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Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_3779_Библиотеки_им_академика_М_И_Перельмана
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enable heart contractions. Cardiomyocytes are connected to each other by gap junctions.
They are organized in fibers, which in turn are organized in sheets. The sheets are
separated by cleavage planes. The fiber and sheet orientation varies throughout the
ventricles. At any small segment of myocardium, there always exist some fibers, which
respond to the stress in any direction. The structure of the atria and ventricular orientation
has been recently studied by 3D diffusion tensor magnetic resonance imaging [7,8].
The outer layer of the heart is epicardium. It consists of a thin layer of connective tissue
and fat. Pericardium is the thick, membranous sac, which surrounds the heart. Together
with endocardium, it protects and lubricates the heart with the pericardial fluid. It helps to
reduce friction between pericardial membranes.
2.2.2 Electrical activity
Cardiomyocytes are the muscle fibers that form the chambers walls of the heart. They are
spatially organized for optimal adenosine triphosphate (ATP) and calcium delivery to
sarcomeric myosin and ionic pumps during every excitation-contraction cycle. The 3D
structure of the human left ventricular myocyte has been recently studied in Ref. [9].
Interactions of actin and myosin filaments are responsible for the cell contraction, which is
regulated by the electrical activity of the cell through the cellular membrane permeability.
There is interconnection of the membrane potential and membrane permeability to some
small inorganic ions: permeability varies during the heart cycle due to the change of the
potential difference across the membrane, whereas the potential difference depends on the
relative permeability to the ions. This complex interplay of coupled physiological
processes is often addressed by numerical simulations [10e15].
The fluid inside the heart cells contains mainly potassium (K
þ
amount of sodium (Na
contains mostly Na
), chlorine (Cl), and calcium (Ca2þ) ions. The extracellular fluid
þ
and Clions with some amount of Kþions. The depolarization and
repolarization of the cell membrane during an action potential is driven by the flow of
current carried by Na
action potential results from the rapid opening of Na
the consequent inward flow of Na
by a smaller inward current of Ca
þ
,Ca2þ, and Kþions. The steep upstroke in the beginning of the
þ
ions, which depolarizes the membrane. It is followed
2þ
ions. It balances an outward current of Kþions and
þ
maintains the plateau of the action potential. Finally, the outward current carried by K
ions becomes significant, which causes repolarization of the membrane and returns it to
the initial resting state.
þ
) ions together with some
channels following a stimulus and
þ
The principal scheme of the conducting system of the heart is shown in Fig. 2.3. The
sinoatrial node (SA node) spontaneously generates electrical impulse (action potential),
which initiates myocardium excitation and, thus, cardiac cycle. The rate of the impulses is
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Figure 2.3
Conducting system of the heart. Source: OpenStax, Anatomy and Physiology. OpenStax CNX. Available
at http://cnx.org/content/col11496/.
controlled by the nerves. The SA node is located in the myocardial wall near the junction
of sinus venarum and right atrium. Electrical signals arising in the SA node causes
auricles contraction. Then, they travel to the atrioventricular node (AV node), which is
located between the auricles and the ventricles. The action potential is conducted through
the left and right His bundles to the appropriate Purkinje fibers on each side of the
ventricles, which causes ventricular contractions [16].
An action potential is conducted along the muscle fibers at a speed that depends on the
diameter of the fiber, its branching, and electric current available to depolarize the next
section of the fiber represented by a cardiomyocite. The fiber and fiber sheet orientation
also cause substantial effect to the propagation of the action potential. It propagates two to
three times faster along the fibers, than across it within the sheet. The speed of action
potential propagation orthogonal to sheets is two to three times slower than orthogonal to
fibers within the sheets.
Electrical impulses from the SA node propagate through all tissues in the body and
attenuate with the distance from the SA node. The electrical activity of the heart can be
recorded by the electrodes placed on the surface of the thorax. This process is called
electrocardiography (ECG). Computational simulations of ECG help to reveal the features
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of impulse propagation from the SA node and provide new insights to the diagnostic of
arrhythmia and other heart diseases [17,18].
