Gestational age at birth affects maturation of baroreflex control.

OBJECTIVES: To assess the effect of prone sleeping, the major risk factor for sudden infant death syndrome, in the control of blood pressure (BP) in preterm infants born across a range of gestational ages. STUDY DESIGN: Daytime polysomnography was performed at 2-4 weeks, 2-3 months, and 5-6 months postterm age. The participants were 21 very preterm (mean gestation 29.4 ± 0.3 weeks), 14 preterm (mean gestation 33.1 ± 0.3 weeks), and 17 term (mean gestation 40.1 ± 0.3 weeks). BP was measured via a Finometer cuff (Finapres Medical Systems, Amsterdam, The Netherlands) placed around the wrist. Data were recorded both supine and prone. Baroreflex sensitivity (BRS) was calculated via cross-spectral analysis of spontaneous fluctuations in BP. RESULTS: BRS was lower in the prone position in very preterm infants at 2-4 weeks in active sleep (P < .05). Maturation of BRS was delayed in very preterm compared with both preterm and term infants. CONCLUSIONS: Maturation of BRS after term-equivalent age is altered in very preterm infants. Reduced BRS may result in an impaired ability of very preterm infants to respond to cardiovascular stress during infancy and may predispose them to cardiovascular disease later in life.

Preterm lambs given intravenous dopamine show increased dopamine in their cerebrospinal fluid.

AIM: Dopamine is used as an inotropic medication in preterm infants. The preterm human blood brain barrier (BBB) is permeable to intravascular dopamine, and the impact of exogenous dopamine on the preterm brain remains unknown. The preterm lamb model may be suitable for studying the cerebral impact of dopamine therapy whether its BBB permeability is similar to preterm human infants. We aimed to examine BBB permeability to exogenous dopamine in the preterm lamb, by measuring dopamine levels in the cerebrospinal fluid (CSF). METHODS: Nine preterm foetal lambs (125-130 days, term = 147 days) were given either dopamine at 10 µg/kg/min (dopamine, n = 4) or saline (control, n = 5). CSF, and plasma samples were taken for dopamine assay. RESULTS: The median (range) baseline CSF dopamine level for the combined control and dopamine groups (n = 9) was 0.10(0.03-0.16) ng/mL, and baseline plasma dopamine was 0.30(0.13-0.84) ng/mL. The dopamine lambs showed increase in CSF dopamine to 3.91(1.87-11.35) ng/mL with plasma dopamine increased to 14.2 (9.1-57.9) ng/mL. No change was found in the control lambs. CONCLUSION: In the preterm lamb, the BBB permeability and pharmacokinetics to dopamine infusion are similar to findings in the preterm human infant, supporting applicability of the preterm lamb model for studying effects of dopamine infusion in the preterm human brain.

Autonomic dysfunction in children with sleep disordered breathing.

PURPOSE: Sleep disordered breathing (SDB) has adverse effects on cardiovascular health in adults, partly due to changes in autonomic activity. However, there have been limited studies in children. We analysed the impact of SDB and sleep stage on autonomic control of heart rate in 7-12-year-old children, utilizing spectral heart rate variability (HRV) as a measure of autonomic activity. METHODS: Eighty children underwent overnight polysomnography. Subjects were grouped according to their obstructive apnoea-hypopnoea index (OAHI): controls, OAHI ≤1 event/h and no history of snoring; primary snorers (PS) OAHI ≤1, Mild (OAHI 1-5) and moderate/severe (MS) OAHI >5. HRV was analysed during Wake, nonrapid eye movement (NREM) 1&2, slow wave sleep (SWS) and REM. RESULTS: Compared with controls, total power, low (LF) and high frequency (HF) power were reduced in all SDB severities during REM. LF/HF ratio was less in MS SDB (median = 0.34; range, 0.20-0.49; p < 0.05) versus controls (0.38; 0.26-0.55; p < 0.05) and PS (0.39; 0.23-0.57; p < 0.05) during SWS. In all groups, total power, LF and HF power were highest during NREM 1&2 while LF/HF ratio was lowest during SWS. Blood pressure was elevated in SDB in all sleep states. CONCLUSIONS: HRV was altered in 7-12-year-old children with SDB, which may signify an overall depression of autonomic tone, perhaps a consequence of their elevated blood pressure during sleep coupled with repeated exposure to SDB event-related cardiovascular disturbance. Further research is warranted to elucidate the long-term effects on the cardiovascular system of subjects exhibiting impaired HRV and elevated BP in childhood.

