ST-segment depression during sleep in obstructive sleep apnea

ST-Segment Depression During Sleep in Obstructive Sleep Apnea

Patrick Hanly, MD, Zion Sasson, MD, Naheed Zuberi, BSC, HK, and Kim Lunn, BA, RN

It was hypothesized that obstructive sleep apnea may precipitate myocardial ischemia, reflected by ST-segment depression, in some patients during sleep. Overnight sleep studies and simultaneous khannel Holter monitoring were performed on 23 consecutive patients with obstructive sleep apnea without a history of coronary artery disease. Each patient was randomly assigned to nasal continuous positive airway pressure for the first half of the night and the atternate for the second half of the night. An episode of significant ST depression was defined as ~1 mm from baseline for ~1 mire ute. The total duration (minutes) of ST depression was indexed to the total sleep time (minutes per hour of sleep). Seven patients (30%) had ST depression during sleep. In all 7 patients the dun tion of ST depression decreased during nasal cob tinuous positive airway pressure (30 + 18 vs 11 + 13 minutes per hour of sleep) in association with a reduction in the apneschypopnea index (65 f 36 vs 7 + G/hour), arousal index (49 f 14 vs 6 + 4/hour) and the duration that oxygen saturation was <90% (44 2 27 vs 12 + 23% total sleep time). When patients were not on nasal continuous positive airway pressure, the apneehypopnea and arousal indexes were higher during periods of ST depression than when ST segments were isoelectric, whereas oxygen saturation was not different. These 7 patients underwent exercise testing, which was positive for inducible myocardial ischemia in 1 patient. It is concluded that ST depression is relatively common in patients with obstruc+ tive apnea during sleep and that the duration of ST depression is significantly reduced by nasal continuous positive airway pressure. ST depression in these patients may reflect true myocardial ischemia or nonspecific changes associated with recurrent obstructive apneas.

(AmJCardiol1993;71:1341-1349)

From the Sleep Laboratory, Department of Medicine, Wellesley Hos- pital, University of Toronto, Toronto, Ontario, Canada. This study was supported by The Physician Services Inc. Foundation, Toronto, Ontario, Canada. Manuscript received October 19,1992; revised manuscript received January 4, 1993, and accepted January 5.

Address for reprints: Patrick J. Hanly, MD, Room 247 JB, Welles- ley Hospital, 160 Wellesley St. E., Toronto, Ontario, M4Y 153, Canada.

0 bstructive sleep apnea and coronary artery disease share many risk factors and many coexist in some persons. Both conditions frequently

occur in men and in obese persons, and their peak prevalen& is during the sixth decade of life.lj* In addition, a number of retrospective studies have indicated an association between obstructive sleep apnea and myocardial infarction.3,4 The pathophysiology of this interaction has not been determined although a number of possi- bilities can be considered. Obstructive apneas during sleep are characteristically associated with hypoxemia and reduced intrathoracic pressure, an extremely stress- ful combination for the balance of myocardial oxygen supply and demand. Negative intrathoracic pressure in- creases both preload, by increasing venous return, and afterload by increasing transmyocardial pressure, both of which increase ventricular wall stress and myocardial oxygen demand. At the same time apnea reduces myocardial oxygen supply, causing progressive oxygen de- saturation of coronary arterial blood.5 Nasal continuous positive airway pressure corrects both hypoxemia and intermittent changes in intrathoracic pressure during sleep in patients with obstructive apnea. The objective of this study was to determine whether patients with obstructive sleep apnea develop myocardial ischemia, reflected by ST-segment depression, during sleep and whether the severity of ST depression is reduced by nasal continuous positive airway pressure.

METHODS We studied 23 consecutive patients with moderate or

severe obstructive sleep apnea recently diagnosed by clinical assessment and overnight sleep studies. All patients returned to the sleep laboratory for a second overnight sleep study, where they were randomly allocated to receive nasal continuous positive airway pressure or room air for the fist half, and were switched to the other modality for the latter half of the study. The two halves of the study were exactly the same in all other respects. In addition to the usual sleep and cardiorespiratory measurements, all patients had 3-channel Holter monitoring during the sleep study and 17 had an exercise test short- ly afterward. Patients were not previously screened for symptomatic coronary artery disease.

