Arterial Blood Pressure Response to Transient Arousals From NREM Sleep in Nonapneic Snorers With Sleep Fragmentation

Arterial Blood Pressure Response to Transient Arousals From NREM Sleep in Nonapneic Snorers With Sleep Fragmentation* Frederic Lofaso, MD; Francoise Goldenberg, MD ; Marie Pia d'Ortho, MD; Andre Coste, MD; and Alain Harf, MD

Study objectives: To assess the hemodynamic effects of graded arousals during nonrapid eye movement (NREM) sleep in patients with partial upper airway obstruction during sleep without obstructive sleep apnealhypopnea, overnight beat-to-beat BP was recorded in six patients. Setting: At the end of each nonapneic obstructive event, EEG responses were graded as follows: grade 2, grade 1, and grade 0 were defined as increased high-frequency EEG lasting> 15 s, 3 to 15 s, and no EEG arousals according to the American Sleep Disorders Association, respectively. Measurements and results: The following were observed during grade 0, 1, and 2 EEG patterns (mean±SD): systolic pressure increased b y 7.I±1.5, I1.7±1.9, and I4.2±3A (p<0.005) , respectively; diastolic pressure increased by 4.6±0.6, 6.7±1.7, and 9.4±3.0 (p<0.005), respectively; heart rate increased by 2.9±OA, 3.9±2.2, and 8.6 ± 4.6 (p < 0.005), respectively. Conclusions: We conclude that nonapneic-nonhypopneic obstructive events are followed by arterial systemic pressure increa se s whose magnitude vari es with the grade of th e arousal. (CHE ST 1998; 113:985-91 ) Key words: arousal; blood pressure; snoring; upp er airway resistance Abbreviations: ASDA=American Sleep Disord ers Association; NREM=no rapid eye movem ent ; OSAS=obstructive sleep apnea syndro me; RE M = rapid eye moveme nt

I t has long been recognized that the obstructive

sleep apnea syndrom e (OSAS) is associated with acute increases in arterial BP at the termination of respiratory events.' This phenomenon has been ascribed to hypoxemia.s" to the hemodynamic effects of intrathora cic pressure changes ,4-6 to interruptions in respirati on.?:" and to disruption of sleep.1O-l4 For othe rs, the magnitude of the increase in arterial BP does not vary with the grade of the arousal.!" Recent reports have dem onstrated that an abnormal amount of breathi ng effort due to partial upper airway obstruction , even in the absence of sleep apnea or oxygen desaturation, can disru pt slee p architecture by causing arcusals.lv!" The purp ose of this study was to examine whe ther the termination of nonapneic-nonhypopn eic obstructive events coincide s with an abrupt increase in arterial BP similar to 'From the Service de Physiologie-Explorations Fonctionnelles, Institut National de la Sante at de Ia Recherche Medicale, H6pital Henri Mondor, Cret eil, Franc e . Manuscript received January 28, ]997; revision accepted Octob er 7, ] 997. Reprint requ ests: F. Lofaso, MD , Seruice de Physiologie-Explorations Fonctionn elles, Hopit al Henri Mondor, 94010 Creteil, France

that seen in OSAS, despite the absenc e of oxygen desaturation and interruption of ventilation. In addition, the relatio nship between the magn itude of the arterial BP increase and the change in the EEG pattern was examined. We recorded acute increases in syste mic arterial BP at the tim e of the abrupt reduction in upper airway obstruction, and found that this BP rise was primarily du e to slee p disruption .

