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At least 109 records · Page 6

Examining Individual Differences in Temporal Profiles of Cardiovascular Responses to the Head Down Tilt during Fluid Loading

Upon returning to Earth after an extended exposure to micro-gravity in space many astronauts have experienced symptoms of light headedness and fainting associated with post-flight orthostatic intolerance (low blood pressure). The main reason for this condition is the reduced fluid volume in the body while in space. A preventative treatment was proposed to prevent this condition by fluid loading to restore lost plasma volume by giving crew members salt tablets and water prior to re-entry. In order to simulate micro-gravity effects on earth test subjects are placed in a supine position with their head below the level of their heart (6 head down tilt-HDT). The purpose of the present study is to define individual differences in the time course of cardiac stroke volume responses to HDT (6 hours) and the effectiveness of fluid loading for mitigating orthostatic intolerance when standing . Echocardiography and impedance cardiography data will be collected on 8 men and 8 women to examine heart function to HDT. A second objective is to determine if the effects of fluid loading vary due to individual differences (e.g., age, gender, height, weight, physical fitness, etc.).

orthostatic intolerance↗

Gender Differences in Bed Rest: Preliminary Analysis of Vascular Function

Orthostatic intolerance is a recognized consequence of spaceflight. Numerous studies have shown that women are more susceptible to orthostatic intolerance following spaceflight as well as bed rest, the most commonly used ground-based analog for spaceflight. One of the possible mechanisms proposed to account for this is a difference in vascular responsiveness between genders. We hypothesized that women and men would have differing vascular responses to 90 days of 6-degree head down tilt bed rest. Additionally, we hypothesized that vessels in the upper and lower body would respond differently, as has been shown in the animal literature. Thirteen subjects were placed in bedrest for 90 days (8 men, 5 women) at the Flight Analogs Unit, UTMB. Direct arterial and venous measurements were made with ultrasound to evaluate changes in vascular structure and function. Arterial function was assessed, in the arm and leg, during a reactive hyperemia protocol and during sublingual nitroglycerin administration to gauge the contributions of endothelial dependent and independent dilator function respectively. Venous function was assessed in dorsal hand and foot veins during the administration of pharmaceuticals to assess constrictor and dilator function. Both gender and day effects are seen in arterial dilator function to reactive hyperemia, but none are seen with nitroglycerin. There are also differences in the wall thickness in the arm vs the leg during bed rest, which return toward pre-bed rest levels by day 90. More subjects are required, especially females as there is not sufficient power to properly analyze venous function. Day 90 data are most underpowered.

Platts, Steven H.↗

Psychophysiological investigations of the biomedical problems of manned spaceflight

The Final Report on psychophysiological investigations of the biomedical problems of manned spaceflight is presented. In the first project, statistical analyses of human autonomic data were performed. The objectives were the following: to establish a relational data base containing human psychophysiological data obtained from Shuttle flight experiments and ground-based research over a 20 year period; to enable multi-user access and retrieval of these data for subsequent analyses and for possible inclusion in the proposed Life Sciences Data Archive; and to enable/conduct statistical analyses across several experiments on large subject populations which can thereby provide definitive answers to questions on human autonomic and behavioral responses and adaptation to environmental stressors on Earth and in space. The second project studied motion sickness. The objectives were: to test/develop hardware and procedures to be incorporated into preflight training of crewmembers of Spacelab-J; and to examine spin-off applications of AFT. The third project studied orthostatic intolerance. The objective was to test the feasibility of applying autogenic-feedback training as a potential treatment for postflight orthostatic intolerance.

Source record↗

Using Concurrent Cardiovascular Information to Augment Survival Time Data for Evaluating Orthostatic Tilt Test Performance

Head-up tilt (HUT) tests often are used in research to measure orthostatic intolerance (OI) (inability to appropriately control blood pressure while upright) in clinical populations and otherwise healthy individuals after interventions. Post-space flight orthostatic intolerance is a well-known phenomenon, and countermeasures to its development has been an active area of research at NASA. In the NASA HUT protocol, subjects lie horizontally on an automatic tilt table for baseline measurements before being raised to 80deg head-up tilt for a defined period of time or until signs or symptoms of presyncope ensues (light-headedness, nausea, dizziness, sweating, weakness or fainting). Multiple measures are collected to evaluate the cardiovascular system's ability to respond appropriately to the orthostatic challenge. However if the intended duration of the HUT is short, the ability to detect changes in OI due to an intervention or its prevention by a countermeasure may be limited by a small number of failures to permit comparisons based on survival time alone. Thus, the time-trajectory of the cardiovascular data becomes an important additional source of information. In particular, we will show how various measures of trajectory variability can effectively augment survival analysis for the assessment of OI in a joint model when high censoring rates are present.