Sleep studies: We recorded a 2-channel electroencephalogram (C3-AZ, Cd-Al), electrooculogram and sub- mental electromyogram using surface electrodes. Airflow was detected by monitoring expired carbon dioxide at the nose and mouth through nasal cannulas adapted for this purpose (PB 223, Puritan-Bennett Corporation, Overland Park, Kansas). Respiratory effort was monitored by respiratory plethysmography with transducers placed around the chest and abdomen (Respitrace, Am-

ST DEPRESSION IN SLEEP APNEA 1341

TABLE I Heart Rate and Blood Pressure During Rest and Exercise in Seven Patients With and 10 Without ST Depression During Sleep

Rest Exercise

Pt. HR(r) SBP DBP Duration (min) Stage HR(e) % SBP DBP CP STD

Patients With ST Depression During Sleep

1 75 125 95 9 III 160 88 205 10 0 0 2 75 130 80 9 III 143 91 190 80 0 0 3 66 120 90 9 Ill 170 88 120 90 0 0 4 131 160 100 1.4 I 156 101 210 100 0 0 5* 103 114 80 2.2 I 150 84 160 80 0 Equiv. 6 85 130 90 6 II 156 97 160 100 0 0 7* 108 150 95 3.4 II 136 92 160 95 0 +

Mean 92 133 90 5.7 153 92 172 92 ?SD k21 k15 27 23.1 -t-10 +-5 229 28

Patients Without ST Depression During Sleep

1 90 120 90 9 Ill 180 96 215 90 0 0 2 81 130 80 7.3 Ill 169 85 130 80 0 0 3 80 130 90 10 Ill 154 93 190 90 0 0 4 90 130 90 9 Ill 162 93 130 90 0 0 5* 90 130 80 4 II 165 95 230 100 0 0 6 70 130 80 8.2 III 145 86 140 80 0 0 7 74 150 90 9 Ill 150 90 240 90 0 0 8 120 150 100 4 II 150 87 220 100 0 0 9 81 160 100 10 IV 142 86 160 100 0 0

lo* 80 120 90 9 Ill 167 85 170 70 0 0 Mean 86 135 89 8 158 90 183 89 &SD +13 212 27 k2 kll a4 240 +9

*Nonspecific ST-segment changes on resting electrocardiogram. CP = chest pain during exercise; DBP = diastolic blood pressure (mm Hg); HRM = maximal heart rate duringexercise (beats/min); HRW = heart rate at rest (beats/min); SBP =

systolic blood pressure (mm Hg); Stage = stage at which exercise test was stopped; STD = ST-segment depression during exercise: % = maximal heart rate during exercise expressed as a percentage of maximal predtcted heart rate during exercise.

bulatory Monitoring, Ardsley, New York). Arterial oxygen saturation was recorded with a pulse oximeter (Biox 3740, Ohmeda, Boulder, Colorado). Transcutaneous partial pressure of carbon dioxide was recorded by a sen- sor placed on the anterior chest wall (Kontron 7640, Medilog Ltd.). The electrocardiogram and heart rate were recorded from standard limb leads. All variables were continuously recorded on a polygraph (model 78E, Grass Instruments, Quincy, Massachusetts) at a paper speed df 10 mm/s. Transcutaneous partial pressure of carbon dioxide was displayed on a slow recorder (paper speed 20 cm/hour) which was synchronized to the Grass polygraph. Finally, body position was recorded with both a mercury switch attached to a belt on the patient’s abdomen (Vitalog Monitoring Inc., Redwood City, Cal- ifornia) and audio visual monitoring.

