ResearchPDF Available

Models for Living Organism’s Functioning at Normal and Pathological Conditions

Authors:

Abstract

A human organism as well as any living organism should be considered as a complex dynamic system created by nature
Lecturer: Lushchyk U.B., MD
u.lushchyk@gmail.com
u.lushchyk@gmail.com
www
www.
.lushchyk
lushchyk.
.org
org
www.istyna.kiev.ua
www.istyna.kiev.ua
Coauthors I.P. Babii
Coauthors I.P. Babii
V.V. Novytskyy
V.V. Novytskyy
Models for Living Organism’s Functioning at
Normal and Pathological Conditions
Modern Models for the Living
Modern Models for the Living
Organism’s Functioning at Normal
Organism’s Functioning at Normal
and Pathological Conditions
and Pathological Conditions
A human organism as well as any living organism should be
A human organism as well as any living organism should be
considered as a complex dynamic system created by nature
considered as a complex dynamic system created by nature
According to the systems’ modeling
According to the systems’ modeling
we consider the following essential components
we consider the following essential components
needed for functioning of the system
needed for functioning of the system
1.
1. structural elements
structural elements (
(in the living system
in the living system:
:
organs and subsystems
organs and subsystems (
(cardiovascular
cardiovascular,
,
nervous
nervous,
, musculoskeletal
musculoskeletal,
, digestive
digestive,
, secretion
secretion,
,
endocrine etc.
endocrine etc.)
),
,
2.
2. conductors inside a subsystem,
conductors inside a subsystem,
3.
3. intersystem conductors,
intersystem conductors,
4.
4. parameters indication system,
parameters indication system,
5. data processing system
5. data processing system,
,
6.
6. feedback system,
feedback system,
7.
7. checking, control systems and various types of
checking, control systems and various types of
regulation.
regulation.
Clockwork
Clockwork
The mechanical and cybernetic
The mechanical and cybernetic
models of the complex
models of the complex
systems
systems
could be the more
could be the more
similar to prototypes
similar to prototypes
for the
for the
living system in mathematical
living system in mathematical
modeling.
modeling.
Very these models are
Very these models are
combined
combined
by principle of
by principle of
dynamic nature –
dynamic nature –
the system
the system
reacts fast
reacts fast
both inside and
both inside and
outside
outside
Mechanical system
Mechanical system
Peculiar features of the mechanical
Peculiar features of the mechanical
system lie in the fact
system lie in the fact
that the
that the
system functioning is controlled by
system functioning is controlled by
principle of susceptibility to
principle of susceptibility to
mechanical changes.
mechanical changes.
It means that identification sensors
It means that identification sensors
react to changing of pressure,
react to changing of pressure,
temperature, amplitude of
temperature, amplitude of
movement etc,
movement etc,
Mechanical system
Mechanical system
The mechanical system
The mechanical system
is sensitive to changes of a
is sensitive to changes of a
certain gradient (differences
certain gradient (differences
of a
of a
background and an actual
background and an actual
index) of that or another
index) of that or another
parameter
parameter
(a gradient
(a gradient
becomes a parameter
becomes a parameter
of sensitivity for the system).
of sensitivity for the system).
An analogy
An analogy
Water-supply system
Water-supply system
functions very on this
functions very on this
principle namely water
principle namely water
spontaneously flows from
spontaneously flows from
high pressure to low
high pressure to low
pressure.
pressure.
In the living system
In the living system
cardiovascular, partially
cardiovascular, partially
digestive and secretion
digestive and secretion
subsystems correspond to
subsystems correspond to
this type of functioning.
this type of functioning.
Cybernetic system
Cybernetic system
When we consider the model
When we consider the model
of the cybernetic system, it
of the cybernetic system, it
is more sensitive structure
is more sensitive structure
with numerous indicators
with numerous indicators
and powerful control
and powerful control
system.
system.
It is so kind of electronic
It is so kind of electronic
system with large
system with large
superstructures of
superstructures of
consecutive and parallel
consecutive and parallel
conductors’ connection.
conductors’ connection.
Cybernetic system
Cybernetic system
Therefore
Therefore
in comparison with the mechanical
in comparison with the mechanical
system chances of emergency
system chances of emergency
breakage of the system are quite
breakage of the system are quite
high, as in case of breakage of
high, as in case of breakage of
one segment the whole system
one segment the whole system
could be blocked.
could be blocked.