EEG spectral analysis of apnoeic events confirms visual scoring in childhood sleep disordered breathing.

PURPOSE: This study compared electroencephalogram (EEG) spectral analysis with standard visual scoring to assess the validity of clinical classification of arousals at respiratory event termination in children with obstructive sleep apnoea (OSA). METHODS: Twenty children (six M/14 F) aged 7-12 years, diagnosed with moderate to severe OSA participated in this study. Overnight polysomnography was performed, and sleep stages and arousals visually scored using clinical paediatric measures. The EEG was spectrally analysed in six 5-s epochs across respiratory events, namely two consecutive 5-s epochs pre-event onset and a 5s epoch post-event onset, 5-s before event termination, and two contiguous 5-s epochs post-event termination. EEG spectral power distribution was compared across respiratory events visually categorised as full cortical arousals, subcortical activations, or non-arousals using specialised software (Sleep Research System 5.0). RESULTS: There was no difference in power spectra between events in REM and NREM sleep and these were combined. There was a statistically significant fall from pre-arousal baseline values in delta and theta spectral power at respiratory event terminations associated with cortical arousals only. No change in power was detected at respiratory event terminations associated with subcortical activations or non-arousals. CONCLUSIONS: The lack of significant EEG spectral power changes at respiratory event terminations not associated with visually identified cortical arousals indicates undetected micro-arousals are not present. The results support the validity of clinical classifications of arousals at respiratory event termination.

Postnatal development of baroreflex sensitivity in infancy.

Baroreflex sensitivity (BRS) using spontaneous sequence analysis in the time domain is not fully applicable in infancy, as the time delay for heart period to change (heart period delay, HPD) after an arterial pressure change is unknown. We estimated and compared HPD and BRS in the frequency (BRS(sp), HPD(sp)) and time domains (BRS(seq), HPD(seq)) from systolic blood pressure (SBP) and heart period fluctuations. Continuous SBP, using photoplethysmography, and heart period measurements were performed on 30 term infants at 2-4 weeks, 2-3 months and 5-6 months postnatal age. Cross-spectral analysis between SBP and heart period fluctuations was used to estimate BRS(sp) and HPD(sp). Spontaneous sequence analysis was used to estimate BRS using a fixed beat delay of 1-12 beats (BRS(seq)) or a variable delay identified by a novel method accounting for epoch-epoch variability in HPD (BRS(seqvar)). HPD(sp) averaged 3.4 s (approximately 7 beats); BRS(sp) averaged 11.4 ms mmHg(1). BRS(seq) and BRS(seqvar) were consistently lower than BRS(sp) (P < 0.05), but the three BRS estimates were strongly correlated using a HPD of approximately 5-6 beats. BRS(seqvar) resulted in the average estimate (8.9 ms mmHg(1)) closest to BRS(sp) and overall had the strongest correlation with BRS(sp) (R(2) = 0.61; P < 0.001). All three BRS estimates increased progressively with postnatal age, with BRS(sp) averaging 6.4, 10.5 and 16.0 ms mmHg(1) at 2-4 weeks, 2-3 months and 5-6 months, respectively (P < 0.05). Accounting for the HPD of infancy provides estimates of BRS in the time domain that closely parallel spectral estimates, and provides a novel analytical tool to assess normal development and dysfunction of the baroreflex in infants.

The heart rate response to spontaneous arousal from sleep is reduced in children with Down syndrome referred for evaluation of sleep-disordered breathing.

