Important role of carotid chemoreceptor afferents in control of breathing of adult and neonatal mammals

This review provides a summary and prospective on the importance of carotid/peripheral chemoreceptors to the control of breathing during physiologic conditions. For several days after carotid body denervation (CBD), adult mammals hypoventilate (+10 mmHg increase in Pa(CO(2))) at rest and during exercise and CO(2) sensitivity is attenuated by about 60%. In addition, if the rostral ventrolateral medulla is cooled during NREM sleep after CBD, a sustained apnea is observed. Eventually, days or weeks after CBD, a peripheral ventilatory chemoreflex redevelops and there is a normalization of breathing (rest and exercise) and CO(2) sensitivity. The site (s) of the regained chemosensitivity has not been established. This plasticity/redundancy after CBD appears greater in neonates than in adult mammals. These data suggest the carotid and other peripheral chemoreceptors provide an important excitatory input to medullary respiratory neurons that is essential for breathing when wakeful stimuli and central chemoreceptors are absent.     

Sleep-disordered breathing in nonobese diabetic subjects with autonomic neuropathy.

To assess the occurrence and nature of sleep-disordered breathing (SDB) in 26 adult, nonobese diabetics (18 with autonomic neuropathy (DAN+) (age 45 (41-50) yrs; body mass index (BMI) 24.1 (22-26) kg x m(-2)) and eight without autonomic neuropathy (DAN-) (age 45 (35-55) yrs; BMI 24.8 (23-26) kg x m(-2))) overnight full sleep studies and measurements of central and peripheral carbon dioxide (CO2) chemosensitivity were performed. DAN+ were divided in two subgroups, according to the presence (DAN+PH+; n=10) or absence (DAN+PH-; n=8) of postural hypotension. Ten normal subjects were studied as controls (age 42 (36-48) yrs; BMI 24.4 (23-25) kg x m(-2)). In contrast to DAN- and controls, who did not show SDB, five DAN+ (four DAN+PH- and one DAN+PH+) had an apnoea/hypopnoea index > or = 10 and four DAN+ (two DAN+PH- and two DAN+PH+) had an apnoea index > or = 5. All the events were obstructive, occurring mainly during rapid eye movement (REM) sleep. Ten DAN+ exhibited a mean lowest oxygen saturation < 90% during REM sleep. No periodic breathing or central sleep apnoeas were found in DAN+PH+, although they had an enhanced central chemoresponsiveness to CO2. Both DAN+ subgroups showed a marked reduction in peripheral CO2 chemosensitivity. In conclusion, adult nonobese diabetics with autonomic neuropathy, independent of the severity of their dysautonomy, have obstructive sleep apnoea/hypopnoea with a frequency > 30%. A decrease in peripheral carbon dioxide chemosensitivity prevents adult nonobese diabetics with autonomic neuropathy and postural hypotension from experiencing posthyperventilatory central sleep apnoea, despite an increased hypercapnic central drive.     

Effect of ventilatory drive on carbon dioxide sensitivity below eupnea during sleep

We determined the effects of changing ventilatory stimuli on the hypocapnia-induced apneic and hypopneic thresholds in sleeping dogs. End-tidal carbon dioxide pressure (PET(CO2)) was gradually reduced during non-rapid eye movement sleep by increasing tidal volume with pressure support mechanical ventilation, causing a reduction in diaphragm electromyogram amplitude until apnea/periodic breathing occurred. We used the reduction in PET(CO2) below spontaneous breathing required to produce apnea (DeltaPET(CO2)) as an index of the susceptibility to apnea. DeltaPET(CO2) was -5 mm Hg in control animals and changed in proportion to background ventilatory drive, increasing with metabolic acidosis (-6.7 mm Hg) and nonhypoxic peripheral chemoreceptor stimulation (almitrine; -5.9 mm Hg) and decreasing with metabolic alkalosis (-3.7 mm Hg). Hypoxia was the exception; DeltaPET(CO2) narrowed (-4.1 mm Hg) despite the accompanying hyperventilation. Thus, hyperventilation and hypocapnia, per se, widened the DeltaPET(CO2) thereby protecting against apnea and hypopnea, whereas reduced ventilatory drive and hypoventilation narrowed the DeltaPET(CO2) and increased the susceptibility to apnea. Hypoxia sensitized the ventilatory responsiveness to CO2 below eupnea and narrowed the DeltaPET(CO2); this effect of hypoxia was not attributable to an imbalance between peripheral and central chemoreceptor stimulation, per se. We conclude that the DeltaPET(CO2) and the ventilatory sensitivity to CO2 between eupnea and the apneic threshold are changeable in the face of variations in the magnitude, direction, and/or type of ventilatory stimulus, thereby altering the susceptibility for apnea, hypopnea, and periodic breathing in sleep.     

