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A method and apparatus for measuring pressure buildup in a body compartment that encases muscular tissue. The method includes assessing the body compartment configuration and identifying the effect of pulsatile components on at least one compartment dimension. This process is used in preventing tissue necrosis, and in decisions of whether to perform surgery on the body compartment for prevention of Compartment Syndrome. An apparatus is used for measuring excess pressure in the body compartment having components for imparting ultrasonic waves such as a transducer, placing the transducer to impart the ultrasonic waves, capturing the reflected imparted ultrasonic waves, and converting them to electrical signals, a pulsed phase-locked loop device for assessing a body compartment configuration and producing an output signal, and means for mathematically manipulating the output signal to thereby categorize pressure build-up in the body compartment from the mathematical manipulations.

Dietary potassium and protein intakes predict net endogenous acid production in humans. Intracellular buffers, including exchangeable bone mineral, play a crucial role in balancing chronic acid-base perturbations in the body; subsequently, chronic acid loads can potentially contribute to bone loss. Bone is lost during space flight, and a dietary countermeasure would be desirable for many reasons. We studied the ability of diet protein and potassium to predict levels of bone resorption markers in males and females. Identical twin pairs (8 M, 7 F) were assigned to 2 groups: bed rest (sedentary, SED) or bed rest with supine treadmill exercise in a lower body negative pressure chamber (EX). Diet was controlled for 3 d before and 30 d of bed rest (BR). Urinary Ca, N-telopeptide (NTX), and pyridinium crosslinks (PYD) were measured before and on days 5, 12, 19, and 26 of BR. Data were analyzed by Pearson correlation (P<0.05). The ratio of dietary animal protein/potassium intake was not correlated with NTX before BR for males or females, but they were positively correlated in both groups of males during bed rest. Dietary animal protein/potassium and urine Ca were correlated before and during bed rest for the males, and only during bed rest for the females. Conversely, the ratio of dietary vegetable protein/potassium intake was negatively correlated with urinary calcium during bed rest for the females, but there was no relationship between vegetable protein/potassium intake and bone markers for the males. These data suggest that the ratio of animal protein/potassium intake may affect bone, particularly in bed rest subjects. These data show that the type of protein and gender may be additional factors that modulate the effect of diet on bone metabolism during bed rest. Altering this ratio may help prevent bone loss on Earth and during space flight.

The following topics were covered: System Specificity in Responsiveness to Intermittent -Gx Gravitation during Simulated Microgravity in Rats; A Brief Overview of Animal Hypergravity Studies; Neurovestibular Adaptation to Short Radius Centrifugation; Effect of Artificial Gravity with Exercise Load by Using Short-Arm Centrifuge with Bicycle Ergometer as a Countermeasure Against Disused Osteoporosis; Perception of Body Vertical in Microgravity during Parabolic Flight; Virtual Environment a Behavioral and Countermeasure Tool for Assisted Gesture in Weightlessness: Experiments during Parabolic Flight; Artificial Gravity: Physiological Perspectives for Long-Term Space Exploration; Comparison of the Effects of DL-threo-Beta-Benzyloxyaspartate on the Glutamate Release from Synaptosomes before and after Exposure of Rats to Artificial Gravity; Do Perception and Postrotatory Vestibulo-Ocular Reflex Share the Same Gravity Reference?; Vestibular Adaptation to Changing Gravity Levels and the Orientation of Listing's Plane; Compound Mechanism Hypothesis on +Gz - Induced Brain Injury and Dysfunction of Learning and Memory; Environmental Challenge Impairs Prefrontal Brain Functions; Effect of 6-Days of Support Withdrawal on Characteristics of Balance Function; Hypergravity-Induced Changes of Neuronal Activities in CA1 Region of Rat Hippocampus; Audiological Findings in Antiorthostatic Position Modelling Microgravitation; Investigating Human Cognitive Performance during Spaceflight; The Relevance of the Minimization of Torque Exchange with the Environment in Weightlessness is Confirmed by Asimulation Study; Characteristics of the Eyes Pursuit Function during Readaptation to Terrestrial Gravity after Prolonged Flights Aboard the International Space Station; Comparison of Cognitive Performance Tests for Promethazine Pharmacodynamics in Human Subjects; Structural Reappraisal of Dendritic Tree of Cerebellar Purkinje Cell for Novel Functional Modeling of Elementary Sensorimotor Adaptive Processes; Orpheus 0 G or Ear in Microgravity to Establish Symptoms Concomittant of Inner and Middle Ear and Osteoporosis in Microgravity; Understanding Visual Perception in the Perspective of Gravity; Cortical Regions Associated with Orthostatic Stress in Conscious Humans; Restoration of Central Blood Volume: Application of a Simple Concept and Simple Device to Counteract Cardiovascular Instability in Syncope and Hemorrhage; WISE-2005: Integrative Cardiovascular Responses with LBNP during 60-Day Bed Rest in Women; Intracranial Pressure Increases during Weightlessness. A Parabolic Flights Study; Lower Limb & Portal Veins Echography for Predicting Risk of Thrombosis during a 90-D Bed Rest; Calf Tissue Liquid Stowage and Muscular and Deep Vein Distension in Orthostatic Tests after a 90-Day Head Down Bed Rest; Morphology of Brain Vessels in the Tail Suspended Rats Exposed to Intermittent 2 G; Alterations in Vasoreactivity of Femoral Artery Induced by Hindlimb Unweighting are Related to the Changes of Contractile Protein in Rats; and Respiratory Sinus Arrhythmia: A Marker of Decreased Parasympathetic Modulation after Short Duration.

Several classic twin studies show genetic effects on markers of bone health, including bone mineral density and parathyroid hormone (PTH). This study was performed to assess the relative contribution of genetics to biochemical markers of bone metabolism. Fifteen sets of identical twins (8 male, 7 female) were housed in a clinical research center where diet was controlled (15% protein, 55% carbohydrate, 30% fat) for 3 consecutive days. Each day, 24-h urine pools were collected and N-telopeptide (NTX), deoxypyridinoline (DPD), calcium, and serum PTH were measured. The broad-sense heritability factor (H2) is an estimation of the portion of the total variance of a given phenotype that is attributable to genetic variance. H2 was estimated from the correlation coefficient of the phenotype data. H2 for NTX was 94% for males and 80% for females, DPD was 88% for males and 97% for females, urinary calcium excretion was 97% for males and 90% for females, and PTH was 92% for males and 79% for females. Since environmental variability was minimized for the 3 days of data collection, these heritability factors are likely overestimated. Nonetheless, the data support the concept that PTH is a predominantly heritable trait, and suggest that NTX, DPD, and calcium excretion are as well. These biochemical data support the previously documented heritability of bone health.

A method is presented for determining diastolic intracranial pressure (ICP) in a patient. A first change in the length of a path across the skull of the patient caused by a known change in ICP is measured and used to determine an elasticity constant for the patient. Next, a second change in the length of the path across the patient's skull occurring between systolic and diastolic portions of the patient's heartbeat is measured. The patient's diastolic ICP is a function of the elasticity constant and the second change.

INTRODUCTION: Current space suits have limited movement due to gas pressurization during exposure to the vacuum of space. Alternatively, if pressure is applied by an elastic garment vs. pneumatic garment to produce mechanical counter pressure (MCP), several advantages are possible. In this study, we investigate local microcirculatory and other effects produced with and without a prototype MCP glove and sleeve during exposure to varying levels of vacuum. METHODS: The entire arms of eight male volunteers were studied at normal ambient pressure and during 5 min exposures to -50, -100, and -150 mm Hg with and without the MCP glove and sleeve. Pressure distribution, skin microvascular flow, and temperature were measured. RESULTS: The MCP glove and sleeve generated over 200 mm Hg on the middle finger, dorsum of the hand, and the wrist. However, pressure was significantly lower on the forearm and the upper arm. Without the glove and sleeve, only two of eight subjects tolerated -100 mm Hg. Also, no subject tolerated -150 mm Hg. However, subjects tolerated all vacuum pressures wearing the glove and sleeve. Skin microvascular flow and temperature remained within control values with the glove and sleeve at a chamber pressure of -150 mm Hg. DISCUSSION: The MCP glove and sleeve counteracts adverse effects of vacuum exposures due to lower pressure differentials. Pressure levels over the hand and wrist are similar to those of the current U.S. space suit glove and sleeve, but additional development is required to increase MCP over the forearm and upper arm.

