Arousal responses to somatosensory and mild hypoxic stimuli are depressed during quiet sleep in healthy term infants

STUDY OBJECTIVES: To compare arousal responses to somatosensory and hypoxic stimuli in sleeping human infants and to determine whether sleep state and postnatal age exerted similar changes in these arousal responses. DESIGN: We delivered somatosensory (nasal air-jet) stimulation and mild hypoxia (15% oxygen) to 10 healthy term infants aged 2 to 4 weeks, 2 to 3 months, and 5 to 6 months during identified sleep states. Hypoxic challenges were terminated at arousal, when the oxygen saturation fell below 85%, or at 5 minutes (failure to arouse). RESULTS: Infants failed to arouse to a greater percentage of hypoxia tests during quiet sleep (QS) than during active sleep (AS) at 2 to 3 months and 5 to 6 months of age (P < 0.01). Infants failed to arouse to a greater percentage of hypoxic challenges during QS at 2 to 3 months and 5 to 6 months than at 2 to 4 weeks of age. Arousal latency to hypoxia was significantly longer in QS than in AS at each study age; however, arousal latency was not affected by postnatal age. Arousal thresholds to somatosensory stimulation were significantly greater in QS than in AS, except at 2 to 4 weeks of age. In AS, arousability to the air-jet was greater at 2 to 3 months compared to 2 to 4 weeks of age (P < 0.05); in QS it was lower at 5 to 6 months compared to 2 to 4 weeks of age (P < 0.05). Arousal latency to hypoxia and arousal thresholds to air-jet stimulation were not correlated within infants. CONCLUSION: We conclude that arousal responses of infants to somatosensory and respiratory stimuli are similarly affected by sleep state and postnatal age. Infants are less arousable to both stimulus modalities in QS than in AS, and less arousable at 5 to 6 months of age than at 2 to 4 weeks in QS.     

Arousal and ventilatory responses to mild hypoxia in sleeping preterm infants

A failure to adequately respond to hypoxia has been implicated in the Sudden Infant Death Syndrome (SIDS). Preterm infants are at increased risk for SIDS, thus we compared ventilatory and arousal responses to mild hypoxia [15% oxygen (O₂)] in preterm and term infants. Eight preterm and 15 term infants were serially studied with daytime polysomnography during which nasal airflow was monitored by pneumotachograph at 2–5 weeks, 2–3 and 5–6 months. At each age, in both groups, hypoxia induced a significant decrease in oxygen saturation (SpO₂) during both active sleep (AS) and quiet sleep (QS). Infants invariably aroused in AS; and in QS either aroused or failed to arouse. In preterm infants arousal latency in AS was longer than in term infants ( P  < 0.05) at 2–5 weeks. Compared with term infants, preterm infants reached significantly lower SpO₂ levels at 2–5 weeks in both AS and QS non-arousing tests and at 2–3 months in QS. A biphasic hypoxic ventilatory response was observed in QS non-arousing tests in both groups of infants at all three ages. We conclude that the greater desaturation during a hypoxic challenge combined with the longer arousal latency in preterm infants could contribute to greater risk for SIDS.     

Maturation of the initial ventilatory response to hypoxia in sleeping infants

In infants most previous studies of the hypoxic ventilatory response (HVR) have been conducted only during quiet sleep (QS) and arousal responses have not been considered. Our aim was to quantify the maturation of the HVR in term infants during both active sleep (AS) and QS over the first 6 months of life. Daytime polysomnography was performed on 15 healthy term infants at 2-5 weeks, 2-3 and 5-6 months after birth and infants were challenged with hypoxia (15% O2, balance N2). Tests in AS always resulted in arousal; in QS tests infants either aroused or did not arouse. A biphasic HVR was observed in non arousing tests at all three ages studied. The fall in SpO2 was more rapid in arousal tests at all three ages. At 2-5 weeks, in non-arousing QS tests, there was a greater fall in respiratory frequency (f) despite a smaller fall in SpO2 compared with 2-3 and 5-6 months. When infants aroused there was no difference in the HVR between sleep states or with postnatal age. However, when infants failed to arouse from QS, arterial desaturation was less in the younger infants despite a poorer HVR. We suggest that arousal in response to hypoxia, particularly in AS, is a vital survival mechanism throughout the first 6 months of life.     

