European Biophysics Journal Wave propagation through viscous fluid-filled elastic tube under initial pressure: theoretical and biophysical model --Manuscript Draft-Manuscript Number: EBJO-D-22-00016R1 Full Title: Wave propagation through viscous fluid-filled elastic tube under initial pressure: theoretical and biophysical model Article Type: Original Article Keywords: Navier-Stokes equations, pulse wave velocity, arterial wall elasticity, viscosity, biophysical model Corresponding Author: Dejan Žikić, Ph.D. Faculty of Medicine, University of Belgrade Belgrade, SERBIA Corresponding Author Secondary Information: Corresponding Author's Institution: Faculty of Medicine, University of Belgrade Corresponding Author's Secondary Institution: First Author: Dejan Žikić, Ph.D. First Author Secondary Information: Order of Authors: Dejan Žikić, Ph.D. Katarina Žikić Order of Authors Secondary Information: Funding Information: Science and Technology Development Center, Ministry of Education (32040, 41022) Abstract: The velocity of propagation of pulse waves through the arteries is one of the indicators of the health condition of the cardiovascular system. By measuring the pulse wave velocity, cardiologists estimate the elasticity of the wall of blood vessels and the changes that occur with aging. Using the Moens-Korteweg equation, an erroneous assessment is made in the analysis. The paper presents the solution of Navier-Stokes equations for propagation of pulse waves through an elastic tube filled with viscous fluid under initial pressure. The equation for pulse wave velocity depending on viscosity, density and initial fluid pressure, density and elasticity of wall and geometry of the tube is derived. The results of the equation were compared with the experimental results measured on a biophysical model of the cardiovascular system. Response to Reviewers: C1: In my opinion, the readability of the paper could be improved by splitting and moving parts of the lengthy derivations to an appendix of the paper. A1:According to the reviewer's suggestions, we moved the derivation of the equation for the pulse wave velocity to the Appendix of the paper. Dr Dejan Žikić C2:The value of the mathematical model would be increased if its sensitivity analysis is performed, e.g., sensitivity and importance indexes, etc., could be calculated (see G. Qian, A. Mahdi 2020 Mathematical Biosciences). A2:The reviewer is right; the sensitivity analysis of the model is very important especially in biological and biochemical models. With our model, it's a little different. Since our model is in the field of fluid physics (or fluid biophysics), the sensitivity is analyzed differently from the biological models described in the paper recommended by the reviewer. Our assumption was that before, during and after the experiment, the parameters of the model do not change (unlike, for example: biochemical reactions, cell models or cancer research where the parameters change over time). Powered by Editorial Manager® and ProduXion Manager® from Aries Systems Corporation We analyzed the sensitivity by changing the parameters of the model (pressure, density, viscosity) and monitoring the output signal at a constant input signal (amplitude of pressure change and pulse wave frequency). Also, we changed the sample rate of the ADC and found that the best measurement frequency is 1KHz (higher frequency has no effect on the result). And of course, we repeated the measurements under the same conditions dozens of times. Our further research is to compare the mathematical model with the measured results in patients and then we will apply some of the SA methods. C3Page 3, l. 53-55, the text could be reformulated to make it more understandable. A3:The reviewer is right; we accidentally misspelled. We corrected the text according to the reviewer's suggestions C4:Page 14, l. 7-14 the text could be reformulated to make it more understandable. A4: We corrected the text according to the reviewer's suggestions. C5: Page 16, l. 38-40, the text could be reformulated to make it more understandable. A5:We corrected the text according to the reviewer's suggestions. C6:Page 17, l. 16-20, the text could be reformulated to make it more understandable. A6:We corrected the text according to the reviewer's suggestions. Powered by Editorial Manager® and ProduXion Manager® from Aries Systems Corporation Authors' Response to Reviewers' Comments Click here to access/download;Authors' Response to Reviewers' Comments;Answers to reviewer.docx ANSWERS TO REVIEWERS We thank the reviewer for his very helpful comments and compliments for our work. We find constructive suggestions very useful for improving manuscripts. As indicated below, we have checked all comments provided by reviewer and made any necessary changes accordingly. Reviewer #1: C1: In my opinion, the readability of the paper could be improved by splitting and moving parts of the lengthy derivations to an appendix of the paper. A1: According to the reviewer's suggestions, we moved the derivation of the equation for the pulse wave velocity to the Appendix of the paper. C2: The value of the mathematical model would be increased if its sensitivity analysis is performed, e.g., sensitivity and importance indexes, etc., could be calculated (see G. Qian, A. Mahdi 2020 Mathematical Biosciences). A2: The reviewer is right; the sensitivity analysis of the model is very important especially in biological and biochemical models. With our model, it's a little different. Since our model is in the field of fluid physics (or fluid biophysics), the sensitivity is analyzed differently from the biological models described in the paper recommended by the reviewer. Our assumption was that before, during and after the experiment, the parameters of the model do not change (unlike, for example: biochemical reactions, cell models or cancer research where the parameters change over time). We analyzed the sensitivity by changing the parameters of the model (pressure, density, viscosity) and monitoring the output signal at a constant input signal (amplitude of pressure change and pulse wave frequency). Also, we changed the sample rate of the ADC and found that the best measurement frequency is 1KHz (higher frequency has no effect on the result). And of course, we repeated the measurements under the same conditions dozens of times. Our further research is to compare the mathematical model with the measured results in patients and then we will apply some of the SA methods. C3 Page 3, l. 53-55, the text could be reformulated to make it more understandable. A3: The reviewer is right; we accidentally misspelled. We corrected the text according to the reviewer's suggestions C4: Page 14, l. 