Erythropoietin under real and simulated microgravity conditions in humans

1996 ◽  
Vol 81 (2) ◽  
pp. 761-773 ◽  
Author(s):  
H. C. Gunga ◽  
K. Kirsch ◽  
F. Baartz ◽  
A. Maillet ◽  
C. Gharib ◽  
...  

The aim of this study was to analyze the time course of erythropoietin (EPO) during Earth-bound microgravity simulations such as bed rest, isolation and confinement (IC), head-down tilt (HDT; -6 degrees), and immersion to evaluate which factors could contribute to alterations in EPO under real microgravity conditions during and after short- (< 10 days) and long-term (> 6 mo) spaceflights. During bed rest (24h), no significant changes in EPO could be observed. Subjects confined in a diving chamber facility for 60 days showed a decrease in EPO. In the recovery period a slight increase was observed, but EPO concentrations did not reach the pre-IC control level. In the control period before HDT, subjects showed normal resting values for EPO, but on day 2 of HDT the EPO concentrations were decreased (P < 0.01). Later the EPO levels remained below the control value and were increased after HDT (P < 0.05). After immersion (24 h) increased EPO concentrations could be determined (P < 0.05). During a short-term spaceflight the astronauts showed in-flight (day 4) decreased and unchanged EPO concentrations. During a long-term spaceflight, 24 h after recovery, the cosmonaut showed slightly elevated EPO concentration, which increased markedly during the following days. It is concluded that 1) HDT (-6 degrees) causes a rapid decrease in EPO in humans, 2) IC per se leads to diminished EPO concentrations, 3) EPO regulation in humans during short- and long-term spaceflights might be different, 4) changes in central blood volume, i.e., central venous pressure, seem to be involved in the modulation of EPO production and release under simulated and real microgravity conditions, and 5) the HDT (-6 degrees) Earth-bound simulation reflects mostly the changes in EPO production and release observed under real microgravity conditions in humans.

2021 ◽  
pp. 1-16
Author(s):  
Laurence R. Harris ◽  
Michael Jenkin ◽  
Rainer Herpers

BACKGROUND: Humans demonstrate many physiological changes in microgravity for which long-duration head down bed rest (HDBR) is a reliable analog. However, information on how HDBR affects sensory processing is lacking. OBJECTIVE: We previously showed (25) that microgravity alters the weighting applied to visual cues in determining the perceptual upright (PU), an effect that lasts long after return. Does long-duration HDBR have comparable effects? METHODS: We assessed static spatial orientation using the luminous line test (subjective visual vertical, SVV) and the oriented character recognition test (PU) before, during and after 21 days of 6° HDBR in 10 participants. Methods were essentially identical as previously used in orbit (25). RESULTS: Overall, HDBR had no effect on the reliance on visual relative to body cues in determining the PU. However, when considering the three critical time points (pre-bed rest, end of bed rest, and 14 days post-bed rest) there was a significant decrease in reliance on visual relative to body cues, as found in microgravity. The ratio had an average time constant of 7.28 days and returned to pre-bed-rest levels within 14 days. The SVV was unaffected. CONCLUSIONS: We conclude that bed rest can be a useful analog for the study of the perception of static self-orientation during long-term exposure to microgravity. More detailed work on the precise time course of our effects is needed in both bed rest and microgravity conditions.


1997 ◽  
Vol 82 (6) ◽  
pp. 1726-1733 ◽  
Author(s):  
Francis Louisy ◽  
Philippe Schroiff ◽  
Antonio Güell

Louisy, Francis, Philippe Schroiff, and Antonio Güell.Changes in leg vein filling and emptying characteristics and leg volumes during long-term head-down bed rest. J. Appl. Physiol. 82(6): 1726–1733, 1997.—Leg venous hemodynamics [venous distensibility index (VDI), arterial flow index (AFI), half-emptying time (T1/2)], and leg volumes (LV) were assessed by mercury strain-gauge plethysmography with venous occlusion and volometry, respectively, in seven men before, during, and after 42 days of 6° head-down bed rest. Results showed a high increase in VDI up to day 26 of bed rest (+50% vs. control at day 26, P < 0.05), which tended to subside thereafter (+20% increase vs. control value at day 41, P < 0.05). VDI changes were associated with parallel changes in T1/2 (+54% vs. control at day 26 of bed rest, P < 0.05, and +25% vs. control at day 41, P < 0.05) and with a decrease in AFI (−49% at day 41 vs. control, P < 0.05). LV continuously decreased throughout bed rest (−13% vs. control at day 41, P < 0.05) but was correlated with VDI only during the first month of bed rest. These results show that during long-term 6° head-down bed rest alterations of leg venous compliance are associated with impairment of venous emptying capacities and arterial flow. Changes in skeletal muscle mass and fluid shifts may account for venous changes during the first month of bed rest but, subsequently, other physiological factors, to be determined, may also be involved in leg venous hemodynamic alterations.