MATERIALS AN D M ETHOD S

Patients

Six men wer e studied. Mean age was 45± 11 years (range, 33 to 65 years ). Mean body mass index was 27::':3 kglm2 • All six subjects had heavy snoring confirm ed by a roommate or bed partn er and daytime sleepiness with an Epwor th sleepin ess scale!" > 10. Patient s wer e included in the study after a home polysomnography study, including EEG (C4 -A1, C 3 -A2 ) , electro -oculography, chin electro myography, electromyography of the tibialis ante rior muscle of both legs, oron asal airflow recordin gs, rib cage movement recordi ngs (Multi-Parameter Analysis record er 21Medilog 9200; Oxford Medical Instru ments; Abingdon, England ), and arte rial pu lse oximetry (Nellcor BS; Nellcor Inc; Hayward Calif). · CHEST / 113 / 4 / APRIL, 1998

985

To he eligible for the study, sub jec ts had to have an at-hom e polysomnograph y study th at met th e following crite ria: apn ea hypopn ea index <5/h of sleep (apnea was defin ed as cessa tion of airflow lasti ng ~ 1 0 s and hypopn eu as a :=:50% lall in oronasal airflow for 10 s or a full ill oro nasal airflow with an oxygen desaturation ~ 3% of the preced ing base line level); and arousal ind cx > lO/h of slee p (arousals wer e det ected on the basis of an abrupt shift in EEG frequen cy, includin g alpha and/or frequen cie s > 16 Hz but not spind les, and wer e sco re d according to standa rd crite ria Hl). To re late clinical co mplaints and slee p fragmentation to an upper airway obstruction without obs tru ctive slee p apn eu/hypopnea , a sleep polygraph ic investi gation , includ ing respiratory effor t evaluation, was pcrform cd as recommended.20 Th e study was approved by the Research Ethics Committee of o nr institution, and each subject gave con sen t in acco rdance with the co mmittee's req uirem ents. Clinical Tria l Th e clinical trial cons iste d of a rep eat polysomnograph y study, includi ng EEG (C 4 -A], C 3- A2 ) , electro-oculography, chin electro myograph y, thoracic and abdo minal movem ent recording, and arterial pulse oxime try (Ne llco r BS, Nellcor Inc.). Du ring th e study night , oro nasa l airflow was q uant ified using a tight-fitting facial mask and a No .2 pn eu motachograp h (F leisch; Lau sann e, Switze rland ) connected to a differ en tial pressure transdu cer (Validyne MI'45 ::':5 em H 2 0 ; Northridge, Calif). In add ition, respiratory effort was monitored by measuri ng esophage al pressure (Caeltec, Dunvegan, Isle of Sky e, UK), and BP and heart rate were monitored by reco rdin g digita l art erial beat-to-beat systolic/d iastolic pr essur e at th e th ird finger of the left han d using an infrared pleth ysmo graphic volum e clamp mcthod (F mapres, Ohm eda; Maurepas, France ). As previously proposed,11.12 the left hand was taped to the epigastric area to avoid artifactual BI' modifi cation s caused by changes in hydrostatic pressur e associated with ha nd movemen t. All Sign als we re recorded using a I-t-chann el paper recorde r (Electroencephalograph, Nihon Kohden; Toky o, Japan) d igitized at 128 Hz and sampled using an analogid numeric system (M P I0 0; Biopac System ; Go leta , Ca lif) for subseque nt ana lysis. Data A naly sis A nonapneic-nonhypopneic obstructive event was defined as tho occurrence , in th e absence of hyp op nea (airflow dr op < 50 % of the pr eceding base line during 10 s or air flow drop wit h desatu ration <:3% of th e preceding baseline level ), of a progressive cha nge in the sha pe of the inspiratory flow contour cha rac teri zed hy increasi ng limitarion '" and of a concomitant increase in the esop hagea l pressur e swing, with te rmination of th e ve nt as abrupt normalization of both the inspiratory flow con tour and the esop hagea l pressu re swing. E sop hagea l pressur e swings were caleu lated as the differen ce between the maxima l expiratory value and the minimal inspiratory value. Esop hageal pressure swing decr ease was quantified as th e decreas e in esophagea l pr essur e swing at th e termination of the respiratory event, ie, th e diffe ren ce between esophageal swings imm edi ately before and after th e termination of th e resp iratory event. BP param ete rs and heart rate wer e analyzed over two lO-s periods before and afte r th e te rmin ation of the re sp iratory eve nt. TIP parame te rs were taken into account only during th e expiratory phase of the br eat hin g cycle . Th ey co rre sponded to at least thr ee data points for each 10-s pe riod . Sleep staging was performed accord ing to stan dard crit eria.w Only respirato ry even ts fro m non rapid eye movem ent (N RE M) slee p periods wer e used . EEG change s during th e 10 s befo re

