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At least 505 records · Page 28

Validation of fluorescent-labeled microspheres for measurement of relative blood flow in severely injured lungs

The aim of the study was to validate a nonradioactive method for relative blood flow measurements in severely injured lungs that avoids labor-intensive tissue processing. The use of fluorescent-labeled microspheres was compared with the standard radiolabeled-microsphere method. In seven sheep, lung injury was established by using oleic acid. Five pairs of radio- and fluorescent-labeled microspheres were injected before and after established lung injury. Across all animals, 175 pieces were selected randomly. The radioactivity of each piece was determined by using a scintillation counter. The fluorescent dye was extracted from each piece with a solvent without digestion or filtering. The fluorescence was determined with an automated fluorescent spectrophotometer. Perfusion was calculated for each piece from both the radioactivity and fluorescence and volume normalized. Correlations between flow determined by the two methods were in the range from 0.987 +/- 0.007 (SD) to 0.991 +/- 0.002 (SD) after 9 days of soaking. Thus the fluorescent microsphere technique is a valuable tool for investigating regional perfusion in severely injured lungs and can replace radioactivity.

Non-NASA Center↗

Cardiopulmonary baroreceptor control of muscle sympathetic nerve activity in heat-stressed humans

Whole body heating decreases central venous pressure (CVP) while increasing muscle sympathetic nerve activity (MSNA). In normothermia, similar decreases in CVP elevate MSNA, presumably via cardiopulmonary baroreceptor unloading. The purpose of this project was to identify whether increases in MSNA during whole body heating could be attributed to cardiopulmonary baroreceptor unloading coincident with the thermal challenge. Seven subjects were exposed to whole body heating while sublingual temperature, skin blood flow, heart rate, arterial blood pressure, and MSNA were monitored. During the heat stress, 15 ml/kg warmed saline was infused intravenously over 7-10 min to increase CVP and load the cardiopulmonary baroreceptors. We reported previously that this amount of saline was sufficient to return CVP to pre-heat stress levels. Whole body heating increased MSNA from 25 +/- 3 to 39 +/- 3 bursts/min (P < 0. 05). Central blood volume expansion via rapid saline infusion did not significantly decrease MSNA (44 +/- 4 bursts/min, P > 0.05 relative to heat stress period) and did not alter mean arterial blood pressure (MAP) or pulse pressure. To identify whether arterial baroreceptor loading decreases MSNA during heat stress, in a separate protocol MAP was elevated via steady-state infusion of phenylephrine during whole body heating. Increasing MAP from 82 +/- 3 to 93 +/- 4 mmHg (P < 0.05) caused MSNA to decrease from 36 +/- 3 to 15 +/- 4 bursts/min (P < 0.05). These data suggest that cardiopulmonary baroreceptor unloading during passive heating is not the primary mechanism resulting in elevations in MSNA. Moreover, arterial baroreceptors remain capable of modulating MSNA during heat stress.

NASA Discipline Cardiopulmonary↗

Altered central nervous system processing of baroreceptor input following hindlimb unloading in rats

The effect of cardiovascular deconditioning on central nervous system processing of baroreceptor afferent activity was evaluated following 14 days of hindlimb unloading (HU). Inactin-anesthetized rats were instrumented with catheters, renal sympathetic nerve electrodes, and aortic depressor nerve electrodes for measurement of mean arterial pressure, heart rate, renal sympathetic nerve activity (RSNA), and aortic depressor nerve activity (ADNA). Baroreceptor and baroreflex functions were assessed during infusion of phenylephrine and sodium nitroprusside. Central processing of baroreceptor afferent input was evaluated by linear regression relating RSNA to ADNA. The maximum baroreflex-elicited increase in RSNA was significantly reduced in HU rats (122 +/- 3.8 vs. 144 +/- 4.9% of baseline RSNA), whereas ADNA was not altered. The slope (-0.18 +/- 0.04 vs. -0.40 +/- 0.04) and y-intercept (121 +/- 3.2 vs. 146 +/- 4.3) of the linear regression relating increases in efferent RSNA to decreases in afferent ADNA during hypotension were significantly reduced in HU rats. There were no differences during increases in arterial pressure. Results demonstrate that the attenuation in baroreflex-mediated increases in RSNA following HU is due to changes in central processing of baroreceptor afferent information rather than aortic baroreceptor function.

