Effect of Microgravity on the Peripheral Subcutaneous Veno-Arteriolar Reflex in Humans (Xenon1) - 05.13.15

Overview | Description | Applications | Operations | Results | Publications | Imagery

ISS Science for Everyone

Science Objectives for Everyone
Effect of Microgravity on the Peripheral Subcutaneous Veno-Arteriolar Reflex in Humans (Xenon1) investigated the mechanism of orthostatic intolerance (the inability to regulate blood pressure while upright) and will lay an important foundation for the development of treatments for orthostatic intolerance following space flight. After space flight, orthostatic intolerance can occur, which can severely inhibit the functional cerebral capacity of crewmembers during reentry and landing.
Science Results for Everyone
Right after returning from space flight, some crew members are not able to regulate blood pressure while standing, known as orthostatic intolerance. This concerns scientists, as it can limit a crew member’s abilities during reentry and landing. The veno-arteriolar reflex is a mechanism in the body that normally helps sustain an adequate supply of blood to the brain when a person stands. Data collected from crew members on the performance of this reflex before flight and after landing were compared with their blood pressure and heart rate while lying down. The data indicate that spaceflight does not reduce the veno-arteriolar reflex, which suggests that something else may be involved in post-flight orthostatic intolerance.

The following content was provided by Anders Gabrielsen, M.D., and is maintained in a database by the ISS Program Science Office.
Experiment Details


Principal Investigator(s)
Anders Gabrielsen, M.D., Danish Aerospace Medical Center of Research National University Hospital (Rigshospitalet), Copenhagen, Denmark

Peter Norsk, M.D., University of Copenhagen, Copenhagen, Denmark

NASA Johnson Space Center, Human Research Program, Houston, TX, United States

Sponsoring Space Agency
National Aeronautics and Space Administration (NASA)

Sponsoring Organization
Human Exploration and Operations Mission Directorate (HEOMD)

Research Benefits
Information Pending

ISS Expedition Duration
August 2001 - December 2002

Expeditions Assigned

Previous ISS Missions
Xenon tracers have not been used before, but orthostatic intolerance experiments have been conducted previously on the Space Shuttle and Mir.

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Experiment Description

Research Overview

  • The goal of Effect of Microgravity on the Peripheral Subcutaneous Veno-Arteriolar Reflex in Humans (Xenon1) is to determine how space flight and microgravity affect the quality of the veno-arteriolar (V-A) reflex, a mechanism in the body that prevents blood from pooling in the feet. This reflex is important for preventing swelling (edema) and sustaining an adequate blood supply to the brain while a person is standing.

  • Using 133Xenon, a harmless radioactive molecule, blood flow in the small blood vessels below the skin of astronauts will be visualized while they hold various postures that will test the V-A reflex.

  • An additional goal is to use the results of this study to help understand some of the postflight effects of space travel, including dizziness and fainting.

ISS Science Challenge Student Reflection

ISS Science Challenge Selected Project
We chose this science experiment because we were curious to find out what the Veno-Arteriolar Reflex is and why it is important to the human body. We found that this reflex is essential to pumping blood through the lower half of the human body. Without this reflex, blood would not get pumped back up to the heart from the legs. Astronauts are incapacitated for a few days after returning to Earth because the VA reflex is not necessary in space.
-Sarthak, Grade 11, Thomas Jefferson High School for Science and Technology, Herndon, Virginia
-Pratap, Grade 11, Dougherty Valley High School, San Ramon, California
-Calvin, Grade 11, Mission San Jose High School, Fremont, California
-Bhavna, Grade 12, Santa Teresa High School, San Jose, California


When the body’s legs are lower in relationship to the heart, the body triggers what is called a local veno-arteriolar reflex, where small subcutaneous (below the surface of the skin) blood vessels constrict, forcing blood from the feet toward the head. If this reflex is not properly triggered or if blood circulation is impeded, the blood pressure drops, causing dizziness and, possibly, fainting. This effect is called orthostatic intolerance. Due to a number of possible reasons—reduced fluid volume, muscle atrophy, neurovestibular adaptation—astronauts suffer from orthostatic intolerance during entry and landing, and for a few days postflight, potentially interfering with their ability to perform entry and landing tasks and prolonging their recovery period. Xenon-1 tested the local veno-arteriolar reflex in an effort to understand the source of, and ways to combat, postflight orthostatic intolerance.

Prior to and following Expeditions 3, 4, and 5, station crewmembers were placed on a gurney as a small amount of Xenon-133, a radioactive isotope dissolved in sterile saline solution, was injected into the subcutaneous tissue of their lower legs. Arterial blood pressure was recorded by a continuous pressure device on the crewmember’s index finger. This measurement, which was taken with the Xenon-1 detector unit, was used to trace the movement of the Xenon tracer following injection. As the measurements were taken, the Xenon memory box recorded and displayed the counting rate.