986

and afte r th e end of respiratory even ts wer e looked for. Arousal scor ing ana lysis was performed by on e of us (F .G.), who was aware of th e time at which respiratory events wer e terminated, hut was not aware of th e chan ges in respirat ory effo rt and in TIP at the time of the respirat ory event. E EG chan ges we re gra ded as follows: grade 2, shift in EEG frequency lasting > 15 sand inclu din g alpha activity and/or frcqu encies > 16 Hz, accord ing to th e sta ndard crit eria of awaken ing;22 grade 1, shift in E EG frequen cy lastin g from 3 to 15 s and including alpha activity and/or frequen cies > 16 Hz, exce pt sp ind les, according to standard crit eria of arou sal.' ? grade 0, no EEG change s or minor EEG cha nge s, usua lly not classified as arousals in the American Sleep Disorde rs Association (ASDA) crite ria.'? Grade 0 EEG changes we re further classified as follows: grade Oa, shift in EEG fre quency lasting < 3 s and including alpha activity and/or frequencies > 1fi Hz, exee p' sp indles; grad e Gb, low-frequency EEG cha nge s (K-co mplexes and/or delta wave bu rst ) witho ut any increas e in E EG frequ ency exce pt spind les; grade Oc, no increase in cort ical high frequency an d no occurrenc e of K-complexes o r delt a wave bur sts. Stat istical Analysis For each patient and each type of EEG chan ge , the cha nges in art eri al pressur e and in esophageal pressure at the end of thc nonapneic- no nhypopneic respirat ory events were averaged and Friedman 's two-way analysis of varian ce was perform ed . Wh ere appropriate (p value < 0.0.5), pairwise co m par isons we re per formed using a Wi lcoxon matc hed paired test. T he level of significance was set at 5%.

R E SUL T S

Epworth slee piness sca le -" an d main slee p and res pira tory p aram eters during th e polysomnograph y with arte rial BP measure ment are presented in Tahl e 1. A mean (2:: SD) of 167 (2:: 145) nonapneicnonhypopneic resp iratory events we re observed per pati ent du rin g N H.E M slee p. D istribution of EE G p atterns dnring th ese non apn cic-n on lrypopncic respira tory eve nts is presented in Table 2. Systolic and diastolic BPs and heart rate rose after the e nd of the respiratory events, reaching a peak within 10 s after eve nt termination (Fig 1). BP and heart rat e changes in re spo nse to different grades EE G modifications are show n in panels A (top) and B (center) of F igu re 2, respectively. The following we re obse rved du ring grade 0, 1, and 2 EEG p atterns (rnean z SD ): systo lic press ure increased by 7.1± 1.5, 11.7 ±1.9, and 14.2± 3.4 (p
or

Clinical Investigations

Table I-Epworth Sleepiness Score and Sleep and Respiratory Data During Polysomnography With Arterial BP Measurements *

Patient

Epworth Sleepiness Scale

19 21

A B C D

II

12 II

E F

12

TST, min

WASO, min

Stages 1+ 2, % TST

426 398 279 362 360 182

80 112 146 163 160 lO2

93 72 84 77 65 58

Stages 3+ 4, % TST

RE'\;I, % TST

AHI, Events per Hour of Sleep

4 2 3

0

7

17

II

16 13 25 19

0 lO lO 17

Nonap neic-Nonhypopneic Respiratory Events per Hour of Sleep

59 22 54 12 14 23

I

1 3

*TST = total sleep time; WASO= wake after sleep onset ; AHI= apnoea-hypopn oea index; UAR=upper airway resistance.

Esophageal pressure swing decreases in response to different grades of arousals are shown in panel C (bottom) of Figure 2. No differenc es in esophageal pressure swing changes were observed across grades. The mean fall in arterial oxygen saturation was < 0.3% for each grade of arousal, with no significant differences across grades.

