ISSN 2079-0570, Advances in Gerontology, 2019, Vol. 9, No. 4, pp. 453–458. © Pleiades Publishing, Ltd., 2019.

Russian Text © The Author(s), 2019, published in Uspekhi Gerontologii, 2019, Vol. 32, Nos. 1–2, pp. 145–151.

Adaptation to Dosed Hypoxia-Hyperoxia as a Factor

in the Improvement of Quality of Life for Elderly Patients
with Cardiac Pathology
O. S. Glazacheva, *, E. N. Dudnika, M. A. Zaparaa,
V. G. Samarcevaa, and W. W. Koflera
a
Sechenov First Moscow State Medical University, Moscow, 119991 Russia
*e-mail: glazachev@mail.ru
Received July 6, 2018; revised September 10, 2018; accepted September 17, 2018

Abstract—The effectiveness and safety of technology based on the principles of adaptive medicine—the inter-
val hypoxic–hyperoxic training (IHHT) method—was studied in order to substantiate new approaches to
maintain the quality of life of elderly patients with cardiac pathology. It has been proven that the use of IHHT
technology for elderly people with chronic coronary artery disease in the prescribed regime leads to a substan-
tial increase in the subjective perception of the quality of life and psycho-emotional status and a decrease in
the number of attacks of angina pectoris. This was accompanied by an increase in the level of physical working
capacity, exercise tolerance, and normalization of the lipid and carbohydrate metabolism. Treatments involv-
ing interval hypoxic-hyperoxic training are well tolerated and do not cause side effects; they can be used for
the complex rehabilitation of elderly patients with cardiac and comorbid pathology in the development of
optimal individualized regimens.

Keywords: adaptation, quality of life, elderly patient, hypoxia, hyperoxia

DOI: 10.1134/S2079057019040052

INTRODUCTION Drug supply alone is clearly not enough to main-

The unprecedented global demographic changes
observed in the 21st century, which are associated with
an increase in life expectancy throughout the world,
are a manifestation of the problem of population
aging. According to the forecasts of Help Age Interna-
tional, elderly people (60 years or older) will make up
more than 1/5 of the world’s population by 2050, and
their number will be 2.03 bln in relation to the current
809 mln (11%) [15, 20]. Since 2006, the number of
elderly citizens in Russia has also been growing
steadily [2].
Thus, an acute medical and social problem for
healthcare and social support services for society is the
maintenance of the quality of life (QL) among people
of elderly and senile age, primarily, its psychosomatic
and emotional components.
The quality of life of elderly people in Russia is
alarming: according to the data for 2015, Russia occu-
pied the 65th place in the world according to the
Global Age Watch Index in the elderly [14]. Elderly
and senile people currently demonstrate an extremely
low level of involvement in social life, poor health, and
a low level of material support. There is a high propor-
tion of elderly people with somatic disorders, predom-
inantly cardiovascular, orthopedic, oncological, and
mental, cognitive disorders [2, 8].
tain a proper QL and health of the elderly. A number
of systematic studies have proved that a combined
course of the application of individually selected phys-
ical activities, physiotherapeutic techniques, and psy-
chological training, as well as the education of the
elderly about the control of risk factors of chronic dis-
eases in the form of multimodal rehabilitation pro-
grams, are the most effective approach to the rehabil-
itation and maintenance of the QL in the elderly [6, 8,
15, 16].
The most important role in the creation and imple-
mentation of multimodal rehabilitation programs
(MRPs) is played by multidisciplinary approaches,
well-coordinated work with specialists in various fields
(psychologists, physical therapists, medical special-
ists, exercise training instructors, and social workers),
as well as the development and implementation of new
effective, nondrug technologies for physical rehabili-
tation, psychological training, etc. In particular, the
method of interval hypoxic training (IHT) presents
certain prospects.
The idea of hypoxia exclusively as a damage factor
has recently undergone significant changes, and the
use of moderate hypoxia or its repeated short-term
hypoxic effects is pathogenetically substantiated and
promising in general for the purpose of increases in the
adaptive reserve of the body and correction of patho-

