Antonio Güell

Comparison of a 4-day confinement and head-down tilt on endocrine response and cardiovascular variability in humans

The aim of this study was to determine the effects of a 4-day head-down tilt (HDT; − 6°) and 4-day confinement on several indicators that might reflect a state of cardiovascular deconditioning on eight male subjects. Measurements were made of endocrine responses, heart rate variability and spontaneous baroreflex response (SBR) slope before, during and after each intervention. Plasma volume decreased by 10% after the 4-day HDT. The concentration of active renin was increased and that of urinary atrial natriuretic peptide decreased during the 4-day experiment in both groups. Plasma arginine vasopressin concentration decreased significantly only after 4-day confinement. After the 4-day HDT, one of the spectrum analysis parameters was statistically changed: the parasympathetic indicator decreased significantly (P < 0.05) whereas the sympathetic indicator and the total power spectrum were unaltered. After 4-day confinement spectrum analysis parameters were not statistically altered. A significant decrease of SBR (P < 0.05) was noticed only after the 4-day HDT. These data would suggest that exposure to a 4-day HDT was sufficient to induce a cardiovascular deconditioning which may have been induced by confinement and inactivity.

Activity of the sympathoadrenal system in cosmonauts during 25-day space flight on station Mir

The activity of the sympathoadrenal system in cosmonauts was studied by measuring plasma and urinary catecholamines and their metabolites and conjugates. The appliance Plasma 02 was used for collecting, processing, and storing blood and urine samples from the cosmonauts during the course of a 25-day flight on board the station Mir. Plasma and urine concentrations of adrenaline (A), noradrenaline (NA), and dopamine (DA) as well as urinary levels of vanillylmandelic acid (VMA) and homovanillic acid (HVA), and plasma levels of catecholamine sulphates were determined before, during and after the space flight. Plasma NA levels were slightly elevated on day 9 and plasma A on day 20, whereas plasma DA levels were unchanged. However, most of the changes were within the normal range of control values. Sulphates of plasma catecholamines did not change during flight but they were significantly elevated after landing. Urinary levels of A, NA, DA, VMA, and HVA were comparable with preflight values but were elevated at the different intervals studied after landing. The results obtained suggest that in the short period of about 9 days of the cosmonauts stay in space the sympathoadrenal system was slightly activated indicating a mild stressful influence of the initial period of flight. This short-term space flight compared to long-term flight did not as markedly activate the sympathoadrenal system during the process of re-adaptation to Earths gravity after landing. Our data suggest that weightlessness is not a stressful factor activating the sympathoadrenal system but it sensitizes the responsiveness of this system during the re-adaptation period after space flight.

HAEMODYNAMICS OF LEG VEINS DURING A 30-DAYS-6 HEAD-DOWN BEDREST WITH AND WITHOUT LOWER BODY NEGATIVE PRESSURE

SummaryVenous distensibility of the lower limbs was assessed in six healthy men who were submitted twice successively to 1 month of −6° head-down bedrest, with and without lower body negative pressure (LBNP) (LBNP subjects and control subjects, respectively). Venous capacity (Δ Vv,max, in ml·100 ml−1) of the legs was determined by mercury strain gauge plethysmography with venous occlusion. Plethysmographic measurements were made on each subject before (Dc), during (D6 and D20) and after (5th day of recovery, D+5) bedrest. During bedrest, LBNP was applied daily, several times a day to the subjects submitted to this procedure. Results showed a gradual increase in Vv,max (ml·100 ml−1) throughout the bedrest, both in the control group [Δ Vv,max = 2.11 SD 0.54 at Dc, 2.69 SD 0.29 at D6, 4.39 SD 2.08 at D20, 2.39 SD 0.69 at D+5, P<0.001 (ANOVA)] and in the LBNP group [Δ Vv,max = 2.07 SD 0.71 at Dc, 2.85 SD 1.19 at D6, 3.75 SD 1.74 at D20, 2.43 SD 0.94 at D+5, P<0.001 (ANOVA)], without significant LBNP effect. These increases were of the same order as those encountered during spaceflight. It is concluded that −6° head-down bedrest is a good model to simulate the haemodynamic changes induced by exposure to weightlessness and that LBNP did not seem to be a good technique to counteract the adverse effects of weightlessness on the capacitance vessels of the lower limbs. This latter conclusion raises the question of the role and magnitude of leg venous capacitance in venous return and cardiac regulation.

