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At least 199 records · Page 11

Determination of muscle-specific glucose flux using radioactive stereoisomers and microdialysis

The purpose of the present study was to evaluate a novel approach for determining skeletal muscle-specific glucose flux using radioactive stereoisomers and the microdialysis technique. Microdialysis probes were inserted into the vastus lateralis muscle of human subjects and perfused (4 microl/min) with a Ringer solution containing small amounts of radioactive D- and L-glucose as the internal reference markers for determining probe recovery as well as varying concentrations of insulin (0-10 microM). The rationale behind this approach was that both stereoisomers would be equally affected by the factors that determine probe recovery, with the exception of L-glucose, which is nonmetabolizable and would not be influenced by tissue uptake. Therefore, any differences in the probe recovery ratios between the D- and L-stereoisomers represent changes in skeletal muscle glucose uptake directly at the tissue level. There were no differences in probe recovery between the D- (42.3 +/- 3.5%) and L- (41.2 +/- 3.5) stereoisomers during the control period (no insulin), which resulted in a D/L ratio of 1.04 +/- 0.03. However, during insulin perfusion (1 microM), The D/L ratio increased to 1.62 +/- 0.08 and 1.58 +/- 0.07 (P < 0.05) during the two collection (0-15 and 15-30 min) periods, respectively. This was accomplished solely by an increase (P < 0.05) in D-glucose probe recovery, as L-glucose probe recovery remained unchanged. In a second set of experiments, the perfusion of 10 microM insulin did not increase the D/L ratio (1.40 +/- 0.11) above that observed during 1.0 microM (1.41 +/- 0.07) insulin perfusion. These data suggest that this method is sufficiently sensitive to detect differences in insulin-stimulated glucose uptake; thus the use of radioactive stereoisomers in conjunction with the microdialysis technique provides a novel and useful technique for determining tissue-specific glucose flux and insulin sensitivity.

Non-NASA Center↗

Real-time three-dimensional echocardiographic study of left ventricular function after infarct exclusion surgery for ischemic cardiomyopathy

BACKGROUND: Infarct exclusion (IE) surgery, a technique of left ventricular (LV) reconstruction for dyskinetic or akinetic LV segments in patients with ischemic cardiomyopathy, requires accurate volume quantification to determine the impact of surgery due to complicated geometric changes. METHODS AND RESULTS: Thirty patients who underwent IE (mean age 61+/-8 years, 73% men) had epicardial real-time 3-dimensional echocardiographic (RT3DE) studies performed before and after IE. RT3DE follow-up was performed transthoracically 42+/-67 days after surgery in 22 patients. Repeated measures ANOVA was used to compare the values before and after IE surgery and at follow-up. Significant decreases in LV end-diastolic (EDVI) and end-systolic (ESVI) volume indices were apparent immediately after IE and in follow-up (EDVI 99+/-40, 67+/-26, and 71+/-31 mL/m(2), respectively; ESVI 72+/-37, 40+/-21, and 42+/-22 mL/m(2), respectively; P:<0.05). LV ejection fraction increased significantly and remained higher (0.29+/-0.11, 0.43+/-0.13, and 0.42+/-0.09, respectively, P:<0.05). Forward stroke volume in 16 patients with preoperative mitral regurgitation significantly improved after IE and in follow-up (22+/-12, 53+/-24, and 58+/-21 mL, respectively, P:<0.005). New York Heart Association functional class at an average 285+/-144 days of clinical follow-up significantly improved from 3.0+/-0.8 to 1.8+/-0.8 (P:<0.0001). Smaller end-diastolic and end-systolic volumes measured with RT3DE immediately after IE were closely related to improvement in New York Heart Association functional class at clinical follow-up (Spearman's rho=0.58 and 0.60, respectively). CONCLUSIONS: RT3DE can be used to quantitatively assess changes in LV volume and function after complicated LV reconstruction. Decreased LV volume and increased ejection fraction imply a reduction in LV wall stress after IE surgery and are predictive of symptomatic improvement.

