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BioSci 24237 BIOLOGICAL RHYTHMS AND SLEEP

BioSci 24237 BIOLOGICAL RHYTHMS AND SLEEP. CLASS #18 Jet Lag and Shift Work March 11, 2003. Jet lag in a hamster: abrupt 5-h delay in L-D cycle ...7 days to adapt. Jet Lag - Symptoms:. Sleep disturbance: difficulties initiating and/or maintaining sleep

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BioSci 24237 BIOLOGICAL RHYTHMS AND SLEEP

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  1. BioSci 24237BIOLOGICAL RHYTHMS AND SLEEP CLASS #18 Jet Lag and Shift Work March 11, 2003

  2. Jet lag in a hamster: abrupt 5-h delay in L-D cycle ...7 days to adapt

  3. Jet Lag - Symptoms: • Sleep disturbance: difficulties initiating and/or maintaining sleep • Decrements of daytime vigilance and attention • Gastrointestinal distress • Tired muscles • Headaches • Reduced cognitive skills • Poor psychomotor coordination • Moodiness • General malaise

  4. Rate of Adaptation to Jet Lag“as little as 30 min per day, as much as 3 hours per day” • Eastward (advance) versus westward (delay) direction • Number of time zones crossed • Intensity of zeitgeber exposure • Timing of zeitgeber exposure • Age and gender • Individual differences

  5. Upon arrival • Desynchronization of endogenous rhythms with exogenous: 1. Light-dark cyle • Activity-rest cycle • Meal times

  6. SLEEP AFTER WESTWARD (DELAY) TRAVEL

  7. SLEEP AFTER EASTWARD (ADVANCE) TRAVEL

  8. INDIVIDUAL DIFFERENCES IN RATE OF ADAPTATION

  9. 75 17 65 13 55 45 9 35 25 5 BASELINE RECOVERY BASELINE RECOVERY Women Men WAKE MINUTES PERCENT NIGHT EFFECT 0.08 NIGHT EFFECT 0.08 GENDER EFFECT ns GENDER EFFECT ns INTERACTION 0.04 INTERACTION 0.03

  10. JET LAG IN THE LAB: PROTOCOL 19 03 11 19 03 11 19 23 07 15 23 07 15 23 Normal night Night of sleep deprivation Daytime sleep recovery

  11. PLASMA CORTISOL (µg/dL) 20 15 10 5 0 18 22 02 06 10 14 18 22 02 06 10 14 18 22 CLOCK TIME NOCTURNAL SLEEP NOCTURNAL SLEEP DEPRIVATION DAYTIME SLEEP

  12. PLASMA CORTISOL (µg/dL) 20 15 10 5 0 18 22 02 06 10 14 18 22 02 06 10 14 18 22 CLOCK TIME NOCTURNAL SLEEP NOCTURNAL SLEEP DEPRIVATION DAYTIME SLEEP

  13. PLASMA GH (µg/L) 20 15 10 5 0 18 22 02 06 10 14 18 22 02 06 10 14 18 22 CLOCK TIME NOCTURNAL SLEEP NOCTURNAL SLEEP DEPRIVATION DAYTIME SLEEP

  14. The Jet Lag Syndrome : Biological Causes • Abrupt behavioral modification of all external zeitgebers • Homeostatic component adapts rapidly • Circadian component adapts slowly • Sleep loss • External desynchronization • Misalignment of 24-hour rhythms: internal desynchronization

  15. A study of “real” jet lag Study 1: Brussels Studies 2,3,4: 2, 10 and 21 days after arrival in Chicago Studies 5,6 and 7: 2, 10 and 21 days after return to Brussels

  16. Adaptation of prolactin profile reveals circadian component

  17. Adaptation of prolactin profile reveals circadian component

  18. Treatment of Jet Lag • Pharmacological intervention to facilitate sleep and increase vigilance • Appropriately timed exposure to light • Appropriately timed exposure to exercise • Melatonin

  19. Westward (delay) jet lag in the lab * Placebo or triazolam

  20. Mean 24-hr profiles of plasma cortisol (±SEM) obtained during baseline conditions and one, three and five days after an 8-hour delay of the sleep-wake and light-dark cycles treated either with placebo (left panels) or with 0.5 mg triazolam (right panels). Bed times in darkness are shown by black bars.

  21. Mean 24-hr profiles of plasma cortisol (±SEM) obtained during baseline conditions and one, three and five days after an 8-hour delay of the sleep-wake and light-dark cycles treated either with placebo (left panels) or with 0.5 mg triazolam (right panels). Bed times in darkness are shown by black bars.

