systems, 190–193 sympathetic nervous system, 187–190 vascular tone, 193–194 Chronic hypercapnia, gene expression, 112 Chronic hypertension, sleep apnea, 279–280 Chronic hypoxia, gene expression, 112 Chronic-sustained hypoxia, cognitive function, 143–144 CID, 153 c-Jun kinase (JNK), 135 Clonidine, 241, 252 Closed-system plethysmography, 47 CNS (see Central nervous system) Cognition, hypoxia, 141–148 Cognitive impairments, 112 Collision-induced decay (CID), 153 Congenital abnormalities, craniofacial structure, 10 Congestive heart failure, 11 Continuous oxyhemoglobin saturation, 186 Continuous positive airway pressure (CPAP), 110 Continuous pulse, 188 CPAP, 110 Cranial nerves, apnea, 268–282 Craniofacial anatomy, 112 Craniofacial structure abnormalities, 10 CREB, 118 CREB-binding protein, 137–138 Cyclic AMP-responsive elementbinding-protein (CREB), 118 Subject Index Cyclicons, 121 Cycloheximide, 150 Cystophora cristata, apnea, 321 D Delivery, preterm lamb, 225–227 Dementia, 4–5 Desynchronized respiratory drive, Diazepam, apnea, 287–288 Differential pressure signal, calibration, 44 Diving physiology, 320 sleep apnea marine animals, 325–327 Diving seals, bradycardia, 326–327 DNAse, 121 Dolphins (Tursiops truncatus), 318–319 EEG patterns asymmetric, 328 symmetry, 329–332 Inia geoffrensis EEG symmetry patterns, 329 Lagenorhynchus obliquidens diurnal behavior, 330 sleep periods, 319 Dopamine, 187–188 Dorsolateral pons, parabrachial region, 66 Dorsolateral rostral pons, 95 Dugongs, 318–319 E EEG electrode implantation mice, 33–34 rats, 21–22 EEG patterns sleep marine animals, 328–332 symmetry sea lions, 331 seals, 331 sirenians, 331 Subject Index EEG recordings mice, 34–35 rats, 24–25 computer analysis, 25–27 visual analysis, 24–25 Elderly sleep apnea, 8–9 SRBD, 8–9 Electrospray ionization (ESI), 153 Electrospray ionization-mass spectrometry (ESI-MS), 153 EMG electrode implantation mice, 33–34 rats, 21–22 EMG recordings mice, 34–35 rats, 24–25 computer analysis, 25–27 visual analysis, 24–25 English bulldog model OSDB pathogenesis, 304–306 SDB, 297–312 cardiovascular consequences, 301–302 characterization, 298–302 vs humans, 300–301 Environmental hypoxia c-fos proteins, 135 Jun B proteins, 135 Epinephrine, 184 Episodic eucapnic hypoxia, vs episodic hypocapnic hypoxia, acute blood pressure elevation, 187–188 Episodic hypocapnic hypoxia vs episodic eucapnic hypoxia, acute blood pressure elevation, 187–188 Episodic hypoxia, 184–186 arterial blood pressure, 185–186, 191 losartan, 191–192 chronic blood pressure, 187–188 rats 375 [Episodic hypoxia] peripheral sympathetic nervous system, 187–188 renin angiotensin systems, 190–193 sympathetic nervous system, 187–190 vascular tone, 193–194 Eschrichtius robustus, 330 Eserine, 59 ESI, 153 ESI-MS, 153 EST, databases, 153 Eucapnic hypoxia, systolic blood pressure, 187–188 Euphoria, 143–144 Excessive daytime sleepiness, 4–5, 141–142 Expiration, temperature and water vapor pressure, 44 Expressed sequence tag (EST), databases, 153 F 5-HT (see Serotonin) Fluoxetine, 70 Fur seals, 319 G GABA, 79, 119 trigeminal motoneurons, 310 Galanin-containing neurons, c-fos gene, 119 Gamma-aminobutyric acid (GABA), 79, 119 trigeminal motoneurons, 310 Gene expression CNS assessment, 113–116 hypoxic regulation, 129 neuroanatomical approach, 119 sleep-wake cycle, 117–119 Genetic factors, 10–11 Genetic studies, OSA, 112–116 376 Subject Index Genioglossus muscle, motoneurons, 123 ventral surface, 30 Gestation, preterm lamb, 225–227 Globicephala scammoni asymmetric EEG patterns, 328 Glottal closure, spontaneous apnea, preterm lamb, 230 Glucose transporter (Glut-1), 140 