All sleep studies were scored manually and sleep stage and arousals were determined by established crite- ria using the electroencephalogram, electrooculogram and elec&oqograrn6 An arousal was defmed as an awakening from sleep for >5 seconds, as evidenced by simultaneous OL activity on the electroencephalogram, electromyogram activation, and eye movements. The arousal index was defined as the number of arousals per hour of sleep. Obstructive apnea was defmed as absence of tiow for >lO seconds in the presence of continued respiratory efforts. Hypopnea was detied as a reduction in the amplitude of respiratory effort of 250% from the sleeping baseline level for >lO seconds. The apnea- hypopnea index was detied as the number of apneas and hypopneas per hour of sleep. Oxygen saturation dur-

1342 THE AMERICAN JOURNAL OF CARDIOLOGY VOLUME 71

ing sleep was expressed in 2 ways: (1) the duration oxygen saturation was <90%, expressed as a percentage of total sleep time; and (2) mean oxygen saturation, calculated by averaging the high and low oxygen saturation for each 30-second epoch. Mean transcutaneous partial pressure of carbon dioxide during sleep was calculated from the average value over 36-second intervals.

Halter monitoring reordings: Continuous Holter monitoring was performed during sleep in all patients and was synchronized to the sleep study by running both from the same clock. Modiiied lead II, Vs and V2 and the Markette 100 computerized Holter analysis system were used to analyze the ST-segment trend for myocardial ischemia. An episode of myocardial ischemia was delined as ST-segment depression of >l mm from baseline for 20.08 second after the J point, lasting for at least 1 minute and separated from the next episode by at least 1 minute. Only 1 lead, that showing the most ischemic episodes, was used for analysis so as to avoid duplica- tion of ischemic episodes by the other leads. Of the 7 patients who developed ST depression during sleep lead V5 was used for analysis in 6, and lead II in the remaining patient. The Holter tapes were fitted and analyzed by an experienced research technician and reviewed by an experienced investigator, both of whom were un- aware of the timing of nasal continuous positive airway pressure and room air treatments. By integrating data from the Holter monitors and the sleep study, the duration of ST depression (minutes) was indexed to the total sleep time to give the duration of ST-segment depression during sleep (minutes per hour of sleep).

JUNE 1, 1993

ST SEGMENT TREND (ENTIRE STUDY)

+5 Channel I

+5 ml

-5.‘. ’ -5 ml 0 I 2 3 4 5 6

< ----------- cpAp -m-Bmm--m- >

I 23:05:47 AWAKE OFF CPAP BASELINE

FlGllRE 1. ST-segment depression (STD) in patient 3 (Table I). Top, displays the ST-segment trend in lead V5 for the eR tire study with the dark lines indicating signilicant ST depression. Note that almost all ST depression occurred with the subject off nasal continuous positive aimay pre+ sure (CPAP). Bottom shows examples of electrocardio&apb ic tracing+ while the subject is awake and asleep (off co* tirmous positive aimay pressure), indicating diirent ST- and l-wave morphology.

~~erclse test Seventeen of the patients in this study, and all patients with an abnormal Holter monitor showing ST depression during sleep, underwent a maximal graded treadmill stress test using the standard Bruce pro- tocol to assess more specitically inducible myocardial ischemia. An ischemic electrocardiographic response was defined as 21 mm horizontal or downsloping ST- segment depression below the PR segment for 20.08 second after the J point on 3 consecutive beats.

Statistical analysis Inter- and intragroup differences between groups were analyzed by unpaired Student’s t test and paired Student’s t test, respectively, with p ~0.05 considered significant.

RESULTS The 23 patients studied had moderate or severe ob-

structive sleep apnea. There were 21 men and 2 women (mean age 48 f 12 years and mean body mass index 36 rt 7 kg/m*). The mean apnea-hypopnea index was 64 f 22/hour with a mean arousal index of 57 f 29/hour. The mean duration that oxygen saturation was ~90% was 55 + 22% of the total sleep time. No patient had a history of coronary artery disease. Seven patients had significant ST depression during sleep and the remaining 16 patients did not. There were no sigticant differences in age between these 2 groups (52 + 15 vs 46 + 10 years), body mass index (37 + 7 vs 36 f 7 kg/m*), heart rate, and severity of apnea and hypoxemia during sleep. Four of the 7 patients who had ST depression during sleep were receiving medical therapy for chronic hypertension which included captopril, enalapril, atenolol, prazosin and thiazide diuretics. No patient was receiving digox-

3:08:30 ASLEEP OFF CPAP STD 1.4 mm

in, an&rhythmic, antidepressant or anticonvulsant med- ications at the time of this study.

