Respiratory-related pharyngeal constrictor muscle activity in normal human adults

Electromyographic activity of the superior, middle, and inferior pharyngeal constrictor (PC) muscles was examined in 10 normal adult humans during wakefulness and sleep. Wire electrodes were inserted close to the midline of the posterior pharyngeal wall at the level of the soft palate (superior PC), tip of the epiglottis (middle PC), and corniculate tubercle (inferior PC). In general, the three PC muscles exhibited similar patterns of activation. The PCs were activated during swallows, repetitive "pa" sounds, changes in head position, and the last portions of slow inspiratory and expiratory vital capacity maneuvers. Respiratory-related PC activity was infrequent during quiet breathing during wakefulness; variable and inconsistent phasic activation in expiration in one or more of the PCs was present in seven of the 10 subjects, particularly after a swallow. Progressive hyperoxic hypercapnia and progressive isocapnic hypoxia were associated with recruitment of phasic PC activity, which was predominantly expiratory; however, variable discharge patterns were observed within a given muscle and a given subject. When phasic PC activity was present, preactivation during late inspiration was frequently observed. PC activity was absent in NREM sleep and exhibited sporadic, nonrespiratory-related bursts of activity during REM sleep. Passively induced hypocapnic hyperventilation in NREM sleep was not associated with PC activation. The results indicate that the PCs have very similar patterns of activation and exhibit phasic expiratory activity during relatively high ventilatory output states in wakefulness.     

Respiratory responses to tracheobronchial stimulation during sleep and wakefulness in the adult cat

The response to tracheal stimulation (50 microliters of tap water) during wakefulness, non-rapid eye movement (NREM) sleep and rapid eye movement (REM) sleep was investigated in adult cats. In wakefulness, repetitive coughing occurred on 80% of the trials. In NREM and REM sleep, the most frequent response (approximately 69% and 58% of the trials, respectively) was arousal, followed by coughing. Apneas occurred following the stimulus and before arousal in 11% and 24% of the trials in NREM and REM sleep, respectively. In NREM sleep, the tracheal stimulus sometimes evoked expiratory efforts following a normal inspiratory effort (11% of the trials). These were much weaker than the expiratory efforts during coughing in wakefulness. In REM sleep, stimulation in 11% of the trials elicited increased inspiratory efforts. Although these may have been diminutive preparatory inspirations for coughing, they were much smaller than preparatory inspirations associated with coughing in wakefulness, and they were never followed by active expiratory efforts. Arousal from either NREM or REM sleep in response to tracheal stimulation was sometimes associated with an augmented breath. This response, which is common upon spontaneous arousal, may lead to deeper aspiration of the tracheal fluid. We conclude that in cats coughing requires wakefulness and that airway stimuli in sleep cause a variety of respiratory responses, some of which may be maladaptive.     

Compensatory sleep responses to wakefulness induced by the dopamine autoreceptor antagonist (-)DS121

The effect of the dopamine autoreceptor antagonist (-)DS121 on wakefulness, locomotor activity, body temperature and subsequent compensatory sleep responses was examined in the rat. Animals entrained to a light-dark cycle were treated at 5 h after lights-on (CT-5) with 0.5, 1, 5 or 10 mg/kg i.p. (-)DS121 or methylcellulose vehicle. An additional group received 5 mg/kg i.p. (-)DS121 or vehicle 6 h after lights-off (CT-18). At CT-5, (-)DS121 dose-dependently increased wakefulness, locomotor activity and body temperature, and decreased both non-rapid eye movement sleep (NREM) and rapid eye movement sleep (REM) during the first 4 h post-treatment relative to vehicle controls. REM interference lasted up to 3 h longer than NREM. Low doses of (-)DS121 (0.5 and 1 mg/kg) produced relatively little waking that was not followed by significant compensatory sleep responses. In contrast, higher doses (5 and 10 mg/kg) produced compensatory hypersomnolence (robust increases in NREM immediately after the primary waking effect) that was proportional to the duration of drug-induced wakefulness. NREM recovery 24 h post-treatment was the same for the 5 mg/kg (65.4 +/- 9.9 min) and 10 mg/kg (64.8 +/- 9.3 min) doses, but was not proportional to prior wake duration. NREM displaced by drug-induced wakefulness was recovered completely by 24 h post-treatment at the 5 mg/kg dose, but only 63.5% recovered at 10 mg/kg. In contrast, equivalent wakefulness produced by sleep deprivation yielded 100% NREM recovery. At CT-18, (-)DS121 (5 mg/kg) increased wakefulness without disproportionately increasing locomotor activity, and was compensated fully by 24 h post-treatment. These data show that (-)DS121 dose-dependently increases wakefulness, which is followed by hypersomnolence that is proportional to drug-induced wake-promoting efficacy.     