Chemoreceptive mechanisms elucidated by studies of congenital central hypoventilation syndrome.

Humans born with the condition of central hypoventilation during non-rapid eye movement sleep, termed congenital central hypoventilation syndrome (CCHS), invariably have absent or greatly diminished central hypercapnic ventilatory chemosensitivity. Genetic and pathological studies of CCHS may enable identification of the genes or areas of the central nervous system involved in the syndrome and thus implicated in central hypercapnic ventilatory chemosensitivity. Functional studies of CCHS permit a more quantitative assessment of the importance of ventilatory chemosensitivity in the regulation of breathing during wakefulness and sleep. The experimental evidence suggests that central hypercapnic ventilatory chemosensitivity is crucial in regulating alveolar ventilation during non-rapid eye movement sleep but not during rapid eye movement sleep or during many of the behaviors occurring during wakefulness. Presumably, other neural drives to breathe supervene to enable adequate ventilation. However, although physiological studies in CCHS subjects have been greatly instructive, their accurate interpretation will have to await future determination of the potential genetic and/or neuroanatomic basis of the syndrome.     

Treatment of central sleep apnea in patients with heart failure: Now and future

Heart failure (HF) is known to be associated with sleep-disordered breathing (SDB). In addition to disturbing patients’ sleep, SDB is also associated with a deterioration in the cardiac function and an increased mortality and morbidity. Central sleep apnea (CSA), typically characterized by Cheyne-Stokes breathing (CSB), is increasingly found in patients with HF compared to the general population. An important pathogenetic factor of CSA seen in HF patients is an instability in the control of the respiratory system, characterized by both hypocapnia and increased chemosensitivity. Sympathetic overactivation, pulmonary congestion and increased chemosensitivity associated with HF stimulate the pulmonary vagal irritant receptor, resulting in chronic hyperventilation and hypocapnia. Additionally, the repetitive apnea and arousal cycles induce cyclic sympathetic activation, which may worsen the cardiac prognosis. Correcting CSB may improve both patient’s quality of life and HF syndrome itself. However, a treatment for HF in patients also experiencing CSA is yet to be found. In fact, conflicting results from numerous clinical studies investigating sleep apnea with HF guide to a troubling question, that is whether (or not) sleep apnea should be treated in patients with HF? This editorial attempts to both collect the current evidence about randomized control trials investigating CSA in patients with HF and highlight the effect of specific CSA treatments on cardiovascular endpoints.     

