Comparison of arousal responses to tracheal and face mask occlusions in sleeping newborn piglets.

The arousal responses after occlusion of the airway at the mid-trachea were compared with the responses after occlusion of the airway in a face mask in chronically instrumented 3- to 5-day-old piglets. For each site of occlusion arousal latency was significantly longer from active sleep than from quiet sleep. There was a significant increase in the frequency of early arousals after face mask occlusions compared with tracheal occlusions in both sleep states. During quiet sleep the frequency of arousal by 1 s after occlusion was 0.55 with face mask occlusions compared with 0.28 with tracheal occlusion (P less than 0.01). During active sleep the frequency of arousal by 3 s after a face mask occlusion was 0.32 compared with 0.08 after tracheal occlusion (P less than 0.05). Arousal from quiet sleep occurred before changes in arterial oxygen saturation. During active sleep mean saturation at arousal was not different between face mask and tracheal occlusions. Exposure of the upper airway to the pressures generated during airway occlusions results in earlier arousal in both quiet and active sleep, indicating a potential role for upper airway mechanoreceptors in initiating arousal in the newborn piglet.     

Arousal response to upper airway obstruction in young lambs: comparison of nasal and tracheal occlusion

Experiments were done on seven lambs to determine if site of occlusion--nasal versus tracheal--influences the cardiopulmonary and arousal responses from sleep to upper airway obstruction. Each lamb was anesthetized and instrumented for sleep staging and measurements of heart rate and arterial hemoglobin oxygen saturation. A tracheostomy was also done and a fenestrated tracheostomy tube placed in the trachea. Prior to an experiment, A 5F balloon-tipped catheter was inserted through the decannulation cannula into the tracheostomy tube so that tracheal occlusions could be accomplished by inflating the balloon. In addition, a 5F balloon-tipped catheter was inserted into the inlet of a pre-formed silicone mask sealed to the animals snout with silicone rubber foam so that nasal occlusions could be accomplished by inflating the balloon. During an experiment, measurements were made in quiet sleep and in active sleep during control periods of tidal breathing and during experimental periods of nasal or tracheal occlusion. Upper airway obstruction was terminated by deflating the balloon once the animal aroused from sleep. Arousal occurred sooner following nasal occlusion than during tracheal occlusion in quiet sleep; 64 percent of arousals occurred within five seconds of nasal occlusion whereas only 14 percent of arousals occurred within five seconds of tracheal occlusion in quiet sleep. In addition, SaO2 and heart rate decreased more before arousal following tracheal occlusion than following nasal occlusion. However, there was not a significant effect of site of obstruction on time to arousal or the change in SaO2 before arousal in active sleep.(ABSTRACT TRUNCATED AT 250 WORDS)     

Influence of sleep state on frequency of swallowing, apnea, and arousal in human infants.

Apnea and arousal are modulated with sleep stage, and swallowing may interfere with respiratory rhythm in infants. We hypothesized that swallowing itself would display interaction with sleep state. Concurrent polysomnography and measurement of swallowing allowed time-matched analysis of 3,092 swallows, 482 apneas, and 771 arousals in 17 infants aged 1-34 wk. The mean rates of swallowing, apnea, and arousal were significantly different, being 23.3 +/- 8.5, 9.4 +/- 8.8, and 15.5 +/- 10.6 h(-1), respectively (P < 0.001 ANOVA). Swallows occurred before 25.2 +/- 7.9% and during 74.8 +/- 6.3% of apneas and before 39.8 +/- 6.0% and during 60.2 +/- 6.0% of arousals. The frequencies of apneas and arousals were both strongly influenced by sleep state (active sleep > indeterminate > quiet sleep, P < 0.001), whether or not the events coincided with swallowing, but swallowing rate showed minimal independent interaction with sleep state. Interactions between swallowing and sleep state were predominantly influenced by the coincidence of swallowing with apnea or arousal.     

