Acta Astronautica 69 (2011) 1148–1152
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Acta Astronautica
journal homepage: www.elsevier.com/locate/actaastro
Academy Transactions Note
Assessment of individual adaptation to microgravity during long
term space flight based on stepwise discriminant analysis of heart
rate variability parameters$
Roman M. Baevsky a, Anna G. Chernikova a,n, Irina I. Funtova a, Jens Tank b
a
b
RF SRC, Institute of Biomedical Problems of the RAS, 123007, Choroshevskoe Shossee, 76a, Moscow, Russia
Hannover Medical School, Institute of Clinical Pharmacology, Hannover, Germany
a r t i c l e in f o
abstract
Article history:
Received 14 January 2011
Received in revised form
5 July 2011
Accepted 6 July 2011
Available online 2 August 2011
Optimization of the cardiovascular system under conditions of long term space flight is
provided by individual changes of autonomic cardiovascular control. Heart rate
variability (HRV) analysis is an easy to use method under these extreme conditions.
We tested the hypothesis that individual HRV analysis provides important information
for crew health monitoring. HRV data from 14 Russian cosmonauts measured during
long term space flights are presented (two times before and after flight, monthly in
flight). HRV characteristics in the time and in the frequency domain were calculated.
Predefined discriminant function equations obtained in reference groups (L1 ¼ 0.112n
HR 1.006nSI 0.047npNN50 0.086nHF; L2¼0.140nHR 0.165nSI 1.293npNN50þ 0.623
nHF) were used to define four functional states. (1) Physiological normal, (2) prenosological,
(3) premorbid and (4) pathological. Geometric mean values for the ISS cosmonauts based on
L1 and L2 remained within normal ranges. A shift from the physiological normal state to the
prenosological functional state during space flight was detected. The functional state
assessed by HRV improved during space flight if compared to pre-flight and early postflight functional states. Analysis of individual cosmonauts showed distinct patterns depending on the pre-flight functional state. Using the developed classification a transition process
from the state of physiological normal into a prenosological state or premorbid state during
different stages of space flight can be detected for individual Russian cosmonauts. Our
approach to an estimation of HR regulatory pattern can be useful for prognostic purposes.
& 2011 Elsevier Ltd. All rights reserved.
Keywords:
Cardiovascular system
Autonomic nervous system
Heart rate variability
Microgravity
Space flight
1. Introduction
Among psychological strain, extreme physical loads,
unusual noise and others, space flight is characterized by
the specific factor of microgravity. Numerous investigations during short and long term space missions showed
that functional parameters of the cardiovascular and
respiratory systems remain within normal ranges typical
$
n
This paper was presented during the 61st IAC in Prague.
Corresponding author. Tel.: þ 7 499 193 6244.
E-mail address: anna.imbp@mail.ru (A.G. Chernikova).
0094-5765/$ - see front matter & 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.actaastro.2011.07.011
for life at 1g. However, during microgravity regulatory
mechanisms control and adjust physiological functions of
different end organs individually in each astronaut leading to adaptation and fairly big changes may occur in the
regulatory systems. In other words, homeostasis maintenance ‘‘costs’’ have to be paid.
Changes of blood pressure (BP) and heart rate (HR)
seen in cosmonauts during space flight may be relatively
small if compared to patients with cardiovascular diseases. Nevertheless, these small changes are the result of
compensatory changes of the regulatory systems and
measurements of cardiovascular and respiratory control
contain important information for crew health control.
R.M. Baevsky et al. / Acta Astronautica 69 (2011) 1148–1152
Consequently, a concept of health [1] was developed in
Russia from the very beginning of space medicine. The
concept is focused on practical issues of health control
during space flight including the system of medical
monitoring and predicting deviations in the functional
state of crew members. Therefore, the prediction of
probable changes in crew health state is one of the key
objectives of medical monitoring in space flight. Preference was given to the method of heart rate variability
(HRV) analysis in order to keep the measurements simple
and reliable during manned space flights [2–5].