7-14 the text could be reformulated to make it more understandable. A4: We corrected the text according to the reviewer's suggestions. C5: Page 16, l. 38-40, the text could be reformulated to make it more understandable. A5: We corrected the text according to the reviewer's suggestions. C6: Page 17, l. 16-20, the text could be reformulated to make it more understandable. A6: We corrected the text according to the reviewer's suggestions. Manuscript (with track changes) Wave propagation through viscous fluid-filled elastic tube under initial pressure: theoretical and biophysical model Dejan Žikić1 & Katarina Žikić2 1 Institute of Biophysics, Faculty of Medicine, University of Belgrade, Serbia 2 Faculty of Physics, University of Belgrade, Serbia Corresponding author: Dejan Žikić, Associate Professor Institute of Biophysics, Faculty of Medicine University of Belgrade, 11000 Belgrade, Serbia https://orcid.org/0000-0003-3247-9071 Tel: +381 11 360 7159 Fax: +381 11 360 7061 e-mail: dzikic@gmail.com 1 Abstract The velocity of propagation of pulse waves through the arteries is one of the indicators of the health condition of the cardiovascular system. By measuring the pulse wave velocity, cardiologists estimate the elasticity of the wall of blood vessels and the changes that occur with aging. Using the Moens-Korteweg equation, an erroneous assessment is made in the analysis. The paper presents the solution of Navier-Stokes equations for propagation of pulse waves through an elastic tube filled with viscous fluid under initial pressure. The equation for pulse wave velocity depending on viscosity, density and initial fluid pressure, density and elasticity of wall and geometry of the tube is derived. The results of the equation were compared with the experimental results measured on a biophysical model of the cardiovascular system. Keywords: Navier-Stokes equations, pulse wave velocity, arterial wall elasticity, viscosity, biophysical model 2 1. Introduction Investigation of the waveforms of arterial blood pressure and flow through blood vessels plays an important role in understanding the nature and disorders of the cardiovascular system. The beginning of the interest of scientists in the wave nature of blood dates to the beginning of the 19th century when Young (1808) published a paper on the wave motion of blood and derived the first formula for pulse wave velocity. In 1877, Moens and Korteweg simultaneously derived the equation for the velocity of a pulse wave propagating through a fluid-filled elastic tube of thin walls (Moens 1877, Moens 1878, Korteweg 1878). This equation is still used today in medicine to study the age of the cardiovascular system. The greatest mathematical contribution was made by Womersley in the middle of the last century (Womersley 1955) who solved the pulse wave velocity profile in a rigid tube filled with a viscous fluid. In addition, he offered a solution for the pulse wave velocity profile through an elastic tube and developed a mathematical analysis of blood flow in the arteries. In his work, he included viscosity in the pulse wave velocity calculation (Womersley 1957). To better understand the physics of cardiovascular processes, mathematical and experimental biophysical models were mainly used. In mathematical models, the equations describe the principles of the physical laws of a process, then the theoretical model is experimentally confirmed on the biophysical model. Khir and Parker (2002) and later Li (Li et al. 2011), used the water-hammer equation to determine pulse wave velocity. Westerhof et al. (1972) determined pulse wave velocity from waveforms of fluid pressure and flow. Feng and Khir (2010) applied both equations to detect reflected waves in flow pressure signals. In his work, Khir used a pressure-velocity loop to determine the arrival time of reflected waves (Khir et al. 2007). Lazovic et al. (2015), detected reflected waves that appear on the radial artery with aging. Papageorgiou and Jones (1987a) investigated the various materials used in models for arteries and blood vessels. They found that if elastic tubes with a nonlinear stress / strain ratio are used in the models, the differences between real systems and physical models are minimal. They found (1987b) that the differences between real systems and physical models are minimal when elastic tubes are used in the models where the ratio of stress and relative elongation is not. The influence of viscosity on pulse wave velocity was 3 experimentally shown by Stojadinović et al. (2015). The influence of gravity on wave propagation was experimentally shown by Žikić et al. (2019). One of the parameters used in medicine to determine the age of the cardiovascular system is the pulse wave velocity - PWV. The Moens-Korteweg equation is mainly used to estimate arterial elasticity from measured PWV values. As this equation does not depend on blood viscosity, diastolic pressure, blood vessel wall density as well as the influence of gravity, using this relation in medical research introduces an error in the interpretation of results and can be misdiagnosed. Morgan and Kiely (1954) offered a solution for calculating PWV through a viscous fluid in an elastic tube but without initial pressure and without pipe wall density. Womersley (1955, 1957) also solved this problem with viscosity but offered a solution in a complex equation that only physicists can solve. Also, this equation cannot be applied if the fluid is under initial pressure and the wall density of the elastic tube is neglected. Other scientists have also investigated how PWV changes with initial fluid pressure (Atabek et al. 1966; Atabek 1968; Demiray and Akgün 1997) but the offered equations are very complicated especially for medical doctors and the results of their equations do not agree with the experimental results. One of the reasons for the interest in this phenomenon of wave propagation is related to research in hemodynamics. The main area that cardiovascular physics deals with is the wave propagation of blood through blood vessels. With aging, the biophysical parameters of the blood and blood vessels change, and the correct interpretation of cardiovascular parameters can greatly contribute to accurate diagnosis and successful therapy. The aim of this paper is to show the mathematical derivation of the equation for pulse waves velocity through a viscous fluid-filled elastic tube with initial fluid pressure and to prove experimentally the accuracy of the equation. 