Feiveson, Alan H.↗

Modelflow Estimates of Stroke Volume Do Not Correlate With Doppler Ultrasound Estimates During Upright Posture

Orthostatic intolerance affects 60‐80% of astronauts returning from long‐duration missions, representing a significant risk to completing mission‐critical tasks. While likely multifactorial, a reduction in stroke volume (SV) represents one factor contributing to orthostatic intolerance during stand and head up tilt (HUT) tests. Current measures of SV during stand or HUT tests use Doppler ultrasound and require a trained operator and specialized equipment, restricting its use in the field. BeatScope (Finapres Medical Systems BV, The Netherlands) uses a modelflow algorithm to estimate SV from continuous blood pressure waveforms in supine subjects; however, evidence supporting the use of Modelflow to estimate SV in subjects completing stand or HUT tests remain scarce. Furthermore, because the blood pressure device is held extended at heart level during HUT tests, but allowed to rest at the side during stand tests, changes in the finger arterial pressure waveform resulting from arm positioning could alter modelflow estimated SV. The purpose of this project was to compare Doppler ultrasound and BeatScope estimations of SV to determine if BeatScope can be used during stand or HUT tests. Finger photoplethysmography was used to acquire arterial pressure waveforms corrected for hydrostatic finger‐to‐heart height using the Finometer (FM) and Portapres (PP) arterial pressure devices in 10 subjects (5 men and 5 women) during a stand test while simultaneous estimates of SV were collected using Doppler ultrasound. Measures were made after 5 minutes of supine rest and while subjects stood for 5 minutes. Next, SV estimates were reacquired while each arm was independently raised to heart level, a position similar to tilt testing. Supine SV estimates were not significantly different between all three devices (FM: 68+/-20, PP: 71+/-21, US: 73+/-21 ml/beat). Upon standing, the change in SV estimated by FM (‐18+/-8 ml) was not different from PP (‐21+/-12), but both were significantly less than US (‐37+/-16 ml, p<.05). Raising finger BP devices to heart level caused no significant change in SV measured with any of the devices (FM: 1.5+/-19, PP: 1.7+/-26, US: 0.5+/-6), although variability was 3‐6x greater as assessed by both blood pressure devices compared to US. Retrospective analysis of blood pressure data to assess SV in 11 supine subjects revealed significantly different estimates between methods (FM: 95+/-17, US: 75+/-32, p<.05), but the change in SV resulting from HUT was similar between methods (FM: ‐37+/-9, US: ‐40+/-18 ml). However, the correlation coefficient determined from pairs of SV estimated by US and FM was weak (r2=0.03). These data suggest Modelflow cannot be used in lieu of Doppler ultrasound to estimate SV during stand or HUT tests. Further investigation should focus on identifying factors contributing to differences between these measurement techniques in order to make use of a simple method for assessing beat‐by‐beat changes in SV during postural changes, especially during field testing.

Ferguson, Connor R.↗

Numerical simulation of the influence of gravity and posture on cardiac performance

A numerical model of the cardiovascular system was used to quantify the influences on cardiac function of intrathoracic pressure and intravascular and intraventricular hydrostatic pressure, which are fundamental biomechanical stimuli for orthostatic response. The model included a detailed arterial circulation with lumped parameter models of the atria, ventricles, pulmonary circulation, and venous circulation. The venous circulation was divided into cranial, central, and caudal regions with nonlinear compliance. Changes in intrathoracic pressure and the effects of hydrostatic pressure were simulated in supine, launch, sitting, and standing postures for 0, 1, and 1.8 G. Increasing intrathoracic pressure experienced with increasing gravity caused 12% and 14% decreases in cardiac output for 1 and 1.8 G supine, respectively, compared to 0 G. Similar results were obtained for launch posture, in which the effects of changing intrathoracic pressure dominated those of hydrostatic pressure. Compared to 0 G, cardiac output decreased 0.9% for 1 G launch and 15% for 1.8 G launch. In sitting and standing, the position of the heart above the hydrostatic indifference level caused the effects of changing hydrostatic pressure to dominate those of intrathoracic pressure. Compared to 0 G, cardiac output decreased 13% for 1 G sitting and 23% for 1.8 G sitting, and decreased 17% for 1 G standing and 31% for 1.8 G standing. For a posture change from supine to standing in 1 G, cardiac output decreased, consistent with the trend necessary to explain orthostatic intolerance in some astronauts during postflight stand tests. Simulated lower body negative pressure (LBNP) in 0 G reduced cardiac output and mean aortic pressure similar to I G standing, suggesting that LBNP provides at least some cardiovascular stimuli that may be useful in preventing postflight orthostatic intolerance. A unifying concept, consistent with the Frank-Starling mechanism of the heart, was that cardiac output was proportional to cardiac diastolic transmural pressure for all postures and gravitational accelerations.

