Lower body negative pressure identifies altered central vein characteristics without accompanying changes to baroreflexes in astronauts within hours of landing.

Cardiovascular deconditioning and altered baroreflexes predispose returning astronauts to Orthostatic Intolerance. We assessed 7 astronauts (1 female) before and following long-duration spaceflight (146 ± 43 days) with minimal upright posture prior to testing. We applied lower body negative pressure (LBNP) of up to - 30 mmHg to supine astronauts instrumented for continual synchronous measurements of cardiovascular variables, and intermittent imaging the Portal Vein (PV) and Inferior Vena Cava (IVC). During supine rest without LBNP, postflight elevations to total peripheral resistance (TPR; 15.8 ± 4.6 vs. 20.8 ± 7.1 mmHg min/l, p < 0.05) and reductions in stroke volume (SV; 104.4 ± 16.7 vs. 87.4 ± 11.5 ml, p < 0.05) were unaccompanied by changes to heart rate (HR) or estimated central venous pressure (CVP). Small increases to systolic blood pressure (SBP) and diastolic blood pressure (DBP) were not statistically significant. Autoregressive moving average modelling (ARMA) during LBNP did not identify differences to either arterial (DBP → TPR and SBP → HR) or cardiopulmonary (CVP → TPR) baroreflexes consistent with intact cardiovascular control. On the other hand, IVC and PV diameter-CVP relationships during LBNP revealed smaller diameter for a given CVP postflight consistent with altered postflight venous wall dynamics.

Impaired cerebrovascular autoregulation and reduced CO2 reactivity after long duration spaceflight.

Long duration habitation on the International Space Station (ISS) is associated with chronic elevations in arterial blood pressure in the brain compared with normal upright posture on Earth and elevated inspired CO(2). Although results from short-duration spaceflights suggested possibly improved cerebrovascular autoregulation, animal models provided evidence of structural and functional changes in cerebral vessels that might negatively impact autoregulation with longer periods in microgravity. Seven astronauts (1 woman) spent 147 ± 49 days on ISS. Preflight testing (30-60 days before launch) was compared with postflight testing on landing day (n = 4) or the morning 1 (n = 2) or 2 days (n = 1) after return to Earth. Arterial blood pressure at the level of the middle cerebral artery (BP(MCA)) and expired CO(2) were monitored along with transcranial Doppler ultrasound assessment of middle cerebral artery (MCA) blood flow velocity (CBFV). Cerebrovascular resistance index was calculated as (CVRi = BP(MCA)/CBFV). Cerebrovascular autoregulation and CO(2) reactivity were assessed in a supine position from an autoregressive moving average (ARMA) model of data obtained during a test where two breaths of 10% CO(2) were given four times during a 5-min period. CBFV and Doppler pulsatility index were reduced during -20 mmHg lower body negative pressure, with no differences pre- to postflight. The postflight indicator of dynamic autoregulation from the ARMA model revealed reduced gain for the CVRi response to BP(MCA) (P = 0.017). The postflight responses to CO(2) were reduced for CBFV (P = 0.056) and CVRi (P = 0.047). These results indicate that long duration missions on the ISS impaired dynamic cerebrovascular autoregulation and reduced cerebrovascular CO(2) reactivity.

Cardiovascular regulation during long-duration spaceflights to the International Space Station.

Early evidence from long-duration flights indicates general cardiovascular deconditioning, including reduced arterial baroreflex gain. The current study investigated the spontaneous baroreflex and markers of cardiovascular control in six male astronauts living for 2-6 mo on the International Space Station. Measurements were made from the finger arterial pressure waves during spontaneous breathing (SB) in the supine posture pre- and postflight and during SB and paced breathing (PB, 0.1 Hz) in a seated posture pre- and postflight, as well as early and late in the missions. There were no changes in preflight measurements of heart rate (HR), blood pressure (BP), or spontaneous baroreflex compared with in-flight measurements. There were, however, increases in the estimate of left ventricular ejection time index and a late in-flight increase in cardiac output (CO). The high-frequency component of RR interval spectral power, arterial pulse pressure, and stroke volume were reduced in-flight. Postflight there was a small increase compared with preflight in HR (60.0 ± 9.4 vs. 54.9 ± 9.6 beats/min in the seated posture, P < 0.05) and CO (5.6 ± 0.8 vs. 5.0 ± 1.0 l/min, P < 0.01). Arterial baroreflex response slope was not changed during spaceflight, while a 34% reduction from preflight in baroreflex slope during postflight PB was significant (7.1 ± 2.4 vs. 13.4 ± 6.8 ms/mmHg), but a smaller average reduction (25%) during SB (8.0 ± 2.1 vs. 13.6 ± 7.4 ms/mmHg) was not significant. Overall, these data show no change in markers of cardiovascular stability during long-duration spaceflight and only relatively small changes postflight at rest in the seated position. The current program routine of countermeasures on the International Space Station provided sufficient stimulus to maintain cardiovascular stability under resting conditions during long-duration spaceflight.