Glutamate, brainstem motoneurons, 310 Glycine, trigeminal motoneurons, 310 G proteins, 76 additive activation, 78 Gray seals (Halichoerus grypus) apnea, 321 sleep state, 323 Gray whales (Eschrichtius robustus), 330 Guanine nucleotide binding proteins (G proteins), 76 additive activation, 78 H Halichoerus grypus apnea, 321 sleep state, 323 Harbor porpoise (Phocoena phocoena) EEG symmetry patterns, 329 Harbor seals (Phoca vitellina) apnea, 321 Harp seals, 324 HERE, 132 Hereditary factors, 113 Hering-Breuer reflex, 94, 273 HIF, 135–137 High-performance liquid chromatography (HPLC), 250 HIPBS, 140 Hippocampal formation learning, 144 memory, 144 Hooded seals (Cystophora cristata) apnea, 321 Hostility, 143–144 HPLC, 250 5-HT (see Serotonin) Humpback whales, motion and sleep, 330 Hydralazine, hypotension, 277–278 5-Hydroxytryptamine (5-HT) (see Serotonin) Hydrurga leptonyx, apnea, 321 Hypercapnia daytime neurocognitive functioning, 142 gene expression, 112 ventilatory response OSA, 207 Hypertension, 30 English bulldog OSDB, 302 episodic eucapnic hypoxia vs episodic hypocapnic hypoxia, 187–188 obstructive sleep apnea chronic canine model, 210–212 sleep apnea, 279–280 sleep apnea syndrome, 183 Hypocapnic hypoxia, systolic blood pressure, 187–188 Hypoglossal motoneurons, cholinergic modulation, 73 Hypoglossal nucleus, cholinergic modulation, 68–72 Hypotension, hydralazine, 277–278 Hypoxemia daytime neurocognitive functioning, 142 nocturnal, 142 Hypoxia cardiovascular effects rat, 183–195 carotid body, 131 catecholaminergic cells, 129–131 cognition, 141–148, 147–148 cognitive function, 143–144 differential regional susceptibility, 144–147 Subject Index 377 [Hypoxia] environmental, 135 episodic, 184–186 eucapnic systolic blood pressure, 187–188 gene expression, 112 hypoxia-inducible genes, 140–144 molecular regulatory mechanisms in vitro model systems, 128–141 natural sleep, 29 proteomic approaches, 154–155 respiratory control, 141–148 TH gene, 129 PC12 cells, 131–140 TH gene expression PC12 cells, 140–144 ventilatory response OSA, 207 Hypoxia-associated bradycardia, atropine, 188 Hypoxia-inducible genes, hypoxia, 140–144 Hypoxia-inducible protein binding sequence (HIPBS), 140 Hypoxia inducible transcription factor (HIF), 135–137 Hypoxia-responsive element (HERE), 132 I IEF, 151–152 IEGs, 116, 117 Immediate-early genes (IEGs), 116 transcriptional activity, 117 Infants, central apneas, 7–8 Inia geoffrensis, EEG symmetry patterns, 329 In situ hybridization techniques, 115– 116 interpretation, 116 Inspiration, temperature and water vapor pressure, 44 Intermittent hypoxia cardiovascular effects [Intermittent hypoxia] rat, 183–195 cognition, 147–148 proteomic approaches, 154–155 Interneurons, 129 Intrathoracic pressure deflection, total upper airway occlusion, 45 Irritability, 143–144 Isoelectric focusing (IEF), 151–152 J JNK, 135 Jun B gene, 116, 117 Jun B proteins, environmental hypoxia, 135 K Koch, Robert, 60 Koch’s postulates, cholinergic modulation, active REM/ paradoxical sleep, 6062 Kolliker-Fuse subnuclei, 95 ă L Lagenorhynchus obliquidens diurnal behavior, 330 Lamb, preterm (see Preterm lamb) Laryngeal dynamics, preterm lamb, 227–232 Larynx during apneas and periodic breathing preterm lamb, 228–229 preterm lamb, 228 Learning disruption, 142 hippocampal formation, 144 Left ventricular function, obstructive sleep apnea, chronic canine model, 214–216 Leopard seals (Hydrurga leptonyx) apnea, 321 378 Subject Index Leptin, 79 Leptonychotes weddellii diving, 320, 325 LightCycler, 122 Losartan, arterial blood pressure, episodic hypoxia, 191–192 L-PIA, 274–276 L-tryptophan, 311–312 Lung ventilation