2.2.3 Myocardial perfusion, ischemia, and infarction
The blood supply of the myocardium is maintained by the coronary arteries, which are
mostly located in epicardium. Coronary blood flow is well autoregulated. It remains stable
in a wide range of perfusion pressure. Therefore, it maintains sufficient myocardium
supply with nutrients.
Ischemia is insufficient tissue supply with oxygen and other nutrients. Infarction is the
tissue necrosis due to the prolonged ischemia. Myocardial ischemia is characterized by an
unbalanced myocardial oxygen supply and demand. It leads to the loss of myocardial
contractility, changes in the membrane potential, ventricular fibrillation, and complete
heart block. Irreversible damage includes ATP decrease, stop of anaerobic glycolysis, pH
and lactate increase, high level of osmolality, membrane damage, cellular and
mitochondrial swelling, amorphous densities in the mitochondria, etc. [19]. These changes
are the reasons for cardiac dysfunction, arrhythmias, myocardial infarction, and a sudden
death.
The usual mechanism for the development of acute myocardial infarction is the rupture or
erosion of a vulnerable atherosclerotic coronary plaque with the subsequent totally
occluding thrombus. The other possible scenarios are partial occlusion or occlusion in the
presence of collateral circulation. Acute myocardial infarction is classified into six types
[20].
Microvascular dysfunction in patients with hypercholesterolemia, hypertension, and
diabetes mellitus may be a reason for abnormal myocardial perfusion even in the absence
of epicardial coronary artery disease (CAD) [21]. Microvascular dysfunction is related to
the endothelial function abnormality, which causes autoregulatory mechanisms disorder.
Typically, the overture to the obstructive CAD is a long-term process. Patients are often
asymptomatic for decades. Then, the process rapidly develops in less than an hour. The
ischemia duration is an important factor of its severity. Ischemia duration less than 40 min
results in reversible cellular and functional alterations. Ischemia lasting for more than
40 min often leads to the progressive functional loss and irreversible damage [19].
Ischemic tissue indicates the following pathological abnormalities: loss of oxidative
phosphorylation, accumulation of the toxic compounds due to anaerobic metabolism, and
acidosis resulted from catabolic reaction [19].
Thus, urgent reperfusion of coronary flow must be provided for the patients with acute
myocardial infarction. The invasive treatments such as stenting, angioplasty, thrombolysis,
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and coronary bypass may be applied. The no-reflow phenomenon may be observed in the
patients with coronary microvascular dysfunction. Therefore, both epicardial coronary flow
and microvascular perfusion should be considered and restored [21].
A range of noninvasive testing tools have been developed for clinical evaluation of
coronary flow and perfusion, which provide the benefits of increased comfort and less
pain. They include single-photon emission computerized tomography, myocardial contrast
echocardiography, positron emission tomography (PET), stress cardiovascular magnetic
resonance imaging, and cardiac computed tomography. Noninvasive cardiac imaging plays
an important role in the diagnosis of coronary artery disease and in the decision-making
for surgical interventions [22].
2.3 Large vessels
The heart supplies blood with the energy. The vessels conduct the blood through all parts
of the organism. The vessels carrying blood from the heart ventricles to the
microcirculation are called arteries, and the vessels carrying blood from the
microcirculation to the auricles are called veins. At first glance, vessels are just elastic
tubes. However, they have many additional features. Vascular wall may contain different
amount of elastin fibers, collagen fibers, and muscle cells. The vascular wall may be
affected by the regulatory and autoregulatory mechanisms, muscles, sphincters, and
chemicals. Some vessels have a system of unidirectional valves.
2.3.1 Vascular network anatomy
There are two loops, which are formed by the vessels (see Fig. 2.4). In the systemic loop
the aorta starts upward from the left ventricle, and then it turns to the 180
downward. Two coronary arteries are started immediately form the aortic root. They
supply the heart. There are three branches coming from the aortic arch: brachiocephalic
artery, left common carotid artery, and left subclavian artery. These arteries supply the
head and upper extremities. The descending part of the aorta is divided into thoracic and
abdominal parts. The radius of the descending aorta decreases with the distance from the
heart. The thoracic aorta supplies the lung’s muscles and other tissues of the thoracic
region. The abdominal aorta supplies the organs and tissues of the abdominal cavity
(stomach, kidneys, liver, etc.). The abdominal aorta is divided into two common iliac
arteries, which supply the lower extremities.