2. Methods 2.1 Mathematical equations Moens-Korteweg equation 4 Moens and Korteweg ingeniously derived the equation for PWV. They assumed that the pulse wave increases the initial volume of the cylinder 𝑉𝑜 = 𝜋𝑅𝑜2 ∆𝑧 (Figure 1) of width ∆z to 𝑉 = 𝜋(𝑅0 + ∆𝑅0 )2 (∆𝑧 + 𝜕𝑢 ∆𝑧) and 𝜕𝑧 derived three equations: 𝜕𝑢 2 2 ∆𝑉 𝜋(𝑅0 + ∆𝑅0 ) (∆𝑧 + 𝜕𝑧 ∆𝑧) − 𝜋𝑅𝑜 ∆𝑧 = 𝑉𝑜 𝜋𝑅𝑜2 ∆𝑧 2 2 2∆𝑅0 ∆𝑅0 𝜕𝑢 2∆𝑅0 𝜕𝑢 ∆𝑅0 𝜕𝑢 2∆𝑅0 𝜕𝑢 ∆𝑝 = +( 2 ) + + +( 2 ) = + =− 𝑅0 𝜕𝑧 𝑅0 𝜕𝑧 𝜕𝑧 𝑅0 𝜕𝑧 𝐾 𝑅𝑜 𝑅𝑜 where ∆𝑉 is the change in volume, K- bulk modulus of fluid, ( ∆𝑅0 2 2∆𝑅0 𝜕𝑢 ∆𝑅0 2 𝜕𝑢 ) , 𝑅 𝜕𝑧 , ( 𝑅 2 ) 𝜕𝑧 𝑅𝑜2 0 𝑜 (1) ≈0 The difference in pressures on the front and back of the disk (Figure 2) can be expressed from the pressure gradient, and the axial acceleration of the fluid is: 𝑚𝑎 = − 𝜕(∆𝑝) 𝜕2 𝑢 𝑙𝐴 = 𝜌𝑙𝐴 2 𝜕𝑧 𝜕𝑡 or 𝜕(∆𝑝) 𝜕2𝑢 = −𝜌 2 𝜕𝑧 𝜕𝑡 (2) Due to the increase in pressure ∆p in the fluid, the force F1 tends to separate the two half-cylinders (Figure 3a). On the other hand, this force is opposed by hoop stress 𝜎𝜃 𝐹1 = ∆𝑝𝑆1 = 2∆𝑝(𝑅0 + ∆𝑅0 )𝑙 = 2𝑆2 𝜎𝜃 = 2ℎ𝑙𝐸 2𝜋∆𝑅0 ∆𝑅0 = 2𝐸 ℎ𝑙 2𝜋𝑅0 𝑅0 Arranging this equation gives the third Moens-Korteweg equation ∆𝑝 = 𝐸ℎ ∆𝑅0 ∆𝑅0 ~𝐸ℎ 2 (𝑅0 + ∆𝑅0 )𝑅0 𝑅𝑜 (3) After differentiating the second and third equations and arranging using the first equation, a wave equation is obtained 𝜕2𝑢 2𝜌𝑅0 𝜌 𝜕 2 𝑢 = ( + ) 2 𝜕𝑧 2 𝐸ℎ 𝐾 𝜕𝑡 For an elastic tube and an incompressible fluid ( 𝐾 → ∞), the equation becomes the Moens-Korteweg equation 5 𝜕 2 𝑢 2𝜌𝑅0 𝜕 2 𝑢 1 𝜕2 𝑢 = = 2 2 2 2 𝜕𝑧 𝐸ℎ 𝜕𝑡 𝑐0 𝜕𝑡 𝑐0 = √ 𝐸ℎ 2𝜌𝑅0 (4) Where c0 is the pulse wave velocity – PWV. As can be seen from the equation, viscosity, tube wall density and initial fluid pressure do not affect the PWV. Bramwell and Hill derived the equation for PWV without values for E, h, and R0 (since they are not constant and depend on the artery itself). If we replace ∆R0 in equation (1) from equation (3) and assume that ∂u/∂z is small it follows: ∆𝑉 2∆𝑅0 2 𝑅0 2 ∆𝑝 2𝑅0 ∆𝑝 = = = 𝑉𝑜 𝑅0 𝑅0 𝐸ℎ 𝐸ℎ The rearrangement resulted in: 𝐸ℎ 𝑉𝑜 ∆𝑝 = 2𝑅0 ∆𝑉 And by substituting in equation (4), the Bramwell-Hill equation is obtained: 𝑐0 = √ 𝑉𝑜 ∆𝑝 𝜌 ∆𝑉 (5) 2.2 Pulse wave velocity when the fluid is under initial pressure Let the initial pressure in the tube be p0. Due to the increase in pressure, the radius also increases: R=R0+R and the length of the tube l=l0+l. In the derivation of equation (3) it is shown that the hoop stress is equal 𝜎𝜃 = 𝑝0 𝑅0 2𝜋∆𝑅0 ∆𝑅0 𝑅 − 𝑅0 = 2ℎ𝑙𝐸 = 2𝐸 ℎ𝑙 = 2𝐸 ℎ𝑙 ℎ 2𝜋𝑅0 𝑅0 𝑅0 By arranging, the final radius with the initial pressure in the tube is 𝑅= 𝑅0 𝑝 𝑅 1− 0 0 𝐸ℎ The same pressure acts on the cross section of the cylinder (Figure 3b) and is opposed by longitudinal stress 6 Formatted: Justified 𝐹2 = 𝑝0 𝜋𝑅02 = 𝜋[(𝑅0 + ℎ)2 − 𝑅02 ]𝜎𝑙 ~2𝜋𝑅0 ℎ𝜎𝑙 By arranging, the hoop stress is 2 times higher than the longitudinal stress 𝜎𝑙 = 𝑝0 𝑅0 𝜎𝜃 = 2ℎ 2 After substitution 𝐸 ∆𝑅0 ∆𝑙 = 2𝐸 𝑅0 𝑙0 𝑅 − 𝑅0 𝑙 − 𝑙0 =2 𝑅0 𝑙0 𝑙= 𝑙0 1 𝑝0 𝑅0 ( + 1)~𝑙0 (1 + ) 2 1 − 𝑝0 𝑅0 2𝐸ℎ 𝐸ℎ Due to the increase in fluid pressure in the tube by p0, the disk volume is: 𝑉 = 𝑅 2 𝜋𝑙 Or 2 𝑝0 𝑅0 𝑝0 𝑅0 ∆𝑝 𝑅0 𝑝0 𝑅0 ∆𝑝 ∆𝑝 (1 + 2𝐸ℎ ) ∆𝑝 (1 + 2𝐸ℎ ) 2 𝑉 = 𝑅 𝜋𝑙 = ( ) = 𝜋𝑙0 𝑅02 = 𝑉 ) 𝜋𝑙0 (1 + 0 𝑝 𝑅 ∆𝑉 2𝐸ℎ ∆𝑉 ∆𝑉 ∆𝑉 𝑝 𝑅 2 𝑝 𝑅 2 (1 − 0 0 ) (1 − 0 0 ) (1 − 0 0 ) 𝐸ℎ 𝐸ℎ 𝐸ℎ 𝑝0 𝑅0 ∆𝑝 𝐸ℎ 1 + 2𝐸ℎ 𝑉 = ∆𝑉 2𝑅0 𝑝 𝑅 2 (1 − 0 0 ) 𝐸ℎ (6) Using equation (6) and Bramwell-Hill equation (5), the PWV can be calculated with the initial fluid pressure in the tube: √ 𝑐= 𝐸ℎ 𝑝 𝑅 𝐸ℎ 𝑝 √ + 0 0 + 0 2𝑅0 𝜌 (1 2𝐸ℎ ) 2𝑅0 𝜌 4𝜌 = 𝑝 𝑅 𝑝 𝑅 1− 0 0 1− 0 0 𝐸ℎ 𝐸ℎ (7) 2.3 Wave propagation through an elastic tube filled with a viscous fluid Fluid motion is governed by continuity equation (8) and Navier–Stokes equations (9,10): 𝑑𝜌 + ∇(ρv) = 0 𝑑𝑡 𝜕𝑣𝑧 𝜕𝑣𝑧 𝜕𝑣𝑧 𝜕𝑝 1 𝜕 𝜕𝑣𝑧 𝜕 2 𝑣𝑧 𝜌( + 𝑣𝑟 + 𝑣𝑧 )=− +𝜇( (𝑟 )+ ) + 𝜌𝑔𝑧 𝜕𝑡 𝜕𝑟 𝜕𝑧 𝜕𝑧 𝑟 𝜕𝑟 𝜕𝑟 𝜕𝑧 2 (8) (9) 7 𝜌( 𝜕𝑣𝑟 𝜕𝑣𝑟 𝜕𝑣𝑟 𝜕𝑝 1 𝜕 𝜕𝑣𝑟 𝜕 2 𝑣𝑟 𝑣𝑟 + 𝑣𝑟 + 𝑣𝑧 )=− +𝜇( (𝑟 )+ − ) 𝜕𝑡 𝜕𝑟 𝜕𝑧 𝜕𝑟 𝑟 𝜕𝑟 𝜕𝑟 𝜕𝑧 2 𝑟 2 (10) where is density, 𝑣𝑧 is the axial velocity of the fluid, 𝑣𝑟 is the radial velocity of the fluid, is the dynamic viscosity. By solving these equations (Appendix) we obtain pulse wave velocities for the case of small viscosity and high viscosity: 𝐸ℎ 𝑝 + 0 1 𝑡 1 𝜇 𝜎 2 3𝑡 2𝑅0 𝜌 4𝜌 𝑐= − )) (1 + − √ (1 − 𝜎 + 2 𝑝 𝑅 4 𝑅0 2𝜔𝜌 4 8 1 − 0 0 (1 + 𝑡 ) 𝐸ℎ 4 And for high viscosity √ 𝑐= 𝑐0 5 − 4𝜎 + 6𝑡 √ 𝑅 2 𝜔𝜌 0 𝜇 = ±√ 𝐸ℎ 𝑝0 𝜔𝜌 1 + 𝑅 √ 2𝑅0 𝜌 4𝜌 0 𝜇 5 − 4𝜎 + 6𝑡 (11) (12) The last equation (eq.12) has no application for medical research due to its high viscosity values, so it will not be discussed further in the paper. Equations of fluid motion We will assume that the fluid is incompressible and viscous. It is also assumed that the fluid propagates pulsatingly through a cylindrical tube of thin elastic walls. Fluid motion is governed by continuity equation (8) and Navier–Stokes equations (9,10): 𝑑𝜌 + ∇(ρv) = 0 𝑑𝑡 𝜕𝑣𝑧 𝜕𝑣𝑧 𝜕𝑣𝑧 𝜕𝑝 1 𝜕 𝜕𝑣𝑧 𝜕 2 𝑣𝑧 𝜌( + 𝑣𝑟 + 𝑣𝑧 )=− +𝜇( (𝑟 )+ ) + 𝜌𝑔𝑧 𝜕𝑡 𝜕𝑟 𝜕𝑧 𝜕𝑧 𝑟 𝜕𝑟 𝜕𝑟 𝜕𝑧 2 𝜕𝑣𝑟 𝜕𝑣𝑟 𝜕𝑣𝑟 𝜕𝑝 1 𝜕 𝜕𝑣𝑟 𝜕 2 𝑣𝑟 𝑣𝑟 𝜌( + 𝑣𝑟 + 𝑣𝑧 )=− +𝜇( (𝑟 )+ − ) 𝜕𝑡 𝜕𝑟 𝜕𝑧 𝜕𝑟 𝑟 𝜕𝑟 𝜕𝑟 𝜕𝑧 2 𝑟 2 (8) (9) (10) where is density, 𝑣𝑧 is the axial velocity of the fluid, 𝑣𝑟 is the radial velocity of the fluid, is the dynamic viscosity. The assumption is that the motion is axisymmetric without tangential velocity 𝑣𝜃 = 0. We will also assume that the fluid is not affected by gravity, i.e. that the z axis is in a horizontal position, so the last term in eq. 9 can be ignored. Next, we describe the movement of the tube wall with two equations: longitudinal and radial 8 𝜕2𝜂 𝐸ℎ 𝜂 𝜕𝜁 =𝑝− ( +𝜎 ) (11) (1 − 𝜎 2 )𝑅0 𝑅0 𝜕𝑡 2 𝜕𝑧 𝜕2𝜁 𝐸ℎ 𝜕 2 𝜁 𝜎 𝜕𝜂 𝜕𝑣𝑧 𝜕𝑣𝑟 𝜌0 ℎ 2 = + + ) ( )−𝜇( (12) (1 − 𝜎 2 ) 𝜕𝑧 2 𝑅0 𝜕𝑧 𝜕𝑡 𝜕𝑟 𝜕𝑧 Where 𝜂 and 𝜁 are the components of the displacement of the point on the tube wall in the axial and radial 𝜌0 ℎ directions, respectively, E – Young's modulus of elasticity, ρ0 –the density of the tube wall. The assumption is that the pulse wave has a sinusoidal shape and that 𝜂, 𝜁, 𝑣𝑟 𝑎𝑛𝑑 𝑣𝑧 change in the same way. Let them be 𝑝 = 𝑃𝑒 𝑖(𝐾𝑧−𝜔𝑡) , 𝜂 = Ω𝑒 𝑖(𝐾𝑧−𝜔𝑡) , 𝜁 = Λ𝑒 𝑖(𝐾𝑧−𝜔𝑡) , 𝑣𝑧 = 𝑢(𝑟)𝑒 𝑖(𝐾𝑧−𝜔𝑡) 𝑖 𝑣𝑟 = 𝑤(𝑟)𝑒 𝑖(𝐾𝑧−𝜔𝑡) (𝑤, 𝑢 – functions of 𝑟, 𝑃, Ω, Λ – constants). After substitution in equations (9), (10), (11) and (12) and 𝑖𝜔𝜌 𝜇 differentiation ( = 𝛼2, 𝜕 2 𝑣𝑟 𝜕𝑧 2 ≈ 0, 𝜕2𝑢 𝜕𝑧 2 ≈ 0 ) follows: 𝜕 2 𝑢 1 𝜕𝑢 𝑖𝐾 + + 𝛼2𝑢 = 𝑃 𝜕𝑟 2 𝑟 𝜕𝑟 𝜇 𝜕 2 𝑤 1 𝜕𝑤 1 1 𝜕𝑝 + + (𝛼 2 − 2 ) 𝑤 = 𝜕𝑟 2 𝑟 𝜕𝑟 𝑟 𝜇 𝜕𝑟 𝐸ℎ Ω 𝑖𝐾𝜎 −𝜌0 ℎ𝜔2 Ω = 𝑃 − Λ) ( + (1 − 𝜎 2 ) 𝑅02 𝑅0 𝐸ℎ 𝑖𝐾𝜎 𝜕𝑢 −𝜌0 ℎ𝜔2 Λ = (−𝐾 2 Λ + Ω) − 𝜇 ( |𝑟=𝑅0 + 𝑖𝐾𝑤) (1 − 𝜎 2 ) 𝑅0 𝜕𝑟 (13) (14) (15) (16) Equations (13) and (14) are partial Bessel equations. Assuming that P is in the form: 𝑃 = 𝐴1 ∙ 𝐽0 (𝑦𝑟), where 𝐴1 is a constant and a non-homogeneous solution in the form 𝑢(𝑟) = 𝐵1 ∙ 𝐽0 (𝑦𝑟), by substituting in equation (13) and differentiating, a particular solution is obtained 𝑢(𝑟) = 𝑖𝐾𝐴1 1 ∙ 𝐽 (𝑦𝑟) 𝜇 (𝛼 2 − 𝑦 2 ) 0 Assumption that a homogeneous solution in the form 𝑢(𝑟) = 𝐶1 𝐽0 (𝛼𝑟) , 𝐽0 (𝛼) where C1 is a constant to be determined and in the final form: 𝑢(𝑟) = 𝐶1 𝐽0 (𝛼𝑟) 𝑖𝐾𝐴1 1 + ∙ 𝐽 (𝑦𝑟) 𝐽0 (𝛼) 𝜇 (𝛼 2 − 𝑦 2 ) 0 (17) 9 Similar mathematical operations are repeated to solve equation (14). Let non-homogeneous solution be