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Efficacy of fluid loading as a countermeasure to the hemodynamic and hormonal changes of 28-h head-down bed rest.
Edgell, H, Grinberg, A, Beavers, KR, Gagné, N, Hughson, RL
Physiological reports. 2018;(19):e13874
Abstract
After exposure to microgravity, or head-down bed rest (HDBR), fluid loading is often used with the intent of increasing plasma volume and maintaining mean arterial pressure during orthostatic stress. Nine men (aged 18-32 years) underwent three randomized trials with lower body negative pressure (LBNP) before and after: (1) 4-h of sitting with fluid loading (1 g sodium chloride/125 mL of water starting 2.5-h before LBNP), (2) 28-h of 6-degree HDBR without fluid loading, and (3) 28-h of 6-degree HDBR with fluid loading. LBNP was progressive from 0 to -40 mmHg. After 28-h HDBR, fluid loading did not protect against the loss of plasma volume (-280 ± 64 mL without fluid loading, -207 ± 86 with fluid loading, P = 0.472) nor did it protect against a drop of mean arterial pressure (P = 0.017) during LBNP (Post-28 h HDBR response from 0 to -40 mmHg LBNP 88 ± 4 to 85 ± 4 mmHg without fluid loading and 93 ± 4 to 88 ± 5 mmHg with fluid loading, P = 0.557 between trials). However, fluid loading did protect against the loss of stroke volume index and central venous pressure observed after 28-h HDBR. Fluid loading also attenuated the increase of angiotensin II seen after 28-h HDBR and throughout the LBNP protocol (Post-28 h HDBR response from 0 to -40 mmHg LBNP 16.6 ± 3.4 to 23.7 ± 5.0 pg/mL without fluid loading and 6.1 ± 0.8 to 12.2 ± 2.3 pg/mL with fluid loading, P < 0.001 between trials). Our results indicate that fluid loading did not protect against plasma volume loss due to HDBR or change blood pressure responses to LBNP. However, changes in central venous pressure, stroke volume and fluid regulatory hormones could potentially influence longer duration studies and those with more severe orthostatic stress.
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An international collaboration studying the physiological and anatomical cerebral effects of carbon dioxide during head-down tilt bed rest: the SPACECOT study.
Marshall-Goebel, K, Mulder, E, Donoviel, D, Strangman, G, Suarez, JI, Venkatasubba Rao, C, Frings-Meuthen, P, Limper, U, Rittweger, J, Bershad, EM
Journal of applied physiology (Bethesda, Md. : 1985). 2017;(6):1398-1405
Abstract
Exposure to the microgravity environment results in various adaptive and maladaptive physiological changes in the human body, with notable ophthalmic abnormalities developing during 6-mo missions on the International Space Station (ISS). These findings have led to the hypothesis that the loss of gravity induces a cephalad fluid shift, decreased cerebral venous outflow, and increased intracranial pressure, which may be further exacerbated by increased ambient carbon dioxide (CO2) levels on the ISS. Here we describe the SPACECOT study (studying the physiological and anatomical cerebral effects of CO2 during head-down tilt), a randomized, double-blind crossover design study with two conditions: 29 h of 12° head-down tilt (HDT) with ambient air and 29 h of 12° HDT with 0.5% CO2 The internationally collaborative SPACECOT study utilized an innovative approach to study the effects of headward fluid shifting induced by 12° HDT and increased ambient CO2 as well as their interaction with a focus on cerebral and ocular anatomy and physiology. Here we provide an in-depth overview of this new approach including the subjects, study design, and implementation, as well as the standardization plan for nutritional intake, environmental parameters, and bed rest procedures.NEW & NOTEWORTHY A new approach for investigating the combined effects of cephalad fluid shifting and increased ambient carbon dioxide (CO2) is presented. This may be useful for studying the neuroophthalmic and cerebral effects of spaceflight where cephalad fluid shifts occur in an elevated CO2 environment.
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3.
21 Days head-down bed rest induces weakening of cell-mediated immunity - Some spaceflight findings confirmed in a ground-based analog.
