Genioglossus reflex inhibition to upper-airway negative-pressure stimuli during wakefulness and sleep in healthy males

During wakefulness, obstructive sleep apnoea patients appear to compensate for an anatomically narrow upper airway by increasing upper airway dilator muscle activity, e.g. genioglossus, at least partly via a negative-pressure reflex that may be diminished in sleep. Previous studies have assessed the negative-pressure reflex using multi-unit, rectified, moving-time-average EMG recordings during brief pulses of negative upper-airway pressure. However, moving-time averaging probably obscures the true time-related reflex morphology, potentially masking transient excitatory and inhibitory components. This study aimed to re-examine the genioglossus negative-pressure reflex in detail, without moving-time averaging. Bipolar fine-wire electrodes were inserted per orally into the genioglossus muscle in 17 healthy subjects. Two upper airway pressure catheters were inserted per nasally. Genioglossus EMG reflex responses were generated via negative-pressure stimuli (∼−10 cmH₂O at the choanae, 250 ms duration) delivered during wakefulness and sleep. Ensemble-averaged, rectified, genioglossus EMG recordings demonstrated reflex activation (onset latency 26 ± 1 ms; peak amplitude 231 ± 29% of baseline) followed by a previously unreported suppression (peak latency 71 ± 4 ms; 67 ± 8% of baseline). Single-motor-unit activity, clearly identifiable in ∼10% of trials in six subjects, showed a concomitant increase in the interspike interval from baseline (26 ± 9 ms, P = 0.01). Genioglossus negative-pressure reflex morphology and amplitude of the initial peak were maintained in non-rapid eye movement (NREM) sleep but suppression amplitude was more pronounced during NREM and declined further during REM sleep compared to wakefulness. These data indicate there are both excitatory and inhibitory components to the genioglossus negative-pressure reflex which are differentially affected by state.     

Genioglossal muscle response to CO2 stimulation during NREM sleep

STUDY OBJECTIVES: The objective was to evaluate the responsiveness of upper airway muscles to hypercapnia with and without intrapharyngeal negative pressure during non-rapid eye movement (NREM) sleep and wakefulness. DESIGN: We assessed the genioglossal muscle response to CO2 off and on continuous positive airway pressure (CPAP) (to attenuate negative pressure) during stable NREM sleep and wakefulness in the supine position. SETTING: Laboratory of the Sleep Medicine Division, Brigham and Women's Hospital. PATIENTS OR PARTICIPANTS: Eleven normal healthy subjects. INTERVENTIONS: During wakefulness and NREM sleep, we measured genioglossal electromyography (EMG) on and off CPAP at the normal eupneic level and at levels 5 and 10 mm Hg above the awake eupneic level. MEASUREMENTS AND RESULTS: We observed that CO2 could increase upper-airway muscle activity during NREM sleep and wakefulness in the supine position with and without intrapharyngeal negative pressure. The application of nasal CPAP significantly decreased genioglossal EMG at all 3 levels of PETCO2 during NREM sleep (13.0 +/- 4.9% vs. 4.6 +/- 1.6% of maximal EMG, 14.6 +/- 5.6% vs. 7.1 +/- 2.3% of maximal EMG, and 17.3 +/- 6.3% vs. 10.2 +/- 3.1% of maximal EMG, respectively). However, the absence of negative pressure in the upper airway did not significantly affect the slope of the pharyngeal airway dilator muscle response to hypercapnia during NREM sleep (0.72 +/- 0.30% vs. 0.79 +/- 0.27% of maximal EMG per mm Hg PCO2, respectively, off and on CPAP). CONCLUSIONS: We conclude that both chemoreceptive and negative pressure reflex inputs to this upper airway dilator muscle are still active during stable NREM sleep.     

