Subchronic toxicity of chlorine dioxide and related compounds in drinking water in the nonhuman primate.

Subchronic toxicities of ClO2, NaClO2, NaClO3 and NH2Cl were studied in the African Green monkeys (Cercopithecus aethiops). The chemicals were administered in drinking water during 30-60 days subchronic rising dose protocols. The only unexpected and significant toxic effect was elicited by ClO2; this chemical inhibited thyroid metabolism in the animals at a dose of ca. 9.0 mg/kg/day. A statistically significant decrease of serum thyroxine occurred after the fourth week of exposure to 100 mg/l.concentration. The extent of thyroid suppression was dose dependent in each individual monkey, and was reversible after cessation of exposure. NaClO2 and NaClO3 failed to elicit similar effects in doses up to ca. 60 mg/kg/day. Also, NaClO4 or NH2Cl did not cause T-4 suppression in doses of 10 mg/kg/day. The selective thyroid effect of ClO2 was unexplained and it appeared to be paradoxical since ClO2 was rapidly reduced by the oral and gastric secretions to nonoxidizing species (presumably Cl-). No evidence of thyroid effects were detected in the serum of human volunteers who ingested approximately 1 mg/l. of ClO2 in drinking water as a result of routine use in the community water treatment process. Sodium chlorite induced dose-dependent oxidative stress on hematopoesis, causing decreased hemoglobin and red cell count and increased methemoglobin content. At the same time, serum transaminase (SGPT) levels showed significant subclinical elevation. The hematologic effects of NaClO2 rebounded during exposure indicating compensatory hemopoietic activity taking effect during oxidative stress. Sodium chlorate and chloramine did not induce detectable hematologic changes in the animals.

Renal responsiveness to aldosterone during exposure to simulated microgravity.

We measured renal functions and hormones associated with fluid regulation after a bolus injection of aldosterone (Ald) during head-down tilt (HDT) bed rest to test the hypothesis that exposure to simulated microgravity altered renal responsiveness to Ald. Six male rhesus monkeys underwent two experimental conditions (HDT and control, 72 h each) with each condition separated by 9 days of ambulatory activities to produce a crossover counterbalance design. One test condition was continuous exposure to 10 degrees HDT; the second was a control, defined as 16 h per day of 80 degrees head-up tilt and 8 h prone. After 72 h of exposure to either test condition, monkeys were moved to the prone position, and we measured the following parameters for 4 h after injection of 1-mg dose of Ald: urine volume rate (UVR); renal Na(+)/K(+) excretion ratio; renal clearances of creatinine, Na(+), osmolality, and free water; and circulating hormones [Ald, renin activity (PRA), vasopressin (AVP), and atrial natriuretic peptide (ANP)]. HDT increased Na(+) clearance, total renal Na(+) excretion, urine Na(+) concentration, and fractional Na(+) excretion, compared with the control condition, but did not alter plasma concentrations of Ald, PRA, and AVP. Administration of Ald did not alter UVR, creatinine clearance, Ald, PRA, AVP, or ANP but reduced Na(+) clearance, total renal Na(+) excretion, urinary Na(+)/K(+) ratio, and osmotic clearance. Although reductions in Na(+) clearance and excretion due to Ald were greater during HDT than during control, the differential (i.e., interaction) effect was minimal between experimental conditions. Our data suggest that exposure to microgravity increases renal excretion of Na(+) by a natriuretic mechanism other than a change in renal responsiveness to Ald.

Active lifestyle offsets HRT-induced suppression of T cell reactivity to mitogens.