Numerous prospective clinical studies showed that there
is a cardiovascular continuum of complex changes going on
and different risk factors contribute to cardiovascular diseases preceding the end organ damage. HRV and blood
pressure variability analysis support this hypothesis and early
changes in the regulatory systems can be detected, which are
independent predictors for clinical outcome in patients [6–8].
A prenosological approach was developed in Russia, which
implies recognition of transition states between health and
disease based on data from space medicine [9–11] and from
large epidemiological studies. Four classes or functional
states were described based on HRV analysis parameters.
The classification system was originally developed in space
medicine but is now widely used in practical medicine in
Russia [1]. The present paper illustrates the use of the HRV
classification system to assess small changes of the functional
state of Russian cosmonauts onboard the ISS during long
term space flight.
2. Methods
2.1. Subjects
All HRV data were obtained from ECG recordings
(sample rate 1000 Hz) in 14 Russian crew members of
the International Space Station (ISS, men, n ¼14, age from
35 to 54 years) during the last flight months (5 and 6
month) and analyzed using the HRV classification system.
The classification system was developed from ECG data in
reference group 192 healthy subjects (visitors of health
center, men and women, n¼192, age from 38 to 63 years).
The classification system was further tested in Russian
cosmonauts during space flights onboard the MIR station
(men, n¼ 34, age range 35–55 years), in healthy subjects
during a 120-day head down tilt bedrest study (men,
n ¼6, age range 28–36 years), and in healthy subjects
studied during 8-month isolation (men, n ¼4, age range
37–48 years). Measurements in all groups were carried
out under resting conditions. All subjects signed a written
consent form. The study protocol was approved by the
institutional ethical commission.
2.2. HRV analysis
Analysis of HRV parameters was performed according to
the standards of the European Society of Cardiologists and
North-American Society of Electrostimulation and Electrophysiology [12]. HRV characteristics in the time domain
(SD, standard deviation; CV, coefficient of variation; rmssd,
root mean square of successive differences; pNN50, number
1149
of RR-interval pairs differing by more than 50 ms, SI,
triangular index or stress index for characterization of the
histogram) and in the frequency domain (TP, total spectral
power of HRV; VLF, HRV power in the very low frequency
range; LF, HRV power in the low frequency range; and HF,
HRV power in the high frequency range) were calculated as
described elsewhere [13].
3. Results
3.1. Stepwise discriminant analysis
A classification system based on HRV analysis was
developed using data from well characterized 192 volunteers (women n ¼51, age range 38–62 years; men, n ¼141,
age range 39–63 years, reference group). This reference
group contained patients and healthy subjects. The most
informative parameters for sufficiently high accuracy of
recognizing specific functional states were mean heart
rate (HR), the triangular histogram index (SI), pNN50 and
the HF spectral power. The standard form of discriminant
function equations for the first two canonic variables (L1
and L2) is given below
L1 ¼ 20:112nHR1:006nSI20:047npNN500:086nHF;
L2 ¼ 0:140nHR0:165nSI 21:293npNN50 þ 0:623nHF:
Canonic variables were calculated from absolute
values of HRV parameters. Analysis of standardized coefficients in these equations shows that SI has the highest
weight in the first equation, while pNN50 and HF have the
highest weight in the second equation.
Comparison of the physiological normal state with the
other functional states was made by analysis of reference
data arrays obtained from mathematical modeling and incremental discriminant analysis to deduce the decision rule.
Parameters L1 and L2 were referred to as coordinates
of the phase plane configuring the space of functional
states as shown in Fig. 1. The functional states are situated
on the phase plane in such a way that the physiological
normal state is characterized by positive L1 and negative
L2 values. The center is in the lower right quadrant of the
phase plane. The remaining functional states are located
in the other quadrants, i.e. prenosological state in the
upper right, premorbid state – in the upper left and
pathological state – in the lower left quadrant.
The averaged L1 and L2 values for the different groups
are shown as geometric means (Fig. 1). The geometric
means of all study groups were within the normal range.
However, a shift towards the prenosological area was
detected during the bedrest study as well as during
isolation and long term space flight.
HRV data from 14 Russian cosmonauts obtained
before, each month during 5–6 month in space, and after
space flight were analyzed and the canonical variables
were calculated. Fig. 2 illustrates the geometric means of
the 14 cosmonauts.
