Table Of ContentFOREWORD
One of the most important developments of the twentieth century has been the
introduction of humans into space. For the first time, we could study humans in an
environment free of the effects of Earth's gravity. Inspired by the Russian theoretician
Konstantin Eduardovich Tsiolkovskiy, Robert Goddard launched the first rocket in
1926; Sputnik I was launched in 1957; and the first human was launched into space in
1961. Since that historic flight, scientists and researchers have studied the effects of
spaceflight on the human systems.
The process by which the human body adapts to the unaccustomed environment of
spaceflight conditions is reflected in shifts in fluid and electrolyte homeostasis, shifts in
which the cardiovascular system and kidneys play key roles. In this book, noted re
searchers from the United States and Russia bring together their observations on fluid
and electrolyte regulation and review the work of other leading scientists in this disci
pline. This work covers nearly 40 years of studying humans in space. The book opens
with a brief review of human physiological responses to the spaceflight environment,
putting into perspective the overall human adaptation process. Next follow chapters pre
senting the homeostatic mechanisms affecting fluids and electrolytes during short and
long flights—the length of the latter now exceeding 1 year. The next chapters focus on
classic alternatives to flight studies, those of microgravity simulations and animal mod
els. The sixth chapter reviews the philosophies underlying the development of "counter-
measures," means of alleviating deleterious reactions to spaceflight conditions. The book
concludes with a brief overview of the present state of the field, with suggestions for
future studies and benefits for both space and Earth-based medicine.
This collaborative work is the result of many years of cooperation and friendship
among the three authors. Their collaboration has helped to lay the foundation for ongo
ing international endeavors and a permanent human presence in space.
Arnauld E. Nicogossian, M.D.
NASA Headquarters
Washington, D.C.
PREFACE
The seeds of this long-awaited volume were sown in 1971 with the first meeting of
the Joint U.S.-U.S.S.R. Working Group on Space Biology and Medicine. Initially led by
C. A. Berry for the U.S., and by N. N. Gurovskiy and later O. G. Gazenko for the
U.S.S.R., this Group provided a forum in which specialists in various aspects of biologi
cal and medical sciences, including the authors of this book, could meet and exchange
information and plans for spaceflight studies. Despite the shadow of the Cold War that
predominated in those days, scientists from both countries came to the clear realization
that working together was the best way to accomplish the difficult and critically impor
tant tasks of ensuring the reliability and safety of spaceflight.
In the 27 years since their first meeting, the authors of this volume, Drs. Carolyn
L. Huntoon, Anatoliy I. Grigoriev, and Yuri V. Natochin, have forged warm personal
relationships in addition to an enduring and productive collaboration. These distin
guished specialists and well-known authors have dedicated nearly 30 years to investigat
ing the intricacies of physiological homeostasis in extreme environments.
Carolyn L. Huntoon, Ph.D., is a physiologist, biochemist, and specialist in space
life sciences. Her graduate education included participating in the initial biomedical
studies of astronauts in the U.S. Gemini Program in 1965-66. The studies Dr. Huntoon
designed, conducted, and reported in the subsequent Apollo, Skylab, and Space Shuttle
programs stand at the foundation of space medicine. She is recognized for her successes
in research, operations, and management at the National Aeronautics and Space Admini
stration's Johnson Space Center in Houston, Texas. Dr. Huntoon currently serves as
Special Assistant to the NASA Administrator.
Anatoliy I. Grigoriev, M.D., is a physiologist and specialist in space medicine. A
Professor at Moscow State University, Dr. Grigoriev is a scientist and manager at the
State Scientific Center Institute for Biomedical Problems of the Russian Federation's
Ministry of Health. Dr. Grigoriev has been in charge of medical support for space
flights and in-flight biomedical research for several years. He also currently serves as
the Chief Surgeon for the Russian Space Agency.
Yuri V. Natochin, M.D., is a physiologist and specialist in general and evolution
ary physiology. A Professor at St. Petersburg University, Dr. Natochin has headed scien
tific studies of fluid and electrolyte metabolism in animals and humans since the begin
ning of the space age. He has directed laboratories at the Institute for Biomedical Prob
lems, and now manages the Renal Physiology Laboratory at the I. M. Sechenov Institute
for Evolutionary Physiology and Biochemistry. Dr. Natochin is responsible for the over
all coordination of physiological studies in Russia. He also chairs the Council on Physi-
ology, and serves as academician-secretary for the Physiology Division of the Russian
Academy of Sciences.