Arousal from sleep in healthy adults is associated with a large, transient increase in heart rate (HR). Individuals with Down syndrome (DS) have attenuated cardiovascular responses to autonomic tests during wakefulness. We tested the hypothesis that the HR response to arousal from sleep is reduced in children with DS and obstructive sleep apnea (OSA) compared with healthy children. Twenty children aged 3-17 yr referred for investigation of sleep-disordered breathing (10 DS, and 10 OSA controls) matched for age and obstructive apnea/hypopnea index underwent routine overnight polysomnography. In addition, 10 nonsnoring controls from the general community were studied. Beat-by-beat HR was analyzed from 15 s pre- to 15 s post-spontaneous arousals and compared between groups using two-way ANOVA with repeated measures. Data are presented as means + or - SE. For both rapid eye movement (REM) and non-REM (NREM), arousals were associated with a significant increase in HR in all groups (peak response NREM: DS, 118 + or - 1% at 3 s; OSA controls, 124 + or - 2% at 4 s; and healthy controls, 125 + or - 3% at 4 s; and peak response REM: DS, 116 + or - 2% at 4 s; OSA controls, 123 + or - 3% at 4 s; and healthy controls, 125 + or - 4 at 4 s; P < 0.001 for all). Post hoc analysis revealed that HR in the DS group was significantly lower than both control groups at 1-4 s in NREM and at 4 to 5 s in REM (P < 0.05 for all). In conclusion, the HR response to spontaneous arousal from sleep is reduced in children with DS and OSA compared with healthy children. This attenuated cardiovascular response could be due to reduced sympathetic activation or blunted vagal withdrawal and may have implications for the child with DS and OSA.

Influence of swaddling experience on spontaneous arousal patterns and autonomic control in sleeping infants.

OBJECTIVE: To investigate the effects of swaddling experience on infant sleep, spontaneous arousal patterns and autonomic control. STUDY DESIGN: Twenty-seven healthy term infants, who were routinely swaddled at home (n=15) or "naïve" to swaddling (n=12), were monitored with daytime polysomnography in swaddled and unswaddled conditions at 3 to 4 weeks and at 3 months after birth. RESULTS: Swaddling did not alter sleep time, spontaneous arousability, or heart rate variability in routinely swaddled infants at either age. During active sleep at 3 months, cortical arousal frequency was decreased, and total sleep time was increased by swaddling in infants who were naïve to swaddling. Heart rate variability when swaddled was also highest in the naïve group. CONCLUSIONS: The effects of infant swaddling on sleep time, arousability, and autonomic control are influenced by previous swaddling experience. Infants in the naïve to swaddling group exhibited decreased spontaneous cortical arousal, similar to responses observed in future victims of sudden infant death syndrome. Infants in unfamiliar sleeping conditions may therefore be more susceptible to cardiorespiratory challenges that fail to stimulate arousal and may lead to sudden infant death syndrome.

Acute and chronic effects of endotoxin on cerebral circulation in lambs.

The impact of endotoxemia on cerebral endothelium and cerebral blood flow (CBF) regulation was studied in conscious newborn lambs. Bacterial endotoxin [LPS, 2 microg/kg iv] was infused on 3 consecutive days. Cerebrovascular function was assessed by monitoring CBF and cerebral vascular resistance (CVR) over 12 h each day and by the endothelium-dependent vasodilator bradykinin (BK) (n = 10). Inflammatory responses were assessed by plasma tumor necrosis factor-alpha (TNF-alpha, n = 5). Acutely, LPS disrupted the cerebral circulation within 1 h, with peak cerebral vasoconstriction at 3 h (CBF -28 and CVR +118%, P < 0.05) followed by recovery to baseline by 12 h. TNF-alpha and body temperature peaked approximately 1 h post-LPS. BK-induced vasodilatation (CVR -20%, P < 0.05) declined with each LPS infusion, was abolished after 3 days, and remained absent for at least the subsequent 5 days. Histological evidence of brain injury was found in four of five LPS-treated newborns. We conclude that endotoxin impairs cerebral perfusion in newborn lambs via two mechanisms: 1) acute vasoconstriction (over several hours); and 2) persistent endothelial dysfunction (over several days). Endotoxin-induced circulatory impairments may place the newborn brain at prolonged risk of CBF dysregulation and injury as a legacy of endotoxin exposure.

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.

Determining sleep quality in children with sleep disordered breathing: EEG spectral analysis compared with conventional polysomnography.