2008 ◽  
Vol 23 (3) ◽  
pp. 253-257
Author(s):  
Olivia Adayr Xavier Suarez ◽  
Katsumasa Hoshino

PURPOSE: The usefulness of body movements that occur during sleep when assessing perinatal asphyxia and predicting its long-term consequences is contradictory. This study investigated whether neonatal rats manifest these movements in compensatory rebound after asphyxia, and if these alterations play an important role in its pathogenesis. METHODS: Eight neonatal rats (aged 6-48h) were implanted with small EMG and EKG electrodes and sleep movements were recorded over a 30-minute control period. Recordings were continued during asphyxia caused by the enclosure of the animal in a polyvinyl sheet for 60 minutes, followed by a 30-minute recovery period. RESULTS: Heart rate was lowered to bradycardic level during asphyxia causing behavioral agitation and increased waking time during the initial phase (30 minutes). Sleep-related movements were also significantly reduced from 12.5 ± 0.5 (median ± SE/2min) to 9.0 ± 0.44 in the final half of the period (Anova, p<0.05). Movement frequency increased in the recovery period to 15.0 ± 0.49 (Anova, p<0.05). CONCLUSION: These data show that newborn rats present compensatory rebound of body movements during sleep which may help in the diagnosis of asphyxia and other problems related to sleep parameters.


1994 ◽  
Vol 267 (2) ◽  
pp. R380-R386 ◽  
Author(s):  
C. Y. Cheung

Endothelin is a potent vasoconstrictor synthesized by vascular endothelial cells. In the adult, endothelin has been shown to stimulate the release of atrial natriuretic factor (ANF) through a direct action on atrial cardiocytes. The present study was designed to investigate, in the fetus, whether endothelin would similarly release ANF into the circulation. In addition, the effects of endothelin on fetal cardiovascular and urinary functions were explored. Chronically catheterized ovine fetuses between 126 and 139 days gestation (term 147 days) were used for the study. After a 30-min control period, the fetuses were infused intravenously with vehicle (n = 6) or endothelin-1 (n = 9) at 25 ng.min-1.kg-1 for 30 min, and this was followed by a 60-min recovery period. In response to endothelin infusion, plasma ANF levels were significantly elevated. Endothelin infusion acutely increased fetal arterial pressure without affecting venous pressure. Fetal heart rate decreased, and blood volume was reduced. Fetal urine flow rate and urinary excretion of electrolytes did not change during the endothelin infusion but were elevated during the recovery period. The fetus developed hypoxia and acidemia. Thus our study demonstrates that endothelin is effective in stimulating ANF release in the fetus, and this effect appears to be unrelated to the venous pressure changes. In addition, the results suggest that endothelin is a potent vasoconstrictor of the fetal systemic and umbilical vascular beds. The decrease in blood volume and increase in urinary excretion of fluid and electrolytes in response to endothelin are consistent with the known actions of ANF, which is elevated during endothelin infusion.


1969 ◽  
Vol 47 (1) ◽  
pp. 1-6 ◽  
Author(s):  
Alison M. Jarratt ◽  
N. W. Nowell

Blood sugar levels and adrenal weights (where possible) were recorded, after a 24-h fast, in normal intact, adrenal-demedullated, and adrenalectomized rats kept at 4 °C for up to 130 days. These were compared with data from control rats kept at 21 °C. Hypoglycemia (relative to the control value) prevailed in both normal intact and, more profoundly, in adrenal-demedullated rats during the first 24 h of chilling but no deaths occurred. Adrenalectomized rats, whose blood sugar level at 21 °C was subnormal, at 4 °C soon showed extreme hypoglycemia and died. More prolonged chilling in normal intact rats resulted in hyperglycemia which lasted until after the 25th day. In contrast, in chilled adrenal-demedullated animals the blood sugar remained at the control level throughout this period. At the 50th day the blood sugar of normal intact animals fell to the control value and remained so thereafter. A similar fall in adrenal-demedullated rats resulted in hypoglycemia, but a rise to control values was recorded from the 75th day. Adrenocortical hypertrophy was generally more extensive in the demedullated animals than in the normal intact animals but was absent in both groups by the 130th day. We conclude that the adrenal medulla, besides helping to provide extra blood glucose during exposure to short-term chilling, is also responsible for the sustained hyperglycemia of rats chilled for prolonged periods and thus assists in their acclimation to long-term cold stress.