Non-NASA Center↗

Baroreflex buffering and susceptibility to vasoactive drugs

BACKGROUND: The overall effect of vasoactive drugs on blood pressure is determined by a combination of the direct effect on vascular tone and an indirect baroreflex-mediated effect, a baroreflex buffering of blood pressure. Differences in baroreflex function affect the responsiveness to vasoactive medications, particularly baroreflex buffering of blood pressure; however, the magnitude is not known. METHODS AND RESULTS: We characterized baroreflex function and responses to vasoactive drugs in patients with idiopathic orthostatic intolerance, patients with essential hypertension, patients with monogenic hypertension and brachydactyly, patients with multiple system atrophy, and control subjects. We used phenylephrine sensitivity during ganglionic blockade as a measure of baroreflex buffering. Phenylephrine (25 microg) increased systolic blood pressure 6+/-1.6 mm Hg in control subjects, 6+/-1.1 mm Hg in orthostatic intolerance patients, 18+/-3.9 mm Hg in patients with essential hypertension, 31+/-3.4 mm Hg in patients with monogenic hypertension, and 25+/-3.4 mm Hg in patients with multiple system atrophy. Similar differences in sensitivities between groups were observed with nitroprusside. The sensitivity to vasoactive drugs was highly correlated with baroreflex buffering function and to a lesser degree with baroreflex control of heart rate. In control subjects, sensitivities to nitroprusside and phenylephrine infusions were correlated with baroreflex heart rate control and sympathetic nerve traffic. CONCLUSIONS: Our findings are consistent with an important effect of baroreflex blood pressure buffering on the sensitivity to vasoactive drugs. They suggest that even moderate changes in baroreflex function may have a substantial effect on the sensitivity to vasoactive medications.

NASA Discipline Regulatory Physiology↗

Computational Models of the Cardiovascular System and Its Response to Microgravity

Computational models of the cardiovascular system are powerful adjuncts to ground-based and in-flight experiments. We will provide NSBRI with a model capable of simulating the short-term effects of gravity on cardiovascular function. The model from this project will: (1) provide a rational framework which quantitatively defines interactions among complex cardiovascular parameters and which supports the critical interpretation of experimental results and testing of hypotheses. (2) permit predictions of the impact of specific countermeasures in the context of various hypothetical cardiovascular abnormalities induced by microgravity. Major progress has been made during the first 18 months of the program: (1) We have developed an operational first-order computer model capable of simulating the cardiovascular response to orthostatic stress. The model consists of a lumped parameter hemodynamic model and a complete reflex control system. The latter includes cardiopulmonary and carotid sinus reflex limbs and interactions between the two. (2) We have modeled the physiologic stress of tilt table experiments and lower body negative pressure procedures (LBNP). We have verified our model's predictions by comparing them with experimental findings from the literature. (3) We have established collaborative efforts with leading investigators interested in experimental studies of orthostatic intolerance, cardiovascular control, and physiologic responses to space flight. (4) We have established a standardized method of transferring data to our laboratory from the ongoing NSBRI bedrest studies. We use this data to estimate input parameters to our model and compare our model predictions to actual data to further verify our model. (5) We are in the process of systematically simulating current hypotheses concerning the mechanism underlying orthostatic intolerance by matching our simulations to stand test data from astronauts pre- and post-flight. (6) We are in the process of developing a JAVA version of the simulator which will be distributed amongst the cardiovascular team members. Future work on this project involves modifications of the model to represent a rodent (rat) model, further evaluation of the bedrest astronaut and animal data, and systematic investigation of specific countermeasures.