STUDY OBJECTIVES: To identify the extent of sleep disruption in children with various severities of sleep disordered breathing (SDB) using both conventional visually scored assessment of sleep stages and arousal indices together with EEG power spectral analysis. DESIGN: Sleep stages and power spectral analysis of the sleep EEG in children with varying severities of SDB with matched control subjects with no history of snoring were compared across the whole night, across sequential hours from sleep onset, and across sleep stages. MEASUREMENTS: Overnight polysomnography was performed on 90 children (49M/41F) aged 7-12 y with SDB and 30 age-matched healthy controls (13M/17F). Sleep stages were visually scored and the EEG spectra were analyzed in 5-s epochs. RESULTS: Conventional visual scoring indicated that, although sleep duration was reduced in severely affected children, sleep quality during the essential stages of SWS and REM was preserved, as evidenced by the lack of any significant decrease in their duration in SDB severity groups. This finding was supported by the lack of substantial differences in EEG spectral power between the groups over the whole night, within specific hours, and in individual sleep stages. CONCLUSIONS: Both conventional scoring and EEG spectral analysis indicated only minor disruptions to sleep quality in children with SDB when assessed across the night, in any specific hour of the night, or in any specific sleep stage. These results suggest that reduced daytime functioning previously reported in children with SDB may not be due to sleep disruption. We speculate that in children, in contrast to adults, a stronger sleep drive may preserve sleep quality even in severe SDB.

Cerebral arterial and venous contributions to tissue oxygenation index measured using spatially resolved spectroscopy in newborn lambs.

BACKGROUND: Bedside assessments of cerebral oxygenation are sought to monitor cerebral injury in patients undergoing intensive care. Spatially resolved spectroscopy measures tissue oxygenation index (TOI, %) which reflects mixed cerebral arterial and venous oxygenations. We aimed to evaluate arterial and venous components of TOI (cerebral arterial to venous volume ratio [A:V ratio]) in the newborn lamb brain using cerebral arterial and venous blood samples, and to investigate the impact of acute hypoxemia on the A:V ratio and TOI. METHOD: Nine lambs were ventilated with varied inspired oxygen to generate arterial oxygen saturations between 25% and 100%. Cerebral arterial and venous oxygen saturations analyzed using cooximeter of arterial and superior sagittal sinus blood were used to estimate TOI (TOIcox), assuming cerebral A:V ratio of 25:75. TOIcox was compared with the TOI measured by spatially resolved spectroscopy (TOIsrs). Actual cerebral arterial and venous volume fractions were reestimated using TOIsrs = cerebral arterial volume fraction cerebral arterial oxygen saturation + cerebral venous volume fraction*cerebral venous oxygen saturation. RESULTS: Median (range) TOIsrs was 48.5% (32.0-64.1%), and TOIcox was 48.4% (13.7-74.4%), and the two were significantly correlated (R = 0.77). The mean difference between TOIsrs and TOIcox was 2.4% (limits of agreement ± 18.1%). The TOIsrs - TOIcox difference varied with oxygen saturations, with TOIsrs higher than TOIcox at low saturations, and lower at high saturations. Cerebral arterial volume fraction was 22.9-27.5% in normoxia and markedly increased in hypoxemia. CONCLUSION: TOI corresponds with cerebral oxygenation. The variable agreement of TOIsrs with TOIcox may reflect changes in cerebral A:V ratio due to arterial oxygenation-related vasoreactivity.

Stimulus type does not affect infant arousal response patterns.

Previous studies have examined infant arousal responses to various arousal stimuli; however it is unclear whether the patterns of responses to different stimuli are comparable within subjects across early development. The aim of the study was to compare the effects of both respiratory and somatosensory stimulation on arousal processes in the same infants throughout the first 6 months of life. Ten healthy term infants were studied with daytime polysomnography at 2-4 weeks, 2-3 and 5-6 months. Infants were challenged with both hypoxia (15% O(2), balanced N(2)) and a pulsatile air-jet to the nostrils. Stimulus-induced sub-cortical activations (SCA) and cortical arousals (CA) were expressed as percentages of total arousals. Heart rate (HR) changes and electroencephalogram (EEG) desynchronization were also contrasted for the two stimuli. During active sleep (AS), there was no significant effect of stimulus type on proportions of CA at any of the ages studied. During quiet sleep (QS), hypoxia elicited higher CA proportions than the air-jet at 2-3 and 5-6 months (P < 0.01). Overall, HR responses associated with SCA and CA and the duration of EEG desynchronization during CA were similar for both stimuli. Mild hypoxia and nasal air-jet stimulation produce qualitatively similar patterns of arousal responses during the first 6 months of life, supporting the concept of a final common neural pathway of cortical activation. Quantitatively, full CA from QS is more likely with hypoxia, in keeping with it being a life-threatening stimulus. This study supports the nasal air-jet as an appropriate stimulus for assessing developmental patterns of infant arousal process.