Regulation of end-expiratory lung volume during sleep in premature infants

To investigate the regulation of end-expiratory lung volume (EEV) in premature infants, we recorded airflow, tidal volume, diaphragm electromyogram (EMG), and chest wall displacement during sleep. In quiet sleep, EEV during breathing was 10.8 +/- 3.6 (SD) ml greater than the minimum volume reached during unobstructed apneas. In active sleep, no decrease in EEV was observed during 28 of 35 unobstructed apneas. Breaths during quiet sleep had a variable extent of expiratory airflow retardation (braking), and inspiratory interruption occurred at substantial expiratory flow rates. During active sleep, the expiratory flow-volume curve was nearly linear, proceeding nearly to the volume axis at zero flow, and diaphragm EMG activity terminated near the peak of mechanical inspiration. Expiratory duration (TE) and inspiratory duration (TI) were significantly shortened in quiet sleep vs. active sleep although tidal volume was not significantly different. In quiet sleep, diaphragmatic braking activity and shortened TE combined to maintain EEV during breathing substantially above relaxation volume. In active sleep, reduced expiratory braking and prolongation of TE resulted in an EEV that was close to relaxation volume. We conclude that breathing strategy to regulate EEV in premature infants appears to be strongly influenced by sleep state.     

Influence of repeated exposure to rapidly developing hypoxaemia on the arousal and cardiopulmonary response to rapidly developing hypoxaemia in lambs

Experiments were done on four lambs to determine if repeated exposure to rapidly developing hypoxaemia influences the cardiopulmonary and arousal response from sleep. Each lamb was anaesthetized and instrumented for sleep staging and measurements of arterial haemoglobin oxygen saturation. No sooner than three days after surgery, measurements were made in quiet sleep and active sleep during control periods when the animal was breathing 21% oxygen and during experimental periods of rapidly developing hypoxaemia when the animal was breathing 5% oxygen for approximately 100 epochs of sleep. Arousal occurred from both sleep states during rapidly developing hypoxaemia but was delayed in active sleep compared to quiet sleep. The time to arousal and the decrease in arterial haemoglobin oxygen saturation were significantly increased with repeated exposure to rapidly developing hypoxaemia during both quiet sleep and active sleep. Thus, our data provide evidence that repeated exposure to rapidly developing hypoxaemia produces an arousal response decrement in lambs. Since it is possible that alterations in the arousal response to respiratory stimuli play a role in sudden infant death, studies to investigate the mechanism of the arousal response decrement following repeated exposure to rapidly developing hypoxaemia are warranted.     

Effects of nasal CPAP therapy on respiratory and spontaneous arousals in infants with OSA.

Obstructive sleep apnea (OSA) in infants has been shown to resolve frequently without a cortical arousal. It is unknown whether infants do not require arousal to terminate apneas or whether this is a consequence of the OSA. We studied the apnea and arousal patterns of eight infants with OSA before and after treatment with nasal continuous positive airway pressure (CPAP). These infants were age matched to eight untreated infants with OSA and eight normal infants. Polysomnographic studies were performed on each infant. We found that the majority of central and obstructive apneas were terminated without arousal in all OSA infants. After several weeks of nasal CPAP treatment, the proportion of apneas terminating with an arousal during rapid-eye-movement sleep increased in treated infants compared with untreated infants. Spontaneous arousals during rapid-eye-movement sleep were reduced in all OSA infants; however, during CPAP treatment, the spontaneous arousals increased to the normal control level. We conclude that OSA in infants possibly depresses the arousal response and treatment of these infants with nasal CPAP partially reverses this depression.     

Postnatal maturation of laryngeal chemoreflexes in the preterm lamb.