Non-NASA Center↗

Effects of whole body heating on dynamic baroreflex regulation of heart rate in humans

The purpose of this project was to identify whether dynamic baroreflex regulation of heart rate (HR) is altered during whole body heating. In 14 subjects, dynamic baroreflex regulation of HR was assessed using transfer function analysis. In normothermic and heat-stressed conditions, each subject breathed at a fixed rate (0. 25 Hz) while beat-by-beat HR and systolic blood pressure (SBP) were obtained. Whole body heating significantly increased sublingual temperature, HR, and forearm skin blood flow. Spectral analysis of HR and SBP revealed that the heat stress significantly reduced HR and SBP variability within the high-frequency range (0.2-0.3 Hz), reduced SBP variability within the low-frequency range (0.03-0.15 Hz), and increased the ratio of low- to high-frequency HR variability (all P < 0.01). Transfer function gain analysis showed that the heat stress reduced dynamic baroreflex regulation of HR within the high-frequency range (from 1.04 +/- 0.06 to 0.54 +/- 0.6 beats. min(-1). mmHg(-1); P < 0.001) without significantly affecting the gain in the low-frequency range (P = 0.63). These data suggest that whole body heating reduced high-frequency dynamic baroreflex regulation of HR associated with spontaneous changes in blood pressure. Reduced vagal baroreflex regulation of HR may contribute to reduced orthostatic tolerance known to occur in humans during heat stress.

Non-NASA Center↗

Dose-response relationship for light intensity and ocular and electroencephalographic correlates of human alertness

Light can elicit both circadian and acute physiological responses in humans. In a dose response protocol men and women were exposed to illuminances ranging from 3 to 9100 lux for 6.5 h during the early biological night after they had been exposed to <3 lux for several hours. Light exerted an acute alerting response as assessed by a reduction in the incidence of slow-eye movements, a reduction of EEG activity in the theta-alpha frequencies (power density in the 5-9 Hz range) as well as a reduction in self-reported sleepiness. This alerting response was positively correlated with the degree of melatonin suppression by light. In accordance with the dose response function for circadian resetting and melatonin suppression, the responses of all three indices of alertness to variations in illuminance were consistent with a logistic dose response curve. Half of the maximum alerting response to bright light of 9100 lux was obtained with room light of approximately 100 lux. This sensitivity to light indicates that variations in illuminance within the range of typical, ambient, room light (90-180 lux) can have a significant impact on subjective alertness and its electrophysiologic concomitants in humans during the early biological night.

Clinical Trial↗

Dissociation of muscle sympathetic nerve activity and leg vascular resistance in humans

We examined the hypothesis that the increase in inactive leg vascular resistance during forearm metaboreflex activation is dissociated from muscle sympathetic nerve activity (MSNA). MSNA (microneurography), femoral artery mean blood velocity (FAMBV, Doppler), mean arterial pressure (MAP), and heart rate (HR) were assessed during fatiguing static handgrip exercise (SHG, 2 min) followed by posthandgrip ischemia (PHI, 2 min). Whereas both MAP and MSNA increase during SHG, the transition from SHG to PHI is characterized by a transient reduction in MAP but sustained elevation in MSNA, facilitating separation of these factors in vivo. Femoral artery vascular resistance (FAVR) was calculated (MAP/MBV). MSNA increased by 59 +/- 20% above baseline during SHG (P < 0.05) and was 58 +/- 18 and 78 +/- 18% above baseline at 10 and 20 s of PHI, respectively (P < 0.05 vs. baseline). Compared with baseline, FAVR increased 51 +/- 22% during SHG (P < 0.0001) but returned to baseline levels during the first 30 s of PHI, reflecting the changes in MAP (P < 0.005) and not MSNA. It was concluded that control of leg muscle vascular resistance is sensitive to changes in arterial pressure and can be dissociated from sympathetic factors.

Non-NASA Center↗

Sensitivity of the human circadian pacemaker to nocturnal light: melatonin phase resetting and suppression

Ocular exposure to early morning room light can significantly advance the timing of the human circadian pacemaker. The resetting response to such light has a non-linear relationship to illuminance. The dose-response relationship of the human circadian pacemaker to late evening light of dim to moderate intensity has not been well established. Twenty-three healthy young male and female volunteers took part in a 9 day protocol in which a single experimental light exposure6.5 h in duration was given in the early biological night. The effects of the light exposure on the endogenous circadian phase of the melatonin rhythm and the acute effects of the light exposure on plasma melatonin concentration were calculated. We demonstrate that humans are highly responsive to the phase-delaying effects of light during the early biological night and that both the phase resetting response to light and the acute suppressive effects of light on plasma melatonin follow a logistic dose-response curve, as do many circadian responses to light in mammals. Contrary to expectations, we found that half of the maximal phase-delaying response achieved in response to a single episode of evening bright light ( approximately 9000 lux (lx)) can be obtained with just over 1 % of this light (dim room light of approximately 100 lx). The same held true for the acute suppressive effects of light on plasma melatonin concentrations. This indicates that even small changes in ordinary light exposure during the late evening hours can significantly affect both plasma melatonin concentrations and the entrained phase of the human circadian pacemaker.