Postnatal development of ventilatory and arousal responses to hypoxia in human infants

During the first year of life there is significant maturation of the hypoxic ventilatory response (HVR) in human infants. Compared with adults, healthy term infants have an immature HVR until at least 6 months of age. There are few studies in infants on the effects of sleep state on the HVR but these suggest that at early postnatal ages there is initially no sleep-state related difference; this is followed by a developmental trend towards the adult situation in which the response is depressed in REM sleep compared with NREM. Maternal cigarette smoking is a major risk factor for SIDS and the mechanism for this may involve a depressed HVR in the exposed infant; however studies are limited and the wide variation in cigarette consumption makes interpretation of results difficult. Arousal responses to hypoxia are of vital importance and a failure to arouse has been implicated in SIDS. Sleeping infants frequently fail to arouse in response to hypoxia in QS, whereas in AS they invariably arouse; furthermore arousal latency is longer in QS compared with AS. The oxygen saturation at which infants arouse is not different between sleep states, suggesting that desaturation is more rapid in AS. In QS younger infants arouse more readily than at older ages and arousal is depressed by maternal smoking. These findings suggest that depression of the arousal response to hypoxia in AS may have life-threatening consequences. Infants at increased risk for SIDS have been shown to have both depressed ventilatory and arousal responses to hypoxia, thus they may be at even greater risk.     

Arousal and ventilatory responses to hypoxia in sleeping infants: effects of maternal smoking

Our aim was to determine whether maternal cigarette smoking affects arousal and ventilatory responses to hypoxia in infants. Infants born to non-smoking (NS, n = 15) and smoking mothers (SM, n= 9) were studied at 2-5 weeks, 2-3 and 5-6 months. Ventilatory responses to 15% O(2) were determined preceding arousal. At each age and in both groups, infants aroused more frequently and earlier to hypoxia in active sleep (AS) than quiet sleep (QS). Arousal latency was longer in SM infants (in QS) at 5-6 months (P < 0.05). Baseline respiratory parameters were not different between groups, except that, at 2-3 months, SM infants had higher SP(O2) during AS than NS infants. Maternal smoking did not affect ventilatory responses preceding hypoxia-induced arousal in either sleep-state at any age. We conclude that mild hypoxia stimulates ventilation and arousal in infants up to 6 months and that arousability is depressed in SM infants at 5-6 months; however, ventilatory responses preceding arousal are not adversely affected by smoking.     

Ventilatory responses preceding hypoxia-induced arousal in infants: effects of sleep-state

Augmented ventilation and/or arousal in response to hypoxia are important protective mechanisms during sleep. We aimed to quantify ventilatory responses preceding hypoxia-induced arousal in infants and determine the effects of sleep-state. Fifteen term infants were studied at 2-4 weeks, 2-3 and 5-6 months of age. Ventilatory responses to 15% oxygen inhalation were expressed as breath-by-breath changes from normoxic levels and averaged over 5, 10 and 15 breaths preceding arousal. Minute ventilation preceding arousal significantly increased above normoxic levels only in AS at 5-6 months. There were no sleep-state related differences in minute ventilation, oxygen saturation or carbon dioxide levels (expressed as changes from normoxic values) at 5, 10 or 15 breaths preceding arousal. However, the rate of oxygen desaturation during hypoxia in AS was two to four times faster than in QS at each age. We conclude that the ventilatory responses preceding hypoxia-induced arousal do not differ between sleep-states and that arousal occurs at similar levels of desaturation in both states.     

