Physiological Changes in the Cardiovascular System During Space Flight　― Current Countermeasures and Future Vision ―

Abstract

Background

With the recent acceleration of manned space exploration, health care in space has become an important issue. Cardiovascular problems, mainly caused by the microgravity environment in space, include decreased red blood cell volume, myocardial atrophy and aerobic capacity, and reduced orthostatic tolerance after return. However, complete physiological countermeasures have not been established and more research is needed.

Methods and Results

A search on PubMed was conducted for English-language articles on cardiovascular changes in space and their countermeasures and post return rehabilitation. Early in space flight, diuresis associated with fluid shifts causes changes in erythrocyte volume, and after prolonged stays, the vestibular and cardiocirculatory systems are induced to show orthostatic intolerance due to decreased blood pressure increasing reflexes, decreased circulating plasma volume, and myocardial atrophy. The main countermeasures include aerobic exercise and strength training in space 6 days a week, for approximately 2 h a day, and a rehabilitation program after return to re-adapt to the Earth’s gravitational environment.

Conclusions

In the near future, when people with heart disease and the elderly will fly in space, new health management techniques that combine the knowledge accumulated in space flight and cardiac rehabilitation on the ground will be necessary for in-flight countermeasures against cardiovascular changes in space and for post-return rehabilitation.

Human space exploration began in the 1960s, but it has entered a new phase in recent years. From exploration led by nations, private space companies have become the core of human space activity in low Earth orbit (LEO), and private missions of astronauts, such as Inspiration 4, the Axiom-mission, and Polaris Dawn, have commenced abroad in recent years.^1,2 In contrast, the current target of human space exploration that is traditionally led by a nation’s space agencies, such as the National Aeronautics and Space Administration (NASA), Japan Aerospace Exploration Agency (JAXA), and European Space Agency (ESA), is to carry out a manned lunar landing for the first time in 50 years since the Apollo program, and to build infrastructure for a stay on the moon in preparation for further exploration of Mars.

There are many medical issues, including cardiovascular, to be solved for future human space exploration.³ The International Space Station (ISS) travels around the Earth at approximately 400 km above the ground, and there are 3 big environmental issues that are different to Earth.

First, microgravity. Living in microgravity reduces bone density 10 times faster than osteoporosis in the elderly⁴ and causes muscle atrophy equivalent to 6 months’ worth of muscle atrophy in the elderly in 1 day. Muscle atrophy during space flight is more pronounced in antigravity muscles (slow muscles) such as the trunk and quadriceps, and fast-twitching of slow muscles also occurs.⁵ The first 1–2 weeks are the most marked, with a decrease of approximately 1.0% per day in the triceps muscle, followed by a gradual progression.^6,7 The rate of space flight bone loss by dual-energy X-ray absorptiometry (DXA) is 1–2%/month (12–24%/year) in the proximal femur. This is due to the fact that microgravity decreases calcium absorption from the intestinal tract and increases calcium excretion.⁸

Second, space radiation. ISS astronauts are exposed to 3 types of primary cosmic rays: galactic cosmic rays, proton rays supplemented by the Earth’s magnetic field, and solar particle rays generated by solar activity, as well as secondary cosmic rays and neutrons generated when these primary cosmic rays pass through the ISS ship’s walls. Astronauts are exposed to 0.5–1 mSv of cosmic radiation per day,⁹ which is equivalent to half a year of natural radiation on Earth. Because of the long-term cancer risk, astronauts are closely monitored for levels of radiation. As a protective measure, attempts have been made to reduce the effects of exposure through physical shielding and the use of antioxidants,^10,11 but these are not perfect and there are concerns about the serious effects that could be caused if manned space flights were to take place outside the Van Allen belt, such as in the case of a future flight to Mars.

