Neuro-ophthalmological changes in healthy females exposed to a 5-day dry immersion: a pilot study.

After exposure to microgravity, astronauts undergo microgravity-induced thoraco-cephalic fluid shift, which may lead to ocular changes called "spaceflight associated neuro-ocular syndrome" (SANS). The onset of SANS may be multifactorial, including a potential elevation in intracranial pressure. Moreover, little is known about the impact of spaceflight on SANS in women due to the fact that fewer female astronauts have spent time in long-term missions. The objective is to determine whether similar ophthalmological changes occur in healthy women after short-term exposure to microgravity. The auto-refractometer was used to determine objective refraction. The best corrected distance visual acuity was assessed with a Monoyer chart. The ocular axial length was assessed using optical biometry. The applanation tonometry was used to determine intraocular pressure. Peripapillary retinal nerve fibre layer thickness (pRNFLT), macular total retinal thickness, and ganglion cell complex (GCC) were measured using optical coherence tomography. Ocular axial length is reduced after DI. pRNFL is thickest after DI specifically in the temporal, temporal-inferior, and nasal-inferior quadrants. Macular total retinal at the inferior quadrant of the 6-mm ring is thickest after DI. Global GCC is thinnest after DI. In this study, 5 days of DI induces slight but significant ophthalmological changes in women. However, these subtle changes do not correspond to criteria defined in SANS.

Autonomic Nervous System Adaptation and Circadian Rhythm Disturbances of the Cardiovascular System in a Ground-Based Murine Model of Spaceflight.

Whether in real or simulated microgravity, Humans or animals, the kinetics of cardiovascular adaptation and its regulation by the autonomic nervous system (ANS) remain controversial. In this study, we used hindlimb unloading (HU) in 10 conscious mice. Blood pressure (BP), heart rate (HR), temperature, and locomotor activity were continuously monitored with radio-telemetry, during 3 days of control, 5 days of HU, and 2 days of recovery. Six additional mice were used to assess core temperature. ANS activity was indirectly determined by analyzing both heart rate variability (HRV) and baroreflex sensitivity (BRS). Our study showed that HU induced an initial bradycardia, accompanied by an increase in vagal activity markers of HRV and BRS, together with a decrease in water intake, indicating the early adaptation to fluid redistribution. During HU, BRS was reduced; temperature and BP circadian rhythms were altered, showing a loss in day/night differences, a decrease in cycle amplitude, a drop in core body temperature, and an increase in day BP suggestive of a rise in sympathetic activity. Reloading induced resting tachycardia and a decrease in BP, vagal activity, and BRS. In addition to cardiovascular deconditioning, HU induces disruption in day/night rhythmicity of locomotor activity, temperature, and BP.

How does head position induced intracranial pressure changes impact sympathetic activity and cerebral blood flow?

PURPOSE: Acute head-down-tilt (HDT) simulates short duration hemodynamic impact of microgravity. We sought to determine whether an increase in ICP caused by acute HDT affects sympathetic nervous system activity and cerebral blood flow velocities (CBFV) in healthy male volunteers. METHODS: HDT protocol was established as follows: basal condition immediately followed by gradual negative angles (-10°, -20° and -30°) lasting 10mn and then a return to basal condition. Velocities in the MCA (CBFV) were monitored using TCD. Sympathetic activity was assessed using MSNA. Baroreflex sensitivity (BRS) was measured using the sequence method. ICP changes were assessed using ultrasonography of the optic nerve sheath diameter (ONSD). Cerebral autoregulation (CA) was evaluated by transfer function and the autoregulatory index (Mxa). RESULTS: Twelve male volunteers (age: 35 ± 2 years) were included. Neither blood pressure nor heart rate was significantly modified during HDT. ONSD increased significantly at each step of HDT and remained elevated during Recovery. MSNA burst incidence increased at -30°. A positive correlation between variations in ONSD and variations in MSNA burst incidence was observed at -20°. CBFV were significantly diminished at -20° and -30. In the LF band, the transfer function coherence was reduced at -30° and the transfer function phase was increased at -30° and during Recovery. DISCUSSION: We found that an acute though modest increase in ICP induced by HDT was associated with an increase of sympathetic activity as assessed by MSNA, and with a reduction of CBFV with preserved CA.

Soluble guanylate cyclase chronic stimulation effects on cardiovascular reactivity in cafeteria diet-induced rat model of metabolic syndrome.

