Centrifugation as a countermeasure during bed rest and dry immersion: What has been learned?

OBJECTIVES: We review the studies that have evaluated intermittent short-radius centrifugation as a potential countermeasure for cardiovascular, musculoskeletal, and sensorimotor deconditioning in simulated weightlessness. METHODS: The findings from 18 experimental protocols that have used bed rest and dry immersion for comparing the protective effects of centrifugation versus standing upright or walking, and the effects of continuous vs. periodic exposure to centrifugation are discussed. RESULTS: Centrifugation for as little as 30 min per day was found to be effective in mitigating orthostatic intolerance and strength in postural muscle after 5 days of bed rest, but it was not effective in mitigating plasma volume loss. CONCLUSION: To determine the optimal prescription for centrifugation as a countermeasure, we recommend further studies using (a) bed rest of longer duration, (b) individualized prescriptions of centrifugation combined with exercise, and

Effects of five days of bed rest with intermittent centrifugation on neurovestibular function.

OBJECTIVES: We tested whether intermittent short-radius centrifugation was effective for mitigating alteration in balance and gait following bed rest. METHODS: Ten male subjects were exposed to 5 days of 6° head-down tilt bed rest with: (a) no countermeasure; (b) daily 1-g centrifugation for a continuous 30-min period; and (c) daily 1-g centrifugation for six periods of 5 min. During and after the bed rest, subjects were asked to scale the severity of neurovestibular symptoms that followed centrifugation or 80° head-up tilt. Following the bed rest, equilibrium scores were derived from anterior-posterior sway while standing on a foam pad with the eyes open or closed while making pitch head movements, and gait was evaluated by grading subjects' performance during various locomotion tasks. RESULTS: At the beginning of bed rest, one single 30-min period of centrifugation induced more severe neurovestibular symptoms than six periods of 5-min centrifugation. After bed rest, although equilibrium scores and gait performance were not significantly altered, subjects felt less neurovestibular dysfunction with orthostatic stress when centrifugation was used. CONCLUSION: Centrifugation was effective at reducing the severity of neurovestibular symptoms after bed rest, but this decrease was not different between one or multiple daily sessions.

Musculoskeletal effects of 5 days of bed rest with and without locomotion replacement training.

OBJECTIVES: The present study evaluated the effectiveness of a short and versatile daily exercise regime, named locomotion replacement training (LRT), to maintain muscle size, isometric strength, power, and endurance capacity of the leg muscles following 5 days of head-down tilt (HDT) bed rest. METHODS: 10 male subjects (age 29.4 ± 5.9 years; height 178.8 ± 3.7 cm; body mass 77.7 ± 4.1 kg) performed, in random order, 5 days of 6° head-down tilt bed rest (BR) with no exercise (CON), or BR with daily 25 min of upright standing (STA) or LRT. RESULTS: Knee extensor and plantar flexor cross-sectional area (CSA) were reduced by 2-3 % following bed rest (P < 0.01) for CON and STA, yet maintained for LRT. Knee extensor isometric strength (MVC) decreased by 8 % for CON (P < 0.05), was maintained for STA, and increased with 12 % for LRT (P < 0.05). Plantar flexor MVC remained unaltered during the study. Maximum jump height declined (~1.5 cm) for all conditions (P < 0.001). Neural activation and knee extensor fatigability did not change with bed rest. Bone resorption increased during BR and neither LRT nor STA was able to prevent or attenuate this increase. CONCLUSION: LRT was adequate to maintain muscle size and to even increase knee extensor MVC, but not muscle power and bone integrity, which likely requires more intense and/or longer exercise regimes. However, with only some variables showing significant changes, we conclude that 5 days of BR is an inadequate approach for countermeasure assessments.

Effects of five days of bed rest with and without exercise countermeasure on postural stability and gait.

