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At least 325 records · Page 18

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↗

Forearm training attenuates sympathetic responses to prolonged rhythmic forearm exercise

We previously demonstrated that nonfatiguing rhythmic forearm exercise at 25% maximal voluntary contraction (12 2-s contractions/min) evokes sympathoexcitation without significant engagement of metabolite-sensitive muscle afferents (B.A. Batman, J.C. Hardy, U.A. Leuenberger, M.B. Smith, Q.X. Yang and L.I. Sinoway. J. Appl. Physiol. 76: 1077-1081, 1994). This is in contrast to the sympathetic nervous system responses observed during fatiguing static forearm exercise where metabolite-sensitive afferents are the key determinants of sympathetic activation. In this report we examined whether forearm exercise training would attenuate sympathetic nervous system responses to rhythmic forearm exercise. We measured heart rate, mean arterial blood pressure (MAP), muscle sympathetic nerve activity (microneurography), plasma norepinephrine (NE), and NE spillover and clearance (tritiated NE kinetics) during nonfatiguing rhythmic forearm exercise before and after a 4-wk unilateral forearm training paradigm. Training had no effect on forearm mass, maximal voluntary contraction, or heart rate but did attenuate the increase in MAP (increase in MAP: from 15.2 +/- 1.8 before training to 11.4 +/- 1.4 mmHg after training; P < 0.017), muscle sympathetic nerve activity (increase in bursts: from 10.8 +/- 1.4 before training to 6.2 +/- 1.1 bursts/min after training; P < 0.030), and the NE spillover (increases in arterial spillover: from 1.3 +/- 0.2 before training to 0.6 +/- 0.2 nmol.min-1.m-2 after training, P < 0.014; increase in venous spillover: from 2.0 +/- 0.6 before training to 1.0 +/- 0.5 nmol.min-1.m-2 after training, P < 0.037) seen in response to exercise performed by the trained forearm. Thus forearm training reduces sympathetic responses during a nonfatiguing rhythmic handgrip paradigm that does not engage muscle metaboreceptors. We speculate that this effect is due to a conditioning-induced reduction in mechanically sensitive muscle afferent discharge.

NASA Discipline Musculoskeletal↗

An optimized index of human cardiovascular adaptation to simulated weightlessness

Prolonged exposure to weightlessness is known to produce a variety of cardiovascular changes, some of which may influence the astronaut's performance during a mission. In order to find a reliable indicator of cardiovascular adaptation to weightlessness, we analyzed data from nine male subjects after a 24-hour period of normal activity and after a period of simulated weightlessness produced by two hours in a launch position followed by 20 hours of 6 degrees head-down tilt plus pharmacologically induced diuresis (furosemide). Heart rate, arterial pressure, thoracic fluid index, and radial flow were analyzed. Autoregressive spectral estimation and decomposition were used to obtain the spectral components of each variable from the subjects in the supine position during pre- and post-simulated weightlessness. We found a significant decrease in heart rate power and an increase in thoracic fluid index power in the high frequency region (0.2-0.45 Hz) and significant increases in radial flow and arterial pressure powers in the low frequency region (<0.2 Hz) in response to simulated weightlessness. However, due to the variability among subjects, any single variable appeared limited as a dependable index of cardiovascular adaptation to weightlessness. The backward elimination algorithm was then used to select the best discriminatory features from these spectral components. Fisher's linear discriminant and Bayes' quadratic discriminant were used to combine the selected features to obtain an optimal index of adaptation to simulated weightlessness. Results showed that both techniques provided improved discriminant performance over any single variable and thus have the potential for use as an index to track adaptation and prescribe countermeasures to the effects of weightlessness.

NASA Discipline Number 14-10↗

Acute Total and Chronic Partial Sleep Deprivation: Effects on Neurobehavioral Functions, Waking EEG and Renin-Angiotensin System