Kamm, Roger D.↗

Artemis Sustained Translational Acceleration Limits: Human Tolerance Evidence from Apollo to ISS

The designers of the next generation of lunar landers may adopt novel, crew-body orientations outside of our flight history or applied to flight durations and environments outside of our experience. Current sustained translational acceleration requirements in NASA-STD-3001 are applicable only to crewmembers in a seated posture and are thus inadequate to address human tolerance in non-seated configurations. Initial designs for the Apollo Lunar Module (LM) included seats for both commander and pilot; however, these were subsequently removed from the vehicle due to mass constraints and a willingness to accept the unknown risks for short-duration missions given the limited human physiologic data at the time. In the years since Apollo, our evidence base has grown immensely. Initial Artemis mission timelines under consideration will be longer than the longest Apollo mission, by a significant margin, with timeframes more analogous to longer Space Shuttle missions. Given the incidence of postflight orthostatic intolerance following shuttle missions, a significant risk may exist for lander design(s) pursuing a standing crew configuration similar to Apollo LM. New sustained translational acceleration limits developed to address this risk are presented herein. These limits were derived from evaluations of Apollo biomedical and flight profile data during lunar descent and ascent operations, Soyuz and Space Shuttle flight profile and post-landing biomedical data, and analogue bed rest post-exposure data on orthostatic intolerance.

James M. Pattarini↗

Certain cardiovascular indices predict syncope in the postural tachycardia syndrome

Patients with postural tachycardia syndrome (POTS) represent a patient population with orthostatic intolerance; some are prone to syncope, others are not. The underlying neurocardiovascular mechanisms are not completely understood. The current study was undertaken to assess if certain cardiovascular indices are predictive of syncope in POTS. We compared the response to tilt-up and the Valsalva maneuver in four groups: POTS patients who fainted (POTS-f; n = 11;31 +/- 11 years): POTS patients who did not faint (POTS-nf; n = 9; 29 +/- 9 years); normal controls (NLS; n = 13; 39 +/- 11 years); patients with generalized autonomic failure with orthostatic hypotension and syncope (n = 10; 59 +/- 14 years). Beat-to-beat heart rate (HR), systolic arterial pressure, diastolic arterial pressure (DAP) and pulse pressure (PP) were monitored using Finapres. Cardiac output, stroke volume (SV) and end-diastolic volume (EDV), and calculated total peripheral resistance (TPR) were recorded using thoracic electrical bioimpedance. An autonomic reflex screen which quantitates the distribution and severity of autonomic failure was also done. With the patient supine, all POTS patients (POTS-nf; POTS-f) had increased HR (p < 0.001) and reduced SV/EDV (p < 0.001) when compared with NLS. On tilt-up, POTS-f patients were significantly different from both NLS and POTS-nf patients; the most consistent alteration was a fall instead of an increase in TPR; other changes were a greater reduction in PP, a reduction (instead of an increment) in DAP, and a different pattern of changes during the Valsalva maneuver (excessive early phase II, attenuated or absent late phase II). Our results suggest alpha-adrenergic impairment with increased pooling or hypovolemia in POTS-f patients. We conclude that it is possible to identify the mechanism of syncope in POTS patients, and perhaps other patients with orthostatic intolerance and an excessive liability to syncope.

NASA Discipline Number 14-10↗

Alternative Compression Garments

Orthostatic intolerance after spaceflight is still an issue for astronauts as no in-flight countermeasure has been 100% effective. Future anti-gravity suits (AGS) may be similar to the Shuttle era inflatable AGS or may be a mechanical compression device like the Russian Kentavr. We have evaluated the above garments as well as elastic, gradient compression garments of varying magnitude and determined that breast-high elastic compression garments may be a suitable replacement to the current AGS. This new garment should be more comfortable than the AGS, easy to don and doff, and as effective a countermeasure to orthostatic intolerance. Furthermore, these new compression garments could be worn for several days after space flight as necessary if symptoms persisted. We conducted two studies to evaluate elastic, gradient compression garments. The purpose of these studies was to evaluate the comfort and efficacy of an alternative compression garment (ACG) immediately after actual space flight and 6 degree head-down tilt bed rest as a model of space flight, and to determine if they would impact recovery if worn for up to three days after bed rest.