OBJECTIVES: We tested whether intermittent standing or a combination of heel raising, squatting and hopping exercises was sufficient to prevent alteration in balance and gait following a 5-day bed rest. METHODS: This cross-over design study was performed with 10 male subjects during 6° head down tilt: (a) with no countermeasure; (b) while standing 25 min per day; (c) during locomotion-like activities 25 min per day. Gait was evaluated by grading subjects' performance during various locomotion tasks. Equilibrium scores were derived from peak-to-peak anterior-posterior sway while standing on a foam pad with the eyes open or closed or while making pitch head movements. RESULTS: When no countermeasure was used, head movements led to decreased postural stability and increased incidence of falls immediately after bed rest compared to before. When upright standing or locomotion-like exercises were used, postural stability and the incidence of falls were not significantly different after the bed rest from the baseline. CONCLUSION: These results indicate that daily 25-min of standing or locomotion-like exercise proves useful against postural instability following a 5-day bed rest. The efficacy of these countermeasures on locomotion could not be evaluated, however, because gait was not found to be altered after a 5-day bed rest.

Study protocol, implementation, and verification of a short versatile upright exercise regime during 5 days of bed rest.

OBJECTIVES: This work provides a reference for future papers originating from this study by providing basic results on body mass, urine volume, and hemodynamic changes to 5 days of bed rest (BR) and by describing acute cardio-respiratory/mechanographic responses to a short versatile upright exercise battery. METHODS: Ten male subjects (mean ± SEM age: 29.4 ± 1.5 years; height: 178.8 ± 1.5 cm; body mass: 77.7 ± 1.5 kg) performed, in random order, 5 days of 6° head-down tilt (HDT) BR with no exercise (CON), or BR with daily 25 minutes of quiet upright standing (STA) or upright locomotion replacement training (LRT). RESULTS: Plasma volume, exercise capacity and orthostatic tolerance decreased similarly between interventions following 5 days of BR. Upright heart rate during LRT and STA increased throughout BR; from 137 ± 4 bpm to 146 ± 4 bpm for LRT (P<0.01); and from 90 ± 3 bpm to 102 ± 6 bpm (P<0.001) for STA. CONCLUSION: the overall similarity in the response to BR, and increase in upright heart rate during the LRT sessions suggest early and advancing cardiovascular deconditioning during 5 days of BR bed rest, which was not prevented by the versatile exercise regime.

Effects of 21 days of bed rest, with or without artificial gravity, on nutritional status of humans.

Spaceflight and bed rest models of microgravity have profound effects on physiological systems, including the cardiovascular, musculoskeletal, and immune systems. These effects can be exacerbated by suboptimal nutrient status, and therefore it is critical to monitor nutritional status when evaluating countermeasures to mitigate negative effects of spaceflight. As part of a larger study to investigate the usefulness of artificial gravity as a countermeasure for musculoskeletal and cardiovascular deficits during bed rest, we tested the hypothesis that artificial gravity would have an effect on some aspects of nutritional status. Dietary intake was recorded daily before, during, and after 21 days of bed rest with artificial gravity (n = 8) or bed rest alone (n = 7). We examined body composition, hematology, general blood chemistry, markers of oxidative damage, and blood levels of selected vitamins and minerals before, during, and after the bed rest period. Several indicators of vitamin status changed in response to diet changes: serum alpha- and gamma-tocopherol and urinary 4-pyridoxic acid decreased (P < 0.001) and plasma beta-carotene increased (P < 0.001) in both groups during bed rest compared with before bed rest. A decrease in hematocrit (P < 0.001) after bed rest was accompanied by a decrease in transferrin (P < 0.001), but transferrin receptors were not changed. These data provide evidence that artificial gravity itself does not negatively affect nutritional status during bed rest. Likewise, artificial gravity has no protective effect on nutritional status during bed rest.

Recovery of postural equilibrium control following spaceflight.

Decreased postural stability is observed in most astronauts immediately following spaceflight. Because ataxia may present postflight operational hazards, it is important to determine the incidence of postural instability immediately following landing and the dynamics of recovery of normal postural equilibrium control. It is postulated that postflight postural instability results from in-flight adaptive changes in central nervous system (CNS) processing of sensory information from the visual, vestibular, and proprioceptive systems. The purpose of the present investigation was to determine the magnitude and time course of postflight recovery of postural equilibrium control and, hence, readaptation of CNS processing of sensory information. Thirteen crew members from six spaceflight missions were studied pre- and postflight using a modified commercial posturography system. Postural equilibrium control was found to be seriously disrupted immediately following spaceflight in all subjects. Readaptation to the terrestrial environment began immediately upon landing, proceeded rapidly for the first 10-12 hours, and then proceeded much more slowly for the subsequent 2-4 days until preflight stability levels were reachieved. It is concluded that the overall postflight recovery of postural stability follows a predictable time course.