Third, habitable space is a closed and isolated environment in space. There is psychological and mental stress from staying in a space with a different circadian rhythm to that on Earth for a long period of time, and being with crews from different cultures, and also next to a dangerous environment that includes space debris and a vacuum. These factors increase the stress hormones, such as cortisol and epinephrine, and combined with the effects of microgravity and cosmic radiation have a negative impact on the immune system.^12,13

The cardiovascular system undergoes several drastic changes in space, mainly due to microgravity. In the early phase of space flight, changes occur in body fluids and electrolytes, the cardiocirculatory system, and red blood cell volume, and it takes the body approximately 1.5 months after the start of the space stay to adapt to the space environment. In the long term, myocardial atrophy and a 10–20% decrease in maximal oxygen uptake capacity occur after a 6-month stay. After returning to Earth, 83% of astronauts who stayed in space for a long time suffer from orthostatic intolerance.^14,15

The effects and countermeasures of space flight on the human body are being systematically studied on the basis of data from previous human space flights and research on the ground. The representative resource that is the world standard is the Human Research Roadmap (HRP), edited by NASA.¹⁶ HRP includes risks related to the effects on the human body in space flight, and it is 1 of the most conformant resources with space medicine and biology research. In recent years, the Enhancing eXploration Platforms and ANalog Definition (EXPAND) program, a research program on the health and performance of private space flight participants, has also been launched.¹⁷ The EXPAND program is operated by Translational Research Institute for Space Health (TRISH), a research organization that brings together medical and engineering universities in the United States and the NASA HRP, and is designed to maximize the collection of valuable information on space flight by standardizing the collection of medical data (e.g., vestibular, cognitive function, physiological changes) before, during, and after commercial space flight missions and storing it in a centralized database. Programs operated by private companies have emerged around the world to provide financial and operational support to companies and researchers who conduct research and development to resolve medical risks in deep space exploration.

This paper focuses on current measures to maintain cardiovascular health and physiological changes in space, as well as rehabilitation after returning to Earth, and also discusses image equipment that is essential for maintaining cardiovascular health in manned space exploration.

Cardiovascular in Space: Phenomenon

The cardiovascular system undergoes a drastic change in space mainly due to microgravity.

The ISS is 400 km above the ground, orbiting the Earth at a speed of approximately 7.7 km/s, and its motion generates centrifugal force. Because this centrifugal force is balanced by the Earth, the apparent gravity inside the ISS is almost zero, a state of microgravity.

Microgravity causes 3 main changes in the cardiovascular system during and after space flight.

The first is the ‘body fluid shift’ that occurs at the earliest stage of space flight (Figure 1). On the ground, body fluids are forced downwards by the hydrostatic pressure gradient and 70% of body fluids are below the level of the heart. However, the loss of this force due to microgravity causes a shift of approximately 2,000 mL of fluid towards the head.^18,19 Within the first 24 h of space flight, the ventricular volume and atrial diameter of astronauts may increase.²⁰ In contrast, research using parabolic flights, which create a period of weightlessness for several tens of seconds in an aircraft, has shown that in 8 subjects the central venous pressure (CVP) decreased by 1.3 mmHg during the period of weightlessness, while the left atrial diameter increased by 3.6 mm and the esophageal intraluminal pressure decreased by 5.6 mmHg.^21,22 Esophageal intra-esophageal pressure is frequently used as a surrogate for measuring intrathoracic pressure, and the study speculates that ‘transthoracic CVP’ (=CVP − intrathoracic pressure), which represents atrial distending pressure, increases in weightlessness, which may explain the increased atrial diameter despite the decreased CVP.

Figure 1.

When entering microgravity, ‘fluid shift’ occurs, whereby water in the blood and other fluids moves toward the head, causing an increase in blood in the chest cavity, which leads to diuresis and a decrease in blood and fluid volume, reaching a state of equilibrium.

Blood in the thoracic cavity also increases and stimulates capacity receptors in the aortic arch and other parts of the body to determine that there is an excess of fluid cause inhibits the secretion of antidiuretic hormone (ADH). Moreover, the secretion of atrial Na-diuretic peptide (ANP) hormone in the atrial myocytes is stimulated, causing diuresis and a reduction in blood and fluid volume to reach equilibrium.