Dependence of high altitude sleep apnea on ventilatory sensitivity to hypoxia

Respiration in man exposed to 5400 m was studied during sleep over a period of 6-8 h at night. Subjects were adult males, and belonged to distinct groups: one was Sherpa high altitude residents of the Himalayas and the other consisted of causasian sojourners from near sea level. All the volunteers had spent at least 32 days at or above 5400 m before the study. The subjects were instrumented for the measurements of breath-by-breath ventilation, SaO2%, eye-movement and heart rate. Nasal prongs were secured for the administration of mixtures of O2, N2 or CO2. Also, ventilatory sensitivity to hypoxia was studied in the awake state by the transient N2 and O2 tests. The lowlanders who showed high respiratory sensitivity to hypoxia also manifested periodic breathing with apnea during sleep. A raised PIO2 and SaO2% decreased ventilation, raised PACO2, attenuated respiratory oscillations and eliminated apnea in the sojourners. CO2 inhalation in air also eliminated apnea but not the periodicity, indicating that respiratory alkalosis caused apnea but periodic breathing was independent of central stimulation by CO2-H+. None of the Sherpa highlanders with low ventilatory sensitivity to hypoxia showed any sustained periodic breathing with apnea. The large breathing oscillations and periodic apnea correlated well with the ventilatory sensitivity to hypoxia (r = 0.85), supporting the hypothesis that a high gain of the peripheral chemoreflex is conductive to periodic breathing. Sherpas by attenuating chemoreflexes have reduced instability as well as cost of breathing at high altitude.     

Sleep‐disordered breathing in spinal cord‐injured patients: A short‐term longitudinal study

Background and objective: Previous studies have demonstrated an increased incidence of sleep apnoea in spinal cord‐injured patients. Many of these studies were performed in long‐term, stable spinal cord injury (SCI). The aims of this study were: (i) to determine the prevalence of sleep‐disordered breathing (SDB) in acute SCI; (ii) to document the change in SDB over time during the rehabilitation period; and (iii) to correlate the degree of SDB with ventilatory parameters. Methods: Sixteen subjects with an acute SCI level T12 and above with complete motor impairment (American Spinal Injury Association impairment scale A or B) were recruited. Assessment, including polysomnography, respiratory function testing, and hypoxic and hypercapnic ventilatory responses, were performed 6–8 weeks post SCI, and repeated 6 months post SCI. Results: Eleven of 16 subjects (73%) had evidence of sleep apnoea, five of whom were moderate to severe. This high incidence persisted during the acute admission, with 9 of 12 subjects (75%) having sleep apnoea on polysomnography 20 weeks following injury. There was no correlation between the severity of SDB and other measures, such as level or completeness of injury, respiratory function tests or measures of ventilatory responses. Conclusions: We have demonstrated a high incidence of sleep apnoea in the acute phase of SCI that persisted during the acute admission. Despite the high incidence of sleep apnoea, patients were relatively asymptomatic. Screening of this population would appear worthwhile given the high prevalence, although the significance of the sleep apnoea and clinical impact is not known.     

Symptom burden of sleep-disordered breathing in mild-to-moderate congestive heart failure patients.

The symptom burden resulting from sleep-disordered breathing (SDB) in patients with mild-to-moderate congestive heart failure (CHF) is unclear. The current authors monitored 24-h activity levels and compared subjective and objective measures of daytime sleepiness in 39 CHF patients, New York Heart Association class 2-3, on optimal medication. A total of 22 patients were classified as SDB (apnoea/hypopnoea index (AHI) median (range) 22.3 (16.6-100) events.h-1), and 17 as no SDB (NoSDB; AHI 3.7 (0-12.3) events.h-1). SDB was defined as AHI>or=15 events.h-1. Patients were assessed by 24-h activity monitoring (actigraphy) for a period of up to 14 days, a single objective sleepiness test (Oxford Sleep Resistance test) and Epworth Sleepiness Scale. The duration of daytime activity was significantly shorter in the SDB group compared with the NoSDB group. The SDB group also had increased time in bed and poorer sleep quality, as shown by the fragmentation index. Objectively the SDB group when compared with the NoSDB group were significantly sleepier, subjectively the groups did not differ. The amount of napping was similar for both groups. Despite the lack of subjective symptoms of daytime sleepiness, congestive heart failure patients with sleep-disordered breathing were objectively sleepier during the day and had reduced daytime activity with longer periods in bed and poorer sleep quality when compared with those without sleep-disordered breathing.     

Long-term noninvasive ventilation in children and adolescents with neuromuscular disorders.