Effects of age and sleeping position on arousal from sleep in preterm infants

STUDY OBJECTIVES: Preterm infants are at increased risk of sudden infant death syndrome (SIDS). We investigated whether the prone sleeping position impaired arousal from sleep in healthy preterm infants and whether this impairment was related to cardiorespiratory variables, temperature or postnatal age. DESIGN: Longitudinal SETTING/PARTICIPANTS: 14 healthy preterm infants (mean 32 +/- 0.4 weeks) were studied using daytime polysomnography on 4 occasions: 36-38 weeks postconception age, 2 to 3 weeks postterm, 2 to 3 months postterm, and 5 to 6 months postterm. Interventions: N/A. MEASUREMENTS: Multiple measurements of arousal threshold (cm H2O) in response to air-jet stimulation applied alternately to the nares were made in both active sleep and quiet sleep when infants slept both prone and supine. RESULTS: Arousal thresholds were significantly higher in both AS and QS when infants slept prone at 36 to 38 weeks postconception age and 2 to 3 months postterm but not at 2 to 3 weeks or 5 to 6 months postterm. These increases were independent of any sleep position-related changes in either rectal or abdominal skin temperature, respiratory rate, oxygen saturation or heart rate. CONCLUSIONS: At the age when the risk of SIDS is highest, the prone position significantly impairs arousal from both active sleep and quiet sleep in healthy infants born prematurely. This impairment in arousability occurred with no clinically significant changes in cardiorespiratory parameters or body temperature. Decreased arousability from sleep in the prone position may explain its role as a risk factor for SIDS.     

Sleeping Like a Baby—Does Gender Influence Infant Arousability?

Introduction:

Victims of the sudden infant death syndrome (SIDS) may have preexisting abnormalities in their arousal pathways, inhibiting the progression of subcortical activation (SCA) to full cortical arousal (CA). Approximately 60% of SIDS victims are male, and it has been suggested that male infants have delayed cortical maturation compared to females. We hypothesized that CA frequency would be lower and CA threshold would be higher in male infants during both active (AS) and quiet (QS) sleep.

Methods:

50 healthy term infants (21 male, 29 female) were studied with daytime polysomnography at 2–4 weeks and 2–3 months after birth. Arousal from sleep was induced using a pulsatile air-jet to the nostrils at increasing pressures.

Results:

At 2–4 weeks, arousability from AS was similar in males and females, however during QS, male infants required a lower stimulus to induce SCA and CA. This gender difference in arousal threshold was not observed at 2–3 months. CA frequencies were similar between genders during both sleep states at both ages, though overall, CA was more frequent in AS than in QS.

Conclusions:

This study demonstrated that at 2–4 weeks, male infants were easier to arouse than female infants during QS. There were no significant effects of gender on total arousability or SCA and CA frequencies at 2–3 months, the age of peak SIDS incidence. Thus, although male infants are at greater risk of SIDS than female infants, this difference is unlikely to be associated with gender differences in CA threshold or frequency.

Citation:

Richardson HL; Walker AM; Horne RSC. Sleeping like a baby—does gender influence infant arousability? SLEEP 2010;33(8):1055-1060.     

The carotid body and arousal in the fetus and neonate

Arousal from sleep is a major defense mechanism in infants against hypoxia and/or hypercapnia. Arousal failure may be an important contributor to SIDS. Areas of the brainstem that have been found to be abnormal in a majority of SIDS infants are involved in the arousal process. Arousal is sleep state dependent, being depressed during AS in most mammals, but depressed during QS in human infants. Repeated exposure to hypoxia causes a progressive blunting of arousal that may involve medullary raphe GABAergic mechanisms. Whereas CB chemoreceptors contribute heavily to arousal in response to hypoxia, serotonergic central chemoreceptors have been implicated in the arousal response to CO₂. Pulmonary or chest wall mechanoreceptors also contribute to arousal in proportion to the ventilatory response and decreases in their input may contribute to depressed arousal during AS. Little is known about specific arousal pathways beyond the NTS. Whether CB chemoreceptor stimulation directly stimulates arousal centers or whether this is done indirectly through respiratory networks remains unknown. This review will focus on arousal in response to hypoxia and CO₂ in the fetus and newborn and will outline what we know (and do not know) about the involvement of the carotid body in this process.     

