Control of Breathing in Clinical Disorders

Short-term potentiation is a mechanism in the brain stem that promotes breathing stability and prevents healthy subjects from hypoventilating in the period immediately after a hypoxic challenge. Because short-term potentiation appears impaired in patients with brain damage, Mitrouska and coworkers  determined whether theophylline would improve breathing stability in these patients. Brief exposure (45 seconds) to hypocapnic hypoxia produced similar increases in ventilation in 8 stable patients with brain damage and in 10 healthy subjects. In the healthy subjects, inhalation of a hyperoxic gas at the end of the hypoxic challenge was accompanied by a decline in ventilation without a ventilatory undershoot (indicating activation of short-term potentiation); the response was equivalent for placebo and theophylline. In the patients, inhalation of a hyperoxic gas at the end of the hypoxic challenge was accompanied by a significant ventilatory undershoot when the patients received placebo. The undershoot in the patients was attenuated, but not prevented, by theophylline. The authors conclude that theophylline largely prevents the ventilatory undershoot that occurs in patients with brain damage during the recovery period after hypoxic stimulation, and the effect is probably mediated through activation of short-term potentiation.

Familial dysautonomia, Riley-Day syndrome, affects the central and peripheral autonomic nervous systems. In 22 patients with familial dysautonomia and 23 healthy subjects, Bernardi and coworkers  studied the respiratory, cardiovascular, and cerebrovascular responses to isocapnic hypoxia and hyperoxic hypercapnia. Compared with the control group, the patients had elevated end-tidal carbon dioxide tension, lower oxygen saturation, lower R-R interval, and higher blood pressure. Baseline ventilation was normal, and the respiratory and cardiovascular responses to hyperoxic hypercapnia were normal in the patients. Progressive isocapnic hypoxia resulted in blunted increases in ventilation, paradoxical decreases in R-R interval and blood pressure, and lack of increase in midcerebral artery flow velocity. Hyperventilation induced longer apneic spells (52 versus 11 seconds) with profound desaturation (76%), marked hypotension, and increase in R-R interval. The authors conclude that patients with familial dysautonomia develop central depression in response to even moderate hypoxia with lack of expected change in the cerebral circulation, leading to hypotension, bradycardia, hypoventilation, and potentially to respiratory arrest.

Severity of obstructive apneas may be related to mechanical properties of the passive upper airway and/or impairment of control mechanisms during sleep. Younes  studied the contribution of these factors in 82 patients (range of apnea–hypopnea index, 2 to 146 events per hour). During rapid dial down of CPAP to near atmospheric pressure, the lowest inspiratory flow rate was taken as an index of passive collapsibility; the minimum effective level of CPAP was taken to reflect the pressure that the upper airway dilators needed for generating stable breathing. The index of passive collapsibility was greater in men and obese patients. The minimum effective level of CPAP was higher in men, supine position, older patients, and obese patients. Mechanical load accounted for only 34% of the variability in severity of obstructive apneas. At a given mechanical load, severity was greater in the supine position and during REM, but independent of age, sex, and body mass index. Periods of stable breathing were experienced by 82% of patients. The author concludes that most patients with obstructive sleep apnea can mount effective compensation to an elevated mechanical load, at least part of the time, and that differences in mechanical load account for about a third of the variability in severity of apneas. An editorial commentary by Naughton   accompanies this article.

Cherniack  recalls early studies of periodic breathing.

To determine the characteristics of arousal from sleep in infants who eventually die from sudden infant death syndrome (SIDS), Kato and coworkers  analyzed recordings obtained in 16 infants who had been studied some days or weeks before dying from SIDS. Compared with a control group of infants, the infants who later died of SIDS had less frequent cortical arousals (complete arousals) during both REM sleep (14.3 versus 23.1 per hour of sleep) and non-REM sleep (3.1 versus 3.6 per hour of sleep). Compared with the control group, the infants who later died of SIDS had more frequent subcortical activations (body movement without EEG change) during REM sleep (4.0 versus 1.4 per hour of sleep). The duration of subcortical activations was greater in the infants who later died of SIDS than in the control group (median duration, 7 versus 5 seconds). Compared with the control group, the infants who later died of SIDS had more frequent subcortical activations in the first part of the night (from 9:00 P.M. to 12:00 A.M.) and fewer cortical arousals during the later part of the night (from 3:00 A.M. to 6:00 A.M.) The authors conclude that infants who die from SIDS exhibit incomplete arousal processes during sleep in the weeks or months before their death. An editorial commentary by Harper   accompanies this article.