453
454 GLAZACHEV et al.
logical states caused by a lack of oxygen. It was noted
that the development of adaptation to hypoxia and an
increase in the general specific resistance of the body
are significantly accelerated when the hypoxic effect is
divided into several separate repeated periods and its
intensity and duration are limited by the physiological
norm, at which the effective compensation of the
occurring functional shifts and rapid recovery after the
end of hypoxia are still possible [3, 9, 11].
The clinically significant effects of IHT are in
many respects similar to the effects of physical training
[11, 17, 19], and the cascade of molecular-cell adaptive
mechanisms includes the activation of transcription
factors, hypoxia-inducible factors (HIFs). HIFs trig-
ger the synthesis of effector proteins, which reduce the
excessive formation of ROSs, repair enzymes, compo-
nents of antioxidant protection, growth factors, and
other bioactive substances that act as effectors of
adaptation to hypoxia [9, 18].
It was established that the effectiveness of IHT can
be increased via the replacement of normoxic pauses
(reoxygenation) with a supply of a hyperoxic gas mix-
ture to the patient by the method of interval hypoxic-
hyperoxic training (IHHT) [3]. As compared to nor-
moxic reoxygenation, the period of created hyperoxia
involves a more pronounced ROS induction; this is
necessary to trigger the cascade of the redox signal
pathway, which leads to a significant synthesis of pro-
tective intracellular protein molecules, mainly with
antioxidant functions (antioxidant protection
enzymes, iron binding proteins, heat shock proteins)
[9]. Experimental studies demonstrated more pro-
nounced membrane-stabilizing effects and a signifi-
cant increase in the stress and hypoxic resistance of
the myocardium and brain, level of antioxidant pro-
tection, and tolerance of physical exertion as a result of
adaptation to IHHT as compared with IHT.
The IHHT method is empirically based on the
stage of treatment of bronchial asthma in sanatoria
and spas with the combined use of IHT and enteric
oxygen therapy (oxygen cocktails) [7]. It has been
tested in pilot studies on patients with metabolic syn-
drome and stable angina pectoris [4, 5]. A controlled
study of elderly patients with initial forms of dementia
found that the introduction of IHT in MRPs leads to
significant improvement in cognitive functions and
increased exercise tolerance [1].
This study was carried out to assess the effective-
ness of the introduction of a course of IHHT proce-
dures in rehabilitation programs for geriatric patients
with cardiac pathology against the background of ade-
quately selected drug therapy in indicators of QL and
cardiometabolic risk factors.
MATERIALS AND METHODS
The study involved 36 elderly patients undergoing
regular follow-ups with a diagnosis of chronic coro-
nary artery disease and angina pectoris of II–III FC
(10 men with a mean age of 68.2 ± 6.1 years) that were
ADVANCES IN GERONTOLOGY
randomized after the initial examination into two
study groups: the IHHT group (n = 17) and the control
group (CG, n = 19). The research protocol was com-
piled in accordance with the provisions of the “Bio-
ethical Rules for Conducting Research on Humans”
and approved by the University’s bioethical commis-
sion; written, informed consent was received from all
patients before the start of the work.
The patients from the IHHT group were subjected
to three weeks of adaptation to interval hypoxia-
hyperoxia with one procedure per day for five days and
breaks of two days (15 trainings). The study was per-
formed with a ReOxy Cardio normobaric device to
obtain hypoxic and hyperoxic gas mixtures based on
feedback (S.A. Aimediq, Luxembourg).
Before starting the course of the procedures, we
determined the individual sensitivity of patients with
hypoxia with a 10-min hypoxic test (HT)—breathing
through a mask with a gas mixture with 12% O2 con-
tent with minute-by-minute monitoring of the heart
rate and saturation of arterial blood hemoglobin with
oxygen (SaO2) [1].
During the IHHT procedures, the duration of sup-
ply of the hypoxic (11–12% O2) and hyperoxic (35%
O2) gas mixtures was controlled with allowance for the
HT results according to the principle of biological
feedback automatically based on monitoring of the
individual values of SaO2 and heart rate [15]. The
duration of one procedure was 45–50 min, 4–6 min
on average for each hypoxic period and 1–2 min for
the hyperoxic period depending on the rate of SaO2
recovery in a particular patient. A record was made in
the observation diary after each training; the proce-
dure date, patient self-reports on the tolerability of the
procedure, complaints, and side effects during the
training were noted. Before and after each procedure,
the blood pressure and heart rate were measured. After
a course of IHHT, the patients kept a self-monitoring
diary for one month. They indicated the presence of
sternal aches, headaches, an assessment of overall well-
being according to the visual analog scale (1–5 points),
the use of medications, and measurements of blood
pressure and heart rate in the morning and evening.
The patients from the control group also under-
went a placebo training that simulated IHHT, receiv-
ing atmospheric air through a mask of the same appa-
ratus. The study participants were not informed about
the differences or their assignment to different groups,
and the procedures were monitored by two nurses.
All patients underwent a comprehensive examina-
tion before and after the course of IHHT or placebo
training. The patients of the IHHT group were also
examined one month after the end of the course to
assess the duration of the effects of adaptation to inter-
val hypoxia–hyperoxia.
The Russian-language version of the MOS SF-36
questionnaire was used to assess QL. Based on the sur-
vey results, eight parameters were calculated: physical
functioning (PF), the role of physical problems in lim-
Vol. 9 No. 4 2019
 ADAPTATION TO DOSED HYPOXIA-HYPEROXIA AS A FACTOR 455