Compared to the Russian cosmonauts measured
onboard the MIR station also the mean values for the
ISS cosmonauts were within normal ranges before flight
and early during flight. Nevertheless, a trend towards a
shift from the lower right to the upper right was present
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R.M. Baevsky et al. / Acta Astronautica 69 (2011) 1148–1152
1
L2
Premorbid
Prenosological
L1
0
-10
-8
-6
-4
-2
0
4
2
Reference
group
Mir
-1
Bedrest
Isolatio n
-2
Physiological
normal
Pathological
-3
Fig. 1. Geometric means calculated using the canonical values L1 and L2 for each class of the reference group, for the MIR crew members during different
stages (1–2 months, 3–4 months and 5–6 months) of space flight (MIR), and for the subpopulations studied during different phases of 8-month isolation
and 120-day bedrest experiments are shown.
Pre-flight-1
Flight 1
Post-flight-1
L2
1
Pre-flight
2
L2
Flight
Post-flight
L1
0
-6
L1
0
-3
3
-2
0
-1
0
1
2
3
A
-4
Fig. 3. Functional states calculated by using the canonical values L1 and
L2 for an individual cosmonaut before, during and after space flight.
-1
Fig. 2. Geometric means calculated by using the canonical values L1 and
L2 for ISS crew members before, during and after space flight (n¼ 14).
during space flight. The functional state determined by
HRV remained relatively stable during space flight and
showed the most pronounced change after landing.
The result becomes more obvious if analyzing individual cosmonauts and distinct patterns can be described
depending on pre-flight HRV values. Figs. 3 and 4 illustrate two different examples of HRV during space flight.
The cosmonaut in Fig. 3 has higher HR before flight
(84 bpm) and lower HRV data in the time domain
(SD ¼22 ms, CV ¼3.1%, rmssd¼ 11 ms, SI ¼382 c.u.). The
HF power of HRV is also relatively low (HF¼88 ms2).
Consequently, he was classified as premorbid functional
state. However, during space flight the functional state of
the cosmonaut improved and remained in the prenosological functional state. The most pronounced change
occurred after landing but the functional state returned
to the pre-flight value within one week.
The cosmonaut in Fig. 4 has low HR before flight
(56 bpm) and high HRV data in the time domain
(SD ¼48 ms, CV¼4.5%, rmssd¼45 ms, SI¼66 c.u.). The
HF power of HRV is relatively high (HF¼845 ms2). In his
case the functional state in terms of HRV is very stable and
remains in the normal range except 30 days before the
flight and early after landing.
R.M. Baevsky et al. / Acta Astronautica 69 (2011) 1148–1152
1151
Fig. 4. Functional states calculated by using the canonical values L1 and
L2 for an individual cosmonaut before, during and after space flight.
We understand that this study has some limitations.
Our functional state evaluation relies virtually on a single
integral parameter, i.e. variability of heart rate. Characterizing the involvement of many different components of
reflex- and neurohumoral regulation with one parameter
is questionable. The reference groups used to develop the
classification system differ in gender, age and BMI compared to cosmonauts and it may be more appropriate to
develop a classification system based exclusively on the
data of cosmonauts with and without in-flight and postflight disturbances including perhaps the pre-flight functional state. Our classification system is based on resting
HRV data only and does not include responses to standardized stimuli as suggested by other studies trying to
predict the outcome in cosmonauts in terms of in-flight
and post-flight disturbances.
4. Discussion
5. Conclusion
The major finding of our study was that the classification
system based on discriminant analysis of HRV data to
calculate a functional state (four classes) of the cosmonaut
before, during and after space flight can be used to characterize individual adaptation to microgravity. Based on
geometric mean values, cosmonauts kept the functional
state in terms of HRV relatively stable during six month in
space. Nevertheless, the monthly measurements during
space flight allowed to detect a trend towards an impairment of HRV and a lower functional state at the end of
flight. The most pronounced changes were detected early
after landing (1–3 days) but returned to pre-flight values at
5–7 days after landing in most cosmonauts. The changes of
HRV seen during space flight depended on pre-flight HRV
parameters. Traditionally, HRV is used to characterize the so
called sympathovagal balance of HR control. Our approach
was based on the combination of four HRV parameters
mainly reflecting vagal HR control (pNN50, SI, HF power)
combined with mean HR and the physiological interpretation is more difficult.