The time of nasal continuous positive airway pressure use was evenly distributed throughout the night. Ten patients received nasal continuous positive airway pressure for the first half of the study and 13 patients received it during the second half of the study. Seven patients developed significant ST depression during sleep, of which 4 patients received continuous positive airway pressure during the first half of the study and 3 received it during the second half of the study.

Exercise tests were performed on all 7 patients with an abnormal Holter study during sleep. One patient developed typical ischemic ST depression of 2 to 3 mm during exercise which was asymptomatic. A follow-up exercise thallium scan demonstrated reversible myocardial ischemia. Another patient in this group had an in- adequate exercise test (stopped early complaining of dyspnea and fatigue) which was equivocal for inducible ischemia. Subsequent dipyridamole thallium scan showed no evidence of reversible myocardial ischemia. Exercise testing in the remaining 5 patients yielded negative results. In the group of 16 patients who had no ST depression during sleep, 10 exercise tests were negative and 6 were not done. The changes in heart rate and sys- temic blood pressure during exercise in these patients are listed on Table I. Mean heart rate during peak exercise was significantly higher than mean heart rate during ST depression while asleep (153 f 10 vs 77 f 8 beats/min). All patients were in sinus rhythm throughout the study.

The duration of significant ST depression during sleep was quite variable among the 7 patients in which


TABLE II Mean Duration of ST-Segment Depression, Heart Rate, Apnea and Sleep Data Off and On Nasal Continuous

Positive Airway Pressure in Seven Patients with ST-Segment Depression During Sleep

Off CPAP On CPAP

ST depression (min/hour sleep) 305 17 11 z!z 13* Heart rate (beats/min) 84 f 14 86 ? 10 Apnea-hypopnea index (/hour) 65 t 35 7 zt 6* Arousal index (/hour) 49 14 2 6 2 4* Oxygen saturation <90% (% total sleep time) 44 k 27 12 f 23* Transcutaneous PC02 (mm Hg) 46 + 6 43 2 6 Total sleep time (hours) 2.4 IT 0.6 2.6 f 0.7 Stage 1 sleep (% total sleep time) 17 -+ 7 7 f 4* Stage 2 sleep (% total sleep time) 59 f 15 31 k 8* Slow-wave sleep (% total sleep time) 829 22 + 17 Rapid eye movement sleep (% total sleep time) 15 e 13 40 -+ 13*

*p CO.05 versus off continuous positive airway pressure. CPAP = continuous positive airway pressure; PC02 = parbal pressure of carbon

dioxide.

jt was found, ranging from 4 to 57 minutes/hour of sleep. However, nasal continuous positive airway pressure significantly reduced the duration of ST depression during sleep in each patient (Figure 1) with a mean reduction from 30 f 18 to 11 + 13 minutes/hour of sleep. In 1 patient ST depression was totally abolished by nasal continuous positive airway pressure.

Table II lists the Holter and sleep study data off and on nasal continuous positive airway pressure in the 7 sleep apnea patients who developed ST depression during sleep. Continuous positive airway pressure significantly reduced apnea-hypopnea and arousal indexes, and the duration oxygen saturation was ~90%. In addition, it improved sleep quality by signilicantly reducing the proportion of stages I and II non-rapid eye movement sleep and increasing the proportion of rapid eye movement sleep. Slow-wave sleep also tended to increase although this did not reach statistical significance. Anal- ysis of the mean distribution of ST depression during sleep while off nasal continuous positive airway pressure in these 7 patients shows that of the total duration of ST depression (62 f 28 minutes/hour of sleep), 77 f 22% occurred during stages I and II sleep, 3 + 8% during slow-wave sleep, and 20 + 19% occurred during rapid eye movement sleep.