DISCUSSION

Patients with upp er airway obstruction without obstructive sleep apn ea/hypopnea exhibit increased respiratory efforts durin g NREM sleep , often with EEG pattern changes. We found that termination of these nonapneic-nonhypopneic obstructive events was consistently followed by a rise in BP, and that the magnitude of this rise increased with the intensity of EEG arousal, although significant but smaller rises were detectable in the absence of apparent EEG arousal. In this study, as previously propos ed,1I-13 BP was analyzed by infrared plethysmograph y. Because this noninvasive indirect method may overestimate BP,12 we measured only arterial BP changes. However, increased arteriolar vasoconstriction at the periphery could increase systolic BP measured at the finger by a phenom enon of reflectance of the pressure wave at the resistance vessels causing amplification and rise

in systolic BP. However, diastolic BP is virtually unaffect ed by this phenomenon.l l We found that magnitude of diastolic pressure increases also varied with the grade of arousal. This indicates that the BP rises that we observed cannot be du e solely to this artifact of pulse wave amplification . Although we analyzed both rapid eye movem en t (RE M) and NREM data , the amount of data was too small to allow comparisons of the different grades of arousal during REM sleep . Only two patients expe rienced nonapneic-nonhypopneic obstructive events both with and without awakening/arousal during REM sleep. This is due in part to the fact that apneas/hypopneas were predominant in REM sleep , whereas nonapneic-nonhypopneic obstructive events were observed less frequently. The age range in our six patients was quit e large, but only one patient was > 50 years (patient E, 65 years). Inter estingly, he was the patient who had the lowest arterial BP response to the different levels of arousal. During grade 2, 1, and 0 EEG patterns, systolic pressure increased by only 10, 9, and 4 mm Hg, respectively. This result corroborates the study of I-Iajduczok et a}23 that demonstrated that sympathetic activity is imp aired with senescence. The cardiovascular consequ enc es of OSAS include a rise in systemic BP after each episode of apnea.1 These postapneic BP elevations contribute signifi-

Table 2-EEG Patterns at the End of Nonapnoeic-Nonhypopnoeic Respiratory Eve nts During NREM Sleep

Patients A B C

D E F Mean SD

Nonapneic-Nonhypopn eic Respirato ry Event s

Grade 2, %

Grade 1,

421 137 250 59 73 59 167 145

16 12 8 12 26 2 13 8

66 48 81 27 53

%

72

57 23

Grad e 0, % I

I

Total Grade 0

Grade Oa

Grade Ob

Grade Oc

18 40 II

3 2 1

61 21 26 30 18

3 2 3 3

12 24 7 49 16 23 21 15

3 14 3 13 2 1 6 6

9

CH EST / 113/ 4/ APRIL, 1998

987

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Pressure

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. -

Arterial 140 . . . . . . . ... .. Pressure (mmll g) 1011 ~o..::..:..:...:..c c.:...:..:...:..:c.:...:..:...:..:.:...:..c,--,--,-.:...:..cc.:...:._--,- _ _~

~

~

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FIGUHE 1. Continuous polysomnographic recordings obtained in a patient , showing BP changes in response to various grades of EEG arousals due to nonapn eic-nonhypopnei c respiratory events, The EEG , electro-oculogram (EOG), chin electromyogram (EM C), air flow (Flow) pneumotachograph recording, esophageal pressure (Peso) recordin g, and arterial BP recordings are shown,

cantly to the nocturnal hypertension and perh aps also to the diurnal hyperten sion seen in patients with obstructive sleep apnea. A recent study demonstrated that acute increases in systemic arterial BP also occur after each respiratory event in the patients with upper airway obstruction without obstructive sleep apnea/hypopnea" We found th at the magnitude of these BP increases is related to the intensity of EEG arousal. Both arterial hypoxemias-' and arousal from sleep lO - 14 have been suggested as the main causes of 988

the nocturnal hemodynamic oscillations seen in patients with OSAS, although Rees et a1'5 found no relationship between the rise in BP and the occurrence of EEG change. To evaluate the respective contributions of hypoxia and arousal, investigators have used a variety of approaches to isolate these two factors from each other. To maintain arte rial oxygen saturation > 90% at the end of apneas, Ringler et apo and Ali et aP2 provided supplementary oxygen to OSAS patients undergoing polysomnography. They found that oxygen supplementation did not alter the Clinical Investigations