Laryngeal chemoreflexes (LCR) are triggered by the contact of liquids with the laryngeal mucosa. In the mature organism, LCR trigger lower airway protective responses (coughing, effective swallowing, and arousal) to prevent aspiration. General belief holds that LCR are responsible for apnea and bradycardia in the newborn mammal, including humans. Our laboratory has recently shown that LCR in full-term lambs are consistently analogous to the mature LCR reported in adult mammals, without significant apneas and bradycardias (St-Hilaire M, Nsegbe E, Gagnon-Gervais K, Samson N, Moreau-Bussiere F, Fortier PH, and Praud J-P. J Appl Physiol 98: 2197-2203, 2005). The aim of the present study was to assess LCR in nonsedated, newborn preterm lambs born at 132 days of gestation (term = 147 days). The preterm lambs were instrumented for recording glottal adductor electromyogram, electroencephalogram, eye movements, heart rate, respiration, and oximetry. A chronic supraglottal catheter was used for injecting 0.5 ml of saline, distilled water, and HCl (pH 2) during quiet sleep, active sleep, and wakefulness on postnatal days 7 (D7) and 14 (D14). Laryngeal stimulation by water or HCl on D7 induced significant apneas, bradycardia, and desaturation, which, at times, appeared potentially life-threatening. No significant apneas, bradycardias, or desaturation were observed on D14. No consistent effects of sleep state could be shown in the present study. In conclusion, laryngeal stimulation by liquids triggers potentially dangerous LCR in preterm lambs on D7, but not on D14. It is proposed that maturation of the LCR between D7 and D14 is partly involved in the disappearance of apneas/bradycardias of prematurity with postnatal age.     

Upper airway stability and apnea during nasal occlusion in newborn infants

Brief end-expiratory airway occlusions were performed in 22 preterm babies, 17 with and 5 without clinical apnea, and 4 full-term babies, 1 with Pierre-Robin syndrome. Airway stability was evaluated by comparing pressures measured simultaneously in the chest and nasal passages during occluded inspiratory efforts. The airway remained patent throughout all 301 trials in 20 babies during rapid-eye-movement (REM) and quiet sleep. Airway closure occurred during 31/102 trials in 6 babies (5 preterm and 1 term with Pierre-Robin syndrome), more commonly in quiet than in REM sleep. Overall and within individuals, mean closing pressures were significantly lower than the mean maximum falls in airway pressure recorded during occlusions without closure. Mixed-obstructive and obstructive apnea was significantly more frequent in babies with airway closure than in those without (5.3 +/- 4.0 vs. 0.4 +/- 0.8 episodes/h). Pauses in breathing greater than or equal to 3 s occurred during 28% of occlusions in preterm infants and 2% of occlusions in full-term babies. There was no significant difference between the mean frequency of pauses during occlusion and during the preceding control period or in the incidence of pauses in occlusions with vs. those without closure. It is concluded that the airway of most preterm and full-term babies is remarkably stable under load. Intermittent closure occurs in certain infants and may be related to airway muscle dysfunction.     

Upper airway anesthesia delays arousal from airway occlusion induced during human NREM sleep.

Six healthy subjects (5 males and 1 female, 26-40 yr old) were studied during non-rapid-eye-movement (NREM) sleep to assess the role of upper airway (UA) afferents in the arousal response to induced airway occlusion. Subjects wore an airtight face mask attached to a low-resistance one-way valve. A valve in the inspiratory circuit allowed instantaneous inspiratory airway occlusion and release; the expiratory circuit remained unoccluded at all times. Each subject was studied during two nights. On one night, occlusions were created during stable stage 2 NREM sleep before and after application of 4% lidocaine to the oral and nasal mucosa. On the other night, the protocol was duplicated with saline ("sham anesthesia") rather than lidocaine. The order of nights was randomized. Occlusions were sustained until electroencephalographic arousal. Three to 12 occlusions were performed in each subject for each of the four parts of the protocol (pre- and post-lidocaine, pre- and post-saline). The auditory threshold for arousal (1,500-Hz tone beginning at 30 dB) was also tested before and after UA lidocaine. For the group, arousal time after UA anesthesia was prolonged compared with preanesthesia arousal time (P less than 0.001); arousal time after sham anesthesia did not significantly increase from before sham anesthesia (P = 0.9). The increase in arousal time with UA anesthesia was greater than the increase with sham anesthesia (P less than 0.001). The auditory arousal threshold did not increase after UA anesthesia. Inspiratory mask pressure, arterial O2 saturation of hemoglobin, and end-tidal PCO2 during occlusions were similar before and after UA anesthesia.(ABSTRACT TRUNCATED AT 250 WORDS)     

