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<article xmlns:xlink="http://www.w3.org/1999/xlink">
  <front>
    <journal-meta />
    <article-meta>
      <title-group>
        <article-title>Mathematical Modeling of Artificial Mitral Heart Valve</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="author">
          <string-name>Hranislav Miloshevich</string-name>
          <xref ref-type="aff" rid="aff2">2</xref>
        </contrib>
        <contrib contrib-type="author">
          <string-name>Yury Zakharov</string-name>
          <xref ref-type="aff" rid="aff1">1</xref>
        </contrib>
        <contrib contrib-type="author">
          <string-name>Yurii Shokin</string-name>
          <xref ref-type="aff" rid="aff0">0</xref>
        </contrib>
        <contrib contrib-type="author">
          <string-name>Dmitry Dolgov</string-name>
          <xref ref-type="aff" rid="aff1">1</xref>
        </contrib>
        <contrib contrib-type="author">
          <string-name>Irene Grigorieva</string-name>
          <xref ref-type="aff" rid="aff1">1</xref>
        </contrib>
        <aff id="aff0">
          <label>0</label>
          <institution>Institute of Computational Technologies SB RAS</institution>
          ,
          <addr-line>Novosibirsk</addr-line>
          ,
          <country country="RU">Russia</country>
        </aff>
        <aff id="aff1">
          <label>1</label>
          <institution>Kemerovo State University</institution>
          ,
          <addr-line>Kemerovo</addr-line>
          ,
          <country country="RU">Russia</country>
        </aff>
        <aff id="aff2">
          <label>2</label>
          <institution>University of Pristina</institution>
          ,
          <country country="RS">Serbia</country>
        </aff>
      </contrib-group>
      <pub-date>
        <year>2016</year>
      </pub-date>
      <fpage>380</fpage>
      <lpage>392</lpage>
      <abstract>
        <p>The research shows the mathematical model, describing the dynamics of the artificial aortic heart valve and the model of blood thrombus moving in large vessels, as well as the method of numerical calculation of these models. There are represented numerical modelling results of the tricuspid valve operation and the blood thrombus moving in large vessels.</p>
      </abstract>
      <kwd-group>
        <kwd>Mathematical modeling</kwd>
        <kwd>artificial mitral heart valve</kwd>
        <kwd>aneurysm</kwd>
        <kwd>immersed boundary method</kwd>
      </kwd-group>
    </article-meta>
  </front>
  <body>
    <sec id="sec-1">
      <title>Introduction</title>
      <p>The research of heart and blood-vascular system diseases is a task that has
extremely high socio-economic importance and a long history. The knowledge
of the human cardiovascular system is actual as never before and during the
last few decades the methods of mathematical modeling are widely used in their
accumulation.</p>
      <p>In the world 80-90% of non-traumatic subarachnoid hemorrhages are
occurred due to the bursting of intracranial aneurysm [10]. The aneurysm
rupture leads to neurological deficits related to brain tissue damage or even death.
Approximately 50% of patients with aortic aneurysm bursting die before the
hospitalization [11]. Each year, about 250 thousand heart valve restoration or
surrogation operations are carried out in the world and the number of these
operations and their necessity is increasing year by year [9].</p>
      <p>The cardiovascular system is extremely complex. The heart is a complex
multi-valve muscular organ. Blood vessels are multilayered structure that
substantially differs from each other, depending on the type of vessel and its position.