Stenger, M. B.↗

Gradient Compression Stockings may Prevent Recovery after Bed Rest Deconditioning

Introduction: Astronauts continue to wear a compression garment during and immediately after landing to prevent orthostatic intolerance (OI). We recently developed a custom-fitted, 3-piece garment that consists of thigh-high stockings with biker-style shorts that provides continuous, gradient compression: 55 mmHg at the ankle that decreases to approximately 20 mmHg at the top of the leg and 15 mmHg over the abdomen. This garment has been shown to be effective in preventing symptoms of OI during a short stand test after Space Shuttle missions, but symptoms may persist for several days after a long-duration mission in some astronauts. The purpose of this study was to confirm the effectiveness of wearing these elastic, gradient compression garments during orthostatic testing after 2 weeks of 6 degree head-down tilt bed rest as a model of spaceflight and to determine whether they would impact recovery after bed rest. Methods: Eight (5 treatment, 3 control) of 16 subjects have completed this study to-date. All subjects wore the 3-piece garment from waking until tilt testing (~3 h) as a simulation of the timeline for astronauts on landing day (BR+0). Control subjects removed the garment after the tilt test. Treatment subjects wore the garment for the remainder of the day and wore lower compression thigh-high only garments on the day after bed rest (BR+1). Blood pressure, heart rate, and stroke volume responses to a 15-min 80 degree head-up tilt test were determined before 2 weeks of 6 degree head-down tilt, and on BR+0 and BR+1. Plasma volume (PV) was measured before each of these test sessions. Data are mean SE. Results: Compression garments prevented signs of OI on BR+0; all subjects in both groups completed the full 15-min test. Heart rate responses to tilt were lower on BR+0 than all other test days. Control subjects demonstrated a marginal PV decrease after bed rest, but showed typical recovery the day after bed rest (BR+0: 2.32 plus or minus 0.15 L to BR+1: 2.79 plus or minus 0.15 L). Treatment subjects did not recover PV the day after bed rest (BR+0: 2.61 plus or minus 0.23 L to BR+1: 2.61 plus or minus 0.23 L). Conclusion: Abdomen-high compression garments, which are effective in preventing post-bed rest orthostatic intolerance, may slow recovery of PV. Modified garments with reduced compression may be necessary to prevent prolonging recovery.

Stenger, Michael B.↗

Orthostatic stress is necessary to maintain the dynamic range of cardiovascular control in space

In the upright position, gravity fills the low-pressure systems of human circulation with blood and interstitial fluid in the sections below the diaphragm. Without gravity one pressure component in the vessels disappears and the relationship between hydrostatic pressure and oncotic pressure, which regulates fluid passage across the capillary endothelium in the terminal vascular bed, shifts constantly. The visible consequences of this are a puffy face and "bird" legs. The plasma volume shrinks in space and the range of cardiovascular control is reduced. When they stand up for the first time after landing, 30-50% of astronauts suffer from orthostatic intolerance. It remains unclear whether microgravity impairs cardiovascular reflexes, or whether it is the altered volume status that causes the cardiovascular instability following space flight. Lower body negative pressure was used in several space missions to stimulate the cardiovascular reflexes before, during and after a space flight. The results show that cardiovascular reflexes are maintained in microgravity. However, the astronauts' volume status changed in space, towards a volume-retracted state, as measurements of fluid-regulating hormones have shown. It can be hypothesized that the control of circulation and body fluid homeostasis in humans is adapted to their upright posture in the Earth's gravitational field. Autonomic control regulates fluid distribution to maintain the blood pressure in that posture, which most of us have to cope with for two-thirds of the day. A determined amount of interstitial volume is necessary to maintain the dynamic range of cardiovascular control in the upright posture; otherwise orthostatic intolerance may occur more often.

manned↗

Deterioration of left ventricular chamber performance after bed rest : "cardiovascular deconditioning" or hypovolemia?