The structure of veins is similar to that of arteries. The average radius of the arteries and
veins decreases with the distance from the heart. However, the total cross section of the
vessels increases with the distance from the heart. Approximately 80% of the total blood
volume is located in the systemic circulation. Veins contain approximately 80% of the
+
and goes
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Figure 2.4
The scheme of the cardiovascular system. Source: OpenStax, Anatomy and Physiology. OpenStax CNX.
Available at http://cnx.org/content/col11496/.
total blood volume. Systemic arteries and veins are organized into networks due to
numerous anastomoses. Pulmonary arteries and veins are organized into trees.
2.3.2 Vascular wall structure, elasticity, viscoelasticity
The vessel walls can change their cross-sectional shape and area in response to the applied
stresses, e.g., by transmural pressure. Elastic properties and thickness of the vessel depend
on its proximity to the heart and on its function. The elasticity is determined by the
structure and composition of the vascular wall. Regulatory mechanisms also affect
vascular elasticity (see Section 2.3.3).
The walls of all large vessels in the human body are structurally decomposed into three
layers: intima, media, and adventitia (see Fig. 2.5).
Intima and adventitia are much thinner than media. Intima is primarily composed of a
layer of endothelial cells lining the vessel wall. Adventitia primarily consists of fibroblasts,
fibrocytes, and bundles of collagen fibers. Medium is composed of elastic membranes,
collagen fibers, and smooth muscle cells. The relative ratio of these three components in
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Media
Adventitia
Intima
Smooth muscular
cells
External
elastic
membrane
Endothelium
Internal
elastic
membrane
Figure 2.5
Typical structure of the blood vessel. Source: Blausen.com staff (2014). Medical gallery of Blausen
Medical 2014. WikiJournal of Medicine 1 (2). http://doi.org/10.15347/wjm/2014.010.
the media accounts for the elastic properties of particular vessel. Elastin fibers have a
modulus of elasticity of 0.6 MPa. They can stretch up to 250% of their original length.
Collagen fibers are much stiffer with a modulus of elasticity approximately 500 MPa [23].
The pressure load is distributed between the elastin and collagen. For the low pressure, the
major role in the elastic response is played by elastin fibers. Contribution of collagen
fibers increases with the pressure increase (Fig. 2.6).
Stressestrain relationship for elastin (A), collagen (B), and mixed (C) fibers.
Figure 2.6
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Arteries and superficial veins are generally thicker and have more smooth muscle cells
and more elastic fibers than deep veins. Arteries can be classified into elastic and
muscular according to the composition of a vessel wall. Elastic arteries have a relatively
large diameter and are closer to the heart (e.g., aorta or carotid artery). Generally, the
number of elastic membranes decreases with the decrease of the vessel diameter.
Muscular arteries (e.g., femoral artery, abdominal artery, cerebral arteries) have few
elastic membranes. In veins of medium and large size, the media typically consist of two
or three layers of smooth muscle cells and bundles of collagen and elastin fibers. Their
external layer is the thickest one. The walls of the deep veins are thin. Primarily, they
consist of collagen. The shape of the cross section of the deep veins substantially
changes depending on transmural pressure. It may be circular, elliptic, dumbbell-like, or
almost collapsed.
Vascular wall elasticity was studied in many clinical and laboratory researches [23e29 ].
The mechanical properties of blood vessels are classified as passive (accounting for
elastin and collagen fibers contractions) and passive-active (accounting also for
smooth muscles contractions). In the most experimental studies, passive properties
are considered. Passive-active properties are related to the regulatory processes (see
Section 2.3.3).