Blood has a heterogeneous structure including formed elements. Some authors
consider the blood as an incompressible viscous Newtonian fluid [13]
including formed blood elements [8]. Sometimes the blood circulation is presented as
non-Newtonian fluid flow [3].</p>
      <p>This research presents a mathematical model of blood circulation in large
blood vessels, suitable for modelling of vascular malformations and operation
of artificial heart valves. Artificial heart valves are one of the most complex
prosthetic devices in cardio surgery. They enable you to deal effectively with
diseases and injuries of natural valves, but their operation time is much less
than a human life, which means that the patients need to be re-prosthesis every
few years. Mechanical valves have high reliability and durability, but can lead
to a serious deformation of the blood circulation, the formation of the blood
cell clot and as a result to the thrombus formation. Biomaterial valves don’t
have this drawback, but they are less durable, and their production is a difficult
technical problem, which is not completely resolved at the present time.</p>
      <p>Also in this research we investigate the mechanism of the formation of blood
aneurysms in the large blood vessels. The research [10], [16] shows that the
formation of blood aneurysms is caused by swelling one of the layers of its wall,
of intima, which is the most subtle and least durable. It defects the vessel shape
and the average blood circulation in it.</p>
      <p>The mathematical models, written in the form of quite complex differential
equations that can be solved by various numerical methods, are often used as a
modeling tool of the blood circulation. One of the most commonly used methods
is the finite element method (FEM) [6], [17]. FEM is widely tested on the
problems of elasticity theory and hydrodynamics. Furthermore there is a sufficient
number of sets, realizing this method. FEM enables to take into account the
complex shape of the solution field for the deflection of the blood vessel walls
and valve leaflets, but the need to take into account the interaction between
the fluid and flexible walls leads to a constant reconfiguration of the analysis
grid to comply the changing shape of the object, consequently the finite element
method has a high temporal and spatial complexity. There is another approach
to solving problem of blood circulation in vessels based on the applying of the
lattice Boltzmann method [15], [1]. This approach uses the methods of
statistical mechanics, numerically solving Boltzmann discrete equation, the direction
of the fluid flow is defined in the lattice sites and the fluid flow is possible only
in the directions of the lattice. Another common method for researching of the
hemodynamics, vascular structures and heart valves problems is the method of
the immersed boundary. The immersed boundary method is a relatively new
technique that was proposed for the modeling of the heart valves operation [7],
[12]. It enables you to simulate the deformation of arbitrarily thin valve leaflets.</p>
      <p>In this research we consider the blood circulation in the large elastic blood
vessels and artificial heart valve as a three-dimensional variable flow of the
incompressible fluid with variable density and viscosity [4], [5]. The resulting system of
the differential equations with appropriate boundary and initial conditions
describes the artificial tricuspid aortic valve operation, the formation and growth
of the blood aneurysm in large blood vessels. The immersed boundary method
is used in conjunction with the method of nets to solve the differential problems.
2</p>
    </sec>
    <sec id="sec-2">
      <title>Problem definition</title>
      <p>The blood consists of plasma and measured formed elements, which account
for about 45% of the total volume. The size of the formed elements is small
compared to the size of a large vessel: for example, aortic diameter is 3 *10−2m,
and the diameter of an erythrocyte is 6 * 10−9m. The research [14] shows that
the blood plasma behaves like a Newtonian fluid, which makes the blood an
incompressible inhomogeneous two-component liquid with variable viscosity and
density. The blood vessel walls and valve leaflets we will consider as fluid-tight
surfaces that have certain rigidity. Also the blood vessel walls and valve leaflets
can be deformed under the influence of the fluid pressure.</p>
      <p>The source of the fluid flow in vessels and heart valves is the pressure
generated by contraction of the heart muscle. Therefore, we will describe its flow in
the blood vessels and heart valves by Navier-Stokes equations system with
variable density and viscosity and the pressure drop is set up at the input-output of
the solution field, depending on the time:
 u</p>
      <p>1
+ (u · ∇)u = −  ∇ + ∇ + f</p>
      <p>+ ∇ · ( u) = 0

with the initial conditions and the boundary conditions
u(,¯ 0) = u0
u| 1, 4 = u</p>
      <p>
        ,  | 2, 3 = 0
  2 =  
  3 =  
x(, ,  ) ∈  ˜ are the points of the solution field, u(, ,  ) is the vector of the
velocity field,  (x,  ) is the pressure,  =  (∇u + (∇u) ) is the viscous stress
tensor,  (x,  ) is the fluid viscosity,  (x,  ) is the vector of the body forces. The
fluid density is defined by the formula
 =  ( 2 −  1) +  1
(
        <xref ref-type="bibr" rid="ref1">1</xref>
        )
(
        <xref ref-type="bibr" rid="ref2">2</xref>
        )
(
        <xref ref-type="bibr" rid="ref3">3</xref>
        )
(
        <xref ref-type="bibr" rid="ref4">4</xref>
        )
(
        <xref ref-type="bibr" rid="ref5">5</xref>
        )
and the viscosity is a function of the flow rate, its density and their gradients.