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Grade of Arou sal From Sleep FI GUHE 2. Systolic pressure (squares) and diastolic pressure (diamonds) changes (top, A ), heart rate changes (center, B ), and esophageal pressure swing decrease (bottom, C) in response to various grades of arou sal at the end of nonapneic respirato ry events. The left-sided panels show the values observed dur ing grade 2, 1, and 0 arousals. In the right-sided panels, grade 0 arousals are divided into three subgroups (see "Materials and Meth ods" for definition ). 1\'0 differences were observed across grade 0 subtypes. Systolic and diastolic BP increases wer e significantly higher for grade 2 and grade 1 than for grade O. Heart rate increases were Significantly higher for grade 2 than for grade O. No differences in esophageal pressure swing changes were observed across grades. Values are means:tSE M.

BP increase after apnea termination . In addition , Ringler et ap o indu ced nonrespirato ry (auditory) arousals in OSAS pati ents treated by nasal positive airway pressure and observed that the BP increase after auditory arousal was similar to th e BP increase afte r obstruc tive apnea. Similarly, Ali et al!' demonstr ated that arousals induced by peri odic leg movements induce an increase of BP in the same order as the rises seen after obstructive apn eas. Davies et al 13

also induced arousals by auditory stimulation in normal subjects. In th eir study, the magnitude of th e BP increase was proportional to the degree of arou sal, as defin ed by the du ration of the increa se in high-frequency EEG activity. In our study, in pa tients with upp er airway obstruction without obstruc tive sleep apnea/hypopnea, we also found th at the magnitude of the BP li se was closely related to the degree of arousal. Th ese data corroborate the findings fro m the studi es on OSAS, providing additional evide nce that arousals related to obstructive respi ratory events may be accompanied by significant BP rises even in the absen ce of oxygen desaturation. Other factors than arousal or hypoxia have been suggested as possibly being responsible for the BP elevation in OSAS. Th ese factors include reinflation of the lung, which may cha nge cardiovascular performanc e via a number of mechanisms.I'? and te rmination of deep negative pleural pressure dips generated by frustrated inspiratory e fforts during obstructive apn ea.25 These factors may also be involved in pati ents with upp er airway obstruction without obstructive sleep apn ea/hyp opnea, either in combination with arousals or alone, since we observed some increase in BP in th e absence of arou sals (E E G pattern scored as grade s 0). In a discu ssion of the lung volume changes in patients with upp e r airway obstru ction witho ut obstru ctive sleep apnea/hypopnea , Stoo hs and Cuil leminault'" pointed out th at the mean decrease in tid al volume during non apn eic-nonhypopneic respirato ry events was only 100 mL. It can be po stulated th at such a small increase in end-inspiratory thoracic volume at the end of a respiratory event will result in insignificant inflation -associated cardi ovascular responses. A second factor may be intrathoracic pressure changes , which are known to influ ence BP . BP decreases from expiration to inspiration , and when pleural pressure becom es more negative during inspiration, such as in pati ents with asthma, inspiratory arte rial pressure decreases further:5 Becau se part of the incr ease in BP occur ling at the end of respirato ry events may be ascribable to a reduction in th e inspiratory declin e of art erial BP, we decid ed to avoid this possible mechanical effect by measuling arterial BP duling expiration. However, because mean intrathoracic pressure is more negative dming an obstructive respirato ry event, left ventricular ejection may decrease following increases in left ventric ular afterload - and in venous return.f which increase enddiastolic volume of thi s cardi ac chambe r: this increase of end-diastolic volume of light ventricle can also decrease the left ventricular diastolic compliance and therefore the left ventricular preload th rough the mecha nisms of the ventricular int erdeCHEST / 113 / 4 / APRIL, 1998