WISE 2005: vascular responses to 60-day bed rest in women.

WISE-2005 studied 24 women during a 60-day head down bed rest (HDBR) who look part in an exercise countermeasure (LBNP-treadmill plus flywheel, EX) and no-exercise (No-EX). We conducted a series of experiments to explore changes in cardiovascular function and the ability of EX to prevent these changes. Resting arterial diameter in the arm was not affected but the leg arteries (femoral and popliteal) were significantly reduced in Np-EX, but was increased in EX. In this study we report on drug stimulated responses with sublingual nitroglycerin and infused isoproterenol. Heart rate increased in response to nitroglycerin with larger increases in No-EX after HDBR. Likewise during isoproterenol infusion the HR increase was greater after HDBR in the No-EX group. In all cases, the higher HR was associated with lower stroke volume in No-EX while stroke volume was protected in EX. These data do not support a change in sensitivity of beta-adrenergic receptors after HDBR. The leg vascular resistance decreased in response to isoproterenol and it decreased to a greater extent in No-EX than EX. These data were consistent with observations of lower leg vascular resistance during orthostatic challenge tests after HDBR. We conclude that consistent changes in cardiovascular function in the No-EX were detected by different methods that point to mechanisms contributing to orthostatic intolerance after HDBR.

WISE-2005: orthostatic tolerance is poorly predicted by acute changes in cardiovascular variables.

Twenty-four (24) healthy women from 25-40 years of age underwent orthostatic tolerance tests consisting of passive tilt and lower body negative pressure before and after completing 60-days of continuous -6 degree head down tilt bed rest (HDBR). Prior to HDBR, participants were assigned to one of three groups: control, exercise or nutrition. We aimed to identify any acute head up tilt changes in mean arterial pressure, pulse pressure, total peripheral resistance, cardiac output, stroke volume, or heart rate, which might predict tolerance or changes in tolerance with HDBR. Generally, these attempts were largely unsuccessful. The results indicate that the mechanisms of orthostatic failure are not strongly related to the way in which the body responds to the initial challenge. Additionally, the observation that some variables were predictive of tolerance before and not after tilt may indicate a change in the strategies used to maintain blood pressure, or differential adaptations to HDBR.

WISE 2005: altered cerebrovascular autoregulation after 60 day head-down bed rest.

We tested the hypothesis that 60 days of head-down bed rest (HDBR) would affect cerebrovascular autoregulation and that this change would be correlated with changes in tolerance to the upright posture. Twenty-four healthy women (32 +/- 4 yrs) participated in a 60-d bed rest study at the MEDES Clinic in Toulouse, France. End tidal CO2 (ETCO2), continuous blood pressure (BP), middle cerebral artery (MCA) velocity and time to presyncope (endpoint) were measured during an orthostatic tolerance test conducted before/after bed rest. Given the large range of change in tolerance even within assigned countermeasure groups, we separated subjects for this analysis on the basis of the change in endpoint (Delta endpoint) pre- to post-bed rest. Autoregulation and CO2 responsiveness were evaluated on a different day from a two-breath test with intermittent hypercapnic exposure. Autoregressive moving average (ARMA) modeled the two confounding inputs, BP and CO2, on cerebrovascular blood flow. The cerebrovascular resistance index (CVRi) was expected to decrease following a decrease in BP at the MCA to assist in maintenance of cerebral blood flow. Subjects with the smallest Delta endpoint after bed rest had a 78% increase in the gain of the BP --> CVRi response. Meanwhile, the groups with greater decline in orthostatic tolerance post-HDBR had no change in the gain of this response. ETCO2 was lower overall following HDBR, decreasing from 41.8 +/- 3.4 to 40.2 +/- 3.0 in supine rest, 37.9 +/- 3.4 to 33.3 +/- 4.0 in early tilt, and 29.5 +/- 4.4 to 27.1 +/- 5.1 at pre-syncope. There was however, higher MCA velocity at any ETCO2 for post- compared to pre-HDBR. In summary, changes in autoregulation were found only in those subjects who had the smallest change from pre- to post-HDBR orthostatic tolerance. The changes may assist in buffering changes in cerebral blood flow during orthostatic hypotension post-HDBR. The reduction in ETCO2 after bed rest might be due to a change in chemoreceptor response to blood CO2, but the cerebrovascular system seems to have completely compensated.

WISE-2005: reduced cerebral blood flow velocity with nitroglycerin--comparison with common carotid artery blood flow.