In this research we use a simple linear relationship between fluid density and
viscosity:
      </p>
      <p>=  ( 2 −  1) +  1
with the initial conditions
and the boundary conditions on the boundary of the inflow:</p>
      <p>+ u · ∇ = 0
 (x, 0) =   (x),  ∈  ˜
 (,¯ )| 2 =   (,¯ )
︁∫
︁∫</p>
      <p>f(x,  ) =</p>
      <p>F(,¯ ) ·  (x −  (,¯ ))  ¯
(,¯ ) =</p>
      <p>u(x,  ) ·  (x −  (,¯ ))  x
Here,  1,  1 is the density and viscosity of the carrier fluid (blood plasma in this
case),  2,  2 is the density and viscosity of the admixtures (formed elements),
 (x,  ) is an admixtures concentration determined from the transfer equation</p>
      <p>
        In this approach, the displacement of the vessel walls and valve leaflets occurs
under the influence of fluid flow in consideration of the walls rigidity, but the
tissues tension and deformation forces give the contribution to the sum of the
forces in the motion equations
(
        <xref ref-type="bibr" rid="ref6">6</xref>
        )
(
        <xref ref-type="bibr" rid="ref7">7</xref>
        )
(
        <xref ref-type="bibr" rid="ref8">8</xref>
        )
(
        <xref ref-type="bibr" rid="ref9">9</xref>
        )
(
        <xref ref-type="bibr" rid="ref10">10</xref>
        )
(
        <xref ref-type="bibr" rid="ref11">11</xref>
        )
(
        <xref ref-type="bibr" rid="ref12">12</xref>
        )
(
        <xref ref-type="bibr" rid="ref13">13</xref>
        )
where  is the elastic coefficient,  =  
/ ⃒⃒  
⃒⃒,   is the flexural rigidity
coefficient. If we assume that the Lagrangian coordinates (, , 
) are chosen in such
a way that coordinate pair (,  ) defines the single fiber for the fixture  , and
the formula  ( 0,  0,  ) determines the parametric representation of the fiber
is the vector of the body forces, is the deformation resistance force. The
equations (
        <xref ref-type="bibr" rid="ref10">10</xref>
        ) and (
        <xref ref-type="bibr" rid="ref11">11</xref>
        ) use an integral transformation that uses three-dimensional
Dirac function for the transition from Lagrangian to Eulerian coordinates. The
equation (
        <xref ref-type="bibr" rid="ref11">11</xref>
        ) shows that the immersed boundary moves according to the local
velocity of the ambient fluid, which is an analog of the adhesion condition:
(, , , 

)
= u( (, , , 
),  )
Adhesion condition is used to determine the movement of the immersed elastic
boundary bounded by fluid flow. The formula from [7] is used to describe the
deformation forces
 =

+
 2 (︂
 2
 
︂(  2 0
 2
      </p>
      <p>2 )︂
−  2
 0(, , 
) =  (, , , 
3</p>
    </sec>
    <sec id="sec-3">
      <title>Solution method</title>
      <p>In this research we will use immersed boundary method [12] to determine the
movement of the valve leaflets and deformation of the vessel walls. In accordance
with this method, we will calculate the fluid flow in the  ˜ parallelepiped, which
includes</p>
      <p>(see Fig. 1). The adhesion condition is required at the  ˜ boundaries.
We will use a rectangular, actually non-uniform staggered grid  ˜ℎ with ℎ  , ℎ  ,
ℎ</p>
      <p>
        pitches and staggered nodes, where the pressure, the velocity divergence and
the concentration are determined at the center of the socket and the components
of the velocity vector and external forces are determined at the socket boundaries
to determine the fluid flow. The splitting scheme on physical factors is used to
solve the equations (
        <xref ref-type="bibr" rid="ref1">1</xref>
        ) - (
        <xref ref-type="bibr" rid="ref4">4</xref>
        ):
 * −  
△

= −( 
· ∇) * −  ∇
1
      </p>
      <p>+  
 △  +1</p>
      <p>− ∇ ·   +1 =
  +1</p>
      <p>−  *
△

= −
1
 △
  +1
 2∇ *
△

4</p>
    </sec>
    <sec id="sec-4">
      <title>Results</title>
      <p>The results of the numerical modelling of the artificial heart valve ”UniLine”
operation as well as the formation and growth of the blood aneurysm in large
blood vessels are presented in this paragraph. The calculations were performed
for the case of constant and variable density and viscosity in non-dimensional
variables.</p>
      <p>
        The numerical scheme consists of the following steps:
− The intermediate velocity field  * is determined according to the known
velocity values from the preceding time layer. For this purpose the equation
(
        <xref ref-type="bibr" rid="ref14">14</xref>
        ) is solved by the stabilizing correction method.