Total sleep deprivation leads to decrements in neurobehavioral performance and changes in electroencephalographic (EEG) oscillations as well as the incidence of slow eye movements ad detected in the electro-oculogram (EOG) during wakefulness. Although total sleep deprivation is a powerful tool to investigate the association of EEG/EOG and neurobehavioral decrements, sleep loss during space flight is usual only partial. Furthermore exposure to the microgravity environment leads to changes in sodium and volume homeostasis and associated renal and cardio-endocrine responses. Some of these changes can be induced in head down tilt bedrest studies. We integrate research tools and research projects to enhance the fidelity of the simulated conditions of space flight which are characterized by complexity and mutual interactions. The effectiveness of countermeasures and physiologic mechanisms underlying neurobehavioral changes and renal-cardio endocrine changes are investigated in Project 3 of the Human Performance Team and Project 3 of the Cardiovascular Alterations Team respectively. Although the. specific aims of these two projects are very different, they employ very similar research protocols. Thus, both projects investigate the effects of posture/bedrest and sleep deprivation (total or partial) on outcome measures relevant to their specific aims. The main aim of this enhancement grant is to exploit the similarities in research protocols by including the assessment of outcome variables relevant to the Renal-Cardio project in the research protocol of Project 3 of the Human Performance Team and by including the assessment of outcome variables relevant to the Quantitative EEG and Sleep Deprivation Project in the research protocols of Project 3 of the Cardiovascular Alterations team. In particular we will assess Neurobehavioral Function and Waking EEG in the research protocols of the renal-cardio endocrine project and renin-angiotensin and cardiac function in the research protocol of the Quantitative EEG and Waking Neurobehavioral Function project. This will allow us to investigate two additional specific aims: 1) Test the hypothesis that chronic partial sleep deprivation during a 17 day bed rest experiment results in deterioration of neurobehavioral function during waking and increases in EEG power density in the theta frequencies, especially in frontal areas of the brain, as well as the nonREM- REM cycle dependent modulation of heart-rate variability. 2) Test the hypothesis that acute total sleep deprivation modifies the circadian rhythm of the renin-angiotensin system, changes the acute responsiveness of this system to posture beyond what a microgravity environment alone does and affects the nonREM-REM cycle dependent modulation of heart-rate variability.

Dijk, Derk-Jan↗

Spaceflight Did Not Impair Cardiovascular Responses to Upright Posture in an Elderly Astronaut

Some of the cardiovascular changes associated with spaceflight have similarities to those associated with aging. We studied the neuroendocrine and hemodynamic responses to upright posture in a 77 year old astronaut before and after spaceflight and compared them to those of a group of 20 younger (41 plus or minus 1 years) astronauts. While arterial pressure responses to standing were similar between the young and old astronauts, hemodynamic profiles were quite different. The elderly astronaut achieved adequate standing arterial pressure primarily by maintaining stroke volume and thus cardiac output. In spite of very high norepinephrine release, he had very little increase in heart rate or total peripheral resistance. This pattern persisted on all test occasions. These responses suggest high sympathetic responses, down-regulated adrenergic receptors and decreased venous compliance typical of aging. In contrast, younger astronauts did not maintain stroke volume or cardiac output with standing, but had significant increases in heart rate and resistance. These results suggest that this elderly subject had cardiovascular responses to standing that are expected in an aged person. These responses were not deleteriously affected by spaceflight. We suggest that healthy, fit elderly individuals are able to withstand the stresses of extreme environments and are not necessarily limited in their activities simply due to their chronological age.

Rossum, Alfred C.↗

Duration of diastole versus cycle length as correlates of left ventricular ejection time

Studies were done on 82 normal subjects to evaluate cycle length vs duration of diastole as determinants of left ventricular ejection time. Cycle length and its reciprocal, heart rate, had the highest correlation with left ventricular ejection time. Removal of the self-correlation of left ventricular ejection time within cycle length reduces the correlation so that, of all intervals, duration of diastole had the highest correlation as a determinant of left ventricular ejection time. Cycle length and heart rate remain valuable as spuriously close but not misleading correlates for predicting or correcting left ventricular ejection time.

Weisdorf, D.↗

Body acceleration distribution and O2 uptake in humans during running and jumping

The distribution of body acceleration and associated oxygen uptake and heart rate responses are investigated in treadmill running and trampoline jumping. Accelerations in the +Gz direction were measured at the lateral ankle, lumbosacral region and forehead of eight young men during level treadmill walking and running at four speeds and trampoline jumping at four heights, together with corresponding oxygen uptake and heart rate. With increasing treadmill speed, peak acceleration at the ankle is found always to exceed that at the back and forehead, and acceleration profiles with higher frequency components than those observed during jumping are observed. Acceleration levels are found to be more uniformly distributed with increasing height in jumping, although comparable oxygen uptake and heat rates are obtained. Results indicate that the magnitude of the biomechanical stimuli is greater in trampoline jumping than in running, which finding could be of use in the design of procedures to avert deconditioning in persons exposed to weightlessness.