NASA Discipline Cardiopulmonary↗

Development of a hydraulic model of the human systemic circulation

Physical and numeric models of the human circulation are constructed for a number of objectives, including studies and training in physiologic control, interpretation of clinical observations, and testing of prosthetic cardiovascular devices. For many of these purposes it is important to quantitatively validate the dynamic response of the models in terms of the input impedance (Z = oscillatory pressure/oscillatory flow). To address this need, the authors developed an improved physical model. Using a computer study, the authors first identified the configuration of lumped parameter elements in a model of the systemic circulation; the result was a good match with human aortic input impedance with a minimum number of elements. Design, construction, and testing of a hydraulic model analogous to the computer model followed. Numeric results showed that a three element model with two resistors and one compliance produced reasonable matching without undue complication. The subsequent analogous hydraulic model included adjustable resistors incorporating a sliding plate to vary the flow area through a porous material and an adjustable compliance consisting of a variable-volume air chamber. The response of the hydraulic model compared favorably with other circulation models.

NASA Program Biomedical Research and Countermeasur↗

Three-dimensional organization of vestibular-related eye movements to off-vertical axis rotation and linear translation in pigeons

During linear accelerations, compensatory reflexes should continually occur in order to maintain objects of visual interest as stable images on the retina. In the present study, the three-dimensional organization of the vestibulo-ocular reflex in pigeons was quantitatively examined during linear accelerations produced by constant velocity off-vertical axis yaw rotations and translational motion in darkness. With off-vertical axis rotations, sinusoidally modulated eye-position and velocity responses were observed in all three components, with the vertical and torsional eye movements predominating the response. Peak torsional and vertical eye positions occurred when the head was oriented with the lateral visual axis of the right eye directed orthogonal to or aligned with the gravity vector, respectively. No steady-state horizontal nystagmus was obtained with any of the rotational velocities (8-58 degrees /s) tested. During translational motion, delivered along or perpendicular to the lateral visual axis, vertical and torsional eye movements were elicited. No significant horizontal eye movements were observed during lateral translation at frequencies up to 3 Hz. These responses suggest that, in pigeons, all linear accelerations generate eye movements that are compensatory to the direction of actual or perceived tilt of the head relative to gravity. In contrast, no translational horizontal eye movements, which are known to be compensatory to lateral translational motion in primates, were observed under the present experimental conditions.

NASA Discipline Neuroscience↗

Effect of viewing distance on the generation of vertical eye movements during locomotion

Vertical head and eye coordination was studied as a function of viewing distance during locomotion. Vertical head translation and pitch movements were measured using a video motion analysis system (Optotrak 3020). Vertical eye movements were recorded using a video-based pupil tracker (Iscan). Subjects (five) walked on a linear treadmill at a speed of 1.67 m/s (6 km/h) while viewing a target screen placed at distances ranging from 0.25 to 2.0 m at 0. 25-m intervals. The predominant frequency of vertical head movement was 2 Hz. In accordance with previous studies, there was a small head pitch rotation, which was compensatory for vertical head translation. The magnitude of the vertical head movements and the phase relationship between head translation and pitch were little affected by viewing distance, and tended to orient the naso-occipital axis of the head at a point approximately 1 m in front of the subject (the head fixation distance or HFD). In contrast, eye velocity was significantly affected by viewing distance. When viewing a far (2-m) target, vertical eye velocity was 180 degrees out of phase with head pitch velocity, with a gain of 0. 8. This indicated that the angular vestibulo-ocular reflex (aVOR) was generating the eye movement response. The major finding was that, at a close viewing distance (0.25 m), eye velocity was in phase with head pitch and compensatory for vertical head translation, suggesting that activation of the linear vestibulo-ocular reflex (lVOR) was contributing to the eye movement response. There was also a threefold increase in the magnitude of eye velocity when viewing near targets, which was consistent with the goal of maintaining gaze on target. The required vertical lVOR sensitivity to cancel an unmodified aVOR response and generate the observed eye velocity magnitude for near targets was almost 3 times that previously measured. Supplementary experiments were performed utilizing body-fixed active head pitch rotations at 1 and 2 Hz while viewing a head-fixed target. Results indicated that the interaction of smooth pursuit and the aVOR during visual suppression could modify both the gain and phase characteristics of the aVOR at frequencies encountered during locomotion. When walking, targets located closer than the HFD (1.0 m) would appear to move in the same direction as the head pitch, resulting in suppression of the aVOR. The results of the head-fixed target experiment suggest that phase modification of the aVOR during visual suppression could play a role in generating eye movements consistent with the goal of maintaining gaze on targets closer than the HFD, which would augment the lVOR response.

