Neuroendocrine and immune responses to 16-day bed rest with realistic launch and landing G profiles.

BACKGROUND: Spaceflight is associated with increased glucocorticoids and catecholamines, both well-known for their immunosuppressive effects. The objective of this study was to develop a model of spaceflight by using a human centrifuge to reproduce launch and landing G forces along with bed rest to simulate microgravity. HYPOTHESIS: Acute changes in G forces are causal factors in neuroendocrine and immune changes. METHODS: Ten subjects underwent realistic launch G-force profiles followed by 16 d of 60 head-down tilt bed rest. At the end of the bed rest, subjects were subjected to realistic landing G-force profiles. Stress hormones and changes in leukocyte and lymphocyte subsets were measured in blood and urine samples over the course of the study. RESULTS: Similar to shorter Shuttle missions (i.e., < or = 9 d), plasma cortisol was significantly decreased at simulated landing while urinary epinephrine was significantly increased. Urinary cortisol was significantly increased after simulated launch. The pattern of leukocyte and lymphocyte changes also mirrored the changes found in shorter 9-d spaceflights. CONCLUSIONS: These data suggest a role for both catecholamines and glucocorticoids in mediating changes in leukocyte and lymphocyte subsets during simulated microgravity coupled with hypergravity. Our results were also strikingly similar to those from actual Shuttle missions and support our conclusion that we have developed a model of spaceflight.

Cognitive performance following premature awakening from zolpidem or melatonin induced daytime sleep.

BACKGROUND: The hypnotic zolpidem and the hormone melatonin were evaluated and directly compared for their effects on performance when subjects sleeping under their influence were prematurely awakened from daytime sleep. METHOD: Non-sleep deprived volunteers (eight men and five women) received single oral doses of 5 or 10 mg melatonin (Mel-5; Mel-10), 10 or 20 mg zolpidem (Zol-10; Zol-20), or placebo immediately before retiring at 13:00. Performance testing and subjective evaluations occurred prior to dosing and following forced awakening at 15:00, 2 h after dosing. RESULTS: Compared with placebo, on being awakened under Zol-20, significant performance decrements were prevalent on 9 of 10 cognitive tasks, including grammatical reasoning, mathematical processing, and word memory. Recovery required up to 6 h post-awakening for the more complex tasks. Loss of coordination and nausea were also present on awakening under Zol-20. On being awakened under Zol-10, significant but relatively less severe and shorter duration performance decrements occurred for 4 of the 10 tasks and recovered by 4 h post-awakening. Under Mel-5 or Mel-10, performance decrements seldom occurred and were considerably less severe, briefer, and less systematic than for zolpidem. CONCLUSION: Findings indicated that when operational personnel sleeping with the aid of either 10 or 20 mg zolpidem are prematurely awakened, it would be prudent to evaluate their general well-being and possible need for assistance prior to their being permitted to depart crew-rest or to perform tasks and duties. In contrast, we found little to no evidence of deteriorated well-being or need for assistance when awakened while sleeping under the influence of melatonin.

Hypnotic efficacy of zaleplon for daytime sleep in rested individuals.

STUDY OBJECTIVES: The primary objective of this study was to determine whether zaleplon (10 mg) effectively promoted sleep during the daytime in well-rested individuals when compared to placebo. A secondary objective was to see if, while not expected, the use of zaleplon impacted the performance of well-rested individuals upon awakening. DESIGN: Repeated measures with 2 within-subject factors: drug (placebo/zaleplon) and trial (hourly testing during waking hours). Polysomnographic variables were recorded during a 3.5-hour nap following drug administration. Performance measures and subjective reports were collected during every waking trial of each session. SETTING: The study was conducted at the Chronobiology and Sleep Laboratory located at Brooks Air Force Base. PARTICIPANTS: Twelve participants, 6 men and 6 women. INTERVENTIONS: 10-mg zaleplon or placebo capsules, single afternoon dose. Drug administration was counterbalanced and double-blinded. MEASUREMENTS AND RESULTS: Zaleplon allowed participants to obtain significantly more slow-wave sleep than under placebo. There was also a trend for participants under zaleplon to accomplish a greater amount of sleep than under placebo. Performance was not adversely impacted following a 3.5-hour daytime sleep under zaleplon, nor were any undesirable symptoms induced. CONCLUSIONS: Zaleplon improves sleep quality when used by rested individuals to accomplish daytime sleep.

Fatigue models for applied research in warfighting.

The U.S. Department of Defense (DOD) has long pursued applied research concerning fatigue in sustained and continuous military operations. In 1996, Hursh developed a simple homeostatic fatigue model and programmed the model into an actigraph to give a continuous indication of performance. Based on this initial work, the Army conducted a study of 1 wk of restricted sleep in 66 subjects with multiple measures of performance, termed the Sleep Dose-Response Study (SDR). This study provided numerical estimation of parameters for the Walter Reed Army Institute of Research Sleep Performance Model (SPM) and elucidated the relationships among several sleep-related performance measures. Concurrently, Hursh extended the original actigraph modeling structure and software expressions for use in other practical applications. The model became known as the Sleep, Activity, Fatigue, and Task Effectiveness (SAFTE) Model, and Hursh has applied it in the construction of a Fatigue Avoidance Scheduling Tool. This software is designed to help optimize the operational management of aviation ground and flight crews, but is not limited to that application. This paper describes the working fatigue model as it is being developed by the DOD laboratories, using the conceptual framework, vernacular, and notation of the SAFTE Model. At specific points where the SPM may differ from SAFTE, this is discussed. Extensions of the SAFTE Model to incorporate dynamic phase adjustment for both transmeridian relocation and shift work are described. The unexpected persistence of performance effects following chronic sleep restriction found in the SDR study necessitated some revisions of the SAFTE Model that are also described. The paper concludes with a discussion of several important modeling issues that remain to be addressed.

Performance following a sudden awakening from daytime nap induced by zaleplon.

BACKGROUND: Zaleplon appears to be a prime candidate for assisting individuals in obtaining sleep in situations not conducive to rest (i.e., a short period during the day). However, should an early unexpected awakening and return to duty be required, the effect on performance is not known. HYPOTHESIS: Zaleplon (10 mg) would negatively affect human performance for some duration, compared with placebo, after a sudden awakening from a short period (1 h) of daytime sleep. METHODS: There were 16 participants, 8 men and 8 women, who volunteered to participate in this study. The study was conducted using a counterbalanced, double-blind, repeated measures design. At 1 h prior to drug administration, and at each of 7 h postdrug, performance measures (cognition, memory, balance, and strength) and subjective symptom reports were recorded. RESULTS: Zaleplon had a statistically significant (p < 0.05) negative impact on balance through the first 2 h postdose when compared with placebo. In addition, symptoms related to "drowsiness" were statistically more prevalent under zaleplon than under placebo through the first 3 h postdrug. Of the eight measures of cognitive performance, six were significantly negatively impacted in the zaleplon condition through 2 h postdose when compared with placebo, with one remaining significantly degraded through 3 h postdose. Zaleplon also had a significantly negative impact on memory at 1 h and 4 h postdose. CONCLUSIONS: Zaleplon (10 mg), when used as a daytime sleep aid, causes drowsiness (and related symptoms) up to 3 h postdose, and may impact task performance, especially more complex tasks, for at least 2-3 h postdose.