Kelsen, J, Bartels, LE, Dige, A, Hvas, CL, Frings-Meuthen, P, Boehme, G, Thomsen, MK, Fenger-Grøn, M, Dahlerup, JF
Cytokine. 2012;(2):403-9
Abstract
Several studies indicate a weakening of cell-mediated immunity (CMI) and reactivation of latent herpes viruses during spaceflight. We tested the hypothesis that head-down bed rest (HDBR), a ground-based analog of spaceflight, mimics the impact of microgravity on human immunity. Seven healthy young males underwent two periods of 3 weeks HDBR in the test facility of the German Aerospace Center. As a nutritional countermeasure aimed against bone demineralisation, 90 mmol potassium bicarbonate (KHCO(3)) was administered daily in a crossover design. Blood samples were drawn on five occasions. Whole blood was stimulated with antigen i.e. Candida albicans, purified protein derivative (PPD) tuberculin, tetanus toxoid and Cytomegalovirus (CMV) (CMV-QuantiFERON). Flow cytometric analysis included CD4(+)CD25(+)CD127(-)FOXP3(+) regulatory T cells (Tregs), γδ T cells, B cells, NK cells and dendritic cells. In one of the two bed rest periods, we observed a significant decrease in production of interleukin-2 (IL-2), interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α) following phytohemagglutinin (PHA) stimulation, with a rapid normalization being observed after HDBR. The cytokine levels showed a V-shaped pattern that led to a relativeTh2-shift in cytokine balance. Only three individuals responded to the specific T cell antigens without showing signs of an altered response during HDBR, nor did we observe reactivation of CMV or Epstein-Barr virus (EBV). Of unknown significance, dietary supplementation with KHCO(3) counteracted the decrease in IL-2 levels during HDBR, while there was no impact on other immunological parameters. We conclude that discrete alterations in CMI may be induced by HDBR in selected individuals.
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Effects of encouraged water drinking on thermoregulatory responses after 20 days of head-down bed rest in humans.
Sato, M, Kanikowska, D, Iwase, S, Shimizu, Y, Inukai, Y, Nishimura, N, Sugenoya, J
International journal of biometeorology. 2009;(5):443-9
Abstract
We tested the hypothesis that encouraged water drinking according to urine output for 20 days could ameliorate impaired thermoregulatory function under microgravity conditions. Twelve healthy men, aged 24 +/- 1.5 years (mean +/- SE), underwent -6 degrees head-down bed rest (HDBR) for 20 days. During bed rest, subjects were encouraged to drink the same amount of water as the 24-h urine output volume of the previous day. A heat exposure test consisting of water immersion up to the knees at 42 degrees C for 45 min after a 10 min rest (baseline) in the sitting position was performed 2 days before the 20-day HDBR (PRE), and 2 days after the 20-day HDBR (POST). Core temperature (tympanic), skin temperature, skin blood flow and sweat rate were recorded continuously. We found that the -6 degrees HDBR did not increase the threshold temperature for onset of sweating under the encouraged water drinking regime. We conclude that encouraged water drinking could prevent impaired thermoregulatory responses after HDBR.
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5.
Effects of tilting and volume loading on plasma levels and urinary excretion of relaxin, NT-pro-ANP, and NT-pro-BNP in male volunteers.
Heringlake, M, Heide, C, Bahlmann, L, Eichler, W, Pagel, H, Schmucker, P, Wergeland, R, Armbruster, FP, Klaus, S
Journal of applied physiology (Bethesda, Md. : 1985). 2004;(1):173-9
Abstract
The polypeptide relaxin (RLX) has been suggested to play a role in cardiorenal integration and to be related to the natriuretic peptide system. We hence examined the effects of variations in thoracic blood volume and intravenous volume loading on plasma and urinary RLX levels and associated changes in natriuretic peptide levels in healthy men. Two groups of eight subjects were randomly tilted into a 15 degrees feet-down or a 15 degrees head-down position. Ten volunteers were crossover subjected to an infusion of 15 ml/kg of 0.9% NaCl (over 60 min) or control during an observation period of 10 h. Blood and urine were sampled at timed intervals. RLX, NH(2)-terminal prohormones of atrial natriuretic peptide (NT-pro-ANP), and NH(2)-terminal prohormones of brain natriuretic peptide (NT-pro-BNP) were determined by enzyme, radio-, and electrochemoluminescence immunoassays, respectively. NT-pro-ANP levels (in percentage of baseline levels) were higher (P < 0.05) during the head-down (124 +/- 13%) than during the feet-down position (82 +/- 6%). NT-pro-BNP and RLX were not affected by tilting. Volume loading induced a short-lasting increase in plasma NT-pro-ANP, a delayed increase in plasma NT-pro-BNP, had no effect on plasma RLX, and induced a parallel increase in urine flow, renal excretion of sodium, RLX, and NT-pro-BNP. It is concluded that variations in thoracic blood volume in healthy men are not associated with variations in plasma RLX. Increased urinary RLX and NT-pro-BNP excretion during volume loading suggest renal production and a possible role of kidney-derived RLX and brain natriuretic peptide in sodium homeostasis in men.