OBJECTIVE: The purpose of the study was to investigate the combined impact of hormone replacement therapy (HRT) and active lifestyle on the phenotypic profile and in vitro activities of specific immune cells in postmenopausal women. METHODS: Healthy postmenopausal women aged 45-70 were assigned to one of four groups: (a) HRT/sedentary (n = 9); (b) HRT/active (n = 12); (c) no HRT/sedentary (n = 10); and (d) no HRT/active (n = 9). Blood samples were collected from each subject on 3 days within 1 week. The mean value of three samples was used to assess the in vitro response of T lymphocytes to the mitogens phytohemagglutinin and concanavalin A and natural killer cell activity. One of three blood samples was utilized for phenotypic analysis of circulating leukocytes. RESULTS: The mitogenic reactivity of T lymphocytes in whole blood cultures for the groups receiving HRT was lower than from the groups not receiving HRT. There also was a trend for T lymphocyte reactivity to be higher in the active women when compared to the sedentary women. In contrast, the phenotypic profile of leukocytes and natural killer cell activity were not significantly different for samples collected from the four groups. CONCLUSIONS: These data suggest that the suppressive effect of HRT on T cell function in postmenopausal women may be attenuated by a physically active lifestyle.

Left ventricular, systemic arterial, and baroreflex responses to ketamine and TEE in chronically instrumented monkeys.

Effects of prescribed doses of ketamine five minutes after application and influences of transesophageal echocardiography (TEE) on left ventricular, systemic arterial, and baroreflex responses were investigated to test the hypothesis that ketamine and/or TEE probe insertion alter cardiovascular function. Seven rhesus monkeys were tested under each of four randomly selected experimental conditions: (1) intravenous bolus dose of ketamine (0.5 ml), (2) continuous infusion of ketamine (500 mg/kg/min), (3) continuous infusion of ketamine (500 mg/kg/min) with TEE, and (4) control (no ketamine or TEE). Monkeys were chronically instrumented with a high fidelity, dual-sensor micromanometer to measure left ventricular and aortic pressure and a transit-time ultrasound probe to measure aortic flow. These measures were used to calculate left ventricular function. A 4-element Windkessel lumped-parameter model was used to estimate total peripheral resistance and systemic arterial compliance. Baroreflex response was calculated as the change in R-R interval divided by the change in mean aortic pressure measured during administration of graded concentrations of nitroprusside. The results indicated that five minutes after ketamine application heart rate and left ventricular diastolic compliance decreased while TEE increased aortic systolic and diastolic pressure. We conclude that ketamine may be administered as either a bolus or continuous infusion without affecting cardiovascular function 5 minutes after application while the insertion of a TEE probe will increase aortic pressure. The results for both ketamine and TEE illustrate the classic "Hawthorne Effect," where the observed values are partly a function of the measurement process. Measures of aortic pressure, heart rate, and left ventricular diastolic pressure should be viewed as relative, as opposed to absolute, when organisms are sedated with ketamine or instrumented with a TEE probe.

Predicting orthostatic intolerance: physics or physiology?

To adequately assess the viability of any particular causal theory of orthostatic intolerance, physical and physiological parameters thought to be associated with orthostasis must be evaluated simultaneously within the same individual. Time, cost, and complexity of instrumentation generally limit studies of orthostatic intolerance to a single independent effect for any given sample of subjects. We, therefore, measured 6 key physical and physiological variables associated with various theories of orthostatic intolerance in 14 males to test the hypothesis that physical factors rather than physiological reflex mechanisms were dominant in contributing to orthostatic tolerance. Measurements included height, plasma volume (expressed as percent of total weight), variation in R-R interval, leg compliance, and carotid-cardiac (high pressure), and cardiopulmonary (low pressure) baroreflex sensitivity. Subjects' orthostatic intolerance was quantified by time to syncope during progressive supine lower body decompression. Correlations, regression coefficients, and indices of replicability were calculated using 500 to 1,000 bootstrap resamplings of the original 14 observations. Although all six measurements correlated with time to syncope when evaluated individually, only height (negative), percent plasma volume weight (positive), and, to a lesser extent, carotid-cardiac baroreflex sensitivity yielded consistent (reproducible) results when all measures were tested simultaneously. These results suggest that while orthostatic intolerance may be dependent upon a variety of physiological reflexes, physical factors such as height and plasma volume tend to dominate the prediction of time to syncope during lower body negative pressure (LBNP). Physiological reflexes, which act to maintain adequate profusion to the brain during normal terrestrial posture in humans, may be overwhelmed by the additional orthostatic challenge imposed by progressive lower body decompression.

Errors in measurement of +Gz acceleration tolerance.