In addition, the transfer of albumin-containing fluid from the intravascular to extravascular space reduces plasma volume. In fact, it has been shown that within the first 24 h of space flight, plasma volume decreases by approximately 17%.²³ A rapid decrease in plasma volume leads to an increase in hematocrit, and as a result, in space, erythropoietin levels decrease and red blood cell mass decreases.²⁴ Red blood mass is known to be reduced by more than 10–12% in the first 10 days in space.²⁵

This decrease in plasma volume and red blood cell volume causes a total decrease in vascular volume of 11%, which is called ‘space anemia’.²⁶ We can say that this situation is the state of the human body adapting to space.

However, some reports show that long stays in space (i.e., >180 days) result in higher red blood cell, hematocrit and hemoglobin densities than before the flight,²⁷ and the mechanism is still unclear.

The second change is decreasing orthostatic intolerance. Immediately after returning to Earth after a space flight, many astronauts experience a decrease in their ability to stay standing.

On the ground, it has been suggested that there are 2 main mechanisms that help to prevent a drop in blood pressure when standing up: (1) a decrease in arterial blood pressure due to a change in posture from supine to standing caused by a decrease in venous return and cardiac output, which lead to a pressure receptor reflex that regulates the cardiovascular system;²⁸ and (2) another mechanism that involves the peripheral vestibular system.²⁹

The vestibular system is a gravity-sensing organ located deep within the dura mater (it consists of otoliths that sense linear acceleration and semicircular canals that sense rotational acceleration; Figure 2). When the vestibular system senses a change in gravity, it activates the sympathetic nervous system and causes an increase in arterial pressure by the vestibular-blood pressure reflex. However, in a microgravity environment, the arterial pressure becomes uniform, so the need to control blood pressure decreases, which leads to reduced function of these reflexes (baroreflex: cardiovascular system, vestibular-blood pressure reflex). In addition, astronauts who stay in microgravity for long periods of time are also said to be at increased risk of developing low blood pressure when standing up immediately after returning to Earth due to a decrease in circulating plasma volume and stroke volume. It has been reported that 83% of astronauts who have returned to Earth from long durations in space and 20–30% of astronauts from short durations show orthostatic intolerance.^14,15

Figure 2.

Astronauts who stay in microgravity for long periods of time experience a decline in the function of the circulatory system’s pressure receptors and the vestibular system’s blood pressure reflexes. This is compounded by a decrease in circulating blood volume and myocardial atrophy, resulting in a drop in blood pressure upon standing immediately after returning to Earth.

In a study that examined autonomic nervous system disorders before and after a 4–5-day shuttle mission, the carotid baroreflex response (induced by changes in pressure in the neck) via the vagus nerve and changes in heart rate and blood pressure caused by the transition from supine to standing were evaluated. The results suggested that the decrease in vagal control of the sinus node or the low adrenergic response caused by space flight may contribute to the decrease in orthostatic tolerance.³⁰ In a study that classified astronauts into a pre-syncope group and a pre-syncope group based on whether they could stand unaided for 10 min on the day of landing before and after the shuttle mission, the latter group had significantly smaller increases in plasma norepinephrine concentration, lower peripheral vascular resistance, and greater decreases in systolic and diastolic blood pressure than the former group.³¹

The third change is loss of cardiac muscle and aerobic capacity. Prolonged space flight causes myocardial remodeling and atrophy if no measures are taken. There is a report that magnetic resonance imaging (MRI) measurements after space flight showed that the left ventricular weight of 4 male astronauts decreased by an average of 12±6.9%, even after a space flight of only 10 days.³²

After flight, the maximum oxygen uptake decreased, and even in short-term flight missions of 9–14 days, the maximum oxygen uptake decreased to 22% on the day of landing. In short-term microgravity, the difference in peak heart rate, blood pressure, and systemic arteriovenous oxygen difference does not change, but systemic maximum oxygen uptake decreases due to a decrease in intravascular stroke volume, and cardiac output when returning to Earth.³³

Microgravity has been reported to cause physiological adaptations through changes in protein composition and function of the endoplasmic reticulum (ER), ribosomes, and mitochondria, resulting in reduced protein synthesis and atrophy. In cardiomyocytes exposed to microgravity, protein translation through the ER is reduced and there is a marked decrease in tropomyosin and myosin regulatory light chains, which are 2 cytoskeletal proteins essential for mitochondrial localization. These 2 proteins are also indicators of muscle atrophy.³⁴

Cardiovascular in Space: Ongoing Countermeasure

On the ground, orthostatic intolerance is associated with several factors, including decreased plasma and stroke volumes and constricted arterioles.²⁰

In contrast, the decrease in standing blood pressure in astronauts who have spent long periods in microgravity is caused by a decrease in the blood pressure increase reflex of the vestibular and cardiovascular systems, a decrease in terrestrial plasma volume,¹⁴ and atrophy of the myocardium.