Since the first launch of a human being into space in 1961, flight durations have
been extended, supporting technologies have become vastly more sophisticated, and the
numbers of variables that can be studied, both in Earth-based laboratories and in flight,
have grown exponentially. The authors' approaches to studying fluid and electrolyte
regulation in weightlessness have evolved in parallel with the evolution of human space
exploration. Their meticulous tests of hypotheses, their mastery of experimental meth
ods, and their pursuit of deeper theoretical mechanisms all underscore the importance of
the scientific exchanges that took place between the two countries. The clear benefits
provided by mutual understanding of each country's studies and findings are apparent in
this book.
At its heart, this book provides detailed, well-argued answers to several fundamen
tal questions in physiology that have been raised during the course of human space
exploration. Particular attention is paid to potential differences between reactions—and
their regulatory mechanisms—in space vs. those on Earth, and the possible conse
quences of those differences. Analyses of vast amounts of research material are pre
sented, from studies conducted aboard short missions (the Voskhod, Soyuz, and Space
Shuttle programs) and long missions (the Skylab, Salyut, and Mir programs). Also dis
cussed are results from biological experiments conducted in weightlessness simulations
and aboard the Kosmos biosatellite series, and the development of preventive measures
designed to maintain physiological homeostasis in space.
It is with great pleasure that we introduce this book, which is undoubtedly the most
comprehensive treatise on the regulation of fluid and electrolyte balance in space. We
hope that the issues in space physiology raised in this volume will promote continued
exploration of the physiological aspects of human reliability and safety in spaceflight.
On a broader scale, we also hope that the information presented will help in the resolu
tion of open questions in general physiology and medicine.
Charles A. Berry, M.D., Houston, March 1998
Oleg G. Gazenko, M.D., Moscow, March 1998
INTRODUCTION
Our intent in writing this book was to summarize and draw conclusions from the
results of more than 30 years of research on fluid and electrolyte metabolism in humans
and animals in spaceflight environments. We envision this topic as being of interest not
only to specialists in space medicine, but also to those concerned with general physiol
ogy and the physiology of body fluids. We believe that understanding the physiology ol
fluid and electrolyte metabolism during the process of adaptation to microgravity pro
vides a unique perspective on the physiological processes that maintain the milieu in-
terieur, particularly those associated with the kidney.
The extraordinary progress in biological sciences made during the 20th century
took place in the context of biology becoming differentiated into many individual—al
beit interrelated—areas. Nevertheless, even in the most profound study of trees, one
must not lose sight of the forest. To paraphrase from Best and Taylor's Physiological
Basis of Medical Practice,1 mammalian physiology involves studying the dynamic inter
relationships that exist among cells, tissues, and organs, interrelationships that lead ulti
mately to the level of the whole organism. So, too, is the science of space physiology, in
which those who study the functional status of each physiological system must never
lose sight of the whole organism. Space physiology and medicine, in particular, demand
an integrated approach to the use of basic and applied science in solving practical prob
lems associated with maintaining crew health and productivity in space. Appropriate
solutions for these problems can be found only through scientific knowledge of how the
human body operates in the spaceflight environment.
Research in biochemistry, biophysics, molecular biology, cytology, and many other
branches of biology is essential to understanding the functions of an organism. Studies
that involve the methods and approaches of these disciplines provide the foundation for
constructing a unified physiological concept of the true nature of the processes occurring
in the human body in space. Only integration of the knowledge obtained by using ap
proaches from various disciplines can provide a modern understanding of the nature of
physiological changes under unusual situations, such as those experienced in spaceflight.
A group of Nobel Prize laureates from Great Britain, in anticipation of the 1993 Interna
tional Congress of Physiological Sciences in Glasgow, noted that "without this integra
tion, the molecular information could become a confusing cataloguing of structure and
mechanisms."2
Born in the early 1960s, space physiology is one of the youngest branches of
physiology. The first studies relevant to fluid-electrolyte metabolism in spaceflight envi
ronments were begun at that time. The authors were present at the inception of this
research, and for more than 30 years they have collaborated, debated the use of various
approaches, and endeavored to understand each other.