Table 1. Indicators of MOS SF-36 and SAQ life quality questionnaires subscales
Scale Group Before IHHT After IHHT (or placebo) After 1 month
MOS SF-36 questionnaire
Physical functioning (PF) IHHT 48.2 ± 13 55.7 ± 12* 51.7 ± 14
Control 44 ± 11.2 47.5 ± 11.9** –
Role physical (RP) IHHT 47 ± 17.8 61.7 ± 18.8* 55.8 ± 19
Control 50.5 ± 9.3 52.3 ± 14.2 –
Body pain (BP) IHHT 22 ± 39.4 48.5 ± 43.7 58.8 ± 39.4*
Control 25 ± 11.8 27.3 ± 8.9** –
Vitality (VT) IHHT 50.2 ± 12.5 47.2 ± 10.3* 48.5 ± 3.9
Control 46.3 ± 11.5 50.2 ± 10.8 –
Social functioning (SF) IHHT 49.9 ± 15.5 55.5 ± 14 58.1 ± 11.8
Control 50.2 ± 14.7 51.4 ± 12.3 –
Role-emotional (RE) IHHT 50.8 ± 15.8 59.7 ± 11.9 61.1 ± 13.5*
Control 50.9 ± 15.6 51.6 ± 9.9 –
Mental health (MH) IHHT 60.4 ± 16.7 62 ± 13.7 65.8 ± 11.9*
Control 57.8 ± 13.4 61.5 ± 11.8 –
General health (GH) IHHT 37.2 ± 48.4 51.1 ± 41 57.1 ± 32.7*
Control 42.5 ± 21.1 44 ± 25.6 –
Seattle angina questionnaire
Physical limitation IHHT 39.8 ± 16.3 48 ± 9.6* 47.2 ± 11.2*
Control 53.5 ± 19.3 50.1 ± 19.5 –
Angina stability IHHT 52.9 ± 26.3 75.2 ± 23.4* 75.2 ± 21.6*
Control 68.3 ± 29 69.6 ± 20 –
Angina frequency IHHT 49.4 ± 27.2 75.8 ± 19.6* 74.1 ± 18.9*
Control 71.3 ± 34.7 72.1 ± 28.6 –
Treatment satisfaction IHHT 58.5 ± 16.4 75.1 ± 15.9* 77.3 ± 17.2*
Control 77.1 ± 21.9 78.9 ± 19.1 –
Disease perception IHHT 45.5 ± 13.2 58.8 ± 16.5 59.9 ± 16.3*
Control 56.6 ± 23.8 58.8 ± 22* –
Here and in Table 2: * the significance of differences with respect to initial data in one group, p < 0.05; ** the significance of intergroup
differences at the same observation stage, p < 0.05.

