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Effects of moderate heart failure and functional overload on rat plantaris muscle

It is thought that changes in sarco(endo)plasmic reticulum Ca(2+)-ATPase (SERCA) of skeletal muscle contribute to alterations in skeletal muscle function during congestive heart failure (CHF). It is well established that exercise training can improve muscle function. However, it is unclear whether similar adaptations will result from exercise training in a CHF patient. Therefore, the purpose of this study was to determine whether skeletal muscle during moderate CHF adapts to increased activity, utilizing the functional overload (FO) model. Significant increases in plantaris mass of the CHF-FO and sham-FO groups compared with the CHF and control (sham) groups were observed. Ca(2+) uptake rates were significantly elevated in the CHF group compared with all other groups. No differences were detected in Ca(2+) uptake rates between the CHF-FO, sham, and sham-FO groups. Increases in Ca(2+) uptake rates in moderate-CHF rats were not due to changes in SERCA isoform proportions; however, FO may have attenuated the CHF-induced increases through alterations in SERCA isoform expression. Therefore, changes in skeletal muscle Ca(2+) handling during moderate CHF may be due to alterations in regulatory mechanisms, which exercise may override, by possibly altering SERCA isoform expression.

Non-NASA Center↗

Lumbar spine disc height and curvature responses to an axial load generated by a compression device compatible with magnetic resonance imaging

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.

Non-NASA Center↗

What can posturography tell us about vestibular function?

Patients with balance disorders want answers to the following basic questions: (1) What is causing my problem? and (2) What can be done about my problem? Information to fully answer these questions must include status of both sensory and motor components of the balance control systems. Computerized dynamic posturography (CDP) provides quantitative assessment of both sensory and motor components of postural control along with how the sensory inputs to the brain interact. This paper reviews the scientific basis and clinical applications of CDP. Specifically, studies describing the integration of vestibular inputs with other sensory systems for postural control are briefly summarized. Clinical applications, including assessment, rehabilitation, and management are presented. Effects of aging on postural control along with prevention and management strategies are discussed.

NASA Discipline Neuroscience↗

Evidence for central venous pressure resetting during initial exposure to microgravity

We measured central venous pressure (CVP); plasma volume (PV); urine volume rate (UVR); renal excretion of sodium (UNa); and renal clearances of creatinine, sodium, and osmolality before and after acute volume infusion to test the hypothesis that exposure to microgravity causes resetting of the CVP operating point. Six rhesus monkeys underwent two experimental conditions in a crossover counterbalance design: 1) continuous exposure to 10 degrees head-down tilt (HDT) and 2) a control, defined as 16 h/day of 80 degrees head-up tilt and 8 h prone. After 48 h of exposure to either test condition, a 120-min course of continuous infusion of isotonic saline (0.4 ml. kg(-1). min(-1) iv) was administered. Baseline CVP was lower (P = 0.011) in HDT (2.3 +/- 0.3 mmHg) compared with the control (4.5 +/- 1.4 mmHg) condition. After 2 h of saline infusion, CVP was elevated (P = 0.002) to a similar magnitude (P = 0.485) in HDT (DeltaCVP = 2.7 +/- 0.8 mmHg) and control (DeltaCVP = 2.3 +/- 0.8 mmHg) conditions and returned to preinfusion levels 18 h postinfusion in both treatments. PV followed the same pattern as CVP. The response relationships between CVP and UVR and between CVP and UNa shifted to the left with HDT. The restoration of CVP and PV to lower preinfusion levels after volume loading in HDT compared with control supports the notion that lower CVP during HDT may reflect a new operating point about which vascular volume is regulated. These results may explain the ineffective fluid intake procedures currently employed to treat patients and astronauts.

