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SLEEP APNEA and AUTONOMIC NERVOUS SYSTEM

SLEEP APNEA and AUTONOMIC NERVOUS SYSTEM. Levent ÖZTÜRK, M.D. Trakya University Faculty of Medicine Department of Physiology. Uyku Apne Sendromu ve Metabolizma İlişkisi Paneli. Outline. Assessment of autonomic function Autonomic system during sleep

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SLEEP APNEA and AUTONOMIC NERVOUS SYSTEM

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  1. SLEEP APNEAandAUTONOMIC NERVOUS SYSTEM Levent ÖZTÜRK, M.D. Trakya University Faculty of Medicine Department of Physiology Uyku Apne Sendromu ve Metabolizma İlişkisi Paneli

  2. Outline • Assessment of autonomic function • Autonomic system during sleep • Autonomic system in OSAS during sleep and wakefulness • Pathophysiologic mechanisms in which autonomic system may be involved in OSAS

  3. Assessment of Autonomic Function • Heart rate responses • Heart rate variability • Pulse transit time • Stress tests • Blood pressure monitorization

  4. Heart Rate Responses • Heart rate response to Valsalva maneuver • Subject blows maximally through a mouthpiece attached to a manometer above 40 mmHg pressure. • ECG is recorded while subject lays semi-recumbent. • He is instructed to blow hard for 15 sec and then suddenly release his breath. • The ratio of the longest R-R during release to the shortest R-R interval during strain is calculated (Valsalva Ratio) • Heart rate response to deep breathing • Test is performed in the supine position. • The subject takes a slow deep breath over 5 sec and exhales over 5 sec for a period of one minute. • The ratio (E/I) of the mean of the maximum R-R intervals during deep expiration to the mean of the minimum R-R intervals during deep inspiration is calculated.

  5. Blood Pressure Monitorization • Postural response • BP is recorded after 5 min of rest. • The subject is instructed to stand up quickly, and BP is recorded immediately. • SBP difference (Postural Response) is calculated. • Sustained handgrip • A dynamometer is squeezed to a pressure of 30% of maximum for 3 min. • BP is measured at 30-sec intervals. • The change in DBP is recorded (Handgrip response).

  6. Autonomic System During Sleep NREM REM • High degree parasympathetic neural tone • Prominent respiratory sinus arrhythmia • Marked stability of autonomic regulation • Baroreceptor gain is high and contributes to the cardiovascular homeostasis • Muscle sympathetic nerve activity falls with the transition from wake to NREM sleep; reaching half the awake value during stage 4. • During transition from NREM to REM,bursts of vagus nerve activity may result in pauses in heart rhythm and frank asystole. • Marked by profound MSNA higher than in wakefulness • Sympathetic nerve activity is concentrated in short, irregular periods. • Increases in heart rate and arterial blood pressure reach to levels to those in wakefulness. • Cardiac efferent vagal tone and baroreceptor regulation are generally suppressed during REM sleep. • Breathing patterns may become highly irregular and may lead, in susceptible individuals, to oxygen desaturation.

  7. Recordings of Sympathetic-Nerve Activity (SNA) and Mean Blood Pressure (BP) in a Single Subject while Awake and while in Stages 2, 3, 4, and REM Sleep Somers V et al. N Engl J Med 1993;328:303-307

  8. Sympathetic-Nerve Activity during Sleep Stages Somers V et al. N Engl J Med 1993;328:303-307

  9. Heart Rate, Mean Blood Pressure, Sympathetic-Burst Frequency, and Burst Amplitude during Wakefulness and Non-REM Sleep (Eight Subjects) and REM Sleep (Six Subjects) Somers V et al. N Engl J Med 1993;328:303-307

  10. Autonomic System in OSAS During Sleep and Wakefulness • Catecholamine production and circulating catecholamine levels are high during sleep and wakefulness (Fletcher 1987, Carlson 1993, Somers 1995) • Muscle sympathetic nerve activity, MSNA, -independent from obesity- is elevated during wakefulness (Narkiewicz & Somers 1997, Leuenberger 1995, Saito 1988) • Autonomic stress test responses are impaired (Veale 1992, Smith 1998)

  11. Autonomic test scores in OSAS EVENING MORNING Autonomic stress tests in obstructive sleep apnea syndrome and snoring VEALE et al. Sleep1992;15:505-513.

  12. Significant associations of individual parametersof the autonomic test battery and OSA werealso observed. AHI was associated with A)tilt-induceddrop in systolic blood pressure (R = 0.58, P= 0.007), and with B)blood pressure drop (earlyphase 2) with Valsalva maneuver (R = 0.52, P = 0.017). Association of autonomic dysfunction and mild obstructivesleep apnea WOODSON et al. Otolaryngol Head Neck Surg 2004;130:643-8.

  13. OSAS is associated with a significant worsening in HRV, HRT,and QT dynamicity parameters. Furthermore, HRT and QTdynamicity parameters are found to be correlated with AHI. In contrast to HRT, and QT dynamicity, nighttime HRV wasnot linked to the severity of OSA. Our results may indicatethat HRV and QT dynamicity parameters can be usefulnoninvasive methods that may detect autonomic nervoussystem activity and ventricular vulnerability in OSAS. Increased myocardial vulnerability and autonomic nervous system imbalance in obstructivesleep apnea syndrome AYTEMİR K, et al. Respir Med (2006), doi:10.1016/j.rmed.2006.10.016

  14. Chemoreflex Function

  15. Autonomic System and Pathophysiology • Endothelial Function • Adipocyte Function • Adipokines • Localization of Fat Storage • Glucose Regulation

  16. 1-Endothelial Function

  17. 1-Endothelial Function

  18. 1-Endothelial Function Endothelium Derived Vasoconstrictors Endothelin-1 Angiotensin II Tromboxane A2 Prostaglandin H2 Superoxide anions Endothelium Derived Vasodilatators Nitric oxide Prostacyclin C-type natriuretic factor Serotonin ATP Substance P Asetilcholine Interactions between autonomic nervous system activity and endothelial function: A model for the development of cardiovascular disease HARRIS et al. Psychosomatic Medicine 2004;66:153-164.

  19. 2-Adiposit FonksiyonuADİPOKİNLER

  20. OSAS leptin The association of the severity of obstructive sleep apnea with plasma leptin levels. Öztürk et al. Arch Otolaryngol Head Neck Surg 129:538-40,2003.

  21. OSAS adiponectin ZhangXL et al. Respiration 2006;73:73-77

  22. OSAS Resistin Resistin levels in patients withobstructive sleep apnoea syndrome – the link to subclinical inflammation? Harsch et al. Med Sci Monit 10:CR510-5,2004.

  23. 2-Adipocyte FunctionFAT STORAGE Snitker et al. Obesity Rev 2000;1:5-15

  24. 2-Adipocyte FunctionFAT STORAGE

  25. 3-Glucose Regulation Intermediate pathways linking sleep apnea,glucoseintolerance, insulin resistance, and Type 2 DM. Disorders of glucose metabolism in sleep apnea. Punjabi NM & Polotsky VY J Appl Physiol 99:1998-2007,2005.

  26. DYSAUTONOMY IMPAIRED GLUCOSE REGULATION SLEEP APNEA

  27. Location of Fat Storage Adipokines e.g. leptin Impaired Glucose Regulation Endothelial Dysfunction Metabolic Syndrome Smith et al. 1998 Sleep Medicine Reviews

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