NASA Discipline Neuroscience↗

Myogenic expression of an injectable protease-resistant growth hormone-releasing hormone augments long-term growth in pigs

Ectopic expression of a new serum protease-resistant porcine growth hormone-releasing hormone, directed by an injectable muscle-specific synthetic promoter plasmid vector (pSP-HV-GHRH), elicits growth in pigs. A single 10 mg intramuscular injection of pSP-HV-GHRH DNA followed by electroporation in three-week-old piglets elevated serum GHRH levels by twofold to fourfold, enhanced growth hormone secretion, and increased serum insulin-like growth factor-I by threefold to sixfold over control pigs. After 65 days the average body weight of the pigs injected with pSP-HV-GHRH was approximately 37% greater than the placebo-injected controls and resulted in a significant reduction in serum urea concentration, indicating a decrease in amino acid catabolism. Evaluation of body composition indicated a uniform increase in mass, with no organomegaly or associated pathology.

Non-NASA Center↗

Physiological response to submaximal isometric contractions of the paravertebral muscles

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.

NASA Center ARC↗

A system for low field imaging of laser-polarized noble gas

We describe a device for performing MRI with laser-polarized noble gas at low magnetic fields (<50 G). The system is robust, portable, inexpensive, and provides gas-phase imaging resolution comparable to that of high field clinical instruments. At 20.6 G, we have imaged laser-polarized (3)He (Larmor frequency of 67 kHz) in both sealed glass cells and excised rat lungs, using approximately 0.1 G/cm gradients to achieve approximately 1 mm(2) resolution. In addition, we measured (3)He T(2)(*) times greater than 100 ms in excised rat lungs, which is roughly 20 times longer than typical values observed at high ( approximately 2 T) fields. We include a discussion of the practical considerations for working at low magnetic fields and conclude with evidence of radiation damping in this system. Copyright 1999 Academic Press.

NASA Program Biomedical Research and Countermeasur↗

Effects of microgravity on urinary osteopontin

Increased risk of renal stone formation during space flight has been linked primarily to increased calcium excretion from bone demineralization induced by space flight. Other factors contributing to increased risk include increased urinary calcium oxalate supersaturation, while urinary citrate, magnesium and volume are all decreased. The aim of this study was to increase the predictive value of stone risk profiles for crew members during space flight by evaluating the excretion of urinary protein inhibitors of calcium crystallization so that more comprehensive stone risk profiles could relate mineral saturation to the concentrations of inhibitor proteins. Levels of urinary osteopontin (uropontin) are reported in a series of 14 astronauts studied before, during, and after space flights. During space flight, a compensatory increase in uropontin excretion was not observed. However, the uropontin excretion of a majority of astronauts was increased during the period after space flight and was maximal at 2 wk after landing. The downward shift in the molecular size of uropontin observed in samples obtained during space flight was shown to result from storage at ambient temperature during flight, rather than an effect of microgravity on uropontin synthesis.

NASA Experiment Number 9401651↗

Initial clinical experience of real-time three-dimensional echocardiography in patients with ischemic and idiopathic dilated cardiomyopathy

The geometry of the left ventricle in patients with cardiomyopathy is often sub-optimal for 2-dimensional ultrasound when assessing left ventricular (LV) function and localized abnormalities such as a ventricular aneurysm. The aim of this study was to report the initial experience of real-time 3-D echocardiography for evaluating patients with cardiomyopathy. A total of 34 patients were evaluated with the real-time 3D method in the operating room (n = 15) and in the echocardiographic laboratory (n = 19). Thirteen of 28 patients with cardiomyopathy and 6 other subjects with normal LV function were evaluated by both real-time 3-D echocardiography and magnetic resonance imaging (MRI) for obtaining LV volumes and ejection fractions for comparison. There were close relations and agreements for LV volumes (r = 0.98, p <0.0001, mean difference = -15 +/- 81 ml) and ejection fractions (r = 0.97, p <0.0001, mean difference = 0.001 +/- 0.04) between the real-time 3D method and MRI when 3 cardiomyopathy cases with marked LV dilatation (LV end-diastolic volume >450 ml by MRI) were excluded. In these 3 patients, 3D echocardiography significantly underestimated the LV volumes due to difficulties with imaging the entire LV in a 60 degrees x 60 degrees pyramidal volume. The new real-time 3D echocardiography is feasible in patients with cardiomyopathy and may provide a faster and lower cost alternative to MRI for evaluating cardiac function in patients.

NASA Discipline Cardiopulmonary↗

Do plasma melatonin concentrations decline with age?