measurement, 37–42 potential error sources, 43–44 M MALDI-TOF, 152 Male gender, 10 Mammals, rapid neural development, 242 Manatees, 318–319 Marine animals apnea pattern, 321–322 human medicine relationships, 327 sleep asymmetric EEG patterns, 328–332 hemispheres, 331–332 sleep apnea diving, 325–327 EEG, 323–324 manipulation, 324–325 sleep-associated apnea, 320–327 diving physiology, 320 sleep observation history, 320– 321 sleep state, 323 Marine mammals, 318–319 Maternal care, brain structure and function, 244 Matrix-assisted laser desorption/ ionization/time-of-flight (MALDI-TOF), 152 Memory hippocampal formation, 144 [Memory] impairment, 143–144 Metabolic rate measurement, 40–41 potential error sources, 45–46 Mice (see also Rodents) polysomnography, 35 sleep recordings, 32–37 EEG and EMG recording analysis, 34–35 EEG and neck EMG electrode implantation, 33–34 other physiological parameters, 36 potential problems, 35–36 Micropunches, 114 Microstimulation experiments, 97–100 tract-tracing methods, 101–102 Minute ventilation, 253 Mirounga angustirostris apnea periods, 319, 322 diving, 320 sleep manipulation, 324–325 Mirounga leonina apnea, 321 Mirtazapine, 270–272 Molecular beacons, 121 Molecular regulatory mechanisms, hypoxia, in vitro model systems, 128–141 Molecular studies, OSA, 112–116 mRNA aminergic receptor upper airway motoneurons, 123–128 detection sensitivity, 113–115 neurotransmitter receptor upper airway motoneuron proteins, 120–128 PCR, 114 quantitative RT-PCR, 125–127 Subject Index 379 N Natural sleep, hypoxia, 29 Neck EMG electrode implantation, mice, 33–34 Neonatal experience, adult ventilatory phenotypes, 254–257 Neonatal interventions, adult ventilatory consequences, 252–254 Neonatal models, ventilatory behavior, 239–257 Neonatal modulation, adult behavior, 243–246 Neonatal perturbations, adult ventilatory phenotype, 247–248 Neonatal respiratory instability preterm lamb, 223–236 historical perspective, 224–225 Nerve growth factor (NGF), 79 Neural circuit, conditioning, 245 Neural system behavior, active sleep, 246–247 Neurocognitive changes, 4–5 Neurotransmitter receptor mRNA, upper airway motoneuron proteins, 120–128 Neurotrophic proteins, 79 NGF, 79 Nitro-L-arginine methyl ester, 194 Nocturnal hypoxemia, 142 Nonrapid eye movement (NREM), chronic canine model, 201 Norepinephrine, 120, 184, 250 brainstem motoneurons, 310 postsynaptic effects, 123 Normobaric chamber, 185 Northern elephant seals (Mirounga angustirostris) apnea periods, 319, 322 diving, 320 sleep manipulation, 324–325 Northern fur seals, EEG symmetry patterns, 331 NREM, chronic canine model, 201 NTS, 94 Nucleus tractus solitarii (NTS), 94 O Obesity, 10 Ob gene, 79 Obstructive sleep apnea (OSA) arterial hypertension, 109–110 chronic canine model, 199–217 acoustic-induced sleep fragmentation, 204–205 arousal responses, 208–210 cardiovascular function, 210– 216 description, 199–205 experimental protocol, 204 schematic, 201 sleep analysis algorithm, 203 sleep architecture, 205–206 ventilatory control, 206–208 genetic studies, 112–116 molecular studies, 112–116 pathophysiologic components, 111 Obstructive sleep-disordered breathing (OSDB), 297 children, 7–8 English bulldog model cardiovascular consequences, 301–302 neural mechanisms, 309–312 pathogenesis, 304–306 strengths and weaknesses, 302– 304 Ondansetron, 269–270 Optimal intermittent hypoxia profile, 148 Orexins, 119 OSA (see Obstructive sleep apnea) OSDB (see Obstructive sleepdisordered breathing) Otariidae, 319 Oxycycler model A44XO, 147 Oxygen sensitive type I cells, 129 380 Subject Index P p300, 137–138 PACAP, 77 Parabrachial complex, 95 Paradoxical