989

penden ce.F' Thu s, a re turn to norm al intra thoracic pressure afte r the end of the obstructive respiratory event may increase BP by raising left ventri cular ejection. Such a ph en omenon may explain the increase in BP th at occurred in our study after th e end of nonapneic-nonhypopneic respiratory eve nts, even in the absence of visible EEG cha nges. However, th e putative role of a decrease in intrathoracic pressure in decreasing left ventricula r ejection under conditions appropriate to sleep apnea synd rome has not yet been confirme d by expe rime ntal studiesP In addition, in our study, alth ough esophageal pressure did become more negative during these respiratory events, the mean esophageal pressur e swing increase was < 10 em H 20 , a value mu ch lower than in the slee p apnea syndrome . Since non e of th ese previous hypotheses is satisfactory , we suggest that an increase in BP (during grade Oc arousals) may occur as a result of b rainste m activation caused by th e respiratory event and sufficiently marked to produce an autonomic respon se but not cort ical arousal. This hypothesis has been suggeste d previously by Davies et al,13 who obse rved that auditory stimuli could also induce BP inc reases (with magnitude s similar to th ose in our study during grade 0 arousals) without causing E E G arousal. A rec ent study investi gated a subpopulation of patients with upp er airway obstruction without obstructive sleep apn ea/hypopnea and without detectable EEG arousals.s" In our study, one third of nonapneic-nonhypopneie respiratory events were not associate d with arousals accordin g to ASDA crite ria (grades 0), but were associate d with abrupt BP increases. Among th ese respiratory events without arousal , many (80%) were associated with EEG changes, which were usually of low frequency (grade Ob: K-complexes and/or delta wave bursts). Since it has been demonstrated th at a minimal EEG event, such as a K complex, may induce an increase of the sympathetic discharge,28 we chec ked whether these events with min imal E E G cha nges (grade s Oa and Ob) were associated with larger arte rial BP elevation s than even ts with no EEG changes (grade Oc), We found no differen ces, suggesting that use of arousability crite ria that are more sensitive than ASDA crite ria does not provide any additional clinical information on the cardiovascular consequences of upper airway obstruction without obstru ctive sleep apn ea/hypopnea. In conclusion, we found that, similar to OSAS patients, snore rs with upper airway obstru ction with out obstructive sleep apnea/hypopnea exhibited abrupt tr ansient systemic BP elevations at termination of respirato ry events. In addition, the magnitude of the transient BP increases during NREM slee p varie d with th e grade of th e arousal associated with 990

the non apn eic-nonhypopneic resp iratory event. However, BP increases were also seen in the abse nce of det ectabl e EEG arou sal. Because the oth er factors generally believed to produce postapn eic BP elevation in OSAS are absent or insignific ant in pati ents with upper airway obstruction witho ut obstructive sleep apnea/hypopnea, we believe that arousal is the main cause of the systemic BP increases seen after termin ation of nonapneic-nonhypopn eic obstructive events. In addition, given that BP increases also occurred without apparent E EG arousal, beat-to-beat BP evaluation may be a more sensitive means of identifying nonapneic-nonhypopneic respiratory events than conventional evaluation of EEG changes. ACKNOWLEDGM ENT : We are grateliil to Djibril Bokar Thire, Nathalie Gadenne, Denise Henry, and Richard Morales for their skillful techn ical assistance.