In the living system
In the living system
nervous,
nervous,
digestive,
digestive,
secretion,
secretion,
endocrine,
endocrine,
partially cardiovascular
partially cardiovascular
subsystems correspond to
subsystems correspond to
the electronic-cybernetic
the electronic-cybernetic
type.
type.
Cybernetic system
Cybernetic system
Mixed mechanic-electronic (hybrid)
Mixed mechanic-electronic (hybrid)
model
model
Very this distribution
Very this distribution
of various algorithms in a subsystem’s
of various algorithms in a subsystem’s
functions inside the human organism
functions inside the human organism
enables to consider its functioning
enables to consider its functioning
on the whole
on the whole
as a
as a mixed mechanic-electronic (hybrid)
mixed mechanic-electronic (hybrid)
model.
model.
At the present level of the science
At the present level of the science
development
development the living organism is
the living organism is
simulated in particular as the cybernetic
simulated in particular as the cybernetic
system
system
with numerous constant and variable
with numerous constant and variable
parameters, which characterize its
parameters, which characterize its
dynamics,
dynamics,
participate actively in the processes
participate actively in the processes
of regulation and control.
of regulation and control.
Mixed mechanic-electronic (hybrid)
Mixed mechanic-electronic (hybrid)
model
model
Naturally, that the question arises:
Naturally, that the question arises:
«What type of the system control prevails
«What type of the system control prevails
in functioning of the hybrid system?»
in functioning of the hybrid system?»
It is possible that the muscular system in
It is possible that the muscular system in
the human organism is as a mediator
the human organism is as a mediator
between the electronic and mechanical
between the electronic and mechanical
systems.
systems.
The hierarchy of functioning of the
The hierarchy of functioning of the
living system
living system
According to the hierarchy of functioning of
According to the hierarchy of functioning of
the living system we consider the
the living system we consider the
organism as an integral system with
organism as an integral system with
numerous indicators that function by
numerous indicators that function by
principle of feed-back and submit to single
principle of feed-back and submit to single
center.
center.
Only such hierarchy enables to make a
Only such hierarchy enables to make a
principle of subordination and precise
principle of subordination and precise
submission of different control levels.
submission of different control levels.
Therefore we should multisided consider complex
Therefore we should multisided consider complex
hierarchy of the living system and virtually imagine it in
hierarchy of the living system and virtually imagine it in
many dimensions:
many dimensions:
1. Macro- and microlevel of
1. Macro- and microlevel of
processes’ organization in the
processes’ organization in the
living organism.
living organism.
2. Level of providing vital activity
2. Level of providing vital activity
in the organism
in the organism
3.
3. Levels of subsystems’
Levels of subsystems’
functioning
functioning
4.
4. A level of the intrasystem
A level of the intrasystem
balance in every subsystem of
balance in every subsystem of
living organism
living organism
5.
5. Hierarchical level of the
Hierarchical level of the
balance control
balance control
2. Level of providing vital activity
2. Level of providing vital activity
in the organism:
in the organism:
minimum for life preservation,
minimum for life preservation,
average (background) - for
average (background) - for
providing background vital
providing background vital
activity of the organism,
activity of the organism,
high (reserve) - for supporting
high (reserve) - for supporting
the organism at overloads.
the organism at overloads.
Therefore we should multisided consider complex
Therefore we should multisided consider complex
hierarchy of the living system and virtually imagine it in
hierarchy of the living system and virtually imagine it in
many dimensions:
many dimensions:
3. Levels of subsystems’
3. Levels of subsystems’
functioning:
functioning:
structural (reverse and
structural (reverse and
irreversible damages)
irreversible damages)
hydrodynamic level
hydrodynamic level
hemodynamic level
hemodynamic level
energy level.
energy level.
Therefore we should multisided consider complex
Therefore we should multisided consider complex
hierarchy of the living system and virtually imagine it in
hierarchy of the living system and virtually imagine it in
many dimensions:
many dimensions:
Therefore we should multisided consider complex
Therefore we should multisided consider complex
hierarchy of the living system and virtually imagine it in
hierarchy of the living system and virtually imagine it in
many dimensions:
many dimensions:
4.