sleep, cholinergic modulation, Koch’s postulates, 60–62 Patent upper airways, serotonin, English bulldog, 310 PCR, mRNA, 114 Peptide mass fingerprinting, 153 Peptide sequence tag, 153 Perinatal period, active sleep, 241–243 Periodic breathing, larynx during, preterm lamb, 228–229 Periodic breathing episodes, preterm lamb, 231 Periodic nocturnal apneic episodes, 109 Peripheral sympathetic nervous system episodic hypoxia rat, 187–188 Personality maladjustments, 142 Petrosal ganglion, sensory neurons, 129 Pharyngeal airway, collapse, Pharyngeal dilator muscles, Phasic negative intraluminal pressure, Phenylisopropyl-adenosine (L-PIA), 274–276 Phoca caspica, sleep state, 323 Phoca vitellina, apnea, 321 Phocids, 319 (see also Seals) asymmetric EEG patterns, 328 diving, 325 true seals, 319 Phocoena phocoena EEG symmetry patterns, 329 Pilot whales (Globicephala scammoni) asymmetric EEG patterns, 328 Pinnipeds, 318–319 Pituitary adenylate cyclase-activating peptide (PACAP), 77 Plasma renin activity, 192 Plethysmography closed-system, 47 pressure deflection, 45 rodents, 37–49 Pneumotachography, 39 Polymerase chain reaction (PCR), mRNA, 114 Polysomnography, mice, 35 Polyvinylidenedifluoride (PVDF) membranes, 152 Pontine ACh release, protein profiling, 72–77 Pontine apneic sites, distribution, 98 Pontine cholinergic neurotransmission pontine respiratory neurons, 67 REM sleep generation, 61 upper airway hypotonia, 65 Pontine respiratory group (PRG), 66 Pontine respiratory neurons, pontine cholinergic neurotransmission, 67 Postganglionic sympathetic neurons, 129 Postnatal care, preterm lamb, 225–227 Prazosin, 187–188 Pressure deflection, plethysmograph, 45 Presynaptic cholinergic vesicle, 74 Preterm lamb breathing pattern and laryngeal dynamics, 227–232 chronic instrumentation, 227–228 larynx and ventilation, 228 delivery, 225–227 gestation, 225–227 neonatal respiratory instability, 223– 236 postnatal care, 225–227 respiration studies, 227–234 ventilatory response respiratory stimuli, 232–234 PRG, 66 Proposed apneic pathways, 99 Protein expression Subject Index 381 [Protein] brain hypoxia, 149–155 extraction and separation, 150–151 malfunction, 72 profiling pontine ACh release, 72–77 REM sleep and breathing, 72–77 Proteomics, 150–154 analysis, 150–154 diagram, 151 approaches intermittent hypoxia, 154–155 Psychological changes, hypoxia, 143–144 Psychosocial maladjustments, 142 PVDF membranes, 152 Q Quantitative real-time-PCR (RT-PCR) advantages, 122–123 mRNA, 125–127 single-cell level, 120–123 R Rapid eye movement (REM), chronic canine model, 201 Rapid eye movement (REM) sleep, apnea, 282–283 carbachol model, 309–310 cholinergic modulation Koch’s postulates, 60–62 experimental models mechanistic studies, 58–59 generation cholinergic model, 59 pontine cholinergic neurotransmission, 61 protein profiling, 72–77 Rats (see also Rodents) cardiovascular effects intermittent hypoxia, 183–195 episodic hypoxia [Rats] peripheral sympathetic nervous system, 187–188 sleep apnea, 265–266 serotonin, 269–272 sleep recordings, 21–32 blood pressure, 30–31 chronic EEG and EMG recordings, 24 EEG and neck EMG electrode implantation, 21–22 respiratory muscle activities, 30 respiratory stimuli triggers, 27–29 telemetry, 22 wire electrode implantation, 21–22 SRBD, 265–288 cranial nerves, 268–282 glossopharynx, 272–282 polygraphic presentation, 266 Real-time-PCR (RT-PCR) advantages, 122–123 mRNA, 125–127 single-cell level, 120–123 Recurring nocturnal obstructive episodes, 112 Ref-1, 135 Reflex apnea, serotonin, 268 REM (see Rapid eye movement) Renin angiotensin systems, chronic episodic hypoxia, 190–193 Repetitive