REF ERENCES

2 3

4

5 6 7 8 9

10 11 12

13 14 15

Coccagna G, Montovani M, Briguani F, et ai. Continuous recording of thc pul monary and systemic arterial pressure du ring sleep in syndromes of hypersomn ia with periodic breathing. Bull Eur Physiopathol Respir 1972; 8:1159-72 Shepard JJ. Gas exchange and hemodynamics during sleep. Med Clin NOJi h Am 1985; 69:1243-64 O'Do nnell C, Ayuse T, King E, et ai. Airway obstruction during sleep increases blood pressure without arousal. J Appl Physiol 1996; 80:773-81 Buda AJ, Pinsky MR, Ingels NB, et al. Effect of intrathoracic pressure on left ventricular performance. N En gl J Med 1979; .301:453-59 Jardin F, Bourdarias JP. Influence of abnormal breath ing conditions on right ventricular function. Intensive Care Med 1991; 17:129-35 Lloyd 1'. Effect of inspiration on inferior vena caval blood flow in dogs. J Appl Physiol 1983; .55:1701-08 Howell J, Per mutt S, Proctor D, et al. Effect of inflation of the lung on differen t parts on pulmonary vascular hed. J Appl l'hysiol 1961; 16:71-76 Marini JJ, Culver BIl Butler J. Mechanical effects of lung distension with positive pressure on cardiac function. Am Rev Hespir Dis 1981; 124:382-86 Kaufman M, Iwamoto G, Ashton J, et al. Response to inflation of vagal afferent s with endings in the lungs of dogs. Circ Res 1982; 51:525-31 H.ingler J, Rasner R, Shannon R, et ai. Hypoxemia alone does not explain blood pressure elevations after obstructive apneas. J Appl Physiol 1990; 69:2143-48 Ali NJ, Davies HJ, Fleetham JA, et al, Periodic movements of the legs durin g sleep associated with rises in systemic blood pressure. Sleep 1991; 14:163-65 Ali N, Davies R, Fleet ham J, et al. The acute effects of contin uous positive airway pressure on oxygen administrat ion on blood pressure during obstructive sleep apnea. Chest 1992; 101:1.526-32 Davies R, Belt 1', Roberts S, et al. Arterial blood pressure responses to graded transient arousal from sleep in normal hum ans. J Appl Physiol 1993; 74:1123-30 Hingler J, Garpestad E, Basner H, et ai. Systemic blood pressure elevation after airway occlusion du ring NRE M sleep. Am J Crit Care Med 1994; 150:1062-66 Hees K, Spence D, Earis J, et al. Arousal responses from Clinical Investigations

16 17

18 19 20

21 22

apneic events during non-rap id-eye-moveme nt sleep . Am J Hespir Crit Care Med 1995; 152:1016-21 Guilleminault C, Stoohs H, Duncan S. Snoring (1): daytime sleepiness in heavy snorers. Chest 1991; 99:40-48 Guilleminault C, Stoohs R, Clerk A, et al. A cause of excessive daytime sleepiness: the upper airway resistance syndrome. Ches t 1993; 104:781-87 Murray W. A new method for measuring daytime sleepiness: the Epworth sleepiness scale. Sleep 1991; 14:540-45 American Sleep Disorders Association. EEG arousals: scoring rules and examples. Sleep 1992; 15:174-84 Guilleminault C, Stoohs R, Clerk A, et al. Excessive daytime somnolence in women with abnormal respiratory effort during sleep. Sleep 1993; 16:s137-38 Liistro G, Stanescu C, Veriter C, et aI. Pattern of snoring in obstructive sleep apnea patients an in heavy snorers . Sleep 1991; 14:517-25 Bechtschaffen A, Kales A. A manual of standardized termi-

AMER ICAN

CO L LEGE

OF

raCHEST

PHYSIC

23

24 25 26 27 28

nology, techniques and scoring system for sleep stages of human subjects. Washington, DC: National Institutes of Health 1968; publication No. 204 Hajduczok G, Chapleau MW, Johnson SL, et al. Increase in sympathetic activity with age: 1. Role of impairment of arterial barore flexes. Am J Physiol 1991; 260:H l1I3-20 Guilleminault C, Stoohs R, Shiomi T, et al. Upper airway resistance syndrome, nocturna l blood pressure monitoring, and bord erline hypertension. Chest 1996; 109:901-08 Parish JM, Shepard JW Jr. Cardiovascular effects of sleep disorders. Chest 1990; 97:1220-26 Stoohs H, Guilleminault C. Snoring during NHEM sleep: respiratory timing, esophageal pressure and EEG arousal. Hespir Physiol 1991; 85:151-67 Scharf S. The effect of decreased intrathoracic pressure on ventri cular function. J Sleep Res 1995; 4S:53-58 Somers V, Dyken M, Mark A, et al. Sympathetic-nerve activity during sleep in normal subjects. N Engl J Med 1993; 328:303-07

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