ited activity (RP), body pain (BP), vitality (VT), social
functioning (SF), the role of emotional problems in
limited life activity role-emotional (RE), mental
health (MH), and general health (GH). Each indica-
tor was calculated in accordance with a scale from 0 to
100 points: the lower the score was, the worse was the
QL characteristic. The patients were additionally tested
with the Seattle angina questionnaire (SAQ) [13].
To assess tolerance to physical exertion (TPE),
exercise spiroergometry testing was performed with
the CARDIOVIT CS-200 Ergo-Spiro complex
(SCHILLER, Switzerland), a system involving the use
of a treadmill with the M-BRUCE protocol. The cri-
teria for termination of the load test were in accor-
dance with the ACC/AHA recommendations: Prac-
tice Guidelines for Exercise Testing [10]. All patients
underwent blood sampling, followed by the determi-
nation of the lipid profile and glucose level, to assess
metabolic status.
Statistical analysis of the results was carried out
with the Statistica 11.0 program (StatSoft Inc., United
States). The data of descriptive statistics—the average
value ±σ (M ± σ)—were used to describe indicators
presented in the form of quantitative variables. The
one-sample t-test, Wilcoxon criterion, and Mann-
Whitney criterio, were used to assess the significance
of intragroup and intergroup differences in psychological
and clinical-physiological indices, respectively. The dif-
ferences were considered significant at p < 0.05.
RESULTS AND DISCUSSION
According to the results of the initial examination,
load testing, and QL assessment, the patients of the
compared groups did not significantly differ. A signif-
icant improvement in QL self-assessment by the
elderly patients was established after the course of
IHHT and in the long term (Table 1). A significant
increase in values was revealed on the PA, RA, and V
scales; one month after the course, it was found for the
MH and ES scales. A significant increase in the indi-
cators of QL self-assessments and improvement in the

ADVANCES IN GERONTOLOGY Vol. 9 No. 4 2019

456 GLAZACHEV et al.

Table 2. Indicators of load tolerance in the cardiac-pulmonary stress test in dynamics in patients of both groups
Parameter Group Before IHHT After IHHT After 1 month
Time of work up to failure, s IHHT 303 ± 147 362 ± 124* 342 ± 113
Control 325 ± 112 332 ± 76 –
HRmax, bpm IHHT 118.4 ± 14.1 123.9 ± 10.7 122.3 ± 10.2
Control 124.1 ± 9.3 125.8 ± 11.3 –
Metabolic equivalent IHHT 3.5 ± 1.2 39.1 ± 1 4.2 ± 1.2*
Control 3.7 ± 0.9 3.8 ± 1** –
VO2max, mL/kg IHHT 13.4 ± 2.5 16.9 ± 1.4 14.1 ± 2.4
Control 12.2 ± 3.7 12 ± 6.3** –
AT/VO2, mL/kg IHHT 11.5 ± 1.3 13.8 ± 2* 13.8 ± 0.3*

main manifestations of the disease were noted in the
IHHT group on the main SAQ scales: the limitation of
physical exertion (p = 0.008), seizure stability (p =
0.003), seizure frequency (p = 0.0006), and satisfac-
tion with treatment (p = 0.002) with the preservation
of effects after one month. Significant dynamics in the
QL characteristics were not noted in the control
group.
The improvement of the patients’ subjective per-
ception of QL and their mental state under the influ-
ence of the IHHT course was generally accompanied
by a significant increase in the initially reduced
parameters (relative to the age standards) of exercise
tolerance: an increase in oxygen consumption at the
level of the anaerobic threshold AT/VO2 (p = 0.02)
and the VO2max values of the duration of exercise per-
formance until failure, which were higher than in the
control group (p = 0.02). V. B. Shatilo et al. described
effects in a similar direction but after a longer course
of adaptation to passive hypoxia–normoxia in the
elderly [16] or after the application of MRPs with reg-
ular physical exercising [16]. No significant dynamics
of the analyzed parameters were noted in the control
group (Table 2).

8
* *
7 **
*
6 *

3
* *
2 **
* * **
1

0
Before After One month Before After
the course the course after the course the course
IHHT group Control group
TCh TG HDL LDL Glucose

Fig. 1. Indicators of the cholesterol profile and blood plasma glucose level in patients of both groups in the initial state, after the
course of interval hypoxic–hyperoxic training (IHHT or placebo), and one month after the end of training. * Significance of dif-
ferences with respect to the initial values in the group, p < 0.05; ** significance of intergroup differences at the same observation
stage, p < 0.05. TCh—total cholesterol, mM/L; TG—triglycerides, mM/L; HDL—high density lipoproteins, mM/L; LDL—low
density lipoproteins, mM/L.