NASA Discipline Cardiopulmonary↗

Animal models for osteoporosis

Animal models will continue to be important tools in the quest to understand the contribution of specific genes to establishment of peak bone mass and optimal bone architecture, as well as the genetic basis for a predisposition toward accelerated bone loss in the presence of co-morbidity factors such as estrogen deficiency. Existing animal models will continue to be useful for modeling changes in bone metabolism and architecture induced by well-defined local and systemic factors. However, there is a critical unfulfilled need to develop and validate better animal models to allow fruitful investigation of the interaction of the multitude of factors which precipitate senile osteoporosis. Well characterized and validated animal models that can be recommended for investigation of the etiology, prevention and treatment of several forms of osteoporosis have been listed in Table 1. Also listed are models which are provisionally recommended. These latter models have potential but are inadequately characterized, deviate significantly from the human response, require careful choice of strain or age, or are not practical for most investigators to adopt. It cannot be stressed strongly enough that the enormous potential of laboratory animals as models for osteoporosis can only be realized if great care is taken in the choice of an appropriate species, age, experimental design, and measurements. Poor choices will results in misinterpretation of results which ultimately can bring harm to patients who suffer from osteoporosis by delaying advancement of knowledge.

NASA Discipline Regulatory Physiology↗

Application of multivariate statistics to vestibular testing: discriminating between Meniere's disease and migraine associated dizziness

Meniere's disease (MD) and migraine associated dizziness (MAD) are two disorders that can have similar symptomatologies, but differ vastly in treatment. Vestibular testing is sometimes used to help differentiate between these disorders, but the inefficiency of a human interpreter analyzing a multitude of variables independently decreases its utility. Our hypothesis was that we could objectively discriminate between patients with MD and those with MAD using select variables from the vestibular test battery. Sinusoidal harmonic acceleration test variables were reduced to three vestibulo-ocular reflex physiologic parameters: gain, time constant, and asymmetry. A combination of these parameters plus a measurement of reduced vestibular response from caloric testing allowed us to achieve a joint classification rate of 91%, independent quadratic classification algorithm. Data from posturography were not useful for this type of differentiation. Overall, our classification function can be used as an unbiased assistant to discriminate between MD and MAD and gave us insight into the pathophysiologic differences between the two disorders.

NASA Discipline Neuroscience↗

Relationship between early diastolic intraventricular pressure gradients, an index of elastic recoil, and improvements in systolic and diastolic function

BACKGROUND: Early diastolic intraventricular pressure gradients (IVPGs) have been proposed to relate to left ventricular (LV) elastic recoil and early ventricular "suction." Animal studies have demonstrated relationships between IVPGs and systolic and diastolic indices during acute ischemia. However, data on the effects of improvements in LV function in humans and the relationship to IVPGs are lacking. METHODS AND RESULTS: Eight patients undergoing CABG and/or infarct exclusion surgery had a triple-sensor high-fidelity catheter placed across the mitral valve intraoperatively for simultaneous recording of left atrial (LA), basal LV, and apical LV pressures. Hemodynamic data obtained before bypass were compared with those with similar LA pressures and heart rates obtained after bypass. From each LV waveform, the time constant of LV relaxation (tau), +dP/dt(max), and -dP/dt(max) were determined. Transesophageal echocardiography was used to determined end-diastolic (EDV) and end-systolic (ESV) volumes and ejection fractions (EF). At similar LA pressures and heart rates, IVPG increased after bypass (before bypass 1.64+/-0.79 mm Hg; after bypass 2.67+/-1.25 mm Hg; P<0.01). Significant improvements were observed in ESV, as well as in apical and basal +dP/dt(max), -dP/dt(max), and tau (each P<0.05). Overall, IVPGs correlated inversely with both ESV (IVPG=-0.027[ESV]+3.46, r=-0.64) and EDV (IVPG=-0.027[EDV]+4.30, r=-0.70). Improvements in IVPGs correlated with improvements in apical tau (Deltatau =5.93[DeltaIVPG]+4.76, r=0.91) and basal tau (Deltatau =2.41[DeltaIVPG]+5.13, r=-0.67). Relative changes in IVPGs correlated with changes in ESV (DeltaESV=-0.97[%DeltaIVPG]+23.34, r=-0.79), EDV (DeltaEDV=-1.16[%DeltaIVPG]+34.92, r=-0.84), and EF (DeltaEF=0.38[%DeltaIVPG]-8.39, r=0.85). CONCLUSIONS: Improvements in LV function also increase IVPGs. These changes in IVPGs, suggestive of increases in LV suction and elastic recoil, correlate directly with improvements in LV relaxation and ESV.

