Cardiovascular disease in space: A systematic review.

BACKGROUND: With expanding commercial space programs, uncertainty remains about the cardiovascular effects of space environmental exposures including microgravity, confinement, isolation, space radiation, and altered bacterial virulence. Current limited data suggests additional health threats compared to Earth. METHODS: We systematically reviewed PubMed, CENTRAL, Web of Science, EMBASE and Cochrane databases for prospective studies on spaceflight and cardiovascular outcomes. Search terms combined cardiovascular disease topics with spaceflight concepts. No date or language restrictions were imposed. RESULTS: 35 studies representing 2696 space travelers met inclusion criteria. Studies were grouped into spaceflight associations with: atherosclerosis, mortality, cardiac function, orthostatic intolerance, and arrhythmias. Atherosclerosis evidence was limited, with animal studies linking space radiation to endothelial damage, oxidative stress, and inflammation. However, human data showed no significantly increased atherosclerotic disease in astronauts. Mortality studies demonstrated lower cardiovascular mortality in astronauts compared to the general population however there was conflicting data. Cardiac function studies revealed physiologic ventricular atrophy, increased arterial stiffness, and altered blood flow distribution attributed to microgravity exposure. Effects appeared transient and reversible post-flight. Orthostatic intolerance studies found astronauts experienced altered heart rate variability, baroreflex response, and blood pressure changes post-flight. Arrhythmia studies showed increased ventricular ectopy during spaceflight, but limited data on long term flights. CONCLUSIONS: Environmental space hazards impact the cardiovascular system through multiple mechanisms. Microgravity causes cardiac atrophy and orthostatic intolerance while space radiation may potentially accelerate atherosclerosis. Further research is needed, especially regarding long-term spaceflights.

Cervical spine and muscle adaptation after spaceflight and relationship to herniation risk: protocol from 'Cervical in Space' trial.

BACKGROUND: Astronauts have a higher risk of cervical intervertebral disc herniation. Several mechanisms have been attributed as causative factors for this increased risk. However, most of the previous studies have examined potential causal factors for lumbar intervertebral disc herniation only. Hence, we aim to conduct a study to identify the various changes in the cervical spine that lead to an increased risk of cervical disc herniation after spaceflight. METHODS: A cohort study with astronauts will be conducted. The data collection will involve four main components: a) Magnetic resonance imaging (MRI); b) cervical 3D kinematics; c) an Integrated Protocol consisting of maximal and submaximal voluntary contractions of the neck muscles, endurance testing of the neck muscles, neck muscle fatigue testing and questionnaires; and d) dual energy X-ray absorptiometry (DXA) examination. Measurements will be conducted at several time points before and after astronauts visit the International Space Station. The main outcomes of interest are adaptations in the cervical discs, muscles and bones. DISCUSSION: Astronauts are at higher risk of cervical disc herniation, but contributing factors remain unclear. The results of this study will inform future preventive measures for astronauts and will also contribute to the understanding of intervertebral disc herniation risk in the cervical spine for people on Earth. In addition, we anticipate deeper insight into the aetiology of neck pain with this research project. TRIAL REGISTRATION: German Clinical Trials Register, DRKS00026777. Registered on 08 October 2021.

Biomechanical changes in the lumbar spine following spaceflight and factors associated with postspaceflight disc herniation.

