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D A Ludwig

Publications and source records attributed to D A Ludwig.

At least 19 recordsLinked to original sources

Effects of exposure to simulated microgravity on neuronal catecholamine release and blood pressure responses to norepinephrine and angiotensin.

We tested the hypothesis that exposure to microgravity reduces the neuronal release of catecholamines and blood pressure responses to norepinephrine and angiotensin. Eight men underwent 30 days of 6 degrees head-down tilt (HDT) bedrest to simulate exposure to microgravity. Plasma norepinephrine and mean arterial blood pressure (MAP) were measured before and after a cold pressor test (CPT) and graded norepinephrine infusion (8, 16 and 32 ng/kg/min) on day 6 of a baseline control period (C6) and on days 14 and 27 of HDT. MAP and plasma angiotensin II (Ang-II) were measured during graded Ang-II infusion (1, 2 and 4 ng/kg/min) on C8 and days 16 and 29 of HDT. Baseline total circulating norepinephrine was reduced from 1017ng during the baseline control period to 610 ng at day 14 and 673ng at day 27 of HDT, confirming a hypoadrenergic state. An elevation of norepinephrine (+178 ng) to the CPT during the baseline control period was eliminated by HDT days 14 and 27. During norepinephrine infusion, similar elevations in plasma norepinephrine (7.7 pg/ml/ng/kg/min) caused similar elevations in MAP (0.12 mmHg/ng/kg/min) across all test days. Ang-II infusion produced higher levels of plasma Ang-II during HDT (47.3 pg/ml) than during baseline control (35.5 pg/ml), while producing similar corresponding elevations in blood pressure. While vascular responsiveness to norepinephrine appears unaffected, impaired neuronal release of norepinephrine and reduced vascular responsiveness to Ang-II might contribute to the lessened capacity to vasoconstrict after spaceflight. The time course of alterations indicates effects that occur within two weeks of exposure.

Adult

Evidence for increased cardiac compliance during exposure to simulated microgravity.

We measured hemodynamic responses during 4 days of head-down tilt (HDT) and during graded lower body negative pressure (LBNP) in invasively instrumented rhesus monkeys to test the hypotheses that exposure to simulated microgravity increases cardiac compliance and that decreased stroke volume, cardiac output, and orthostatic tolerance are associated with reduced left ventricular peak dP/dt. Six monkeys underwent two 4-day (96 h) experimental conditions separated by 9 days of ambulatory activities in a crossover counterbalance design: 1) continuous exposure to 10 degrees HDT and 2) approximately 12-14 h per day of 80 degrees head-up tilt and 10-12 h supine (control condition). Each animal underwent measurements of central venous pressure (CVP), left ventricular and aortic pressures, stroke volume, esophageal pressure (EsP), plasma volume, alpha1- and beta1-adrenergic responsiveness, and tolerance to LBNP. HDT induced a hypovolemic and hypoadrenergic state with reduced LBNP tolerance compared with the control condition. Decreased LBNP tolerance with HDT was associated with reduced stroke volume, cardiac output, and peak dP/dt. Compared with the control condition, a 34% reduction in CVP (P = 0.010) and no change in left ventricular end-diastolic area during HDT was associated with increased ventricular compliance (P = 0.0053). Increased cardiac compliance could not be explained by reduced intrathoracic pressure since EsP was unaltered by HDT. Our data provide the first direct evidence that increased cardiac compliance was associated with headward fluid shifts similar to those induced by exposure to spaceflight and that reduced orthostatic tolerance was associated with lower cardiac contractility.

Animals

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.

Acceleration

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.

Adaptation, Physiological

Effects of vestibular and oculomotor stimulation on responsiveness of the carotid-cardiac baroreflex.

Twelve healthy men underwent measurement of their carotid-cardiac baroreflex response during varying conditions of vestibulo-oculomotor stimulation to test the hypothesis that vestibular and/or oculomotor stimulation associated with head movements in the yaw plane inhibit baroreflex control of heart rate. We assessed the carotid-cardiac baroreflex response by plotting R-R intervals (in milliseconds) at each of eight neck pressure steps with their respective carotid distending pressures (in millimeters mercury). Baroreflex sensitivity was measured under four experimental conditions: 1) sinusoidal whole body yaw rotation of the subject in the dark without visual fixation (combined vestibular-oculomotor stimulation); 2) yaw oscillation of the subject while tracking a small head-fixed light moving with the subject (vestibular stimulation without eye movements); 3) subject stationary while fixating on a small light oscillating in yaw at the same frequency, peak acceleration, and velocity as the chair (eye movements without vestibular stimulation); and 4) subject stationary in the dark (no eye or head motion). Head motion alone reduced baseline baroreflex responsiveness by 30% from 3.8 +/- 0.5 to 2.6 +/- 0.5 ms/mmHg. Eye motion alone also reduced the baroreflex response by 13% (0.5 ms/mmHg) to 3.3 +/- 0.5 ms/mmHg. During head motion, the effect of eye motion was negligible (2.7 +/- 0.4 ms/mmHg). These results suggest that vestibular stimulation associated with head movements in yaw inhibits vagally mediated baroreflex control of heart rate, whereas oculomotor stimulation is less of a factor and only in the absence of vestibular stimulation.