The aim of the current study was to investigate the long-term impact of nocturnal noninvasive (positive-pressure) ventilation (NIV) on sleep, sleep-disordered breathing (SDB) and respiratory function in children and adolescents with progressive neuromuscular disorders (NMD). Thirty patients (12.3 +/- 4.1 yrs) with various inherited NMD were treated with NIV for ventilatory insufficiency (n=14) or symptomatic SDB (n=16). Patients were prospectively followed with sleep studies, spirometry and peak inspiratory muscle pressure. Ten patients were studied before and after 3 nights withdrawal from NIV. NIV normalised nocturnal gas exchange in all patients and diurnal gas exchange in patients with ventilatory insufficiency. The effects persisted over 25.3 +/- 12.7 months. Nocturnal transcutaneous partial pressure of carbon dioxide improved from (baseline versus latest control) 7.1 +/- 1.3 to 5.5 +/- 0.6 kPa (53.7 +/- 9.9 to 41.6 +/- 4.8 mmHg), diurnal carbon dioxide arterial tension from 6.3 +/- 1.6 to 5.4 +/- 0.5 kPa (47.5 +/- 11.9 to 40.6 +/- 3.6 mmHg). NIV improved respiratory disturbance index, arousals from sleep, nocturnal heart rate and sleep architecture. Vital capacity decreased in five adolescents with Duchenne muscular dystrophy -183 +/- 111 mL x yr(-1) but remained stable in 25 children with other conditions (8 +/- 78 mL x yr(-1)). Three nights withdrawal of NIV in 10 previously stable patients resulted in prompt deterioration of SDB and gas exchange back to baseline but could be instantly normalised by resumption of NIV. Noninvasive (positive-pressure) ventilation has favourable long-term impact on nocturnal and diurnal gas exchange and sleep and in patients with non-Duchenne neuromuscular disorders on vital capacity as well. It is indicated in children and adolescents with symptomatic sleep-disordered breathing or ventilatory insufficiency due to neuromuscular disorders.     

Assessing ventilatory control in infants at high risk of sleep disordered breathing: A study of infants with cleft lip and/or palate

Neonatal exposure to intermittent hypoxia results in altered ventilatory response to subsequent hypoxia in animal models. The effect of similar exposure in human infants is unknown. Our objective was to determine the impact of sleep disordered breathing (SDB) in early infancy on ventilatory response in infants. We recruited consecutive infants with cleft lip and/or palate (CL/P) to undergo ventilatory response testing using exposure to a hypoxic (15% O₂) gas mixture during sleep. This population is at high risk of SDB because of smaller airway caliber and abnormal palatal muscle attachments predisposing them to airway obstruction of ranging severity from birth. Ventilatory responses were compared between infants with a low apnea–hypopnea index (AHI; AHI < 15 events/hr) and a high AHI (AHI ≥ 15 events/hr). Testing was successfully completed in 22 of 23 infants who underwent testing at 4.4 ± 4.8 months. Infants with high AHI had lower weight z‐scores, higher number of oxygen desaturation events during sleep, but similar oxygen saturation (S_pO₂) nadir compared to infants with low AHI. The pattern of ventilatory response to hypoxia differed between the two groups; infants with high AHI had an earlier ventilatory decline and a blunted maximal ventilatory response to hypoxia. Infants with a high AHI use a different strategy to augment ventilation in response to hypoxia; while infants with a low AHI initially increased respiratory rate, tidal volume was the first parameter to increase in infants with high AHI. These results demonstrate that SDB in infancy is associated with altered ventilatory response to hypoxia. Pediatr Pulmonol. 2013; 48:265–273. © 2012 Wiley Periodicals, Inc.     

Acute cardiopulmonary failure from sleep-disordered breathing

Sleep-disordered breathing (SDB) comprises a diverse set of disorders marked by abnormal respiration during sleep. Clinicians should realize that SDB may present as acute cardiopulmonary failure in susceptible patients. In this review, we discuss three clinical phenotypes of acute cardiopulmonary failure from SDB: acute ventilatory failure, acute congestive heart failure, and sudden death. We review the pathophysiologic mechanisms and recommend general principles for management. Timely recognition of, and therapy for, SDB in the setting of acute cardiopulmonary failure may improve short- and long-term outcomes.     