BACKGROUND CONTEXT: For chronic low back pain, the causal mechanisms between pathological features from imaging and patient symptoms are unclear. For instance, disc herniations can often be present without symptoms. There remains a need for improved knowledge of the pathophysiological mechanisms that explore spinal tissue damage and clinical manifestations of pain and disability. Spaceflight and astronaut health provides a rare opportunity to study potential low back pain mechanisms longitudinally. Spaceflight disrupts diurnal loading on the spine and several lines of evidence indicate that astronauts are at a heightened risk for low back pain and disc herniation following spaceflight. PURPOSE: To examine the relationship between prolonged exposure to microgravity and the elevated incidence of postflight disc herniation, we conducted a longitudinal study to track the spinal health of twelve NASA astronauts before and after approximately 6 months in space. We hypothesize that the incidence of postflight disc herniation and low back complaints associates with spaceflight-included muscle atrophy and pre-existing spinal pathology. STUDY DESIGN: This is a prospective longitudinal study. PATIENT SAMPLE: Our sample included a cohort of twelve astronaut crewmembers. OUTCOME MEASURES: From 3T MRI, we quantified disc water content (ms), disc degeneration (Pfirrmann grade), vertebral endplate irregularities, facet arthropathy and/ fluid, high intensity zones, disc herniation, multifidus total cross-sectional area (cm2), multifidus lean muscle cross-sectional area (cm2), and muscle quality/composition (%). From quantitative fluoroscopy we quantified, maximum flexion-extension ROM (°), maximum lateral bending ROM (°), and maximum translation (%). Lastly, patient outcomes and clinical notes were used for identifying postflight symptoms associated with disc herniations from 3T MRI. METHODS: Advanced imaging data from 3T MRI were collected at three separate time points in relation to spending six months in space: (1) within a year before launch ("pre-flight"), (2) within a week after return to Earth ("post-flight"), and (3) between 1 and 2 months after return to Earth ("recovery"). Fluoroscopy of segmental kinematics was collected at preflight and postflight timepoints. We assessed the effect of spaceflight and postflight recovery on longitudinal changes in spinal structure and function, as well as differences between crew members who did and did not present a symptomatic disc herniation following spaceflight. RESULTS: Half of our astronauts (n=6) experienced new symptoms associated with a new or previously asymptomatic lumbar disc protrusion or extrusion following spaceflight. We observed decreased multifidus muscle quality following spaceflight in the lower lumbar spine, with a reduced percentage of lean muscle at L4L5 (-6.2%, p=.009) and L5S1 (-7.0%, p=.006) associated with the incidence of new disc herniation. Additionally, we observed reduced lumbar segment flexion-extension ROM for L2L3 (-17.2%, p=.006) and L3L4 (-20.5%, p=.02) following spaceflight, and furthermore that reduced ROM among the upper three lumbar segments (-24.1%, p=.01) associated with the incidence of disc herniation. Existing endplate pathology was most prevalent in the upper lumbar spine and associated with reduced segmental ROM (-20.5%, p=.02). CONCLUSIONS: In conclusion from a 10-year study investigating the effects of spaceflight on the lumbar spine and risk for disc herniation, we found the incidence of lumbar disc herniation following spaceflight associates with compromised multifidus muscle quality and spinal segment kinematics, as well as pre-existing spinal endplate irregularities. These findings suggest differential effects of spinal stiffness and muscle loss in the upper versus lower lumbar spine regions that may specifically provoke risk for symptomatic disc herniation in the lower lumbar spine following spaceflight. Results from this study provide a unique longitudinal assessment of mechanisms and possible risk factors for developing disc herniations and related low back pain. Furthermore, these findings will help inform physiologic countermeasures to maintain spinal health in astronauts during long-duration missions in space.

Human Health during Space Travel: State-of-the-Art Review.

The field of human space travel is in the midst of a dramatic revolution. Upcoming missions are looking to push the boundaries of space travel, with plans to travel for longer distances and durations than ever before. Both the National Aeronautics and Space Administration (NASA) and several commercial space companies (e.g., Blue Origin, SpaceX, Virgin Galactic) have already started the process of preparing for long-distance, long-duration space exploration and currently plan to explore inner solar planets (e.g., Mars) by the 2030s. With the emergence of space tourism, space travel has materialized as a potential new, exciting frontier of business, hospitality, medicine, and technology in the coming years. However, current evidence regarding human health in space is very limited, particularly pertaining to short-term and long-term space travel. This review synthesizes developments across the continuum of space health including prior studies and unpublished data from NASA related to each individual organ system, and medical screening prior to space travel. We categorized the extraterrestrial environment into exogenous (e.g., space radiation and microgravity) and endogenous processes (e.g., alteration of humans' natural circadian rhythm and mental health due to confinement, isolation, immobilization, and lack of social interaction) and their various effects on human health. The aim of this review is to explore the potential health challenges associated with space travel and how they may be overcome in order to enable new paradigms for space health, as well as the use of emerging Artificial Intelligence based (AI) technology to propel future space health research.

Synovial Fluid Cytokines, Chemokines and MMP Levels in Osteoarthritis Patients with Knee Pain Display a Profile Similar to Many Rheumatoid Arthritis Patients.

