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Reproducibility of human vagal carotid baroreceptor-cardiac reflex responses.

Published information on the reproducibility of human baroreflex responses in the absence of interventions is limited. Therefore, we analyzed retrospectively vagally mediated carotid baroreceptor-cardiac reflex responses of 34 healthy young adult volunteers whom we studied twice, 7-10 days apart (all 34 subjects) or 10 wk apart (8 subjects). We delivered a sequence of neck pressure changes during held expiration: A computer-driven bellows initially raised pressure to approximately 40 mmHg for five heart beats, and then reduced pressure in a stepwise series of R-wave-triggered 15-mmHg decrements to about -65 mmHg. R-R interval changes were plotted as functions of the carotid distending (systolic less neck) pressure occurring within each interval. Each experimental session yielded one stimulus-response relation, which comprised the average of seven separate trials. Six measures were derived from these relations: minimum, maximum, and range of R-R intervals; maximum slope; and operational point [(R-R interval shortening/R-R interval range) x 100%]. Linear regression correlation coefficients for measurements made on two occasions were all highly significant (range: 0.64-0.99). Our results indicate that human vagally mediated carotid baroreceptor-cardiac reflex responses, studied serially under exacting experimental conditions, are highly reproducible.

Adult

Attenuation of human carotid-cardiac vagal baroreflex responses after physical detraining.

Astronauts who are occupied with prelaunch schedules may have to limit their regular physical exercise routines. To assess a potential effect on blood pressure control, carotid baroreceptor-cardiac reflex responses of 16 men (30-45 years of age) were evaluated before and after 2 weeks of exercise detraining that followed 10 weeks of regular scheduled exercise (30 min/d, 4 d/week at 75% Vo2max). At mid-expiration, the subjects held their breath and 40 mm Hg of pressure was applied to a neck chamber for four heart beats, followed by 15-mm Hg, R-wave triggered decrements to -65 mm Hg. Changes of R-R intervals were plotted against carotid distending pressure (systolic-neck chamber pressure). After detraining, the baroreflex stimulus-response relationship had a reduced slope [4.0 +/- 0.5 vs. 2.8 +/- 0.4 msec/mmHg (p = 0.0008)] and range of response [191 +/- 19 vs. 145 +/- 17 ms (p = 0.002)]. In addition, there was a resetting of the relationship on the R-R interval axis. Both the minimum and maximum R-R interval responses to the stimulus were significantly reduced after detraining [953 +/- 32 vs. 909 +/- 36 ms (p = 0.035) and 1145 +/- 36 vs. 1054 +/- 39 (p = 0.002)]. Baseline systolic pressure did not change with detraining (116 +/- 2 vs. 114 +/- 2 mm Hg) and the carotid baroreceptor-cardiac response relationship did not shift on the pressure axis. These results suggest that detraining from regular exercise can compromise vagally-mediated mechanisms of blood pressure regulation.

Adult

Investigation of anti-motion sickness drugs in the squirrel monkey.

Early attempts to develop an animal model for anti-motion sickness drugs, using dogs and cats; were unsuccessful. Dogs did not show a beneficial effect of scopolamine (probably the best single anti-motion sickness drug for humans thus far) and the findings in cats were not definitive. The authors have developed an animal model using the squirrel monkey (Saimiri sciureus) of the Bolivian phenotype. Unrestrained monkeys in a small lucite cage were tested in an apparatus that induces motion sickness by combining vertical oscillation and horizontal rotation in a visually unrestricted laboratory environment. Signs of motion sickness were scored using a rating scale. Ten susceptible monkeys (weighing 800-1000 g) were given a total of five tests each, to establish the baseline susceptibility level. Based on the anticholinergic activity of scopolamine, the sensitivity of squirrel monkey to scopolamine was investigated, and the appropriate dose of scopolamine for this species was determined. Then various anti-motion sickness preparations were administered in subsequent tests: 100 ug scopolamine per monkey; 140 ug dexedrine; 50 ug scopolamine plus 70 ug dexedrine; 100 ug scopolamine plus 140 ug dexedrine; 3 mg promethazine; 3 mg promethazine plus 3 mg ephedrine. All these preparations were significantly effective in preventing motion sickness in the monkeys. Ephedrine, by itself, which is marginally effective in humans, was ineffective in the monkeys at the doses tried (0.3-6.0 mg). The squirrel monkey appears to be a good animal model for antimotion sickness drugs. Peripherally acting antihistamines such as astemizole and terfenadine were found to be ineffective, whereas flunarizine, and an arginine vasopressin V1 antagonist, showed significant activity in preventing motion sickness.