4. A level of the intrasystem balance in every
A level of the intrasystem balance in every
subsystem of living organism:
subsystem of living organism:
structural balance
structural balance
functional balance
functional balance
conduction balance
conduction balance
energy balance
energy balance
mechanical balance
mechanical balance
electronic balance (cellular, h
electronic balance (cellular, humoral
umoral etc)
etc)
5.
5. Hierarchical level of
Hierarchical level of
the balance control:
the balance control:
autonomous
autonomous
subsystemic
subsystemic
central
central
intersystemic
intersystemic
Therefore we should multisided consider complex
Therefore we should multisided consider complex
hierarchy of the living system and virtually imagine it in
hierarchy of the living system and virtually imagine it in
many dimensions:
many dimensions:
Thus
Thus
the human organism is a complex
the human organism is a complex
many-sided living system with
many-sided living system with
numerous changeable parameters
numerous changeable parameters
of its functioning on different levels
of its functioning on different levels
of its organization with many
of its organization with many
indication systems and feedback
indication systems and feedback
connection.
connection.
The present level of
The present level of
mathematical modeling
mathematical modeling
development enables to
development enables to
investigate profoundly the
investigate profoundly the
hierarchy of the models’
hierarchy of the models’
functioning of the hybrid
functioning of the hybrid
systems
systems
and study new unexplored algorithms
and study new unexplored algorithms
of
of auto
autoregulation in the living organism.
regulation in the living organism.
Our experience of patients’
Our experience of patients’
treatment
treatment
Our large experience of treatment patients in coma -
Our large experience of treatment patients in coma - apal
apall
lic
ic
syndrome (AS) and the analysis of restoration of their
syndrome (AS) and the analysis of restoration of their
functions in the rehabilitation process made us interested in
functions in the rehabilitation process made us interested in
the aspect of estimation of reserve potential of the human
the aspect of estimation of reserve potential of the human
organism and capacity of self-restoration with numerous and
organism and capacity of self-restoration with numerous and
deep damages in the brain, multi-injuries. Our considerations
deep damages in the brain, multi-injuries. Our considerations
we tried to present in the next models from minimum capability
we tried to present in the next models from minimum capability
to maximum adaptation.
to maximum adaptation.
A minimal model
A minimal model
The human body could be an initial stage for modeling the
The human body could be an initial stage for modeling the
living system, which is structurally formed, has all organs
living system, which is structurally formed, has all organs
but not all are functioning. In most cases very this model
but not all are functioning. In most cases very this model
could be as a standard for modeling any comatose states.
could be as a standard for modeling any comatose states.
Our results have shown that most patients with AS had
Our results have shown that most patients with AS had
satisfactory blood, urine tests etc. It says that a living
satisfactory blood, urine tests etc. It says that a living
organism was statically preserved, however from dynamic
organism was statically preserved, however from dynamic
positions it was not able to function adequately. This
positions it was not able to function adequately. This
means that considering the simple model we have a
means that considering the simple model we have a
structurally preserved body, but is not capable to function
structurally preserved body, but is not capable to function
- a body in shock (coma with expressed disbalance in
- a body in shock (coma with expressed disbalance in
functioning of vitally important organs).
functioning of vitally important organs).
A chaotic model
A chaotic model
Now we will complicate the model - a body start
Now we will complicate the model - a body start
functioning as a chaotic system, organs and
functioning as a chaotic system, organs and
systems chaotically work in their autonomous
systems chaotically work in their autonomous
background mode. This model reminds an
background mode. This model reminds an
orchestra that keeps training without a bandleader
orchestra that keeps training without a bandleader
before a concert. Chaos of sounds of different
before a concert. Chaos of sounds of different
instruments could be heard. Sometimes
instruments could be heard. Sometimes
occasionally they fall together in euphony. The
occasionally they fall together in euphony. The
model of initial resuscitation can be considered by
model of initial resuscitation can be considered by
the example of an organism which begins to «wake
the example of an organism which begins to «wake
up» from shock.
up» from shock.