Time course of continuous positive airway pressure effects on central sleep apnoea in patients with chronic heart failure

Continuous positive airway pressure (CPAP) causes a variable immediate reduction in the frequency of central apnoeas and hypopnoeas in patients with congestive heart failure (CHF) and central sleep apnoea (CSA), but has beneficial mid-term effects on factors known to destabilize the ventilatory control system. We, therefore, tested whether CPAP therapy leads, in addition to its short-term effects on CSA, to a significant further alleviation of CSA after 12 weeks of treatment on the same CPAP level in such patients. CPAP therapy was initiated in 10 CHF patients with CSA. During the first night on CPAP, the pressure was stepwise increased to a target pressure of 8–12 cmH₂O or the highest level the patients tolerated (<12 cmH₂O). Throughout the second night (baseline CPAP), the achieved CPAP of the first night was applied. After 12 weeks of CPAP treatment, we performed a follow-up polysomnography (12 weeks CPAP) on the same CPAP level (8.6 ± 1.1 cmH₂0). We found a significant reduction of the apnoea-hypopnoea index (AHI) between the diagnostic polysomnography and baseline CPAP night (41.8 ± 19.2 versus 22.2 ± 12.6 events per hour; P  = 0.005). The AHI further significantly decreased between the baseline CPAP night and the 12 weeks CPAP night on the same CPAP level (22.2 ± 12.6 versus 12.8 ± 11.0 events per hour; P  = 0.028). We conclude that, in addition to its immediate effects, CPAP therapy leads to a time-dependent alleviation of CSA in some CHF patients, indicating that in such patients neither clinical nor scientific decisions should be based on a short-term trial of CPAP.     

Catecholamine neurones in rats modulate sleep, breathing, central chemoreception and breathing variability

Brainstem catecholamine (CA) neurones have wide projections and an arousal-state-dependent activity pattern. They are thought to modulate the processing of sensory information and also participate in the control of breathing. Mice with lethal genetic defects that include CA neurones have abnormal respiratory control at birth. Also the A6 region (locus coeruleus), which contains CA neurones sensitive to CO₂ in vitro , is one of many putative central chemoreceptor sites. We studied the role of CA neurones in the control of breathing during sleep and wakefulness by specifically lesioning them with antidopamine β-hydroxylase–saporin (DBH-SAP) injected via the 4th ventricle. After 3 weeks there was a 73–84% loss of A5, A6 and A7 tyrosine hydroxylase (TH) immunoreactive (ir) neurones along with 56–60% loss of C1 and C2 phenyl ethanolamine- N -methyltransferase (PNMT)-ir neurones. Over the 3 weeks, breathing frequency decreased significantly during air and 3 or 7% CO₂ breathing in both wakefulness and non-REM (NREM) sleep. The rats spent significantly less time awake and more time in NREM sleep. REM sleep time was unaffected. The ventilatory response to 7% CO₂ was reduced significantly in wakefulness at 7, 14 and 21 days (−28%) and in NREM sleep at 14 and 21 days (−26%). Breathing variability increased in REM sleep but not in wakefulness or NREM sleep. We conclude that CA neurones (1) promote wakefulness, (2) participate in central respiratory chemoreception, (3) stimulate breathing frequency, and (4) minimize breathing variability in REM sleep.     