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6.
Fluid volume and osmoregulation in humans after a week of head-down bed rest.
Bestle, MH, Norsk, P, Bie, P
American journal of physiology. Regulatory, integrative and comparative physiology. 2001;(1):R310-7
Abstract
Body fluid homeostasis was investigated during chronic bed rest (BR) and compared with that of acute supine conditions. The hypothesis was tested that 6 degrees head-down BR leads to hypovolemia, which activates antinatriuretic mechanisms so that the renal responses to standardized saline loading are attenuated. Isotonic (20 ml/kg body wt) and hypertonic (2.5%, 7.2 ml/kg body wt) infusions were performed in eight subjects over 20 min following 7 and 10 days, respectively, of BR during constant sodium intake (200 meq/day). BR decreased body weight (83.0 +/- 4.8 to 81.8 +/- 4.4 kg) and increased plasma osmolality (285.9 +/- 0.6 to 288.5 +/- 0.9 mosmol/kgH(2)O, P < 0.05). Plasma ANG II doubled (4.2 +/- 1.2 to 8.8 +/- 1.8 pg/ml), whereas other endocrine variables decreased: plasma atrial natriuretic peptide (42 +/- 3 to 24 +/- 3 pg/ml), urinary urodilatin excretion rate (4.5 +/- 0.3 to 3.2 +/- 0.1 pg/min), and plasma vasopressin (1.7 +/- 0.3 to 0.8 +/- 0.2 pg/ml, P < 0.05). During BR, the natriuretic response to the isotonic saline infusion was augmented (39 +/- 8 vs. 18 +/- 6 meq sodium/350 min), whereas the response to hypertonic saline was unaltered (32 +/- 8 vs. 29 +/- 5 meq/350 min, P < 0.05). In conclusion, BR elicits antinatriuretic endocrine signals, but it does not attenuate the renal natriuretic response to saline stimuli in men; on the contrary, the response to isotonic saline is augmented.
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7.
Increased vasomotor sympathetic nerve activity and decreased plasma nitric oxide release after head-down bed rest in humans: disappearance of correlation between vasoconstrictor and vasodilator.
Kamiya, A, Iwase, S, Michikami, D, Fu, Q, Mano, T, Kitaichi, K, Takagi, K
Neuroscience letters. 2000;(1):21-4
Abstract
We hypothesized that the relationship between resting levels of sympathetic vasoconstrictor nerve traffic and dilator substance nitric oxide (NO) release is altered after exposure to microgravity, resulting in abnormal peripheral resistance. To examine the hypothesis, we assessed muscle sympathetic nerve activity (MSNA) (microneurography), an indicator of NO release (plasma nitrite/nitrate concentrations) and leg vascular resistance (venous occlusion plethysmography) in 20 healthy male volunteers before and after 14 days of 6 degrees head-down bed rest (HDBR), the ground-based analogue of microgravity. MSNA increased, while plasma nitrite/nitrate concentrations decreased after HDBR. A significant positive correlation observed between MSNA and plasma nitrite/nitrate concentrations before HDBR disappeared after HDBR. Leg vascular resistance increased after HDBR. In conclusion, an imbalance between sympathetic vasoconstrictor traffic and NO release might contribute to elevated peripheral vascular resistance following HDBR.