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At least 127 records · Page 7

Role of heat shock protein Hsp25 in the response of the orofacial nuclei motor system to physiological stress

Although expression of the small heat shock protein family member Hsp25 has been previously observed in the central nervous system (CNS), both constitutively and upon induction, its function in the CNS remains far from clear. In the present study we have characterized the spatial pattern of expression of Hsp25 in the normal adult mouse brain as well as the changes in expression patterns induced by subjecting mice to experimental hyperthermia or hypoxia. Immunohistochemical analysis revealed a surprisingly restricted pattern of constitutive expression of Hsp25 in the brain, limited to the facial, trigeminal, ambiguus, hypoglossal and vagal motor nuclei of the brainstem. After hyperthermia or hypoxia treatment, significant increases in the levels of Hsp25 were observed in these same areas and also in fibers of the facial and trigeminal nerve tracts. Immunoblot analysis of protein lysates from brainstem also showed the same pattern of induction of Hsp25. Surprisingly, no other area in the brain showed expression of Hsp25, in either control or stressed animals. The highly restricted expression of Hsp25 implies that this protein may have a specific physiological role in the orofacial motor nuclei, which govern precise coordination between muscles of mastication and the pharynx, larynx, and face. Its rapid induction after stress further suggests that Hsp25 may serve as a specific molecular chaperone in the lower cholinergic motor neurons and along their fibers under conditions of stress or injury. Copyright 1998 Elsevier Science B.V.

Non-NASA Center↗

Pulmonary hypoxic vasoconstriction: how strong? How fast?

We have developed a minimally invasive technique for studying regional blood flow in conscious sheep, bypassing the complications of open-chest surgery, flow probes and tracer infusion. We quantitate regional perfusion continuously on the basis of regional clearance of methane (methane is produced in the sheep rumen, enters the circulation and is eliminated nearly completely (greater than 95%) in the lung). Tracheal intubation with a dual-lumen catheter isolates the gas exchange of the right apical lobe (RAL; less than 15% of the lung) from that of the remainder of the lung, which serves as a control (CL). We measure RAL and CL methane elimination by entraining expirates in constant flows, sampled continuously for methane. Results obtained with this technique and from regional oxygen uptake are in excellent agreement. We have found that hypoxic vasoconstriction is far more potent and stable during eucapnic hypoxia than during hypocapnic hypoxia. The time course of the vasoconstriction suggests that many of the data in the literature may have been obtained prior to steady state.

NASA Discipline Regulatory Physiology↗

Risk Assessment of Physiological Effects of Atmospheric Composition and Pressure in Constellation Vehicles

To limit the risk of fire and reduce denitrogenation time to prevent decompression sickness to support frequent extravehicular activities on the Moon, a hypobaric (PB = 414 mmHg) and mildly hypoxic (ppO2 = 132 mmHg, 32% O2 - 68% N2) living environment is considered for the Crew Exploration Vehicle (CEV) and Lunar Surface Access Module (LSAM). With acute change in ppO2 from 145-178 mmHg at standard vehicular operating pressure to less than 125 mmHg at desired lunar surface vehicular operating pressures, there is the possibility that some crewmembers may develop symptoms of Acute Mountain Sickness (AMS). The signs and symptoms of AMS (headache plus nausea, dizziness, fatigue, or sleeplessness), could impact crew health and performance on lunar surface missions. An exhaustive literature review on the topic of the physiological effects of reduced ppO2 and absolute pressure as may contribute to the development of altitude symptoms or AMS was performed. The results of the nine most rigorous studies were collated, analyzed and contents on AMS and hypoxia symptoms summarized. There is evidence for an absolute pressure effect per se on AMS, so the higher the altitude for a given hypoxic alveolar O2 partial pressure (PAO2), the greater the AMS response. About 25% of adults are likely to experience mild AMS near 2,000 m altitude following a rapid ascent from sea level while breathing air (6,500 feet, acute PAO2 = 75 mmHg). The operational experience with the Shuttle staged denitrogenation protocol at 528 mmHg (3,048 m) while breathing 26.5% O2 (acute PAO2 = 85 mmHg) in astronauts adapting to microgravity suggests a similar likely experience in the proposed CEV environment. We believe the risk of mild AMS is greater given a PAO2 of 77 mmHg at 4,876 m altitude while breathing 32% O2 than at 1,828 m altitude while breathing 21% O2. Only susceptible astronauts would develop mild and transient AMS with prolonged exposure to 414 mmHg (4,876 m) while breathing 32% O2 (acute PAO2 = 77 mmHg). So the following may be employed for operational risk reduction: 1) develop procedures to increase PB as needed in the CEV, and use a gradual or staged reduction in cabin pressure during lunar outbound; 2) train crews for symptoms of hypoxia, to allow early recognition and consider pre-adaptation of crews to a hypoxic environment prior to launch, 3) consider prophylactic acetazolamide for acute pressure changes and be prepared to treat any AMS associated symptoms early with both carbonic anhydrase inhibitors and supplemental oxygen.