PURPOSE: Numerous reports that secretion of the putative sleep-promoting hormone melatonin declines with age have led to suggestions that melatonin replacement therapy be used to treat sleep problems in older patients. We sought to reassess whether the endogenous circadian rhythm of plasma melatonin concentration changes with age in healthy drug-free adults. METHODS: We analyzed the amplitude of plasma melatonin profiles during a constant routine in 34 healthy drug-free older subjects (20 women and 14 men, aged 65 to 81 years) and compared them with 98 healthy drug-free young men (aged 18 to 30 years). RESULTS: We could detect no significant difference between a healthy and drug-free group of older men and women as compared to one of young men in the endogenous circadian amplitude of the plasma melatonin rhythm, as described by mean 24-hour average melatonin concentration (70 pmol/liter vs 73 pmol/liter, P = 0.97), or the duration (9.3 hours vs 9.1 hours, P = 0.43), mean (162 pmol/liter vs 161 pmol/liter, P = 0.63), or integrated area (85,800 pmol x min/liter vs 86,700 pmol x min/liter, P = 0.66) of the nocturnal peak of plasma melatonin. CONCLUSION: These results do not support the hypothesis that reduction of plasma melatonin concentration is a general characteristic of healthy aging. Should melatonin replacement therapy or melatonin supplementation prove to be clinically useful, we recommend that an assessment of endogenous melatonin be carried out before such treatment is used in older patients.

Non-NASA Center↗

Dynamics of airborne fungal populations in a large office building

The increasing concern with bioaerosols in large office buildings prompted this prospective study of airborne fungal concentrations in a newly constructed building on the Gulf coast. We collected volumetric culture plate air samples on 14 occasions over the 18-month period immediately following building occupancy. On each sampling occasion, we collected duplicate samples from three sites on three floors of this six-story building, and an outdoor sample. Fungal concentrations indoors were consistently below those outdoors, and no sample clearly indicated fungal contamination in the building, although visible growth appeared in the ventilation system during the course of the study. We conclude that modern mechanically ventilated buildings prevent the intrusion of most of the outdoor fungal aerosol, and that even relatively extensive air sampling protocols may not sufficiently document the microbial status of buildings.

NASA Program Biomedical Research and Countermeasur↗

Interaction of genetic predisposition and environmental factors in the pathogenesis of idiopathic orthostatic intolerance

BACKGROUND: The hemodynamic and autonomic abnormalities in idiopathic orthostatic intolerance (IOI) have been studied extensively. However, the mechanisms underlying these abnormalities are not understood. If genetic predisposition were important in the pathogenesis of IOI, monozygotic twins of patients with IOI should have similar hemodynamic and autonomic abnormalities. METHODS: We studied two patients with IOI and their identical twins. Both siblings in the first twin pair had orthostatic symptoms, significant orthostatic tachycardia, increased plasma norepinephrine levels with standing, and a greater than normal decrease in systolic blood pressure with trimethaphan infusion. RESULTS: Both siblings had a normal response of plasma renin activity to upright posture. In the second twin pair, only one sibling had symptoms of orthostatic intolerance, an orthostatic tachycardia, and raised plasma catecholamines with standing. The affected sibling had inappropriately low plasma renin activity with standing and was 8-fold more sensitive to the pressor effect of phenylephrine than the unaffected sibling. CONCLUSIONS: We conclude that in some patients, IOI seems to be strongly influenced by genetic factors. In others, however, IOI may be mainly caused by nongenetic factors. These findings suggest that IOI is heterogenous, and that both genetic and environmental factors contribute individually or collectively to create the IOI phenotype.

NASA Discipline Regulatory Physiology↗

Is the spatial distribution of brain lesions associated with closed-head injury predictive of subsequent development of attention-deficit/hyperactivity disorder? Analysis with brain-image database

PURPOSE: To determine whether there is an association between the spatial distribution of lesions detected at magnetic resonance (MR) imaging of the brain in children after closed-head injury and the development of secondary attention-deficit/hyperactivity disorder (ADHD). MATERIALS AND METHODS: Data obtained from 76 children without prior history of ADHD were analyzed. MR images were obtained 3 months after closed-head injury. After manual delineation of lesions, images were registered to the Talairach coordinate system. For each subject, registered images and secondary ADHD status were integrated into a brain-image database, which contains depiction (visualization) and statistical analysis software. Using this database, we assessed visually the spatial distributions of lesions and performed statistical analysis of image and clinical variables. RESULTS: Of the 76 children, 15 developed secondary ADHD. Depiction of the data suggested that children who developed secondary ADHD had more lesions in the right putamen than children who did not develop secondary ADHD; this impression was confirmed statistically. After Bonferroni correction, we could not demonstrate significant differences between secondary ADHD status and lesion burdens for the right caudate nucleus or the right globus pallidus. CONCLUSION: Closed-head injury-induced lesions in the right putamen in children are associated with subsequent development of secondary ADHD. Depiction software is useful in guiding statistical analysis of image data.