in the form 𝑤 = 𝐷1 ∙ 𝐽1 (𝑦𝑟), and by changing to equation (14) and differentiating, a particular solution is obtained 𝑤=− 𝑦𝐴1 1 ∙ 𝐽 (𝑦𝑟) 𝜇 (𝛼 2 − 𝑦 2 ) 1 Here, too, the assumption is that the homogeneous solution is in the form 𝑤 = 𝐶2 𝐽1 (𝛼𝑟) , 𝐽0 (𝛼) where C2 is a constant, so it is in the final form: 𝐽1 (𝛼𝑟) 𝑦𝐴1 1 − ∙ 𝐽 (𝑦𝑟) 𝐽0 (𝛼) 𝜇 (𝛼 2 − 𝑦 2 ) 1 From the equation of continuity (8) => (18) 𝜕𝑤 𝑤 + + 𝑖𝐾𝑢 = 0 𝜕𝑟 𝑟 By substituting equations (17) and (18) into equation (19) and arranging it, we get (19) 𝑤(𝑟) = 𝐶2 − (𝑖𝐾𝐶1 𝐽0 (𝛼𝑟) 𝑖 2 𝐾 2 𝐴1 1 + ∙ 𝐽 (𝑦𝑟)) 𝐽0 (𝛼) 𝜇 (𝛼 2 − 𝑦 2 ) 0 = 𝛼𝐶2 𝐽0 (𝛼𝑟) 𝑦 2 𝐴1 1 𝐶2 𝐽1 (𝛼𝑟) 1 𝑦𝐴1 1 − ∙ 𝐽 (𝑦𝑟) + − ∙ 𝐽 (𝑦𝑟) 𝐽0 (𝛼) 𝜇 (𝛼 2 − 𝑦 2 ) 0 𝑟 𝐽0 (𝛼) 𝑟 𝜇 (𝛼 2 − 𝑦 2 ) 1 By solving we get 𝐶2 = − 𝑖𝐾 𝐶 𝛼 1 and after series expansion of Bessel coefficients: 𝑦𝑟 2 (2) 𝑦𝑟 4 (2) 𝐽0 (𝑦𝑟) = 1 − + 2 2 +⋯ ≈1 (12 ) (1 )(2 ) 1 𝑦𝑟 𝑦𝑟 3 𝑦𝑟 5 (2) (2) (2) 𝑦𝑟 𝐽1 (𝑦𝑟) = − + +⋯ ≈ 1 2 12 ∙ 3 22 2 𝑖𝜔𝜌 𝑖𝜔𝜌 𝑖 𝜔 As well as (𝛼 2 − 𝑦 2 ) = − 𝑖2𝐾2 = − 2 ≈ 𝛼2 𝜇 𝜇 𝑐 Due to the viscosity the velocities of the fluid along the inner wall of the vessel (when r = R0) are 𝑢|𝑟=𝑅0 = 𝐶1 𝐽0 (𝛼𝑟) 𝑖𝐾𝐴1 1 𝐽0 (𝛼𝑟) 𝐴1 + ∙ 𝐽 (𝑦𝑟) = 𝐶1 + 𝐽0 (𝛼) 𝜇 (𝛼 2 − 𝑦 2 ) 0 𝐽0 (𝛼) 𝜌𝑐 𝑤|𝑟=𝑅0 = 𝐶2 𝐽1 (𝛼𝑟) 𝑦𝐴1 1 𝑖𝐾 2 𝐽1 (𝛼𝑟) 𝐴1 − ∙ 𝐽 (𝑦𝑟) = − (𝐶1 + ∙𝑅 ) 𝐽0 (𝛼) 𝜇 (𝛼 2 − 𝑦 2 ) 1 2 𝛼 𝐽0 (𝛼) 𝜌𝑐 0 10 and we have 𝑑𝑢 𝐽1 (𝛼𝑅0 ) 𝑖𝐾𝐴1 1 𝐽1 (𝛼𝑅0 ) 𝐴1 𝐾 2 𝑅0 |𝑟=𝑅0 = −𝐶1 𝛼 + ∙ (−𝑦)𝐽1 (𝑦𝑅0 ) = −𝐶1 𝛼 + 2 2 𝑑𝑟 𝐽0 (𝛼) 𝜇 (𝛼 − 𝑦 ) 𝐽0 (𝛼) 𝜌𝑐 2 𝐸ℎ With substitutions: 𝐵 = (1−𝜎2 ) , 𝑃 = 𝐴1 ∙ 𝐽0 (𝑦𝑟) and 𝐽0 (𝑦𝑟) ≈ 1 in equation (15) we have 1 𝐵 𝑖𝐾𝜎𝐵 𝐴 + (𝜔2 − Λ=0 )Ω − 𝜌0 ℎ 1 𝜌0 𝑅0 𝜌0 𝑅02 Since the velocity of the wall is equal to the velocity of the fluid along the wall of the vessel, equalizing the equations 𝑢= 𝑑𝜁 𝐽0 (𝛼𝑟) 𝐴1 𝑖(𝐾𝑥−𝜔𝑡) | = −𝑖𝜔Λ𝑒 𝑖(𝐾𝑥−𝜔𝑡) = (𝐶1 + )𝑒 𝑑𝑡 𝑟=𝑅0 𝐽0 (𝛼) 𝜌𝑐 𝐴1 𝐽0 (𝛼𝑅0 ) + 𝐶1 + 𝑖𝜔Λ = 0 𝜌𝑐 𝐽0 (𝛼) 𝑑𝜂 𝑖𝐾 2 𝐽1 (𝛼𝑅0 ) 𝐴1 𝑤= | = −𝑖𝜔Ω𝑒 𝑖(𝐾𝑥−𝜔𝑡) = − (𝐶1 + ∙ 𝑅 ) 𝑒 𝑖(𝐾𝑥−𝜔𝑡) 𝑑𝑡 𝑟=𝑅0 2 𝛼 𝐽0 (𝛼) 𝜌𝑐 0 𝑖𝐾𝑅0 𝑖𝐾 𝐽1 (𝛼𝑅0 ) 𝐴 + 𝐶1 − 𝑖𝜔Ω = 0 2𝜌𝑐 1 𝛼 𝐽0 (𝛼) And the last equation, with substitutions in (16) => (21) (22) −𝜔2 Λ = −𝐾 2 𝐵ℎ 𝑖𝐾𝜎 𝐵ℎ 𝜇 𝐽1 (𝛼𝑅0 ) 𝐴1 𝐾 2 𝑅0 𝑖 2 𝐾 2 2 𝐽1 (𝛼𝑅0 ) 𝐴1 Λ+ Ω− + − + ∙ 𝑅 )) (−𝐶1 𝛼 (𝐶1 (𝛼) 𝜌0 ℎ 𝑅0 𝜌0 ℎ 𝜌0 ℎ 𝐽0 𝜌𝑐 2 2 𝛼 𝐽0 (𝛼) 𝜌𝑐 0 𝜔2 𝑐2 ≪ 1 , 𝛼 𝐾2 2 𝐽1 (𝛼𝑅0 ) 𝐴1 + ∙𝑅 )≪1 (𝐶1 2 𝛼 𝐽0 (𝛼) 𝜌𝑐 0 We obtain − 𝜇 𝐾 2 𝑅0 𝜇𝛼 𝐽1 (𝛼𝑅0 ) 𝐵ℎ 𝑖𝐾𝜎 𝐵ℎ ∙ 𝐴1 + 𝐶 + (𝜔2 − 𝐾 2 )Λ + Ω=0 𝜌0 ℎ𝜌𝑐 2 𝜌0 ℎ 𝐽0 (𝛼) 1 𝜌0 ℎ 𝑅0 𝜌0 ℎ (23) The system of equations (20), (21), (22) and (23) is solved by setting the coefficients A1, C1, Λ and Ω to be equal to 0: 11 1 𝜌𝑐 | 𝑖𝜔𝑅0 2𝜌𝑐 2 | 1 𝜌0 ℎ | 𝜇 𝜔2 𝑅0 − ∙ 3 𝜌0 ℎ𝜌𝑐 2 𝐽0 (𝛼𝑅0 ) 𝐽0 (𝛼) 𝑖𝜔 𝐽1 (𝛼𝑅0 ) 𝛼𝑐 𝐽0 (𝛼) 0 𝑖𝜔 −𝑖𝜔 0 𝐵 𝜌0 𝑅02 𝑖𝜔𝜎 𝐵 𝑅0 𝑐 𝜌0 𝜔2 − 0 𝜇𝛼 𝐽1 (𝛼𝑅0 ) 𝜌0 ℎ 𝐽0 (𝛼) | 𝑖𝜔𝜎𝐵 | = 0 𝜌0 𝑅0 𝑐 𝜔2 𝐵 | 𝜔2 − 2 𝑐 𝜌0 − By simplifying this determinant, we obtain | 1− 2 𝐽1 (𝛼𝑅0 ) 𝛼𝑅0 𝐽0 (𝛼𝑅0 ) 1 | − 1 𝐽1 (𝛼𝑅0 ) 𝛼𝑅0 𝐽0 (𝛼𝑅0 ) 2 𝐵ℎ 𝜌𝑐 2 𝑅0 𝜎𝐵 − 2 𝜌𝑐 𝑅0 1 | 𝜎𝐵ℎ =0 𝜌𝑐 2 𝑅0 | 𝜌0 ℎ 𝐵ℎ − 𝜌𝑅0 𝜌𝑐 2 𝑅0 1+ Using substitutions 𝐸ℎ 𝜌0 ℎ = 𝑥, =𝑡 (24) 2𝜌𝑐 2 𝑅0 𝜌𝑅0 and after solving the determinant, the so-called frequency equation in term of variable x was obtained (4 − 2𝛼𝑅0 𝐽0 (𝛼𝑅0 ) 2 𝛼𝑅0 𝐽0 (𝛼𝑅0 ) 𝐽0 (𝛼𝑅0 ) − 1) − 4𝜎 + 1 + 2𝛼𝑅0 ]𝑥 ) 𝑥 + [2𝑡 ( 𝐽1 (𝛼𝑅0 ) 2 𝐽1 (𝛼𝑅0 ) 𝐽1 (𝛼𝑅0 ) 𝛼𝑅0 𝐽0 (𝛼𝑅0 ) − 2𝑡(1 − 𝜎 2 ) − (1 − 𝜎 2 ) = 0 2 𝐽1 (𝛼𝑅0 ) Using the values for viscosity of blood, diameter of aorta or main arteries, blood density and density of artery wall, we obtained that |𝛼𝑅0 | ≫ 1, ie that they are in the ranges of 𝛼𝑅0 = 3 − 12 and 𝑡 = 0.1 − 0.4. After asymptotic expansion of the Bessel function 𝐽0 (𝛼𝑅0 ) 1 ~−𝑖+ 𝐽1 (𝛼𝑅0 ) 2𝛼𝑅0 and by substituting in the frequency equation and arranging, the quadratic equation is obtained (−2𝛼𝑅0 𝑖 − 3)𝑥 2 + [4𝜎 − 2 + 2𝛼𝑅0 𝑖 + 𝑡𝛼𝑅0 𝑖 + 3𝑡 𝑡 ] 𝑥 + (1 − 𝜎 2 ) (1 + − 𝑡𝛼𝑅0 𝑖) = 0 2 2 12 This quadratic equation can be solved for 𝜎 = 0, 𝜎 = 1 2 and 𝜎 = 1. For an artery 𝜎 = 0.49, so the roots of 1 2 quadratic equation for 𝜎 = , are: 𝑡 𝑖 𝜎 2 3𝑡 𝑖(1 − 𝜎 2 ) 𝑥1 = 1 + + − ) and 𝑥2 = (2 − 2𝜎 + 2 𝛼𝑅0 2 4 2𝛼𝑅0 Substituting in (24) 𝐾 2 𝐸ℎ 𝐾2 = 2 𝑐02 = 𝑥 2 𝜔 2𝜌𝑅0 𝜔 We look for solutions in the following form and only for x1 (for 𝜇 → 0, 𝑥2 → ∞) 𝐾 𝐾1 + 𝑖𝐾2 𝑐 = 𝑐0 = √𝑥1 𝜔 0 𝜔 After substitution √𝑖 = √2 (1 2 + 𝑖) and solving the root of a complex number 𝜎 2 3𝑡 𝜎 2 3𝑡 𝑡 2 (1 − 𝜎 + 4 − 8 ) 2𝑖 (1 − 𝜎 + 4 − 8 ) 𝐾1 + 𝑖𝐾2 + = 𝑐0 √𝑥1 = √1 + + 2 𝜔 2𝜔𝜌 2𝜔𝜌 √ √ 𝑅0 𝑅0 𝜇 𝜇 𝜎 2 3𝑡 − ) 4 8 2𝜔𝜌 √ 𝐾2 𝜇 𝑅0 𝑐0 = 𝜎 2 3𝑡 𝜔 𝑡 (1 − 𝜎 + 4 − 8 ) 1+4+ 2𝜔𝜌 √ 𝑅 𝜇 0 (1 − 𝜎 + 𝜎 2 3𝑡 𝐾1 𝑡 (1 − 𝜎 + 4 − 8 ) 𝑐 =1+ + , 𝜔 0 4 2𝜔𝜌 √ 𝑅0 𝜇 By substituting c0 with equation (7) which is a function of the initial pressure and arranging, we obtain the final equation (25) for the pulse wave velocity 𝐸ℎ 𝑝 √ + 0 𝜔 1 𝑡 1 𝜇 𝜎 2 3𝑡 2𝑅0 𝜌 4𝜌 𝑐= =± − )) (1 + − √ (1 − 𝜎 + 2 𝑝 𝑅 𝐾1 4 𝑅0 2𝜔𝜌 4 8 1 − 0 0 (1 + 𝑡 ) 𝐸ℎ 4 And (25) 2 𝑝0 𝑅0 (1 − 𝜎 + 𝜎 − 3𝑡) 4 8 𝐸ℎ 𝐾2 = ±𝜔 𝐸ℎ 𝑝0 𝑡 2𝜔𝜌 √ √ 2𝑅0 𝜌 + 4𝜌 (1 + 4) 𝜇 𝑅0 1− 13 If we assume that t is very small it can be neglected (𝑡 = 0) 𝑎𝑛𝑑 the initial fluid is zero (𝑝0 = 0) we get the same equation derived by Morgan and Kiely for small viscosity 𝑐= 𝜔 𝐸ℎ 1 𝜇 𝜎2 = ±√ (1 + − √ (1 − 𝜎 + )) 𝐾1 2𝑅0 𝜌 𝑅0 2𝜔𝜌 4 (26) And if we neglect both σ and μ we get the Moens-Korteweg equation (4) for PWV. In case of high viscosity, or |𝛼𝑅0 | ≪ 1, we use serial expansions 𝐽0 (𝛼𝑅0 ) ≈ 1 − 𝛼 2 𝑅02 , 4 𝐽1 (𝛼𝑅0 ) ≈ 𝛼𝑅0 𝛼 2 𝑅02 (1 − ) 2 8 After substituting in the frequency equation and solving the quadratic equations we obtain 𝑐= 𝜔 = 𝐾1 𝐾2 = ±𝜔√ 𝑐0 5 − 4𝜎 + 6𝑡 √ 𝑅2 𝜔𝜌 0 𝜇 = ±√ 𝐸ℎ 𝑝0 𝜔𝜌 1 + 𝑅 √ 2𝑅0 𝜌 4𝜌 0 𝜇 5 − 4𝜎 + 6𝑡 (27) 1 𝜇 √5 − 4𝜎 + 6𝑡 𝐸ℎ 𝑝0 √𝜔𝜌 𝑅0 + 2𝑅0 𝜌 4𝜌 Equation (27) has no application for medical research due to its high viscosity values, so it will not be discussed further in the paper. 2.4 Biophysical model A biophysical model of the cardiovascular system was used for the experimental validation of the equation (Figure 4). A similar model was used in Stojadinović et al. (2015) and Žikić et al. (2019). In the first experiment, pulse wave velocities were measured with increasing initial fluid pressure. The transmural pressure (difference in pressure between two sides of a wall of a tube) was changed from 0 mmHg to 120 mmHg with a step of 20 mmHg. A silicone transparent isotropic tube with an inner diameter of 10 mm and a wall thickness of 1 mm with a modulus of elasticity E = 5.19 MPa was used. The fluid was distilled water with a density of 998 kg/m3 and a viscosity of 0.99 mPa·s at 23 °C. PWV was determined from the equation d/t where d is the distance between the sensors (Figure 4) and t is the propagation time of the pulse wave between the sensors. In all experiments, the distance d between the sensors was 1m.PWV was determined 14 by measuring pulse pressure waveforms of fluid at 1 m and the time difference between the waves was determined. In Stojadinović et al. (2015) and Žikić et al. (2019) is a detailed explanation of the model and the determination of PWV. In another experiment, pulse wave