Most acceleration studies estimate a subject's G-level tolerance by taking only one determination (test) for a given condition. The purpose of this study was to examine the error structure and reliability of an individual's acceleration tolerance and to provide design considerations for future experimentation. A hierarchical (nested) design was used to estimate the sources of variation in measuring G-level tolerance. Six males rode relaxed in the USAF School of Aerospace Medicine human-use centrifuge and were exposed to a 0.1 G/s onset rate profile until greyout. Each subject was tested on three randomly selected days with three repeated determinations within a day. This design allowed for an estimate of both day-to-day and measurement error within a testing session. A single +Gz tolerance determination was found to be moderately unreliable (reliability coefficient = 0.74). Under the best of circumstances a subject's G-level tolerance cannot be estimated with any more accuracy than about +/- 0.3 G with 95% confidence. This degree of accuracy can only be obtained with multiple measurements.

A statistical note on the redundancy of nine standard baroreflex parameters.

An accepted method for measuring the responsiveness of the carotid-cardiac baroreflex to arterial pressure changes is to artificially stimulate the baroreceptors in the neck with a pressurized neck chamber. Nine physiological responses to this type of stimulation are quantified and used as indicators of the baroreflex response function. Thirty male humans between the ages of 27 and 46 underwent the carotid-cardiac baroreflex test. The data for the nine response parameters were analyzed by principle component factor analysis. The results indicated that 92.5% of the total variance across all nine parameters could be explained in four dimensions. The first two dimensions reflected location points for R-R interval and carotid distending pressure, respectively. The third factor was composed of measures reflecting the gain (responsiveness) of the reflex. The fourth dimension was the ratio of baseline R-R interval to the maximal R-R interval response during simulated hypertension. The data suggest that the analysis of all nine baroreflex parameters is likely to be redundant and researchers should account for these redundancies either in their analyses or conclusions.

Carotid baroreceptor influence on forearm vascular resistance during low level lower body negative pressure.

The degree of forearm vasoconstriction induced by low levels of lower body negative pressure (LBNP) provides a measure of the responsiveness of the cardiopulmonary baroreflex. The validity of this measurement is based on the assumption that this vasoconstriction response is not influenced by unloading of carotid baroreceptors. To test the hypothesis that arterial baroreceptor unloading does not alter the degree of forearm vascular resistance during low levels of LBNP, we exposed 12 subjects to -15 and -20 mm Hg LBNP with and without additional artificial (+10 mm Hg neck pressure) unloading of the carotid baroreceptors. There was no measurable influence of carotid unloading on forearm vascular resistance at either level of LBNP. We conclude that forearm vascular resistance measured during cardiopulmonary baroreceptor unloading is unaffected by carotid baroreceptor unloading within the magnitude encountered during low levels of LBNP.

Logistic risk model for the unique effects of inherent aerobic capacity on +Gz tolerance before and after simulated weightlessness.

Small sample size (n less than 10) and inappropriate analysis of multivariate data have hindered previous attempts to describe which physiologic and demographic variables are most important in determining how long humans can tolerate acceleration. Data from previous centrifuge studies conducted at NASA/Ames Research Center, utilizing a 7-14 d bed rest protocol to simulate weightlessness, were included in the current investigation. After review, data on 25 women and 22 men were available for analysis. Study variables included gender, age, weight, height, percent body fat, resting heart rate, mean arterial pressure, VO2max, and plasma volume. Since the dependent variable was time to greyout (failure), two contemporary biostatistical modeling procedures (proportional hazard and logistic discriminant function) were used to estimate risk, given a particular subject's profile. After adjusting for pre-bed-rest tolerance time, none of the profile variables remained in the risk equation for post-bed-rest tolerance greyout. However, prior to bed rest, risk of greyout could be predicted with 91% accuracy. All of the profile variables except weight, MAP, and those related to inherent aerobic capacity (VO2max, percent body fat, resting heart rate) entered the risk equation for pre-bed-rest greyout. A cross-validation using 24 new subjects indicated a very stable model for risk prediction, accurate within 5% of the original equation. The result for the inherent fitness variables is significant in that a consensus as to whether an increased aerobic capacity is beneficial or detrimental has not been satisfactorily established. We conclude that tolerance to +Gz acceleration before and after simulated weightlessness is independent of inherent aerobic fitness.