Scheuring, Richard A.↗

Hindlimb Suspension as a Model to Study Ophthalmic Complications in Microgravity Status Report: Optimization of Rat Retina Flat Mounts Staining to Study Vascular Remodeling

Preliminary data from a prior tissue‐sharing experiment has suggested that early growth response protein‐1 (Egr1), a transcription factor involved in various stress responses in the vasculature, is induced in the rat retina after 14 days of hindlimb suspension (HS) and may be evidence that mechanical stress is occurring secondary to the cephalad fluid shift. This mechanical stress could cause changes in oxygenation of the retina, and the subsequent ischemia‐ or inflammation‐driven hypoxia may lead to microvascular remodeling. This microvascular remodeling process can be studied using image analysis of retinal vessels and can be then be quantified by the VESsel GENeration Analysis (VESGEN) software, a computational tool that quantifies remodeling patterns of branching vascular trees and capillary or vasculogenic networks. Our project investigates whether rodent HS is a valid model to study the effects of simulated‐weightlessness on ocular structures and their relationship with intracranial pressure (ICP). One of the hypotheses to be tested is that HS‐induced cephalad fluid shift is accompanied by vascular engorgement that produces changes in retinal oxygenation, leading to oxidative stress, hypoxia, microvascular remodeling, and cellular degeneration. We have optimized the procedure to obtain flat mounts of rat retina, staining of the endothelial lining in vasculature and acquisition of high quality images suitable for VESGEN analysis. Briefly, eyes were fixed in 4% paraformaldehyde for 24 hours and retinas were detached and then mounted flat on microscope slides. The microvascular staining was done with endothelial cell‐specific isolectin binding, coupled to Alexa‐488 fluorophore. Image acquisition at low magnification and high resolution was performed using a new Leica SP8 confocal microscope in a tile pattern across the X,Y plane and multiple sections along the Z‐axis. This new confocal microscope has the added capability of dye separation using the Linear Unmixing method and allows us to remove the autofluorescence originating from the photoreceptor layer. In summary, we have an improved method for studying the retinal microvasculature that will provide an increase in the quality of images captured and will be applied throughout the various animal cohorts of the recentlyinitiated study that will evaluate rodent HS as a model to study ophthalmic complications in microgravity.