velocities were measured with fluids of different densities and viscosities. The fluid pressure was 0 mmHg. Aqueous alcohol solutions with a concentration of 10-60% were used. Silicone tube of the same dimensions and properties as in the first experiment was used. 3. Results Table 1 shows the densities and viscosities of the fluids used in the experiments. The results of PWV measurements with increasing fluid pressure are shown in Figure 5. The figure also shows the calculated PWV values using the Moens-Korteweg equation, the Morgan-Kiely equation, and the model using equation (2511) in both cases: when the parameter is neglected (t = 0) and when used for the calculation (t ≠ 0). The results of measuring PWV with a change in alcohol concentration and calculated PWV using MorganKiely equation, Moens-Korteweg equation and equation (2511) are shown in Figure 6. Figure 7 shows the measured values of PWV and calculated PWV using Morgan-Kiely equation and equation (1125) for better visibility and comparison. 4. Discussion With age, the wall thickness of blood vessels increases. One of the most frequently observed is an increase in the thickness of the intima-medium of the carotid artery (Homma et al. 2001; Tanaka et al. 2001; van den Munckhof et al. 2012; Engelen et al. 2013; Dinenno et al. 2000; Green et al. 2010). The increase in artery wall thickness was found to be 5m/year in both women and men (Homma et al. 2001; Tanaka et al. 2001; van den Munckhof et al. 2012; Engelen et al. 2013). Increasing the wall thickness leads to a decrease in the lumen and inner radius of the blood vessel, so to compensate, the diameter of the artery gradually 15 Formatted: Justified increases with age in both the central (van den Munckhof et al. 2012; Engelen et al. 2013; Dinenno et al. 2000; Green et al. 2010; Schmidt-Trucksass et al. 1999) and peripheral vessels (Green et al. 2010; Sandgrenet al. 1998; van der Heijden 2000). An increase of 0.017 mm/year with atherosclerosis and 0.03 mm/year in those with pre-existing disease (Eigenbrodt et al. 2006) or 0.5% per year was observed, despite maintaining a constant body surface area. Therefore, the elastic tube that most closely corresponds to the ratio of the thickness of blood vessels of the radius of arteries in persons aged 40 and over was used in the biophysical model, i.e. the ratio h/R0≈0.2. Also, medical PWV measurements are performed in middle-aged and elderly people, when the structure of the blood vessel wall begins to change. A comparison of the experimental results and the model shows that the results of the equation presented in this paper, (eq. 2511), almost overlap. In addition to the measured values of PWV with pressure change in Figure 5, the calculated values using other models and equations are also shown. If the Moens-Korteweg equation (eq. 4) is used PWV has the same value for any initial fluid pressure. This can be seen from the equation (eq. 4) because PWV does not depend on pressure. If the equation derived by Morgan and Kiely (eq. A16 eq. 26 for t = 0 and p0 = 0) is used, the same PWV value is obtained again for all initial pressure values, but the values will be less since the equation depends on the viscosity of the fluid than the values of the Moens-Korteweg equation. The slope of the measured PWV values is 0.00388 m/s•mmHg while the slope of the values from equation (11) is 0.00342 m/s•mmHg. If t in equation (eq. 2511) is neglected (t = 0), then higher values of PWV are obtained, and for the value of the initial transmural pressure of 0 mmHg it has the same value as the Morgan and Kiely model (eq. A1626), so they start from the same point on the graph. The lower values obtained by equation (11) compared to the experimental ones are most likely due to the increase in fluid temperature, as a result of which the viscosity and density of the fluid changed. Figure 6 shows the measured PWV values for fluids of different viscosities and densities with the same initial pressure. The figure also shows the values obtained by the Morgan Kiely model (eq. A1626) and the model shown in the paper (eq. 2511). If equation (eq. 4) is used (Figure 7), increasing values of PWV are obtained, since only the density value changes in the equation. The measured values of PWV have the same 16 form of change as calculated by the Morgan Kiely model and with equation (11). The measured PWV values at 60% alcohol are slightly lower compared to the models, which is most likely either due to alcohol evaporation, so the viscosity value has changed or due to a change in fluid temperature. The values of equation (11) and the measured values in this case also almost overlap, while the Morgan Kiely model has higher PWV values and a larger range of values. In equation (11), the coefficient t was used, so the PWV values are more similar to those measured compared to the Morgan Kiely model. And this proves, as with measurements with a change in initial pressure, that the density of the tube wall plays an important role in the propagation of waves. In this case, too, slightly lower PWV values were obtained by equation (11) compared to the measured ones. One of the reasons is that the temperature affected the experimental setup. These experimental results and the results obtained by the presented model in the paper show that when analyzing the values of PWV measurements in medicine, blood viscosity, artery wall density and especially diastolic arterial pressure should be taken into account. If the effect of fluid pressure on PWV were neglected, then the age of the cardiovascular vessel wall in persons with hypertension would be incorrectly estimated.If the same PWV value is measured in two patients, one of whom has hypertension, and uses the Moens Korteweg equation for analysis, the same values of artery wall stiffness will be estimated, which is incorrect according to the presented results. Also, in people whose blood viscosity is increased due to diabetes, medications, cytostatic therapy and other conditions already mentioned, the medical diagnosis will be errorness and may slow down therapy and recovery. Since the diameter of the artery narrows from proximal to distal, the mean radius of the artery and the value of diastolic pressure when the person is lying down should be used to calculate PWV. 5. Conclusion The solution of Navier-Stokes equations for pulse propagation of waves through an elastic tube filled with viscous fluid is presented. Derivation of equations for calculating the pulse wave velocities depending on the viscosity, density and initial fluid pressure, density and elasticity of the pipe wall as well as the geometry of the tube itself is presented. The results of the equation were compared with the