BACKGROUND: Orthostatic intolerance after bed rest is characterized by hypovolemia and an excessive reduction in stroke volume (SV) in the upright position. We studied whether the reduction in SV is due to a specific adaptation of the heart to head-down tilt bed rest (HDTBR) or acute hypovolemia alone. METHODS AND RESULTS: We constructed left ventricular (LV) pressure-volume curves from pulmonary capillary wedge pressure and LV end-diastolic volume and Starling curves from pulmonary capillary wedge pressure and SV during lower body negative pressure and saline loading in 7 men (25+/-2 years) before and after 2 weeks of -6 degrees HDTBR and after the acute administration of intravenous furosemide. Both HDTBR and hypovolemia led to a similar reduction in plasma volume. However, baseline LV end-diastolic volume decreased by 20+/-4% after HDTBR and by 7+/-2% after hypovolemia (interaction P<0.001). Moreover, SV was reduced more and the Starling curve was steeper during orthostatic stress after HDTBR than after hypovolemia. The pressure-volume curve showed a leftward shift and the equilibrium volume of the left ventricle was decreased after HDTBR; however, after hypovolemia alone, the curve was identical, with no change in equilibrium volume. Lower body negative pressure tolerance was reduced after both conditions; it decreased by 27+/-7% (P<0.05) after HDTBR and by 18+/-8% (P<0.05) after hypovolemia. CONCLUSIONS: Chronic HDTBR leads to ventricular remodeling, which is not seen with equivalent degrees of acute hypovolemia. This remodeling leads to a greater decrease in SV during orthostatic stress after bed rest than hypovolemia alone, potentially contributing to orthostatic intolerance.

NASA Discipline Cardiopulmonary↗

Arterial Structure and Function in Women and Men Following Long Duration Bed Rest

Orthostatic intolerance is a well-recognized consequence of space flight and bed rest (BR), with a greater incidence reported in women. We hypothesized that leg, but not arm, arterial structure and function would be altered following prolonged BR, as a model of space flight, and that women would be more susceptible to BR-induced deconditioning than men. METHODS: Ten volunteers (5 males, 5 females) completed 90 d of 6 head-down BR. Subjects participated in tests of brachial (BA) and anterior tibial (AT) artery endothelium-dependent (flow mediated dilation [FMD] following 5-7 min of arterial occlusion) and endothelium-independent (0.4 mg sublingual nitroglycerin [SN]) vasodilation before BR (PRE) and on days 7 (BR7), 21 (BR21), and 90 (BR90) of BR. Vessel diameter and intimal medial thickness (IMT) were measured by ultrasound. IMT, baseline diameter, and percent change in diameter from baseline during FMD and SN tests were compared across BR and between genders using repeated measures two-way ANOVA with Bonferroni post-hoc tests in which PRE and women were control conditions. RESULTS: Baseline vessel diameter was lower in women than in men in both the BA (p=0.005) and AT (p=0.01) across all days. Baseline AT diameter decreased during BR (p=0.01) and tended to be more profound in women (interaction, p=0.06). AT diameter was reduced in women at BR21 and BR90 (p<0.01) but not in men. In contrast, there was no BR effect on baseline BA diameter. IMT also decreased in the AT (p<0.001) but not in the BA during BR; AT IMT was reduced by BR21 (p<0.05). As a group, there was no effect of BR on AT FMD, BA FMD, and AT SN-dilation, although BA SN-dilation was significantly reduced on BR21 (p=0.01). Across all BR days, women exhibited higher AT FMD (p=0.03), BA FMD (p=0.02), and BA SN-dilation (p=0.01) and tended to demonstrate greater AT SN-dilation (p=0.11). CONCLUSIONS: These preliminary results suggest that arterial remodeling occurs during BR in the leg (decreased diameter and IMT), but not in the arm, and that women appear to be more responsive to BR than men. These changes in the leg, coupled with larger responses to direct and indirect stimulation of the arterial smooth muscle, may be related to the greater incidence of orthostatic intolerance in women after BR and space flight.