Delayed blood pressure recovery after head-up tilting during sleep in preterm infants.

Dramatic changes in cardiovascular control occur in sleep during infancy, when sleep time is at a lifetime maximum. In infants born preterm there are significant cardiovascular complications later in life, and also an increased risk for sudden infant death syndrome (SIDS), possibly a result of inadequate compensation to a cardiorespiratory challenge in sleep. We aimed to examine the consequences of preterm birth on heart rate (HR) and blood pressure (BP) responses to head-up tilting (HUT) during sleep in infants. Preterm (n = 25) and term (n = 20) infants were studied using daytime polysomnography at 2-4 weeks', 2-3 months' and 5-6 months' term-corrected age (CA). BP was recorded using a photoplethysmographic cuff (Finometer); 15 degrees HUTs were performed during both quiet and active sleep. Preterm infants responded to HUT with increased HR and BP, followed by a bradycardia and a subsequent return of HR and BP to baseline. Overall, HUT responses were similar between term and preterm infants at matched ages. Notably, however, return of BP to baseline was considerably delayed in preterm infants ( approximately 37 beats post-tilt) compared with term infants ( approximately 23 beats post-tilt) at both 2-4 weeks' and 2-3 months' CA (P < 0.05). Our study has demonstrated that preterm infants respond to a BP perturbation with changes in HR that match those of term infants. However, delayed recovery of BP during sleep in the preterm infant may be indicative of underlying deficits or immaturity in vascular function or control, which may contribute to their vulnerability to SIDS and cardiovascular complications later in life.

Minimizing the risks of sudden infant death syndrome: to swaddle or not to swaddle?

OBJECTIVE: To evaluate the effects of swaddling on infant arousability, particularly the progression of subcortical activation (SCA) to full cortical arousal (CA), because impaired arousal may contribute to sudden infant death syndrome. STUDY DESIGN: Healthy term infants, who were routinely swaddled (n = 15) or unswaddled (n = 12) at home, were studied with daytime polysomnography at 3 to 4 weeks and 3 months after birth. When both swaddled and unswaddled, arousability was assessed with a pulsatile jet of air at the nostrils. RESULTS: Larger increases in overall arousal thresholds (SCA plus CA) with swaddling were observed in infants who were easiest to arouse when unswaddled. Swaddling did not alter SCA or CA frequencies of routinely swaddled infants at either age. In infants who were naïve to swaddling, arousal thresholds were increased and CA frequency decreased during swaddled quiet sleep at 3 months. CONCLUSIONS: This study provides a scientific basis for assessing the safety of swaddling in infant care practice. The decreased cortical arousals observed in infants unfamiliar with swaddling may correspond to the increased risk of sudden infant death syndrome for inexperienced prone sleepers.

Changes in cerebral blood flow, cerebral metabolites, and breathing movements in the sheep fetus following asphyxia produced by occlusion of the umbilical cord.

Severe global fetal asphyxia, if caused by a brief occlusion of the umbilical cord, results in prolonged cerebral hypoperfusion in fetal sheep. In this study, we sought evidence to support the hypothesis that cerebral hypoperfusion is a consequence of suppressed cerebral metabolism. In the 24 h following complete occlusion of the umbilical cord for 10 min, sagittal sinus blood flow velocity was significantly decreased for up to 12 h. Capillary blood flow, measured using microspheres, decreased at 1 and 5 h after cord occlusion in many brain regions, including cortical gray and white matter. Microdialysis probes implanted in the cerebral cortex revealed an increase in extracellular glucose concentrations in gray matter for 7-8 h postasphyxia, while lactate increased only briefly, suggesting decreased cerebral glucose utilization over this time. Although these data, as well as the concurrent suppression of breathing movements and electrocortical activity, support the concept of hypometabolic hypoperfusion, the significant increase of pyruvate and glycerol concentrations in dialysate fluid obtained from the cerebral cortex at 3-8 h after cord occlusion suggests an eventual loss of membrane integrity. The prolonged increase of breathing movements for many hours suggests loss of the pontine/thalamic control that produces the distinct pattern of fetal breathing movements.