measured experimental 17 values of pulse wave velocities on a biophysical model using fluids of different viscosities, densities and at different values of initial pressure. The comparison shows that the model presented in this paper agrees with the measured values in both cases: when the initial fluid pressure changes and when the viscosity and density of the fluid change. Compared to other models used in medical research today, the presented model uses all variables that affect the result. Using the equation for calculating the pulse wave velocities presented in this paper, the age of the blood vessel wall will be more accurately estimated .Using the equation for calculating pulse wave velocities presented in this paper, the age of the blood vessel wall will be more accurately estimated, and therefore more precise therapy will be determined and the progress of the disease or the effect of the therapy will be monitored. Appendix Equations of fluid motion As already mentioned, fluid motion is governed by continuity equation (8) and Navier – Stokes equations (9,10). We will assume that the fluid is incompressible and viscous and that the fluid propagates pulsatingly through a cylindrical tube of thin elastic walls. We will also assume that the motion is axisymmetric without tangential velocity 𝑣𝜃 = 0, as well as that the fluid is not affected by gravity, i.e. that the z axis is in a horizontal position, so the last term in eq. 9 can be ignored. Next, we describe the movement of the tube wall with two equations: longitudinal and radial 𝜌0 ℎ 𝜕2𝜂 𝐸ℎ 𝜂 𝜕𝜁 =𝑝− ( +𝜎 ) (1 − 𝜎 2 )𝑅0 𝑅0 𝜕𝑡 2 𝜕𝑧 (A1) 𝜌0 ℎ 𝜕2𝜁 𝐸ℎ 𝜕 2 𝜁 𝜎 𝜕𝜂 𝜕𝑣𝑧 𝜕𝑣𝑟 = + ) ( 2+ )−𝜇( 2 2 (1 − 𝜎 ) 𝜕𝑧 𝜕𝑡 𝑅0 𝜕𝑧 𝜕𝑟 𝜕𝑧 (A2) where 𝜂 and 𝜁 are the components of the displacement of the point on the tube wall in the axial and radial directions, respectively, E – Young's modulus of elasticity, ρ0 –the density of the tube wall. The assumption is that the pulse wave has a sinusoidal shape and that 𝜂, 𝜁, 𝑣𝑟 𝑎𝑛𝑑 𝑣𝑧 change in the same way. Let them be 18 𝑝 = 𝑃𝑒 𝑖(𝐾𝑧−𝜔𝑡) , 𝜂 = Ω𝑒 𝑖(𝐾𝑧−𝜔𝑡) , 𝜁 = Λ𝑒 𝑖(𝐾𝑧−𝜔𝑡) , 𝑣𝑧 = 𝑢(𝑟)𝑒 𝑖(𝐾𝑧−𝜔𝑡) 𝑖 𝑣𝑟 = 𝑤(𝑟)𝑒 𝑖(𝐾𝑧−𝜔𝑡) (𝑤, 𝑢 – functions of 𝑟, 𝑃, Ω, Λ – constants). After substitution in equations (9), (10), (A1) and (A2) and 𝑖𝜔𝜌 𝜇 differentiation ( = 𝛼2, 𝜕 2 𝑣𝑟 𝜕𝑧 2 ≈ 0, 𝜕2𝑢 𝜕𝑧 2 ≈ 0 ) follows: 𝜕 2 𝑢 1 𝜕𝑢 𝑖𝐾 + + 𝛼2𝑢 = 𝑃 𝜕𝑟 2 𝑟 𝜕𝑟 𝜇 𝜕 2 𝑤 1 𝜕𝑤 1 1 𝜕𝑝 2 + + (𝛼 − 2 ) 𝑤 = 𝜕𝑟 2 𝑟 𝜕𝑟 𝑟 𝜇 𝜕𝑟 𝐸ℎ Ω 𝑖𝐾𝜎 −𝜌0 ℎ𝜔2 Ω = 𝑃 − Λ) ( + (1 − 𝜎 2 ) 𝑅02 𝑅0 𝐸ℎ 𝑖𝐾𝜎 𝜕𝑢 −𝜌0 ℎ𝜔2 Λ = (−𝐾 2 Λ + Ω) − 𝜇 ( |𝑟=𝑅0 + 𝑖𝐾𝑤) (1 − 𝜎 2 ) 𝑅0 𝜕𝑟 (A3) (A4) (A5) (A6) Equations (A3) and (A4) are partial Bessel equations. Assuming that P is in the form: 𝑃 = 𝐴1 ∙ 𝐽0 (𝑦𝑟), where 𝐴1 is a constant and a non-homogeneous solution in the form 𝑢(𝑟) = 𝐵1 ∙ 𝐽0 (𝑦𝑟), by substituting in equation (A3) and differentiating, a particular solution is obtained 𝑢(𝑟) = 𝑖𝐾𝐴1 1 ∙ 𝐽 (𝑦𝑟) 𝜇 (𝛼 2 − 𝑦 2 ) 0 Assumption that a homogeneous solution in the form 𝑢(𝑟) = 𝐶1 𝐽0 (𝛼𝑟) , 𝐽0 (𝛼) where C1 is a constant to be determined and in the final form: 𝑢(𝑟) = 𝐶1 𝐽0 (𝛼𝑟) 𝑖𝐾𝐴1 1 + ∙ 𝐽 (𝑦𝑟) 𝐽0 (𝛼) 𝜇 (𝛼 2 − 𝑦 2 ) 0 (A7) Similar mathematical operations are repeated to solve equation (A4). Let non-homogeneous solution be in the form 𝑤 = 𝐷1 ∙ 𝐽1 (𝑦𝑟), and by changing to equation (A4) and differentiating, a particular solution is obtained 𝑤=− 𝑦𝐴1 1 ∙ 𝐽 (𝑦𝑟) 𝜇 (𝛼 2 − 𝑦 2 ) 1 Here, too, the assumption is that the homogeneous solution is in the form 𝑤 = 𝐶2 𝐽1 (𝛼𝑟) , 𝐽0 (𝛼) where C2 is a constant, so it is in the final form: 19 𝐽1 (𝛼𝑟) 𝑦𝐴1 1 − ∙ 𝐽 (𝑦𝑟) 𝐽0 (𝛼) 𝜇 (𝛼 2 − 𝑦 2 ) 1 From the equation of continuity (8) => (A8) 𝜕𝑤 𝑤 + + 𝑖𝐾𝑢 = 0 𝜕𝑟 𝑟 By substituting equations (A7) and (A8) into equation (A9) and arranging it, we get (A9) 𝑤(𝑟) = 𝐶2 − (𝑖𝐾𝐶1 𝐽0 (𝛼𝑟) 𝑖 2 𝐾 2 𝐴1 1 + ∙ 𝐽 (𝑦𝑟)) 𝐽0 (𝛼) 𝜇 (𝛼 2 − 𝑦 2 ) 0 = 𝛼𝐶2 𝐽0 (𝛼𝑟) 𝑦 2 𝐴1 1 𝐶2 𝐽1 (𝛼𝑟) 1 𝑦𝐴1 1 − ∙ 𝐽 (𝑦𝑟) + − ∙ 𝐽 (𝑦𝑟) 𝐽0 (𝛼) 𝜇 (𝛼 2 − 𝑦 2 ) 0 𝑟 𝐽0 (𝛼) 𝑟 𝜇 (𝛼 2 − 𝑦 2 ) 1 By solving we get 𝐶2 = − 𝑖𝐾 𝐶 𝛼 1 and after series expansion of Bessel coefficients: 𝑦𝑟 2 (2) 𝑦𝑟 4 (2) 𝐽0 (𝑦𝑟) = 1 − + 2 2 +⋯ ≈1 (12 ) (1 )(2 ) 𝑦𝑟 1 𝑦𝑟 3 𝑦𝑟 5 (2) (2) (2) 𝑦𝑟 𝐽1 (𝑦𝑟) = − + +⋯ ≈ 1 2 12 ∙ 3 2 𝑖𝜔𝜌 𝑖𝜔𝜌 𝑖 2 𝜔2 As well as (𝛼 2 − 𝑦 2 ) = 𝜇 − 𝑖 2 𝐾 2 = 𝜇 − 𝑐 2 ≈ 𝛼 2 Due to the viscosity the velocities of the fluid along the inner wall of the vessel (when r = R0) are 𝑢|𝑟=𝑅0 = 𝐶1 𝐽0 (𝛼𝑟) 𝑖𝐾𝐴1 1 𝐽0 (𝛼𝑟) 𝐴1 + ∙ 𝐽 (𝑦𝑟) = 𝐶1 + 𝐽0 (𝛼) 𝜇 (𝛼 2 − 𝑦 2 ) 0 𝐽0 (𝛼) 𝜌𝑐 𝑤|𝑟=𝑅0 = 𝐶2 𝐽1 (𝛼𝑟) 𝑦𝐴1 1 𝑖𝐾 2 𝐽1 (𝛼𝑟) 𝐴1 − ∙ 𝐽 (𝑦𝑟) = − (𝐶1 + ∙𝑅 ) 𝐽0 (𝛼) 𝜇 (𝛼 2 − 𝑦 2 ) 1 2 𝛼 𝐽0 (𝛼) 𝜌𝑐 0 and we have 𝑑𝑢 𝐽1 (𝛼𝑅0 ) 𝑖𝐾𝐴1 1 𝐽1 (𝛼𝑅0 ) 𝐴1 𝐾 2 𝑅0 |𝑟=𝑅0 = −𝐶1 𝛼 + ∙ (−𝑦)𝐽1 (𝑦𝑅0 ) = −𝐶1 𝛼 + 2 2 (𝛼) (𝛼 ) 𝑑𝑟 𝐽0 𝜇 −𝑦 𝐽0 (𝛼) 𝜌𝑐 2 𝐸ℎ With substitutions: 𝐵 = (1−𝜎2 ) , 𝑃 = 𝐴1 ∙ 𝐽0 (𝑦𝑟) and 𝐽0 (𝑦𝑟) ≈ 1 in equation (A5) we have 1 𝐵 𝑖𝐾𝜎𝐵 𝐴 + (𝜔2 − Λ=0 )Ω − 𝜌0 ℎ 1 𝜌0 𝑅0 𝜌0 𝑅02 (A10) 20 Since the velocity of the wall is equal to the velocity of the fluid along the wall of the vessel, equalizing the equations 𝑢= 𝑑𝜁 𝐽0 (𝛼𝑟) 𝐴1 𝑖(𝐾𝑥−𝜔𝑡) |𝑟=𝑅0 = −𝑖𝜔Λ𝑒 𝑖(𝐾𝑥−𝜔𝑡) = (𝐶1 + )𝑒 𝑑𝑡 𝐽0 (𝛼) 𝜌𝑐 𝐴1 𝐽0 (𝛼𝑅0 ) + 𝐶1 + 𝑖𝜔Λ = 0 𝜌𝑐 𝐽0 (𝛼) 𝑑𝜂 𝑖𝐾 2 𝐽1 (𝛼𝑅0 ) 𝐴1 𝑤= | = −𝑖𝜔Ω𝑒 𝑖(𝐾𝑥−𝜔𝑡) = − (𝐶1 + ∙ 𝑅 ) 𝑒 𝑖(𝐾𝑥−𝜔𝑡) 𝑑𝑡 𝑟=𝑅0 2 𝛼 𝐽0 (𝛼) 𝜌𝑐 0 (A11) 𝑖𝐾𝑅0 𝑖𝐾 𝐽1 (𝛼𝑅0 ) 𝐴 + 𝐶1 − 𝑖𝜔Ω = 0 2𝜌𝑐 1 𝛼 𝐽0 (𝛼) And the last equation, with substitutions in (A6) => (A12) −𝜔2 Λ = −𝐾 2 𝐵ℎ 𝑖𝐾𝜎 𝐵ℎ 𝜇 𝐽1 (𝛼𝑅0 ) 𝐴1 𝐾 2 𝑅0 𝑖 2 𝐾 2 2 𝐽1 (𝛼𝑅0 ) 𝐴1 Λ+ Ω− + − + ∙ 𝑅 )) (−𝐶1 𝛼 (𝐶1 𝜌0 ℎ 𝑅0 𝜌0 ℎ 𝜌0 ℎ 𝐽0 (𝛼) 𝜌𝑐 2 2 𝛼 𝐽0 (𝛼) 𝜌𝑐 0 𝜔2 𝑐2 ≪ 1 , 𝛼 𝐾2 2 𝐽1 (𝛼𝑅0 ) 𝐴1 + ∙𝑅 )≪1 (𝐶1 2 𝛼 𝐽0 (𝛼) 𝜌𝑐 0 We obtain − 𝜇 𝐾 2 𝑅0 𝜇𝛼 𝐽1 (𝛼𝑅0 ) 𝐵ℎ 𝑖𝐾𝜎 𝐵ℎ ∙ 𝐴1 + 𝐶 + (𝜔2 − 𝐾 2 )Λ + Ω=0 𝜌0 ℎ𝜌𝑐 2 𝜌0 ℎ 𝐽0 (𝛼) 1 𝜌0 ℎ 𝑅0 𝜌0 ℎ (A13 - 23) The system of equations (A10), (A11), (A12) and (A13) is solved by setting the coefficients A1, C1, Λ and Ω to be equal to 0: 1 𝜌𝑐 | 𝑖𝜔𝑅0 2𝜌𝑐 2 | 1 𝜌0 ℎ | 𝜇 𝜔2 𝑅0 − ∙ 3 𝜌0 ℎ𝜌𝑐 2 𝐽0 (𝛼𝑅0 ) 𝐽0 (𝛼) 𝑖𝜔 𝐽1 (𝛼𝑅0 ) 𝛼𝑐 𝐽0 (𝛼) 0 𝜇𝛼 𝐽1 (𝛼𝑅0 ) 𝜌0 ℎ 𝐽0 (𝛼) 0 𝑖𝜔 −𝑖𝜔 0 𝐵 𝜌0 𝑅02 𝑖𝜔𝜎 𝐵 𝑅0 𝑐 𝜌0 𝜔2 − | 𝑖𝜔𝜎𝐵 | = 0 𝜌0 𝑅0 𝑐 𝜔2 𝐵 | 𝜔2 − 2 𝑐 𝜌0 − By simplifying this determinant, we obtain 21 | 1− 2 𝐽1 (𝛼𝑅0 ) 𝛼𝑅0 𝐽0 (𝛼𝑅0 ) 1 | − 1 𝐽1 (𝛼𝑅0 ) 𝛼𝑅0 𝐽0 (𝛼𝑅0 ) 2 1 𝐵ℎ 𝜌𝑐 2 𝑅0 𝜎𝐵 − 2 𝜌𝑐 𝑅0 | 𝜎𝐵ℎ =0 𝜌𝑐 2 𝑅0 | 𝜌0 ℎ 𝐵ℎ − 𝜌𝑅0 𝜌𝑐 2 𝑅0 1+ Using substitutions 𝐸ℎ 𝜌0 ℎ = 𝑥, =𝑡 (A14) 2𝜌𝑐 2 𝑅0 𝜌𝑅0 and after solving the determinant, the so-called frequency equation in term of variable x was obtained (4 − 2𝛼𝑅0 𝐽0 (𝛼𝑅0 ) 2 𝛼𝑅0 𝐽0 (𝛼𝑅0 ) 𝐽0 (𝛼𝑅0 ) − 1) − 4𝜎 + 1 + 2𝛼𝑅0 ]𝑥 ) 𝑥 + [2𝑡 ( 𝐽1 (𝛼𝑅0 ) 2 𝐽1 (𝛼𝑅0 ) 𝐽1 (𝛼𝑅0 ) 𝛼𝑅0 𝐽0 (𝛼𝑅0 ) − 2𝑡(1 − 𝜎 2 ) − (1 − 𝜎 2 ) = 0 2 𝐽1 (𝛼𝑅0 ) Using the values for viscosity of blood, diameter of aorta or main arteries, blood density and density of artery wall, we obtained that |𝛼𝑅0 | ≫ 1, ie that they are in the ranges of 𝛼𝑅0 = 3 − 12 and 𝑡 = 0.1 − 0.4. After asymptotic expansion of the Bessel function 𝐽0 (𝛼𝑅0 ) 1 ~−𝑖+ 𝐽1 (𝛼𝑅0 ) 2𝛼𝑅0 and by substituting in the frequency equation and arranging, the quadratic equation is obtained (−2𝛼𝑅0 𝑖 − 3)𝑥 2 + [4𝜎 − 2 + 2𝛼𝑅0 𝑖 + 𝑡𝛼𝑅0 