Postural effects on pharyngeal protective reflex mechanisms

STUDY OBJECTIVES: Pharyngeal muscle dilators are important in obstructive sleep apnea pathogenesis because the failure of protective reflexes involving these muscles yields pharyngeal collapse. Conflicting results exist in the literature regarding the responsiveness of these muscles during stable non-rapid eye movement sleep. However, variations in posture in previous studies may have influenced these findings. We hypothesized that tongue protruder muscles are maximally responsive to negative pressure pulses during supine sleep, when posterior tongue displacement yields pharyngeal occlusion. DESIGN: We studied all subjects in the supine and lateral postures during wakefulness and stable non-rapid eye movement sleep by measuring genioglossus and tensor palatini electromyograms during basal breathing and following negative pressure pulses. SETTING: Upper-airway physiology laboratory of Sleep Medicine Division, Brigham and Women's Hospital. SUBJECTS/PARTICIPANTS: 17 normal subjects. MEASUREMENTS AND RESULTS: We observed an increase in genioglossal responsiveness to negative pressure pulses in sleep as compared to wakefulness in supine subjects (3.9 percentage of maximum [%max] +/- 1.1 vs 4.4 %max +/- 1.0) but a decrease in the lateral decubitus position (4.1 %max +/- 1.0 vs 1.5 %max +/- 0.4), the interaction effect being significant. Despite this augmented reflex, collapsibility, as measured during negative pressure pulses, increased more while subjects were in the supine position as compared with the lateral decubitus position. While the interaction between wake-sleep state and position was also significant for the tensor palatini, the effect was weaker than for genioglossus, although, for tensor palatini, baseline activity was markedly reduced during non-rapid eye movement sleep as compared with wakefulness. CONCLUSION: We conclude that body posture does have an important impact on genioglossal responsiveness to negative pressure pulses during non-rapid eye movement sleep. We speculate that this mechanism works to prevent pharyngeal occlusion when the upper airway is most vulnerable to collapse eg, during supine sleep.     

Dose-dependent effects of the 5-HT1A receptor agonist 8-OH-DPAT on sleep and wakefulness in the rat

SUMMARY  Sleep and wakefulness were studied in rats following administration of a selective 5-HT_1A agonist (8-OH-DPAT), a non-selective 5-HT_1A antagonist [(-) pindolol] and a combination of 8-OH-DPAT and (—) pindolol.
8-OH-DPAT (1.0–4.0 μg) injected into the dorsal raphe nucleus increased slow-wave sleep and decreased wakefulness. Administration of the 5-HT_1A agonist by subcutaneous route induced biphasic effects such that low doses (0.010 mg kg^-1) decreased wakefulness and increased slow-wave sleep while higher doses (0.375 mg kg^-1) induced opposite effects. REM sleep was suppressed and REM latency was increased, what could be tentatively ascribed to a non-specific effect (hypothermia). (-) Pindolol (1.0–4.0 mg kg^-1) induced an initial increase of wakefulness and a decrease of NREM sleep and REM sleep. Thereafter, NREM sleep showed a marked increase while REM sleep remained depressed. Pretreat-ment with (—) pindolol reversed the effects of both small and large doses of 8-OH-DPAT on slow-wave sleep and wakefulness.
The opposite effects, observed on the waking EEG after activation of either serotonin autoreceptors or postsynaptic 5-HT_1A receptors with adequate doses of 8-OH-DPAT, tend to indicate an active role for the 5-HT_1A receptor in the control of the waking state.     

Respiration in NREM and REM sleep after upper airway surgery for obstructive sleep apnoea

SUMMARY  To verify whether upper airway surgery in obstructive sleep apnoea syndrome affects differently respiration in NREM and REM sleep, 22 patients were studied by polysomnography before and three months after surgical treatment. On the average, treatment improved respiration during both sleep states, but no significant interaction was found between sleep state and effect of surgical treatment. According to the response to treatment, three groups of patients were identified: the first group ( N = 6), with an improvement in apnoea-hypopnoea index (AHI), percentage of sleep time spent in apnoea and hypopnoea (time in AH) and mean oxyhaemoglobin saturation (SaO₂) in both NREM and REM sleep; the second group ( N = 5), with an improvement in AHI only in NREM sleep, associated with improvement in mean SaO₂ in both sleep states; the third group ( N = 11), without any improvement in AHI and time in AH, either associated ( N = 5) or not ( N = 6) with an improvement in mean SaO₂ in both sleep states. An increase in the percentage of hypopnoeas out of the total AHI after treatment could partly account for the apparent discrepancy between AHI and mean SaO₂ behaviour in the subjects of the second group, but not in the patients of the third group who improved their mean SaO₂. Mixed apnoeas occurred before surgery in six subjects; they remained numerous after surgery only in two subjects who did not show any SaO₂ improvement. In conclusion, the degree of improvement in respiration after upper airway surgery was similar in every patient in NREM and REM sleep.     