Effects of gas properties and waveform asymmetry on gas transport in a branching tube network.

Local gas transport coefficients, quantifying longitudinal dispersion through a symmetrical constant-diameter tube network, have been measured during oscillation with both symmetrical and nonsymmetrical waveforms. Experiments were carried out over a range of conditions that would prevail in the central to lower airways during high-frequency ventilation at moderate frequency (5 Hz) and tidal volume (15-80 ml). Gas transport coefficients resulting from oscillation of three different resident-trace gas pairs were measured using a new analytic technique. This technique allowed rapid determination of the transport coefficient distribution along the entire network. Results demonstrate a small but significant influence attributable to changes in gas properties that is similar to that found in a straight tube and indicate that augmented dispersion is an important mechanism of axial transport. Gas transport coefficients were found to be unaffected by changes in flow waveform symmetry, suggesting that previously reported improvements in gas exchange associated with decreasing inspiratory to expiratory time ratios are not due to a change in local conditions such as asymmetry in the velocity profile.

Space flight and neurovestibular adaptation.

Space flight represents a form of sensory stimulus rearrangement requiring modification of established terrestrial response patterns through central reinterpretation. Evidence of sensory reinterpretation is manifested as postflight modifications of eye/head coordination, locomotor patterns, postural control strategies, and illusory perceptions of self or surround motion in conjunction with head movements. Under normal preflight conditions, the head is stabilized during locomotion, but immediately postflight reduced head stability, coupled with inappropriate eye/head coordination, results in modifications of gait. Postflight postural control exhibits increased dependence on vision which compensates for inappropriate interpretation of otolith and proprioceptive inputs. Eye movements compensatory for perceived self motion, rather than actual head movements have been observed postflight. Overall, the in-flight adaptive modification of head stabilization strategies, changes in head/eye coordination, illusionary motion, and postural control are maladaptive for a return to the terrestrial environment.

Transient cardio-respiratory responses to visually induced tilt illusions.

Although the orthostatic cardio-respiratory response is primarily mediated by the baroreflex, studies have shown that vestibular cues also contribute in both humans and animals. We have demonstrated a visually mediated response to illusory tilt in some human subjects. Blood pressure, heart and respiration rate, and lung volume were monitored in 16 supine human subjects during two types of visual stimulation, and compared with responses to real passive whole body tilt from supine to head 80 degrees upright. Visual tilt stimuli consisted of either a static scene from an overhead mirror or constant velocity scene motion along different body axes generated by an ultra-wide dome projection system. Visual vertical cues were initially aligned with the longitudinal body axis. Subjective tilt and self-motion were reported verbally. Although significant changes in cardio-respiratory parameters to illusory tilts could not be demonstrated for the entire group, several subjects showed significant transient decreases in mean blood pressure resembling their initial response to passive head-up tilt. Changes in pulse pressure and a slight elevation in heart rate were noted. These transient responses are consistent with the hypothesis that visual-vestibular input contributes to the initial cardiovascular adjustment to a change in posture in humans. On average the static scene elicited perceived tilt without rotation. Dome scene pitch and yaw elicited perceived tilt and rotation, and dome roll motion elicited perceived rotation without tilt. A significant correlation between the magnitude of physiological and subjective reports could not be demonstrated.

Delayed pulmonary dysfunction in head-injured patients.

Intracranial pressure (ICP), cardiopulmonary function, and the degree of neurological dysfunction were measured in 13 patients with serious head injury to determine the relationship of these indices to the development of delayed pulmonary dysfunction. All patients had serious isolated head injury with Glasgow Coma Scale scores of 7 or less 6 hours after injury and elevated ICP at the time of admission to the protocol. Three patients developed arterial pO2 of less than or equal to 80 torr despite the initiation of elevated inspired oxygen fraction (FIO2 greater than or equal to 0.5) and positive end expiratory pressure (greater than or equal to 5 cm H2O. One of these three patients had a decline in neurological function, quantified by the Albany Head-Injury Watch Sheet, associated with hypoxemia. The only patients who developed intrapulmonary shunt fractions of more than 15% were five patients who had increased pulmonary vascular resistance (PVR) and elevated or increasing cardiac index, suggesting persistent perfusion to areas of the lung which normally are hypoperfused due to hypoxic pulmonary vasoconstriction. This mismatching of the distribution of ventilation and perfusion was confirmed using the multiple inert gas elimination technique in two patients with an increased shunt fraction. Unperfused gas exchange units were also found to be present, as confirmed by an abnormal multiple inert gas elimination techniques, high PVR and dead space/tidal volume ratio (VD/VT), and low extravascular lung water. Abnormalities of ICP and cerebral perfusion pressure could not be correlated with changes in any of the cardiopulmonary functions studied.