We have developed an ultrasonic device to monitor ICP waveforms non-invasively from cranial diameter oscillations using a NASA-developed pulsed phase lock loop (PPLL) technique. The purpose of this study was to attempt to validate the PPLL device for reliable recordings of ICP waveforms and analysis of ICP dynamics in vivo. METHODS: PPLL outputs were recorded in patients during invasive ICP monitoring at UCSD Medical Center (n=10). RESULTS: An averaged linear regression coefficient between ICP and PPLL waveform data during one cardiac cycle in all patients is 0.88 +/- 0.02 (mean +/- SE). Coherence function analysis indicated that ICP and PPLL waveforms have high correlation in the lst, 2nd, and 3rd harmonic waves associated with a cardiac cycle. CONCLUSIONS: PPLL outputs represent ICP waveforms in both frequency and time domains. PPLL technology enables in vivo evaluation of ICP dynamics non-invasively, and can acquire continuous ICP waveforms during spaceflight because of compactness and non-invasive nature.

INTRODUCTION: Spinal lengthening in microgravity is thought to cause back pain in astronauts. A spinal compression harness can compress the spine to eliminate lengthening but the loading condition with harness is different than physiologic conditions. Our purpose was to compare the effect of spine compression with a harness in supine position on disk height and spinal curvature in the lumbar spine to that of upright position as measured using a vertically open magnetic resonance imaging system. METHODS: Fifteen healthy subjects volunteered. On day 1, each subject lay supine for an hour and a baseline scan of the lumbar spine was performed. After applying a load of fifty percent of body weight with the harness for thirty minutes, the lumbar spine was scanned again. On day 2, after a baseline scan, a follow up scan was performed after kneeling for thirty minutes within the gap between two vertically oriented magnetic coils. Anterior and posterior disk heights, posterior disk bulging, and spinal curvature were measured from the baseline and follow up scans. RESULTS: Anterior disk heights increased and posterior disk heights decreased compared with baseline scans both after spinal compression with harness and upright posture. The spinal curvature increased by both loading conditions of the spine. DISCUSSION: The spinal compression with specially designed harness has the same effect as the physiologic loading of the spine in the kneeling upright position. The harness shows some promise as a tool to increase the diagnostic capabilities of a conventional MR system.

STUDY DESIGN: Axial load-dependent changes in the lumbar spine of supine healthy volunteers were examined using a compression device compatible with magnetic resonance imaging. OBJECTIVE: To test two hypotheses: Axial loading of 50% body weight from shoulder to feet in supine posture 1) simulates the upright lumbar spine alignment and 2) decreases disc height significantly. SUMMARY OF BACKGROUND DATA: Axial compression on the lumbar spine has significantly narrowed the lumbar dural sac in patients with sciatica, neurogenic claudication or both. METHODS: Using a device compatible with magnetic resonance imaging, the lumbar spine of eight young volunteers, ages 22 to 36 years, was axially compressed with a force equivalent to 50% of body weight, approximating the normal load on the lumbar spine in upright posture. Sagittal lumbar magnetic resonance imaging was performed to measure intervertebral angle and disc height before and during compression. RESULTS: Each intervertebral angle before and during compression was as follows: T12-L1 (-0.8 degrees +/- 2.5 degrees and -1.5 degrees +/- 2.6 degrees ), L1-L2 (0.7 degrees +/- 1.4 degrees and 3.3 degrees +/- 2.9 degrees ), L2-L3 (4.7 degrees +/- 3.5 degrees and 7.3 degrees +/- 6 degrees ), L3-L4 (7.9 degrees +/- 2.4 degrees and 11.1 degrees +/- 4.6 degrees ), L4-L5 (14.3 degrees +/- 3.3 degrees and 14.9 degrees +/- 1.7 degrees ), L5-S1 (25.8 degrees +/- 5.2 degrees and 20.8 degrees +/- 6 degrees ), and L1-S1 (53.4 degrees +/- 11.9 degrees and 57.3 degrees +/- 16.7 degrees ). Negative values reflect kyphosis, and positive values reflect lordosis. A significant difference between values before and during compression was obtained at L3-L4 and L5-S1. There was a significant decrease in disc height only at L4-L5 during compression. CONCLUSIONS: The axial force of 50% body weight in supine posture simulates the upright lumbar spine morphologically. No change in intervertebral angle occurred at L4-L5. However, disc height at L4-L5 decreased significantly during compression.

The purpose of this investigation was to determine whether ischemia, which reduces oxygenation in the extensor carpi radialis (ECR) muscle, causes a reduction in muscle force production. In eight subjects, muscle oxygenation (TO2) of the right ECR was measured noninvasively and continuously using near infrared spectroscopy (NIRS) while muscle twitch force was elicited by transcutaneous electrical stimulation (1 Hz, 0.1 ms). Baseline measurements of blood volume, muscle oxygenation and twitch force were recorded continuously, then a tourniquet on the upper arm was inflated to one of five different pressure levels: 20, 40, 60 mm Hg (randomized order) and diastolic (69 +/- 9.8 mm Hg) and systolic (106 +/- 12.8 mm Hg) blood pressures. Each pressure level was maintained for 3-5 min, and was followed by a recovery period sufficient to allow measurements to return to baseline. For each respective tourniquet pressure level, mean TO2 decreased from resting baseline (100% TO2) to 99 +/- 1.2% (SEM), 96 +/- 1.9%, 93 +/- 2.8%, 90 +/- 2.5%, and 86 +/- 2.7%, and mean twitch force decreased from resting baseline (100% force) to 99 +/- 0.7% (SEM), 96 +/- 2.7%, 93 +/- 3.1%, 88 +/- 3.2%, and 86 +/- 2.6%. Muscle oxygenation and twitch force at 60 mm Hg tourniquet compression and above were significantly lower (P < 0.05) than baseline value. Reduced twitch force was correlated in a dose-dependent manner with reduced muscle oxygenation (r = 0.78, P < 0.001). Although the correlation does not prove causation, the results indicate that ischemia leading to a 7% or greater reduction in muscle oxygenation causes decreased muscle force production in the forearm extensor muscle. Thus, ischemia associated with a modest decline in TO2 causes muscle fatigue.

STUDY DESIGN: Brief (30-second) isometric trunk extensions at 5%, 20%, 40%, 60%, and 80% of maximal voluntary contraction (MVC) and 3 minutes of prolonged trunk extension (20% MVC) in erect position were studied in nine healthy male subjects. OBJECTIVES: To investigate the intercorrelation between intramuscular pressure and tissue oxygenation of the paravertebral muscles during submaximal isometric contractions and further, to evaluate paravertebral electromyogram and intramuscular pressure as indicators of force development. SUMMARY OF BACKGROUND DATA: Local physiologic responses to muscle contraction are incompletely understood. METHODS: Relative oxygenation was monitored with noninvasive near-infrared spectroscopy, intramuscular pressure was measured with a transducer-tipped catheter, and surface electromyogram was monitored at three recording sites. RESULTS: The root mean square amplitudes of the paravertebral electromyogram (L4, left and right; T12, right) and intramuscular pressure measured in the lumbar multifidus muscle at L4 increased with greater force development in a curvilinear manner. A significant decrease in the oxygenation of the lumbar paravertebral muscle in response to muscle contraction was found at an initial contraction level of 20% MVC. This corresponded to a paravertebral intramuscular pressure of 30-40 mm Hg. However, during prolonged trunk extension, no further decrease in tissue oxygenation was found compared with the tissue oxygenation level at the end of the brief contractions, indicating that homeostatic adjustments (mean blood pressure and heart rate) over time were sufficient to maintain paravertebral muscle oxygen levels. CONCLUSION: At a threshold intramuscular pressure of 30-40 mm Hg during muscle contraction, oxygenation in the paravertebral muscles is significantly reduced. The effect of further increase in intramuscular pressure on tissue oxygenation over time may be compensated for by an increase in blood pressure and heart rate. Surface electromyogram amplitudes and intramuscular pressure can be used as indicators of paravertebral muscle force.