BACKGROUND: There are currently no effective disease-modifying drugs to prevent cartilage loss in osteoarthritis and synovial fluid is a potentially valuable source of biomarkers to understand the pathogenesis of different types of arthritis and identify drug responsiveness. The aim of this study was to compare the differences between SF cytokines and other proteins in patients with OA (n = 21) to those with RA (n = 27) and normal knees (n = 3). METHODS: SF was obtained using ultrasound (US) guidance and an external pneumatic compression device. RA patients were categorized as active (n = 20) or controlled (n = 7) based upon SF white blood cell counts (> or <300 cells/mm3). Samples were cryopreserved and analyzed by multiplex fluorescent bead assays (Luminex). Between-group differences of 16 separate biomarker proteins were identified using ANOVA on log10-transformed concentrations with p values adjusted for multiple testing. RESULTS: Only six biomarkers were significantly higher in SF from active RA compared to OA-TNF-α, IL-1-ß IL-7, MMP-1, MMP-2, and MMP-3. Only MMP-8 levels in RA patients correlated with SF WBC counts (p < 0.0001). Among OA patients, simultaneous SF IL-4, IL-6, IL-8, and IL-15 levels were higher than serum levels, whereas MMP-8, MMP-9, and IL-18 levels were higher in serum (p < 0.05). CONCLUSION: These results support the growing evidence that OA patients have a pro-inflammatory/catabolic SF environment. SF biomarker analysis using multiplex testing and US guidance may distinguish OA phenotypes and identify treatment options based upon targeted inflammatory pathways similar to patients with RA.

Back Pain in Outer Space.

Space travel has grown during the past 2 decades, and is expected to surge in the future with the establishment of an American Space Force, businesses specializing in commercial space travel, and National Aeronautics and Space Administration's planned sustained presence on the moon. Accompanying this rise, treating physicians are bracing for a concomitant increase in space-related medical problems, including back pain. Back pain is highly prevalent in astronauts and space travelers, with most cases being transient and self-limiting (space adaptation back pain). Pathophysiologic changes that affect the spine occur during space travel and may be attributed to microgravity, rapid acceleration and deceleration, and increased radiation. These include a loss of spinal curvature, spinal muscle atrophy, a higher rate of disc herniation, decreased proteoglycan and collagen content in intervertebral discs, and a reduction in bone density that may predispose people to vertebral endplate fractures. In this article, the authors discuss epidemiology, pathophysiology, prevention, treatment, and future research.

Comparison of Internal Jugular Vein Cross-Section Area During a Russian Tilt-Table Protocol and Microgravity.

BACKGROUND: To date, we lack U.S. data on the effects of the long-used Russian tilt-table training protocol known as the Russian pre-launch tilt-table training protocol on internal jugular vein cross sectional area (IJV-CSA) in microgravity.CASE REPORT: A case study of a single healthy male astronaut volunteer was used for this study. The right IJV-CSA was measured using real time ultrasound at set times throughout the Russian pre-launch tilt-table training protocol, a method of physiological preparation for microgravity using tilt-table training. In microgravity, the subjects right IJV-CSA was measured again for comparison. The mean difference from in-flight right IJV-CSA for pre-tilt (0) was 0.438 cm², for 15 was 0.887 cm², for 30 was 0.864 cm², for 50 was 1.15 cm², and for post-tilt (0) the difference was 0.305 cm².DISCUSSION: The cross-sectional areas of the subjects right IJV-CSA were significantly different between in-flight values and several angles of the Russian tilt-table protocol, except for the 0 measurement. In summary, this case-study represents the first time IJV-CSA has been compared between various angles of a tilt-table training protocol and microgravity in the same astronaut subject. The findings support prior cohort studies studying the same principles. Further investigation is merited; both to better describe the relationship between the cardiovascular effects of tilt-table simulations of microgravity and their correlating in-flight values, and to evaluate and study the Russian tilt-table protocol effects on cardiovascular physiology from a training and preparation perspective.David J, Scheuring RA, Morgan A, Olsen C, Sargsyan A, Grishin A. Comparison of internal jugular vein cross-section area during a Russian tilt-table protocol and microgravity. Aerosp Med Hum Perform. 2021; 92(3):207211.