Current measures to reduce orthostatic intolerance during readaptation to 1G include exercise during the mission, fluid loading at the end of the mission, the administration of drugs such as the mineralocorticoid fludrocortisone, elevated posture during re-entry and landing, taking a maximum of 8 pills (containing 1 g of salt) with approximately 912 mL of liquid designed to make an isotonic saline beverage 2 h before re-entry, space suit cooling, and lower body compression clothing of 20–40 mmHg.³⁵ However, the amount of terrestrial plasma has been shown to decrease by 7–20% compared with pre-flight.³⁶

There is also a report that mild electrical stimulation of the vestibular system improves the decline of the vestibular blood pressure reflex, and that orthostatic hypotension on the return from space was improved in 4 out of 6 astronauts.^37,38

This technology is expected to be useful for astronauts who need to be able to perform activities autonomously immediately upon arrival after spending several months in a weightless environment on a ship, such as during a flight to Mars, as well as for the declining orthostatic tolerance of the elderly.

Long-term space missions reduce maximum aerobic capacity (V̇O₂ peak).³⁹ Exercise is important as a countermeasure, and astronauts should exercise approximately 2.5 h per day, 6 days per week. Two types of exercise are used to maintain cardiorespiratory fitness: treadmill and cycle ergometer-based exercise, which are also used as the main form of exercise prescription in cardiac rehabilitation on land.⁴⁰

There are 2 treadmills on the space station: the Treadmill Vibration Isolation System (TVIS) and the Combined Operating Load-Bearing External Resistance Treadmill (COLBERT). Astronauts wear shoulder and waist bands, known as harnesses, to prevent their bodies from floating, and run while applying a load equivalent to their body weight vertically toward the device using springs.

In contrast, cycle ergometers (CEVIS) are pedaled with the body immobilized with the feet on clip pedals. On the ground, gravity allows you to step on the pedals, but in microgravity, purely lower limb muscle strength is required. The harness load on the treadmill and the load and pace on the ergometer can also be changed, each with its own personalized training content.⁴¹

These in-space workouts allowed 7 of the 14 astronauts to achieve their pre-flight peak oxygen consumption in space, and 4 of them trained harder than the astronauts with lower peak oxygen consumption.³⁹

However, the effects of exercise countermeasure strategies (i.e., type of exercise [aerobic or resistance training]) and amount of exercise (i.e., intensity, duration, and frequency) on adaptation deficits due to low gravity, in terms of cardiorespiratory/metabolic health, is controversial.⁴²

In addition, during long-term space flight, due to restrictions on food supply it is necessary to prescribe more efficient exercise to maintain musculoskeletal and aerobic capacity in order to reduce the amount of calories consumed through exercise, and it is also necessary to take a nutritional approach to the problem.⁴³

Recently, high-intensity interval training, which is considered to have greater potential to transform cardiac rehabilitation on the ground, has been devised as a method for maintaining physical function in space and it is attracting attention as a time-efficient method.^44,45

Astronauts who have completed a long-term stay on the ISS undergo a 45-day rehabilitation and recovery program after returning to Earth to restore their physical functions (Figure 3).

Figure 3.

Astronauts who have spent extended periods in microgravity experience changes in their vestibular and somatosensory systems, making sensory integration difficult and impairing posture control. Additionally, they exhibit reduced flexibility, agility, mobility, and oxygen capacity, necessitating rehabilitation programs to facilitate re-adaptation to Earth’s gravitational environment.

There are 2 characteristics of astronauts’ bodies after their time in space. The first is that immediately after returning, the astronauts’ bodies have adapted to microgravity, and the vestibular and somatosensory systems that are used to perceive body position have changed. Although the information from the eyes does not change, it is difficult to integrate these senses, and as a result, the astronauts are unable to control their posture, which can lead to dizziness and difficulty walking.