Non-NASA Center↗

Analysis and visualization of single-trial event-related potentials

In this study, a linear decomposition technique, independent component analysis (ICA), is applied to single-trial multichannel EEG data from event-related potential (ERP) experiments. Spatial filters derived by ICA blindly separate the input data into a sum of temporally independent and spatially fixed components arising from distinct or overlapping brain or extra-brain sources. Both the data and their decomposition are displayed using a new visualization tool, the "ERP image," that can clearly characterize single-trial variations in the amplitudes and latencies of evoked responses, particularly when sorted by a relevant behavioral or physiological variable. These tools were used to analyze data from a visual selective attention experiment on 28 control subjects plus 22 neurological patients whose EEG records were heavily contaminated with blink and other eye-movement artifacts. Results show that ICA can separate artifactual, stimulus-locked, response-locked, and non-event-related background EEG activities into separate components, a taxonomy not obtained from conventional signal averaging approaches. This method allows: (1) removal of pervasive artifacts of all types from single-trial EEG records, (2) identification and segregation of stimulus- and response-locked EEG components, (3) examination of differences in single-trial responses, and (4) separation of temporally distinct but spatially overlapping EEG oscillatory activities with distinct relationships to task events. The proposed methods also allow the interaction between ERPs and the ongoing EEG to be investigated directly. We studied the between-subject component stability of ICA decomposition of single-trial EEG epochs by clustering components with similar scalp maps and activation power spectra. Components accounting for blinks, eye movements, temporal muscle activity, event-related potentials, and event-modulated alpha activities were largely replicated across subjects. Applying ICA and ERP image visualization to the analysis of sets of single trials from event-related EEG (or MEG) experiments can increase the information available from ERP (or ERF) data. Copyright 2001 Wiley-Liss, Inc.

Non-NASA Center↗

How the science and engineering of spaceflight contribute to understanding the plasticity of spinal cord injury

Space programs support experimental investigations related to the unique environment of space and to the technological developments from many disciplines of both science and engineering that contribute to space studies. Furthermore, interactions between scientists, engineers and administrators, that are necessary for the success of any science mission in space, promote interdiscipline communication, understanding and interests which extend well beyond a specific mission. NASA-catalyzed collaborations have benefited the spinal cord rehabilitation program at UCLA in fundamental science and in the application of expertise and technologies originally developed for the space program. Examples of these benefits include: (1) better understanding of the role of load in maintaining healthy muscle and motor function, resulting in a spinal cord injury (SCI) rehabilitation program based on muscle/limb loading; (2) investigation of a potentially novel growth factor affected by spaceflight which may help regulate muscle mass; (3) development of implantable sensors, electronics and software to monitor and analyze long-term muscle activity in unrestrained subjects; (4) development of hardware to assist therapies applied to SCI patients; and (5) development of computer models to simulate stepping which will be used to investigate the effects of neurological deficits (muscle weakness or inappropriate activation) and to evaluate therapies to correct these deficiencies.

Review↗

See-saw nystagmus and brainstem infarction: MRI findings

A patient with see-saw nystagmus had a lesion localized by Magnetic Resonance Imaging (MRI) to the paramedian ventral midbrain with involvement of the right interstitial nucleus of Cajal. This the first MRI study of see-saw nystagmus associated with a presumed brainstem vascular event. Our findings support animal and human studies suggesting that dysfunction of the interstitial nucleus of Cajal or its connections is central in this disorder.

Non-NASA Center↗

Medical and surgical applications of space biosensor technology

Researchers in space life sciences are rapidly approaching a technology impasse. Many of the critical questions on the impact of spaceflight on living systems simply cannot be answered with the limited available technologies. Research subjects, particularly small animal models like the rat, must be allowed to function relatively untended and unrestrained for long periods to fully reflect the impact of microgravity and spaceflight on their behavior and physiology. These requirements preclude the use of present hard-wired instrumentation techniques and limited data acquisition systems. Implantable sensors and miniaturized biotelemetry are the only means of capturing the fundamental and critical data. This same biosensor and biotelemetry technology has direct application to Earth-based medicine and surgery. Continuous, on-line data acquisition and improved measurement capabilities combined with the ease and flexibility offered by automated, wireless, and portable instruments and data systems, should provide a boon to the health care industry. Playing a key role in this technology revolution is the Sensors 2000! (S2K!) Program at NASA Ames Research Center. S2K!, in collaboration with space life sciences researchers and managers, provides an integrated capability for sensor technology development and applications, including advanced biosensor technology development, spaceflight hardware development, and technology transfer and commercialization. S2K! is presently collaborating on several spaceflight projects with dual-use medical applications. One prime example is a collaboration with the Fetal Treatment Center (FTC) at the University of California at San Francisco. The goal is to develop and apply implantable chemical sensor and biotelemetry technology to continuously monitor fetal patients during extra-uterine surgery, replacement into the womb, through birth and beyond. Once validated for ground use, the method will be transitioned to spaceflight applications to remotely monitor key biochemical parameters in flight animals. Successful application of NASA implantable biosensor and biotelemetry technologies should accelerate the advancement of this and other modern medical procedures while furthering the exploration of life in space.