Comparison of postnatal development of heart rate responses to trigeminal stimulation in sleeping preterm and term infants

Autonomic dysfunction has been regarded as a possible cause of the sudden infant death syndrome (SIDS) and it has been suggested that preterm infants, who are at a greater risk of SIDS than term infants, may have immature autonomic control. Our aim was to compare the maturation of cardiac autonomic control during sleep in preterm and term infants by examining heart rate responses to arousing and non-arousing trigeminal stimuli. Preterm infants (n = 15) and term infants (n = 24) were studied longitudinally with daytime polysomnography. Air-jet stimulation of the nares was delivered in both active sleep (AS) and quiet sleep (QS), and heart rate (HR) changes recorded for both arousal and non-arousal responses. Changes in HR (DeltaHR%) were calculated as the relative differences between baseline HR (BHR) and either MaxHR (arousal) or MinHR (non-arousal). Comparisons of HR changes between sleep states and postnatal ages were made with two-way anova for repeated measures and between groups with two-way anova. The increase in HR (DeltaHR%) was greater in term than preterm infants (P < 0.05), but only at 2-3 weeks corrected postnatal age (CPA). In preterm infants, there were no differences in BHR between sleep states, whereas in term infants, BHR was higher in AS than in QS at 2-3 weeks and 2-3 months of age. The smaller DeltaHR% to arousing stimuli in preterm infants compared with term infants at 2-3 weeks suggests that cardiac sympathetic activity in preterm infants may be lower than in term infants. This mechanism may account for the increased risk for SIDS of preterm infants.     

Prone sleeping impairs circulatory control during sleep in healthy term infants: implications for SIDS

STUDY OBJECTIVES: To determine the effects of sleeping position on development of circulatory control in infants over the first 6 months of postnatal age (PNA). DESIGN: Effects of sleeping position, sleep state and PNA on beat-beat heart rate (HR) and mean arterial pressure (MAP) responses to a head-up tilt (HUT) were assessed during sleep in infants at 2-4 wks, 2-3 mo and 5-6 mo PNA. MEASUREMENTS: Daytime polysomnography was performed on 20 full-term infants (12 F/8 M) and MAP was recorded continuously and noninvasively (Finometer). HUTs of 15 degrees were performed during active sleep (AS) and quiet sleep (QS) in both the prone and supine sleeping positions. MAP and HR data were expressed as the percentage change from baseline, and responses were divided into initial, middle and late phases. RESULTS: In the supine position HUT usually resulted in an initial increase (P < 0.05) in HR and MAP, followed by decreases (P < 0.05) in HR and MAP in the middle phase; subsequently HR and MAP returned to baseline in the late phase. By contrast, in the prone position the initial HUT-induced rises in HR and MAP were usually absent, and at 2-3 mo MAP actually decreased (P < 0.05); subsequently HR but not MAP returned to baseline. At 2-3 mo, MAP was lower (P < 0.05) in prone than supine sleeping throughout the HUT. CONCLUSIONS: Prone sleeping alters MAP responses to a HUT during QS at 2-3 mo PNA. Decreased autonomic responsiveness may contribute to the increased risk for SIDS of infants sleeping in the prone position.     

Sleep position alters arousal processes maximally at the high‐risk age for sudden infant death syndrome

An impaired ability to arouse from sleep may play an important role in the pathogenesis of sudden infant death syndrome (SIDS). This study aimed to investigate the effects of prone sleeping on the nature of both induced and spontaneous arousal responses in infants. Thirteen healthy term infants were studied longitudinally at 2–4 weeks, 2–3 months and 5–6 months postnatal age. A pulsatile jet of air to the nostrils was used to induce arousal from both active sleep and quiet sleep in both prone and supine positions. For each stimulus, arousals were classified as sub‐cortical activations and cortical arousals, scored using physiological and electroencephalogram changes and expressed as a percentage of the total number of arousals. Spontaneous arousals were similarly analysed. Increased proportions of cortical arousals, hence decreased proportions of sub‐cortical activations, were observed in the prone position at 2–3 months. This distinct peak in the proportion of cortical arousals occurred regardless of sleep state and regardless of whether the arousal occurred spontaneously or was induced by air‐jet stimulation. The nature of arousal responses in healthy term infants is altered in the prone sleeping position at 2–3 months after birth, the age where SIDS incidence is highest. We postulate that a greater propensity for cortical arousal may be a protective mechanism to promote complete arousal in a vulnerable sleeping position and/or a vulnerable period of maturation. Inadequate or incomplete cortical arousals may explain the increased risk of SIDS associated with the prone position at this age.     