Second, while there is no difference in the maximum number of repetitions (IRM) in the bench press before and after the flight, there is a clear decrease in flexibility, agility and mobility, such as in the time taken to run through cones or the sit-and-reach test. It has also been reported that maximal oxygen uptake decreases by approximately 15% before and after flight.⁴⁶

The rehabilitation program is designed to help the body readjust to the gravitational environment on Earth, and is performed in the following way (Figure 2). Functional training is designed to improve mobility and balance by integrating vestibular and somatosensory information, and involves exercises such as dribbling a basketball on an unstable disc or using cones and ladders. In particular, when throwing a medicine ball, the aim is to strengthen the limbs and trunk while being conscious of the need to exert maximum muscle strength in a short period of time, and to be conscious of the coordination of the series of movements. In the case of Japanese astronauts, rehabilitation after returning to Earth lasts for 45 days. After about 2 weeks, there are no major problems with daily life, and after about a month they return to the same level as before the flight.^46,47

After a space flight, a precise evaluation of myocardial volume is done with MRI, and it was once reported that the myocardium atrophied after flight.⁴⁸

However, recent research has shown that, although the total workload of the heart decreases after 4–6 months of space flight, there is no significant difference in left ventricular volume after space flight, and the left ventricular ejection fraction and ejection rate have increased slightly. This indicates that the exercise program on the ISS is having a positive effect.⁴⁹

Typically, aerobic capacity can be restored through regular aerobic exercise and a gradual return to normal Earth activities, therefore a heart-specific rehabilitation program is not usually necessary.⁵⁰ Unlike early evaluation of the musculoskeletal system, early assessment of cardiac function such as maximum aerobic exercise capacity after return is not essential. The maximum oxygen uptake test is carried out at least a few weeks after returning, and if the level has not recovered to the pre-flight level, the rehabilitation menu will be reconsidered.

Cardiovascular in Space: Future Countermeasure

Advances in exercise equipment and prescription programs on the ISS have improved the efficiency of exercise training in space⁵¹ and have been good for maintaining aerobic capacity and preventing orthostatic intolerance after long-term flights.⁵²

However, astronauts on the ISS train for long periods of time, for approximately 2 h a day, 6 days a week, so there is a need to develop more time-efficient methods. In addition, it is important to devise methods to maintain cardiac function in place of exercise for future long-duration manned flights to Mars, which require space-saving measures, and for regular people, including the elderly, to stay in space.

The method that is expected to be used is a small short-arm centrifuge to create artificial gravity by using centrifugal force, and to repeatedly apply short periods of hypergravity (1.5–2 g) for 30 min or so each day in the spaceship.³⁷

The gravitational load of the short-arm centrifuge may be useful not only for preventing a decline in cardiac regulation function, but also for preventing physiological adaptation disorders in many organs in space, such as bone mass loss, muscle atrophy, vestibular nerve abnormalities, and a decline in the immune system.^53,54 Small centrifuges have been devised to generate artificial gravity in a spacecraft, but there are issues to be overcome in terms of power supply and space occupancy in order to realize them in a spacecraft.

It has been shown that the combination of exercise and centrifugation can effectively prevent the decline in function of the cardiovascular system that occurs with standing.^55,56

In contrast, as a new form of artificial gravity, a study was conducted in which the participants were suspended from a bungee jump rubber and ran along the walls of a 10 m diameter, 5 m high cylinder, with their weight set to one-sixth of that on Earth, as on the moon, to voluntarily generate centrifugal force and economically and effectively apply a load to the body.⁵⁷

This device was shown to have the same effect as running in a short period of time, and to contribute to strengthening cardiopulmonary function and maintaining bone mineral content. However, this study only had two participants, which is a small sample size, so further research is needed.

Ono et al. devised the Lunar Glass as a permanent artificial gravity facility, and they aim to use low gravity for the elderly and rehabilitation, high gravity for training, and normal gravity.⁵⁸

Cardiovascular in Space: Image Equipment

Imaging equipment plays an important role in assessing cardiac function and the onset of disease in space.