Maternal smoking impairs arousal patterns in sleeping infants.

OBJECTIVE: Impairment of the arousal process from sleep is thought to be involved in the pathogenesis of sudden infant death syndrome (SIDS). We hypothesized that a greater propensity for cortical arousal in the prone position may, in a normal infant, be a protective mechanism to promote complete arousal in a vulnerable sleeping position, a protection that is absent in SIDS victims. We aimed to examine the arousal process in a group of infants exposed to maternal smoking, who are thus at higher risk for SIDS. DESIGN: Twelve healthy, full-term infants born to smoking mothers were studied using daytime polysomnography at 2 to 4 weeks, 2 to 3 months and 5 to 6 months postnatal age. Data were compared with 13 healthy infants born to nonsmoking mothers. Arousal was induced by pulsatile air-jet stimulation to the nostrils during active and quiet sleep, in both supine and prone positions. For each stimulus, physiologic and electroencephalogram changes were visually assessed and arousal responses were classified as sub-cortical activation or cortical arousal. RESULTS: In smoke-exposed infants, the progression from sub-cortical activation to cortical arousal was depressed at 2 to 4 weeks and 5 to 6 months. There was no effect of maternal smoking observed at 2 to 3 months; however, a significant dose-dependent relationship between cortical activation proportions and urinary cotinine levels was present in both supine and prone positions. CONCLUSION: We have shown that maternal smoking is associated with impaired arousal processes to trigeminal stimulation that may increase the risk for SIDS. This further highlights the importance of public education of the risks of maternal smoking.

Obstructive sleep apnea leads to transient uncoupling of coronary blood flow and myocardial work in humans.

STUDY OBJECTIVES: Obstructive Sleep Apnea (OSA) is associated with a poor prognosis in patients with coronary artery disease. We hypothesized that abnormalities of coronary blood flow (CBF) associated with obstructive apneas may predispose patients to ischemia. We aimed to determine CBF during respiratory events in patients with OSA. SETTING: University Hospital. PATIENTS: Ten subjects undergoing elective percutaneous coronary intervention DESIGN: We measured CBF and myocardial work (rate-pressure product [RPP]) in a non-culprit coronary artery in patients sleeping in the cardiac catheterization laboratory. Hemodynamic responses were matched to spontaneously occurring respiratory events. MEASUREMENTS AND RESULTS: Events comprised a mixture of obstructive apneas, central apneas and hypopneas. RPP increased at the termination of each type of respiratory event. Following the rise in RPP, there was a delay, identified with breakpoint analysis, before CBF began to increase (P<0.001) that differed in duration with event type: 8 sec for obstructive apnea, 5 sec for central apnea, and 4 sec for hypopnea. The delay in CBF with obstructive apnea was associated with an increase in coronary vascular resistance of 16% +/- 4% (P < 0.05). Stepwise multilinear regression analysis showed the increase in CBF was predicted by the rise in RPP (R=0.52, P<0.001) and presence of arousal from sleep (R=0.30, P<0.05), but not the degree of O2 desaturation. CONCLUSION: Following obstructive apneas there is a transient uncoupling of CBF from myocardial work and an increase in CVR. This disturbed flow-metabolic coupling may lead to nocturnal myocardial ischemia in patients with both OSA and coronary artery disease.

Cardiovascular variability during periodic leg movements in sleep in children.

STUDY OBJECTIVES: Periodic leg movements in sleep (PLMS) are episodes of repetitive and stereotypic leg movements occurring during sleep. In adults, research indicates that PLMS affects sleep quality and duration and are associated with a shift to relatively greater sympathetic influence over cardiovascular variables. However, little research has been performed to investigate the effect of PLMS episodes on cardiac autonomic control in children. This study aimed to quantify the effect of PLMS episodes during NREM2 sleep on heart rate variability (HRV) measures of sympathovagal balance in children. PARTICIPANTS: Overnight polysomnography data from 20 children (7-12 y) referred for assessment of sleep disordered breathing (SDB) were analyzed retrospectively. Ten children with episodes of PLMS were matched for age and SDB severity with a control group of 10 children without PLMS episodes. RESULTS: The LF/HF ratio was significantly higher in the PLM+ compared with both the PLM- periods from PLMS subjects (P < 0.001) and the periods from the control group (P < 0.001). However, this effect could not be parsimoniously interpreted due to the likelihood that leg movements had a direct effect on the lower frequencies. Analysis of the ratio PLM+ to PLM+ plus PLM- indicated parasympathetic inhibition during periods of periodic leg movement and the onset of individual leg movements were associated with cardiac acceleration followed by a return to pre-movement levels. CONCLUSION: This study identified vagal inhibition in association with episodes of PLMS in children. Rapid cardiac acceleration occurring concurrently with the onset of individual leg movements also suggested decreased vagal activity associated with the movements.