Since sleep architecture, oxygen saturation, apnea- hypopnea and arousal indexes improved on nasal continuous positive airway pressure in conjunction with the improvement in the duration of ST depression, we compared these parameters during ST depression to when ST segments were isoelectric, while the patients were off nasal continuous positive airway pressure. The duration of sleep, distribution of sleep stages and mean oxygen saturation were not significantly different when ST depression was present or absent. However, apnea and arousal indexes were significantly higher during ST depression than when ST segments were isoelectric (apnea-hypopnea index, 66 + 42 vs 32 + 19/hour; arousal index, 43 f 22 vs 21 + 16/hour). This difference was seen only during non-rapid eye movement sleep, which was when most ST depression occurred. This suggests that reduction in the duration of ST depression on nasal continuous positive airway pressure was at least partly

due to the reduction in apneas and hypopneas and the associated reduction in arousals from sleep.

DISCUSSION We found asymptomatic ST depression during sleep

in 30% of patients with obstructive sleep apnea who did not have a history of coronary artery disease. Further- more, the duration of ST depression was significantly reduced by nasal continuous positive airway pressure. A number of possible explanations can be considered for these electrocardiographic lindings, including nonspecific changes unrelated to sleep apnea, myocardial ischemia, and nonischemic changes associated with sleep apnea.

Nonspecific changes There are a variety of factors unrelated to obstructive sleep apnea that can cause nonspecific ST- and T-wave changes on Holter monitoring.7 Although 2 of our 7 patients with ST depression had nonspecitic ST- and T-wave changes on their resting electrocardiogram, these changes were minor and did not interfere with accurate interpretation of the Holter recording. We monitored body position carefully and did not find any relationship between it and ST depression. None of our patients had left ventricular hypertrophy or preexcitation syndromes, nor were they taking medica- tions known to affect the ST segments or T waves. Our patients did not have electrolyte abnormalities or evidence of vaIvular heart disease, such as aortic stenosis or mitral valve prolapse, which may confound interpretation of ST depression on Holter monitoring. Accurate electrode placement is important for reliable recording and interpretation of ST depression. Holter monitor leads were placed by a single experienced research technician and were not changed during the study. Finally, our observation that nasal continuous positive airway pressure reduced the duration of ST depression in each patient makes these nonspecilic etiologies less likely.

Myocardial ischemia: None of the patients we studied had a history of angina or myocardial infarction, and only 1 (patient 7 in the ST depression group) had a positive exercise test result, indicating reversible ~ocardial ischemia that was subsequently conlirmed by a stress thallium scan. These findings indicate a 4.3% prevalence of asymptomatic coronary artery disease in our study group, which is similar to what has been reported (2.5 to 5.0%) in the general population.8gg ST-segment depression during sleep in this patient probably repre- sented true myocardial ischemia,tO and the significant reduction in the duration of ST depression on nasal continuous positive airway pressure suggests that these ischemic changes were provoked by recurrent obstructive apneas during sleep.

Inspiration against an occluded upper airway reduces intrathoracic pressure resulting in increased left ventricular preload and afterload, thereby enhancing left ventricular wall stress and myocardial oxygen demand.5 Previous animal experiments have shown that these me- chanical changes alone, in the absence of hypoxemia, may cause myocardial ischemia in dogs with partial oc- clusion of the left anterior descending artery.” However, most obstructive apneas are also accompanied by hypoxemia, which is known to cause myocardial ischemia in patients with coronary artery disease.12 The concurrent

1344 THE AMERICAN JOURNAL OF CARDIOLOGY VOLUME 71 JUNE 1,1993

decrease in myocardial oxygen supply at a tune of increased oxygen demand substantially enhances the risk that myocardial ischemia will develop in patients with significant underlying coronary artery disease.