Lee, Stuart M. C.↗

Gender Differences in Baroreflex Sensitivity after Bed Rest

Two potential contributing factors to post-spaceflight orthostatic intolerance are decreases in baroreflex sensitivity (BRS) and sympathetic nervous system response. The purpose of this study was to examine the shape of the BRS curve and sympathetic response to a wide range of blood pressures (BP) before and during 6 head-down bed rest (BR). METHODS: Normal volunteers were tested one day before BR (20M, 1 0F) and near BR days 30 (20M, 10F), 60 (16M, 8F), and 90 (1 0M, 5F). BP was pharmacologically manipulated by 10-min infusions of phenylephrine (PE) and sodium nitroprusside (SNP) at 3 increasing concentrations with a 20-min rest between PE and SNP. Electrocardiogram and continuous finger blood pressure were recorded. A blood sample was drawn at the end of each infusion to measure plasma norepinephrine levels. The spontaneous baroreflex slope (SBS), a measure of BRS, was calculated as the slope of a sequence of 3 or more beats in which the systolic BP (SBP) and following R-R interval (RR) both increased or decreased. The data included saturated responses at the upper but not the lower end of the BP range. Mean response curves were constructed using second-order mixed model analysis. Results are based on term significance in the models. RESULTS RR: RR was lower during BR than pre BR (p<0.001). Pre BR males were modeled by a linear RR response to SBP (p=0.000) while females had a quadratic response which saturated at high SBP (p=0.019). By day 30, both genders were modeled by a linear response; compared to males, females had an attenuated (lower slope) RR response to changes in SBP (p=0.031). SBS: SBS vs SBP analysis showed a lower SBS during BR (p<0.001) when compared to pre BR. Females had a higher SBS than males pre BR (p=0.006). Females exhibited saturating SBS at higher SBP (p=0.016) on day 30, while males were modeled by a linear SBS response to SBP (p=0.035). NE: Females had different NE response to diastolic BP than males pre BR (p=0.035) and on day 30 (p=0.005). CONCLUSION: NE, RR and SBS responses to BP are affected by gender and BR. Not only do gender and BR baseline differences exist, but gender and BR also influence the slope and saturation of the BRS curves. Attenuated and saturating RR and SBS responses, as well as differences in baseline values, may contribute to the higher rates of orthostatic intolerance in women and after bed rest.

Arzeno, Natalia M.↗

Cerebrovascular regulation in the postural orthostatic tachycardia syndrome (POTS)

Patients with the postural orthostatic tachycardia syndrome (POTS) have symptoms of orthostatic intolerance despite having a normal orthostatic blood pressure (BP), which suggests some impairment of cerebrovascular regulation. Cerebrovascular autoregulation refers to the maintenance of normal cerebral blood flow in spite of changing BP. Mechanisms of autoregulation include myogenic, metabolic and neurogenic vasoregulation. Beat-to-beat recording of blood-flow velocity (BFV) is possible using transcranial Doppler imaging. It is possible to evaluate autoregulation by regressing deltaBFV to deltaBP during head-up tilt. A number of dynamic methods, relating deltaBFV to deltaBP during sudden induced changes in BP by occluding then releasing peripheral arterial flow or by the Valsalva maneuver. The deltaBFV to deltaBP provides an index of autoregulation. In orthostatic hypotension, the autoregulated range is typically expanded. In contrast, paradoxical vasoconstriction occurs in POTS because of an increased depth of respiration, resulting in hypocapnic cerebrovascular constriction, and impaired autoregulation.

Review↗

Cardiovascular Aspects of Space Shuttle Flights: At the Heart of Three Decades of American Spaceflight Experience

The advent of the Space Shuttle era elevated cardiovascular deconditioning from a research topic in gravitational physiology to a concern with operational consequences during critical space mission phases. NASA has identified three primary cardiovascular risks associate with short-duration (less than 18 d) spaceflight: orthostatic intolerance; decreased maximal oxygen uptake; and cardiac arrhythmias. Orthostatic hypotension (OH) was observed postflight in Mercury astronauts, studied in Gemini and Apollo astronauts, and tracked as it developed in-flight during Skylab missions. A putative hypotensive episode in the pilot during an early shuttle landing, and well documented postflight hypotension in a quarter of crewmembers, catalyzed NASA's research effort to understand its mechanisms and develop countermeasures. Shuttle investigations documented the onset of OH, tested mechanistic hypotheses, and demonstrated countermeasures both simple and complex. Similarly, decreased aerobic capacity in-flight threatened both extravehicular activity and post-landing emergency egress. In one study, peak oxygen uptake and peak power were significantly decreased following flights. Other studies tested hardware and protocols for aerobic conditioning that undergird both current practice on long-duration International Space Station (ISS) missions and plans for interplanetary expeditions. Finally, several studies suggest that cardiac arrhythmias are of less concern during short-duration spaceflight than during long-duration spaceflight. Duration of the QT interval was unchanged and the frequency of premature atrial and ventricular contractions was actually shown to decrease during extravehicular activity. These investigations on short-duration Shuttle flights have paved the way for research aboard long-duration ISS missions and beyond. Efforts are already underway to study the effects of exploration class missions to asteroids and Mars.

Charles, John B.↗