Intracranial pressure (ICP) dynamics are important for understanding adjustments to altered gravity. Previous flight observations document significant facial edema during exposure to microgravity, which suggests that ICP is elevated during microgravity. However, there are no experimental results obtained during space flight, primarily due to the invasiveness of currently available techniques. We have developed and refined a noninvasive technique to measure intracranial pressure noninvasively. The technique is based upon detecting skull movements of a few micrometers in association with altered intracranial pressure. We reported that the PPLL technique has enough sensitivity to detect changes in cranial distance associated with the pulsation of ICP in cadavera. In normal operations, however, we place a transducer on the scalp. Thus, we cannot rule out the possibility that the PPLL technique picks up cutaneous pulsation. The purpose of the present study was therefore to show that the PPLL technique has enough sensitivity to detect changes in cranial distance associated with cardiac cycles in vivo.

This article reviews present knowledge of the pathophysiology and diagnosis of acute compartment syndromes. Recent results using compression of legs in normal volunteers provide objective data concerning local pressure thresholds for neuromuscular dysfunction in the anterior compartment. Results with this model indicate that a progression of neuromuscular deficits occurs when IMP increases to within 35 to 40 mm Hg of diastolic blood pressure. These findings provide useful information on the diagnosis and compression thresholds for acute compartment syndromes. Time factors are also important, however, and usually are incompletely known in most cases of acute compartment syndrome. Although the slit catheter is a very good technique for monitoring IMP during rest, these catheters and their associated extracorporeal transducer systems are not ideal. Recently developed miniature transducer-tipped catheters and, perhaps, future development of noninvasive techniques may provide accurate recordings of IMP in patients with acute compartment syndromes.

To assess the usefulness of intramuscular pressure (IMP) measurement for studying muscle function during gait, IMP was recorded in the soleus and tibialis anterior muscles of 10 volunteers during treadmill walking and running by using transducer-tipped catheters. Soleus IMP exhibited single peaks during late-stance phase of walking [181 +/- 69 (SE) mmHg] and running (269 +/- 95 mmHg). Tibialis anterior IMP showed a biphasic response, with the largest peak (90 +/- 15 mmHg during walking and 151 +/- 25 mmHg during running) occurring shortly after heel strike. IMP magnitude increased with gait speed in both muscles. Linear regression of soleus IMP against ankle joint torque obtained by a dynamometer produced linear relationships (n = 2, r = 0.97 for both). Application of these relationships to IMP data yielded estimated peak soleus moment contributions of 0.95-1.65 N . m/kg during walking, and 1.43-2.70 N . m/kg during running. Phasic elevations of IMP during exercise are probably generated by local muscle tissue deformations due to muscle force development. Thus profiles of IMP provide a direct, reproducible index of muscle function during locomotion in humans.

Snakes are useful vertebrates for studies of gravitational adaptation, owing to their elongate body and behavioral diversification. Scansorial species have evolved specializations for regulating hemodynamics during exposure to gravitational stress, whereas, such adaptations are less well developed in aquatic and non-climbing species. We examined responses of the amphibious snake,\italicize (Nerodia rhombifera), to increments of Gz (head-to-tail) acceleration force on both a short- and long-arm centrifuge (1.5 vs. 3.7 m radius, from the hub to tail end of snake). We recorded heart rate, dorsal aortic pressure, and carotid arterial blood flow during stepwise 0.25 G increments of Gz force (referenced at the tail) in conscious animals. The Benz tolerance of a snake was determined as the Gz level at which carotid blood flow ceased and was found to be significantly greater at the short- than long-arm centrifuge radius (1.57 Gz vs. 2.0 Gz, respectively; P=0.016). A similar pattern of response was demonstrated in semi-arboreal rat snakes,\italicize{Elaphe obsoleta}, which are generally more tolerant of Gz force (2.6 Gz at 1.5m radius) than are water snakes. The tolerance differences of the two species reflected cardiovascular responses, which differed quantitatively but not qualitatively: heart rates increased while arterial pressure and blood flow decreased in response to increasing levels of Gz. Thus, in both species of snakes, a reduced gradient of Gz force (associated with greater centrifuge radius) significantly decreases the Gz level that can be tolerated.

The present study was designed to validate our noninvasive ultrasonic technique (pulse phase locked loop: PPLL) for measuring intracranial pressure (ICP) waveforms. The technique is based upon detecting skull movements which are known to occur in conjunction with altered intracranial pressure. In bench model studies, PPLL output was highly correlated with changes in the distance between a transducer and a reflecting target (R2 = 0.977). In cadaver studies, transcranial distance was measured while pulsations of ICP (amplitudes of zero to 10 mmHg) were generated by rhythmic injections of saline. Frequency analyses (fast Fourier transformation) clearly demonstrate the correspondence between the PPLL output and ICP pulse cycles. Although theoretically there is a slight possibility that changes in the PPLL output are caused by changes in the ultrasonic velocity of brain tissue, the decreased amplitudes of the PPLL output as the external compression of the head was increased indicates that the PPLL output represents substantial skull movement associated with altered ICP. In conclusion, the ultrasound device has sufficient sensitivity to detect transcranial pulsations which occur in association with the cardiac cycle. Our technique makes it possible to analyze ICP waveforms noninvasively and will be helpful for understanding intracranial compliance and cerebrovascular circulation.

The purpose of our investigation was to determine if the near infrared spectroscopy technique was sensitive to changes in tissue oxygenation at low levels of isometric contraction in the extensor carpi radialis brevis muscle. Nine subjects were seated with the right arm abducted to 45 degrees, elbow flexed to 85 degrees, forearm pronated 45 degrees, and wrist and forearm supported on an armrest throughout the protocol. Altered tissue oxygenation was measured noninvasively with near infrared spectroscopy. The near infrared spectroscopy probe was placed over the extensor carpi radialis brevis of the subject's right forearm and secured with an elastic wrap. After 1 minute of baseline measurements taken with the muscle relaxed, four different loads were applied just proximal to the metacarpophalangeal joint such that the subjects isometrically contracted the extensor carpi radialis brevis at 5, 10, 15, and 50% of the maximum voluntary contraction for 1 minute each. A 3-minute recovery period followed each level of contraction. At the end of the protocol, with the probe still in place, a value for ischemic tissue oxygenation was obtained for each subject. This value was considered the physiological zero and hence 0% tissue oxygenation. Mean tissue oxygenation (+/-SE) decreased from resting baseline (100% tissue oxygenation) to 89 +/- 4, 81 +/- 8, 78 +/- 8, and 47 +/- 8% at 5, 10, 15, and 50% of the maximum voluntary contraction, respectively. Tissue oxygenation levels at 10, 15, and 50% of the maximum voluntary contraction were significantly lower (p < 0.05) than the baseline value. Our results indicate that tissue oxygenation significantly decreases during brief, low levels of static muscle contraction and that near infrared spectroscopy is a sensitive technique for detecting deoxygenation noninvasively at low levels of forearm muscle contraction. Our findings have important implications in occupational medicine because oxygen depletion induced by low levels of muscle contraction may be directly linked to muscle fatigue.