Theriot, Corey A.↗

2014 Decompression Sickness/Extravehicular Activity Risks Standing Review Panel

The 2014 Decompression Sickness (DCS)/Extravehicular Activity (EVA) Risks Standing Review Panel (from here on referred to as the SRP) met for a site visit in Houston, TX on November 4 - 5, 2014. The SRP reviewed the Research Plans for The Risk of Decompression Sickness and the Risk of Injury and Compromised Performance due to EVA Operations, as well as the Evidence Reports for both of these Risks. The SRP found that the NASA DCS/EVA team did an excellent job of presenting their research plans. The SRP considers it critical that NASA proceeds with the high priority tasks identified in this report (DCS1, DCS3, DCS5). The highest priority is to determine the acceptable DCS and hypoxia risk associated with the planned human exploration beyond low Earth orbit. The risk of DCS is highly dependent upon the pressure within the exploration vehicle. If slightly more hypoxia is permitted then (even with the same percentage of oxygen) the pressure within the exploration vehicle can be lowered thus further mitigating the risk of DCS. The second highest priority is to test and validate the recommended 8.2psi/34% O2 atmosphere. Development of procedures and equipment for human exploration missions are very limited until the results of this testing are completed. The SRP also suggests that DCS7 be separated into two Gaps. Gap DCS7 should deal with DCS treatment while a new Gap should be created to deal with the long-term effects of DCS. The SRP also encourages NASA to increase collaboration with other organizations and pool resources where possible. The current NASA DCS/EVA team has the extensive expertise and a wealth of knowledge in this area. The SRP suggests that increased manpower for this team would be highly productive.

Steinberg, Susan↗

Habitability Assessments And Lessons-learned From 3-day And 11-day Enriched Oxygen Hypobaric Chamber Tests At NASA Johnson Space Center

INTRODUCTION: Decompression sickness (DCS) is a risk to the health and performance of astronauts and high-altitude aircrew. Tolerance to flammability, hypoxia, prebreathe duration, and DCS risk varies across different organizations, vehicles, suits, and destinations, necessitating a variety of DCS risk mitigation approaches. Existing models of altitude DCS risk are often insufficient to enable accurate risk-informed decisions during hardware development, mission planning, and flight operations. METHODS: NASA completed outfitting of a dedicated facility at Johnson Space Center to support testing of up to eight human subjects for multiple days in hypobaric and enriched oxygen atmospheres. The primary purpose of the testing capability is validation of DCS risk mitigation protocols for Artemis missions to the Moon; however, it will also support development and validation of a generalizable altitude DCS risk estimation tool. A 3-day and an 11-day prebreathe validation test were completed in 2022, each with 8 human subjects living at 56.5 kPa (8.2 psia), 34% O2, 66% N2, with 5 simulated EVAs performed on masks at 29.6 kPa (4.3 psi), 85% O2, 15% N2. Facility and organizational lessons-learned and process improvements were recorded during and following the tests, and subjective habitability ratings were recorded daily during the 11-day test. Hypoxia and DCS-related physiological and cognitive outcome measures were recorded during both tests and are reported in companion presentations. RESULTS & DISCUSSION: All subjects completed each of the tests. Primary habitability issues related to mask discomfort during simulated EVAs and poor sleep quality due to thin mattresses. Polybenzimidazole (PBI) clothing was worn by all subjects due to the increased fire risk and may be required for Artemis missions; clothing was found to be acceptable overall with the worst ratings being due to poor fit and inelasticity. Chamber O2 and CO2 sensor inconsistency was observed that did not result in test termination but required post-test follow-up. Forward plans include additional hypobaric testing and integration of existing and future physiological outcome data into an open-source Aerospace Estimation Tool for Hypobaric Exposure Risk (AETHER). NASA is also working to make the testing capability available to commercial companies.

Andrew F J Abercromby↗

Habitability Assessments And Lessons-learned From 3-day And 11-day Enriched Oxygen Hypobaric Chamber Tests At NASA Johnson Space Center