SARS-CoV-2 Pandemic Impacts on NASA Ground Operations to Protect ISS Astronauts.

NASA implements required medical tests and clinical monitoring to ensure the health and safety of its astronauts. These measures include a pre-launch quarantine to mitigate the risk of infectious diseases. During space missions, most astronauts experience perturbations to their immune system that manifest as a detectable secondary immunodeficiency. On return to Earth, after the stress of re-entry and landing, astronauts would be most vulnerable to infectious disease. In April 2020, a crew returned from International Space Station to NASA Johnson Space Center in Houston, Texas, during the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. Post-flight quarantine protocols (both crew and contacts) were enhanced to protect this crew from SARS-CoV-2. In addition, specific additional clinical monitoring was performed to determine post-flight immunocompetence. Given that coronavirus disease 2019 (COVID-19) prognosis is more severe for the immunocompromised, a countermeasures protocol for spaceflight suggested by an international team of scientists could benefit terrestrial patients with secondary immunodeficiency.

Axial loading and posture cues in contraction of transversus abdominis and multifidus with exercise.

Astronauts are at increased risk of spine injury. With a view to developing training approaches for the muscles of the spine in microgravity, this study examined the effects of axial loading and postural cues on the contraction of transversus abdominis and lumbar multifidus in supine lying using a novel exercise device (GravityFit). Thirty (18 males and 12 females) endurance-trained runners without a history of spinal pain aged 33-55 years were recruited. Magnetic resonance imaging (MRI) was performed under one rest and five exercise conditions, which involved variations in axial loading and postural cues. Whole volume of the abdominal and lumbar paraspinal muscles was imaged and transversus abdominis thickness and length and multifidus anteroposterior and mediolateral thickness measured. Transversus abdominis contraction was greatest in the 'stretch tall plus arm extension' (length, - 15%, P < 0.001; thickness, + 19%, P < 0.001) and 'stretch tall plus arm extension and thoracic cue' (length, - 16%, P < 0.001; thickness, + 18%, P < 0.001) conditions. The contraction of multifidus was the greatest in the 'arm extension and thoracic cue' (anteroposterior, + 3.0%, P = 0.001; mediolateral, - 4.2%, P < 0.001) and 'stretch tall plus arm extension and thoracic cue' (anteroposterior, + 6.0%, P < 0.001; mediolateral, - 2.1%, P = 0.022) conditions. This study provides proof-of-principle for an exercise approach that may be used to facilitate the automatically contraction of the transversus abdominis and multifidus muscles. Axial loading of the body, with or without arm loading, most consistently led to contraction of the transversus abdominis and lumbar multifidus muscles, and regional differences existed in the contraction within the muscles.

Serious Altitude Illness at the South Pole.

BACKGROUND: Gradual ascent is impractical for personnel deploying to the South Pole due to logistical challenges. Prevention of altitude illness relies on prophylactic medications such as acetazolamide and behavioral modifications including hydration and avoidance of overexertion. We present three recent cases of altitude illness that occurred in previously healthy individuals at the South Pole.CASE REPORTS: 1) A 52-yr-old woman not on prophylactics presented with headache and intractable vomiting 7 h after arriving and hiking around the station. She was treated with acetazolamide, dexamethasone, oxygen, and supportive care. Her symptoms resolved during the evacuation flight. 2) A 23-yr-old man presented with dyspnea at rest 3 d after arriving without prophylactic treatments. He had a Sao2 of 49%, wheezes and crackles on lung exam, and interstitial infiltrates on chest X-ray. His treatment included oxygen, nifedipine, acetazolamide, and dexamethasone. His symptoms resolved during the evacuation flight. 3) A 40-yr-old man presented with dyspnea after a series of strenuous workouts since his arrival 5 d prior. He had a Sao2 of 41%, and his chest X-ray was consistent with high altitude pulmonary edema. He was treated with oxygen, nifedipine, and fluids before descent to sea level, where his symptoms fully resolved 4 d later.DISCUSSION: These patients illustrate that altitude illness may develop despite medical screening, participant education, and availability of prophylactic medications based on published guidelines. These cases could be attributed to noncompliance and misinformation, bringing to light some of the challenges with managing more diverse populations that deploy to remote environments.Rose JS, Law J, Scheuring R, Ramage MH, McKeith JJ. Serious altitude illness at the South Pole. Aerosp Med Hum Perform. 2020; 91(1):46-50.