NASA Discipline Neuroscience↗

Disruption of postural readaptation by inertial stimuli following space flight

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

NASA Center JSC↗

Horizontal vestibuloocular reflex evoked by high-acceleration rotations in the squirrel monkey. I. Normal responses

The horizontal angular vestibuloocular reflex (VOR) evoked by high-frequency, high-acceleration rotations was studied in five squirrel monkeys with intact vestibular function. The VOR evoked by steps of acceleration in darkness (3,000 degrees /s(2) reaching a velocity of 150 degrees /s) began after a latency of 7.3 +/- 1.5 ms (mean +/- SD). Gain of the reflex during the acceleration was 14.2 +/- 5.2% greater than that measured once the plateau head velocity had been reached. A polynomial regression was used to analyze the trajectory of the responses to steps of acceleration. A better representation of the data was obtained from a polynomial that included a cubic term in contrast to an exclusively linear fit. For sinusoidal rotations of 0.5-15 Hz with a peak velocity of 20 degrees /s, the VOR gain measured 0.83 +/- 0.06 and did not vary across frequencies or animals. The phase of these responses was close to compensatory except at 15 Hz where a lag of 5.0 +/- 0.9 degrees was noted. The VOR gain did not vary with head velocity at 0.5 Hz but increased with velocity for rotations at frequencies of >/=4 Hz (0. 85 +/- 0.04 at 4 Hz, 20 degrees /s; 1.01 +/- 0.05 at 100 degrees /s, P < 0.0001). No responses to these rotations were noted in two animals that had undergone bilateral labyrinthectomy indicating that inertia of the eye had a negligible effect for these stimuli. We developed a mathematical model of VOR dynamics to account for these findings. The inputs to the reflex come from linear and nonlinear pathways. The linear pathway is responsible for the constant gain across frequencies at peak head velocity of 20 degrees /s and also for the phase lag at higher frequencies being less than that expected based on the reflex delay. The frequency- and velocity-dependent nonlinearity in VOR gain is accounted for by the dynamics of the nonlinear pathway. A transfer function that increases the gain of this pathway with frequency and a term related to the third power of head velocity are used to represent the dynamics of this pathway. This model accounts for the experimental findings and provides a method for interpreting responses to these stimuli after vestibular lesions.

NASA Program Biomedical Research and Countermeasur↗

Intracellular Ca2+ transients in mouse soleus muscle after hindlimb unloading and reloading

The objective of this study was to determine whether altered intracellular Ca(2+) handling contributes to the specific force loss in the soleus muscle after unloading and/or subsequent reloading of mouse hindlimbs. Three groups of female ICR mice were studied: 1) unloaded mice (n = 11) that were hindlimb suspended for 14 days, 2) reloaded mice (n = 10) that were returned to their cages for 1 day after 14 days of hindlimb suspension, and 3) control mice (n = 10) that had normal cage activity. Maximum isometric tetanic force (P(o)) was determined in the soleus muscle from the left hindlimb, and resting free cytosolic Ca(2+) concentration ([Ca(2+)](i)), tetanic [Ca(2+)](i), and 4-chloro-m-cresol-induced [Ca(2+)](i) were measured in the contralateral soleus muscle by confocal laser scanning microscopy. Unloading and reloading increased resting [Ca(2+)](i) above control by 36% and 24%, respectively. Although unloading reduced P(o) and specific force by 58% and 24%, respectively, compared with control mice, there was no difference in tetanic [Ca(2+)](i). P(o), specific force, and tetanic [Ca(2+)](i) were reduced by 58%, 23%, and 23%, respectively, in the reloaded animals compared with control mice; however, tetanic [Ca(2+)](i) was not different between unloaded and reloaded mice. These data indicate that although hindlimb suspension results in disturbed intracellular Ca(2+) homeostasis, changes in tetanic [Ca(2+)](i) do not contribute to force deficits. Compared with unloading, 24 h of physiological reloading in the mouse do not result in further changes in maximal strength or tetanic [Ca(2+)](i).

NASA Program Biomedical Research and Countermeasur↗