Impact of a Four‐Day Head‐Down Tilt (–6°) on Lidocaine Pharmacokinetics Used as Probe to Evaluate Hepatic Blood Flow

The impact of a microgravity simulation using a head‐down tilt (–6°) on lidocaine pharmacokinetics used as a probe to evaluate hepatic blood flow is discussed. Eight healthy male subjects were selected for a 7‐day study, including a 4‐day head‐down tilt from day 2 to day 5. Subjects were given 1 mg/kg of lidocaine on days 1 through 5 and 7. Blood sampling, cardiac output, and hepatic artery blood flow velocity measurements were done within 6 hours after administration. Cardiac output increased significantly during head‐down tilt, and returned to basal values during the recovery period. Blood flow velocity in the hepatic artery increased during the first day of the down tilt. Slight side effects (buzzing noise in the ears and sleepy feeling) were reported within minutes after the injection of lidocaine. Lidocaine disposition was modified during head‐down tilt: a significant decrease in maximal concentration (1.47 ± 0.26 mg/L on day 1 and 0.96 ± 0.30 mg/L on day 2); an increase in elimination clearance from 8.24 ± 3.22 mL/kg • minutes−1 to 11.63 ± 3.00 mL/kg • minutes−1; an increase in volume of distribution on day 2 and a decrease to lower than basal value on the other days (2.77 ± 1.73 L/kg on day 1 and 2.33 ± 0.48 L/kg on day 7). Half‐life regularly decreased from 264 ± 210 minutes to 160 ± 60 minutes between day 1 and day 7. With the exception of day 1, no correlation was found between blood flow in the hepatic artery and lidocaine clearance, probably owing to the lack of precision of echo Doppler measurement, which only permitted indirect assessment. The reported pharmacokinetic modifications suggested that the dosage of drugs such lidocaine must be adapted during long‐term administration in microgravity conditions by increasing the dose or reducing the interval of drug intake.

Effects of an 11-day spaceflight on the choroid plexus of developing rats

Cellular distributions of ezrin, a cytoskeletal protein involved in apical cell differentiation in choroid plexus, and carbonic anhydrase II, which is partly involved in the cerebrospinal fluid production, were studied by immunocytochemistry, at the level of choroidal epithelial cells from the lateral, third and fourth ventricles in normal or experimental fetuses, in parallel with the ultrastructure of apical microvilli, observed by transmission electron microscopy. We compared choroid plexuses from developing normal rats (gestational day 15 to birth) with choroid plexuses from 20-day-old rat fetuses, developed for 11 days in space, aboard a space shuttle (NASA STS-66 mission, NIH-R1 experiments), from gestational day 9 to day 20. The main changes observed in fetuses developed in space were demonstrated by immunocytochemistry and concerned the distribution of ezrin and carbonic anhydrase II. Thus, in fetuses developing in space, ezrin was strongly detected in the choroidal cytoplasm and weakly associated to the membrane in the apical domain of the choroid plexus from the fourth ventricle. Such alterations suggested that choroid plexus from rat fetal brain displays a delayed maturation under a micro-gravitational environment. In contrast, intense immunoreactions to anti-carbonic anhydrase II antibodies showed that this enzyme is very abundant in rats developed in space, compared to ground control fetuses.