Respiratory and body movements as indicators of sleep stage and wakefulness in infants and young children

Conventional polysomnographic (PSG) sleep staging to sleep staging based on a static-charge-sensitive bed (SCSB) recording in infants and young children was compared. The study consisted of whole-night clinical sleep studies in 22 children at 24 weeks (SD 24, range 1-79 weeks) of age. Most of the children presented with respiratory disturbances during sleep. From the SCSB record, sleep stages were differentiated according to regularity of breathing, presence of body movements, and most important, presence of high-frequency components of breathing (SCSB spikes). With both methods, three sleep/wake stages were distinguished: rapid eye movement (REM) sleep, non-rapid eye movement (NREM) sleep and wakefulness. The average interscorer reliability of the PSG sleep staging controlled in nine subjects was 88%. The average concordance between the two methods ranged from 82 to 85%, depending on the criteria used for scoring the SCSB. The mean sensitivity of the SCSB to detect NREM sleep ranged from 77 to 90% and the mean sensitivity to detect REM sleep ranged from 61 to 86%. The mean positive predictive value was 89-96% for NREM sleep and 54-67% for REM sleep. In conclusion, REM sleep is characterized by irregular breathing with superimposed fast respiratory movements. These changes are specific enough to allow distinction between episodes of NREM sleep, REM sleep and wakefulness with the non-invasive SCSB method in infants and young children. Incomplete concordance between PSG and SCSB score was most frequently observed during sleep stage transition periods, where the behavioural state and electrophysiological criteria disagreed. When combined with the PSG, the SCSB provides complementary information about the behavioural state of child.     

Effect of sleep on changes in breathing pattern accompanying sigh breaths

We studied the effect of sleep on the characteristics of sigh breaths and the associated changes in breathing pattern in breaths following spontaneous sighs in 4 unrestrained dogs with an intact upper airway. The sigh breath was characterized by its large tidal volume (VT), long TI and TE in comparison with the control breath. The volume of the sigh breath was larger in awake sighs than in those recorded during non-REM (NREM) and REM sleep. The strength of Hering-Breuer reflex as determined by duration of the post-sigh apnea was similar in NREM and REM sleep. Sighs occurring during wakefulness, NREM and REM sleep were associated with augmented activity of the parasternal muscles during inspiration, and a persistent tonic abdominal muscle activity during the expiratory period. Breathing pattern in the post-sigh period was characterized by a smaller VT and longer TE in the first post-sigh breath in all sleep states (compared with the control breath), but the pattern returned to control level within the second or third post-sigh breath in both NREM and REM sleep. Sighs did not precipitate periodic breathing or other forms of abnormal breathing patterns in either wakefulness or sleep. We conclude that the respiratory control mechanisms stabilizing breathing after a sigh in the awake dog are intact in NREM and REM sleep.     

State-related changes in upper airway caliber and surrounding soft-tissue structures in normal subjects

State-dependent changes in upper airway caliber were studied with magnetic resonance imaging (MRI) techniques. We hypothesized that changes in airway caliber during sleep in normal subjects would result from positional and dimensional changes in upper airway soft-tissue structures, including the lateral pharyngeal walls, tongue, and soft palate. We used MRI to study 15 normal subjects during wakefulness and sleep. Sleep was facilitated by one night of sleep deprivation prior to MRI. During sleep, the volume of the retropalatal (RP) airway was reduced by 19% (p = 0.03). The volume of the retroglossal (RG) airway was not significantly reduced during sleep, suggesting that the RP region may be more likely to collapse. The mean minimal cross-sectional airway area was reduced by 228% (p = 0.004) in the RP and by 22% (p = 0.02) in the RG region during sleep as compared with values in anatomically matched axial images during wakefulness. Airway anteroposterior (AP) and lateral dimensions were also significantly reduced in the RP region. Airway narrowing in the RP region was associated with a 7% increase in thickness of the lateral pharyngeal walls (p = 0.04). In nine subjects, sagittal data showed significant posterior displacement of the soft palate during sleep as compared with wakefulness. Multiple linear regression analyses indicated that reduction in the RP airway area during sleep resulted from posterior movement of the soft palate, thickening of the lateral pharyngeal walls, and an increase in tongue oblique distance. We conclude that the lateral pharyngeal walls play an important role in upper airway narrowing during sleep in normal subjects.     