NASA Discipline Regulatory Physiology↗

Sympathetically mediated hypertension in autonomic failure

BACKGROUND: Approximately 50% of patients with primary autonomic failure have supine hypertension. We investigated whether this supine hypertension could be driven by residual sympathetic activity. METHODS AND RESULTS: In patients with multiple system atrophy (MSA) or pure autonomic failure (PAF), we studied the effect of oral yohimbine on seated systolic blood pressure (SBP), the effect of ganglionic blockade (with trimethaphan) on supine SBP and plasma catecholamine levels, and the effect of alpha(1)-adrenoreceptor blockade (phentolamine) on supine SBP. The SBP response to yohimbine was greater in patients with MSA than in those with PAF (area under the curve, 2248+/-543 versus 467+/-209 mm Hg. min; P=0.022). MSA patients with a higher supine SBP had a greater response than those with a lower supine SBP (3874+/-809 versus 785+/-189 mm Hg. min; P=0. 0017); this relationship was not seen in PAF patients. MSA patients had a marked depressor response to low infusion rates of trimethaphan; the response in PAF patients was more variable. Plasma norepinephrine decreased in both groups, but heart rate did not change in either group. At 1 mg/min, trimethaphan decreased supine SBP by 67+/-8 and 12+/-6 mm Hg in MSA and PAF patients, respectively (P<0.0001). Cardiac index and total peripheral resistance decreased in MSA patients by 33.4+/-5.8% and 40.7+/-9.5%, respectively (P=0. 0015). Patients having a depressor response to trimethaphan also had a depressor response to phentolamine. In MSA patients, the pressor response to yohimbine and the decrease in SBP with 1 mg/min trimethaphan were correlated (r=0.98; P=0.001). CONCLUSIONS: Residual sympathetic activity drives supine hypertension in MSA. It contributes to, but does not completely explain, supine hypertension in PAF.

Non-NASA Center↗

Reaching during virtual rotation: context specific compensations for expected coriolis forces

Subjects who are in an enclosed chamber rotating at constant velocity feel physically stationary but make errors when pointing to targets. Reaching paths and endpoints are deviated in the direction of the transient inertial Coriolis forces generated by their arm movements. By contrast, reaching movements made during natural, voluntary torso rotation seem to be accurate, and subjects are unaware of the Coriolis forces generated by their movements. This pattern suggests that the motor plan for reaching movements uses a representation of body motion to prepare compensations for impending self-generated accelerative loads on the arm. If so, stationary subjects who are experiencing illusory self-rotation should make reaching errors when pointing to a target. These errors should be in the direction opposite the Coriolis accelerations their arm movements would generate if they were actually rotating. To determine whether such compensations exist, we had subjects in four experiments make visually open-loop reaches to targets while they were experiencing compelling illusory self-rotation and displacement induced by rotation of a complex, natural visual scene. The paths and endpoints of their initial reaching movements were significantly displaced leftward during counterclockwise illusory rotary displacement and rightward during clockwise illusory self-displacement. Subjects reached in a curvilinear path to the wrong place. These reaching errors were opposite in direction to the Coriolis forces that would have been generated by their arm movements during actual torso rotation. The magnitude of path curvature and endpoint errors increased as the speed of illusory self-rotation increased. In successive reaches, movement paths became straighter and endpoints more accurate despite the absence of visual error feedback or tactile feedback about target location. When subjects were again presented a stationary scene, their initial reaches were indistinguishable from pre-exposure baseline, indicating a total absence of aftereffects. These experiments demonstrate that the nervous system automatically compensates in a context-specific fashion for the Coriolis forces associated with reaching movements.

Clinical Trial↗

The pressor response to water drinking in humans : a sympathetic reflex?

BACKGROUND: Water drinking increases blood pressure profoundly in patients with autonomic failure and substantially in older control subjects. The mechanism that mediates this response is not known. METHODS AND RESULTS: We studied the effect of drinking tap water on seated blood pressure in 47 patients with severe autonomic failure (28 multiple system atrophy [MSA], 19 pure autonomic failure patients [PAF]). Eleven older controls and 8 young controls served as control group. We also studied the mechanisms that could increase blood pressure with water drinking. Systolic blood pressure increased profoundly with water drinking, reaching a maximum of 33+/-5 mm Hg in MSA and 37+/-7 in PAF mm Hg after 30 to 35 minutes. The pressor response was greater in patients with more retained sympathetic function and was almost completely abolished by trimethaphan infusion. Systolic blood pressure increased by 11+/-2.4 mm Hg in elderly but not in young controls. Plasma norepinephrine increased in both groups. Plasma renin activity, vasopressin, and blood volume did not change in any group. CONCLUSIONS: Water drinking significantly and rapidly raises sympathetic activity. Indeed, it raises plasma norepinephrine as much as such classic sympathetic stimuli as caffeine and nicotine. This effect profoundly increases blood pressure in autonomic failure patients, and this effect can be exploited to improve symptoms due to orthostatic hypotension. Water drinking also acutely raises blood pressure in older normal subjects. The pressor effect of oral water is an important yet unrecognized confounding factor in clinical studies of pressor agents and antihypertensive medications.