Vascular wall exhibits both instant elastic and time-dependent viscous response to the
stress. The stressestrain relationship of the vascular wall material depends on the stress
rate. The aortic pressure profile is not symmetrical. The steep pressure increase with high
stress rate is observed during early systole, which turns to smooth decrease and lower
stress rate in late systole and diastole. As a result, the load and unload stressestrain curves
are different as the pressure-time profile is not symmetrical. In addition, viscous behavior
is responsible for the energy dissipation. Viscoelastic properties may be estimated based
on the measurements and numerical simulations [30,31].
In continuum mechanics, elastic properties of a material are characterized by the
constitutive equation quantifying the nonlinear relationship between applie d stress and
responded strain. This relationship can be derived using various different approximations
of the vessel wall material. For example, the vascular wall can be considered as complex
composite, which is described by isotropic matrix reinforced by oriented sets of fibers.
This approach describes nonlinear, anisotropic behavior of the material [28,122]. It is
capable to account for response of the collagen fibers to high blood pressure. The other
possible approach exploits microstructure of vessel walls as a basis for deriving
constitutive equation for the specific vessel [505e507]. Due to significant differences in
the structure of the vessel’s walls, none of the proposed approaches is universal for a ll
types of arteries.
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2.3.3 Arterial regulation and autoregulation
Internal physiological and pathological conditions and external environmental conditions
of the body may vary in a wide range. They may cause substantial change in the blood
pressure and in the tissues and organs metabolic demand. The regulatory mechanisms tend
to maintain blood flow despite the changes of the arterial perfusion pressure or increase
blood flow due to increased metabolic demands (e.g., working hyperemia). The blood
vessels adapt to these changes by adjustment of their diameter through contraction
(vasoconstriction) or relaxation (vasodilation) of the smooth muscle cells. As a result,
hydraulic resistance and elasticity are changed, which, in turn, helps to control required
perfusion rate, as well as nutrients and oxygen consumption. Vasoconstriction results in
the decrease of the diameter and elasticity and in the increase of the hydraulic resistance.
Vasodilation causes an opposite effect.
Various regulatory mechanisms of vessel networks have been studied. These mechanisms
can be divided into neurogenic regulation, humoral regulation, and autoregulation.
Neurogenic regulation modulates the blood flow by the perivascular nerves activity due to
autonomic nervous system signals. Humoral regulation causes both vasomotor effect
through the chemical substances in the blood and the systemic effect achieved by the
calcium, potassium, sodium ions, hormones, etc. The local effect is achieved by the
histamine, serotonin, acetylcholine, etc. [32].
Myogenic, metabolic, tissue pressure, and tubuloglomerular feedback (TGF) hypotheses
are considered as the major mechanisms of autoregulation. According to myogenic
hypothesis, the diameter of arteriole is directly related to the intravascular pressure
through the smooth muscle cells stimulation and response. Thus, myogenic mechanism is
the vascular wall response to the normal stress exerted by the blood flow. In addition, the
vascular wall diameter is inversely related to the shear stress exerted by the blood flow due
to friction between the blood and the wall through the process referred to as
“mechanotransduction” [33,34]. Increased shear stress results in increased NO production
by the endothelial cells and subsequent relaxation of the smooth muscular cells. These two
processes in balance provide stability of the integrated vascular response to the mechanical
interaction of the wall with the blood flow for a wide range of pressure and flow rate
values. Both processes may be of a transient or sustained nature.
According to the metabolic hypothesis, reduction in arterial inflow causes an elevation of
vasodilator metabolites in the tissue and associated increase of the diameter. Decreased
blood flow results in a reduced washout of metabolites such as CO
, lactic acid, and/or
2
increased production of vasodilator substances due to stagnant hypoxia. In addition, partial
pressure of oxygen in the tissues is responsible for autoregulation in organs with high
oxygen consumption (e.g., heart and brain) [35].
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The kidney regulation is aimed at maintaining electrolyte concentrations, osmolality, and
acidebase balance of blood plasma. Kidney participates in blood pressure regulation and
in the maintenance of the water volume in the whole organism. According to the TGF
hypothesis, an increase in arterial pressure leads to increased glomerular filtration. In turn,
the increase in glomerular filtration rate increases the solute and electrolyte concentration
in the tubular fluid. The muscle tension in the afferent arterioles is adjusted proportional to
the difference between the actual and target concentration. Relaxation (vasodilation) of the
afferent arterioles results in increased glomerular filtration pressure and tubular fluid flow.