Intrathoracic pressure changes and cardiovascular effects induced by nCPAP and nBiPAP in sleep apnoea patients

SUMMARY  The effect of nasal continuous positive airway pressure (nCPAP) and nasal bi-level positive airway pressure (nBiPAP) on intrathoracic pressure and haemodynamics during wakefulness was studied in a group of nine patients with severe sleep apnoea. No patient took cardiovascular medication.
Patients were studied with a Swan Ganz catheter, an arterial line and an oesophageal balloon. nCPAP and nBiPAP were applied in the following pressure sequence: 5, 10 and 15 cm H₂O of CPAP and 10/5 and 15/10 cm H₂O of nBiPAP. Measurements were made at the end of a 5-min period at each pressure level. Intrathoracic pressure was noted to increase to a level of approximately 50% of the pressure delivered at the mask. At a CPAP of 10 cm H₂O and above, as well as at BiPAP of 10/5 or higher, there was a decrease in cardiac output (CO) and cardiac index (CI). CI fell below the normal value in two of the patients. Transmural pulmonary artery pressure (PPA_tm) decreased at a CPAP of 15 cm H₂O and at both BiPAP levels. Transmural right atrial pressure (PRA_tm) decreased at both BiPAP levels. There were no differences in CO, CI, PPA_tm and PRA_tm between nCPAP and nBiPAP at equal inspiratory pressures. SaO₂ increased during BiPAP 15/10 cm H₂O, whereas heart rate and arterial blood pressure did not change significantly. The data presented here are consistent with the literature on positive end-expiratory pressure (PEEP) applied via intratracheal tube and are likely to be due to a reduced venous return. It is concluded that nasally applied positive pressure may have acute negative effects on cardiac function in patients with sleep apnoea.     

Antagonism of orexin receptor-1 in the retrotrapezoid nucleus inhibits the ventilatory response to hypercapnia predominantly in wakefulness

Recent data from transgenic mice suggest that orexin plays an important role in the ventilatory response to CO₂ during wakefulness. We hypothesized that orexin receptor-1 (OX₁R) in the retrotrapezoid nucleus (RTN) contributes to chemoreception. In unanaesthetized rats, we measured ventilation using a whole-body plethysmograph, together with EEG and EMG. We dialysed the vehicle and then SB-334867 (OX₁R antagonist) into the RTN to focally inhibit OX₁R and studied the effects of both treatments on breathing in air and in 7% CO₂. During wakefulness, SB-334867 caused a 30% reduction of the hyperventilation induced by 7% CO₂ (mean ± S.E.M., 135 ± 10 ml (100 g)⁻¹ min⁻¹) compared with vehicle (182 ± 10 ml (100 g)⁻¹ min⁻¹) ( P < 0.01). This effect was due to both decreased tidal volume and breathing frequency. There was a much smaller, though significant, effect in sleep (9% reduction). Neither basal ventilation nor oxygen consumption was affected. The number and duration of apnoeas were similar between control and treatment periods. No effect was observed in a separate group of animals who had the microdialysis probe misplaced (peri-RTN). We conclude that projections of orexin-containing neurons to the RTN contribute, via OX₁Rs in the region, to the hypercapnic chemoreflex control during wakefulness and to a lesser extent, non-rapid eye movement sleep.     

Baroreflex-induced sympathetic activation does not alter cerebrovascular CO2 responsiveness in humans