Currently, the definitive diagnosis of chronic compartment syndrome is based on invasive measurements of intracompartmental pressure. We measured the intramuscular pressure and the relative oxygenation in the anterior compartment of the leg in eighteen patients who were suspected of having chronic compartment syndrome as well as in ten control subjects before, during, and after exercise. Chronic compartment syndrome was considered to be present if the intramuscular pressure was at least fifteen millimeters of mercury (2.00 kilopascals) before exercise, at least thirty millimeters of mercury (4.00 kilopascals) one minute after exercise, or at least twenty millimeters of mercury (2.67 kilopascals) five minutes after exercise. Changes in relative oxygenation were measured with use of the non-invasive method of near-infrared spectroscopy. In all patients and subjects, there was rapid relative deoxygenation after the initiation of exercise, the level of oxygenation remained relatively stable during continued exercise, and there was reoxygenation to a level that exceeded the pre-exercise resting level after the cessation of exercise. During exercise, maximum relative deoxygenation in the patients who had chronic compartment syndrome (mean relative deoxygenation [and standard error], -290 +/- 39 millivolts) was significantly greater than that in the patients who did not have chronic compartment syndrome (-190 +/- 10 millivolts) and that in the control subjects (-179 +/- 14 millivolts) (p < 0.05 for both comparisons). In addition, the interval between the cessation of exercise and the recovery of the pre-exercise resting level of oxygenation was significantly longer for the patients who had chronic compartment syndrome (184 +/- 54 seconds) than for the patients who did not have chronic compartment syndrome (39 +/- 19 seconds) and the control subjects (33 +/- 10 seconds) (p < 0.05 for both comparisons).

Snakes have provided useful vertebrate models for understanding circulatory adaptation to gravity, attributable to their elongate body shape and evolutionary diversificaton in terms of ecology and behavior. Recently we have studied cardiovascular responses of snakes to hypergravic acceleration forces produced acutely in the head-to-tail direction (+Gz) on a short-arm centrifuge. Snakes were held in a nearly straight position within a horizontal plastic tube and subjected to a linear force gradient during acceleration. Carotid blood flow provided an integrated measure of cardiovascular performance. Thus, cardiovascular tolerance of snakes to stepwise increments of Gz was measured as the caudal Gz force at which carotid blood flow ceased. Tolerance to increasing Gz varies according to adaptive evolutionary history inferred from the ecology and behavior of species. With respect to data for six species we investigated, multiple regression analysis demonstrates that Gz tolerance correlates with gravitational habitat, independently of body length. Relative to aquatic and non-climbing species, carotid blood flow is better maintained in arboreal or scansorial species, which tolerate hypergravic forces of +2 to +3.5 Gz. Additionally, semi-arboreal rat snakes (Elaphe obsoleta) exhibit plasticity of responses to long-term, intermittent +1.5 Gz stress. Compared to non-acclimated controls, acclimated snakes show greater increases of heart rate during head-up tilt or acceleration, greater sensitivity of arterial pressure to circulating catecholamines, higher blood levels of prostaglandin ratios favorable to maintenance of arterial blood pressure, and medial hypertrophy in major arteries and veins. As in other vertebrates, Gz tolerance of snakes is enhanced by acclimation, high arterial pressure, comparatively large blood volume, and body movements. Vascular studies of snakes suggest the importance to acclimation of local responses involving vascular tissue, in addition to centrally mediated responses to fluid shifts.

Variations in the levels of muscle hemoglobin and of myoglobin oxygen saturation can be detected non-invasively with near-infrared spectroscopy. This technique could be applied to the diagnosis of chronic compartment syndrome, in which invasive testing has shown increased intramuscular pressure associated with ischemia and pain during exercise. We simulated chronic compartment syndrome in ten healthy subjects (seven men and three women) by applying external compression, through a wide inflatable cuff, to increase the intramuscular pressure in the anterior compartment of the leg. The tissue oxygenation of the tibialis anterior muscle was measured with near-infrared spectroscopy during gradual inflation of the cuff to a pressure of forty millimeters of mercury (5.33 kilopascals) during fourteen minutes of cyclic isokinetic dorsiflexion and plantar flexion of the ankle. The subjects exercised with and without external compression. The data on tissue oxygenation for each subject then were normalized to a scale of 100 per cent (the baseline value, or the value at rest) to 0 per cent (the physiological minimum, or the level of oxygenation achieved by exercise to exhaustion during arterial occlusion of the lower extremity). With external compression, tissue oxygenation declined at a rate of 1.4 +/- 0.3 per cent per minute (mean and standard error) during exercise. After an initial decrease at the onset, tissue oxygenation did not decline during exercise without compression. The recovery of tissue oxygenation after exercise was twice as slow with compression (2.5 +/- 0.6 minutes) than it was without the use of compression (1.3 +/- 0.2 minutes).

In addition to extensive use of lower extremity physical exercise training as a countermeasure for the work capacity component of spaceflight deconditioning, some form of additional head-to-foot (+Gz) gravitational (orthostatic) stress may be required to further attenuate or prevent the signs and symptoms (nausea, vertigo, instability, fatigue) of the general reentry syndrome (GRS) that can reduce astronaut performance during landing. Orthostatic (head-to-foot) stress can be induced by standing, by lower body negative pressure, and by +Gz acceleration. One important question is whether acceleration training alone or with concurrent leg exercise would provide sufficient additive stimulation to attenuate the GRS. Use of a new human-powered centrifuge may be the answer. Thus, the purpose for this study was to compare heart rate (HR), i.e., a stress response during human-powered acceleration, in four men (35-62 yr) and two women (30-31 yr) during exercise acceleration versus passive acceleration (by an off-board operator) at 100% (maximal acceleration = A(max)), and at 25%, 50%, and 75% of A(max). Mean (+/-SE) A(max) was 43.7 +/- 1.3 rpm (+3.9 +/- 0.2Gz). Mean HR at exercise A(max) was 189 +/- 13 b/min (50-70 sec run time), and 142 +/- 22 b/min at passive A(max) (40-70 sec run time). Regression of mean HR on the various +Gz levels indicated explained variance (correlations squared) of r(exp 2) = 0.88 (exercise) and r(exp 2) = 0.96 (passive): exercise HR of 107 +/- 4 (25%) to 189 +/- 13 (100%) b/min were 43-50 b/min higher (p less than 0.05) than comparable passive HR of 64 +/- 2 to 142 +/- 22 b/min. Thus, exercise adds significant physiological stress during +Gz acceleration. Inflight use of this combined exercise and acceleration countermeasure may maintain work capacity as well as normalize acceleration and orthostatic tolerances which could attenuate or perhaps eliminate the GRS.

By virtue of its tallness and terrestrial environment, the giraffe is a uniquely sensitive African animal to investigate tissue adaptations to gravitational stress. One decade ago, we studied transcapillary fluid balance and local tissue adaptations to high cardiovascular and musculoskeletal loads in adult and fetal giraffes. Previous studies by Goetz, Pattersson, Van Citters, Warren and their colleagues revealed that arterial pressure near the giraffe heart is about twice that in humans, to provide more normal blood pressure and perfusion to the brain. Another important question is how giraffes avoid pooling of blood and tissue fluid (edema) in dependent tissue of the extremities. As monitored by radiotelemetry, the blood and tissue fluid pressures that govern transcapillary exchange vary greatly with exercise. These pressures, combined with a tight skin layer, move fluid upward against gravity. Other mechanisms that prevent edema include precapillary vasoconstriction and low permeability of capillaries to plasma proteins. Other anatomical adaptations in dependent tissues of giraffes represent developmental adjustments to high and variable gravitational forces. These include vascular wall hypertrophy, thickened capillary basement membrane and other connective tissue adaptations. Our results in giraffe suggest avenues of future gravitational research in other animals including humans.