Effect of hypoxia on ventilatory and arousal responses to CO2 during NREM sleep with and without flurazepam in young adults

We examined the ventilatory response to CO2 at two levels of oxygenation during wakefulness and sleep in healthy young adults before and after the ingestion of a single dose of 30 mg flurazepam. Progressive hypercapnia was produced at two levels of arterial O2 saturation (greater than 99 and 87%) by having subjects re-breathe from a tight-fitting face mask and a reservoir bag containing gas mixtures with two different O2 concentrations. Ventilation was measured with an inductive plethysmograph. O2 saturation was measured with an ear oximeter. Sleep was monitored using standard techniques by recording the electroencephalogram, eye movements, and chin electromyogram. During wakefulness, hypoxia increased the slope of the ventilatory response to CO2 and shifted the response slightly to the left. NREM sleep lowered the slope of the CO2 response under both hyperoxic and hypoxic conditions. The slope of the hyperoxic CO2 response curve was not affected by flurazepam during wakefulness or sleep. After administration of flurazepam to the subjects, the shift of the CO2 response curve to the left produced by hypoxia (additive effect) during NREM sleep was slightly less as compared to control, but hypoxia still increased the slope of the CO2 ventilatory response. During hypoxic hypercapnia, the PCO2 at arousal from sleep was significantly lower than during hyperoxic hypercapnia, but the level of ventilation at arousal during hypercapnia was similar in the control condition and after flurazepam. We conclude that (a) both natural and flurazepam-induced sleep depress ventilatory responses to hyperoxic and hypoxic hypercapnia and alter, in a complex fashion, the effects of hypoxia and hypercapnia on ventilation; and (b) hypoxia and hypercapnia interact as arousal stimuli in both natural and flurazepam-induced sleep.     

Mild hypoxia does not suppress auditory arousal from NREM sleep

STUDY OBJECTIVES: The depressive effects of hypoxia on the central nervous system are well known. The purpose of this study was to determine the influence of mild overnight hypoxia on the ability of healthy individuals to arouse from non-rapid-eye-movement (NREM) sleep to auditory tones. DESIGN: Randomized cross-over. SETTING: Participants slept in a sound-insulated room with the physiologic recordings and experimental interventions controlled from a separate room. PARTICIPANTS: Eleven healthy men aged 18 to 24 years. Interventions: On separate nights, participants were exposed to mild overnight hypoxia (SaO2 approximately 90%) or medical air in single-blind fashion. During established sleep, subjects were administered 1 of 10 auditory tones (500 Hz, 54-90 dB, 5 seconds duration) via earphones, or a sham tone (recording period with no tone). MEASUREMENTS AND RESULTS: The probability and intensity of arousal responses in the 30 seconds following tones or shams were compared between gas conditions and between stage 2 and slow-wave sleep. Arousal probability and intensity increased with tone intensity and were significantly lower during slow-wave compared with stage 2 sleep but were not different between hypoxia and normoxia nights. CONCLUSION: These data suggest that mild overnight hypoxia does not impair the neural mechanisms involved in arousal from sleep to auditory stimuli.     