Non-NASA Center↗

Patients' choice of portable folding chairs to reduce symptoms of orthostatic hypotension

Patients with neurogenic orthostatic hypotension may use portable folding chairs to prevent or reduce symptoms of low blood pressure. However, a concomitant movement disorder may limit the use of these chairs in daily living. In this prospective study, 13 patients with orthostatic hypotension, balance disturbance associated with motor disability, or both examined three commercially available portable folding chairs. A questionnaire was used to document the characteristics in chair design that were relevant for satisfactory use to these patients. Armrests, seat width, and an adjustable sitting height were found to be important features of a portable folding chair. One chair was selected by 11 of 13 patients to fit most needs.

NASA Discipline Cardiopulmonary↗

Haptic stabilization of posture: changes in arm proprioception and cutaneous feedback for different arm orientations

Postural sway during quiet stance is attenuated by actively maintained contact of the index finger with a stationary surface, even if the level of applied force (<1 N) cannot provide mechanical stabilization. In this situation, changes in force level at the fingertip lead changes in center of foot pressure by approximately 250 ms. These and related findings indicate that stimulation of the fingertip combined with proprioceptive information about the hand and arm can serve as an active sensor of body position relative to the point of contact. A geometric analysis of the relationship between hand and torso displacement during body sway led to the prediction that arm and hand proprioceptive and finger somatosensory information about body sway would be maximized with finger contact in the plane of body sway. Therefore, the most postural stabilization should be possible with such contact. To test this analysis, subjects touched a laterally versus anteriorly placed surface while in each of two stances: the heel-to-toe tandem Romberg stance that reduces medial-lateral stability and the heel-to-heel, toes-outward, knees-bent, "duck stance" that reduces fore-aft stability. Postural sway was always least with finger contact in the unstable plane: for the tandem stance, lateral fingertip contact was significantly more effective than frontal contact, and, for the duck stance, frontal contact was more effective than lateral fingertip contact. Force changes at the fingertip led changes in center of pressure of the feet by approximately 250 ms for both fingertip contact locations for both test stances. These results support the geometric analysis, which showed that 1) arm joint angles change by the largest amount when fingertip contact is maintained in the plane of greatest sway, and 2) the somatosensory cues at the fingertip provide both direction and amplitude information about sway when the finger is contacting a surface in the unstable plane.

Non-NASA Center↗

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↗

Effects of menstrual cycle phase and oral contraceptives on alertness, cognitive performance, and circadian rhythms during sleep deprivation

The influence of menstrual cycle phase and oral contraceptive use on neurobehavioral function and circadian rhythms were studied in healthy young women (n = 25) using a modified constant routine procedure during 24 h of sleep deprivation. Alertness and performance worsened across sleep deprivation and also varied with circadian phase. Entrained circadian rhythms of melatonin and body temperature were evident in women regardless of menstrual phase or oral contraceptive use. No significant difference in melatonin levels, duration, or phase was observed between women in the luteal and follicular phases, whereas oral contraceptives appeared to increase melatonin levels. Temperature levels were higher in the luteal phase and in oral contraceptive users compared to women in the follicular phase. Alertness on the maintenance of wakefulness test and some tests of cognitive performance were poorest for women in the follicular phase especially near the circadian trough of body temperature. These observations suggest that hormonal changes associated with the menstrual cycle and the use of oral contraceptives contribute to changes in nighttime waking neurobehavioral function and temperature level whereas these factors do not appear to affect circadian phase.