Acute cardiovascular changes with obstructive events in children with sleep disordered breathing.

STUDY OBJECTIVES: Obstructive apneas in adults are associated with acute changes in blood pressure (BP) and heart rate (HR) that may contribute to poor cardiovascular outcome. Children with sleep disordered breathing (SDB) are similarly at risk for cardiovascular complications. We aimed to test the hypothesis that BP and HR are augmented during obstructive events in children equivalent to levels reported in adults. DESIGN: Beat-by-beat mean arterial pressure (MAP) and HR were analyzed over the course of obstructive events (pre, early, late, and post-event) during NREM and REM sleep and compared using 2-way ANOVA with post hoc analyses. SETTING: Pediatric sleep laboratory. PATIENTS OR PARTICIPANTS: 30 children (15M/15F) aged 7-12 y referred for investigation of SDB INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: All children underwent overnight polysomnography with continuous BP recording. MAP and HR increased significantly from late to post event in both sleep states (mean +/- SEM, NREM: MAP, 74 +/- 3 to 93 +/- 3 mm Hg; HR, 76 +/- 2 to 97 +/- 2 bpm. REM: MAP, 76 +/- 3 to 89 +/- 3 mm Hg; HR, 76 +/- 2 to 91 +/- 2 bpm. P < 0.05 for all). NREM sleep state and arousal from sleep were significant independent predictors of the magnitude of cardiovascular change from late to post event (P < 0.05 for all). CONCLUSIONS: Children with SDB experience significant changes in HR and BP during obstructive events with magnitudes that are similar to levels reported in adults. These changes are more pronounced during NREM sleep and with arousal. These acute cardiovascular changes may have important implications for poor cardiovascular outcome in children with OSA as repetitive cardiovascular perturbations may contribute to the development of hypertension.

Cerebral sympathetic nerve activity has a major regulatory role in the cerebral circulation in REM sleep.

Sympathetic nerve activity (SNA) in neurons projecting to skeletal muscle blood vessels increases during rapid-eye-movement (REM) sleep, substantially exceeding SNA of non-REM (NREM) sleep and quiet wakefulness (QW). Similar SNA increases to cerebral blood vessels may regulate the cerebral circulation in REM sleep, but this is unknown. We hypothesized that cerebral SNA increases during phasic REM sleep, constricting cerebral vessels as a protective mechanism against cerebral hyperperfusion during the large arterial pressure surges that characterize this sleep state. We tested this hypothesis using a newly developed model to continuously record SNA in the superior cervical ganglion (SCG) before, during, and after arterial pressure surges occurring during REM in spontaneously sleeping lambs. Arterial pressure (AP), intracranial pressure (ICP), cerebral blood flow (CBF), cerebral vascular resistance [CVR = (AP - ICP)/CBF], and SNA from the SCG were recorded in lambs (n = 5) undergoing spontaneous sleep-wake cycles. In REM sleep, CBF was greatest (REM > QW = NREM, P < 0.05) and CVR was least (REM < QW = NREM, P < 0.05). SNA in the SCG did not change from QW to NREM sleep but increased during tonic REM sleep, with a further increase during phasic REM sleep (phasic REM > tonic REM > QW = NREM, P < 0.05). Coherent averaging revealed that SNA increases preceded AP surges in phasic REM sleep by 12 s (P < 0.05). We report the first recordings of cerebral SNA during natural sleep-wake cycles. SNA increases markedly during tonic REM sleep, and further in phasic REM sleep. As SNA increases precede AP surges, they may serve to protect the brain against potentially damaging intravascular pressure changes or hyperperfusion in REM sleep.