NASA Discipline General Space Life Sciences↗

Nutrients affecting brain composition and behavior

This review examines the changes in brain composition and in various brain functions, including behavior, that can follow the ingestion of particular foods or nutrients. It details those that are best understood: the increases in serotonin, catecholamine, or acetylcholine synthesis that can occur subsequent to food-induced increases in brain levels of tryptophan, tyrosine, or choline; it also discusses the various processes that must intervene between the mouth and the synapse, so to speak, in order for a nutrient to affect neurotransmission, and it speculates as to additional brain chemicals that may ultimately be found to be affected by changes in the availability of their nutrient precursors. Because the brain chemicals best known to be nutrient dependent overlap with those thought to underlie the actions of most of the drugs used to treat psychiatric diseases, knowledge of this dependence may help the psychiatrist to understand some of the pathologic processes occurring in his/her patients, particularly those with appetitive symptoms. At the very least, such knowledge should provide the psychiatrist with objective criteria for judging when to take seriously assertions that particular foods or nutrients do indeed affect behavior (e.g., in hyperactive children). If the food can be shown to alter neurotransmitter release, it may be behaviorally-active; however, if it lacks a discernible neurochemical effect, the likelihood that it really alters behavior is small.

NASA Program Space Medicine↗

The excitability of plant cells: with a special emphasis on characean internodal cells

This review describes the basic principles of electrophysiology using the generation of an action potential in characean internodal cells as a pedagogical tool. Electrophysiology has proven to be a powerful tool in understanding animal physiology and development, yet it has been virtually neglected in the study of plant physiology and development. This review is, in essence, a written account of my personal journey over the past five years to understand the basic principles of electrophysiology so that I can apply them to the study of plant physiology and development. My formal background is in classical botany and cell biology. I have learned electrophysiology by reading many books on physics written for the lay person and by talking informally with many patient biophysicists. I have written this review for the botanist who is unfamiliar with the basics of membrane biology but would like to know that she or he can become familiar with the latest information without much effort. I also wrote it for the neurophysiologist who is proficient in membrane biology but knows little about plant biology (but may want to teach one lecture on "plant action potentials"). And lastly, I wrote this for people interested in the history of science and how the studies of electrical and chemical communication in physiology and development progressed in the botanical and zoological disciplines.

NASA Discipline Plant Biology↗

Controversies in cardiovascular care: silent myocardial ischemia

The objective evidence of silent myocardial ischemia--ischemia in the absence of classical chest pain--includes ST-segment shifts (usually depression), momentary left ventricular failure, and perfusion defects on scintigraphic studies. Assessment of angina patients with 24-hour ambulatory monitoring may uncover episodes of silent ischemia, the existence of which may give important information regarding prognosis and may help structure a more effective therapeutic regimen. The emerging recognition of silent ischemia as a significant clinical entity may eventually result in an expansion of current therapy--not only to ameliorate chest pain, but to minimize or eliminate ischemia in the absence of chest pain.