The aim of this study was to determine the effects of a 12.5 day spaceflight on the endocrine status of Rhesus monkeys. Male monkeys (three to four years old; 4 kg) were adapted to chair restraint and trained for 20 months. Blood samples were obtained from four control (C) and two flight (F) monkeys preflight (PF), post-flight (Recovery-R; days 0, 3, 11, and 17), and before and after a mission length simulation (S). Cortisol, T4, T3, testosterone (T), and IGF-1 were measured by RIA (radioimmunassay). Growth hormone (GH) was measured by an in vitro bioassay. Cortisol (16-34 ug/dl), T4 (3.9-7.4 ug/dl), and T (0.2-0.4 mg/ml) did not differ between F and C or between PF, R, and S samples. The low T values reflect the immaturity of the animals. In F, T3 fell from C levels of 208 +/- 4 ng/dl to 44 on R+0 and 150 on R+3, then returned to C. F showed a 55% decrease in GH at R+0 and decreases of 93, 89, and 80%, respectively, at R+3, 11, and 17. IGF-1 decreased from PF levels of 675 ng/ml to 365 (R+0) and 243 (R+3), but returned to C at R+11. GH and IGF-1 levels before and after S did not differ from each other or from C. The cause of the transitory decrease in T3 is unknown. The suppressed GH levels for 17 days after flight may reflect reduced proprioceptive input during flight. The faster recovery of IGF-1 suggests that factors other than reduced GH secretion are involved.

Our objective was to understand how weight bearing with varying gravitational fields affects blood perfusion in the sole of the foot. Human subjects underwent whole body tilting at four angles: upright [1 gravitational vector from head to foot (Gz)], 22 degrees (0.38 Gz), 10 degrees (0.17 Gz), and supine (0 Gz), simulating the gravitational fields of Earth, Mars, Moon, and microgravity, respectively. Cutaneous capillary blood flow was monitored on the plantar surface of the heel by laser Doppler flowmetry while weight-bearing load was measured. At each tilt angle, subjects increased weight bearing on one foot in graded load increments of 1 kg beginning with zero. The weight bearing at which null flow first occurred was determined as the closing load. Subsequently, the weight bearing was reduced in reverse steps until blood flow returned (opening load). Mean closing loads for simulated Earth gravity, Mars gravity, Moon gravity, and microgravity were 9.1, 4.6, 4.4, and 3.6 kg, respectively. Mean opening loads were 7.9, 4.1, 3.5, and 3.1 kg, respectively. Mean arterial pressures in the foot (MAP(foot)) calculated for each simulated gravitational field were 192, 127, 106, and 87 mmHg, respectively. Closing load and opening load were significantly correlated with MAP(foot) (r =0.70, 0.72, respectively) and were significantly different (P < 0.001) from each other. The data suggest that decreased local arterial pressure in the foot lowers tolerance to external compression. Consequently, the human foot sole may be more prone to cutaneous ischemia during load bearing in microgravity than on Earth.

This article reviews recent flight and ground-based studies of cardiovascular adaptation to spaceflight. Prominent features of microgravity exposure include loss of gravitational pressures, relatively low venous pressures, headward fluid shifts, plasma volume loss, and postflight orthostatic intolerance and reduced exercise capacity. Many of these short-term responses to microgravity extend themselves during long-duration microgravity exposure and may be explained by altered pressures (blood and tissue) and fluid balance in local tissues nourished by the cardiovascular system. In this regard, it is particularly noteworthy that tissues of the lower body (e.g., foot) are well adapted to local hypertension on Earth, whereas tissues of the upper body (e.g., head) are not as well adapted to increase in local blood pressure. For these and other reasons, countermeasures for long-duration flight should include reestablishment of higher, Earth-like blood pressures in the lower body.

Sensitivity of carotid blood flow to increased gravitational force acting in the head-to-tail direction(+Gz) was studied in diverse species of snakes hypothesized to show adaptive variation of response. Tolerance to increased gravity was measured red as the maximum graded acceleration force at which carotid blood flow ceased and was shown to vary according to gravitational adaptation of species defined by their ecology and behavior. Multiple regression analysis showed that gravitational habitat, but not body length, had a significant effect on Gz tolerance. At the extremes, carotid blood flow decreased in response to increasing G force and approached zero near +1 Gz in aquatic and ground-dwelling species, whereas in climbing species carotid flow was maintained at forces in excess of +2 Gz. Tolerant (arboreal) species were able to withstand hypergravic forces of +2 to +3 Gz for periods up to 1 h without cessation of carotid blood flow or loss of body movement and tongue flicking. Data suggest that the relatively tight skin characteristic of tolerant species provides a natural antigravity suit and is of prime importance in counteracting Gz stress on blood circulation.

Cardiovascular functions were studied in semi-arboreal rat snakes (Elaphe obsoleta) following long-term, intermittent exposure to +1.5 Gz (head-to-tail acceleration) on a centrifuge. Snakes were held in a nearly straight position within horizontal plastic tubes during periods of centrifugation. Centrifugal acceleration, therefore, subjected snakes to a linear force gradient with the maximal force being experienced at the tail. Compared to non-centrifuged controls, Gz-acclimated snakes showed greater increases of heart rate during head-up tilt or acceleration, greater sensitivity of arterial pressure to circulating catecholamines, higher blood levels of corticosterone, and higher blood ratios of prostaglandin F 2 alpha/prostaglandin E2. Cardiovascular tolerance to increased gravity during graded Gz acceleration was measured as the maximum (caudal) acceleration force at which carotid arterial blood flow became null. When such tolerances were adjusted for effects of body size and other continuous variables incorporated into an analysis of covariance, the difference between the adjusted mean values of control and acclimated snakes (2.37 and 2.84 Gz, respectively) corresponded closely to the 0.5 G difference between the acclimation G (1.5) and Earth gravity (1.0). As in other vertebrates, cardiovascular tolerance to Gz stress tended to be increased by acclimation, short body length, high arterial pressure, and comparatively large blood volume. Voluntary body movements were important for promoting carotid blood flow at the higher levels of Gz stress.

Previously reported effects of chronic centrifugation on renal function in mammals are contradictory. The present study was conducted as an effort to provide a comprehensive analysis of renal response to chronic centrifugation (12 days at +2 Gz). Sixteen male Sprague-Dawley rats (210-230 g) were used: eight centrifuged (EC) and eight off centrifuge controls (OCC). During centrifugation EC had lower body weight and food consumption. EC showed a decrease (72%) in water intake for the first two days (T1 and T2) followed by significant increases from T4-T6. EC urine output increased two-fold over the first four days, returning to baseline by T9. EC urea excretion was elevated on T3 through T5. Creatinine, Na(+), K(+), and osmolar excretion were lower than OCC over the last four days of the study. Assuming constant plasma osmolarity and creatinine levels, EC free water clearance (C(sub H2O)) was elevated significantly on T4 when the peak urine output was exhibited. EC also had a greater C(sub H2O) over the last four days, associated with a significantly lower osmolar clearance and GFR. The initial diuresis exhibited during centrifugation can be attributed to a reduced water resorption and increased urea excretion. This diuresis was mediated independent of changes in GFR over the first eight days. However, differences in excretion seen after eight days of centrifugation are probably GFR mediated which would imply animals established a new homeostatic setpoint by that time. Centrifugation elicites an acute alteration in fluid homeostasis followed by adaptation within a week.

Previous research has shown animal body mass to be significantly affected by centrifugation. At the onset of centrifugation, animals have a selective loss of fat, causing an initial body mass loss. Body mass gain will resume at the same rate as uncentrifuged animals, but this subsequent gain will be lower. For this study, two different ages of Sprague Hawley neonate families were observed during centrifugation. Eight litters (dam with eight neonates) of postnatal day (PN) seven and four litters (dam with ten neonates) of PN 14 were separated into two separate groups each, centrifuge (+2G(sub z)) and environmental controls (EC) and placed into either the centrifuge or an animal holding unit in the centrifuge rotunda for a total of 16 days. P7: Total litter start mass of +2G(sub z) litter = 138.90 g/end = 311.0 g EC litter = 150.85 g/end = 516.9 g. P14: Total litter start mass of +2G(sub z) litter = 287.70 g/end = 762.5g; EC litter = 245 g/end = 942.9 g. An initial body mass loss was observed in both groups of +2G(sub z) animals for two days after the onset of centrifugation, but then an increase began to occur. Literature suggests adult animals at +2G(sub z), will have an initial loss, but will resume similar growth rates over time as compared to control animals. The P7 +2G(sub z) animals began to gain body mass, but showed a significantly slower growth rate than their EC animals for the duration of the test (pace). The P14 +2G(sub z) animals began to show similar growth rates to their EC after day nine. At day 16, both groups of +2Gz animals were significantly smaller than the EC animals (pace). At +2Gz, animals experience an initial body mass loss. Older animals are able to resume similar growth rates as their controls, but younger animals showed growth rates to be significantly reduced.