Changes in left ventricular contractility with the phase of respiration

The end-systolic wall stress (sigma(es))-velocity of circumferential fiber shortening (V(cfsc)) relation was defined during the respiratory cycle, in order to obtain a totally noninvasive measure of left ventricular contractility. Eight young, healthy subjects were studied with echocardiography and calibrated carotid pulse tracings, while performing slow paced breathing. Left ventricular sigma(es) vs. V(efsc) relation was determined by fitting linear regression line to data points obtained at different times during the respiratory cycle. Data are given as mean+/-1SD. Left ventricular sigma(es) and V(efsc) exhibited small but significant changes during the respiratory cycle: sigma(es) was highest in late inspiration (56.9+/-4.8 g/cm2) and lowest in late expiration (49.2+/-3.7 g/cm2); inversely, V(cfsc) was lowest during late inspiration (1.18+/-0.17 circ/s) and highest during late expiration (1.34+/-0.20 circ/s). The relation was significant in each subject (r = -0.64+/-0.13) and remained inverse and significant, when it was determined separately for inspiration and expiration (r = -0.61+/-0.17 and -0.68+/-0.12, respectively). At identical end-systolic wall stress, the velocity of shortening was greater during inspiration then expiration, suggesting that contractility was reduced during the expiratory phase. The reduced expiratory contractility might reflect increased vagal influence on the ventricular myocardium.     

The determinants of respiratory rate during mechanical ventilation

The independent and interactive effect of feedback related to volume, CO2, inspiratory flow, and arousal state on the regulation of respiratory rate in mechanically ventilated humans is not well characterized. We examined the rate response of eight normal volunteers during both quiet wakefulness and non-rapid-eye-movement (NREM) sleep, while mechanically ventilated through a nasal mask in an assist/control mode with a machine back-up rate of 2 breaths/min. Tidal volume (VT) was set slightly above spontaneous VT and then increased by 0.2 L every 3 min up to 1.8 L or 25 ml/kg. Either an inspiratory flow of 40 L/min or an inspiratory time of 2 s (iso-T(I)) was set, with CO2 added (F(I)CO2 > 0) or F(I)CO2 = 0. Measurements were made during both quiet wakefulness and NREM sleep. We found that as VT increased, the respiratory rate decreased; the rate decline was observed during wakefulness and sleep, and under isocapnic as well as hypocapnic conditions. Increasing inspiratory flow raised the respiratory rate during wakefulness and NREM sleep. During NREM sleep, hypocapnia resulted in wasted ventilator trigger efforts. In summary, both VT and inspiratory flow settings affect the respiratory rate, and depending on state, can affect CO2 homeostasis. Ventilator settings appropriate for wakefulness may cause ventilatory instability during sleep.     

Forced oscillation technique for the evaluation of severe sleep apnoea/hypopnoea syndrome: a pilot study

The forced oscillation technique (FOT) is a noninvasive method of potential clinical interest for quantitatively assessing airway mechanics during sleep. We investigated the applicability of FOT as a diagnostic tool for noninvasive assessment of airflow obstruction in patients with sleep apnoea/hypopnoea syndrome (SAHS) during sleep. In seven patients previously diagnosed with severe SAHS (mean+/-SD apnoea/ hypopnoea index (AHI) 67+/-14) we performed a full polysomnography (PSG) together with on-line measurement of respiratory impedance (IZI) using FOT. For each patient we determined: 1) number of respiratory events conventionally detected by full PSG, those obtained by FOT and their degree of concordance; and 2) the characteristics and values of IZI during the respiratory events. FOT was well tolerated and easily applied in conjunction with a conventional sleep setup. The mean number of respiratory events x h(-1) detected by PSG and FOT were 55+/-16 and 58+/-17, respectively, with a strong concordance. IZI increased from a baseline of 11+/-4 to 50+/-20 cmH2O x L(-1) x s during apnoea (mean+/-SD). In all but one patient intermittent increases of IZI occurred immediately before each obstructive apnoea. In four patients, the increases of IZI developed at end-expiration whereas in two others occurred during inspiration. During hypopnoea most of the patients showed decreases of IZI during expiration. In conclusion, forced oscillation technique can be used as a noninvasive and complementary tool for the diagnosis of respiratory events and provides an on-line quantitative approach for continuous monitoring of airflow obstruction during sleep in patients with sleep apnoea/hypopnoea syndrome.     