Animals

Dynamic posture analysis of Spacelab-1 crew members.

Dynamic posture testing was conducted on the science crew of the Spacelab-1 mission on a single axis linear motion platform. Tests took place in pre- and post-flight sessions lasting approximately 20 min each. The pre-flight tests were widely spaced over the several months prior to the mission while the post-flight tests were conducted over the first, second, fourth, and sixth days after landing. Two of the crew members were also tested on the day of landing. Consistent with previous postural testing conducted on flight crews, these crew members were able to complete simple postural tasks to an acceptable level even in the first few hours after landing. Our tests were designed to induce dynamic postural responses using a variety of stimuli and from these responses, evaluate subtle changes in the postural control system which had occurred over the duration of the flight. Periodic sampling post-flight allowed us to observe the time course of readaptation to terrestrial life. Our observations of hip and shoulder position, when subjected to careful analysis, indicated modification of the postural response from pre- to post-flight and that demonstrable adjustments in the dynamic control of their postural systems were taking place in the first few days after flight. For transient stimuli where the platform on which they were asked to stand quickly moved a few centimeters fore or aft then stopped, ballistic or open loop 'programs' would closely characterize the response. During these responses the desired target position was not always achieved and of equal importance not always properly corrected some 15 seconds after the platform ceased to move. The persistent observation was that the subjects had a much stronger dependence on visual stabilization post-flight than pre-flight. This was best illustrated by a slow or only partial recovery to an upward posture after a transient base-of-support movement with eyes open. Postural responses to persistent wideband pseudorandom base-of-support translation were modeled as time invarient linear systems arrived at by Kalman adaptive filter techniques. Derived model parameters such as damping factor and fundamental frequency of the closed loop system showed significant modification between pre- and post-flight. This phenomenon is best characterized by movement of the poles toward increasing stability. While pre-flight data tended to show shoulders and hips moving in phase with each other, post-flight data showed a more disjoint behavior.(ABSTRACT TRUNCATED AT 400 WORDS)

Adaptation, Physiological

Spectral indices of cardiovascular adaptations to short-term simulated microgravity exposure.

We investigated the effects of exposure to microgravity on the baseline autonomic balance in cardiovascular regulation using spectral analysis of cardiovascular variables measured during supine rest. Heart rate, arterial pressure, radial flow, thoracic fluid impedance and central venous pressure were recorded from nine volunteers before and after simulated microgravity, produced by 20 hours of 6 degrees head down bedrest plus furosemide. Spectral powers increased after simulated microgravity in the low frequency region (centered at about 0.03 Hz) in arterial pressure, heart rate and radial flow, and decreased in the respiratory frequency region (centered at about 0.25 Hz) in heart rate. Reduced heart rate power in the respiratory frequency region indicates reduced parasympathetic influence on the heart. A concurrent increase in the low frequency power in arterial pressure, heart rate, and radial flow indicates increased sympathetic influence. These results suggest that the baseline autonomic balance in cardiovascular regulation is shifted towards increased sympathetic and decreased parasympathetic influence after exposure to short-term simulated microgravity.

Adaptation, Physiological

Zinc and copper balances in healthy adult males during and after 17 wk of bed rest.