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Space Applications
While a person is standing (orthostasis), blood has a tendency to pool in the legs and feet. This collecting of blood in the lower body can lead to a blood pressure drop in the upper body, and if less blood gets to the brain, the astronauts may experience dizziness or fainting. It is a condition called orthostatic intolerance, and it can affect astronauts for several days after returning from space. The veno-arteriolar (V-A) reflex acts together with other reflexes to prevent this. When blood pooling is detected in the lower limbs, the V-A reflex constricts blood vessels just below the skin (subcutaneous vessels) to prevent edema and pooling of blood and thereby maintain blood pressure and blood supply to the brain. Treatments for this condition are currently under investigation (one is the drug Midodrine, which is being tested by ISS astronauts). The exact mechanism that creates orthostatic intolerance is still not completely understood. This study's method of visualizing blood flow will allow the roles of the subcutaneous vessels and the V-A reflex to be characterized, allowing for possible treatments in the future.

Earth Applications
This study will have great implications in the medical community on Earth. Currently, there are no specific tests for orthostatic intolerance for it is not completely understood what causes orthostatic intolerance. What this experiment may lead to is a better understanding and improved treatment programs for orthostatic intolerance.

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Operational Requirements
All operations for this experiment are conducted on the ground. Crew will participate in one session preflight and another immediately post-flight. Crew members should not exercise on test day.

Operational Protocols
A Xenon tracer will be injected into the subcutaneous tissue of the lower leg, approximately 10 centimeters (3.94 inches) above the ankle. A Continuous Blood Pressure Device (CBPD) will be attached to the crewmember's index finger. This will measure the crewmember's subcutaneous vascular resistance, which helps to regulate arterial blood pressure and prevent dizziness when standing. A Xenon Detector Unit, which is connected to the Xenon Memory Box, is slowly moved over the injection area while the Box displays counting information. The researchers will mark with a pen the spot that showed the highest count on the Box. The Xenon Detector Unit is attached to this spot using double-sided adhesive tape.

Thirty minutes after the injection, the researchers will measure the subcutaneous blood flow (called the 133Xenon washout technique) while the crewmember keeps his or her leg in a relaxed, supine (lying flat on the back) position. Additional measurements are taken with the leg lowered 40 centimeters (15.75 inches) below the heart, and again with the leg in a relaxed, supine position. The crewmember will hold each position for 7 minutes. When all the measurements have been completed, the Xenon Memory Box will be connected to a computer and the recorded information will be downloaded.

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Results/More Information

The last group of subjects for this experiment returned after Expedition 5. Data from all subjects were collected successfully. Gabrielsen and Norsk (2007) findings show veno-arteriolar reflex reduced subcutaneous blood flow by 37 +/- 9% before flight and by 64 +/- 8% following landing, with no statistical difference between the two responses. The mean arterial pressures and heart rates in supine astronauts were very similar before and after flight. These data indicate that this reflex is not attenuated by weightlessness, and suggests that the veno-arteriolar reflex is not a contributor to postflight orthostatic intolerance. (Evans et al. 2009)

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Results Publications

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Ground Based Results Publications

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ISS Patents

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Related Publications

    Ertl AC, Diedrich A, Biaggioni I, Levine BD, Robertson RM, Cox JF, Zuckerman JH, Pawelczyk JA, Ray CA, Buckey, Jr. JC, Lane LD, Shiavi R, Gaffney FA, Costa F, Holt C, Blomqvist CG, Eckberg DL, Baisch FJ, Robertson D.  Human muscle sympathetic nerve activity and plasma noradrenaline kinetics in space. Journal of Physiology. 2002; 538: 321-329. DOI: 10.1113/jphysiol.2001.012576.

    Kimmerly DS, Shoemaker JK.  Hypovolemia and neurovascular control during orthostatic stress. American Journal of Physiology: Heart and Circulatory Physiology. 2002; 282(2): H645-655.

    Watenpaugh DE, Buckey, Jr. JC, Lane LD, Gaffney FA, Levine BD, Moore WE, Wright SJ, Blomqvist CG.  Effects of spaceflight on human calf hemodynamics. Journal of Applied Physiology. 2001; 90(4): 1552-1558.

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Related Websites
Life Sciences Data Archive
International Space Station Medical Project (ISSMP)
NASA Fact Sheet

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image During the Xenon1 experiment, the crewmember will be injected with small amounts of 133Xenon, which will act as a tracer. Xenon1 will test the local veno-arteriolar reflex in an effort to understand the source of, and ways to combat, postflight orthostatic intolerance. Image courtesy of NASA, Johnson Space Center.
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image During the Xenon experiment, which is performed preflight and postflight, the crew will be injected with small amounts of 133Xenon, which will act as a tracer. A Xenon Detector Unit will be attached to each crewmember's leg slightly above the ankle as demonstrated in this photo. This will measure the crewmember's subcutaneous vascular resistance every seven minutes, which helps to regulate arterial blood pressure and prevent dizziness when standing. Image courtesy of NASA, Johnson Space Center.
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