Serratus Anterior Contraction During Resisted Arm Extension (GravityFit) Assessed by MRI.

BACKGROUND: Scapular stabilization is a common focus of shoulder rehabilitation. OBJECTIVE: Examine contraction of serratus anterior during a bilateral arm extension exercise with axial compression using an exercise device (GravityFit) by magnetic resonance imaging (MRI). METHODS: MRI was performed under two conditions: rest and static arm extension with axial compression. Load was set at 20% of age, sex and weight estimated bench press one-repetition maximum. A T2-weighted sequence was used to collect 14 axial images of the upper thoracic spine and shoulder bilaterally. Mean muscle length and thickness were calculated for the whole muscle and in equidistant subregions of the muscle in its anterior (superficial), central and posterior (deep) portions. Adjustment of p-values to guard against false positives was performed via the false discovery rate method. RESULTS: Nine participants without a history of shoulder or spine pathology were included. When compared to rest, arm extension with the exercise device led to 11% increased overall muscle thickness (P = 0.038) and 6.1% decreased overall muscle length (P = 0.010). Regionally, thickness increased in anterior (superficial, +19%; P = 0.040) and central (+17%; P = 0.028) portions of the muscle more than posterior (deep, +3.9%, P = 0.542). CONCLUSION: Contraction of serratus anterior occurred during static arm extension with axial compression produced by a novel exercise approach, as measured via MRI. The activation of serratus anterior differed across its length with greater contraction of the anterior and central portions. This may indicate compartmentalization of function within this muscle. Overall, the proof-of-principle findings justify the use of this exercise approach for the activation of serratus anterior.

Concerns About Ankle Injury Prophylaxis and Acceptance of the Parachute Ankle Brace Among Jumpmaster Students.

Introduction: Several studies have shown that the parachute ankle brace (PAB) is safe, cost-effective, and reduces the rates of ankle injuries during military parachuting. However, the acceptability and usability of the PAB has not been well established in units that regularly do airborne exercises. Many anecdotal concerns in the past may be limiting common use. The purpose of the study is to ascertain the attitudes toward the PAB among experienced paratroopers. Methods: One hundred experienced paratroopers training to be jumpmasters at the Advanced Airborne School (Fort Bragg, NC) voluntarily responded to a 13-item, paper questionnaire to assess attitudes toward the PAB, its use, and concerns about future ankle injuries. The survey was offered to all 100 students enrolled in an Advanced Airborne School course. Results were input into an online database using Qualtrics and qualitative responses were evaluated for thematic content and categorized appropriately. Analysis was performed using Qualtrics and SPSS for descriptive statistics, two-sample t-tests, and chi-square tests. The Wilcoxon signed-rank test was used to evaluate Likert-type responses. Results: Of the 100 paratroopers who responded to the survey 32% had over 10 yr of military service, 58% had over 5 yr of service, and 32% had over 5 yr on active jump status. Results show that none of the respondents had ever used the PAB; 62% had never heard of the PAB, and 72% had never observed use of the PAB. A majority of respondents (87%) had never injured an ankle during a parachute landing fall (PLF), but 79% believed that an ankle injury could affect their career potential as a paratrooper. Almost one-half of the respondents (47%) had seen that ankle injuries affect another paratrooper's career. A third of the respondents (35%) said that they had concerns that would keep them from using the PAB, whereas 21% were uncertain, as they had never heard of it. Only 19% of the respondents were willing to use measures such as taping, lace-up bracing, semi-rigid brace inside a normal boot, specialized jump boot with stabilizing braces built in, or outside-the-boot braces to prevent ankle injury. However, 40% said that they were likely to use these measures on jumps after experiencing an ankle injury. Discussion: Previous research clearly establishes the advantages of the PAB. None of the participants had ever used the PAB but expressed a fear about how an ankle injury might impact their future career potential. Yet half of the jumpmasters indicated a willingness to use prophylactic measures after an ankle injury. Conclusion: This survey assessed the attitude and knowledge related to the PAB among jumpmaster students. Results show that despite the benefits of the PAB, a negative attitude exists toward the PAB, and it is not currently being used. This survey clearly demonstrates the need either to educate paratroopers on the existence of the PAB or to explore other designs that may be more readily accepted in the airborne community.