2007 ◽  
Vol 293 (2) ◽  
pp. H1265-H1272 ◽  
Author(s):  
Antoine Ayer ◽  
Vladan Antic ◽  
Abdul G. Dulloo ◽  
Bruce N. Van Vliet ◽  
Jean-Pierre Montani

Whereas the sympathetic nervous system has a well-established role in blood pressure (BP) regulation, it is not clear whether long-term levels of BP are affected by parasympathetic function or dysfunction. We tested the hypothesis that chronic blockade of the parasympathetic nervous system has sustained effects on BP, heart rate (HR), and BP variability (BPV). Sprague-Dawley rats were instrumented for monitoring of BP 22-h per day by telemetry and housed in metabolic cages. After the rats healed from surgery and a baseline control period, scopolamine methyl bromide (SMB), a peripheral muscarinic antagonist, was infused intravenously for 12 days. This was followed by a 10-day recovery period. SMB induced a rapid increase in mean BP from 98 ± 2 mmHg to a peak value of 108 ± 2 mmHg on day 2 of the SMB infusion and then stabilized at a plateau value of +3 ± 1 mmHg above control ( P < 0.05). After cessation of the infusion, the mean BP fell by 6 ± 1 mmHg. There was an immediate elevation in HR that remained significantly above control on the last day of SMB infusion. SMB also induced a decrease in short-term (within 30-min periods) HR variability and an increase in both short-term and long-term (between 30-min periods) BPV. The data suggest that chronic peripheral muscarinic blockade leads to modest, but sustained, increases in BP, HR, and BPV, which are known risk factors for cardiovascular morbidity.


2003 ◽  
Vol 94 (1) ◽  
pp. 53-59 ◽  
Author(s):  
Mark Babcock ◽  
Mahdi Shkoukani ◽  
Salah E. Aboubakr ◽  
M. Safwan Badr

Long-term facilitation (LTF) is a prolonged increase in ventilatory motor output after episodic peripheral chemoreceptor stimulation. We have previously shown that LTF is activated during sleep following repetitive hypoxia in snorers (Babcock MA and Badr MS. Sleep 21: 709–716, 1998). The purpose of this study was 1) to ascertain the relative contribution of inspiratory flow limitation to the development of LTF and 2) to determine the effect of eliminating inspiratory flow limitation by nasal CPAP on LTF. We studied 25 normal subjects during stable non-rapid eye movement sleep. We induced 10 episodes of brief repetitive isocapnic hypoxia (inspired O2 fraction = 8%; 3 min) followed by 5 min of room air. Measurements were obtained during control and at 20 min of recovery (R20). During the episodic hypoxia study, inspiratory minute ventilation (V˙i) increased from 6.7 ± 1.9 l/min during the control period to 8.2 ± 2.7 l/min at R20 (122% of control; P < 0.05). Linear regression analysis confirmed that inspiratory flow limitation during control was the only independent determinant of the presence of LTF ( P = 0.005). Six subjects were restudied by using nasal continuous positive airway pressure to ascertain the effect of eliminating inspiratory flow limitation on LTF.V˙i during the recovery period was 97 ± 10% ( P > 0.05). In conclusion, 1) repetitive hypoxia in sleeping humans is followed by increasedV˙i in the recovery period, indicative of development of LTF; 2) inspiratory flow limitation is the only independent determinant of posthypoxic LTF in sleeping human; 3) elimination of inspiratory flow limitation abolished the ventilatory manifestations of LTF; and 4) we propose that increased V˙i in the recovery period was a result of preferential recruitment of upper airway dilators by repetitive hypoxia.