Blood pressure changes during orthostatic stress: evidence of gender differences in neuroeffector distribution.

BACKGROUND: Research has demonstrated that exogenous adrenergic agonists produce dose-related vasoconstriction in men but not women. This suggests that the distribution of adrenergic receptor sites differ with gender. Women may have a higher density of receptor sites in the arterioles (fast acting with low gain) while men may have higher density in the larger vessels (slow acting with high gain). METHODS: To partially test this hypothesis, the time course in beat-to-beat responses in systolic and diastolic BP, and heart rate was compared between six men and six women during the transition from a supine to an upright posture and during prolonged standing. RESULTS: The transient change in systolic and diastolic BP was very rapid in women, but completed within 15 to 30 s after assuming an upright position. Men increased BP at a much slower rate, but continued to produce higher BPs over the complete testing session (up to 15 min). The rate of change for men (15 mm Hg systolic and 10 mm Hg diastolic) was approximately half that for women (30 mm Hg systolic and 15 mm Hg diastolic) during the first 30 s of upright posture. However, after 60 s of standing, absolute change in systolic BP for the men exceeded that of the women by approximately 5 mm Hg for both systolic and diastolic BP. While men's heart rate remained relatively constant during standing, women compensated for the lower change in BP by a continual increase in heart rate throughout the duration of the test. Although both men and women demonstrated increases in norepinephrine at 5 and 15 min during standing, no difference between genders was observed. Similarly, there were no differences in dominant periodicity of heart rate during standing, although women demonstrated slightly higher beat-to-beat variation (RMS) than men. CONCLUSION: The results support the hypothesis of distributional differences in neuroeffector responses between men and women and have implications for how men and women respond to orthostatic stress across a variety of environmental conditions.

Effect of standing or walking on physiological changes induced by head down bed rest: implications for spaceflight.

BACKGROUND/HYPOTHESIS: To simulate exposure to microgravity and to determine the effectiveness of intermittent exposure to passive and active +1 Gz force (head-to-foot) in preventing head-down bed rest (HDBR) deconditioning, 4 d of 6 degrees HDBR were used. METHODS: Volunteers were 9 males, 30-50 yr, who performed periodic standing or controlled walking for 2 or 4 h.d-1 in 15-min bouts, one bout per hour, or remained in a continuous HDBR control condition (0 Gz). RESULTS: Standing 4 h (S4) completely prevented, and standing 2 h (S2) partially prevented, decreases in post-HDBR orthostatic tolerance (survival rates with 30 min of upright tilt at 60 degrees). Walking, both 2 h (W2) and 4 h (W4), and S4 attenuated decreases in peak oxygen uptake compared to 0 Gz. Compared to 0 Gz, both S4 and W4 attenuated plasma volume loss during HDBR. Urinary Ca2+ excretion increased over time with HDBR; the quadratic trend for urinary Ca2+, however, was attenuated with W2 and W4. CONCLUSIONS: We concluded that various physiological systems benefit differentially from passive +1 Gz or activity in +1 Gz and, in addition to the duration of the stimulus, the number of exposures to postural stimuli may be an important moderating factor.

Mediating effect of onset rate on the relationship between +Gz and LBNP tolerance and cardiovascular reflexes.