Thus, this is a negative feedback loop process.
2.3.4 Pulse wave propagation and reflection
The heart ventricles eject the blood by discrete portions in an almost periodical manner.
One part of the ejected blood goes immediately to the arterial network. Due to limited
flow capacity, another part is accumulated in the aorta and large arteries and causes their
elastic expansion due to the pressure, which was supplied by the heart. This portion goes
to the arterial network during diastole due to the elastic contraction of the arteries. Thus, a
pressure wave is generated, which travels along arterial network in forward direction (from
heart to microcirculation). The secondary backward pressure waves are generated due to
reflection of the forward wave from the bifurcations and microcirculation, where lowresistance conduit arteries join high-resistance arterioles. The pulse wave (PW) is the total
of these forward and backward waves. Pulse wave velocity (PWV) is the velocity of the
propagation of the PW peak through the arterial network.
Elasticity of the arteries substantially affects the velocity of the forward and backward
waves, and, thus, it affects shape and amplitude of the PW and PWV. The decrease of
arterial elasticity causes early return of the backward wave to the aortic root. It results in
the pressure increase during later systole instead of diastole, which makes the blood
ejection more difficult and requires more work of the heart muscle. A variety of
cardiovascular diseases (CVDs) may follow the persistent late systolic pressure increase.
Some factors cause arterial elasticity increase and, thus, decrease risk of CVD: exercise,
vasodilator administration. Other factors cause arterial elasticity decrease and, thus,
increase risk of CVD: aging, food and drink preferences, smoking, heart rate, gender,
atherosclerosis, hypertension, diabetes, aortic degeneration, aneurysms, and heart
failure [36].
It is important to study all these factors. For example, abdominal aortic aneurysms (AAA)
are rarely detected at early stages by conventional methods. On the other hand, the
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influence of AAA on PW shape is now well established. Recent physical and
computational experiments allow to reveal several indicators that characterize the impact
of an aneurysm on waveforms [37].
While pulse palpation is an important diagnostic tool in traditional Chinese medicine,
nowadays it can be observed as solving the inverse problem of detecting the properties of
(the health of) vessel walls and the heart function from the PW measurements. In modern
implementation, PW shape is analyzed using 27 complex pulse images, which can be
parameterized by six basic variables: frequency, rhythm, wideness, length, deepness, and
qualities. Such analysis allows to differentiate a number of diseases somehow related to
the change of arterial elasticity, endothelial function, and microcirculatory properties, thus
causing the change in backward waves reflection and PW shape. This technique was
analyzed by numerical simulation [38] and was applied for studying hypertension [39],
atherosclerosis, diabetes, etc.
2.4 Microvasculature
Microcirculatory network is an essential part of the cardiovascular system. It is responsible
for all exchange processes in the body and for the regulation of blood flow in individual
organs. The microcirculatory network is substantially different from the vascular network
of large vessels. It consists of a huge number of very small vessels. The lumen of these
vessels is close to the RBC size. The blood flow is substantially lower than in large
vessels. Thus, the role of blood composition, its non-Newtonian behavior, and biological
properties of RBC and WBC become important for the flow. The structure of the
microvasculature may be modified due to normal processes (e.g., natural growth and
development) and pathological conditions (e.g., tumor growth, wound healing), which
affects perfusion of the tissues.
2.4.1 Anatomy
Microcirculation network is the part of cardiovascular system, which directly performs its
basic function of supplying cells of an organism with nutrients. It consists of arterioles,
capillaries, and venules. Arterioles branch out of the smallest arteries, and after several
successive bifurcations, each terminal arteriole leads to a cluster of capillaries, which then
converge to venules, leading to veins (see Fig. 2.7). The structure of microcirculation
network demonstrates significant variety throughout the body. It is adjusted to every
specific organ where it is embedded in a way that every cell is usually within 20 mm
distance from a microvessel. Microcirculation density increases in the metabolically active
tissues.
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