The effects of long-term bed rest on zinc and copper balances were measured in seven healthy men. Volunteers aged 22-54 y (mean +/- SD, 34 +/- 12 y), 168-185 cm in height (173 +/- 5 cm), and 64-86 kg in weight (74 +/- 9 kg) remained on a metabolic ward for 29 wk. Subjects were ambulatory during weeks 1-5, remained in continuous bed rest for weeks 6-22, and were reambulated during weeks 23-29. Copper and zinc were measured in weekly urine and fecal composites. Dietary intakes provided (mean +/- SD) 19.2 +/- 1.2 mumol Cu (1.22 +/- 0.08 mg), 211 +/- 11 mumol Zn (13.81 +/- 0.72 mg), 25.2 +/- 1.2 mmol Ca (1011 +/- 46 mg), 1086 +/- 46 mmol N (15.21 +/- 0.65 g), and 48.1 +/- 1.4 mmol K (1489 +/- 44 mg)/d. Bed rest increased fecal zinc excretion and decreased zinc balance, whereas copper balance was unchanged. Reambulation decreased fecal zinc excretion and increased both zinc and copper balances. These results suggest that during long-term bed rest or space flight, individuals will lose total body zinc and will retain more zinc and copper when they reambulate.

Adult

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.

Adult

Regional changes in muscle mass following 17 weeks of bed rest.

This work reports on the muscle loss and recovery after 17 wk of continuous bed rest and 8 wk of reambulation in eight normal male volunteers. Muscle changes were assessed by urinary levels of 3-methylhistidine (3-MeH), nitrogen balance, dual-photon absorptiometry (DPA), magnetic resonance imaging (MRI), and isokinetic muscle performance. The total body lean tissue loss during bed rest calculated from nitrogen balance was 3.9 +/- 2.1 (SD) kg (P < 0.05). Although the total loss is minimal, DPA scans showed that nearly all of the lean tissue loss occurred in the lower limbs. Similarly, MRI muscle volume measurements showed greater percent loss in the limbs relative to the back muscles. MRI, DPA, and nitrogen balance suggest that muscle atrophy continued throughout bed rest with rapid recovery after reambulation. Isokinetic muscle strength decreased significantly (P < 0.05) in the thigh and calf with no loss in the arms and with rapid recovery during reambulation. We conclude that there is great variability in the degree and location of muscle loss in bed rest and that the lower limb muscles are primarily affected.

Absorptiometry, Photon

Spaceflight alters autonomic regulation of arterial pressure in humans.

Spaceflight is associated with decreased orthostatic tolerance after landing. Short-duration spaceflight (4-5 days) impairs one neural mechanism: the carotid baroreceptor-cardiac reflex. To understand the effects of longer-duration spaceflight on baroreflex function, we measured R-R interval power spectra, antecubital vein plasma catecholamine levels, carotid baroreceptor-cardiac reflex responses, responses to Valsalva maneuvers, and orthostatic tolerance in 16 astronauts before and after shuttle missions lasting 8-14 days. We found the following changes between preflight and landing day: 1) orthostatic tolerance decreased; 2) R-R interval spectral power in the 0.05 to 0.15-Hz band increased; 3) plasma norepinephrine and epinephrine levels increased; 4) the slope, range, and operational point of the carotid baroreceptor cardiac reflex response decreased; and 5) blood pressure and heart rate responses to Valsalva maneuvers were altered. Autonomic changes persisted for several days after landing. These results provide further evidence of functionally relevant reductions in parasympathetic and increases in sympathetic influences on arterial pressure control after spaceflight.

Adult

Effects of head-down bed rest on complex heart rate variability: response to LBNP testing.

Head-down bed rest is used to model physiological changes during spaceflight. We postulated that bed rest would decrease the degree of complex physiological heart rate variability. We analyzed continuous heart rate data from digitized Holter recordings in eight healthy female volunteers (age 28-34 yr) who underwent a 13-day 6 degree head-down bed rest study with serial lower body negative pressure (LBNP) trials. Heart rate variability was measured on 4-min data sets using conventional time and frequency domain measures as well as with a new measure of signal "complexity" (approximate entropy). Data were obtained pre-bed rest (control), during bed rest (day 4 and day 9 or 11), and 2 days post-bed rest (recovery). Tolerance to LBNP was significantly (P < 0.02) reduced on both bed rest days vs. pre-bed rest. Heart rate variability was assessed at peak LBNP. Heart rate approximate entropy was significantly (P < 0.05) decreased at day 4 and day 9 or 11, returning toward normal during recovery. Heart rate standard deviation and the ratio of high- to low-power frequency did not change significantly. We conclude that short-term bed rest is associated with a decrease in the complex variability of heart rate during LBNP testing in healthy young adult women. Measurement of heart rate complexity, using a method derived from nonlinear dynamics ("chaos theory"), may provide a sensitive marker of this loss of physiological variability, complementing conventional time and frequency domain statistical measures.