INTRODUCTION: Research attempting to establish a relationship between human response to lower body negative pressure (LBNP) and +Gz acceleration has in general, disregarded the moderating effects of negative pressure and +Gz onset rates. Many of the past studies designed to examine the relationship between lower body decompression and +Gz acceleration tolerances have also ignored the problem of differences in body position typically encountered during LBNP and +Gz testing (supine LBNP vs. seated +Gz). METHODS: There were 17 male subjects (24-34 yr) who were tested in a seated LBNP chamber and received 3 pressure onset rates of 0.067, 0.33, and 2.0 mm Hg x s(-1). Relaxed acceleration tolerance was assessed on a 6.1 -m centrifuge using three gradual onset rates of 0.01, 0.05, and 0.2 +Gz x s(-1). LBNP and +Gz tolerances were subjected to principle components (factor) analysis, and the resulting factors correlated with variables derived from autonomic reflex control tests (Valsalva and carotid-cardiac baroreflex responsiveness) and height. RESULTS: The factor model suggested a two-dimensional solution consisting of an acceleration factor and an orthostatic factor. The general pattern of the factor loadings indicates the relationship between tolerances of the two forms of orthostatic stress (acceleration and LBNP) is a function of how fast each stress is delivered. The correlation between LBNP tolerance and acceleration tolerance increases as LBNP onset rate is increased, or +Gz onset rate is decreased. Height was highly correlated (-0.71) and carotid-cardiac baroreflex responsiveness moderately correlated (0.54) with general orthostatic tolerance. Valsalva measures of autonomic reflex control had low correlations with general orthostatic tolerance (<0.30). CONCLUSIONS: Although both LBNP and +Gz exposure can lead to eventual loss of consciousness, syncopal events associated with intolerance to either stress are a function of somewhat different cardiovascular mechanisms. There are however, specific situations where LBNP may constitute a viable substitute for +Gz.

Female exposure to high G: chronic adaptations of cardiovascular functions.

INTRODUCTION: Exposure to microgravity is associated with increased leg venous compliance and reductions in cardiac output, baroreflex functions, and tolerance to orthostatism. However, the effects of chronic exposure to high-G environments are unknown. In addition, there is evidence that females have lower orthostatic tolerance than males, although the underlying mechanisms are unclear. Therefore, we tested the hypotheses that high-G training will enhance baroreflex and orthostatic functions and that females will demonstrate similar adaptations compared with males. METHODS: Calf venous compliance, baroreflex function, and orthostatic performance were measured in six men and seven women before and after repeated exposures on the centrifuge (G-training) for 4 wk, 3 times/wk, with gradual levels of G starting with +3 Gz without G-suit protection during week 1 and advancing to +9 Gz with G-suit protection by the end of week 4. Calf venous compliance was measured by occlusion plethysmography using impedance rheographic recordings of volume change. Baroreflex function was assessed from beat-by-beat changes in heart rate (HR) and mean arterial pressure (MAP) that were measured before, during, and after a Valsalva maneuver strain at 30 mmHg expiratory pressure. The orthostatic performance of reflex responses was assessed from beat-by-beat changes in HR, MAP, stroke volume (SV), cardiac output (Q; by impedance plethysmography), and systemic peripheral resistance during the last 10 cardiac beats of a 4-min squat position and during the initial 10 cardiac beats in a standing position. RESULTS: G-training increased calf compliance in both men and women. SV and Q were increased during the squat-to-stand test in the males, but not in the females, following G-training and provided protection against the development of acute hypotension in the men. CONCLUSIONS: G-training caused adaptations in orthostatic functions opposite to those observed following exposure to microgravity environments. However, adaptations to G-training were limited in females, a finding that may provide a physiological basis for their lower simulated combat tracking performance during simulated aerial combat maneuvers compared with males.

Effects of background field-of-view and depth-plane on the oculogyral illusion.

This study examined the effects of background field-of-view and depth plane on the oculogyral illusion. Seven subjects viewed a stationary fixation stimulus during the postrotatory interval following a 45-sec constant-velocity chair rotation. The duration of the illusory movement of the fixation stimulus during the postrotatory interval was measured, along with the duration of the illusion of whole-body rotation (known as the somatogyral illusion) and the duration of the subject's slow-phase vestibular nystagmus. Subjects viewed the fixation stimulus by itself in a No-background condition or when surrounded by six background fields formed by the combination of two fields-of-view (35 degrees and 115 degrees) and three depth-planes (near, coplanar, and far). The different background fields inhibited the oculogyral illusion relative to the No-background condition but did not differ statistically from each other. The somatogyral durations better matched the oculogyral ones than did nystagmus decay, especially when a background field was present. These results suggest that the oculogyral illusion is more related to the experience of whole-body rotation than to oculomotor mechanisms and that the inhibitory effect of a background scene is only modestly affected by its field-of-view and depth plane.