The earliest questions posed for space research centered on whether humans could
even survive the spaceflight environment, much less perform productive work there. In
the years since, physiological analysis of the "reserve potential" of various functional
systems in the body has become critical, not only for answering the question of whether
humans can survive in microgravity, but also for developing strategies to prevent ad
verse effects of spaceflight factors. Analyses such as these have been conducted in the
course of addressing problems in space physiology, and the results obtained are of inter
est both for functional diagnosis and for understanding physiological capacities during
exposure to unusual environments.
The central problem in space physiology continues to be how humans adapt to the
extreme conditions of spaceflight, i.e., the means by which we maintain our milieufxj
interieur[s] in such an unaccustomed milieu exterieur. In 1878, the French physiologist
Claude Bernard proposed that homeostatic systems in humans regulate the functioning
of various effector organs and systems so as to support consistency in the composition
and amount of fluids in the milieu interieur in the face of the most dramatic oscillations
in conditions in the milieu exterieur. Sixty years later, the English physiologist J. Bar-
croft3 postulated that regulation of the milieu interieur evolved to become increasingly
tighter and more accurate over many years, and that this process had allowed the devel
opment of the ability to perceive the world in terms of abstract knowledge. According to
Barcroft, the chemical and physiological processes associated with mental activity are so
delicate that changes large enough to be measured by a thermometer or hydrogen elec
trode would be enormous to the point of catastrophe. 3
The kidneys play a leading role in supporting the physiochemical constancy of the
milieu interieur.4 In a lecture read in 1939, L. Orbeli asked, "What is the kidney en
deavoring to do? Produce urine of a particular composition or maintain the plasma?
. . .Fluctuations in organic and inorganic substances in urine are extremely large, while
blood plasma retains an extraordinary constancy."5 Early spaceflight investigations fo
cused on this question, and involved tests of renal function, dynamics of endocrine
factors at different times during spaceflight, and renal sensitivity to hormonal effects in
animals and in humans. Results from these investigations have confirmed that the higher
an organism's place on the evolutionary scale, the greater the stability of that organism's
body-fluid volume, chemical composition, osmolality, and pH.
The need for cosmonauts and astronauts to be physically and mentally healthy
during spaceflight hardly requires justification. One of the key goals of space physiol
ogy and medicine continues to be to maintain human performance at optimal levels in
space through providing a working environment that is optimal for all physiological
systems. Programs focused on this goal require in-depth understanding of the factors
that affect humans in this environment as well as the mechanisms through which physi
ological systems react to those factors.
Presented in this book are analyses of the effects on spaceflight on the human
milieu interieur and the strategies taken to ensure its stability. Data are cited on the
major physiochemical constitutents of blood plasma and serum in humans and animals
during and after spaceflights; the status of tissue fluid and electrolyte metabolism; and
the status of renal function and the endocrine mechanisms through which it is regulated.
Results are discussed for short (less than 30 days) and long spaceflights as well as those
from ground-based simulations. Our intent is to share not only the results from these
studies, but also the process by which ideas were developed and implemented over the
course of a 30-year collaboration. The true importance of a multidisciplinary approach
in solving specific problems and in formulating general principles is apparent through
out this work.
We express our sincere gratitude to our colleagues and friends whose work is de
scribed on the pages herein, and whose help made its publication possible.
References
•West, J. B., Ed., Best and Taylor's Physiological Basis of Medical Practice, Williams and Wilkins,
Baltimore, London, 1985.
2Noble, D., 32nd International Congress of Physiological Sciences, Glasgow, 1-6 August 1993. News in
Physiological Sciences, Vol. 7, 1992, p. 48.
3Barcroft, J., Features of the Architecture of Physiological Function, State Publishing House of Biological
and Medical Literature, Moscow-Leningrad, 1937.
4Smith, H. W., The Kidney: Structure and Function in Health and Disease, Oxford University Press, New
York, 1951.