In vitro release of acyclovir from semisolid dosage forms: effect of cyclodextrin and polyethylene glycol

Presynaptic depolarization of trigemino-thalamic (TGT) terminals may contribute to modulation of ascending oro-facial somatosensory information during active (or rapid eye movement) sleep. The relative excitability of TGT terminals was inferred from changes in the current required to maintain an antidromic firing probability of 50% (EC50) during quiet wakefulness as compared to active sleep. Depolarization or hyperpolarization of TGT terminals was defined as a decrease or increase, respectively, in the EC50. Overall, the EC50 of 8 TGT terminals was reduced by a mean 8.8+/-3.6 microA during active sleep relative to quiet wakefulness. This result suggests that depolarization of TGT terminals, which may act to suppress the transfer of sensory information from the trigeminal nucleus to the thalamus, occurs during active sleep.     

Cavitary necrosis complicating pneumonia in children: sequential findings on chest radiography

We tested the hypothesis that the obese (fa/fa) Zucker rat has a sleep organization that differs from that of lean Zucker rats. We used the polygraphic technique to identify and to quantify the distribution of the three main states of the rat: wakefulness (W), non-rapid-eye-movement (NREM), and rapid-eye movement (REM) sleep states. Assessment of states was made with light present (1000-1600), at the rats thermoneutral temperature of 29 degrees C. Obese rats, compared with lean ones, did not show significant differences in the total time spent in the three main states. Whereas the mean durations of W and REM states did not differ statistically, that of NREM did (P = 0.046). However, in the obese rats, the frequencies of switching from NREM sleep to W, which increased, and from NREM to REM sleep, which decreased, were statistically significantly different (P = 0.019). Frequency of switching from either REM or W state was not significantly different. We conclude that sleep organization differs between lean and obese Zucker rats and that it is due to a disparity in switching from NREM sleep to either W or REM sleep and the mean duration of NREM sleep.     

Use of dynamic two-dimensional transesophageal echocardiography for renal cell carcinoma with cavoatrial tumor thrombus

Previous investigations involving continuous blood pressure (BP) monitoring have shown an important alteration of the 24-hour BP profile in patients with obstructive sleep apnea syndrome (OSAS). We investigated the impact of REM sleep on the 24-hour BP cycle in 16 severe OSAS male patients (mean respiratory disturbance index = 66 +/- 16 events/hour of sleep), with hypertension (mean BP 162 +/- 21/105 +/- 11 mmHg World Health Organization (WHO) protocol). Two successive nights of polysomnography were performed, and arterial BP was monitored continuously during the second 24-hour period after brachial artery cannulation. During the daytime, subjects were kept awake and supine. At 3 p.m. BP was continuously monitored during quiet supine wakefulness for 20 minutes. Systolic, diastolic and mean BP and heart rate (HR) were analyzed and tabulated in mean values of 5 minute segments. Sleep/wake information were correlated with cardiovascular variables. Each uninterrupted REM sleep period was identified and comparison between the period of quiet supine wakefulness and REM sleep HR and BP values was performed. 8 OSAS patients presented a normal drop of the mean arterial BP during the nocturnal REM sleep periods compared to quiet supine wakefulness (mean value = -10.8 +/- 7.3 mmHg) ("dippers") while the other 8 subjects ("REM sleep non dippers"), revealed an elevated mean arterial BP during REM sleep (mean value = 18.9 +/- 10.9 mm Hg). The absence of the normal circadian BP dip seen during the nocturnal sleep period is considered as an indication of vascular risk. The REM sleep non dipping may play a role in this risk.     