−
      </p>
      <p>
        +1 is calculated from the formula (
        <xref ref-type="bibr" rid="ref15">15</xref>
        ) by the stabilizing correction method.
− The new velocity field   +1 is determined according to the explicit formulas
(
        <xref ref-type="bibr" rid="ref16">16</xref>
        ).
mated.
      </p>
      <p>
        formulas (
        <xref ref-type="bibr" rid="ref5">5</xref>
        ) and (
        <xref ref-type="bibr" rid="ref6">6</xref>
        ).
− The new concentration values are calculated from the transfer equation (
        <xref ref-type="bibr" rid="ref7">7</xref>
        ).
− The new values of the density and viscosity are defined according to the
− The velocity values at the points of the immersed boundary are
approxibody forces vector are calculated in the grid nodes.
− The displacement of the free boundary is calculated.
− The deformation resistant forces are determined and the projections of the
(
        <xref ref-type="bibr" rid="ref14">14</xref>
        )
(
        <xref ref-type="bibr" rid="ref15">15</xref>
        )
(
        <xref ref-type="bibr" rid="ref16">16</xref>
        )
4.1
      </p>
      <p>The calculation of the artificial heart valve ”UniLine” operation
The artificial heart valve ”UniLine” (see Fig. 2) is a stented tricuspid biological
prosthetic device wherein inanimate, especially treated biological tissues are fixed
on the support frame (stent) covered with a synthetic fabric. The high-precision
leaflets cutting by the laser system, which enables to avoid the collagen fibers
separation on the edge of the cut [2] is used in the production of this valve. We
placed the valve inside a circular cylinder with length of 1 and radius  =0.11.
The coefficient of the vessel walls elasticity is  = 1 * 103, for the valve leaflets
is  = 5 * 103, the flexural rigidity coefficient is   = 2 * 103. The pressure drop
  −   varies continuously from 0 to 6 at times. The pitch on the spatial grid
is 0.01 and in time it is the same (0.01).</p>
      <p>The Figure 3 shows the movement of the valve leaflets and fluid flow through
it at periodic increasing and decreasing of the pressure drop.
As you can see in the Figure 3, the valve leaflets are opened when the pressure
difference is changing, and then reset at pressure balancing.</p>
      <p>Figure 4 by a dotted line shows a graph of fluid flow within the valve according
to the time for the first three cycles. A leap fluid flow corresponds to each pulse,
and the swings of the valve leaflets are reflected in the very slight oscillations of
the graph when closing.</p>
      <p>We use physiological conditions for the pressure presented at Figure 5. In the
picture aorta pressure is input, ventricular pressure is the output one. Extension
strength coefficient   = 2 · 103,   = 1 · 102 while valve opening and   = 20 · 103
when valve closing. Viscosity is  = 0.25 · 10−2 Pa/s, density  = 1 · 103 kg/m3.
Step on space is ℎ  = ℎ  = ℎ  = 2 · 10−3m, step on time  = 1 · 10−4s, vessel
length  = 0.1 m, radius  = 0.03 m. Figure 4 also shows a comparison with
the same calculation of the work [7]. The comparison shows that the rise and
flow rate at the time of full valve opening match quite well. However, in our
calculations, the valve closes a little more slowly, due to the differences in the
parameters for rigidity. You can also note that in [7] the first flow peak is much
smaller than the other. This is due to the fact that in this paper describe the
initial conditions already strained leaflets, whereas in our calculation they rested
without tension.</p>
      <p>For the pressures analysis during ”UniLine” valve operation we monitored
their change at two points of this valve. The valve leaflets were moved under
the influence of the fluid with constant, and then variable viscosity and density.