Bhattacharya, A.↗

Rat cardiovascular responses to whole body suspension - Head-down and non-head-down tilt

Two experiments aimed at examining the versatility of the whole body suspension (WBS) system as a ground-based model for cardiovascular effects of microgravity are described. The first experiment studied heart rate and arterial pressure responses in rats during a 7-day period of head-down tilt (HDT) or nonhead-down tilt (NHDT) and after removal from whole body suspension (WBS). Mean arterial (MAP), systolic, and diastolic pressures increased about 20 percent in HDT rats on the fist day, heart rates were elevated about 10 percent. During postsuspension most cardiovascular parameters returned to presuspension levels. The second experiment evaluated responses to rapid head-up tilt in HDT and NHDT rats. It was observed that, while pulse pressures remained unchanged, MAP, systolic and diastolic pressures, and HR were elevated in HDT and NHDT rats during head-up tilt after one day of suspension. The WBS rats are considered to be useful as a model to better understand responses of rats exposed to microgravity.

Musacchia, X. J.↗

Augmented catecholamine uptake by the heart during hemorrhage in the conscious dog

Changes in arterial and coronary sinus concentrations of norepinephrine (NE) and epinephrine (E) in response to hemorrhage were examined in conscious dogs. Hemorrhage (45 +/- 3.2 ml/kg) decreased mean arterial pressure by 47 +/- 6%, left ventricular (LV) dP/dt by 38 +/- 6%, and mean left circumflex coronary blood flow by 47 +/- 6%, while heart rate increased by 44 +/- 13%. Increases in concentrations of arterial NE (5,050 +/- 1,080 from 190 +/- 20 pg/ml) and E (12,700 +/- 3,280 from 110 +/- 20 pg/ml) were far greater than increases in coronary sinus NE (1,700 +/- 780 from 270 +/- 50 pg/ml) and E (4,300 +/- 2,590 from 90 +/- 10 pg/ml). Net release of NE from the heart at rest was converted to a fractional extraction of 66 +/- 9% after hemorrhage. Fractional extraction of E increased from 16 +/- 6% at rest to 73 +/- 8% after hemorrhage. In cardiac-denervated dogs, hemorrhage (46 +/- 2.8 ml/kg) decreased mean arterial pressure by 39 +/- 15%, LV dP/dt by 36 +/- 10%, and mean left circumflex coronary blood flow by 36 +/- 13%, while heart rate increased by 24 +/- 10%. Hemorrhage increased arterial NE (1,740 +/- 150 from 210 +/- 30 pg/ml) and E (3,050 +/- 880 from 140 +/- 20 pg/ml) more than it increased coronary sinus NE (460 +/- 50 from 150 +/- 30 pg/ml) and E (660 +/- 160 from 90 +/- 20 pg/ml) but significantly less (P less than 0.05) than observed in intact dogs. These experiments indicate that hemorrhage, unlike exercise and sympathetic nerve stimulation, does not induce net overflow of NE from the heart.(ABSTRACT TRUNCATED AT 250 WORDS).

Non-NASA Center↗

Comparison of Physical Workload Across Eva-Simulation Analog Environments: Hybrid Space Suit Simulator and Pressurized Suit Testing

NASA conducts research, testing, and training across a variety of analog environments to support characterization of human performance during Extravehicular Activities (EVAs). Time utilizing pressurized suits in an offloaded environment is both limited and expensive, making it challenging to carry out extensive research with these suits. The Human Physiology, Performance, Protection, and Operations (H-3PO) Laboratory at NASA Johnson Space Center designed a Hybrid Space Suit Simulator (HS3) as a low-cost, workload approximator and easy access research tool to provide relevant physical and cognitive workloads during simulated EVAs. A pilot study was conducted in a 1g analog environment where six healthy subjects (3 male, 3 female) underwent simulated 5-hour EVAs in the HS3. This study used a COSMED K5 portable metabolic analyzer and a Polar H10 heart rate monitor to evaluate physical workload during the EVAs. For direct comparison, EVA tasks and timelines were modeled after a similar study conducted in pressurized suits (Mark-III spacesuit, n=3 male; small xPGS spacesuit, n=3 female) at NASA’s Active Response Gravity Offload System (ARGOS) offloaded to Lunar gravity (1/6 g). The 1g HS3 data demonstrated increased metabolic rate when compared to pressurized, Lunar-offloaded suited simulated EVAs for certain tasks including the kneeling scoop (HS3: 1194±199 BTU/hr, ARGOS: 860±170 BTU/hr, p < 0.05) and 20 lb object relocation (HS3: 1651±136 BTU/hr, ARGOS: 1048±252.8 BTU/hr, p < 0.05), but it did not demonstrate any significant differences in heart rate (p > 0.05). Other simulated EVA tasks, such as a 500 m traverse (HS3: 1431±177 BTU/hr, ARGOS: 1212±294 BTU/hr, p > 0.05), showed similar workload profiles with no significant workload differences between HS3 and ARGOS. The HS3 is a useful research tool for increasing workloads in EVA research without pressurized suits, though it may overestimate workload during certain EVA tasks when used in 1g environments.