NASA Discipline Regulatory Physiology↗

Sympathetic adaptations to one-legged training

The purpose of the present study was to determine the effect of leg exercise training on sympathetic nerve responses at rest and during dynamic exercise. Six men were trained by using high-intensity interval and prolonged continuous one-legged cycling 4 day/wk, 40 min/day, for 6 wk. Heart rate, mean arterial pressure (MAP), and muscle sympathetic nerve activity (MSNA; peroneal nerve) were measured during 3 min of upright dynamic one-legged knee extensions at 40 W before and after training. After training, peak oxygen uptake in the trained leg increased 19 +/- 2% (P < 0.01). At rest, heart rate decreased from 77 +/- 3 to 71 +/- 6 beats/min (P < 0.01) with no significant changes in MAP (91 +/- 7 to 91 +/- 11 mmHg) and MSNA (29 +/- 3 to 28 +/- 1 bursts/min). During exercise, both heart rate and MAP were lower after training (108 +/- 5 to 96 +/- 5 beats/min and 132 +/- 8 to 119 +/- 4 mmHg, respectively, during the third minute of exercise; P < 0.01). MSNA decreased similarly from rest during the first 2 min of exercise both before and after training. However, MSNA was significantly less during the third minute of exercise after training (32 +/- 2 to 22 +/- 3 bursts/min; P < 0.01). This training effect on MSNA remained when MSNA was expressed as bursts per 100 heartbeats. Responses to exercise in five untrained control subjects were not different at 0 and 6 wk. These results demonstrate that exercise training prolongs the decrease in MSNA during upright leg exercise and indicates that attenuation of MSNA to exercise reported with forearm training also occurs with leg training.

Non-NASA Center↗

Effect of a 17 day spaceflight on contractile properties of human soleus muscle fibres

1. Soleus biopsies were obtained from four male astronauts 45 days before and within 2 h after a 17 day spaceflight. 2. For all astronauts, single chemically skinned post-flight fibres expressing only type I myosin heavy chain (MHC) developed less average peak Ca2+ activated force (Po) during fixed-end contractions (0.78 +/- 0. 02 vs. 0.99 +/- 0.03 mN) and shortened at a greater mean velocity during unloaded contractions (Vo) (0.83 +/- 0.02 vs. 0.64 +/- 0.02 fibre lengths s-1) than pre-flight type I fibres. 3. The flight-induced decline in absolute Po was attributed to reductions in fibre diameter and/or Po per fibre cross-sectional area. Fibres from the astronaut who experienced the greatest relative loss of peak force also displayed a reduction in Ca2+ sensitivity. 4. The elevated Vo of the post-flight slow type I fibres could not be explained by alterations in myosin heavy or light chain composition. One alternative possibility is that the elevated Vo resulted from an increased myofilament lattice spacing. This hypothesis was supported by electron micrographic analysis demonstrating a reduction in thin filament density post-flight. 5. Post-flight fibres shortened at 30 % higher velocities than pre-flight fibres at external loads associated with peak power output. This increase in shortening velocity either reduced (2 astronauts) or prevented (2 astronauts) a post-flight loss in fibre absolute peak power (microN (fibre length) s-1). 6. The changes in soleus fibre diameter and function following spaceflight were similar to those observed after 17 days of bed rest. Although in-flight exercise countermeasures probably reduced the effects of microgravity, the results support the idea that ground-based bed rest can serve as a model of human spaceflight. 7. In conclusion, 17 days of spaceflight decreased force and increased shortening velocity of single Ca2+-activated muscle cells expressing type I MHC. The increase in shortening velocity greatly reduced the impact that impaired force production had on absolute peak power.

Clinical Trial↗

Motion sickness and proprioceptive aftereffects following virtual environment exposure

To study the potential aftereffects of virtual environments (VE), tests of visually guided behavior and felt limb position (pointing with eyes open and closed) along with self-reports of motion sickness-like discomfort were administered before and after 30 min exposure of 34 subjects. When post- discomfort was compared to a pre-baseline, the participants reported more sickness afterward (p < 0.03). The change in felt limb position resulted in subjects pointing higher (p < 0.038) and slightly to the left, although the latter difference was not statistically significant (p = 0.08). When findings from a second study using a different VE system were compared, they essentially replicated the results of the first study with higher sickness afterward (p < 0.001) and post- pointing errors were also up (p < 0.001) and to the left (p < 0.001). While alternative explanations (e.g. learning, fatigue, boredom, habituation, etc.) of these outcomes cannot be ruled out, the consistency of the post- effects on felt limb position changes in the two VE implies that these recalibrations may linger once interaction with the VE has concluded, rendering users potentially physiologically maladapted for the real world when they return. This suggests there may be safety concerns following VE exposures until pre-exposure functioning has been regained. The results of this study emphasize the need for developing and using objective measures of post-VE exposure aftereffects in order to systematically determine under what conditions these effects may occur.

NASA Discipline Neuroscience↗