arousal, chronic effect, 189 Respiration studies, preterm lamb, 227–234 Respiratory circuitry, functional anatomical analysis, 93–102 Respiratory control, hypoxia, 141–148 Respiratory disturbances, 3–4 Respiratory exchange ratio, 40 Respiratory muscle activities, rats, 30 Respiratory neuron excitability, sleepdependent decrements, cholinergic pontine mechanisms, 66–68 Respiratory pauses, sleep modification, 249 382 Subject Index Respiratory phenotype, development, 244–245 Respiratory pressure deflection, 37 Respiratory response, topography, 96 Respiratory stimuli arousal responses, 208–210 triggers, 27–29 ventilatory response preterm lamb, 232–234 Risk factors, 9–11 Ritanserin, upper airway, 305 RNA extraction, 115 Rodents (see also Mice; Rats) plethysmography, 37–49 lung ventilation, 37–42 metabolic rate, 40–41 potential error sources, 43–46 practical implementation, 46–48 sleep and breathing chronic studies, 19–48 sleep and breathing research, 19–20 RT-PCR advantages, 122–123 mRNA, 125–127 single-cell level, 120–123 S Scopolamine, 241, 252 Scorpions, 121 SDB (see Sleep-disordered breathing) Sea lions, 318–319, 319 EEG symmetry patterns, 331 Seals, 318–319 Arctocephalus pusillus EEG symmetry patterns, 331 asymmetric EEG patterns, 328 Cystophora cristata apnea, 321 diving, 325 bradycardia, 326–327 EEG symmetry patterns, 331 [Seals] fur, 319 Halichoerus grypus apnea, 321 sleep state, 323 harp, 324 Hydrurga leptonyx apnea, 321 Leptonychotes weddellii diving, 320, 325 Mirounga angustirostris apnea periods, 319, 322 diving, 320 sleep manipulation, 324–325 Mirounga leonina apnea, 321 northern fur EEG symmetry patterns, 331 Phoca caspica sleep state, 323 Phoca vitellina apnea, 321 sleep apnea, 319 true seals, 319 Seizures, 144 Sensory neurons, petrosal ganglion, 129 Serotonin (5-HT), 120, 250, 268 brainstem motoneurons, 310 patent upper airways English bulldog, 310 postsynaptic effects, 123 reflex apnea, 268 sleep apnea rats, 269–272 SIDS, 225 Single-chamber, whole-body plethysmograph, potential error sources, 43 Sirenians, 318–319, 319 EEG symmetry patterns, 331 Sleep active neural system behavior, 246–247 Subject Index [Sleep] perinatal period, 241–243 suppression, 250–251 analysis algorithm, 203 cholinergic modulation, 57–79 marine animals asymmetric EEG patterns, 328– 332 natural hypoxia, 29 rodents chronic studies, 19–48 research, 19–20 Sleep apnea baroreceptor stimulation, 281–282 chemoreceptor stimulation, 272–274 chronic hypertension, 279–280 CNS, 282–288 elderly, 8–9 marine animals diving, 325–327 EEG, 323–324 manipulation, 324–325 rat, 265–266 serotonin rats, 269–272 syndrome systemic hypertension, 183 Sleep-associated apnea marine animals, 320–327 diving physiology, 320 sleep observation history, 320–321 Sleep cycle, cat, 58–59 Sleep-dependent declines, upper airway muscle activity, cholinergic pontine mechanisms, 62–65 Sleep-dependent decrements cholinergic pontine mechanisms, 66–68 respiratory neuron excitability, 66–68 Sleep deprivation, 142 apnea, 286 gene expression, 112 383 Sleep disordered breathing (SDB), 110, 141–143 English bulldog model, 297–312 age-related changes, 307–309 neuronal injury, 143 Sleep disruption, daytime neurocognitive functioning, 142 Sleep periods, dolphins, 319 Sleep recordings mice, 32–37 rats, 21–32 Sleep-related breathing disorders (SRBD) elderly, 8–9 morbid consequences, 4–5 pathogenic mechanisms, 5–7 pathophysiology, 3–11 prevalence, 4–5 public health significance, 4–5 rat, 265–288 polygraphic presentation, 266 Sleep state, marine animals, 323 Sleep-wake cycle, gene expression, 117–119 Sleep-wake states, 20 computerized judgment, 28 Southern elephant