  22. Onset of cortisol increase as a phase marker

  23. Treatment of Jet Lag • Pharmacological intervention to facilitate sleep and increase vigilance • Appropriately timed exposure to light • Appropriately timed exposure to exercise • Melatonin

  24. P P DIM LIGHT PLACEBO P P BRIGHT LIGHT PLACEBO Z Z DIM LIGHT ZOLPIDEM L D B L B L D B L 11 15 19 23 03 07 11 15 19 23 03 07 11 15 19 23 03 07 Day 1 (baseline) Day 2 Day 3

  25. P P P P Z Z PLASMA TSH (% of daytime mean) 400 DIM LIGHT 200 0 400 BRIGHT LIGHT 200 0 400 ZOLPIDEM 200 0 15 23 07 15 23 07 15 23 07 CLOCK TIME

  26. BRIGHT LIGHT DIM LIGHT ZOLPIDEM 200 MINUTES OF WAKE 100 0 300 200 MINUTES OF I+II 100 0 90 60 MINUTES OF SWS 30 0 120 80 MINUTES OF REM 40 0 BAS SH1 SH2 BAS SH1 SH2 BAS SH1 SH2 NIGHTS

  27. PLASMA MELATONIN (pg/ml) 40 DIM LIGHT 20 P P 0 40 BRIGHT LIGHT 20 P P 0 40 ZOLPIDEM 20 Z Z 0 15 23 07 15 23 07 15 23 07 CLOCK TIME

  28. 180 PLASMA CORTISOL (ng/ml) 135 DIM LIGHT 90 45 P P 0 180 135 BRIGHT LIGHT 90 45 P P 0 180 135 ZOLPIDEM 90 45 Z Z 0 15 23 07 15 23 07 15 23 07 CLOCK TIME

  29. Melatonin treatment of jet lag

  30. Treatment of Jet Lag • Pharmacological intervention to facilitate sleep and increase vigilance • Appropriately timed exposure to light • Appropriately timed exposure to exercise • Melatonin

  31. Shift Work - Prevalence: • 20% of the U.S. work force is now engaged in some form of shift work.

  32. Shift Work: Health Impact • Recognized as a risk factor for • sleep disorders • depression • cardiovascular illness • gastro-intestinal disease • infertility • substance abuse • weight gain

  33. 2000 Omnibus Sleep in America Poll

  34. Nighttime versus daytime sleep

  35. Shift Work - "Blue collar jet lag" • 55% of night shift workers report nodding off or falling asleep at work at least once per week. • >30% report such incidents occur more than three times per week.

  36. Sleep Loss - Socioeconomic Consequences • More than 100,000 motor vehicle accidents annually are sleep-related. • Disasters such as Chernobyl, Three Mile Island, Challenger, Bhopal, and Exxon Valdez were officially attributed to errors in judgement induced by sleepiness or fatigue

  37. FATIGUE-RELATED AUTO ACCIDENTSCompiled Data No. of Accidents (n = 6,052) Mitler MM, Et al. Sleep. 1988;11:100.

  38. Shift Work • Ambulatory PSGs on 20 nuclear power workers:25% fell asleep while operating the plant - predominately in the night shift.

  39. Sleeping on the Job

  40. Sleep Inertia

  41. Sleep Inertia - Case 1 • You are asked to defend a physician colleague. He was awakened at 3 am by a call from the emergency room. A patient of his, also a physician, was being evaluated for an acute medical condition. Your colleague's therapeutic recommendations over the phone, which were not what he would have normally recommended, resulted in worsening of the patient's condition.

  42. Sleep Inertia - Case 1 • He had no recall of either the phone call or of his recommendations. The patient sued. Your colleague's peers uniformly stated that his recommendations were totally and completely out of character for him, and would never have been made from a state of full wakefulness.

  43. Shift Work • A state of chronic external and internal desynchronization

  44. Circadian components: Very little adaptation

  45. Homeostatic components: good adaptation

  46. Hormonal profiles in shift work Spiegel K et al, Chronobiol Int,1996. Weibel L et al, Chronobiol Int,1997. Weibel L et al, Endocrinol Metab,1996.

  47. POSSIBLE INTERVENTIONS: Direction of shift rotation Duration on shift Use of bright light in workplace Maintenance of dark in sleep place Decreased environmental noise in sleep place Medications (for sleep, alertness or shifting clock) Napping strategies Recruit worker whose lifestyle matches that of required shift work

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