The effects of weight and chemosensitivity on respiratory sleep abnormalities: a family study

The relationship between low-awake chemosensitivity, exogenous respiratory load (obesity) and respiratory/oxygenation patterns during sleep was evaluated in a family with overall low ventilatory responses to hypoxia and hypercapnia. Six family members were of normal weight, in good health and had normal pulmonary function tests. Only one of these subjects had totally normal responses to the chemical control of breathing. A seventh family member had loaded breathing because of severe obesity. His ventilatory and mouth occlusion pressure responses to hypoxia or hypercapnia were severely blunted. After weight loss (200 percent of ideal body weight to 133 percent) the ventilatory responses were improved but still abnormally low. Significant nocturnal respiratory abnormalities and oxygen desaturation were only seen in the overweight member and improved following weight loss (load reduction).     

The influence of NMDA receptor-mediated processes on breathing pattern in ground squirrels

The effects of blockade of N-methyl-D-aspartate (NMDA) type glutamate receptors by a non-competitive antagonist (MK-801) on cortical arousal, breathing pattern and ventilatory responses to hypoxia (10% O2 in N2) and hypercapnia (5% CO2 in air) were assessed in anesthetized (urethane) and unanesthetized golden-mantled ground squirrels (Spermophilus lateralis). Intra-cerebroventricular administration of MK-801 did not alter ventilation during wakefulness, although it did alter the pattern (breathing frequency and tidal volume components) of the hypercapnic ventilatory response, and suppressed the ventilatory response to hypoxia. Animals did not sleep following treatment with MK-801, and intravenous administration of MK-801 prevented expression of the sleep-like state normally observed in anesthetized animals. In anesthetized animals MK-801 elevated breathing frequency to levels observed without anesthesia, and suppressed the hypoxic ventilatory response. These data suggest that NMDA-type glutamatergic receptor-mediated processes influence cortical arousal and facilitate depression of breathing frequency during anesthesia and the hypoxic ventilatory response. Such processes are not essential for the hypercapnic ventilatory response.     

Respiratory control and respiratory sensation in a patient with a ganglioglioma within the dorsocaudal brain stem

We encountered a young woman with severe central sleep apnea caused by a medullary glioma located slightly dorsal to and to the right of the midline, a region not generally associated with CO(2) chemosensitivity. The patient had normal spirometric readings, lung volumes, diffusing capacity, maximal inspiratory pressure, and alveolar-arterial oxygen difference. While awake, she displayed marked irregularity in her breathing pattern; her end-tidal CO(2) (FET(CO(2))) ranged from 5.3 to 10.9%. During voluntary hyperpnea, she could quickly reduce her FET(CO(2)) to 4.2%, but her PCO(2) did not change after administration of acetazolamide or progesterone. Like patients with congenital central hypoventilation syndrome (CCHS), our patient had a relatively intact ventilatory response to exercise; her PCO(2) was high at the start of exercise and increased slightly thereafter. In contrast to CCHS patients, however, our patient had an intact hypoxic ventilatory response (DeltaVE/ DeltaSa(O(2)) = -0.37 L/min/Sa(O(2))). In further contrast to CCHS patients, our patient had a very short breathholding time and described a sensation of air hunger as the factor limiting her breathholding ability. Her heart rate and blood pressure responses to the Valsalva maneuver were normal.     

Effects of environment light during sleep on autonomic functions of heart rate and breathing

Purpose

Poor sleep hygiene including sleeping in the daytime or with the lights on at night is discovered during the assessment of many sleep disorders including sleep apnea. The aim of this study was to investigate whether environmental light affected autonomic control of heart rate, sleep-disordered breathing (SDB), and/or breathing patterning.