seals ( Mirounga leonina) apnea, 321 Sp5c, 94 Sperm whales, motion and sleep, 330 Spinal trigeminal nucleus caudalis (Sp5c), 94 Spontaneous apnea, active glottal closure, preterm lamb, 230 Spontaneously hypertensive, 266 SRDB (see Sleep-related breathing disorders) Sudden infant death syndrome (SIDS), 225 SWISS-PROT, 153 Sympathetic nervous system, chronic episodic hypoxia, 187–190 384 Subject Index Systemic arterial blood pressure, English bulldog, OSDB, 301–302 Systemic hypertension, sleep apnea syndrome, 183 Systolic blood pressure eucapnic hypoxia, 187–188 hypocapnic hypoxia, 187–188 T Tail cuff method, 30–31 Taq DNA polymerase, 121 Telemetry arterial blood pressure, 31 rats, 22 Temperature, inspiration and expiration, 44 TH (see Tyrosine hydroxylase) Tidal breathing, 36 Tidal volume, 252–253 Tongue, airway obstruction, 68–72 Tongue muscle, medullary hypoglossal nucleus innervation, 69 Total upper airway occlusion, intrathoracic pressure deflection, 45 Tract-tracing methods, microstimulation, 101–102 Transcriptional coactivators, 137–138 Transthoracic echocardiograms, English bulldog, OSDB, 301–302 Trazodone, 311–312 TrEMBL, 153 Triazolam, apnea, 287 Trichechus inunguis, 331 Trigeminal motoneurons, glycine, 310 True seals (phocids), 319 Tryptophan, 311–312 Tumor suppressor protein, VHL, 137 Tursiops truncatus, 318–319 EEG patterns asymmetric, 328 symmetry, 329–331 [Tursiops truncatus] EEG symmetry patterns, 329 sleep periods, 319 Two-dimensional polyacrylamide gel electrophoresis (2D-PAGE), 150–152 Tyrosine hydroxylase (TH), 117, 130 gene hypoxia, 129 gene expression hypoxia PC12 cells, 131–144 signaling pathways, 133 U Ubiquitination, 133–134 Unstable respiratory drive, Upper airway dilator muscle activity bulldogs versus control dogs, 306–307 hypotonia pontine cholinergic neurotransmission, 65 motoneurons aminergic receptor mRNA, 123–128 proteins neurotransmitter receptor mRNA, 120–128 muscle activity age-related changes, 307–309 cholinergic pontine mechanisms, 62–65 English bulldog model, 307–309 sleep-dependent changes, 64 sleep-dependent declines, 62–65 ritanserin, 305 V Vagus nerve, apnea, 268–272 Vascular factors, 11 Vascular tone, chronic episodic hypoxia, 193–194 Ventilation, preterm lamb, 228 Subject Index 385 Ventilatory behavior, neonatal models, 239–257 Ventilatory response OSA hypercapnia, 207 hypoxia, 207 respiratory stimuli preterm lamb, 232–234 Vesamicol, 72 receptor blocker, 75 Vesicular proton pump, 72 Video microscopy, 193–194 Vision impairment, 143–144 von Hippel-Lindau protein, 137–139 W Walrus, 318–319 Water vapor pressure, inspiration and expiration, 44 Weddell seals (Leptonychotes weddellii) diving, 320, 325 Whales, 318–319 Eschrichtius robustus, 330 Globicephala scammoni asymmetric EEG patterns, 328 motion and sleep humpback, 330 sperm, 330 White-sided dolphins (Lagenorhynchus obliquidens) diurnal behavior, 330 Whole-body plethysmography, 39, 41, 48 Wire electrode implantation, rats, 21– 22 Y Yohimbine, 187–188 blood pressure, 188 Z Zacopride, 270, 272 ... using these experimental approaches Sleep-Related Breathing Disorders: Experimental Models and Therapeutic Potential is intended to serve the needs and interests of clinician investigators and basic... Marczin, S A Kharitonov, M H Yacoub, and P J Barnes 171 Sleep-Related Breathing Disorders: Experimental Models and Therapeutic Potential, edited by D W Carley and M Radulovacki 172 Chemokines in... further our understanding of the causes of sleep-related breathing disorders Parts Three and Four also emphasize the potential opportunities for developing improved diagnostic and therapeutic strategies