A model of the control
A model of the control
decentralization
decentralization
The next model is a variant of
The next model is a variant of resuscita
resuscitation, there is a
tion, there is a
start for rhythmic work of the heart and breathing,
start for rhythmic work of the heart and breathing,
however there are no minimum signs of the brain
however there are no minimum signs of the brain
functioning, which clinically are shown by changing
functioning, which clinically are shown by changing
of phases «sleep-cheerfulness». That is so-called
of phases «sleep-cheerfulness». That is so-called
heavy artillery (heart, breathing) started in the
heavy artillery (heart, breathing) started in the
automatic mode, however the leading organ the
automatic mode, however the leading organ the
brain is not able to restore its higher hierarchical
brain is not able to restore its higher hierarchical
function. The model can be associated with the
function. The model can be associated with the
state of
state of apal
apall
lic
ic syndrome.
syndrome.
Thus
Thus
3 models - coma, resuscitation and
3 models - coma, resuscitation and apa
apal
llic
lic
syndrome can be in the basis of the
syndrome can be in the basis of the
process of mathematical modeling, as the
process of mathematical modeling, as the
most primitive, and the next models of
most primitive, and the next models of
«little» and «large» consciousness, self-
«little» and «large» consciousness, self-
service, social and professional adaptation
service, social and professional adaptation
describe more complicated levels of the
describe more complicated levels of the
human organism’s functioning.
human organism’s functioning.
Parameters of the living
Parameters of the living
system model
system model
Parameters of the living system model could
Parameters of the living system model could
be divided into parameters of external
be divided into parameters of external
dynamics (visual and clinical) and internal
dynamics (visual and clinical) and internal
dynamics (instrumental).
dynamics (instrumental).
There are such variants of identification of
There are such variants of identification of
parameters for the living system model:
parameters for the living system model:
Visual,
Visual,
Clinical,
Clinical,
Instrumental.
Instrumental.
In our clinical practice the mentioned approach gave
In our clinical practice the mentioned approach gave
significant results and enabled to come to such
significant results and enabled to come to such
conclusions
conclusions
1. All living organisms function by principle of stable balance
1. All living organisms function by principle of stable balance
of two mutually opposite vectors of influence:
of two mutually opposite vectors of influence:
arteriovenous balance
arteriovenous balance
harmonic development - disproportionate ontogenesis
harmonic development - disproportionate ontogenesis
excitation-braking and etc.
excitation-braking and etc.
2.
2. According to laws of mathematical modeling living
According to laws of mathematical modeling living
organisms exist as integral with precise systemic
organisms exist as integral with precise systemic
hierarchies. Violation of subordination of one or another
hierarchies. Violation of subordination of one or another
system in the brain could result in re-profiling of the size
system in the brain could result in re-profiling of the size
and vector of excitation, violation of processes of
and vector of excitation, violation of processes of
synchronization of all involved links.
synchronization of all involved links.
In our clinical practice the mentioned approach gave
In our clinical practice the mentioned approach gave
significant results and enabled to come to such
significant results and enabled to come to such
conclusions
conclusions
3.
3. The living system functions as a hybrid system at combination and
The living system functions as a hybrid system at combination and
simultaneous existence of two subsystems - mechanical and electronic
simultaneous existence of two subsystems - mechanical and electronic
control with their partial mutual submission. The mechanical system is
control with their partial mutual submission. The mechanical system is
more lasting in comparison with the hybrid one.
more lasting in comparison with the hybrid one.
4.
4. Therefore lack of pathological
Therefore lack of pathological paro
paroxysms, diminishing of their frequency
xysms, diminishing of their frequency
and duration on a background of harmonic development of personality
and duration on a background of harmonic development of personality
of a patient and balancing of regulator systems of various vectors
of a patient and balancing of regulator systems of various vectors
should be considered as an end goal in treatment of patients of
should be considered as an end goal in treatment of patients of
psychoneurological type. Paradoxical reactions could be an exception,
psychoneurological type. Paradoxical reactions could be an exception,
they said about disbalance or failure in the system of reacting and one
they said about disbalance or failure in the system of reacting and one
should consider them and foreseen before the treatment. The
should consider them and foreseen before the treatment. The
paradoxical reactions of a disbalanced organism can result in
paradoxical reactions of a disbalanced organism can result in
considerable worsening of the patient’s state in comparison with the
considerable worsening of the patient’s state in comparison with the
background ill state.
background ill state.
In our clinical practice the mentioned approach gave
In our clinical practice the mentioned approach gave
significant results and enabled to come to such
significant results and enabled to come to such
conclusions
conclusions
5.