CDTect-RIA and CDTect-EIA for determination of serum carbohydrate-deficient transferrin compared

Little is known of the factors that regulate CBF in sleep. We therefore studied 10 lambs to assess the vasodilatory processes that underlie cerebral autoregulation during sleep. Lambs, instrumented to measure CBF (flow probe on the superior sagittal sinus), sleep state, and cerebral perfusion pressure (CPP), were rapidly made hypotensive by inflating a cuff around the brachiocephalic artery to reduce CPP to 30 mm Hg in each state. During control periods, cerebral vascular resistance (CVR in mm Hg/mL/min) was lower in active sleep (2.8 +/- 0.3, mean +/- SD, P < or = 0.001) than in wakefulness (3.9 +/- 0.6) and quiet sleep (4.3 +/- 0.6). The CVR decreased promptly in each state as CPP was lowered. The time (seconds) required for maximal cerebral vasodilation to occur was longer in active sleep (35 +/- 11) than in quiet sleep (20 +/- 6, P < or = 0.001) and wakefulness (27 +/- 11, P < or = 0.05). The CVR decreased less in active sleep (0.6 +/- 0.3, P < or = 0.001) than in quiet sleep (1.5 +/- 0.3), although the changes in CPP induced with brachiocephalic occlusion were equal in each state. In conclusion, our studies provide the first evidence that the vasoactive mechanisms that underlie autoregulation of the cerebral circulation function during sleep. Moreover, our data reveal that the speed and the magnitude of the vasodilatory reserves available for autoregulation are significantly less in active sleep than in quiet sleep.     

Clinical significance of sleep apnea disorders after implantation of a cardioverter-defibrillator in patients with cardiac disease and sustained ventricular tachyarrhythmia

The purpose of our study was to determine the prevalence of sleep related breathing disorders (SRBD) in patients with an implantable cardioverter-defibrillator (ICD) and to evaluate prospectively the possible influence of SRBD on arrhythmia recurrence and circadian arrhythmia variation as well as on cardiac mortality during long-term follow-up. Forty consecutive ICD recipients with cardiac disease and a documented history of spontaneous, life-threatening, ventricular tachyarrhythmias underwent full-night polysomnography and were followed for 2 years. In 16 of 40 patients (40%), SRBD were diagnosed (Apnea/Hypopnea Index (AHI) > 10); in 9 of these 16 patients (56%) central sleep apneas (CSA) occurred (in 8 of these 9 patients in combination with Cheyne-Stokes respiration). Seven of the 16 patients with SRBD (44%) revealed obstructive sleep apneas (OSA). AHI was 32 +/- 15 (12-60) in patients with CSA and 32 +/- 27 (11-86) in patients with OSA. Patients with and without SRBD were comparable concerning left ventricular ejection fraction, NYHA classification, cardiac disease, ICD indication, and concomitant medication. ICD registered ventricular tachyarrhythmias occurred in 10 of 24 patients (42%) without SRBD, in 4 of 9 patients (44%) with CSA, and in 3 of 7 patients (44%) with OSA. The numbers and circadian variation of episodes registered during follow-up in patients without SRBD, with OSA or CSA were comparable (14 +/- 25, median 4 vs 15 +/- 15, median 7 vs 4 +/- 5, median 2.5). The 2-year cardiac mortality was highest in patients with CSA (4/9 (44%) vs. 0/7 patients (0%) with OSA vs 3/24 patients (12.5%) without SRBD. Thus, the prevalence of SRBD in patients with chronic heart failure and a history of malignant ventricular tachyarrhythmias is high (40%) and the occurrence of CSA seems to be predictive for cardiac mortality in these patients. An influence of moderate SRBD on arrhythmia recurrence and circadian variation of spontaneous sustained tachyarrhythmic events could not be demonstrated.     

Scalp recorded direct current brain potentials during human sleep

The direct current (DC) potential recorded from the scalp of awake humans has been considered a reflection of general changes in cortical excitability. This study examined DC potential shifts in humans during a night of continuous sleep. Standard polysomnographic recordings and skin temperature were measured simultaneously. Contrary to expectations, average DC potential level indicated higher negativity during nonrapid eye movement (NREM) sleep than REM sleep and wakefulness. Moreover, a dynamic regulation of the DC potential level was revealed in association with the NREM-REM sleep cycle comprising four successive phases: (i) a steep 'NREM-transition-negative shift' during the initial 10-15 min of the NREM sleep period; (ii) a more subtle 'NREM-positive slope' during the subsequent NREM sleep period; (iii) a steep 'REM-transition-positive shift' starting shortly prior to the REM sleep period, and (iv) a 'REM-negative slope', characterizing the remaining greater part of the REM sleep period. DC potential changes were only weakly related to changes in slow-wave activity (r2 < 0.18). The NREM-negative slope and REM-positive slope could reflect, respectively, gradually increasing and decreasing cortical excitability resulting from widespread changes in the depolarization of apical dendrites. In contrast, the NREM-transition-negative shift and the REM-transition-positive shift may reflect the progression and retrogression, respectively, of a long-lasting hyperpolarization in deeply lying neurons.     