Arousal and cardiopulmonary responses to hyperoxic hypercapnia in lambs

Experiments were done to investigate the arousal and cardiopulmonary responses to hyperoxic hypercapnia in 8 lambs. Each lamb was anaesthetized and instrumented for recordings of electrocorticogram, electro-oculogram, nuchal and diaphragm electromyograms and measurements of arterial blood pressure and haemoglobin oxygen saturation. No sooner than 3 days after surgery, measurements were made in quiet sleep and active sleep during control periods when the animal was breathing 21% oxygen and during experimental periods of hyperoxic hypercapnia when the animal was breathing 10% carbon dioxide and 30% oxygen. Hyperoxic hypercapnia was terminated during each epoch by returning the inspired gas mixture to 21% oxygen once the animal aroused from sleep. Arousal occurred from both sleep states during hyperoxic hypercapnia but was delayed in active sleep compared to quiet sleep (active sleep 58 +/- 17 s; quiet sleep 21 +/- 10 s; mean +/- 1SD). There were no significant changes in heart rate or blood pressure during hyperoxic hypercapnia before arousal. However, respiratory rate and diaphragm electrical activity did increase during hyperoxic hypercapnia before arousal. Thus, our data provide evidence that hypercapnia can initiate arousal from sleep in young lambs. The mechanisms responsible for this response are yet to be determined.     

Nonnutritive swallowing and respiration relationships in preterm lambs.

The aim of the present study was to assess the effects of the different states of alertness on 1) nonnutritive swallowing (NNS) frequency, 2) the relationship between NNS and the respiratory cycle, and 3) the association of NNS with spontaneous apneas. Recordings of sleep states, diaphragm and laryngeal constrictor electrical activity, nasal flow, electrocardiogram, respiratory inductance plethysmography, and pulse oximetry were obtained from six preterm lambs without sedation. Analysis of 2,468 NNS showed that 1) NNS frequency was higher during quiet wakefulness and active sleep (AS) than in quiet sleep; 2) in all states of alertness, a greater number of NNS (38%) were preceded and followed by an inspiration; 3) although NNS and central apneas were rarely coincidental, AS appeared to favor their association; and 4) most obstructive apneas occurred in AS and were coincidental with bursts of NNS. Compared with results in full-term lambs, premature birth does not modify the NNS-respiratory coordination. However, AS in preterm lambs is characterized by a higher association of NNS bursts with obstructive apneas.     

The effect of short-term sleep fragmentation produced by intense auditory stimuli on the arousal response to upper airway obstruction in lambs

Upper airway obstruction is recognized to cause apnoea in newborns as well as in adults. However, very little is known about factors that influence the arousal response from sleep during upper airway obstruction in newborns. Experiments were therefore done to investigate the effect of short-term sleep fragmentation on the arousal response to upper airway obstruction in six lambs aged 8 to 14 days. Each lamb was anaesthetized and instrumented for recordings of electrocorticogram, electro-oculogram, nuchal and diaphragm electromyograms and measurements of systemic arterial blood pressure and oxygen saturation (fiberoptic catheter oximeter). A tracheostomy was done and a fenestrated tracheostomy tube placed in the trachea. Experiments were not done before the third postoperative day. During a study, a 5F balloon tipped catheter was inserted into the tube so that airflow could be obstructed by inflating the balloon. Measurements were made during 30 s control periods and during experimental periods of upper airway obstruction in at least three epochs of quiet sleep and active sleep in each animal. These measurements were made following a period of uninterrupted sleep and repeated following a 36-42 h period of sleep fragmentation. Sleep fragmentation was produced by 30 s of noise separated by 2 min of quiet. Sleep fragmentation produced small but statistically significant increases in the time to arousal and decreases in the haemoglobin oxygen saturation at arousal during upper airway obstruction in quiet sleep but not active sleep. However, these changes, although consistent, were small and are of questionable biological significance. Therefore, I believe it is unlikely that short-term sleep fragmentation per se significantly impairs the arousal response to respiratory stimuli in newborns.     