To investigate differences in movement of each side of the chest wall in patients with hemiplegia, Lanini and coworkers  measured tidal volumes of each hemithorax in eight men with hemiplegia (after cerebrovascular accidents) and nine healthy men using optoelectronic plethysmography. During quiet breathing, equivalent tidal volumes were achieved by the paretic (416 ml) and healthy hemithorax (403 ml). During voluntary hyperventilation, tidal volume was lower on the paretic side than on the healthy side: 582 versus 783 ml. During hypercapnic stimulation, tidal volume was higher on the paretic side than on the healthy side: 1,114 versus 805 ml. The authors conclude that patients with hemiplegia display smaller expansion of the paretic hemithorax than of the healthy hemithorax during voluntary hyperventilation (when breathing is under cortical control) and greater expansion of the paretic hemithorax during chemical stimulation (when breathing is under brainstem control).

In a state of the art review article, Laghi and Tobin  discuss disorders of the respiratory muscles.

Citations 1-10 of 10 total displayed.

Ventilatory Responses to Inhaled Carbon Dioxide, Hypoxia, and Exercise in Idiopathic Hyperventilation

Sandy Jack, Harry B. Rossiter, Michael G. Pearson, Susan A. Ward, Christopher J. Warburton, and Brian J. Whipp
Am. J. Respir. Crit. Care Med. 170: 118 -125. First published online as doi:10.1164/rccm.200207-720OC [Abstract] [Full text]  

Impaired Arousals and Sudden Infant Death Syndrome: Preexisting Neural Injury?

Ronald M. Harper
Am. J. Respir. Crit. Care Med. 168: 1262-1263. [Full text]  

Incomplete Arousal Processes in Infants Who Were Victims of Sudden Death

Ineko Kato, Patricia Franco, Jose Groswasser, Sonia Scaillet, Igor Kelmanson, Hajime Togari, and Andre Kahn
Am. J. Respir. Crit. Care Med. 168: 1298 -1303. First published online as doi:10.1164/rccm.200301-134OC [Abstract] [Full text]  

Cycling Sleep Apnea: The Balance of Compensated and Decompensated Breathing

Matthew T. Naughton
Am. J. Respir. Crit. Care Med. 168: 624-625. [Full text]  

Contributions of Upper Airway Mechanics and Control Mechanisms to Severity of Obstructive Apnea

Magdy Younes
Am. J. Respir. Crit. Care Med. 168: 645 -658. First published online as doi:10.1164/rccm.200302-201OC [Abstract] [Full text]  

Disorders of the Respiratory Muscles

Franco Laghi and Martin J. Tobin
Am. J. Respir. Crit. Care Med. 168: 10-48. [Abstract] [Full text]  

Chest Wall Kinematics in Patients with Hemiplegia

Barbara Lanini, Roberto Bianchi, Isabella Romagnoli, Claudia Coli, Barbara Binazzi, Francesco Gigliotti, Assunta Pizzi, Antonello Grippo, and Giorgio Scano
Am. J. Respir. Crit. Care Med. 168: 109 -113. First published online as doi:10.1164/rccm.200207-745OC [Abstract] [Full text]  

Effects of Theophylline on Ventilatory Poststimulus Potentiation in Patients with Brain Damage

Ioanna Mitrouska, Eumorfia Kondili, George Prinianakis, Nickolaos Siafakas, and Dimitris Georgopoulos
Am. J. Respir. Crit. Care Med. 167: 1124 -1130. First published online as doi:10.1164/rccm.200206-552OC [Abstract] [Full text]  

Putting Numbers to Theories about Periodic Breathing: Putting Your Money Where Your Mouth Is

Neil S. Cherniack
Am. J. Respir. Crit. Care Med. 167: 112-113. [Full text]  

Respiratory and Cerebrovascular Responses to Hypoxia and Hypercapnia in Familial Dysautonomia

Luciano Bernardi, Max Hilz, Brigitte Stemper, Claudio Passino, Goetz Welsch, and Felicia B. Axelrod
Am. J. Respir. Crit. Care Med. 167: 141 -149. First published online as doi:10.1164/rccm.200207-677OC [Abstract] [Full text]