During the WISE-2005 study of 24 women, we observed a reduction (21.6 +/- 0.89%, mean +/- SEM) in cerebral blood flow velocity (CBV) measured by transcranial Doppler ultrasound, following 0.3 mg sublingual nitroglycerin (NG). In parallel, we observed quantitative reductions in leg blood flow (47.3 +/- 7.0%) and corresponding reductions in calculated conductance (Conductance = Femoral Flow / Mean Arterial Pressure; 45.7 +/- 7.2%). To determine if the reduction in CBV was the result of reduced cerebral blood flow or dilation of the middle cerebral artery (MCA), the change in CBV in the MCA was compared with changes in quantitative flow measured in the common carotid artery (CCA). The relationship between CBV and CCA blood flow was tested in five men and four women using hyper- and hypo-ventilation to manipulate arterial PCO2. Changes in CCA blood flow were positively correlated with changes in CBV (p<0.001). We then investigated the CBV and CCA flow responses to sublingual NG in an additional two men and six women. Concurrent with the reduction in CBV there was no change in blood flow through the CCA (p>0.05). These results indicate that the decrease in CBV observed in response to NG was probably the result of dilation of the MCA and that total cerebral blood flow was similar after administration of NG. These results suggest regional differences in the vascular responses to NG during the WISE bed rest. Conduit vessels of both the peripheral and cerebral vasculature dilated; however, the resistance vessels in skeletal muscle constricted causing a reduction in blood flow, while the resistance vessels of the brain appeared to be unaffected by NG so that cerebral blood flow remained constant. These results highlight the need to obtain quantitative measures of cerebral blood flow if there is reason to suspect that the diameter of the MCA might not remain constant.

WISE-2005: developing a non-invasive method to monitor cardiovascular deconditioning.

We have determined the gain of the cardiopulmonary baroreflex (CPBR) by measuring the central venous pressure (CVP) by venous catheter and calculating the total peripheral resistance (TPR) from mean arterial pressure (MAP) by Finometer and cardiac output (QD) by Doppler ultrasound. We tested the hypothesis that the BeatScope software of the Finometer, which calculates cardiac stroke volume (SVF) and cardiac output (QF) from the arterial pulse wave, could provide data with which to estimate CVP and TPR. The estimate of QF was linearly related to QD with a correction factor. Further, we found linear relationships between CVP and SVF that allowed us to establish a prediction of CVP from the SVF as the new input to the CPBR. To test the ability of this method to monitor changes in CPBR we are testing the subjects of the WISE-2005 study before and after 50-days of bed rest. We conclude that the TPR can be assessed with the Finometer and without any invasive method to record the CVP.

Heterogeneity of responses to orthostatic stress in homozygous twins.

Early analysis into the role of genetics on cardiovascular regulation has been accomplished by comparing blood pressure and heart rate in homozygous twins during unstressed, resting physiological conditions. However, many variables, including cognitive and environmental factors, contribute to the regulation of cardiovascular hemodynamics. Therefore, the purpose of this study was to determine the hemodynamic response of identical twins to an orthostatic stress, ranging from supine rest to presyncope. Heart rate, arterial blood pressure, middle cerebral artery blood velocity, an index of cerebrovascular resistance, cardiac output, total peripheral resistance, and end-tidal carbon dioxide were measured in 16 healthy monozygotic twin pairs. Five minutes of supine resting baseline data were collected, followed by 5 min of 60 degrees head-up tilt. After 5 min of head-up tilt, lower body negative pressure was applied in increments of 10 mmHg every 3 min until the onset of presyncope, at which time the subject was returned to the supine position for a 5-min recovery period. The data indicate that cardiovascular regulation under orthostatic stress demonstrates a significant degree of variance between identical twins, despite similar orthostatic tolerance. As the level of stress increases, so does the difference in the cardiovascular response within a twin pair. The elevated variance with increasing stress may be due to an increase in the role of environmental factors, as the influential role of genetics nears a functional limit. Therefore, although orthostatic tolerance times were very similar between identical twins, the mechanism involved in sustaining cardiovascular function during increasing stress was different.

Functional mapping of ultraviolet photosensitivity during metamorphic transitions in a salmonid fish, Oncorhynchus mykiss.

Ultraviolet visual sensitivity appears to be reduced and, possibly, lost during smoltification in anadromous populations of salmonid fishes. Similar changes occur in non-anadromous salmonids over a mass range that is associated with smoltification in their anadromous conspecifics. However, in sexually mature adult salmonids, ultraviolet-sensitive cones are present in the dorso-temporal retina, suggesting that ultraviolet sensitivity (i) may be regained with sexual maturity or (ii) might never be completely lost. Both smoltification and the transition to sexual maturity are regulated, in part, by the hormone thyroxine. Thyroxine treatment of juvenile Oncorhynchus mykiss results in precocial developmental changes that mimic smoltification, including a reduction of ultraviolet sensitivity. However, whether loss of ultraviolet sensitivity in O. mykiss or in other species of salmonids is complete during normal development (or in response to thyroxine treatment) is unclear. In the present study, we have 'mapped' topographically ultraviolet photosensitivity during natural and hormone-induced smoltification. Thyroxine-treated O. mykiss juveniles and anadromous steelhead O. mykiss smolts were examined for ultraviolet visual sensitivity by recording compound action potentials from the optic nerve. By selectively illuminating either the dorsal or the ventral retina, we have shown that the reduction of ultraviolet sensitivity occurs primarily in the ventral retina in both groups of fish. Ultraviolet sensitivity remains intact in the dorsal retina.