Adult

Restoration of plasma volume after 16 days of head-down tilt induced by a single bout of maximal exercise.

Seven healthy men performed maximal exercise 24 h before the end of 16 days exposure to 6 degrees head-down tilt (HDT) to test the hypothesis that such an exercise technique could restore plasma volume (PV) at the end of a simulated space mission. Exercise consisted of supine cycling with graded work rates increasing by 16 W/min to volitional fatigue and required an average of 16 min. The experimental protocol was a standard cross-over design in which the order of treatment (exercise or control) was counterbalanced across all seven subjects. PV, fluid intake (ad libitum), urine output, renal function, and hormones associated with fluid homeostasis were measured before HDT, 24 h before the end of HDT just prior to exercise, and at the end of HDT 24 h after exercise. HDT reduced PV by 16% in both control and exercise conditions. Maximal exercise completely restored plasma volume within 24 h to 3.9 +/- 3.2% of pre-HDT levels despite continued HDT. Compared with control, exercise induced a 660-ml larger positive fluid balance because of greater fluid intake and reduced urine volume during the 24 h after exercise. These results suggest that one bout of maximal leg exercise before return from 16 days of spaceflight may be completely effective in stimulating thirst and restoring plasma volume to preflight levels.

Adult

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.

Adult

Effect of simulated microgravity on cardiopulmonary baroreflex control of forearm vascular resistance.

The stimulus-response characteristics of cardiopulmonary baroreflex control of forearm vascular resistance (FVR) were studied in 11 healthy men before and after 7 days of 6 degrees head-down bedrest to test the hypothesis that microgravity alters this reflex response. We assessed the relationship between stimulus [changes in central venous pressure (delta CVP)] and reflex response (delta FVR) during unloading of cardiopulmonary baroreceptors with lower body negative pressure (LBNP; 0 to -20 mmHg). delta CVP during bedrest and LBNP was estimated from peripheral vein pressures in the dependent right arm. Compared with prebedrest baseline, plasma volume and estimated CVP were decreased by 13 and 33%, respectively, at 7 days of bedrest. Progressive reflex forearm vasoconstriction occurred in response to graded reductions in estimated CVP during LBNP, and delta FVR per unit delta CVP was doubled after bedrest. The increase in sensitivity of the cardiopulmonary baroreflex control of FVR was related to reduced circulating blood volume, suggesting that enhanced peripheral vasoconstriction in individuals adapted to microgravity can be attributed, in part, to hypovolemia. In addition, microgravity appears to alter the stimulus for cardiopulmonary baroreceptors to a lower operational range of CVP, suggesting the possibility of chronic resetting.

Adult

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.

Adult

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Reproducibility of Results

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.

Adult

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.

Adult

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.

Acceleration

Baroreflex responses to acute changes in blood volume in humans.

To test the hypothesis that acute changes in plasma volume affect the stimulus-response relations of high- and low-pressure baroreflexes, eight men (27-44 yr old) underwent measurements for carotid-cardiac and cardiopulmonary baroreflex responses under the following three volemic conditions: hypovolemic, normovolemic, and hypervolemic. The stimulus-response relation of the carotid-cardiac response curve was generated using a neck cuff device, which delivered pressure changes between +40 and -65 mmHg in continuous steps of 15 mmHg. The stimulus-response relationships of the cardiopulmonary baroreflex were studied by measurements of forearm vascular resistance (FVR) and peripheral venous pressure (PVP) during low levels of lower body negative pressure (0 to -20 mmHg). Altered vascular volume had no effect on response relations of the carotid-cardiac baroreflex but did alter the gain of the cardiopulmonary baroreflex (-7.93 +/- 1.73, -4.36 +/- 1.38, and -2.56 +/- 1.59 peripheral resistance units/mmHg for hypovolemic, normovolemic, and hypervolemic, respectively) independent of shifts in baseline FVR and PVP. These results indicate greater demand for vasoconstriction for equal reductions in venous pressure during progressive hypovolemia; this condition may compromise the capacity to provide adequate peripheral resistance during severe orthostatic stress. Fluid loading before reentry after spaceflight may act to restore vasoconstrictive capacity of the cardiopulmonary baroreflex but may not be an effective countermeasure against potential post-flight impairment of the carotid-cardiac baroreflex.

Adult

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.

Acceleration

The effect of square wave exposure profiles upon the performance of passive organic vapor monitoring badges.

Three commercially available passive organic vapor monitoring badges were exposed to ethyl benzene vapor in a dynamic test atmosphere characterized by well defined square wave concentration profiles having periods of 2, 6, and 10 minutes. These concentrations fluctuations between zero and 150 ppm caused no significant bias in the TWA concentration indicated by the badges. A slight, but statistically significant, interaction between badge type and exposure profile is attributable to random analytical error in the data provided by one badge type.

Air Pollutants, Occupational

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.

Air