Six of our 7 patients with ST depression during sleep had no evidence of myocardial ischemia on exercise testing, which suggests that ST depression during sleep in these 6 patients was not caused by myocardial ischemia.13 However, repetitive obstructive apneas associated with large fluctuations in intrathoracic pressure and severe hypoxemia may lead to greater myocardial stress, oxygen demand and ischemia than a symptom-limited exercise test. Consequently, a negative exercise test result may not rule out myocardial ischemia during sleep.

Nonixhemic changes: In addition to reducing the duration of ST depression, nasal continuous positive airway pressure also improved sleep architecture and reduced hypoxemia, apnea and associated arousals from sleep (Table IT). To determine whether the improvement in ST depression was due to these accompanying changes, we compared sleep architecture, oxygen saturation, apnea and arousal indexes when ST depression was present or absent while patients were off nasal continuous positive airway pressure. Sleep architecture and mean oxygen saturation were not different, but apnea and arousal indexes were significantly higher when ST segments were depressed. This suggests that ST depression may be caused by changes associated with recurrent arousals that are required to terminate obstructive apneas. These arousals are characteristically accompanied by hyperventilation, which has been shown to cause both ST depression and T-wave abnormalities.14-16 Pa- tients with obstructive sleep apnea also have heightened sympathetic nervous system activity that improves after treatment with nasal continuous positive airway pressure.17J8 Consequently, ST depression may have been due to intermittent hyperventilation and increased sympathetic nervous system activity associated with arousals from sleep with improvement after correction of these abnormalities by nasal continuous positive airway pressure.

Alteration of intrathoracic pressure during obstructive apnea may render the gastroesophageal sphincter less competent, leading to esophageal reflux and possibly esophageal spasm. l9 These changes, which may be sub- clinical, have been reported to cause ST- and T-wave changes.20 Nasal continuous positive airway pressure would reduce esophageal reflux19 and thereby its associated ST depression. Obstructive apnea has also been reported to increase intracranial pressure21 and reduce cerebral perfusion,22 both of which are corrected by nasal continuous positive airway pressure. Once again, ST- and T-wave changes may accompany these neuro- logic events23 and possibly account for some of the ST depression seen in our patients. These potential explanations are purely speculative at this time and further studies will be required to determine their role.

Whether ST depression in our patients was caused by myocardial ischemia or nonischemic changes related to obstructive sleep apnea, it indicates the importance of

considering sleep apnea in patients who have ST depression on Holter monitoring, particularly if the episodes of ST depression occur predominantly during sleep. This has not been previously recognized as a potential con- founding factor in the interpretation of ambulatory electrocardiographic monitoring.

Acknowledgment: We acknowledge the technical support of Mark Alderson, and thank Elvie Garcia for typing the manuscript.

1. Gislason T, Almqvist M, Eriksson G, Taube A, Bornan G. Prevalence of sleep apnea syndrome among Swedish men -an epidemiological study. J C/in Epidemi- ol 1988;41:571-576. 2. Cupples LA, D’Agostino RB. Some risk factors related to the annual incidence of cardiovascular disease and death using pooled repeated biennial measurements: the Framingham heat study, 30 year follow-up, section 34. In: Kannel WB, Wolf PA, Garrison RJ, eds. The Framingham Study: An Epidemiological Investigation of Cardiovascular Disease. National Heart, Lung, and Blood Institute, 1987. (NIH publication no. 87-2703). 3. Hung J, Whitford EG, Parsons RW, Hillman DR. Association of sleep apnea with myocardial infarction in men. Lmcet 1990;336:261-264. 4. Saitor T, Yoshikawa T, Sakamoto Y, Tanaka K, Inoue T, Ogawa R. Sleep apnea in patients with acute myocardial infarction. Crit Care Med 1991;19:938-941. 5. Parish JM, Shepard JW. Cadiovascular effects of sleep disorders. Chest 1990;97: 122&1226. 6. Kales A, Rechtzchaffen A, eds. A manual of standardized terminology, tech- niques, and scoring system for sleep stages of human subjects. Bethesda, Mayland: National Institute of Neurological Disease and Blindness; 1968. (NIH publication no. 204). 7. Noble Hurst JW

RJ, Zipes DP. Long-term continuous electrocardiographic recording. In: , Schlant RC, Rackley CE, Sannenblick EH, Wager NK, eds. The Heat.