Methods

Seventeen non-obese healthy volunteers without witnessed snoring and apneas were recruited. Studies were performed at home using a type 3 portable monitor combined with actigraphy for sleep-wake timing, using a randomly assigned, crossover between dark, or 1,000 lx of fluorescent lighting environment. The outcomes were low-frequency power divided by high-frequency power (LF/HF ratio) in the analysis of heart rate variability, the apnea-hypopnea index (AHI), and ventilatory pattern variability before and after sleep onset between environments.

Results

The LF/HF ratio and AHI were both significantly higher in light as compared to dark. Before sleep onset, the coefficient of variation (CV) for breath-to-breath tidal volume representing breathing irregularity tended to be higher in light than in dark environment. The CV values for tidal volume after sleep onset were significantly decreased compared with before sleep onset in both sleep environments. Mutual information of the ventilatory pattern was significantly lower before sleep onset than after sleep onset, only in the light environment.

Conclusions

Sleeping in the light has effects like that of a stressor as it is associated with neuroexcitation, SDB, and resting breathing irregularity in healthy volunteers. These findings may be relevant to many sleep disorders associated with poor sleep hygiene.     

Sleep-disordered breathing in patients with the Brugada syndrome

We investigated breathing patterns and the occurrence of arrhythmias and ST-segment changes during sleep in patients with Brugada syndrome. Patients with Brugada syndrome are more likely to die from ventricular arrhythmias during sleep. ST-segment changes have been correlated with risk of sudden cardiac death. Whether sleep disturbances may contribute to arrhythmogenesis is unknown. Patients with Brugada syndrome underwent overnight polysomnography with simultaneous 12-lead electrocardiographic recording. A control group matched by age, gender, and body mass index (BMI) also underwent polysomnography. Twenty patients were included (50 ± 15 years old, 75% men). Despite their normal BMI (24.7 ± 2.7 kg/m(2)), 45% had sleep-disordered breathing (SDB), with a mean apnea-hypopnea index of 17.2 ± 14 events/hour. In patients with a high risk of arrhythmias, 5 (63%) had SDB. In the control group, 27% had SDB. Atrial or ventricular arrhythmias were not observed. Spontaneous ST-segment changes occurred in 2 patients over 45 different time points. Most ST-segment changes were observed during rapid eye movement sleep (31%) or within 1 minute of arousals (44%). Regarding respiratory events, 25 (56%) of ST-segment changes were related to occurrence of apnea or hypopnea. In conclusion, patients with Brugada syndrome have a high prevalence of SDB even in the setting of normal BMI. The higher incidence of nocturnal death in patients with Brugada syndrome may be conceivably related to co-morbid SDB. Moreover, autonomic instability encountered in rapid eye movement sleep and arousals could potentiate the risk of arrhythmias.     

Androgen blockade does not affect sleep-disordered breathing or chemosensitivity in men with obstructive sleep apnea.

As sleep apnea is more prevalent in men and testosterone has known effects on sleep apnea and chemosensitivity, reduction of androgen activity may influence sleep-disordered breathing and respiratory control. We studied the effect of 1 wk of treatment with flutamide, a nonsteroidal antiandrogen, on sleep, respiration, and ventilatory control in eight men with sleep apnea. Results on flutamide were compared with two baseline studies performed before and after the drug treatment period. Although effective androgen blockade was achieved as evidenced by increased hormone levels, flutamide had no effect on sleep architecture or chemoresponsiveness to hypoxia and hypercapnia. There was a trend towards a reduction in respiratory disturbance index in both NREM and REM sleep (41 +/- 4 baseline versus 34 +/- 3 flutamide, p = 0.09 NREM; 53 +/- 4 baseline versus 48 +/- 3 flutamide, p = 0.16 REM), but this was not significant. Our results indicate that androgen blockade had no clinically significant effect on sleep, sleep-disordered breathing, or chemosensitivity in patients with moderate to severe sleep apnea. More specific blockers such as gonadotrophin-releasing hormone analogs may have more clinical effect or, alternatively, androgen blockade may be more beneficial in patients with milder sleep apnea.     