Effect of mandibular and tongue protrusion on upper airway size during wakefulness

Oral appliances for the treatment of obstructive sleep apnea (OSA) produce either mandibular or tongue protrusion, and are thought to enlarge the upper airway (UA). We used videoendoscopy to measure UA cross-sectional area (CSA) and shape in the hypopharynx, oropharynx, and velopharynx during various stages of active mandibular and tongue protrusion during wakefulness in 10 patients with OSA and nine control subjects. Measurements were made in the supine position at end-tidal expiration, and were normalized to the CSA in the normal bite position. Airway shape was expressed as the anteroposterior/lateral (AP/L) diameter ratio. There were no differences between OSA patients and controls in the effects of mandibular and tongue protrusion on UA caliber. Both mandibular and tongue protrusion increased CSA in the hypopharynx and oropharynx (p < 0.001), whereas only tongue protrusion increased CSA in the velopharynx (p < 0.001). Tongue protrusion caused a greater increase in oropharyngeal and velopharyngeal CSA than did mandibular protrusion (p < 0.05). Mandibular protrusion caused a greater increase in CSA in the hypopharynx than in the oropharynx or velopharynx (p < 0.05). Obese patients had a larger relative increase in oropharyngeal CSA with mandibular and tongue protrusion than did subjects of normal weight. Tongue protrusion increased the AP/L diameter ratio in the oropharynx and velopharynx (p < 0.001), and mandibular protrusion did so to a lesser extent in the oropharynx (p < 0.01), resulting in a more circular airway shape. We conclude that mandibular and tongue protrusion increase the CSA and alter the shape of the UA during wakefulness.     

Influence of upper airway pressure oscillations on soft palate muscle electromyographic activity

Snoring is characterized by high-frequency (30-50 Hz) pressure oscillations (HFPO) in the upper airway (UA). The soft palate is a major oscillating structure during snoring, and soft palate muscle (SPM) activity is an important determinant of velopharyngeal patency. Consequently, we examined the effect of artificial HFPO applied to the UA on the integrated electromyographic (EMG) activity of the SPMs in 11 supine mouth-closed anesthetized (pentobarbital sodium/chloralose) dogs breathing spontaneously via a tracheostomy. The EMGs of the palatinus (Pal; n = 11), levator veli palatini (LP; n = 9), and tensor veli palatini (TP; n = 8) were monitored with intramuscular fine-wire electrodes. Peak inspiratory and peak expiratory EMG activity was measured in arbitrary units (au) as the mean of five consecutive breaths. HFPO [+/- 4.5 +/- 0.4 (SE) cmH2O; 30 Hz] applied at the laryngeal end of the isolated UA increased peak inspiratory EMG from 3.3 +/- 2.0 to 8.4 +/- 1.7 au (P < 0.05) for Pal and from 2.0 +/- 1.1 to 7.3 +/- 2.7 au (P < 0.05) for LP. For the TP, increases were evident in four dogs, but mean values for the group did not change (5.8 +/- 2.4 to 11.0 +/- 4.1 au, P = 0.5). The peak expiratory EMG did not change for any SPM (all P > 0.3). Thus HFPO applied to the UA augments inspiratory SPM activity. Reflex augmentation of SPM activity by HFPO may serve to dilate the retropalatal airway and/or stiffen the soft palate during inspiration in an attempt to stabilize UA geometry during snoring.     

Activation of a distinct arousal state immediately after spontaneous awakening from sleep