Metabolic syndrome is linked to an increased risk of cardiovascular complications by a mechanism involving mainly decreased nitric oxide (NO) bioavailability and impaired NO-soluble guanylate cyclase (sGC)- cyclic guanosine monophosphate (cGMP) signalling (NO-sGC-cGMP). To further develop this scientific point, this study aimed to investigate the effects of long-term treatment with BAY 41-2272 (a sGC stimulator) on cardiovascular reactivity of spontaneously hypertensive rats (SHR) as a model of metabolic syndrome. SHR were randomly divided into 3 groups: control group, cafeteria diet (CD)-fed group and CD-fed group treated daily with BAY 41-2272 (5 mg/kg) by gastric gavage for 12 weeks. In vivo measurements of body weight, abdominal circumference, blood pressure and glucose tolerance test were performed. At the end of the feeding period, ex vivo cumulative concentration-response curves were performed on isolated perfused heart (isoproterenol (0.1 nM - 1 µM)) and thoracic aorta (phenylephrine (1 nM-10 µM), acetylcholine (1 nM-10 µM), and sodium nitroprusside (SNP) (0.1 nM-0.1 µM)). We showed that chronic CD feeding induced abdominal obesity, hypertriglyceridemia, glucose intolerance and exacerbated arterial hypertension in SHR. Compared to control group, CD-fed group showed a decrease in ß-adrenoceptor-induced cardiac inotropy, in coronary perfusion pressure and in aortic contraction to phenylephrine. While relaxing effects of acetylcholine and SNP were unchanged. BAY 41-2272 long-term treatment markedly prevented arterial hypertension development and glucose intolerance, enhanced the α1-adrenoceptor-induced vasoconstriction, and restored cardiac inotropy and coronary vasodilation. These findings suggest that BAY 41-2272 may be a potential novel drug for preventing metabolic and cardiovascular complications of metabolic syndrome.

Effects of Venoconstrictive Thigh Cuffs on Dry Immersion-Induced Ophthalmological Changes.

Neuro-ophthalmological changes named spaceflight associated neuro-ocular syndrome (SANS) reported after spaceflights are important medical issues. Dry immersion (DI), an analog to microgravity, rapidly induces a centralization of body fluids, immobilization, and hypokinesia similar to that observed during spaceflight. The main objectives of the present study were 2-fold: (1) to assess the neuro-ophthalmological impact during 5 days of DI and (2) to determine the effects of venoconstrictive thigh cuffs (VTC), used as a countermeasure to limit headward fluid shift, on DI-induced ophthalmological adaptations. Eighteen healthy male subjects underwent 5 days of DI with or without VTC countermeasures. The subjects were randomly assigned into two groups of 9: a control and cuffs group. Retinal and optic nerve thickness were assessed with spectral-domain optical coherence tomography (OCT). Optic nerve sheath diameter (ONSD) was measured by ocular ultrasonography and used to assess indirect changes in intracranial pressure (ICP). Intraocular pressure (IOP) was assessed by applanation tonometry. A higher thickness of the retinal nerve fiber layer (RNFL) in the temporal quadrant was observed after DI. ONSD increased significantly during DI and remained higher during the recovery phase. IOP did not significantly change during and after DI. VTC tended to limit the ONSD enlargement but not the higher thickness of an RNFL induced by DI. These findings suggest that 5 days of DI induced significant ophthalmological changes. VTC were found to dampen the ONSD enlargement induced by DI.

Impacts of Microgravity Analogs to Spaceflight on Cerebral Autoregulation.

It is well known that exposure to microgravity in astronauts leads to a plethora physiological responses such as headward fluid shift, body unloading, and cardiovascular deconditioning. When astronauts return to Earth, some encounter problems related to orthostatic intolerance. An impaired cerebral autoregulation (CA), which could be compromised by the effects of microgravity, has been proposed as one of the mechanisms responsible for orthostatic intolerance. CA is a homeostatic mechanism that maintains cerebral blood flow for any variations in cerebral perfusion pressure by adapting the vascular tone and cerebral vessel diameter. The ground-based models of microgravity are useful tools for determining the gravitational impact of spaceflight on human body. The head-down tilt bed rest (HDTBR), where the subject remains in supine position at -6 degrees for periods ranging from few days to several weeks is the most commonly used ground-based model of microgravity for cardiovascular deconditioning. head-down bed rest (HDBR) is able to replicate cephalic fluid shift, immobilization, confinement, and inactivity. Dry immersion (DI) model is another approach where the subject remains immersed in thermoneutral water covered with an elastic waterproof fabric separating the subject from the water. Regarding DI, this analog imitates absence of any supporting structure for the body, centralization of body fluids, immobilization and hypokinesia observed during spaceflight. However, little is known about the impact of microgravity on CA. Here, we review the fundamental principles and the different mechanisms involved in CA. We also consider the different approaches in order to assess CA. Finally, we focus on the effects of short- and long-term spaceflight on CA and compare these findings with two specific analogs to microgravity: HDBR and DI.