Arousal responses to airway occlusion in sleeping dogs: comparison of nasal and tracheal occlusions

Previous studies have shown that the arousal threshold to hypoxia, hypercapnia, and tracheal occlusions is greatly depressed in rapid-eye-movement (REM) sleep compared with slow-wave sleep (SWS). The aim of this study was to compare the arousal thresholds in SWS and REM sleep in response to an upper airway pressure stimulus. We compared the waking responses to tracheal (T) vs. nasal (N) occlusion in four unanesthetized, naturally sleeping dogs. The dogs either breathed through a tracheal fistula or through the snout using a fiberglass mask. A total of 295 T and 160 N occlusion tests were performed in SWS and REM sleep. The mean time to arousal during N and T tests was variable in the same dog and among the dogs. The mean time to arousal in SWS-tracheal occlusion was longer than that in N tests in only two of the four dogs. The total number of tests inducing arousal within the first 15 s of SWS-nasal occlusion tests was significantly more than that of T tests (N: 47%; T: 27%). There was a marked depression of arousal within the initial 15 s of REM sleep in T tests compared with N tests (N: 21%; T: 0%). The frequency of early arousals in REM tests was less than that of SWS for both N and T tests. The early arousal in N occlusion is in sharp contrast to the well-described depressed arousal responses to hypoxia, hypercapnia, and asphyxia. This pattern of arousal suggests that the upper airway mechanoreceptors may play an important role in the induction of an early arousal from nasal occlusion.     

Hypoxemia alone does not explain blood pressure elevations after obstructive apneas

In patients with obstructive sleep apnea (OSA), substantial elevations of systemic blood pressure (BP) and depressions of oxyhemoglobin saturation (SaO2) accompany apnea termination. The causes of the BP elevations, which contribute significantly to nocturnal hypertension in OSA, have not been defined precisely. To assess the relative contribution of arterial hypoxemia, we observed mean arterial pressure (MAP) changes following obstructive apneas in 11 OSA patients during non-rapid-eye-movement (NREM) sleep and then under three experimental conditions: 1) apnea with O2 supplementation; 2) hypoxemia (SaO2 80%) without apnea; and 3) arousal from sleep with neither hypoxemia nor apnea. We found that apneas recorded during O2 supplementation (SaO2 nadir 93.6% +/- 2.4; mean +/- SD) in six subjects were associated with equivalent postapneic MAP elevations compared with unsupplemented apneas (SaO2 nadir 79-82%): 18.8 +/- 7.1 vs. 21.3 +/- 9.2 mmHg (mean change MAP +/- SD); in the absence of respiratory and sleep disruption in eight subjects, hypoxemia was not associated with the BP elevations observed following apneas: -5.4 +/- 19 vs. 19.1 +/- 7.8 mmHg (P less than 0.01); and in five subjects, auditory arousal alone was associated with MAP elevation similar to that observed following apneas: 24.0 +/- 8.1 vs. 22.0 +/- 6.9 mmHg. We conclude that in NREM sleep postapneic BP elevations are not primarily attributable to arterial hypoxemia. Other factors associated with apnea termination, including arousal from sleep, reinflation of the lungs, and changes of intrathoracic pressure, may be responsible for these elevations.     