We investigated the effect of baroreflex-induced sympathetic activation, produced by lower body negative pressure (LBNP) at −40 mmHg, on cerebrovascular responsiveness to hyper- and hypocapnia in healthy humans. Transcranial Doppler ultrasound was used to measure blood flow velocity (CFV) in the middle cerebral artery during variations in end-tidal carbon dioxide pressure ( P _ET,CO2) of +10, +5, 0, −5, and −10 mmHg relative to eupnoea. The slopes of the linear relationships between P _ET,CO2 and CFV were computed separately for hyper- and hypocapnia during the LBNP and no-LBNP conditions. LBNP decreased pulse pressure, but did not change mean arterial pressure. LBNP evoked an increase in ventilation that resulted in a 9 ± 2 mmHg decrease in P _ET,CO2, which was corrected by CO₂ supplementation of the inspired air. LBNP did not affect cerebrovascular CO₂ response slopes during steady-state hypercapnia (3.14 ± 0.24 vs. 2.96 ± 0.26 cm s⁻¹ mmHg⁻¹) or hypocapnia (1.31 ± 0.18 vs. 1.32 ± 0.19 cm s⁻¹ mmHg⁻¹), or the CFV responses to voluntary apnoea (+51 ± 19 vs. +50 ± 18 %). Thus, cerebrovascular CO₂ responsiveness was not altered by baroreflex-induced sympathetic activation. Our data challenge the concept that sympathetic activation restrains cerebrovascular responses to alterations in CO₂ pressure.     

Inspiratory muscle training attenuates the human respiratory muscle metaboreflex

We hypothesized that inspiratory muscle training (IMT) would attenuate the sympathetically mediated heart rate (HR) and mean arterial pressure (MAP) increases normally observed during fatiguing inspiratory muscle work. An experimental group (Exp, n = 8) performed IMT 6 days per week for 5 weeks at 50% of maximal inspiratory pressure (MIP), while a control group (Sham, n = 8) performed IMT at 10% MIP. Pre- and post-training, subjects underwent a eucapnic resistive breathing task (RBT) (breathing frequency = 15 breaths min⁻¹, duty cycle = 0.70) while HR and MAP were continuously monitored. Following IMT, MIP increased significantly ( P < 0.05) in the Exp group (−125 ± 10 to −146 ± 12 cmH₂O; mean ± s.e.m. ) but not in the Sham group (−141 ± 11 to −148 ± 11 cmH₂O). Prior to IMT, the RBT resulted in significant increases in HR (Sham: 59 ± 2 to 83 ± 4 beats min⁻¹; Exp: 62 ± 3 to 83 ± 4 beats min⁻¹) and MAP (Sham: 88 ± 2 to 106 ± 3 mmHg; Exp: 84 ± 1 to 99 ± 3 mmHg) in both groups relative to rest. Following IMT, the Sham group observed similar HR and MAP responses to the RBT while the Exp group failed to increase HR and MAP to the same extent as before (HR: 59 ± 3 to 74 ± 2 beats min⁻¹; MAP: 84 ± 1 to 89 ± 2 mmHg). This attenuated cardiovascular response suggests a blunted sympatho-excitation to resistive inspiratory work. We attribute our findings to a reduced activity of chemosensitive afferents within the inspiratory muscles and may provide a mechanism for some of the whole-body exercise endurance improvements associated with IMT.     

Automatic CPAP based on impedance-comparison of constant CPAP with an individual pressure range

Summary Introduction   Self-adjusting positive airways pressure treatment based on the impedance of the airways (APAP_FOT) has proven effective in obstructive sleep apnoea syndrome. To avoid patient discomfort during periods of high treatment pressure we lowered the upper pressure limit with APAP_FOT and investigated whether this provided equally as effective treatment as constant CPAP. Methods   37 patients (33 males, 57.9 ± 9.9 years, BMI 32.5 ± 3.8 kg/m²) underwent after diagnostic polysomnography and manual nCPAP titration two treatment nights in randomized order, one with constant nCPAP (mode 1), one with APAP_FOT (mode 2). Under APAP_FOT treatment pressure varied between 4 hPa (set lower limit for all patients) and 13.3 ± 1.4 hPa (individually variable upper pressure limit). Results   AHI was reduced from 32.8 ± 18.1/h to 4.6 ± 4.9/h (mode 1, p < 0.01) and to 5.0 ± 4.1/h (mode 2, p < 0.01). Rapid eye movement sleep (REM) and respiratory arousals improved significantly with both modes. With APAP_FOT, the mean pressure was 5.7 ± 1.7 hPa as compared to 8.3 ± 1.4 hPa with constant nCPAP (p < 0.01). Conclusions   APAP_FOT with a reduced upper pressure is as effective as constant nCPAP for OSAS. With APAP_FOT the mean pressure is substantially reduced.     