Assessment of bone structural property changes due to loading regimens or pharmacological treatment typically requires destructive mechanical testing and sectioning. Our group has accurately and non-destructively estimated three dimensional cross-sectional areal properties (principal moments of inertia, Imax and Imin, and principal angle, Theta) of human cadaver long bones from pixel-by-pixel analysis of three non-coplanar densitometry scans. Because the scanner beam width is on the order of typical small animal diapbyseal diameters, applying this technique to high-resolution scans of rat long bones necessitates additional processing to minimize errors induced by beam smearing, such as dependence on sample orientation and overestimation of Imax and Imin. We hypothesized that these errors are correctable by digital image processing of the raw scan data. In all cases, four scans, using only the low energy data (Hologic QDR-1000W, small animal mode), are averaged to increase image signal-to-noise ratio. Raw scans are additionally processed by interpolation, deconvolution by a filter derived from scanner beam characteristics, and masking using a variable threshold based on image dynamic range. To assess accuracy, we scanned an aluminum step phantom at 12 orientations over a range of 180 deg about the longitudinal axis, in 15 deg increments. The phantom dimensions (2.5, 3.1, 3.8 mm x 4.4 mm; Imin/Imax: 0.33-0.74) were comparable to the dimensions of a rat femur which was also scanned. Cross-sectional properties were determined at 0.25 mm increments along the length of the phantom and femur. The table shows average error (+/- SD) from theory of Imax, Imin, and Theta) over the 12 orientations, calculated from raw and fully processed phantom images, as well as standard deviations about the mean for the femur scans. Processing of phantom scans increased agreement with theory, indicating improved accuracy. Smaller standard deviations with processing indicate increased precision and repeatability. Standard deviations for the femur are consistent with those of the phantom. We conclude that in conjunction with digital image enhancement, densitometry scans are suitable for non-destructive determination of areal properties of small animal bones of comparable size to our phantom, allowing prediction of Imax and Imin within 2.5% and Theta within a fraction of a degree. This method represents a considerable extension of current methods of analyzing bone tissue distribution in small animal bones.

Three-dimensional reconstructions of innervation patterns in rat maculae were carried out using serial section images sent to a Silicon Graphics workstation from a transmission electron microscope. Contours were extracted from mosaicked sections, then registered and visualized using Biocomputation Center software. Purposes were to determine innervation patterns of type II cells and areas encompassed by vestibular afferent receptive fields. Terminals on type II cells typically are elongated and compartmentalized into parts varying in vesicular content; reciprocal and serial synapses are common. The terminals originate as processes of nearby calyces or from nerve fibers passing to calyces outside the immediate vicinity. Thus, receptive fields of the afferents overlap in unique ways. Multiple processes are frequent; from 4 to 6 afferents supply 12-16 terminals on a type II cell. Processes commonly communicate with two type II cells. The morphology indicates that extensive preprocessing of linear acceleratory stimuli occurs peripherally, as is true also of visual and olfactory systems. Clinically, this means that loss of individual nerve fibers may not be noticed behaviorally, due to redundancy (receptive field overlap). However, peripheral processing implies the presence of neuroactive agents whose loss can acutely or chronically alter normal peripheral function and cause balance disorders. (Platform presentation preferred - Theme 11)

Nonhuman primates display an interest in novel places, habituate to new situations, and spend most of their daily activity in the wild in large groups engaging in feeding behaviors. Captivity changes these behaviors, and disrupts normal social hierarchies. In captivity, animals may exhibit stereotypical behaviors which are thought to indicate decreased psychological well-being (PWB). If an animal's behaviors can be made to approach those seen in the wild, and stereotypical behaviors are minimal it is assumed that PWB is adequate. Environmental enrichment (EE) devices have been used to address the Animal Welfare Act's requirement that the PWB of captive nonhuman primates be considered. The purpose of the present study was to examine whether various EE devices improve the PWB of captive squirrel monkeys. The present study used behavioral observation to quantify the effectiveness of several EE devices in reducing stereotypical behaviors in squirrel monkeys housed singly or in groups. Results showed that the EE devices used did not affect the expression of normal or stereotypical behaviors, but that the type of housing did.

Reduction in bone mass of the lower extremity is well documented in individuals with paralysis resulting from spinal cord injury (SCI). The consequent osteopenia leads to elevated fracture risk with fractures occurring more commonly in the femoral shaft and supracondylar regions than the hip. A model has recently been described to estimate geometry and structure of the femoral midshaft from whole body scans by dual X-ray absorptiometry (DXA). Increases in femoral geometric and structural properties during growth were primarily related to mechanical loading as reflected by body mass. In this study, we investigate the relationship between body mass and femoral geometry and structure in adults with normal habitual mechanical loading patterns and those with severely reduced loading. The subjects were 78 ambulatory men (aged 20-72 yrs) and 113 men with complete paralysis from SCI of more than 4 years duration (aged 21 73 yrs). Subregional analysis was performed on DXA whole body scans to obtain bone mineral content (BMC, g), cortical thickness (cm), crosssectional moment of inertia (CSMI, cm4), and section modulus (cm3) of the femoral midshaft. All measured bone variables were significantly lower in SCI compared with ambulatory subjects: -29% (BMC), -33% (cortical thickness), -23% (CSMI), and -22% (section modulus) while body mass was not significantly different. However, the associations between body mass and bone properties were notably different; r2 values were higher for ambulatory than SCI subjects in regressions of body mass on BMC (0.48 vs 0.20), CSMI (0.59 vs 0.32), and section modulus (0.59 vs 0.31). No association was seen between body mass and cortical thickness for either group. The greatest difference between groups is in the femoral cortex, consistent with reduced bone mass via endosteal expansion. The relatively lesser difference in geometric and structural properties implies that there is less effect on mechanical integrity than would be expected from bone mass results alone. The reduced association in SCI subjects between body mass and bone properties is not unexpected. Although mean body mass differs little between ambulatory and SCI individuals, the association between body mass and in vivo skeletal loading is no longer present, as mechanical influences are removed except for transfer activities. The residual association is probably attributable to the strength of this influence during growth. These results highlight the importance of examining geometry and structure in conjunction with bone mass.

The effects of vasoactive agonists on systemic blood vessels were examined with respect to anatomical location and gravity acclimation in the semi-arboreal snake, Elaphe Obsoleta. Major blood vessels were reactive to putative neurotransmitters, hormones or local factors in vessel specific patterns. Catecholamines, adenosine triphosphate, histamine and high potassium (80 mM) stimulated significantly greater tension per unit vessel mass in posterior than anterior arteries. Anterior vessels were significantly more sensitive to catecholamines than midbody and posterior vessels. Angiotensin II stimulated significantly greater tension in carotid artery than in midbody and posterior dorsal aorta. Arginine vasotocin strongly contracted the left and right aortic arches and anterior dorsal aorta. Veins were strongly contracted by catecholamines, high potassium and angiotensin II, but less so by adenosine triphosphate, arginine vasotocin and histamine. Precontracted vessel were relaxed by acetylcholine and sodium nitroprusside, but not by atrial natriuretic peptide or bradykinin. Chronic exposure of snakes to intermittent hypergravity stress ( + 1.5 Gz at tail) did not affect the majority of vessel responses. These data demonstrate that in vitro tension correlates with that catecholamines, as well as other agonists, are important in mediating vascular responses to gravitational stresses in snakes.

Basic concepts in the physiopathology of edema are reviewed. The mechanisms of fluid exchange across the capillary endothelium are explained. Interstitial flow and lymph formation are examined. Clinical disorders of tissue and lymphatic transport, microcirculatory derangements in venous disorders, protein disorders, and lymphatic system disorders are explored. Techniques for investigational imaging of the lymphatic system are explained.

