journal article
LitStream Collection
Home
Wyatt, James K.; Dijk, Derk-Jan; Cecco, Angela Ritz-De; Ronda, Joseph M.; Czeisler, Charles A.
doi: 10.1093/sleep/29.5.609pmid: 16774150
AbstractStudy Objectives:To investigate the effects of a physiologic and a pharmacologic dose of exogenous melatonin on sleep latency and sleep efficiency in sleep episodes initiated across a full range of circadian phases. Design: Double-blind placebo-controlled parallel-group design in a 27-day forced desynchrony paradigm with a 20-hour scheduled sleep-wake cycle.Setting:Private suite of a general clinical research center, in the absence of time-of-day information.Subjects:Thirty-six healthy, 18- to 30-year-old, men (n = 21) and women (n = 15).Interventions:Oral melatonin (0.3 mg or 5.0 mg) or identical-appearing placebo was administered 30 minutes prior to each 6.67-hour sleep episode during forced desynchrony.Measurements and Results:Both doses of melatonin improved polysomnographically determined sleep efficiency from 77% in the placebo group to 83% for sleep episodes occurring during circadian phases when endogenous melatonin was absent. However, this remained below the average sleep efficiency of 88% observed during sleep episodes scheduled during the circadian night, when endogenous melatonin was present. Melatonin did not significantly affect sleep initiation or core body temperature. Melatonin appeared to maintain efficacy across the study and did not significantly affect percentages of slow-wave sleep or rapid eye movement sleep.Conclusions:Exogenous melatonin administration possesses circadian-phase-dependent hypnotic properties, allowing for improved consolidation of sleep that occurs out of phase with endogenous melatonin secretion during the circadian night. The results support the hypothesis that both exogenous and endogenous melatonin attenuate the wake-promoting drive from the circadian system.
Catcheside, Peter G.; Orr, R. Stan; Chiong, Siau Chien; Mercer, Jeremy; Saunders, Nicholas A.; McEvoy,, R. Douglas
doi: 10.1093/sleep/29.5.619pmid: 16774151
AbstractStudy Objectives:The depressive effects of hypoxia on the central nervous system are well known. The purpose of this study was to determine the influence of mild overnight hypoxia on the ability of healthy individuals to arouse from non-rapid-eye-movement (NREM) sleep to auditory tones.Design:Randomized cross-over.Setting:Participants slept in a sound-insulated room with the physiologic recordings and experimental interventions controlled from a separate room.Participants:Eleven healthy men aged 18 to 24 years.Interventions:On separate nights, participants were exposed to mild overnight hypoxia (SaO2 ~90%) or medical air in single-blind fashion. During established sleep, subjects were administered 1 of 10 auditory tones (500 Hz, 54–90 dB, 5 seconds duration) via earphones, or a sham tone (recording period with no tone).Measurements and Results:The probability and intensity of arousal responses in the 30 seconds following tones or shams were compared between gas conditions and between stage 2 and slow-wave sleep. Arousal probability and intensity increased with tone intensity and were significantly lower during slow-wave compared with stage 2 sleep but were not different between hypoxia and normoxia nights.Conclusion:These data suggest that mild overnight hypoxia does not impair the neural mechanisms involved in arousal from sleep to auditory stimuli.
Hlavac, Michael C.; Catcheside, Peter G.; McDonald, Rachel; Eckert, Danny J.; Windler, Samantha; McEvoy, R. Doug
doi: 10.1093/sleep/29.5.624pmid: N/A
AbstractStudy Objectives:Sustained hypoxia is a neurocognitive depressant, which has been shown to impair respiratory load sensation. Hypoxia has also been shown to impair arousal in animal models, but the effects of sustained hypoxia on arousal in humans have not been studied. The aim of this study was to assess the effects of sustained hypoxia on arousal from sleep in normal subjects.Design:Twelve normal male subjects (age, 24.3 ± 1.2 years; body mass index, 24.8 ± 1.4 kg/m2) were studied during stable stage 2 non-rapid eye movement sleep on 2 separate nights 1 week apart.Setting:Sleep physiology laboratory.Participants:Normal healthy volunteers.Interventions:Arousal responses to external resistive loads (18 cm H2O.L−1.sec−1) and occlusions were compared during room-air breathing following sustained normoxia and isocapnic hypoxia (SaO2~85%).Measurements and Results:Time to arousal and minimum esophageal pressure preceding arousal were measured. Time to arousal was significantly increased following hypoxia compared with normoxia for resistive loads (24.6 + 4.4 seconds vs. 12.6 ± 1.9 seconds, p = .007) but not occlusions. Minimum esophageal pressure prior to arousal was more negative following hypoxia for both external loads (-16.8 ± 1.2 vs. −13.5 ± 1.3 cm H2O, p = .035) and occlusions (-19.6 ± 2.2 vs. -15.1 ± 1.5 cm H2O, p = .029).Conclusions:We conclude that sustained isocapnic hypoxia delays arousal to inspiratory loading during sleep and increases the respiratory arousal threshold. This has implications for disorders characterized by sustained nocturnal hypoxia, such as neuromuscular weakness, chronic obstructive pulmonary disease, obesity-hypoventilation syndrome, and severe obstructive sleep apnea.
Tanaka, Susumu; >Honda, Yutaka; Inoue, Yuichi; Honda, Makoto
doi: 10.1093/sleep/29.5.633pmid: 16774153
AbstractStudy Objectives:The impairment of hypocretin neurotransmission system is considered to play a major role in the pathophysiology of narcolepsy. It has been hypothesized that autoimmune abnormalities underlie the etiology of narcolepsy, based on the tight association with HLA-DRB1*1501/DQB1*0602. It remains unclear if autoantibodies against hypocretin receptors (hcrtr1 and hcrtr2) are involved in narcolepsy.Design:We have developed a novel radioligand binding assay to address this question. Sera from 181 patients with narcolepsy, 10 patients with other hypersomnias, and 91 control subjects were used. Human [35S]-Hcrt, hcrtr1, and hcrtr2 were synthesized by in vitro transcription/translation system. The immune complex of autoantibody and each [35S]-protein were immunoprecipitated and quantified using a radioligand-binding assay.Results:We detected autoantibodies against hypocretin in 3 patients, hcrtr1 in 1 patient, and hcrtr2 in 5 patients with narcolepsy. Positive reactions were also found against hcrtr1 in 2 and hcrtr2 in 1 control subjects. No relationships were found between these autoantibodies and HLA-DRB1*1501/DQB1*0602 haplotypes, presence of cataplexy, presence of subjective nocturnal sleep disruption, or the score on the Epworth Sleepiness Scale.Conclusions:Although we have detected autoantibodies against the hypocretin neurotransmission system, our results do not support the hypothesis that autoantibody-mediated dysfunction in the hypocretin system underlies the pathophysiology of narcolepsy.
Showing 1 to 10 of 21 Articles