Sleep and waking states in infancy: normative studies

Twelve-hour polygraphic recordings were obtained in 20 normal healthy term infants at 1 week of age, at monthly intervals up to 4 months, and at 6 months of age. Each minute of these recordings was coded into active sleep (AS), quiet sleep (QS), wakefulness (AW), or indeterminate (IN) based on polygraphic and behavioral variables. For each state, a dozen variables were computed with the help of a laboratory computer. Together these variables describe trends in the development of sleep and wakefulness in the laboratory: an increase in QS and a concomitant decrease in AS, an increase in sustained episodes of these states, and continuous sleep onset in AS throughout this time span. Considerable variability appears to characterize immature sleep patterns, but a reduction in variability was noted between 3 and 4 months of age. The number of sustained sleep-state episodes and the percentage of AS and IN proved to be stable characteristics of individual infants. The large variability among and within infants sheds doubt on the usefulness of polygraphic monitoring of sleep states for early detection of abnormalities.     

Acute cardiovascular responses to arousal from non-REM sleep during normoxia and hypoxia.

STUDY OBJECTIVES: There is uncertainty concerning the relative contribution of arousal, chemoreceptor stimulation, and their potentially interactive effects, to the acute cardiovascular changes observed during sleep in patients with sleep-disordered breathing. The purpose of this study was to compare cardiovascular responses (heart rate, skin blood flow, and pulse transit time, a non-invasive measure of arterial wall stiffness) to auditory induced arousal from stage 2 sleep under conditions of normoxia and overnight mild hypoxia. DESIGN: Randomised crossover. SETTING: Sleep Disorders Unit in a 270-bed teaching hospital. PARTICIPANTS: Eleven healthy male subjects. INTERVENTIONS: Subjects slept wearing a facemask and breathed room air (one night; SaO2 approximately 98%) or an hypoxic gas mixture (two nights; SaO2 approximately 92%). Once in stage 2 sleep, subjects were administered one of 10 auditory tones (500 Hz, range 54-90 dB, 5-sec duration) via earphones or a sham tone (recording with no tone). MEASUREMENTS AND RESULTS: Cardiovascular responses were examined beat-by-beat for 20 seconds before and 30 seconds after auditory tones associated with arousals (3-10 second EEG changes) and after sham tones. Sleep efficiency and the percentage of sleep spent in each stage were not different between hypoxia and normoxia nights. Baseline heart rate was elevated on hypoxia nights compared with normoxia nights (59.5+/-1.7 vs. 54.4+/-1.6 b x min(-1), p=0.007). Heart rate, pulse transit time, and skin blood flow showed significant changes after arousal consistent with rapid parasympathetic withdrawal and sympathetic nervous system activation. No changes were observed after sham tones. There were no differences in time course or magnitude of cardiovascular responses between hypoxia and normoxia nights. CONCLUSIONS: We conclude that while mild hypoxia stimulates autonomic activity it does not augment the cardiovascular response to arousal from stage 2 sleep in normal subjects.     

Ambient temperature is associated with changes in infants' arousability from sleep

STUDY OBJECTIVE: To evaluate the influence of ambient temperature on infants' arousability from sleep. DESIGN: Two groups of healthy infants with a median age of 11 weeks were recorded polygraphically during one night: 31 infants were studied at 24 degreesC and 31 infants at 28 degreesC. To determine their arousal thresholds, the infants were exposed to white noises of increasing intensities during REM and NREM sleep. Arousal thresholds were defined by the auditory stimuli needed to induce arousals. SETTING: N/A. PATIENTS or PARTICIPANTS: N/A. INTERVENTIONS: N/A. MEASUREMENTS and RESULTS: The arousal thresholds decreased across the night in the infants sleeping at 24 degreesC (p=.017). The finding was not found for the infants sleeping at 28 degreesC. When analyzing the arousal responses according to time of the night, it was found that the auditory thresholds were significantly higher at 28 degreesC than at 24 degreesC between 03:00 hr and 06:00 hr (p=.003). These findings were only seen in REM sleep. CONCLUSION: High ambient temperature could add to the difficulty to arouse from REM sleep in the late hours of the night.     