Multivariate changes in coordination of postural control following spaceflight.

Postural and gait instabilities in astronauts returning from spaceflight are thought to result from in-flight adaptation of central nervous system processing of sensory inputs from the vestibular, proprioceptive, and visual systems. We hypothesized that reorganization of posture control relying on these multiple inputs would result in not only greater amounts of sway, but also changes in interjoint coordination. We tested this hypothesis by examining the multivariate characteristics of postural sway and comparing the postural control gain used for maintenance of upright stance during the altered sensory conditions of the Sensory Organization Test (EquiTest, Neurocom Intl.). We used the covariance of hip and ankle kinematics as a measure of joint motion and interjoint coordination, and then utilized discriminant analysis to further examine these characteristics in a group of 10 first-time astronauts. In five of the six conditions, the most important difference was an increased relative utilization of the hip strategy, which would not be evident using conventional balance measures such as peak or root-mean-square sway. This finding was supported by indications of increased hip torque gains relative to lower extremity and neck motion in at least four conditions (p < 0.05). In contrast, ankle torque gains to these motions did not appear to change. These results suggest that after spaceflight, astronauts exhibit significant multivariate changes in multijoint coordination, of which increased sway is only one component. These changes are consistent with reweighting of vestibular inputs and changes in control strategy in a multivariable control system.

Vestibulospinal adaptation to microgravity.

Human balance control is known to be transiently disrupted after spaceflight; however, the mechanisms responsible for postflight postural ataxia are still under investigation. In this report, we propose a conceptual model of vestibulospinal adaptation based on theoretical adaptive control concepts and supported by the results from a comprehensive study of balance control recovery after spaceflight. The conceptual model predicts that immediately after spaceflight the balance control system of a returning astronaut does not expect to receive gravity-induced afferent inputs and that descending vestibulospinal control of balance is disrupted until the central nervous system is able to cope with the newly available vestibular otolith information. Predictions of the model are tested using data from a study of the neurosensory control of balance in astronauts immediately after landing. In that study, the mechanisms of sensorimotor balance control were assessed under normal, reduced, and/or altered (sway-referenced) visual and somatosensory input conditions. We conclude that the adaptive control model accurately describes the neurobehavioral responses to spaceflight and that similar models of altered sensory, motor, or environmental constraints are needed clinically to predict responses that patients with sensorimotor pathologies may have to various visual-vestibular or changing stimulus environments.

Computerized dynamic posturography: What have we learned from space?

Computerized dynamic posturography (CDP) has been under development since 1970. Several reviews summarize key basic and clinical research studies and outline important clinical uses of CDP along with research applications. This report summarizes new information about the otolith control of posture obtained from the study of astronauts. The dynamics of recovery of postural control upon return from orbital flight provide insight to the peripheral vestibular and central nervous system components of vestibular compensation. The dynamics of postural compensation should aid the clinician in the diagnosis and management of imbalance of vestibular origin.

A link-segment model of upright human posture for analysis of head-trunk coordination.

Sensory-motor control of upright human posture may be organized in a top-down fashion such that certain head-trunk coordination strategies are employed to optimize visual and/or vestibular sensory inputs. Previous quantitative models of the biomechanics of human posture control have examined the simple case of ankle sway strategy, in which an inverted pendulum model is used, and the somewhat more complicated case of hip sway strategy, in which multisegment, articulated models are used. While these models can be used to quantify the gross dynamics of posture control, they are not sufficiently detailed to analyze head-trunk coordination strategies that may be crucial to understanding its underlying mechanisms. In this paper, we present a biomechanical model of upright human posture that extends an existing four mass, sagittal plane, link-segment model to a five mass model including an independent head link. The new model was developed to analyze segmental body movements during dynamic posturography experiments in order to study head-trunk coordination strategies and their influence on sensory inputs to balance control. It was designed specifically to analyze data collected on the EquiTest (NeuroCom International, Clackamas, OR) computerized dynamic posturography system, where the task of maintaining postural equilibrium may be challenged under conditions in which the visual surround, support surface, or both are in motion. The performance of the model was tested by comparing its estimated ground reaction forces to those measured directly by support surface force transducers. We conclude that this model will be a valuable analytical tool in the search for mechanisms of balance control.