7th ed. New York: McGraw-Hill Information Services Company, 1990;1834-1841. 8. Froelicher VF, Thomas MM, Pillow C, Lancaster MC. Epidemiologic study of asymptomatic men screened by maximal treadmill testing for latent coronary artery disease. Am J Cardiol 1974;34:77&776. 9. Erikssen J, Enge I, Forfang K, Storstein 0. False positive diagnostic test and coronary angiographic fmdings in 105 presumably healthy males. Circulation 1976; 54~371-376. 10. Gottlieb SO. Asymptomatic or silent myocardial ischemia in angina pectoris: pathophysiology and clinical implications. Cardiol Clin 1991;9:4!Ul. 11. Scharf SM, Graver LM, B&ban K. Cardiovascular effect of periodic occlu- sions of the upper airway in dogs. Am Rev Respir Dis 1992;146:321-329. 12. Barach AL, Steinder A, E&man M, Molomut N. The physiologic action of oxygen and carbon dioxide on the coronary circulation, as shown by blood gas and electrocardiogmphic studies. Am Heart J 1941;22: 13-34. 13. Mulcahy D, Keegan .I, Sparrow J, Park A, Wright C, Fox K. Ischemia in the ambulatory setting: the total ischemic burden: relation to exercise testing and inves- tigative and therapeutic implications. J Am CoN Cardiol 1989;14:1166-1172. 14. McHemy PL, Cogan OJ, Elliott WC, Knoebel SB. False positive ECG response to exercise secondruy to hyperventilation: cineangiographic correlation. Am Heart J 1970;79:683-687. 15. Larry D, Goldschlager N. Electrocardiographic changes during hyperventilation resembling myocardial ischemia in patients with normal coronary xteriograms. Am Heart J 1974;87:383-390. 16. Bibaman L, Sanna RN, Surawicz B. T-wave abnormalities during hyperventilation and isoproterenol infusion. Am Heart J 1971;81:16&174. 17. Hedner J, Ejnell H, Sellgren J, Hedner T, Walhn G. Is high and fluctuating muscle nerve sympathetic activity in the sleep apnea syndrome of pathogen&c importance for the development of hypertension? .I Hypertens 1988;6:S529-S531. 18. Fletcher EC, Miller J, Schaaf JW, Fletcher JG. Urinary catecholamines before and after tracheostomy in patients with obshwtive sleep apnea and hypertension. Seep 1987;10:35-44. 19. Kerr P, Shoenut JP, Millar T, Buckle P, Kryger MH. Nasal CPAP reduces gastroesophageal reflux in obstructive sleep apnea syndrome. Chest 1982; 101: 1539-1544. 20. Hick DG, Morrison JFB, Casey JF, Al-Ashhab W, Williams GJ, Davies GA. Oesophageal motility, luminal pH, and electrocardiographicST segment analysis during spontaneous episodes of angina like chest pain. GUT 1992;33:79-86. 21. Jennum P, Borgesen SE. Intracranial pressure and obstructive sleep apnea. Chest 1989;95:279-283. 22. Meyer JS, Sakai F, Karacan I, Dennan S, Yamamoto M. Sleep apnea, nar- colepsy and dreaming: regional cerebral hemodynamics. AnnNeurol1980;7:47~85. 23. Davies KR, Gelb AW, Manninen PH, Boughner DR, Bisnaire D. Cardiac func- tion in aneurysmal subarachnoid haemorrhage: a study of electrocardiographic and echccardiographic abnormalities. Br J Anesth 1991;67:5863.


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ST-segment depression during sleep in obstructive sleep apnea