1982 ◽  
Vol 60 (12) ◽  
pp. 1519-1525
Author(s):  
David G. Benditt ◽  
Melvin M. Scheinman ◽  
Thomas R. Snow ◽  
Harold C. Strauss

Using standard microelectrode techniques, we evaluated effects of diminished oxygen tension on the magnitude and time course of frequency dependent changes in maximum diastolic transmembrane potential (MDP) and on alteration of action potential duration (APD) in feline Purkinje fibers. MDP was recorded continuously during a control period (cycle length (CL) = 1000 ms), during a 5-min period of rapid drive (CL = 400 ms) and following return to pacing CL = 1000 ms. Rapid drive resulted in hyperpolarization of MDP from control value; and after return to pacing CL = 1000 ms, MDP gradually depolarized, eventually attaining a steady state value within ± 0.5 mV of the control value. The difference between hyperpolarized MDP value and final steady-state value was designated VH, and the decline of MDP towards steady-state value approximated an exponential function (time constant = τVH). Exposure to reduced [Formula: see text] (75 ± 2.1 mmHg vs. control 473 ± 39.1 mmHg) (1 mmHg = 133.322 Pa) resulted in reduction in the magnitude of VH (6.2 ± 3.43 mV vs. 7.8 ± 2.73 mV, mean ± SD, p < 0.005) and shortening of APD within 0–24 min, while measurable prolongation of τVH (75 ± 18.5 vs. 54 ± 9.0 s, p < 0.005) began at 25–49 min following onset of reduced [Formula: see text]. These observations suggest that rate-related changes of MDP in cardiac tisues are oxygen dependent, and they support previously reported analagous observations in nerve which suggested that frequency dependent potential changes may in part reflect alterations of electrogenic Na-K pump activity.


1984 ◽  
Vol 247 (2) ◽  
pp. F352-F364 ◽  
Author(s):  
J. Cardinal ◽  
J. Y. Lapointe ◽  
R. Laprade

Transepithelial (psi T) and basolateral (psi BL) potential difference was measured in rabbit proximal convoluted tubules perfused in vitro. In control solution without protein, the mean psi BL was -54 +/- 2.2 mV (n = 57). Luminal substitution of K by Na had no effect. Complete luminal substitution of glucose and alanine, 110 mM substitution of Na or NaCl produced transient hyperpolarizations of psi BL of 14, 10, and 13 mV, respectively, with a return close to the control value within 4-8 min in all cases. Returning to control solution produced similar time-course transient depolarizations of psi BL of 17, 11, and 16 mV, respectively, again with a return to the control value in 4-10 min. Omission of glucose and alanine in the perfusate produced a decrease in cell volume of 14% that was maximal in 4 min with a complete recovery in the post-control period. A 110 mM luminal or peritubular substitution of Cl by cyclamate produced no significant effect on psi BL after taking into account the large psi T generated by the diffusion of Cl across the paracellular pathway. On the other hand, complete peritubular substitution of K by Na and 110 mM substitution of Na or NaCl produced sustained but reversible depolarizations of psi BL of 37.5, 10.2, and 20.4 mV, respectively. The transient nature of the hyperpolarization following luminal substitution of glucose, alanine, or Na can be interpreted in terms of changes in the intracellular sodium activity that would affect the Na-K-ATPase pump. Similarly, the sustained depolarization seen after a peritubular substitution of K and Na would also be compatible with a decrease in the basolateral ionic pump activity.


1979 ◽  
Vol 237 (4) ◽  
pp. H449-H454 ◽  
Author(s):  
G. M. Hockel ◽  
A. W. Cowley

The effects of continuous intrarenal prostaglandin E2 (PGE2) infusion (7 days) on sodium and water balance, plasma renin activity (PRA), and sodium and water balance, plasma renin activity (PRA), and mean arterial pressure (MAP) were examined in conscious, unilaterally nephrectomized dogs maintained on a fixed sodium intake of 55 meq/day. PGE2 infusion (2 microgram/min) resulted in a sustained threefold increase in both urine output and water intake without a measurable change in glomerular filtration rate. PRA increased from 0.4 +/- 0.1 during the control period to 2.2 +/- 0.9 ng AI.ml-1.h-1 on day 1 and averaged 3.6 +/- 0.5 for the remaining 6 days of PGE2 infusion. Concurrently, MAP increased from 102 +/- 3 to a maximum of 117 +/- 4 mmHg on day 5; changes in PRA and MAP were significantly correlated (r = 0.96, P less than 0.001). Sodium excretion increased from 54.5 +/- 3 to 88.0 +/- 19 meq/day on day 1, and then declined to an average of 64.8 +/- 1 meq/day for the remaining 6 days of infusion. All variables returned to the control level during the recovery period. Intravenous infusion of PGE2 (2 microgram/min) yielded directionally similar but statistically insignificant effects. It is concluded that chronic intrarenal PGE2 infusion results in marked diuresis, polydipsia, a moderate loss of sodium, enhanced PRA, and mild hypertension.


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