These two points are marked in the Figure 6 and hereafter we will call them
”active point” and the ”mid-point”. The ”active point” is located on the one
of the valve spindles at the point of the two adjacent leaflets fastening and the
”mid-point” is located in the center of the leaflet.</p>
      <p>Fig. 6. The arrangement of the points spacing on the tissue annulus.
The Figure 7 shows graphs of the surface traction dependence on the time
for these two points in the various parts of the valve for the cases of constant
density and viscosity ( 1 =  2 = 1,  1 =  2 = 1 * 10−2,  =0%) and variable
density and viscosity ( 1 = 1,  2 = 2,  1 = 1 * 10−2,  2 = 2 * 10−2) for the two
concentration values c = 20% and c = 40%.</p>
      <p>The formation and growth of blood aneurysms in the large
blood vessels
The presented in this research model can be successfully used to research the
formation and growth of aneurysms in the large blood vessels. In this paragraph
we will consider the growth process of the aneurysm in the large blood vessel
under the periodically changing pressure, occurred during the blood circulation
in the vessel. We considered the vessel of a constant cross section, the set of the
cross-section centers is defined by the spline, the vessel radius is  = 0.11 and
the walls rigidity is of  = 2.5 * 103. It is assumed that the aneurysm grows in
areas with high pressure on the walls therefore the vessel rigidity is decreased in
areas with high pressure. The Figure 8 shows the shape of the vessel during the
formation of the aneurysm and also it shows the particle paths.</p>
      <p>When the blood aneurysm is formed, the blood clots, which can be washed
out by the flow and can get into the mainstream of the vessel, are formed in the
area of aneurysm. Therefore we take into account the importance to investigate
how a fairly dense and viscous area of the fluid will be spread in the vessel,
which has the narrowing (angiostenosis). Two stenosis scenarios are under
consideration: 1) insignificant vasoconstriction (15%), that happens gradually, 2)
significant vasoconstriction (72,5%) at a small vessel area. The vessel wall
stiffness is 4.5 *103, that is quite high, clot density is  2 = 2, viscosity is  2 = 3 *102.
In the latter case vessel wall stiffness decreases to 1 *103 due to linear law (before
stenosis) and increses to the initial value at the stenosis area. Fig. 9, 10 show
3)  = 7.5</p>
      <p>Z
X Y</p>
      <p>Z
X Y
modeling results. In case the vessel has insignificant stenosis its part with strong
concentration and, as a result, high density and viscosity is washed out by fluid
flow (from vessel axis), the clot passes vessel constriction area by changing its
form and leaves the computational domain. In case the stenosis is more
significant the scenario takes more time. The clot reaches vessel constriction area, but
only some part of it can passes through stenosis, the clot is washed out
gradually and it never passes the stenosis. This situation leads to slight deformation
of vessel walls before stenosis. The clot does not completely block the vessel and
there is still flow inside, due to the insignificant density and viscosity of the clot,
though its concentration changes more slowly compared with the first case.
5</p>
    </sec>
    <sec id="sec-5">
      <title>Conclusion</title>
      <p>We develop the model of the aneurysm and artificial heart valve operation,
considering the blood circulation with variable density and viscosity. The immersed
boundary method used for the realization of this model enables to get the
movement patterns of the valve leaflets for various shapes, to analyze the stress rates,
occurred during their movement and to predict the formation and growth of
blood aneurysm in the blood vessels.</p>
      <p>The work was carried out with support of state task of Ministry of Science
and Education, project 1.630.2014/K.
0.000e+00 0.25 Concentration 0.75 1.000e+00
0.5
0.000e+00 0.25 Concentration 0.75 1.000e+00
0.5
0.000e+00 0.25 Concentration 0.75 1.000e+00
0.5
0.000e+00 0.25 Concentration 0.75 1.000e+00
0.5
3)  = 19.5
0.000e+00 0.25 Concentration 0.75 1.000e+00
0.5
0.000e+00 0.25 Concentration 0.75 1.000e+00
0.5
1)  = 1.5</p>
      <p>2)  = 25.0
0.000e+00 0.25 Concentration 0.75 1.000e+00
0.5</p>
    </sec>
  </body>
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