Continuous respiratory monitoring for sleep apnea screening by ambulatory hemodynamic monitor

AIM:To validate the sleep-disordered breathing components of a portable electrocardiography and hemodynamic monitor to be used for sleep apnea screening.METHODS:Sleep-disordered breathing(SDB) is associated with cardiovascular disease.Patients with existing cardiovascular disease may have unrecognized SDB or may develop SDB while under the care of a cardiologist.A screening device for SDB,easy to use and appealing to cardiologists,would assist in referral of appropriate patients for full polysomnography(PSG).A cardiac and respiratory monitor(CPAM) was attached to patients undergoing PSG and an apnea/hypopnea index(AHI) generated.The CPAM device produced respiration rate,snoring rate,individual apnea/hypopnea events and an SDB severity score(SDBSS).In addition to AHI,an expert over-reader annotated individual breaths,snores and SDB breathing events to which the automated algorithms were compared.RESULTS:The test set consisted of data from 85 patients(age:50.5 ± 12.4 years).Of these,57 had a positive PSG defined as AHI ≥ 5.0(mean:30.0 ± 29.8,negative group mean:1.5 ± 1.2).The sensitivity and specificity of the SDBSS compared to AHI was 57.9% and 89.3%,respectively.The correlation of snoring rate by CPAM compared to the expert overreader was r = 0.58(mean error:1.52 snores/min),while the automated respiration rate had a correlation of r = 0.90(mean error:0.70 breaths/min).CONCLUSION:This performance assessment shows that CPAM can be a useful portable monitor for screening and follow-up of subjects for SDB.     

Progesterone therapy for sleep apnea syndrome evaluated by occlusion pressure responses to exogenous loading

We investigated the mechanisms of the beneficial effect derived from progesterone therapy for sleep apnea syndrome (SAS). Nine patients with SAS were treated for 7 days with chlormadinone acetate (CMA), a respiratory stimulant known to increase not only CO2 and hypoxic chemosensitivity but also respiratory drive response for ventilatory loading. They were examined as to sleep events and ventilatory control during wakefulness before and during CMA treatment. Apnea-hypopnea index was significantly reduced from 51.1 +/- 5.7 to 43.6 +/- 8.1 episodes/h (p less than 0.05). The ratio of desaturation time with more than 4% SaO2 fall to total sleep time was diminished in seven of nine patients, and its mean value decreased from 44.9 +/- 8.6 to 28.7 +/- 8.1% (p less than 0.05). Both hypercapnic ventilatory response (HCVR) and load response during wakefulness were significantly increased, although isocapnic hypoxic ventilatory response (HVR) was not significantly enhanced by CMA. The degree of augmentation in awake load response as well as in HCVR was positively correlated with that of improvement in sleep-disordered breathing. Moreover, patients who did not show amelioration in oxygen desaturation were found to be incapable of increasing load response despite increased HCVR. We conclude that CMA therapy for sleep apnea syndrome is effective in the patients whose load response as well as respiratory control activity are augmented during wakefulness.     

Hypnosis effect on carbon dioxide chemosensitivity

Hypnosis is an induced state of heightened suggestibility during which certain physiologic variables can be altered. To investigate if carbon dioxide (CO2) chemosensitivity could be blunted during this suggestible state, we measured hypercapnic ventilatory response (HCVR, delta VE/delta PaCO2), oxygen consumption (VO2), breathing pattern (VT and f), inspiratory flow rate (VT/Ti), and inspiratory timing (Ti/Ttot) in 20 healthy subjects. Mouth occlusion pressures (P0.1) were measured in the last nine subjects. Resting oxygen consumption and minute ventilation were measured during awake and hypnotic control states. The HCVR was measured spontaneously and with the suggestion to maintain normal ventilation during both awake and hypnotic conditions. It was found that without a change in metabolism, ventilatory responses to CO2 could be blunted both voluntarily, and to a greater degree, with hypnotic suggestion. These findings may have important implications in clinical settings in which patients suffer from marked dyspnea secondary to increased ventilatory chemosensitivity.