Active glottal closure during central apneas limits oxygen desaturation in premature lambs.

Our laboratory previously reported that active glottal closure was present in 90% of spontaneous central apneas in premature lambs while maintaining a high-apneic lung volume (Renolleau S, Letourneau P, Niyonsenga T, and Praud JP. Am J Respir Crit Care Med 159: 1396-1404, 1999.) The present study aimed at testing whether this mechanism limits postapnea oxygen desaturation. Four premature lambs were instrumented for recording states of alertness, thyroarytenoid muscle and diaphragm electromyographic (EMG) activity, nasal airflow, lung volume changes, and pulse oximetry. One thousand four hundred fifty-two spontaneous central apneas (isolated or during periodic breathing) were analyzed in nonsedated lambs. Apneas, with high lung volume maintained by active glottal closure, were compared with apneas, with a tracheostomy opened at apnea onset. Oxygen desaturation slopes were lower when high-apneic lung volume was actively maintained during both wakefulness and quiet sleep. Furthermore, oxygen desaturation slopes were lower after isolated apneas with continuous thyroarytenoid EMG during wakefulness, compared with apneas with noncontinuous thyroarytenoid EMG (= glottis opened shortly after apnea onset). These results highlight the importance of maintaining high-alveolar oxygen stores during central apneas by active glottal closure to limit desaturation in newborns.     

Effects of high-frequency pressure waves applied to upper airway on respiration in central apnea.

We examined the effects of high-frequency (30-Hz) low-pressure oscillations on respiration in nine patients with central sleep apnea. All patients were studied during sleep and wore a nasal mask through which the oscillations were applied. All tests were performed during periods of repetitive central apneas. Respiratory efforts were monitored from the airflow and calibrated Respitrace signals. After several cycles of apnea were monitored, the oscillatory pressures were applied for brief periods (less than 5 s) at the midpoint of the central apneas. All trials in which arousal occurred were discarded, leaving a total of 106 trials in the nine patients. High-frequency oscillation of the upper airway stimulated respiratory effort(s) in 68% of all trials (72 of 106). Apnea length was significantly shortened in four of the nine patients. In one patient with a tracheostomy, the stimulus applied to his isolated upper airway evoked respiratory efforts during central apnea in 13 of 15 trials. We conclude that high-frequency oscillatory pressures applied to the upper airway can stimulate respiratory efforts during central apnea. This response may be mediated by upper airway receptors involved in nonrespiratory airway defense reflexes and may have implications in the treatment of patients with central sleep apnea.     

Arousal pattern following central and obstructive breathing abnormalities in infants and children

McNamara, Frances, Faiq G. Issa, and Colin E. Sullivan.Arousal pattern following central and obstructive breathing abnormalities in infants and children. J. Appl.Physiol. 81(6): 2651-2657, 1996.We analyzed thepolysomnographic records of 15 children and 20 infants with obstructivesleep apnea (OSA) to examine the interaction between central andobstructive breathing abnormalities and arousal from sleep. Eachpatient was matched for age with an infant or child who had no OSA. Wefound that the majority of respiratory events in infants and childrenwas not terminated with arousal. In children, arousals terminated 39.3 ± 7.2% of respiratory events during quiet sleep and 37.8 ± 7.2% of events during active (rapid-eye-movement) sleep. In infants,arousals terminated 7.9 ± 1.0% of events during quiet sleep and7.9 ± 1.2% of events during active sleep. In both infants andchildren, however, respiratory-related arousals occurred more frequently after obstructive apneas and hypopneas than after central events. Spontaneous arousals occurred in all patients with OSA duringquiet and active sleep. The frequency of spontaneous arousals was notdifferent between children with OSA and their matched controls. Duringactive sleep, however, infants with OSA had significantly fewerspontaneous arousals than did control infants. We conclude that arousalis not an important mechanism in the termination of respiratory eventsin infants and children and that electroencephalographic criteria arenot essential to determine the clinical severity of OSA in thepediatric population.