Adult

Simultaneous cerebrovascular and cardiovascular responses during presyncope.

BACKGROUND AND PURPOSE: Presyncope, characterized by symptoms and signs indicative of imminent syncope, can be aborted in many situations before loss of consciousness occurs. The plasticity of cerebral autoregulation in healthy humans and its behavior during this syncopal prodrome are unclear, although systemic hemodynamic instability has been suggested as a key factor in the precipitation of syncope. Using lower body negative pressure (LBNP) to simulate central hypovolemia, we previously observed falling mean flow velocities (MFVs) with maintained mean arterial blood pressure (MABP). These findings, and recent reports suggesting increased vascular tone within the cerebral vasculature at presyncope, cannot be explained by the classic static cerebral autoregulation curve; neither can they be totally explained by a recent suggestion of a rightward shift in this curve. METHODS: Four male and five female healthy volunteers were exposed to presyncopal LBNP to evaluate their cerebrovascular and cardiovascular responses by use of continuous acquisition of MFV from the right middle cerebral artery with transcranial Doppler sonography, MABP (Finapres), and heart rate (ECG). RESULTS: At presyncope, MFV dropped on average by 27.3 +/- 14% of its baseline value (P < .05), while MABP remained at 2.0 +/- 27% above its baseline level. Estimated cerebrovascular resistance increased during LBNP. The percentage change from baseline to presyncope in MFV and MABP revealed consistent decreases in MFV before MABP. CONCLUSIONS: Increased estimated cerebrovascular resistance, falling MFV, and constant MABP are evidence of an increase in cerebral vascular tone with falling flow, suggesting a downward shift in the cerebral autoregulation curve. Cerebral vessels may have a differential sensitivity to sympathetic drive or more than one type of sympathetic innervation. Future work to induce dynamic changes in MABP during LBNP may help in assessing the plasticity of the cerebral autoregulation mechanism.

Adolescent

Ground-based training for the stimulus rearrangement encountered during spaceflight.

Approximately 65-70% of the crew members now experience motion sickness of some degree during the first 72 h of orbital flight on the Space Shuttle. Lack of congruence among signals from spatial orientation systems leads to sensory conflict, which appears to be the basic cause of space motion sickness. A project to develop training devices and procedures to preadapt astronauts to the stimulus rearrangements of microgravity is currently being pursued. The preflight adaptation trainers (PATs) are intended to: demonstrate sensory phenomena likely to be experienced in flight, allow astronauts to train preflight in an altered sensory environment, alter sensory-motor reflexes, and alleviate or shorten the duration of space motion sickness. Four part-task PATs are anticipated. The trainers are designed to evoke two adaptation processes, sensory compensation and sensory reinterpretation, which are necessary to maintain spatial orientation in a weightless environment. Recent investigations using one of the trainers indicate that self-motion perception of linear translation is enhanced when body tilt is combined with visual surround translation, and that a 270 degrees phase angle relationship between tilt and surround motion produces maximum translation perception.

Adaptation, Physiological

Changes in nerve conduction and Pi/PCr ratio during denervation-reinnervation of the gastrocsoleus muscles of rats.

The purpose of this investigation was to study the changes in nerve conduction and phosphate metabolites of the gastrocsoleus muscles of rats during denervation-reinnervation. Sixteen male Sprague-Dawley rats underwent unilateral crush-denervation of the left sciatic nerves at the sciatic notch. Six rats were used for measurement of motor conduction latency and action potential amplitude of the gastrocsoleus muscle by stimulating the sciatic nerve at one, two and eight weeks after nerve crush. The other ten rats were designated for evaluation of the ratio of inorganic phosphorous (Pi) to phosphocreatine (PCr) by a 31P-phosphoenergetic spectrometer at two weeks and eight weeks after nerve crush. None of the sciatic nerves showed conduction to the gastrocsoleus at one or two weeks after nerve crush. At eight weeks postcrush, the motor conduction latency returned to within normal limits, whereas the action potential amplitude was only 55% of the normal. For the eight-week period of study, the Pi/PCr ratio of the normal control muscles ranged between 0.09 +/- 0.02 and 0.11 +/- 0.02 (mean +/- SD). The denervated muscles showed an increase of Pi/PCr ratio by 54% at two weeks postcrush, compared to the respective contralateral control sides. The ratios returned to the normal value by eight weeks postcrush. In summary, these data suggested that the metabolic recovery of the crush-denervated muscle followed the same pattern as the parameters of nerve conduction.