Evolution of upper airway resistance syndrome

The question of whether upper airway resistance syndrome (UARS) is a distinct disease or an initial feature of obstructive sleep apnoea syndrome is still a matter of debate. We evaluated a retrospective group of UARS patients to determine the evolution of UARS over time and the relationship between clinical evolution and subjects' phenotype. Investigations were performed in 30 patients, in whom UARS was diagnosed between 1995 and 2000 by the use of full polysomnography (PSG) without oesophageal pressure (Pes) measurement. The time between initial and follow-up investigations was 6.6 ± 2.6 years. All subjects had full PSG with Pes measurement and completed a sleep questionnaire, including the Epworth Sleepiness Scale. In 19 subjects, PSG results were compatible with UARS. In nine subjects, obstructive sleep apnoea–hypopnoea syndrome (OSAHS) was diagnosed. In two subjects, PSG did not demonstrate breathing abnormalities. The mean ± SD apnoea–hypopnoea index in the UARS group was 1.5 ± 1.7 h⁻¹ and 25.2 ± 19 h⁻¹ in the OSAHS group ( P  <   0.01). The increase in body mass index (BMI) between initial and follow-up investigations in the UARS group was from 29.4 ± 4 to 31 ± 5.7 kg m⁻² ( P  =   0.014) and in the OSAHS group from 30 ± 4.1 to 32.4 ± 4.7 kg m⁻²( P  =   0.004). Amplitude of Pes swings during respiratory events was significantly higher in OSAHS than that in UARS ( P  =   0.014). Our results suggest that UARS is part of a clinical continuum from habitual snoring to OSAHS. Progression from UARS to OSAHS seems to be related to an increase in the BMI.     

Cerebrovascular reactivity to hypercapnia is unimpaired in breath-hold divers

Hypercapnic cerebrovascular reactivity is decreased in obstructive sleep apnoea and congestive heart disease perhaps as a result of repeated apnoeas. To test the hypothesis that repeated apnoeas blunt cerebrovascular reactivity to hypercapnia, we studied breath hold divers and determined cerebrovascular reactivity by measuring changes in middle cerebral artery velocity (MCAV, cm s⁻¹) per mmHg change in end-tidal partial pressure of CO₂ (     ) in response to two hyperoxic hypercapnia rebreathing manoeuvres (modified Read protocol) in elite breath-hold divers (BHD, n = 7) and non-divers (ND, n = 7). In addition, ventilation and central (beat-to-beat stroke volume measurement with Modelflow technique) haemodynamics were determined. Ventilatory responses to hypercapnia were blunted in BHD versus ND largely due to lower breathing frequency. Cerebrovascular reactivity did not differ between groups (3.7 ± 1.4 versus 3.4 ± 1.3% mmHg⁻¹     in BHD and ND, respectively; P = 0.90) and the same was found for cerebral vascular resistance and MCAV recovery to baseline after termination of the CO₂ challenge. Cardiovascular parameters were not changed significantly during rebreathing in either group, except for a small increase in mean arterial pressure for both groups. Our findings indicate that the regulation of the cerebral circulation in response to hypercapnia is intact in elite breath-hold divers, potentially as a protective mechanism against the chronic intermittent cerebral hypoxia and/or hypercapnia that occurs during breath-hold diving. These data also suggest that factors other than repeated apnoeas contribute to the blunting of cerebrovascular reactivity in conditions like sleep apnoea.     