     

Effects of arousal and sleep state on systemic and pulmonary hemodynamics in obstructive apnea.

During obstructive sleep apnea (OSA), systemic (Psa) and pulmonary (Ppa) arterial pressures acutely increase after apnea termination, whereas left and right ventricular stroke volumes (SV) reach a nadir. In a canine model (n = 6), we examined the effects of arousal, parasympathetic blockade (atropine 1 mg/kg iv), and sleep state on cardiovascular responses to OSA. In the absence of arousal, SV remained constant after apnea termination, compared with a 4.4 +/- 1.7% decrease after apnea with arousal (P < 0.025). The rise in transmural Ppa was independent of arousal (4.5 +/- 1.0 vs. 4.1 +/- 1.2 mmHg with and without arousal, respectively), whereas Psa increased more after apnea termination in apneas with arousal compared with apneas without arousal. Parasympathetic blockade abolished the arousal-induced increase in Psa, indicating that arousal is associated with a vagal withdrawal of the parasympathetic tone to the heart. Rapid-eye-movement (REM) sleep blunted the increase in Psa (pre- to end-apnea: 5.6 +/- 2.3 mmHg vs. 10.3 +/- 1.6 mmHg, REM vs. non-REM, respectively, P < 0.025), but not transmural Ppa, during an obstructive apnea. We conclude that arousal and sleep state both have differential effects on the systemic and pulmonary circulation in OSA, indicating that, in patients with underlying cardiovascular disease, the hemodynamic consequences of OSA may be different for the right or the left side of the circulation.     

Behavioural state influences the cardiovascular response to haemorrhage in lambs

We investigated the effect of behavioural state on the cardiovascular response to an acute venous haemorrhage in 7 lambs aged 13 to 19 days. Each lamb had previously been anaesthetized and instrumented for measurements of electrocorticogram, electro-oculogram, nuchal and diaphragm electromyograms, pulmonary blood flow (electromagnetic flow transducer), aortic and right atrial blood pressures. The lambs were allowed to recover from surgery at least three days before they were studied. Measurements were made during a 1-minute control period and during a 1-minute experimental period that followed a 10 ml/kg body weight haemorrhage during quiet wakefulness, quiet sleep and active sleep; the haemorrhage took approximately 30s. Haemorrhage produced similar decreases in right atrial pressure and pulmonary blood flow during the three behavioural states. However, mean aortic pressure decreased more following haemorrhage during active sleep than during quiet sleep or quiet wakefulness. These results provide evidence that reflex control of the peripheral circulation is altered during active sleep compared to quiet sleep and quiet wakefulness in lambs.     

Sleep apnea and effect of chemostimulation on breathing instability in mice.

Sleep apnea occurs in humans and experimental animals. We examined whether it also arises in adult mice. Ventilation in male adult 129/Sv mice was recorded concomitantly by electroencephalograms and electromyograms for 6 h by use of body plethysmography. Apnea was defined as cessation of plethysmographic signals for longer than two respiratory cycles. While mice breathed room air, 32.3 +/- 6.9 (mean +/- SE, n = 5) apneas were observed during sleep but not in quiet awake periods. Sleep apneas were further classified into two types. Postsigh apneas occurred exclusively during slow-wave sleep (SWS), whereas spontaneous apneas arose during both SWS and rapid eye movement sleep. Compared with room air (9.1 +/- 1.4/h of SWS), postsigh apneas were more frequent in hypoxia (13.7 +/- 2.1) and less frequent in hyperoxia (3.6 +/- 1.7) and hypercapnia (2.8 +/- 2.1). Our data indicated that significant sleep apnea occurs in normal adult mice and suggested that the mouse could be a promising experimental model with which to study the genetic and molecular basis of respiratory regulation during sleep.