Animals

Clinical characterization and etiology of space motion sickness.

An inflight, clinically-oriented investigation of SMS was begun on STS-4 and revealed the following: compared to motion sickness on Earth, autonomic signs are significantly different in space motion sickness (SMS) vs. motion sickness (MS) in that sweating is not present, pallor or flushing may be present, and vomiting is episodic, sudden, and brief. Nausea may be present but is more often absent. Onset ranges from minutes to hours, plateaus, and rapidly resolves in 8-72 h with 36 h as average. Postflight reactions have been mild unless deliberately provoked in the early period of re-exposure to gravity. Postflight there is a period of resistance to all forms of motion sickness. There is some evidence for individual reduction in sensitivity on repeated flights. Etiology could not be proven objectively; however, the sensitivity to angular motion, often pronounced in pitch, and theoretical considerations make an intravestibular conflict the most likely cause. Electro-oculogram (EOG), audio-evoked potentials, measurement of fluid shifts, and other studies are inconsistent with a transient vestibular hydrops or increased intracranial pressure as a cause.

Electrooculography

Effects of prolonged weightlessness on self-motion perception and eye movements evoked by roll and pitch.

Seven astronauts reported translational self-motion during roll stimulation 1-3 h after landing following 5-7 d of orbital flight. Two reported strong translational self-motion perception when they performed pitch head motions during entry and while the orbiter was stationary on the runway. One of two astronauts from whom adequate data were collected exhibited a 132 degrees shift in the phase angle between roll stimulation and horizontal eye position 2 h after landing. Neither of two from whom adequate data were collected exhibited increased horizontal eye movement amplitude or disturbance of voluntary pitch or roll body motion immediately postflight. These results are generally consistent with an otolith tilt-translation reinterpretation model and are being applied to the development of apparatus and procedures intended to preadapt astronauts to the sensory rearrangement of weightlessness.

Electrooculography

Reliability of provocative tests of motion sickness susceptibility.

Accurate prediction of space motion sickness is dependent, in part, upon the reliability of terrestrial-based motion sickness susceptibility tests. In the present study, test-retest reliability values were derived from motion sickness susceptibility scores obtained from two successive exposures to each of three tests: 1) Coriolis Sickness Sensitivity Index (CSSI); 2) Staircase Velocity Movement Test (SVMT); and 3) Parabolic Flight Static Chair Test (PSCT). The reliability of the three tests ranged from 0.70 to 0.88. Normalizing values from predictors with skewed distributions improved the reliability. The apparent inconsistency between our finding of high reliability of predictive tests, and previous reports of low correlations between ground-based predictors and space motion sickness may be due to unreliability in assessment of the sickness criterion. Issues of reliability and validity of predictor and criterion measures, and their implications for future development of ground-based predictive tests are discussed in some detail.

Acceleration

Alterations in renal stone risk factors after space flight.

Exposure to the microgravity environment of space produces a number of physiological changes of metabolic and environmental origin that could increase the potential for renal stone formation. Metabolic, environmental and physicochemical factors that influence renal stone risk potential were examined in 24-hour urine samples from astronauts 10 days before launch and on landing day to provide an immediate postflight assessment of these factors. In addition, comparisons were made between male and female crewmembers, and between crewmembers on missions of less than 6 days and those on 6 to 10-day missions. Results suggest that immediately after space flight the risk of calcium oxalate and uric acid stone formation is increased as a result of metabolic (hypercalciuria, hypocitraturia, pH) and environmental (lower urine volume) derangements, some of which could reflect residual effects of having been exposed to microgravity.

Adult