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Translational Research of Sleep Medicine 睡眠醫學之轉譯研究

Translational Research of Sleep Medicine 睡眠醫學之轉譯研究. Terry B.J. Kuo, MD, PhD ( 郭博昭) Professor and Director, Institute of Brain Science, National Yang-Ming University Director, Brain Research Center, The University System of Taiwan Cheryl C.H. Yang, PhD ( 楊靜修)

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Translational Research of Sleep Medicine 睡眠醫學之轉譯研究

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  1. Translational Research of Sleep Medicine睡眠醫學之轉譯研究 Terry B.J. Kuo, MD, PhD (郭博昭) Professor and Director, Institute of Brain Science, National Yang-Ming University Director, Brain Research Center, The University System of Taiwan Cheryl C.H. Yang, PhD (楊靜修) Professor, Institute of Brain Science, National Yang-Ming University

  2. Hypertension Essential Hypertension > 90% Secondary Hypertension < 10% Renal hypertension Endocrine hypertension Others

  3. Possible Mechanisms of “Essential Hypertension” Heredity Environment Heart and Vessels ventricular hypertrophy, atherosclerosis... Nerve Impairment of autonomic nervous system... BP = CO * TPR Autonomic Nervous System Measurement of autonomic function is difficult in free moving subjects.

  4. Non-invasive Technique Heart Rate Variability HF: Parasympathetic (Vagal) activity LF/HF, LF%: Cardiac sympathetic modulationSympathovagal balance Akselrod et al (1981) Science Arterial Pressure Variability LF (BLF): Vascular sympathetic modulation Sympathetic blockade Kuo et al (1997) Am J Physiol

  5. Heart Rate Variability in Humans HRV HRV Lucini et al (2002) Circulation

  6. Arterial Pressure Variability in Rats WKY SHR WKY SHR WKY SHR Stauss et al (1995) J Auton Nerv Syst

  7. Most of the previous controversial results were obtained without a detailed classification of the sleep-wake states Hypothesis The changes in autonomic functions accompanied with hypertension are consciousness state dependent.

  8. Aims To determine whether the cardiovascular autonomic functions have specific pathological changes in spontaneously hypertensive rats during sleep time

  9. Polysomnographic Analysis in Rats: Electroencephalogram(EEG), Electromyogram (EMG), and Electrocardiogram (ECG) Shaw et al (2002) J Neuroscei Meth

  10. K&Y Lab’s Polysomnography Data Acquisition and Analysis Software ElectrophysiologicAmplifiers Free moving rat Digital Video Recorder Shaw et al (2002) J Neurosci Meth

  11. K&Y Lab’s Polysomnography (II) Kuo and Yang (2004) Taiwan Patent

  12. K&Y Lab’s Wireless BP Recorder

  13. K&Y Lab’s Sleep Scoring System • Step 1: Power spectral analysis of EEG, EMG, and HRV • Step 2: Classification of Sleep Stage • Step 3: Determination of Sleep Structure Kuo et al (2004) Sleep

  14. Power Spectral Analysis Power = 7 MPF = 4 Power = 3 MPF = 7 MPF: Mean Power Frequency Power: Amplitude or Magnitude

  15. Classification of Sleep Stage EMG Power AW: active waking QS: quiet sleep PS: paradoxical sleep AW EEG Frequency QS PS

  16. Mature AW, QS, and PS: persist unchanged for  56 s Transient Interruptions: fail to last for 56 s Determination of Sleep Structure EMG Power AW EEG MPF QS PS

  17. AW QS PS QS PS QS SWA P S a normal rat Yang et al (2003) Neurosci Lett

  18. In Normal Rats During QS.. P S S P SWA Yang et al (2003) Neurosci Lett

  19. QS QS QS QS QS SWA P S a normal human Yang et al (2002) Neurosci Lett

  20. In Normal Humans During QS.. P S S P SWA Yang et al (2002) Neurosci Lett

  21. rat VagalFunction SympatheticFunction human Sleep Depth AW QS PS AW QS REM Sleep Depth Sleep and autonomic functions interaction between cerebral cortical and autonomic functions