Dynamic changes in the direction of blood flow through the ductus arteriosus at birth

Major cardiovascular changes occur at birth, including increased pulmonary blood flow (PBF) and closure of the ductus arteriosus (DA), which acts as a low resistance shunt between the fetal pulmonary and systemic circulations. Although the pressure gradient between these circulations reverses after birth, little is known about DA blood flow changes and whether reverse DA flow contributes to PBF after birth. Our aim was to describe the changes in PBF and DA flow before, during and after the onset of pulmonary ventilation at birth. Flow probes were implanted on the left pulmonary artery (LPA) and DA in preterm fetal sheep ( n = 8) ∼3 days before they were delivered and ventilated. Blood flow was measured in the LPA and DA, before and after umbilical cord occlusion (UCO) and for 2 h after ventilation onset. Following UCO, DA flow decreased from 534 ± 57 ml min⁻¹ to 237 ± 29 ml min⁻¹ which reflected a similar reduction in right ventricular output. Within 5 min of ventilation onset, PBF increased from 11 ± 6 ml min⁻¹ to 230 ± 13 ml min⁻¹ whereas DA flow decreased to −172 ± 54 ml min⁻¹; negative values indicate reverse DA flow (left-to-right shunting). Reverse flow through the DA contributed up to 50% of total PBF at 30 min and a decrease in this contribution accounted for 71 ± 13% of the time-related decrease in PBF after birth. DA blood flow is very dynamic after birth and depends upon the pressure gradient between the pulmonary and systemic circulations. Following ventilation, reverse DA flow provided a significant contribution to total PBF after birth.     

Non-invasive measurement of haemodynamics during sleep apnoea

SUMMARY  Sleep apnoeas are accompanied by large variations in heart rate (HR) and blood pressure (BP). This nocturnal variability in BP may be involved in the increased cardiovascular morbidity of these patients. Due to the complex interaction between asphyxia, intrathoracic pressure, cardiac function and autonomic activation, the exact haemodynamic mechanisms are unclear.
To evaluate the components of the BP surges at resumption of breathing (RB) a non-invasive beat-to-beat measurement was taken of cardiac output (CO) by the pulse contour analysis of the Finapres signal. Six male normotensive patients, free of medication (37–60 y, BMI 26.5–43.0 kg m^-2) were studied during polysomnography (apnoea index: 22–69 h^-1). Systolic blood pressure rose from 126.5 ± 1.3 mmHg at beginning apnoea (P1) to 140.4 ±1.3 at RB ( P <0.01, ANOVA). During sleep Stages 2 and 3, stroke volume decreased during RB to 96% of P1 value (NS). Due to an opposite change in HR, CO tended to rise at RB to 106% of P1. Computed total peripheral resistance rose during RB to 105% of P1 value ( P <0.01).
Therefore, it is concluded that the surge in BP at RB after apnoea is due to concomitant increases in CO and in TPR. Both rises are presumably a consequence of sympathetic nervous activation by the arterial chemoreceptors.     

The effect of sleep on reflex genioglossus muscle activation by stimuli of negative airway pressure in humans.

The present study was designed to determine the effect of sleep on reflex pharyngeal dilator muscle activation by stimuli of negative airway pressure in human subjects. Intra-oral bipolar surface electrodes were used to record genioglossus electromyogram (EMG) responses to 500 ms duration pressure stimuli of 0 and -25 cmH2O applied, via a face-mask, in four normal subjects. Stimuli were applied during early inspiration in wakefulness and in periods of non-rapid-eye-movement (non-REM) sleep, defined by electroencephalographic (EEG) criteria. The rectified and integrated EMG responses to repeated interventions were bin averaged for the 0 and -25 cmH2O stimuli applied in wakefulness and sleep. Response latency was defined as the time when the EMG activity significantly increased above prestimulus levels. Response magnitude was quantified as the in ratio of the EMG activity for an 80 ms post-stimulus period to an 80 ms prestimulus period; data from after the subject's voluntary reaction time for tongue protrusion (range, 150-230 ms) were not analysed. Application of the -25 cmH2O stimuli caused genioglossus muscle activation in wakefulness and sleep, but in all subjects response magnitude was reduced in sleep (mean decrease, 61%; range, 52-82%; P = 0.011, Student's paired t test). In addition, response latency was increased in sleep in each subject (mean latency awake, 38 ms; range, 30-50 ms; mean latency asleep, 75 ms; range, 40-110 ms; P = 0.072, Student's paired t test). Application of the -25 cmH2O stimuli caused arousal from sleep on 90% occasions, but in all cases the reflex genioglossus muscle responses (maximum latency, 110 ms) always proceeded any sign of EEG arousal (mean time to arousal, 643 ms; range, 424-760 ms). These results show that non-REM sleep attenuates reflex genioglossus muscle activation by stimuli of negative airway pressure. Attenuation of this reflex by sleep may impair the ability of the upper airway to defend itself from suction collapse by negative pressures generated during inspiration; this may have implications for the pathogenesis of obstructive sleep apnoea.     