The Biology and Space Exploration video series illustrates NASA's commitment to increasing the public awareness and understanding of life sciences in space. The video series collection, which was initiated by Dr. Joan Vernikos at NASA headquarters and Dr. Alan Hargens at NASA Ames Research Center, will be distributed to universities and other institutions around the United States. The video series parallels the "Biology and Space Exploration" course taught by NASA Ames scientists at Stanford University, Palo Alto, California. In the past, students have shown considerable enthusiasm for this course and have gained a much better appreciation and understanding of space life sciences and exploration. However, due to the unique nature of the topics and the scarcity of available educational materials, most students in other universities around the country are unable to benefit from this educational experience. Therefore, with the assistance of Ames experts, we are producing a video series on selected aspects of life sciences in space to expose undergraduate students to the effects of gravity on living systems. Additionally, the video series collection contains space flight footage, graphics, charts, pictures, and interviews to make the materials interesting and intelligible to viewers.

On the Space Shuttle and MIR, mean CO2 levels have been 0.3% which is ten times that of normal air. There have also been extended periods with levels of 0.7% CO2 with peak concentrations at 2.0%. The Space Station program had proposed that CO2 concentration levels be maintained, on average, at 0.7%, and not to exceed 1.0%. To ensure that these levels of CO2 would not compromise the integrity of the science performed on the Space Station, the effects of chronic exposure of rats to 2.0% and 0.7% CO2 were investigated. Ten male rats per group were placed in individual metabolic cages for monitoring of food and water consumption, as well as fecal and urine production. Cages were placed in a large (4W x 10L x 4H ft.) plexiglass chamber with a controlled atmospheric environment. Following 7 days of cage adaptation, animals were exposed to experimental (2.0% or 0.7% CO2) or control (ambient air) conditions for 30 days. Daily body weight, food and water intake, and fecal and urine excretions were measured for the last three days of adaptation and the first ten days of exposure and then every three to four days for the remaining three weeks. Urine was measured for pH and total CO2. During 2.0% and 0.7% CO2 exposures, animal growth, fecal production and food and water consumption were within normal ranges. Urine excretion was significantly (p less than 0.05) higher in both experimental groups compared to controls. Urine pH of animals exposed to 2.0% CO2 was decreased by 0.32 over the first 6 days of exposure, followed by a 0.63 increase by day 30. In animals exposed to 0.7% CO2, urine pH did not decrease early in the exposure period, but did increase by 0.37 by day 30. Urine CO2 excretion did not change the first 6 days of exposure, but significantly increased in both 2.0% and 0.7% CO2 by day 30 (897 and 402 mmol/day, respectively). These results of chronic exposure to 2.0% and 0.7% CO2 are consistent with renal compensation in response to an altered acid-base homeostasis. These findings may impact science conducted on the Space Shuttle or the Space Station if CO2 concentrations reach 0.7%.

NASA Ames Research Center is responsible for the development of the Space Station Biological Research Project (SSBRP) which will support non-human life sciences research on the International Space Station Alpha (ISSA). The SSBRP is designed to support both basic research to understand the effect of altered gravity fields on biological systems and applied research to investigate the effects of space flight on biological systems. The SSBRP will provide the necessary habitats to support avian and reptile eggs, cells and tissues, plants and rodents. In addition a habitat to support aquatic specimens will be provided by our international partners. Habitats will be mounted in ISSA compatible racks at u-g and will also be mounted on a 2.5 m diameter centrifuge except for the egg incubator which has an internal centrifuge. The 2.5 m centrifuge will provide artificial gravity levels over the range of 0.01 G to 2 G. The current schedule is to launch the first rack in 1999, the Life Sciences glovebox and a second rack early in 2001, a 4 habitat 2.5 in centrifuge later the same year in its own module, and to upgrade the centrifuge to 8 habitats in 2004. The rodent habitats will be derived from the Advanced Animal Habitat currently under development for the Shuttle program and will be capable of housing either rats or mice individually or in groups (6 rats/group and at least 12 mice/group). The egg incubator will be an upgraded Avian Development Facility also developed for the Shuttle program through a Small Business and Innovative Research grant. The Space Tissue Loss cell culture apparatus, developed by Walter Reed Army Institute of Research, is being considered for the cell and tissue culture habitat. The Life Sciences Glovebox is crucial to all life sciences experiments for specimen manipulation and performance of science procedures. It will provide two levels of containment between the work volume and the crew through the use of seals and negative pressure. The glovebox will accommodate use by two crew persons simultaneously and the capability for real time video down-link and data acquisition. In house testbeds and Phase B studies of the centrifuge validated the concepts of vibration isolation and autobalancing systems to meet the ISSA microgravity requirements. The vibration isolation system is effective above the centrifuge rotation frequency while the autobalancing system on the rotor removes vibration at and below the rotation rate. Torque of the Station, induced by spin-up/spindown of the centrifuge, can be minimized by controlling spin-up/spin-down rates. The SSBRP and ISSA will provide the opportunity to perform long-term, repeatable and high quality science. The long duration increments available on the Station will permit multigeneration studies of both plants and animals which have not previously been possible. The u-g habitat racks and the eight habitat centrifuge will accommodate sufficient number of specimens to permit statistically significant sampling of specimens to investigate the time course of adaptation to altered gravity environments. The centrifuge will, for the first time, permit investigators to use gravity itself as a tool to investigate fundamental processes, to investigate the intensity and duration of gravity to maintain normal structure and function, to separate the effects of u-g from other environmental factors and to examine artificial gravity as a potential countermeasure for the physical deconditioning observed during space flight.

Leg compression devices have been used extensively by patients to combat chronic venous insufficiency and by astronauts to counteract orthostatic intolerance following spaceflight. However, the effects of elastic and inelastic leggings on the calf muscle pump have not been compared. The purpose of this study was to compare in normal subjects the effects of elastic and inelastic compression on leg intramuscular pressure (IMP), an objective index of calf muscle pump function. IMP in soleus and tibialis anterior muscles was measured with transducer-tipped catheters. Surface compression between each legging and the skin was recorded with an air bladder. Subjects were studied under three conditions: (1) control (no legging), (2) elastic legging, and (3) inelastic legging. Pressure data were recorded for each condition during recumbency, sitting, standing, walking, and running. Elastic leggings applied significantly greater surface compression during recumbency (20 +/- 1 mm Hg, mean +/- SE) than inelastic leggings (13 +/- 2 mm Hg). During recumbency, elastic leggings produced significantly higher soleus IMP of 25 +/- 1 mm Hg and tibialis anterior IMP of 28 +/- 1 mm Hg compared to 17 +/- 1 mm Hg and 20 +/- 2 mm Hg, respectively, generated by inelastic leggings and 8 +/- 1 mm Hg and 11 +/- 1 mm Hg, respectively, without leggings. During sitting, walking, and running, however, peak IMPs generated in the muscular compartments by elastic and inelastic leggings were similar. Our results suggest that elastic leg compression applied over a long period in the recumbent posture may impede microcirculation and jeopardize tissue viability.(ABSTRACT TRUNCATED AT 250 WORDS).

Sensitivity of carotid blood flow to +Gz (head-to-tail) acceleration was studied in six species of snakes hypothesized to show varied adaptive cardiovascular responses to gravity. Blood flow in the proximal carotid artery was measured in 15 snakes before, during and following stepwise increments of +0.25Gz force produced on a 2.4 m diameter centrifuge. During centrifugation each snake was confined to a straight position within an individually- fitted acrylic tube with the head facing the center of rotation. We measured the centrifugal force at the tail of the snake in order to quantify the maximum intensity of force gradient promoting antero-posterior pooling of blood. Tolerance to increased gravity was quantified as the acceleration force at which carotid blood flow ceased. This parameter varied according to the gravitational adaptation of species defined by their ecology and behavior. At the extremes, carotid blood flow decreased in response to increasing gravity and approached zero near +1Gz in aquatic and ground-dwelling species, whereas in climbing species carotid flow was maintained at forces in excess of +2Gz. Surprisingly, tolerant (arboreal) species withstood hypergravic forces of +2 to +3 G. for periods up to 1 h without cessation of carotid blood flow or apparent loss of consciousness. Data suggest that relatively tight skin of the tolerant species provides a natural antigravity suit which is of prime importance in counteracting Gz stress on blood circulation.