5. A concentration of anticonvulsant drugs in an elbow vein can
A concentration of anticonvulsant drugs in an elbow vein can
considerably differ from the concentration of these drugs in the brain
considerably differ from the concentration of these drugs in the brain
areas, especially at presence of the phenomenon of the arteriovenous
areas, especially at presence of the phenomenon of the arteriovenous
shunting in cavernous or in other sinuses of the brain.
shunting in cavernous or in other sinuses of the brain.
6.
6. Stress reactions, which are fixed in the brain and were not neutralized
Stress reactions, which are fixed in the brain and were not neutralized
during psychotherapy sessions, can be a
during psychotherapy sessions, can be a trig
trigg
ger
er of frightful dreams
of frightful dreams
resulting in a nightly convulsive attack.
resulting in a nightly convulsive attack.
7. Today the complex objectivization of the state of all systems in the brain
7. Today the complex objectivization of the state of all systems in the brain
(exactly the brain!) is urgently required under control of up-to-date
(exactly the brain!) is urgently required under control of up-to-date
diagnostic equipment for adequate and correct tactics of treatment
diagnostic equipment for adequate and correct tactics of treatment
patients with convulsive reactions, preferably from the phase of the
patients with convulsive reactions, preferably from the phase of the
disease debut.
disease debut.
Alexander
Alexander, 33
, 33 years old
years old
Alexander F
Alexander F.,
., born in
born in 1977
1977
Diagnosis
Diagnosis:
: vegetative state
vegetative state as a
as a
result
result
of CCCI (February 2004),
of CCCI (February 2004),
severe brain injury
severe brain injury
Coma duration – 1 week
Coma duration – 1 week
Beginning of the treatment –
Beginning of the treatment –
November 2004
November 2004
He had 4 scheduled courses
He had 4 scheduled courses
of intensive neurorehabiliitation
of intensive neurorehabiliitation
for 30 days each up to July
for 30 days each up to July
2005.
2005.
Andrew
Andrew, 29
, 29 years old
years old
Andrew Y
Andrew Y.,
., born in
born in 1981
1981
Diagnosis
Diagnosis:
: vegetative status
vegetative status as a result of
as a result of
CCCI (August 2001), severe brain
CCCI (August 2001), severe brain
injury,
injury,
subarachnoidal-parenchymatous
subarachnoidal-parenchymatous
hemorrhage, brain edema
hemorrhage, brain edema.
.
Coma duration – 3 weeks
Coma duration – 3 weeks.
.
The beginning of treatment – February
The beginning of treatment – February
2002
2002
He had 5 scheduled courses of
He had 5 scheduled courses of
intensive neurorehabilitation for 30 days
intensive neurorehabilitation for 30 days
each up to
each up to
November 2005
November 2005.
.
Therefore
Therefore
losing” of consciousness of patients with convulsive reactions
losing” of consciousness of patients with convulsive reactions
should be considered as pathologically
should be considered as pathologically sanogeni
sanogenic, which means
c, which means
that the organism’s attempts to find a way out of a non-standard
that the organism’s attempts to find a way out of a non-standard
situation or just to inform about disorders in the living organism.
situation or just to inform about disorders in the living organism.
The hybrid living system in functioning provides with the
The hybrid living system in functioning provides with the
emergency changing to the system of the hard protective re-
emergency changing to the system of the hard protective re-
start of the organism without interference of the patient himself.
start of the organism without interference of the patient himself.
However it doesn’t mean that it is able to overcome all
However it doesn’t mean that it is able to overcome all
breakages in the organism. Not "harm the brain and help it to
breakages in the organism. Not "harm the brain and help it to
control the situation" - such approach might be in the base of
control the situation" - such approach might be in the base of
present tendencies in treatment of patients with convulsive
present tendencies in treatment of patients with convulsive
attacks, unlike the simple blocking of visual convulsive reactions
attacks, unlike the simple blocking of visual convulsive reactions
by high doses of anticonvulsants.
by high doses of anticonvulsants.
Thus
Thus
understanding of peculiar features of the living
understanding of peculiar features of the living
system re-start in a damaged organism enables to
system re-start in a damaged organism enables to
simulate states, to foresee a patient’s state,
simulate states, to foresee a patient’s state,
possible rehabilitation and a level of restoration of
possible rehabilitation and a level of restoration of
the lost functions of the organism. In our clinical
the lost functions of the organism. In our clinical
practice the mentioned approach allowed to make
practice the mentioned approach allowed to make
sure, that there are not any incurable states in
sure, that there are not any incurable states in
medicine, and there is a problem of using
medicine, and there is a problem of using
mathematical modeling in questions of the health
mathematical modeling in questions of the health
restoration.
restoration.