NASA Program Space Medicine↗

Quantification of scaling exponents and crossover phenomena in nonstationary heartbeat time series

The healthy heartbeat is traditionally thought to be regulated according to the classical principle of homeostasis whereby physiologic systems operate to reduce variability and achieve an equilibrium-like state [Physiol. Rev. 9, 399-431 (1929)]. However, recent studies [Phys. Rev. Lett. 70, 1343-1346 (1993); Fractals in Biology and Medicine (Birkhauser-Verlag, Basel, 1994), pp. 55-65] reveal that under normal conditions, beat-to-beat fluctuations in heart rate display the kind of long-range correlations typically exhibited by dynamical systems far from equilibrium [Phys. Rev. Lett. 59, 381-384 (1987)]. In contrast, heart rate time series from patients with severe congestive heart failure show a breakdown of this long-range correlation behavior. We describe a new method--detrended fluctuation analysis (DFA)--for quantifying this correlation property in non-stationary physiological time series. Application of this technique shows evidence for a crossover phenomenon associated with a change in short and long-range scaling exponents. This method may be of use in distinguishing healthy from pathologic data sets based on differences in these scaling properties.

NASA Discipline Number 14-10↗

The Pittsburgh Sleep Diary

Increasingly, there is a need in both research and clinical practice to document and quantify sleep and waking behaviors in a comprehensive manner. The Pittsburgh Sleep Diary (PghSD) is an instrument with separate components to be completed at bedtime and waketime. Bedtime components relate to the events of the day preceding the sleep, waketime components to the sleep period just completed. Two-week PghSD data is presented from 234 different subjects, comprising 96 healthy young middle-aged controls, 37 older men, 44 older women, 29 young adult controls and 28 sleep disorders patients in order to demonstrate the usefulness, validity and reliability of various measures from the instrument. Comparisons are made with polysomnographic and actigraphic sleep measures, as well as personality and circadian type questionnaires. The instrument was shown to have sensitivity in detecting differences due to weekends, age, gender, personality and circadian type, and validity in agreeing with actigraphic estimates of sleep timing and quality. Over a 12-31 month delay, PghSD measures of both sleep timing and sleep quality showed correlations between 0.56 and 0.81 (n = 39, P < 0.001).

NASA Discipline Number 00-00↗

Stress-induced subclinical reactivation of varicella zoster virus in astronauts

Varicella zoster virus (VZV) becomes latent in human ganglia after primary infection. VZV reactivation occurs primarily in elderly individuals, organ transplant recipients, and patients with cancer and AIDS, correlating with a specific decline in cell-mediated immunity to the virus. VZV can also reactivate after surgical stress. The unexpected occurrence of thoracic zoster 2 days before space flight in a 47-year-old healthy astronaut from a pool of 81 physically fit astronauts prompted our search for VZV reactivation during times of stress to determine whether VZV can also reactivate after non-surgical stress. We examined total DNA extracted from 312 saliva samples of eight astronauts before, during, and after space flight for VZV DNA by polymerase chain reaction: 112 samples were obtained 234-265 days before flight, 84 samples on days 2 through 13 of space flight, and 116 samples on days 1 through 15 after flight. Before space flight, only one of the 112 saliva samples from a single astronaut was positive for VZV DNA. In contrast, during and after space flight, 61 of 200 (30%) saliva samples were positive in all eight astronauts. No VZV DNA was detected in any of 88 saliva samples from 10 healthy control subjects. These results indicate that VZV can reactivate subclinically in healthy individuals after non-surgical stress. Copyright 2004 Wiley-Liss, Inc.

Astronauts↗

Crystallization and preliminary X-ray analysis of recombinant human acid beta-glucocerebrosidase, a treatment for Gaucher's disease

Acid beta-glucocerebrosidase (N-acylsphingosyl-1-O-beta-D-glucoside:glucohydrolase) is a lysosomal glycoprotein that catalyzes the hydrolysis of the glycolipid glucocerebroside to glucose and ceramide. Inadequate levels of this enzyme underly the pathophysiology of Gaucher's disease. Cerezyme (Genzyme Corporation, Cambridge, MA, USA) is a partially deglycosylated form of recombinant human acid beta-glucocerebrosidase that is used in the treatment of Gaucher patients. Although acid beta-glucocerebrosidase belongs to a large family of glycosidases, relatively little is known regarding its structural biology. Here, the crystallization and the initial diffraction analysis of Cerezyme are reported. The crystals are C-centered orthorhombic, with unit-cell parameters a = 285.0, b = 110.2, c = 91.7 A. A 99.9% complete data set has been collected to 2.75 A with an R(sym) of 8.8%.

Glucosylceramidase/chemistry↗