Zachary Wusk↗

Human exercise capabilities in space

Maintenance of rest and exercise performance are prime requirements for all astronauts during flight, not only for maintaining day-to-day productivity, but also for coping with unlikely emergencies. Indirect estimates of submaximal work capacity (oxygen uptake) made from changes in the heart rates of 27 Apollo astronauts (less than 15-day flights) indicated a reduction in work capacity (maximal oxygen uptake) of 17 to 21 percent. This percentage decrease was similar to that measured in middle-aged men after 21 to 30 days of -6 deg head-down bed-rest deconditioning without exercise training. Heart-rate changes during submaximal exercise in the nine Skylab astronauts suggested that they were better able to maintain their work capacity because of longer and more intensive in-flight exercise training. The strength of the flexor and extensor muscle groups decreased by 2 to 9 percent in the elbow and by 6 to 20 percent in the knee in the Skylab astronauts, also similar to the decreases in men undergoing 30 days of bed-rest deconditioning. Exercise protocols have been devised that result in maintenance of work capacity and muscular strength during 30 to 49 days of bed-rest deconditioning.

Greenleaf, John E.↗

Cardiac Autonomic Effects of Acute Exposures to Airborne Particulates in Men and Women

The aim of this research was to investigate cardiac autonomic changes associated with acute exposures to airborne particulates. Methods: High fidelity 12-lead ECG (CardioSoft, Houston, TX) was acquired from 19 (10 male / 9 female) non-smoking volunteers (age 33.6 +/- 6.6 yrs) during 10 minutes pre-exposure, exposure and post-exposure to environmental tobacco smoke (ETS), cooking oil fumes, wood smoke and sham (water vapor). To control exposure levels, noise, subject activity, and temperature, all studies were conducted inside an environmental chamber. Results: The short-term fractal scaling exponent (Alpha-1) and the ratio of low frequency to high frequency Heart Rate Variability (HRV) powers (LF/HF, a purported sympathetic index) were both higher in males (p<0.017 and p<0.05, respectively) whereas approximate entropy (ApEn) and HF/(LF+HF) (a purported parasympathetic index) were both lower in males (p<0.036, and p<0.044, respectively). Compared to pre-exposure (p<0.0002) and sham exposure (p<0.047), male heart rates were elevated during early ETS post-exposure. Our data suggest that, in addition to tonic HRV gender differences, cardiac responses to some acute airborne particulates are gender related.

Howarth, M. S.↗

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↗

Vitamin D receptor signaling is required for heart development in zebrafish embryo

Vitamin D has been found to be associated with cardiovascular diseases. However, the role of vitamin D in heart development during embryonic period is largely unknown. Vitamin D induces its genomic effects through its nuclear receptor, the vitamin D receptor (VDR). The present study investigated the role of VDR on heart development by antisense-mediated knockdown approaches in zebrafish model system. In zebrafish embryos, two distinct VDR genes (vdra and vdrb) have been identified. Knockdown of vdra has little effect on heart development, whereas disrupting vdrb gene causes various cardiac phenotypes, characterized by pericardial edema, slower heart rate and laterality defects. Depletion of both vdra and vdrb (vdra/b) produce additive, but not synergistic effects. To determine whether atrioventricular (AV) cardiomyocytes are properly organized in these embryos, the expression of bmp4, which marks the developing AV boundary at 48 h post-fertilization, was examined. Notably, vdra/b-deficient embryos display ectopic expression of bmp4 towards the ventricle or throughout atrial and ventricular chambers. Taken together, these results suggest that VDR signaling plays an essential role in heart development. - Highlights: • VDR signaling is involved in embryonic heart development. • Knockdown of vdrb, but not vdra, causes decreased heart rate in zebrafish embryo. • Loss of vdr results in cardiac laterality defects. • Loss of vdra/b alters atrioventricular boundary formation. • Loss of vdra/b causes abnormal cardiac looping.