𝑖 + 3𝑡 𝑡 ] 𝑥 + (1 − 𝜎 2 ) (1 + − 𝑡𝛼𝑅0 𝑖) = 0 2 2 1 This quadratic equation can be solved for 𝜎 = 0, 𝜎 = 2 and 𝜎 = 1. For an artery 𝜎 = 0.49, so the roots of 1 2 quadratic equation for 𝜎 = , are: 𝑡 𝑖 𝜎 2 3𝑡 𝑖(1 − 𝜎 2 ) 𝑥1 = 1 + + − ) and 𝑥2 = (2 − 2𝜎 + 2 𝛼𝑅0 2 4 2𝛼𝑅0 Substituting in (24) 𝐾 2 𝐸ℎ 𝐾2 = 2 𝑐02 = 𝑥 2 𝜔 2𝜌𝑅0 𝜔 We look for solutions in the following form and only for x1 (for 𝜇 → 0, 𝑥2 → ∞) 𝐾 𝐾1 + 𝑖𝐾2 𝑐 = 𝑐0 = √𝑥1 𝜔 0 𝜔 22 After substitution √𝑖 = √2 (1 2 + 𝑖) and solving the root of a complex number 𝜎 2 3𝑡 𝜎 2 3𝑡 𝑡 2 (1 − 𝜎 + 4 − 8 ) 2𝑖 (1 − 𝜎 + 4 − 8 ) 𝐾1 + 𝑖𝐾2 + = 𝑐0 √𝑥1 = √1 + + 2 𝜔 2𝜔𝜌 2𝜔𝜌 √ √ 𝑅 𝑅 𝜇 0 𝜇 0 𝜎 2 3𝑡 𝐾1 𝑡 (1 − 𝜎 + 4 − 8 ) 𝑐 =1+ + , 𝜔 0 4 2𝜔𝜌 √ 𝑅 0 𝜇 𝜎 2 3𝑡 (1 − 𝜎 + 4 − 8 ) 2𝜔𝜌 √ 𝐾2 𝜇 𝑅0 𝑐0 = 𝜎 2 3𝑡 𝜔 𝑡 (1 − 𝜎 + 4 − 8 ) 1+4+ 2𝜔𝜌 √ 𝑅 𝜇 0 By substituting c0 with equation (7) which is a function of the initial pressure and arranging, we obtain the final equation (A15) for the pulse wave velocity 𝐸ℎ 𝑝 √ + 0 𝜔 1 𝑡 1 𝜇 𝜎 2 3𝑡 2𝑅0 𝜌 4𝜌 𝑐= =± − )) (1 + − √ (1 − 𝜎 + 2 𝑝 𝑅 𝐾1 4 𝑅0 2𝜔𝜌 4 8 1 − 0 0 (1 + 𝑡 ) 𝐸ℎ 4 And (A15) 2 𝑝0 𝑅0 (1 − 𝜎 + 𝜎 − 3𝑡) 4 8 𝐸ℎ 𝐾2 = ±𝜔 𝐸ℎ 𝑝0 𝑡 2𝜔𝜌 √ + + √ 𝑅 2𝑅0 𝜌 4𝜌 (1 4) 𝜇 0 1− If we assume that t is very small it can be neglected (𝑡 = 0) 𝑎𝑛𝑑 the initial fluid is zero (𝑝0 = 0) we get the same equation derived by Morgan and Kiely for small viscosity 𝑐= 𝜔 𝐸ℎ 1 𝜇 𝜎2 = ±√ (1 + − √ (1 − 𝜎 + )) 𝐾1 2𝑅0 𝜌 𝑅0 2𝜔𝜌 4 (A16) And if we neglect both σ and μ we get the Moens-Korteweg equation (4) for PWV. In case of high viscosity, or |𝛼𝑅0 | ≪ 1, we use serial expansions 𝐽0 (𝛼𝑅0 ) ≈ 1 − 𝛼 2 𝑅02 , 4 𝐽1 (𝛼𝑅0 ) ≈ 𝛼𝑅0 𝛼 2 𝑅02 (1 − ) 2 8 After substituting in the frequency equation and solving the quadratic equations we obtain 23 𝑐= 𝜔 = 𝐾1 𝑐0 5 − 4𝜎 + 6𝑡 √ 𝑅2 𝜔𝜌 0 𝜇 = ±√ 𝐸ℎ 𝑝0 𝜔𝜌 1 + 𝑅 √ 2𝑅0 𝜌 4𝜌 0 𝜇 5 − 4𝜎 + 6𝑡 (A17) and 𝐾2 = ±𝜔√ 1 𝜇 √5 − 4𝜎 + 6𝑡 𝐸ℎ 𝑝0 √𝜔𝜌 𝑅0 2𝑅0 𝜌 + 4𝜌 Conflict of interest statement No conflicts of interest, financial or otherwise, are declared by the authors. Acknowledgments This work was supported by Serbian Ministry of Education, Science and Technological Development Grants 32040 and 41022. Fig. 1. Increase in disk radius and width due to pulse wave: du/dz - the narrowing of the disk, u - disk shift, ∆𝑅0 - radius change Fig. 2. The propagation of the pulse wave increases the pressure on one side of the disk by ∆p Fig. 3. Stresses in a circular cylindrical pressure vessel a - hoop stress, b - longitudinal stress Fig. 4. A schematic diagram of the biophysical model of the cardiovascular system: H– automatic hammer, P–pump, reservoir 1 (closed), reservoir 2 (adjustable height), M–manometer, S1, S2 – pressure sensors mounted through the wall of the elastic tube, DAQ—data acquisition device, V – one-way valve. The arrows indicate the flow direction of fluid through the valves and the tubes Fig. 5. Comparison of models and measured values of PWV against initial fluid pressure: MoensKorteweg equation, Morgan Kiely equation and equation (2511) for t = 0 and t ≠ 0. Fig. 6. PWV against alcohol concentration Fig. 7. Comparison of Morgan-Kiely equation, equation (2511) and measured values of PWV against alcohol concentration 24 References Atabek HB (1968) Wave Propagation through a Viscous Fluid Contained in a Tethered, Initially Stressed, Orthotropic Elastic Tube. Biophys J. May; 8(5): 626–649. 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Arterioscler Thromb Vasc Biol 21, 82– 87 Westerhof N, Elzinga G, Sipkema P (1972) Forward and backward waves in the arterial system. Cardiovasc Res 6,648–656. Womersley R (1955) Method for the calculation of velocity, rate of flow and viscous drag in arteries when the pressure gradient is known. J Physiol. Mar 28; 127(3): 553–563. Womersley R (1957) An elastic tube theory of pulse transmission and oscillatory flow in mammalian arteries. Wright Air Development Center (Technical Report WADC-TR) Young T (1808) “Hydraulic investigations, subservient to an intended Croonian lecture on the motion of the blood.” Philosophical Transactions of the Royal Society of London 98, 164-186 [Errata in Ref (26), p. 31]. Žikić D, Stojadinović B and Nestorović Z (2019) Biophysical modeling of wave propagation phenomena: experimental determination of pulse wave velocity in viscous fluid-filled elastic tubes in a gravitation field Eur Biophys J 48:407-411 27 Manuscript (Clean) Wave propagation through viscous fluid-filled elastic tube under initial pressure: theoretical and biophysical model Dejan Žikić1 & Katarina Žikić2 1 Institute of Biophysics, Faculty of Medicine, University of Belgrade, Serbia 2 Faculty of Physics, University of Belgrade, Serbia Corresponding author: Dejan Žikić, Associate Professor Institute of Biophysics, Faculty of Medicine University of Belgrade, 11000 Belgrade, Serbia https://orcid.org/0000-0003-3247-9071 Tel: +381 11 360 7159 Fax: +381 11 360 7061 e-mail: dzikic@gmail.com 1 Abstract The velocity of propagation of pulse waves through the arteries is one of the indicators of the health condition of the cardiovascular system. By measuring the pulse wave velocity, cardiologists estimate the elasticity of the wall of blood vessels and the changes that occur with aging. Using the Moens-Korteweg equation, an erroneous assessment is made in the analysis. The paper presents the solution of Navier-Stokes equations for propagation of pulse waves through an elastic tube filled with viscous fluid under initial pressure. The equation for pulse wave velocity depending on viscosity, density and initial fluid pressure, density and elasticity of wall and geometry of the tube is derived. The results of the equation were compared with the experimental results measured on a biophysical model of the cardiovascular system. Keywords: Navier-Stokes equations, pulse wave velocity, arterial wall elasticity, viscosity, biophysical model 2 1. Introduction Investigation of the waveforms of arterial blood pressure and flow through blood vessels plays an important role in understanding the nature and disorders of the cardiovascular system. The beginning of the interest of scientists in the wave nature of blood dates to the beginning of the 19th century when Young (1808) published a paper on the wave motion of blood and derived the first formula for pulse wave velocity. In 1877, Moens and Korteweg simultaneously derived the equation for the velocity of a pulse wave propagating through a fluid-filled elastic tube of thin walls (Moens 1877, Moens 1878, Korteweg 1878). This equation is still used today in medicine to study the age of the cardiovascular system. The greatest mathematical contribution was made by Womersley in the middle of the last century (Womersley 1955) who solved the pulse wave velocity profile in a rigid tube filled with a viscous fluid. In addition, he offered a solution