Motoneuronal excitability during wakefulness and non-REM sleep: H-reflex recovery function in man

Comparisons were made in 13 normal young adults of alpha motoneuronal excitability during non-rapid-eye-movement (NREM) sleep (stages 2--4) and wakefulness based on a study of the recovery cycle of the H-reflex after a conditioning stimulus. During sleep, excitability was generally decreased and a peak of secondary facilitation, which characteristically occurs 100--300 msec after the conditioning stimulus during wakefulness, was reduced or absent. A variety of mechanisms, including long-loop reflexes and afferent discharges from reflex muscle contraction and cutaneous fibers, has been proposed to account for this phase of facilitation in the waking recovery curve. However, since studies to date indicate the absence of tonic presynaptic or postsynpatic inhibitory influences acting on the monosynatpic reflex pathway during NREM sleep, but report tonic reduction in fusimotor activity at this time, it is suggested that a primary factor underlying the absence of facilitation during sleep is a reduction in central excitability deriving from depressed fusimotor activity.     

Breathing during sleep in normal middle-aged subjects

Although ventilation during sleep has been studied in normal young and elderly subjects, little data are available concerning possible quantitative changes in ventilatory parameters in normal middle-aged subjects. We studied the occurrence of respiratory events and the changes in minute ventilation, tidal volume, and respiratory rate during rapid-eye-movement (REM) and non-REM (NREM) sleep in 40 normal (20 men and 20 women) middle-aged subjects, using polysomnography with pneumotachography and oximetry. Apnea indices greater than 5, with apneas predominantly of the obstructive type, were found in 17.5% of the subjects (30% of the men and 5% of the women). These "apneic" subjects differed from the "nonapneic" subjects only in that they had a higher body mass index. Minute ventilation decreased from wakefulness to sleep by 14% to 19%, owing to a decrease in tidal volume without a significant change in respiratory rate. This decrease was not greater in slow wave (stage 3-4 NREM) or in REM sleep than in stage 2 NREM sleep, nor was it greater in men than in women. It correlated with the minute ventilation during wakefulness: the higher the minute ventilation during wakefulness, the greater the decrease during sleep. The occurrence of respiratory events was not related to the degree of the decrease in minute ventilation from wakefulness to apnea-free sleep.     

The effect of time of day on apnoea index in the sleeping rat

This study tested the hypothesis that apnoea index would be greater during daytime sleep than nighttime sleep in the rat. Electroencephalogram and electromyogram were monitored via biotelemetry implant and respiration was measured using whole body plethysmography in six male rats in two separate 34h recording sessions per animal. Apnoeas were classified as "spontaneous" or "post-sigh". Daily average spontaneous apnoea index was 35 times greater (p<0.0001) during rapid eye movement (REM) sleep than in non-REM (NREM) sleep. In contrast, daily average post-sigh apnoea index was not significantly greater in REM sleep than in non-REM (NREM) sleep (p=0.39). There was a greater post-sigh apnoea index during daytime REM than during nighttime REM (p=0.043) but REM-related spontaneous apnoea index was unaffected by time of day. There was no day to night difference in spontaneous apnoea index or post-sigh apnoea index during NREM sleep. Respiratory variability (coefficient of variation for breath duration and tidal volume) was not affected by time of day in REM or NREM sleep. We conclude that the circadian timing system has no effect on apnoea index during NREM sleep in the rat, but it may influence the propensity for post-sigh apnoea during REM sleep.