  22. Normotensive Rats (WKY) and Spontaneously Hypertensive Rats (SHR)

  23. WKY VascularSympathetic CardiacVagal CardiacSympathetic Kuo and Yang (2005) Circulation

  24. SHR VascularSympathetic CardiacVagal CardiacSympathetic Kuo and Yang (2005) Circulation

  25. Kuo and Yang (2005) Circulation

  26. CardiacVagal CardiacSympathetic VascularSympathetic BaroreflexSensitivities Kuo and Yang (2005) Circulation

  27. Editorial (Circulation 2005:112:786-788)

  28. Differences in Sleep Patternsbetween WKY and SHR

  29. Kuo et al (2004) Sleep

  30. Summary 1 During quiet sleep (slow wave sleep), the sympathetic function should rest in normal condition: the deeper sleep, the lower sympathetic modulation. 2 During quiet sleep, the vagal function should activate. But the increase magnitude is not related with the sleep depth. 3 The baroreflex function should activate during quiet sleep.

  31. Summary 4 The changes of autonomic functions during quiet sleep are reversed during paradoxical sleep (rapid eye movement sleep). 5 The cardiovascular sympathetic function does not rest during quiet sleep in SHR. 6 The baroreflex function does not activate during quiet sleep in SHR. 7 The changes in autonomic functions in SHR may be related to the changes in sleep quantity and quality.

  32. Limitations Human study For the fixed polysomnography The size is too large, users must sleep in an unfamiliar environment. This may affect the accuracy of the collected data. For the ambulatory polysomnography The device is still large, and too expensive. Animal study The wires may cause some interference, including electrical noise and psychological stress

  33. Research Motivation To develop the best equipment for the best sleep research For the human study accurate, miniature, wireless, low cost For the animal study accurate, miniature, wireless, low cost

  34. The Introduction of Low-power, Digital Radio Frequency Technique

  35. 失眠會造成哪些後遺症 • 精神疾病 • 心臟血管疾病 • 意外傷害 • 行為障礙 • 影響工作表現 • 消耗醫療資源

  36. Try to use the new technique

  37. Button-type wireless recording system

  38. K&Y’s Wireless Electrocardiography Receiver Sensor

  39. Receiver Electrocardiogram Sensor

  40. K&Y’s WirelessElectrocardiography • Radio Frequency: 2.4 GHz • Data transmition mode: digital, bi-directional, acknowledged • Sampling resolution: 8-12 bits, 125-1000 samples/s • Power: 1.9V, 1 mA (on), <10 uA (off) • One tiny button-type battery (CR1620: 3 V, 70 mAH) can operate continuously over 2 days. • Target to the smallest digital, wireless ECG sensor • Implemented with a specially designed RF protocol, more efficient to Bluetooth, Zigbee protocols • Applied with other sensor techniques, including body temperature, EEG, EOG, EMG • A prototype of disposable tiny wireless medical instrument • Patent pending

  41. K&Y’s Wireless Polysomnography

  42. K&Y’s Wireless Polysomnography • Continuous recording of multiple physiological signals over 24 hours • Completely wireless • ECG, EMG, EOG, EEG • 3-D acceleration, Body temperature, • Telemetric signal transmission • Easy to use • Sleep recorder, Holter monitor, Actimeter, Body temperature recorder

  43. K&Y’s Wireless Polysomnography for Rats

  44. AW

  45. QS

  46. PS

  47. K&Y’s Wireless Polysomnography for Rats • Continuous recording of multiple physiological signals over 24 hours • Partially wireless • ECG, EMG, EEG • 3-D acceleration, Body temperature, • Telemetric signal transmission • Easy to use • Sleep recorder, ECG recorder, Actimeter, Body temperature recorder 2.3 cm Microcontroller & RF tranciver Amplifiers & Accelerometer 0.6 cm Battery Connector Signal relayed by Wires

  48. K&Y’s Wireless Polysomnography for Mice

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