Bedrest studies of normal subjects provide opportunities to understand physiologic responses to supine posture and inactivity. Furthermore, head-down tilt has been a valuable procedure to investigate adaptation to microgravity and development of countermeasures to maintain the health and well-being of humans during space-flight. Recent bedrest experiments at NASA have ranged in duration from a few hours to 17 weeks. Acute studies of 6 degrees head-down tilt indicate that elevation of capillary blood pressure from 28 to 34 mm Hg and increased capillary perfusion in tissues of the head cause facial and intracranial edema. Intracranial pressure increases from 2 to 17 mm Hg going from upright posture to 6 degrees head-down tilt. Microvessels of the head have a low capacity to constrict and diminish local perfusion. Elevation of blood and tissue fluid pressures/flow in the head may also explain the higher headward bone density associated with long-term head-down tilt. These mechanistic studies of head-down tilt, along with a better understanding of the relative stresses involved with upright posture and lower body negative pressure, have facilitated development of suitable physiologic countermeasures to maintain astronaut health during microgravity. Presently no exercise hardware is available to provide a blood pressure gradient from head to feet in space. However, recent studies in our laboratory suggest that treadmill exercise using a graded lower-body compression suit and 100 mmHg lower body negative pressure provides equivalent or greater physiologic stress than similar upright exercise on Earth. Therefore, exercise within a lower body negative pressure chamber may provide a cost-effective and simple countermeasure to maintain the cardiovascular and neuro-musculoskeletal systems of astronauts during long-duration flight.

The paper discusses the following: Increasing intracranial pressure in humans during simulated microgravity. and near-infrared monitoring of model chronic compartment syndrome in exercising skeletal muscle. Compared to upright-seated posture, 0 deg. supine, 6 deg. HDT, and 15 deg. HDT produced TMD changes of 317 +/- 112, 403 +/- 114, and 474 +/- 112 n1 (means +/- S.E.), respectively. Furthermore, postural transitions from 0 deg. supine to 6 deg. HDT and from 6 deg. to 15 deg. HDT generated significant TMD changes (p less than 0.05). There was no hysteresis when postural transitions to HDT were compared to reciprocal transitions toward upright seated posture. Currently, diagnosis of chronic compartment syndrome (CCS) depends on measurement of intramuscular pressure by invasive catheterization. We hypothesized that this syndrome can be detected noninvasively by near-infrared (NIR) spectroscopy, which tracks variations in muscle hemoglobin/myoglobin oxygen saturation. CCS was simulated in the tibialis anterior muscle of 7 male and 3 female subjects by gradual inflation of a cuff placed around the leg to 40 mmHg during 14 minutes of cyclic isokinetic dorsiflexion exercise. On a separate day, subjects underwent the identical exercise protocol with no external compression. In both cases, tissue oxygenation (T(sub O2) was measured in the tibialis anterior by NIR spectroscopy and normalized to a percentage scale between baseline and a T(sub O2) nadir reached during exercise to ischemic exhaustion. Over the course of exercise, T(sub O2) declined at a rate of 1.4 +/- 0.3% per minute with model CCS, yet did not decrease during control exercise. Post-exercise recovery of T(sub O2) was slower with model CCS (2.5 +/- 0.6 min) than in control (1.3 +/- 0.2 min). These results demonstrate that NIR spectroscopy can detect muscle deoxygenation caused by pathologically elevated intramuscular pressure in exercising skeletal muscle. Consequently, this technique shows promise as a noninvasive diagnostic tool for CCS.

The circulatory systems of vertebrate animals are closed, and blood leaves and returns to the heart at the same level. It is often concluded, therefore, that the heart works only against the viscous resistance of the system, not against gravity, even in vascular loops above the heart in which the siphon principle operates. However, we argue that the siphon principle does not assist blood flow in superior vascular loops if any of the descending vasculature is collapsible. If central arterial blood pressure is insufficient to support a blood column between the heart and the head, blood flow ceases because of vascular collapse. Furthermore, the siphon principle does not assist the heart even when a continuous stream of blood is flowing in a superior loop. The potential energy gained by blood as it is pumped to the head is lost to friction in partially collapsed descending vessels and thus is not regained. Application of the Poiseuille equation to flow in collapsible vessels is limited; resistance depends on flow rate in partially collapsed vessels with no transmural pressure difference, but flow rate is independent of resistance. Thus the pressure developed by the heart to establish a given flow rate is independent of the resistance occurring in the partially collapsed vessels. The pressure depends only on the height of the blood column and the resistance in the noncollapsed parts of the system. Simple laboratory models, involving water flow in collapsible tubing, dispel the idea that the siphon principle facilitates blood flow and suggest that previously published results may have been affected by experimental artifact.

Swelling of the intervertebral disc nucleus pulposus is altered by posture and gravity. We have designed and tested a new osmometer for in vitro determination of nucleus pulposus swelling pressure. The functional principle of the osmometer involves compressing a sample of nucleus pulposus with nitrogen gas until saline pressure gradients across a 0.45 microns Millipore filter are eliminated. Swelling pressure of both pooled dog and pooled pig lumbar disc nucleus pulposus were measured on the new osmometer and compared to swelling pressures determined using the equilibrium dialysis technique. The osmometer measured swelling pressures comparable to those obtained by the dialysis technique. This osmometer provides a rapid, direct, and accurate measurement of swelling pressure of the nucleus pulposus.

Data are presented on the effects of actual and simulated weightlessness on the swelling pressure of nucleus pulposus in rats exposed to 12.5 days of flight aboard Cosmos 1887 or to seven days of tail suspension, respectively. The flight-exposed rats were adapted to normal gravity for over 50 hrs prior to sacrifice and tissue harvesting. In the experiments with flight-exposed rats, swelling pressures were 690, 675, and 622 mm Hg for flight rats, synchronous controls, and vivarium controls, respectively. In experiments with simulated weightlessness, swelling pressures were 295, 610, and 527 mm Hg for tail-suspended rats, cage controls, and vivarium controls, respectively, suggesting that fluid moves into the disc during seven days of simulated weightlessness.

The morphological and physiological effects of 4 weeks of high-frequency electrical stimulation (1 h/day, 5 days/week) on cast-immobilized rabbit hindlimbs were investigated in the tibialis anterior muscle and peroneal nerve. In 2 out of 6 animals, high-frequency stimulation with immobilization caused muscle fiber death, internalization of muscle fiber nuclei, connective tissue proliferation, inflammatory response, altered fiber size distribution and variable staining intensities. The fast-twitch fibers were predominantly affected. Two of six peripheral nerves subjected to immobilization and stimulation showed severe damage. Tetanic forces were significantly reduced in the affected muscles. Therefore, the immobilization and high-frequency stimulation may be detrimental to myoneural structure and function and, thus, this combination of therapies should be applied conservatively.

The compartment syndrome is defined as a condition in which high pressure within a closed fascial space (muscle compartment) reduces capillary blood perfusion below the level necessary for tissue viability'. This condition occurs in acute and chronic (exertional) forms, and may be secondary to a variety of causes. The end-result of an extended period of elevated intramuscular pressure may be the development of irreversible tissue injury and Volkmann's contracture. The goal of treatment of the compartment syndrome is the reduction of intracompartmental pressure thus facilitating reperfusion of ischaemic tissue and this goal may be achieved by decompressive fasciotomy. Controversy exists regarding the critical pressure-time thresholds for surgical decompression and the optimal diagnostic methods of measuring intracompartmental pressures. This paper will update and review some current knowledge regarding the pathophysiology, aetiology, diagnosis, and treatment of the acute compartment syndrome.