INTRODUCTION: Decompression sickness (DCS) is a risk to the health and performance of astronauts and high-altitude aircrew. Tolerance to flammability, hypoxia, prebreathe duration, and DCS risk varies across different organizations, vehicles, suits, and destinations, necessitating a variety of DCS risk mitigation approaches. Existing models of altitude DCS risk are often insufficient to enable accurate risk-informed decisions during hardware development, mission planning, and flight operations. METHODS: NASA completed outfitting of a dedicated facility at Johnson Space Center to support testing of up to eight human subjects for multiple days in hypobaric and enriched oxygen atmospheres. The primary purpose of the testing capability is validation of DCS risk mitigation protocols for Artemis missions to the Moon; however, it will also support development and validation of a generalizable altitude DCS risk estimation tool. A 3-day and an 11-day prebreathe validation test were completed in 2022, each with 8 human subjects living at 56.5 kPa (8.2 psia), 34% O2, 66% N2, with 5 simulated EVAs performed on masks at 29.6 kPa (4.3 psi), 85% O2, 15% N2. Facility and organizational lessons-learned and process improvements were recorded during and following the tests, and subjective habitability ratings were recorded daily during the 11-day test. Hypoxia and DCS-related physiological and cognitive outcome measures were recorded during both tests and are reported in companion presentations. RESULTS & DISCUSSION: All subjects completed each of the tests. Primary habitability issues related to mask discomfort during simulated EVAs and poor sleep quality due to thin mattresses. Polybenzimidazole (PBI) clothing was worn by all subjects due to the increased fire risk and may be required for Artemis missions; clothing was found to be acceptable overall with the worst ratings being due to poor fit and inelasticity. Chamber O2 and CO2 sensor inconsistency was observed that did not result in test termination but required post-test follow-up. Forward plans include additional hypobaric testing and integration of existing and future physiological outcome data into an open-source Aerospace Estimation Tool for Hypobaric Exposure Risk (AETHER). NASA is also working to make the testing capability available to commercial companies.

Andrew Abercromby↗

Development, Validation and Approval of A Planetary Extravehicular Activity Prebreathe Protocol: NASA Exploration Atmosphere Tests 1 & 2

INTRODUCTION: Denitrogenation prebreathe protocols used to mitigate DCS risk for Space Shuttle and International Space Station EVAs are validated for the microgravity environment, but the significantly increased risk of DCS during equivalent ambulatory surface EVAs make these protocols inapplicable to planetary/Lunar missions as planned by the Artemis program. Living in an “Exploration Atmosphere” of 56.5 kPa (8.2 psia), 34% O2, 66% N2 has been recommended by NASA for future Moon and Mars missions as a compromise that balances pre-EVA prebreathe duration, hypoxia, and flammability risk, assuming a 29.6 kPa (4.3 psi) spacesuit. A prebreathe validation campaign at NASA’s Johnson Space Center in 2022–2023 has aimed to validate the prebreathe durations and is being operationalized by NASA for use in upcoming Lunar EVAs. METHODS: Twelve volunteers lived in a hyboparic chamber for 11 days with an “exploration atmosphere” of 56.6kPa/34% O2 66% N2. Subjects acclimated to this atmosphere for 48 hrs and thereafter participated in five 6-hour simulated EVAs at 34kPa/85% O2 / 15% N2 over the course of 11 days. Prior to each simulated EVA, subjects underwent a 20-minute prebreathe at 85% O2. The EVA simulation was designed to include tasks that are physically and ergonomically representative of future planetary EVAs, proportionate to the subject’s VO2max. Decompression stress was evaluated during the simulated EVA by serial doppler and echocardiographs alternating every 15 min, as well as clinical monitoring for DCS signs/symptoms. Venous gas emboli (VGE) and DCS outcomes were verified against NASA Standard 3001, which guides allowable prebreathe protocol acceptance criteria. RESULTS AND DISCUSSION: Venous gas emboli (VGE) were identified during EVAs. No Grade IV VGE were observed. Two cases of mild, Type I DCS were identified in the subjects over the course of 50 EVA exposures. Ten planned EVA exposures were eliminated due to mask fit, metabolic rate, or subject safety concerns. One subject was removed from the study due to presence of left ventricular VGE. Additionally, two doppler techs also experienced DCS, and one case of hypoxia was noted. All cases of DCS resolved with treatment. No cases of severe DCS were observed. The observed incidence (4%, 1.1–13.5% at 95% confidence) met the NASA Standard 3001 criteria leading to the transition of this protocol from research to operational use for upcoming Lunar missions.

Exploration Atmosphere↗

Space crew environment.

Space cabin atmosphere relation to environmental and operational variables, discussing effect of hypoxia and hypercapnia on spacecrew and mission safety

SPACE CABIN ATMOSPHERE↗