Chapter 5 Pharmacology in Space: Pharmacokinetics

Publisher Summary This chapter provides an overview of pharmacokinetics in space. It reviews the possible pharmacokinetic mechanisms affected by microgravity. During spaceflight the human organism undergoes various physiological modifications due to its adaptation to weightlessness. Some of these modifications last only a short time, while others persist during the entire flight. During this adaptation process the human organism reaches a new state of homeostasis. The physiological and biochemical modifications taking place during spaceflight are chronologically divided in three phases: the adaptation phase, the equilibrium phase, and the landing phase. The use of a drug as a probe permits to estimate the changes in specific pharmacokinetic parameters during spaceflight. Spaceflight is known to change many physiological parameters. The pharmacokinetics of drug disposition is determined by the combination of several complex phenomena. Each step of this process may be influenced by physiopathological changes occurring in spaceflight.

Application of space technologies to the surveillance and modelling of waterborne diseases

Earth observing satellites, global positioning and geographic information systems are new tools that currently enable the scientific community to integrate ecological, environmental and medical data to develop predictive models for disease surveillance and modelling. A number of investigators have explored remotely sensed environmental factors that might be associated with waterborne disease ecology and human transmission risk. However, health specialists have not been fully familiarized with the capabilities of space technology, and in some cases it has not proved to be the wonder tool that scientists expected. New satellite capabilities and new sensors now allow exploration of risk factors previously beyond the capabilities of remote sensing and put researchers in a position to analyze the effects of environment on disease outbreaks.

Lower body negative pressure as a countermeasure against orthostatic intolerance for long term space flight

The effectiveness of lower body negative pressure (LBNP) as a countermeasure against orthostatic intolerance associated with bed rest was investigated. Subjects were exposed to antiorthostatic bedrest at 6 degrees head down tilt, with some exposed to LBNP and some exposed to LBNP with exercise during the bedrest period. Tilt table tests were then performed on all subjects, with heart rate and blood pressure measurements taken. Exposure to LBNP seemed effective in preventing syncope in subjects exposed to bedrest. These results are discussed.

Chapter 4 Pharmacology in Space: Pharmacotherapy

Publisher Summary This chapter discusses the pharmacological kits onboard a spacecraft and reviews the use of drugs in space. The need of a selected group of drugs for the use of astronauts during short-term and long-term spaceflights is discussed. Although the usefulness of these drugs is demonstrated, their use also raises several problems. Physiological changes due to weightlessness may induce changes in pharmacokinetic behavior of drugs and influence their dosage regimen. In vitro studies of the antibacterial activity of antibiotics under space conditions have shown an increased resistance of Escherichia Coli to colistin and kanamycin, and a lowered resistance of Staphylococcus Aureus to oxacillin, chloramphenicol, and erythromycin. To arrive at the most appropriate medical kit for a particular mission, the best trade-off of risk versus benefit for the individual and the mission must always be attempted for any pharmacological agent.

Evaluation of spontaneous baroreflex response after 28 days head down tilt bedrest

The spontaneous baroreflex response was evaluated during supine rest and head up tilt (60 degrees) before and immediately after a 28 day 6 degrees HDT bedrest in 6 healthy adult men (age 30-42 years). Sequences of 3 or more beats where RR-interval and systolic blood pressure changed in the same direction were used to evaluate baroreflex response slope (BRS). Prior to bedrest, the mean BRS and RR-interval were 18.0 +/- 3.9 ms/mm Hg and 926 +/- 61 ms at rest and 10.5 +/- 2.5 ms/mm Hg and 772 +/- 63 ms during the first 10 min of 60 degrees tilt. Following bedrest, these values changed to 15.6 +/- 2.7 ms/mm Hg and 780 +/- 53 ms at rest, and to 6.5 +/- 1.2 ms/mm Hg and 636 +/- 44 ms during tilt. Thus, (1) the spontaneous baroreflex can be evaluated in human subjects during experiments of orthostatic stress; (2) the baroreflex slope was reduced on going from supine to the head up tilt position; and (3) 28 days of bedrest reduced the spontaneous baroreflex slope.