Geometric adjustments to account for eye eccentricity in processing horizontal and vertical eye and head movement data.

Neglecting the eccentric position of the eyes in the head can lead to erroneous interpretation of ocular motor data, particularly for near targets. We discuss the geometric effects that eye eccentricity has on the processing of target-directed eye and head movement data, and we highlight two approaches to processing and interpreting such data. The first approach involves determining the true position of the target with respect to the location of the eyes in space for evaluating the efficacy of gaze, and it allows calculation of retinal error directly from measured eye, head, and target data. The second approach effectively eliminates eye eccentricity effects by adjusting measured eye movement data to yield equivalent responses relative to a specified reference location (such as the center of head rotation). This latter technique can be used to standardize measured eye movement signals, enabling waveforms collected under different experimental conditions to be directly compared, both with the measured target signals and with each other. Mathematical relationships describing these approaches are presented for horizontal and vertical rotations, for both tangential and circumferential display screens, and efforts are made to describe the sensitivity of parameter variations on the calculated results.

Disruption of postural readaptation by inertial stimuli following space flight.

Postural instability (relative to pre-flight) has been observed in all shuttle astronauts studied upon return from orbital missions. Postural stability was more closely examined in four shuttle astronaut subjects before and after an 8 day orbital mission. Results of the pre- and post-flight postural stability studies were compared with a larger (n = 34) study of astronauts returning from shuttle missions of similar duration. Results from both studies indicated that inadequate vestibular feedback was the most significant sensory deficit contributing to the postural instability observed post flight. For two of the four IML-1 astronauts, post-flight postural instability and rate of recovery toward their earth-normal performance matched the performance of the larger sample. However, post-flight postural control in one returning astronaut was substantially below mean performance. This individual, who was within normal limits with respect to postural control before the mission, indicated that recovery to pre-flight postural stability was also interrupted by a post-flight pitch plane rotation test. A similar, though less extreme departure from the mean recovery trajectory was present in another astronaut following the same post-flight rotation test. The pitch plane rotation stimuli included otolith stimuli in the form of both transient tangential and constant centripetal linear acceleration components. We inferred from these findings that adaptation on orbit and re-adaptation on earth involved a change in sensorimotor integration of vestibular signals most likely from the otolith organs.

Elevated serum soluble CD200 and CD200R as surrogate markers of bone loss under bed rest conditions.

CD200 is a transmembrane protein that belongs to the immunoglobulin family of proteins and is ubiquitously expressed on a variety of cell types. Upon interaction with its receptors (CD200Rs) expressed on myeloid-derived cells and T lymphocytes, an immunoregulatory signal is delivered to receptor-expressing cells. Previous studies have implicated a role for CD200:CD200R in the regulation of the expression of mRNA markers of osteoclastogenesis/osteoblastogenesis, following interaction of CD200 (on osteoblast precursors) with CD200R1 (on osteoclast precursors). Signaling of CD200R1 is hypothesized to attenuate osteoclastogenesis. We have investigated whether levels of soluble forms of CD200 and/or CD200R1 (sCD200, sCD200R1) are altered in volunteers undergoing 6° head down tilt bed rest to mimic conditions of microgravity known to be associated with preferential osteoclastogenesis and whether countermeasures, reported to be beneficial in attenuation of bone loss under microgravity conditions, would lead to altered sCD200 and sCD200R1 levels. Our data suggest that, as predicted, sCD200 levels fall under bed rest conditions while sCD200R1 levels rise. In subjects undergoing 30-minute per day continuous centrifugation protocols, as a countermeasure to attenuate changes which may lead to bone loss, these alterations in sCD200 and sCD200R1 levels seen under conditions of bed rest were abolished or attenuated. Our results suggest that measurement of sCD200 and/or sCD200R1 may prove a useful and rapid means of monitoring subjects at risk of bone loss and/or accessing the efficacy of treatment regimes designed to counter bone loss.