60 APPLIED LIFE SCIENCES↗

Nonrigid registration-based coronary artery motion correction for cardiac computed tomography

Purpose: X-ray computed tomography angiography (CTA) is the modality of choice to noninvasively monitor and diagnose heart disease with coronary artery health and stenosis detection being of particular interest. Reliable, clinically relevant coronary artery imaging mandates high spatiotemporal resolution. However, advances in intrinsic scanner spatial resolution (CT scanners are available which combine nearly 900 detector columns with focal spot oversampling) can be tempered by motion blurring, particularly in patients with unstable heartbeats. As a result, recently numerous methods have been devised to improve coronary CTA imaging. Solutions involving hardware, multisector algorithms, or {beta}-blockers are limited by cost, oversimplifying assumptions about cardiac motion, and populations showing contraindications to drugs, respectively. This work introduces an inexpensive algorithmic solution that retrospectively improves the temporal resolution of coronary CTA without significantly affecting spatial resolution. Methods: Given the goal of ruling out coronary stenosis, the method focuses on 'deblurring' the coronary arteries. The approach makes no assumptions about cardiac motion, can be used on exams acquired at high heart rates (even over 75 beats/min), and draws on a fast and accurate three-dimensional (3D) nonrigid bidirectional labeled point matching approach to estimate the trajectories of the coronary arteries during image acquisition. Motion compensation is achieved by employing a 3D warping of a series of partial reconstructions based on the estimated motion fields. Each of these partial reconstructions is created from data acquired over a short time interval. For brevity, the algorithm 'Subphasic Warp and Add' (SWA) reconstruction. Results: The performance of the new motion estimation-compensation approach was evaluated by a systematic observer study conducted using nine human cardiac CTA exams acquired over a range of average heart rates between 68 and 86 beats/min. Algorithm performance was based-lined against exams reconstructed using standard filtered-backprojection (FBP). The study was performed by three experienced reviewers using the American Heart Association's 15-segment model. All vessel segments were evaluated to quantify their viability to allow a clinical diagnosis before and after motion estimation-compensation using SWA. To the best of the authors' knowledge this is the first such observer study to show that an image processing-based software approach can improve the clinical diagnostic value of CTA for coronary artery evaluation. Conclusions: Results from the observer study show that the SWA method described here can dramatically reduce coronary artery motion and preserve real pathology, without affecting spatial resolution. In particular, the method successfully mitigated motion artifacts in 75% of all initially nondiagnostic coronary artery segments, and in over 45% of the cases this improvement was enough to make a previously nondiagnostic vessel segment clinically diagnostic.

60 APPLIED LIFE SCIENCES↗

Change in energy expenditure and brain and adrenal content of catecholamines in rats during muscular loading and hypokinesia

In male 1-7 month old rats, the growth and the protein content of skeletal muscles were higher than in female rats while the O2 consumption and the heart rate were lower. This is combined with reduction of the thyroid gland weight and of catecholamine content in adrenals at the age of 7 months. The development of male and female rats (1-7 month) under conditions of systematic muscular loads increases the growth tempo and protein of skeletal muscles and intensifies the degree of reduction of energy expenditure and the heart rate. This is accomplished by the greater reduction of relative weight of the thyroid gland and, at the age of 7 months, by reduction of the noradrenaline content in the brainstem. Hypodynamic conditions have the exact opposite effect.