ADVANCES IN GERONTOLOGY Vol. 9 No. 4 2019

 ADAPTATION TO DOSED HYPOXIA-HYPEROXIA AS A FACTOR
In addition, a 50% decrease in the incidence of
anginal attacks was noted in the IHHT group during
repeated stress tests immediately after the procedures,
and a 75% decrease was seen one month after the course
of treatment as compared with the initial values.
Meanwhile, there were no significant correlations
of the degrees of increase in the indicators of exercise
tolerance and shifts in the values of the QL scales,
which confirms the not always “synchronous”
dynamics of subjectively perceived characteristics of
health status and physical and emotional states and,
conversely, objective parameters of exercise perfor-
mance.
Patients from the IHHT group also showed positive
dynamics of cholesterol metabolism and blood plasma
glucose levels (Fig. 1).
Initially, patients from the IHHT group differed
from the control group by higher values (relative to the
reference values) of triglycerides, glucose, and
decreased HDL. After the procedures, there was a sig-
nificant decrease in the level of triglycerides (p =
0.045) and total cholesterol (p = 0.05) with a signifi-
cant increase in HDL values (p = 0.036) with a ten-
dency toward a decrease in the LDL level (p = 0.07).
As a result, after the course of IHHT and in the long
term, there was a significant decrease in the athero-
genic coefficient, which was initially increased in rela-
tion to the control value—from 4.64 ± 0.63 to 3.64 ±
0.16 (p = 0.05) and 3.78 ± 0.41 (p = 0.041) one month
after the procedure.
According to the data of several authors, HDL have
antioxidant properties, and their antiatherogenicity is
partially dependent on the antioxidant activity of para-
oxonase 1, which is associated with HDL apo-proteins
[13]. This allows us to substantiate the potential of the
technologies of adaptation to interval hypoxia as a
means to modify metabolic risk factors for the devel-
opment and progression of cardiovascular diseases
(the balance of lipoprotein fractions activates reverse
cholesterol transport, and the antioxidant effect of
HDL prevents LDL modification) [13].
A moderate decrease was also noted in the initially
elevated blood glucose values after the IHHT cycle
and in the long term, which indirectly confirms the
potential of the procedures of adaptation to interval
hypoxia for the correction of carbohydrate metabo-
lism and the complex treatment of patients with insu-
lin resistance [12].
CONCLUSIONS
The QL of an elderly person with cardiac pathology
is largely determined not only by socioeconomic
parameters and level of medical support but also his or
her independence from outside help, the presence of
external and internal resources, and the mastery of
coping strategies.
ADVANCES IN GERONTOLOGY Vol. 9 No. 4 2019
457
These characteristics are closely related to the
maintenance of the physical, mental, and emotional
components of the adaptive potential, which must be
the purpose of the use of multimodal rehabilitation
programs equipped with modern physiotherapeutic
methods, in particular, the technology of adaptation
to interval individually dosed hypoxia, alternating with
episodes of moderate hyperoxia.
The study found that the use of technology of inter-
val hypoxic–hyperoxic training in elderly people with
chronic coronary artery disease in the selected course
mode leads to a significant increase in patients’ sub-
jective perception of the QL and their psycho-emo-
tional status, which was accompanied by an increased
level of the physical capacity for work, exercise toler-
ance, a significant decrease in angina manifestations,
and normalization of the lipid and carbohydrate
metabolisms. IHHT training procedures are well tol-
erated and do not cause side effects.
Additional studies are needed to identify the most
optimal modes of the application of the method, pro-
cedure frequency, the periodicity of repetition of
hypoxic-training courses, as well as a more detailed
disclosure of the mechanisms of adaptation to
repeated episodes of hypoxia and hyperoxia.
FUNDING
The study was supported by grant of the Russian Foun-
dation for Basic Research, project no. 17-06-0078, “Quality
of Life in Elderly Patients with Cardiovascular Pathology:
The Impact of the Procedures of Adaptation to Interval
Hypoxia–Hyperoxia.”
COMPLIANCE WITH ETHICAL STANDARDS
Conflict of interest. The authors declare that they have no
conflict of interest.
Statement of compliance with standards of research involv-
ing humans as subjects. The research protocol was compiled
in accordance with the provisions of the “Bioethical Rules
for Conducting Research on Humans” and approved by the
University’s bioethical commission; written informed con-
sent was received from all patients before the work began.
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Translated by L. Solovyova
Vol. 9 No. 4 2019