When conducting cardiac rehabilitation on Earth, the state of heart failure is assessed by checking for pulmonary congestion, pleural effusion, or pneumothorax using chest X-rays, and the presence of moderate valvular disease, changes in left ventricular end-diastolic diameter, and the presence of ventricular aneurysms are checked using echocardiography.

However, there are currently no large imaging devices in space. Imaging equipment used in space is required to be ‘small and multifunctional’ so that ultrasound (US) can be used for a variety of purposes with a single device due to launch costs and living space limitations.

The advantages of US in space are that it can be used repeatedly without causing any harm to the body, can display the internal structures of the body in real time, and can be operated remotely by a medical team on the ground and the images can be shared in real time.⁵⁹ Almost all of the algorithms for treatment on the ISS involve evaluation using US.

In 2021, a study was conducted on the world’s first space flight mission for civilians only, called Inspriation4, in which the Butterfly IQ+ US device with an artificial intelligence guidance function for non-medical professional crews was used to scan the bladder, internal jugular vein (IJV) and eye imaging in full crew autonomy.⁶⁰ The collected data was used to test whether non-medical professionals could obtain clinical-grade images on their own without guidance from ground support. This device is currently also being tested by astronauts on the ISS.

In the 2024 Polaris Dawn mission, in which 4 civilians reached an altitude of 1,408 km and conducted various medical experiments, studies were conducted on the prevalence of decompression sickness in humans, monitoring, detecting and quantifying venous gas embolism using US, and space flight-associated neuro-ophthalmic syndrome, which is an important risk to human health in a long-term space flight.²

As an actual example of how echography was useful for diagnosing medical conditions in space, there is a report of a huge left IJV thrombus that was discovered by chance during an examination of 1 crew member on the 50th day of the flight. For treatment, enoxaparin and apixaban were administered until 4 days before the crew returned to Earth, and the disappearance of the thrombus was confirmed by echography after their return.⁶¹

It is extremely rare for a healthy person on Earth to develop a large IJV thrombus, and recent research has shown that in short-duration missions, stagnation or backflow of the IJV frequently occurs (6/11 [55%] crew members) by the middle of the flight (Day 50), indicating that there is a blood flow problem that needs to be monitored in future missions.⁶² This is a very significant report as it is the first case of remotely directing an echo in space and successfully treating the patient.⁶¹

Conclusions

The aim of cardiac rehabilitation on Earth is to help patients with heart disease recover their physical strength and live a life that is true to themselves, and it includes all the support necessary for daily life, such as exercise therapy,⁶³ nutritional guidance,⁶⁴ medication and self-care management.⁶⁵ The target is people with ischemic heart disease such as myocardial infarction and angina pectoris, as well as people with valvular heart disease and chronic heart failure. Exercise therapy mainly involves aerobic exercise such as treadmill and bicycle ergometer training, as well as resistance training to strengthen and maintain muscle strength.

There are some differences, such as the fact that in space the aim is to maintain the heart function of astronauts who are healthy to begin with so that they can quickly return to life on Earth after their time in space, but the emphasis on nutritional management, aerobic exercise and muscle maintenance exercise is the same, and the equipment used is also a modified version of the equipment used on Earth so that it can be used in microgravity.

Furthermore, in the future, when the time comes when not only healthy people but also elderly people with heart conditions will be able to go into space, a new field will be created that combines the know-how of cardiac rehabilitation accumulated on Earth with the management of cardiac health for space travelers.

Acknowledgments

The author expresses sincere appreciation to Dr. Masataka Sata and Dr. Keisuke Kida for providing a great opportunity to present this paper. The author also acknowledges Dr. Masanori Fujita, who provided instructions on how to write this paper and passed in November 2024, and my colleague of Space Medical Accelerator and Seirei Memorial Hospital. During the preparation of this manuscript, the author used DeepL for proofreading purposes, as the author is not native English speaker.

Disclosures

None.

IRB Information

This study is a literature review and has been determined by the Ethics Review Committee of Seirei Memorial Hospital to be exempt from ethical review.

Data Availability

Not applicable as there is no private data in this paper.