The physiological interpretation of the canonical variables is perhaps of interest. In the first equation the
triangular index of the histogram has the highest weight
and is subtracted from mean HR. In the second equation
the pNN50 and HF power have the highest weights but
different signs. According to the phase plane of the
canonical variables a positive number for L1 and a negative number for L2 result in a normal functional state.
Than higher the histogram index than more negative
becomes L1. This may indicate that the first equation is
more related to the increase in sympathetic heart rate
control. The second equation may reflect parasympathetic
heart rate control, since pNN50 and HF power have the
highest impact on L2. However, the different sign is
difficult to explain. Physiological studies have shown that
there are functional states with simultaneous sympathetic
and vagal activation like prolonged apnea for example.
However, in most cases a decrease in vagal control is
accompanied by an increase in sympathetic heart rate
control and vice versa. Therefore, the two equations may
reflect to some degree how the relationship between the
two players changes during long term space flights.
The detected impairment of heart rate control during
the last months in space may end up in adaptation failure
after landing. The probability of adaptation failure and,
consequently, the early prediction may add important
information to improve the health control and to adjust
the individual training program or the prophylactic actions
before and after landing in individual cosmonauts.
2
L2
Pre-flight
Post-flight
L1
0
-6
-3
0
-2
3
Flight
B
-4
Acknowledgments
This work was supported by grants of the Bundesministerium fuer Bildung und Forschung and the German Aerospace Center (DLR). We thank the cosmonauts for their
participation in the study and the excellent performance.
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Irina Funtova (23.02.1941). She studied
electronics in Moscow, works in the field of
space medicine since 1964 and participated
in development of new techniques for cardiovascular system investigations at orbital
stations ‘‘Salut’’, ‘‘Mir’’. Actively participated
in preparation and carrying out of the
Russian–Austrian and Russian–French space
experiments onboard orbital station ‘‘Mir’’.
Now participates in development of techniques for carrying out researches on the
Russian segment of the International Space
Station (ISS). She is one of leading developers
of devices ‘‘Pulse’’, ‘‘Pneumocard’’ and ‘‘Sonocard’’, which are used on
ISS. She is the author of more than 100 articles.
Anna Chernikova (29.06.1962). She studied
psychology in and worked in the field of
biophysics and mathematical modeling of
cardiovascular system reactions at radiating
influences. Since 1992 she works as a
researcher in space medicine. She participated in carrying out bedrest, immersion
and isolation model experiments and
researches heart rate variability analysis
(HRV) in crew members of orbital station
‘‘Mir’’ and the International space station.
She develops mathematical models of
human functional states by results of HRV
analysis under long influence of microgravity. She is the author of more
than 70 articles.
Roman Baevsky (03.08.1928). He studied
medicine in Saratov. Since 1959 he works
in the field of space medicine, participated in
preparation of the first space flights. He is
known as one of the founders of space
cardiology, as one of the first authors to
write about heart rate variability analysis.
He participated in organization of researches
on orbital stations ‘‘Salut’’ and ‘‘Mir’’ and in
joint researches with scientists of Austria,
USA, France and Germany. The researches of
cardiovascular system in crews of International space station are carried out under his
direction. He is the author of more than 400 articles and 15
monographies.
Jens Tank (20.4.1963). He studied medical
biophysics in Moscow, Russia and medicine
in Dresden, Germany. He is specialized in
clinical pharmacology, internal medicine,
pathophysiology and sports medicine. He is
currently the leader of the research group on
clinical pharmacology of the cardiovascular
system at the institute of clinical pharmacology of the Hannover Medical School. His
major research interests are in the field of
hypertension and disorders of the autonomic
nervous system like autonomic failure, baroreflex failure and orthostatic intolerance.
He is the principal- and co-investigator on space medicine research
projects since 1993 and author of more than 80 articles published in
peer reviewed journals.