5Orbeli, L. A., "Renal Physiology," Selected Works, Nauka, Moscow, Vol. 4, 1966, pp. 85-106.
Acknowledgments
The information presented in this book could not have been obtained without the
cooperation of the cosmonauts, astronauts, and test subjects who participated in these
studies. Thanks also are due for the generous assistance of the staff of the Gagarin
Cosmonaut Training Center in Star City, Russia; the Institute for Biomedical Problems
in Moscow, Russia; and the Clinical and Endocrinology Laboratories at the Johnson
Space Center in Houston, Texas, U.S.A. Dr. Huntoon particularly acknowledges the
long-term guidance and support she received from Drs. Dietlein, Johnson, Potts, Haber,
Miller, Suki, Epstein, and Zielger.
Finally, we gratefully appreciate the invaluable contributions of the following indi
viduals in preparing this volume: Jane M. Krauhs, Ph.D., of KRUG Life Sciences Inc.,
for drafting the joint contributions; Christine F. Wogan, M.S., E.L.S., also of KRUG
Life Sciences, for editing the translated Russian and U.S. text and graphics; and Nancy
G. House, of Futron Corporation, for coordinating and expediting the publication proc
ess with the Russian and U.S. authors.
CONTENTS
Page
FOREWORD vii
PREFACE ix
INTRODUCTION xi
CHAPTER 1: PHYSIOLOGICAL EFFECTS 1
I. Effects of Weightlessness 2
II. Effects of Landing and Readaptation 5
III. Summary 5
References 6
CHAPTER 2: SHORT FLIGHTS 9
I. Assessment Methods 9
II. Early Effects on Fluids and Electrolytes 15
A Body Fluid 15
B. Blood and Urinary Osmolality and Monovalent Ions 18
C. Blood and Urinary Divalent Ions 21
III. Renal-Stone Risk 21
IV. Early Effects on Hormones Regulating Fluid
and Electrolyte Metabolism 22
A. Antidiuretic Hormone 22
B. Atrial Natriuretic Peptide 24
C. Renin-Angiotensin-Aldosterone System 24
D. Cortisol and Adrenocorticotropin 27
E. Catecholamines 28
F. Stress 28
V. Hormones Regulating Calcium or Bone Metabolism 29
VI. Early Effects on Renal Function 29
VII. Readaptation 31
VIII. Conclusions 34
References 35
Page
CHAPTER 3: LONG FLIGHTS 41
I. Assessment Methods 41
II. Fluid and Electrolyte Metabolism on 2- to 52-Week Spaceflights:
Review of Findings 42
A. Skylab 42
1. Body Fluid 42
2. Electrolytes 43
3. Hormones 44
B. Soviet and Russian Flights 47
1. Body Fluid 47
2. Blood Electrolytes 47
3. Urinary Electrolytes 50
4. Hormones 55
5. In-Flight Measurements 57
III. Physiological Responses to Long Flights:
Summary and Discussion 63
A. Fluid Balance, Electrolyte Balance, and Fluid Redistribution . . .. 63
B. Hormonal Regulation of Fluid and Electrolyte Balance 67
C. Renal Responses to Fluid Loads or Deprivation After Long Flights . . 69
IV. Fluid and Electrolyte Status After Landing 72
References 74
CHAPTER 4: SPACEFLIGHT SIMULATIONS 81
I. Simulation Models: Immersion and Bed Rest 81
II. Fluid Balance 82
III. Sodium and Potassium Balance 85
IV. Predicting Fluctuations in Fluid Balance During Bed Rest 88
V. Calcium Balance 91
VI. Renal Osmoregulatory Responses to Immersion and Bed Rest 93
A. Urine-Concentrating Ability/Fluid Deprivation 96
B. Urine-Diluting Ability/Fluid Load 97
VII. Electrolyte Levels in Blood 99
VIII. Fluid-Compartment Volumes 103
IX. Possible Mechanisms for Maintaining Fluid-Electrolyte Homeostasis . . 105
A. Immersion 105
1. Body Position 106
2. Temperature 107
B. Head-Down Bed Rest 109
1. Endocrine Effects 110
2. Circadian Influences 115
3. Prostaglandins 116
4. Glucocorticoid Receptors 116