In contrast to the many neural studies into the mechanisms of sleep onset and maintenance, few studies have focused specifically on awakening from sleep. However, the abrupt electrographic changes and large brief cardio-respiratory activation at awakening suggest that a distinct, transiently aroused, awake state may exist compared to later wakefulness. To test this hypothesis we utilized the acoustic startle reflex, a standard un-conditioned reflex elicited by a sudden loud noise. This reflex is modulated under specific conditions, one being a diminution of startle when a quieter pre-stimulus is presented immediately before the loud stimulus. This pre-pulse inhibition (PPI) is used as a measure of sensorimotor gating, with smaller PPI indicating less filtering of sensory inputs and increased responsiveness to external stimuli. Eight rats with electrodes for recording sleep-wake state were studied. An accelerometer measured startle responses. The startle reflex was elicited by 115 dB, 40 ms tones. PPI was produced by 74 dB, 20 ms tones preceding the 115 dB tone by 100 ms. Responses within 100 ms were measured. Stimuli were applied either 3-10 s after spontaneous awakenings, or in established wakefulness (> 30 s). Responses to the startle stimuli alone were similar in the different awake states (P = 0.821). However, PPI was smaller at awakening from non-REM sleep compared to established wakefulness (45.4 +/- 7.5% vs. 74.3 +/- 6.1%, P = 0.0002). PPI after awakening from REM sleep (52.8 +/- 17.9%) was not significantly different than established wakefulness (P = 0.297). Reduced PPI of the startle reflex at awakening from non-REM sleep supports the hypothesis that wakefulness immediately after spontaneous sleep episodes is neurophysiologically distinct from later wakefulness and associated with reduced gating of motor responses to sensory inputs. Spontaneous activation of this distinct, transiently aroused, state upon awakening may serve a protective function, preparing an animal to respond immediately to potentially threatening stimuli.     

Left ventricular volume in patients with heart failure and Cheyne-Stokes respiration during sleep

In patients with congestive heart failure (CHF), elevated, left ventricular (LV) volume might lead to pulmonary congestion and hypocapnia, which would create a predisposition to the development of Cheyne-Stokes respiration with central sleep apnea (CSR-CSA). In addition, because LV volume affects cardiac output, it should influence the lengths of hyperpneas. We therefore evaluated LV volumes and transcutaneous PCO2 (PtcCO2) during wakefulness and stage 2 sleep in 16 patients with CHF due to nonischemic dilated cardiomyopathy (NIDC). Data were then compared between those with (n = 7) and those without CSR-CSA (n = 9). LV end-diastolic volume (LVEDV) was significantly higher in patients with than those without CSR-CSA (585 +/- 118 versus 312 +/- 41 ml, p < 0.05). Compared with patients without CSR-CSA, those with CSR-CSA had lower mean stage 2 sleep PtcCO2 (36.3 +/- 2.2 versus 41.2 +/- 1.2 mm Hg, p < 0.05) and a lesser change in PtcCO2 from wakefulness to stage 2 sleep (-0.4 +/- 0.3 versus 2.0 +/- 0.4 mm Hg, p < 0.001). Among patients with CSR-CSA, hyperpnea length was inversely related to LVEDV (R = 0.769, p = 0.043) owing to the direct relationship of cardiac output to LVEDV (R = 0.791, p = 0.034). We conclude that CSR-CSA in patients with CHF due to NIDC is associated with increased LV volumes possibly through the direct or indirect influence of LV volume on PaCO2 and cardiac output.     

A multisensor solid-state pressure manometer to identify the level of collapse in obstructive sleep apnea

The cause of failure after uvulopalatopharyngoplasty (UPPP) in idiopathic obstructive sleep apnea (OSA) is poorly understood, but has been speculated to be due, in part, to persistent collapse in the lower oropharynx. In order to determine the specific level of upper airway obstruction during sleep, a multisensor pressure catheter has been developed with five solid-state ultraminiature sensors. Four sensors in the pharynx simultaneously measure multiple pressure levels, with no need to move the catheter during sleep. One distal esophageal port measures the respiratory effort. To evaluate the use of this catheter, manometry in twelve patients was reviewed and compared the use of this catheter, manometry in twelve patients was reviewed and compared to simultaneous videoendoscopy. The initial site of obstruction was the palate in nine patients (75%) and the tongue base in three (25%). Three patients with initial obstruction at the palate manometrically demonstrated distal obstruction on subsequent occluded breaths. Furthermore, simultaneous videoendoscopy in four patients with a palatal level of obstruction also identified marked near-total visual collapse without obstruction of the lower oropharynx that was not identified by pharyngeal manometry. The endoscopy revealed that at the initial site of obstruction, collapse appeared to have occurred passively during expiration and not on inspiration. Inferior to the site of manometric obstruction, collapse occurred during inspiration associated with increased negative inspiratory pressures. These results demonstrate that a multisensor pressure catheter can objectively identify the level of obstruction during sleep.(ABSTRACT TRUNCATED AT 250 WORDS)