Rozanova, V. D.↗

Cardiovascular Deconditioning in Humans: Alteration in Cardiovascular Regulation and Function During Simulated Microgravity

Alterations in cardiovascular regulation and function that occur during and after space flight have been reported. These alterations are manifested, for example, by reduced orthostatic tolerance upon reentry to the earth's gravity from space. However, the precise physiologic mechanisms responsible for these alterations remain to be fully elucidated. Perhaps, as a result, effective countermeasures have yet to be developed. In this project we apply a powerful, new method - cardiovascular system identification (CSI) - for the study of the effects of space flight on the cardiovascular system so that effective countermeasures can be developed. CSI involves the mathematical analysis of second-to-second fluctuations in non-invasively measured heart rate, arterial blood pressure (ABP), and instantaneous lung volume (ILV - respiratory activity) in order to characterize quantitatively the physiologic mechanisms responsible for the couplings between these signals. Through the characterization of all the physiologic mechanisms coupling these signals, CSI provides a model of the closed-loop cardiovascular regulatory state in an individual subject. The model includes quantitative descriptions of the heart rate baroreflex, autonomic function, as well as other important physiologic mechanisms. We are in the process of incorporating beat-to-beat fluctuations of stroke volume into the CSI technique in order to quantify additional physiologic mechanisms such as those involved in control of peripheral vascular resistance and alterations in cardiac contractility. We apply CSI in conjunction with the two general protocols of the Human Studies Core project. The first protocol involves ground-based, human head down tilt bed rest to simulate microgravity and acute stressors - upright tilt, standing and bicycle exercise - to provide orthostatic and exercise challenges. The second protocol is intended to be the same as the first but with the addition of sleep deprivation to determine whether this contributes to cardiovascular alterations. In these studies, we focus on the basic physiologic mechanisms responsible for the alterations in cardiovascular regulation and function during the simulated microgravity in order to formulate hypotheses regarding what countermeasures are likely to be most effective. Compared to our original proposal, the protocol we are using has been slightly modified to lengthen the bed rest period to 16 days and streamline the data collection. These modifications provide us data on a longer bed rest period and have enabled us to increase our subject throughput. Based on review of our preliminary data we have decided to test a countermeasure which is applied the very end of the bed rest period. We will use the same bed rest protocol to test this countermeasure. We anticipate completing the baseline data collection in our first protocol plus testing of the countermeasure in an additional eight subjects, at which time we plan to initiate the second protocol which includes sleep deprivation. In future studies, we plan to apply CSI to test other potential countermeasures in conjunction with the same bed rest, sleep deprivation and acute stressor models. We also anticipate applying CSI for studying astronauts before and after space flight and ultimately, during space flight. The application of CSI is providing information relevant to the development and evaluation of effective countermeasures allowing humans to adapt appropriately upon re-exposure to a gravity field, and to live and work for longer periods of time in microgravity.

Cohen, Richard↗

Human muscle sympathetic neural and haemodynamic responses to tilt following spaceflight

Orthostatic intolerance is common when astronauts return to Earth: after brief spaceflight, up to two-thirds are unable to remain standing for 10 min. Previous research suggests that susceptible individuals are unable to increase their systemic vascular resistance and plasma noradrenaline concentrations above pre-flight upright levels. In this study, we tested the hypothesis that adaptation to the microgravity of space impairs sympathetic neural responses to upright posture on Earth. We studied six astronauts approximately 72 and 23 days before and on landing day after the 16 day Neurolab space shuttle mission. We measured heart rate, arterial pressure and cardiac output, and calculated stroke volume and total peripheral resistance, during supine rest and 10 min of 60 deg upright tilt. Muscle sympathetic nerve activity was recorded in five subjects, as a direct measure of sympathetic nervous system responses. As in previous studies, mean (+/- S.E.M.) stroke volume was lower (46 +/- 5 vs. 76 +/- 3 ml, P = 0.017) and heart rate was higher (93 +/- 1 vs. 74 +/- 4 beats min(-1), P = 0.002) during tilt after spaceflight than before spaceflight. Total peripheral resistance during tilt post flight was higher in some, but not all astronauts (1674 +/- 256 vs. 1372 +/- 62 dynes s cm(-5), P = 0.32). No crew member exhibited orthostatic hypotension or presyncopal symptoms during the 10 min of postflight tilting. Muscle sympathetic nerve activity was higher post flight in all subjects, in supine (27 +/- 4 vs. 17 +/- 2 bursts min(-1), P = 0.04) and tilted (46 +/- 4 vs. 38 +/- 3 bursts min(-1), P = 0.01) positions. A strong (r(2) = 0.91-1.00) linear correlation between left ventricular stroke volume and muscle sympathetic nerve activity suggested that sympathetic responses were appropriate for the haemodynamic challenge of upright tilt and were unaffected by spaceflight. We conclude that after 16 days of spaceflight, muscle sympathetic nerve responses to upright tilt are normal.

Non-NASA Center↗