Polysomnographic sleep and waking states are similar in subsequent siblings of SIDS and control infants during the first six months of life

Twenty-five subsequent siblings of infants who died of Sudden Infant Death Syndrome (SIDS) underwent 12-h overnight polygraphic recordings during the first week of life and at 1, 2, 3, 4, and 6 months of age. The polygraphic tracings from these infants were compared with those from 25 infants without a family history of SIDS. One dozen sleep and waking parameters were examined including state transition probabilities, the ratio between quiet sleep (QS) and active sleep (AS), the incidence and duration of sustained states and the stability of an infant's sleep and waking during the first half year of life. Variability within and between infants was marked with a reduction of variability in measures of QS at 3 months and of AS at 4 months of age. The similarities between subsequent siblings of SIDS and control infants far outweighted the differences. However, subsequent siblings exhibited a tendency, once asleep, to remain asleep longer than controls. This finding was observed in a comparison of 20 infants in each group. When five infants were added to each group, infants in both groups tended to awaken equally from QS, but once in AS the subsequent siblings tended to proceed into QS instead of awaken as the controls did.     

Development of sleep states in normal premature and full-term newborns

The aims of our study were: 1) to answer the question "Do sleep states exist in normal premature infants;" 2) to analyze the development of sleep cycle and sleep state characteristics in premature and full-term newborns. Polygraph recordings were done on 38 normal, appropriate for gestational age newborns, born at 30 to 41 weeks (w) of gestation. All infants fell asleep in active sleep (AS). Postwaking AS was significantly shorter than the next AS. Mean sleep cycle duration increased from approximately 46 min at 31-34 w of conceptional age (CA) to 70 min. at 35-36 w CA. In all infants we observed stable, greater than 5 min AS and quiet sleep (QS) periods, as defined by EEG and REM criteria. Indeterminate sleep was about 30% of the total sleep cycle at 31-34 w; it decreased to 12% at 35-36 w. Both duration and percentage of AS and QS significantly increased at 35-36 w and remained stable up to 39-41 w CA. Values of QS were significantly reduced when defined by additional criteria (respiratory rate, tonic chin EMG or motility). Concordance of QS criteria was not significantly better in older versus younger groups of infants. At all ages, AS values were insensitive to changes in the criteria chosen to define them. The contrast, starting from 31-34 w CA, between AS and QS as defined by EEG and REM criteria could account for state differences in the control of many physiological variables in prematures.     

低氧对人成熟树突状细胞MMP9/TIMP1及CCR7 表达的影响

目的： 观察低氧对人单核细胞来源成熟树突状细胞（mDCs）趋化因子受体（CCR7）,基质金属蛋白酶-9（MMP-9）及其组织抑制剂（TIMP-1）表达的影响,以期为改进DCs疫苗体内迁移能力低下提供新策略。方法： 分离制备人外周血单核细胞（PBMCs）,采用体外常规培养体系 ［粒-巨噬细胞集落刺激因子（GM-CSF）与白细胞介素-4（IL-4）共同刺激］ 诱导DCs,于诱导后第5 d加入TNF-α促成熟,48 h后将mDCs置低氧环境下（1％ O2、5％ CO2、94％ N2）分别继续培养6 h、12 h,设常氧对照组（21% O2、5% CO2）,收获细胞及培养上清;采用RT-PCR技术检测MMP-9、TIMP-1及CCR7的表达;明胶酶谱法检测培养上清中MMP-9的水平与活性,流式细胞术检测mDCs表面CCR7的表达。结果： RT-PCR及酶谱实验结果显示,低氧6 h、12 h处理组mDCs MMP-9水平显著下降;与对照组比较,各低氧处理组mDCs均未检测到TIMP-1 mRNA表达的变化;转录及细胞表面表达分析结果显示,与常氧对照组比较,低氧6 h处理组趋化因子受体CCR7表达显著降低,而12 h处理组其表达显著回升至近常氧组水平。结论： 低氧下调mDCs MMP-9表达,破坏MMP-9/TIMP-1平衡,可能是DCs疫苗体内迁移能力低下的主要因素之一。趋化因子受体CCR7在mDCs对低氧应答中可能起重要作用。