Effects of age and temporal placement of a modeled skill on children's performance on a balance task.

The present investigation explored the effect of age and temporal placement of a modelled skill on performance on a balance task. 60 boys, aged 7 and 9 yr., were randomly assigned to one of three conditions. The model was presented before any trials were attempted, midway, or not at all during 12 trials. A 2 (age) X 3 (model condition) X 12 (trials) repeated-measures design was utilized. Analysis of variance indicated significant effects of age, temporal appearance of the model, and an interaction of model by age for time on-balance. Model affected younger subjects but not older ones. Treatment did not affect off-balance errors. Findings for age and temporal placement are not consistent with some previous research.

EMG changes during acquisition of a motor skill.

Currently there are only a few studies which attempt to explain the neuromuscular changes which accompany skilled motor learning. Conflicting results have created the need for further research concerned with the electromyographical correlates of motor skill acquisition. A shuffleboard task was devised that isolated the triceps as the major agonist and the biceps as the major antagonist. Ten undergraduate males enrolled at Iowa State University participated in the study. Multivariate analysis and single degree of freedom components based on polynomial regression were used to test linear, quadratic and cubic trends for eight EMG characteristics plus movement time obtained from a systematic sampling of practice trials. Results indicated that trial period means for movement time, latency period and time to peak activity for the triceps exhibited significant linear trends (negative) during practice. No changes were seen in the integrated electromyograms for either the triceps or biceps. It was concluded that force parameters as measured by integrated EMG activity could be determined very early in the learning process and the distribution of these forces through various aspects of timing characterized learning.

Validity of VO(2 max) in predicting blood volume: implications for the effect of fitness on aging.

A multiple regression model was constructed to investigate the premise that blood volume (BV) could be predicted using several anthropometric variables, age, and maximal oxygen uptake (VO(2 max)). To test this hypothesis, age, calculated body surface area (height/weight composite), percent body fat (hydrostatic weight), and VO(2 max) were regressed on to BV using data obtained from 66 normal healthy men. Results from the evaluation of the full model indicated that the most parsimonious result was obtained when age and VO(2 max) were regressed on BV expressed per kilogram body weight. The full model accounted for 52% of the total variance in BV per kilogram body weight. Both age and VO(2 max) were related to BV in the positive direction. Percent body fat contributed <1% to the explained variance in BV when expressed in absolute BV (ml) or as BV per kilogram body weight. When the model was cross validated on 41 new subjects and BV per kilogram body weight was reexpressed as raw BV, the results indicated that the statistical model would be stable under cross validation (e.g., predictive applications) with an accuracy of +/- 1,200 ml at 95% confidence. Our results support the hypothesis that BV is an increasing function of aerobic fitness and to a lesser extent the age of the subject. The results may have implication as to a mechanism by which aerobic fitness and activity may be protective against reduced BV associated with aging.

Interwedge variation in the membrane filter method for airborne asbestos fibers.

The poor precision of the current asbestos method (NIOSH P & CAM 139) has been linked to the variation in fiber deposition on the filter, but the cause of this variation had been unknown. A fluidized bed generator was constructed to produce a test atmosphere containing asbestos fibers, and air samples were collected. Fibers were counted at filter positions corresponding to the trench pattern in the cassette directly below the filter. The average fiber counts on wedges taken from above radial trenches were significantly higher (Pr greater than F = 0.0001) than counts on wedges taken from other portions of the filters. The chief cause of variation in asbestos fiber deposition on the filter is the trench pattern in the cassette supporting the filter.

Laser dosimetry control for retinal surgery.

We discuss the initial stages of the development of a feedback control system to provide consistent lesions across a non-uniform retina during laser photocoagulation therapy. The system will control the power supplied to the irradiating laser in the Hybrid Retinal Photocoagulation System, a system which will robotically assist an ophthalmologist in performing laser photocoagulation. Adding automation to this process will make the procedure less tedious and time-consuming for both patient and ophthalmologist. [1] Research performed during the summer of 2000 to determine a suitable microprocessor for this subsystem is the subject. The results explain the choice of microprocessor. Research continues on this subsystem which will use the reflectance signal to generate real time laser power control.