Disc herniations in astronauts: What causes them, and what does it tell us about herniation on earth?

PURPOSE: Recent work showed an increased risk of cervical and lumbar intervertebral disc (IVD) herniations in astronauts. The European Space Agency asked the authors to advise on the underlying pathophysiology of this increased risk, to identify predisposing factors and possible interventions and to suggest research priorities. METHODS: The authors performed a narrative literature review of the possible mechanisms, and conducted a survey within the team to prioritize research and prevention approaches. RESULTS AND CONCLUSIONS: Based on literature review the most likely cause for lumbar IVD herniations was concluded to be swelling of the IVD in the unloaded condition during spaceflight. For the cervical IVDs, the knowledge base is too limited to postulate a likely mechanism or recommend approaches for prevention. Basic research on the impact of (un)loading on the cervical IVD and translational research is needed. The highest priority prevention approach for the lumbar spine was post-flight care avoiding activities involving spinal flexion, followed by passive spinal loading in spaceflight and exercises to reduce IVD hyper-hydration post-flight.

Space adaptation back pain: a retrospective study.

INTRODUCTION: Back pain is frequently reported by astronauts during the early phase of spaceflight as they adapt to microgravity. The epidemiology of space adaptation back pain has not been well defined. This study aims to develop a case definition of space adaptation back pain, determine its incidence, and assess the effectiveness of available treatments. METHODS: Medical records from the Mercury, Apollo, Apollo-Soyuz Test Project (ASTP), Skylab, Mir, International Space Station (ISS), and Shuttle programs were reviewed. All episodes of in-flight back pain that met the criteria for space adaptation back pain were recorded. Pain characteristics, including intensity, location, and duration of the pain, were noted. The effectiveness of specific treatments was also recorded. RESULTS: The incidence of space adaptation back pain among astronauts was determined to be 52% (382/728). Most of the affected astronauts reported mild pain (86%). Moderate pain was reported by 11% of the affected astronauts and severe pain was reported by 3% of the affected astronauts. The most effective treatments were fetal positioning (91%) and the use of analgesic medications and exercise (primarily treadmill and cycle ergometer), which were both 85% effective. DISCUSSION: This retrospective study examines the epidemiology of space adaptation back pain. Space adaptation back pain is usually mild and self-limited. However, there is a risk of functional impairment and mission impact in cases of moderate or severe pain that do not respond to currently available treatments. Therefore, the development of preventive measures and more effective treatments should be pursued.

Musculoskeletal injuries and minor trauma in space: incidence and injury mechanisms in U.S. astronauts.

INTRODUCTION: Astronauts have sustained musculoskeletal injuries and minor trauma in space, but our knowledge of these injuries is based mainly on anecdotal reports. The purpose of our study was to catalog and analyze all in-flight musculoskeletal injuries occurring throughout the U.S. space program to date. METHODS: A database on in-flight musculoskeletal injuries among U.S. astronauts was generated from records at the Johnson Space Center. RESULTS: A total of 219 in-flight musculoskeletal injuries were identified, 198 occurring in men and 21 in women. Incidence over the course of the space program was 0.021 per flight day for men and 0.015 for women. Hand injuries represented the most common location of injuries, with abrasions and small lacerations representing common manifestations of these injuries. Crew activity in the spacecraft cabin such as translating between modules, aerobic and resistive exercise, and injuries caused by the extravehicular activity (EVA) suit components were the leading causes of musculoskeletal injuries. Exercise-related injuries accounted for an incidence of 0.003 per day and exercise is the most frequent source of injuries in astronauts living aboard the International Space Station (ISS). Interaction with EVA suit components accounted for an incidence of 0.26 injuries per EVA. DISCUSSION: Hand injuries were among the most common events occurring in U.S. astronauts during spaceflight. Identifying the incidence and mechanism of in-flight injuries will allow flight surgeons to quantify the amount of medical supplies needed in the design of next-generation spacecraft. Engineers can use in-flight injury data to further refine the EVA suit and vehicle components.