Thank you for
Thank you for
your attention !
your attention !
... So today in medicine, personalized, predictive and preventive approach dominates based on the methods of evidence-based medicine [2,52,[56][57][58][59]. ...
... And practitioners ignore how fast arterial blood moving in a reservoir, the signs of venous stasis and how it may be reflected on the velocity and quality of tissue oxygenation and metabolism [7,21,[55][56][57]. ...
Article
Full-text available
Review: Problems of effective correction and radical solving of cardiovascular disorders are not new. However, the statistic indexes of cardiovascular pathology are growing and they are considerably younger [1-6]; this testifies to lack of effective management strategy and tactics in fight against these diseases [7-13]. Today we can make a real estimation of achieved results: for the last 20-30 years many technologies are created for research of vascular system - USD of vessels, МRТ in angiomode; devices for correction of cardiac disorders are widely used - from numerous technologies for estimation of the heart structure to coronarography and coronarshunting; new fields of radical medicine are successfully implemented, such as cardiac surgery, angiosurgery, phlebology [14-16]. And at the same time, regardless of the most up-to-date technologies for vascular diagnostics and angiosurgery cardiovascular diseases gets top ranking regarding morbidity and death rate [6,9,17,18]. It can be explained by the fact that development and introduction in medical practice of modern vascular technologies are behind a steady tendency to progress and cardiovascular diseases strike younger people. This dissonance testifies to insufficient knowledge and analysis at the application of new technological potential of visualization of the cardiovascular system at structural (in vitro and in vivo) and functional level - in vivo [7,9,10,12,17]. Our 20-year-old experience of research of vascular disorders and successful attempts of their correction [19] has shown that 1) There is a huge layer of unexplored hemodynamic parameters, which are important in the personalized treatment processes. However, long neglecting biomechanics in medicine [20] resulted into excessive emphasis on endothelial dysfunction and cellular metamorphosis beneficial for promoting pharmacological business. As a result, doctors are not ready to think logically with categories of circulation mechanics and applied hydro- and hemodynamics [21]. 2) Physicians and medical staff don't have enough knowledge in angiology, hemodynamics, hydrodynamics, analytical angiocorrection, angiotherapy, treatment management on evidential basis. Without understanding the depth of hemodynamic laws and logics of pathological and sanogenic transformations in blood supply for organs and regional reservoirs as closed system of vascular tubes - vascular blood flow, it is impossible to perform personalized adequate treatment and predict positive outcomes [8,10]. 3) There is an urgent need in development of vascular monitoring technologies based on principles of evidential medicine [2,7,8,10]. Monitoring dynamic changes in any medical process management, doctors may correct on time the decline from sanogenic blood restoration in a particular regional reservoir and logic of blood redistribution in different vascular reservoirs in a patient's body. Keywords: Personalized treatment, Hemodynamics, Cardiovascular diseases, Angiocorrection, Hydrodynamic conflicts, Brain edema, Biomarkers, Angiomarkers, Intracranial hypertension, Vascular screening, Angiotherapy
... During 2010-2017, the methodology of USDG of major arteries and veins gradually developed into Angiomarker technology with the possibility of analysis of about 50 hemodynamic parameters that proved to be significant pathohemodynamic indicators of vascular blood flow disorders, in contrast to structural changes at the macro level [52,53,54,55,56,57,58]. ...
Book
Full-text available
This monograph is devoted to a topical issue - applied angiology, the place of different diagnostic methods in the verification and objectification of vascular structural and functional disorders based on deep knowledge of authors - experts in applied hemodynamics, angiology, angiotherapy - Academician of the Ukrainian Academy of Technological Sciences, Professor, Doctor of Medical Science Ulyana Lushchyk and Professor, Doctor of Physical and Mathematical Sciences Viktor Novytsky and the team of scientists headed by them. Methods of objectification of the cardiovascular system, their advantages and limitations for certain segments of the cardiovascular system, their application in the visualization and monitoring of vascular changes at the macro- and microvascular levels are described in detail.
ResearchGate has not been able to resolve any references for this publication.