for the pulse wave velocity profile through an elastic tube and developed a mathematical analysis of blood flow in the arteries. In his work, he included viscosity in the pulse wave velocity calculation (Womersley 1957). To better understand the physics of cardiovascular processes, mathematical and experimental biophysical models were mainly used. In mathematical models, the equations describe the principles of the physical laws of a process, then the theoretical model is experimentally confirmed on the biophysical model. Khir and Parker (2002) and later Li (Li et al. 2011), used the water-hammer equation to determine pulse wave velocity. Westerhof et al. (1972) determined pulse wave velocity from waveforms of fluid pressure and flow. Feng and Khir (2010) applied both equations to detect reflected waves in flow pressure signals. In his work, Khir used a pressure-velocity loop to determine the arrival time of reflected waves (Khir et al. 2007). Lazovic et al. (2015), detected reflected waves that appear on the radial artery with aging. Papageorgiou and Jones (1987a) investigated the various materials used in models for arteries and blood vessels. They found that if elastic tubes with a nonlinear stress / strain ratio are used in the models, the differences between real systems and physical models are minimal. The influence of viscosity on pulse wave velocity was experimentally shown by Stojadinović et al. (2015). The influence of gravity on wave propagation was experimentally shown by Žikić et al. (2019). 3 One of the parameters used in medicine to determine the age of the cardiovascular system is the pulse wave velocity - PWV. The Moens-Korteweg equation is mainly used to estimate arterial elasticity from measured PWV values. As this equation does not depend on blood viscosity, diastolic pressure, blood vessel wall density as well as the influence of gravity, using this relation in medical research introduces an error in the interpretation of results and can be misdiagnosed. Morgan and Kiely (1954) offered a solution for calculating PWV through a viscous fluid in an elastic tube but without initial pressure and without pipe wall density. Womersley (1955, 1957) also solved this problem with viscosity but offered a solution in a complex equation that only physicists can solve. Also, this equation cannot be applied if the fluid is under initial pressure and the wall density of the elastic tube is neglected. Other scientists have also investigated how PWV changes with initial fluid pressure (Atabek et al. 1966; Atabek 1968; Demiray and Akgün 1997) but the offered equations are very complicated especially for medical doctors and the results of their equations do not agree with the experimental results. One of the reasons for the interest in this phenomenon of wave propagation is related to research in hemodynamics. The main area that cardiovascular physics deals with is the wave propagation of blood through blood vessels. With aging, the biophysical parameters of the blood and blood vessels change, and the correct interpretation of cardiovascular parameters can greatly contribute to accurate diagnosis and successful therapy. The aim of this paper is to show the mathematical derivation of the equation for pulse waves velocity through a viscous fluid-filled elastic tube with initial fluid pressure and to prove experimentally the accuracy of the equation. 2. Methods 2.1 Mathematical equations Moens-Korteweg equation Moens and Korteweg ingeniously derived the equation for PWV. They assumed that the pulse wave increases the initial volume of the cylinder 𝑉𝑜 = 𝜋𝑅𝑜2 ∆𝑧 (Figure 1) of width ∆z to 𝑉 = 𝜋(𝑅0 + 𝜕𝑢 ∆𝑅0 )2 (∆𝑧 + 𝜕𝑧 ∆𝑧) and derived three equations: 4 𝜕𝑢 2 2 ∆𝑉 𝜋(𝑅0 + ∆𝑅0 ) (∆𝑧 + 𝜕𝑧 ∆𝑧) − 𝜋𝑅𝑜 ∆𝑧 = 𝑉𝑜 𝜋𝑅𝑜2 ∆𝑧 2 2 2∆𝑅0 ∆𝑅0 𝜕𝑢 2∆𝑅0 𝜕𝑢 ∆𝑅0 𝜕𝑢 2∆𝑅0 𝜕𝑢 ∆𝑝 = +( 2 ) + + +( 2 ) = + =− 𝑅0 𝜕𝑧 𝑅0 𝜕𝑧 𝜕𝑧 𝑅0 𝜕𝑧 𝐾 𝑅𝑜 𝑅𝑜 2 2∆𝑅 𝜕𝑢 ∆𝑅 2 𝜕𝑢 0 , ( 𝑅20 ) 𝜕𝑧 𝑅0 𝜕𝑧 𝑜 𝑜 ∆𝑅 where ∆𝑉 is the change in volume, K- bulk modulus of fluid, ( 𝑅20 ) , (1) ≈0 The difference in pressures on the front and back of the disk (Figure 2) can be expressed from the pressure gradient, and the axial acceleration of the fluid is: 𝑚𝑎 = − 𝜕(∆𝑝) 𝜕2𝑢 𝑙𝐴 = 𝜌𝑙𝐴 2 𝜕𝑧 𝜕𝑡 or 𝜕(∆𝑝) 𝜕2𝑢 = −𝜌 2 𝜕𝑧 𝜕𝑡 (2) Due to the increase in pressure ∆p in the fluid, the force F1 tends to separate the two half-cylinders (Figure 3a). On the other hand, this force is opposed by hoop stress 𝜎𝜃 𝐹1 = ∆𝑝𝑆1 = 2∆𝑝(𝑅0 + ∆𝑅0 )𝑙 = 2𝑆2 𝜎𝜃 = 2ℎ𝑙𝐸 2𝜋∆𝑅0 ∆𝑅0 = 2𝐸 ℎ𝑙 2𝜋𝑅0 𝑅0 Arranging this equation gives the third Moens-Korteweg equation ∆𝑝 = 𝐸ℎ ∆𝑅0 ∆𝑅0 ~𝐸ℎ 2 (𝑅0 + ∆𝑅0 )𝑅0 𝑅𝑜 (3) After differentiating the second and third equations and arranging using the first equation, a wave equation is obtained 𝜕2𝑢 2𝜌𝑅0 𝜌 𝜕 2 𝑢 = ( + ) 2 𝜕𝑧 2 𝐸ℎ 𝐾 𝜕𝑡 For an elastic tube and an incompressible fluid ( 𝐾 → ∞), the equation becomes the Moens-Korteweg equation 𝜕 2 𝑢 2𝜌𝑅0 𝜕 2 𝑢 1 𝜕2𝑢 = = 𝜕𝑧 2 𝐸ℎ 𝜕𝑡 2 𝑐02 𝜕𝑡 2 𝐸ℎ 𝑐0 = √ 2𝜌𝑅0 (4) 5 Where c0 is the pulse wave velocity – PWV. As can be seen from the equation, viscosity, tube wall density and initial fluid pressure do not affect the PWV. Bramwell and Hill derived the equation for PWV without values for E, h, and R0 (since they are not constant and depend on the artery itself). If we replace ∆R0 in equation (1) from equation (3) and assume that ∂u/∂z is small it follows: ∆𝑉 2∆𝑅0 2 𝑅0 2 ∆𝑝 2𝑅0 ∆𝑝 = = = 𝑉𝑜 𝑅0 𝑅0 𝐸ℎ 𝐸ℎ The rearrangement resulted in: 𝐸ℎ 𝑉𝑜 ∆𝑝 = 2𝑅0 ∆𝑉 And by substituting in equation (4), the Bramwell-Hill equation is obtained: 𝑉𝑜 ∆𝑝 𝑐0 = √ 𝜌 ∆𝑉 (5) 2.2 Pulse wave velocity when the fluid is under initial pressure Let the initial pressure in the tube be p0. Due to the increase in pressure, the radius also increases: R=R0+R and the length of the tube l=l0+l. In the derivation of equation (3) it is shown that the hoop stress is equal 𝑝0 𝑅0 2𝜋∆𝑅0 ∆𝑅0 𝑅 − 𝑅0 = 2ℎ𝑙𝐸 = 2𝐸 ℎ𝑙 = 2𝐸 ℎ𝑙 ℎ 2𝜋𝑅0 𝑅0 𝑅0 𝜎𝜃 = By arranging, the final radius with the initial pressure in the tube is 𝑅= 𝑅0 𝑝 𝑅 1− 0 0 𝐸ℎ The same pressure acts on the cross section of the cylinder (Figure 3b) and is opposed by longitudinal stress 𝐹2 = 𝑝0 𝜋𝑅02 = 𝜋[(𝑅0 + ℎ)2 − 𝑅02 ]𝜎𝑙 ~2𝜋𝑅0 ℎ𝜎𝑙 By arranging, the hoop stress is 2 times higher than the longitudinal stress 𝜎𝑙 = 𝑝0 𝑅0 𝜎𝜃 = 2ℎ 2 6 After substitution 𝐸 ∆𝑅0 ∆𝑙 = 2𝐸 𝑅0 𝑙0 𝑅 − 𝑅0 𝑙 − 𝑙0 =2 𝑅0 𝑙0 𝑙= 𝑙0 1 𝑝0 𝑅0 ( + 1)~𝑙0 (1 + ) 2 1 − 𝑝0 𝑅0 2𝐸ℎ 𝐸ℎ Due to the increase in fluid pressure in the tube by p0, the disk volume is: 𝑉 = 𝑅 2 𝜋𝑙 Or 2 𝑝0 𝑅0 𝑝0 𝑅0 ∆𝑝 𝑅 𝑝0 𝑅0 ∆𝑝 ∆𝑝 (1 + 2𝐸ℎ ) ∆𝑝 (1 + 2𝐸ℎ ) 0 2 2 𝑉 = 𝑅 𝜋𝑙 = ( ) 𝜋𝑙0 (1 + ) = 𝜋𝑙0 𝑅0 2 = 𝑉0 ∆𝑉 𝑝0 𝑅0 ∆𝑉 2𝐸ℎ ∆𝑉 ∆𝑉 𝑝 𝑅 𝑝0 𝑅0 2 0 0 (1 − ) (1 − ) (1 − ) 𝐸ℎ 𝐸ℎ 𝐸ℎ 𝑝0 𝑅0 ∆𝑝 𝐸ℎ 1 + 2𝐸ℎ 𝑉 = ∆𝑉 2𝑅0 𝑝 𝑅 2 (1 − 0 0 ) 𝐸ℎ (6) Using equation (6) and Bramwell-Hill equation (5), the PWV can be calculated with the initial fluid pressure in the tube: 𝐸ℎ 𝑝0 𝑅0 𝐸ℎ 𝑝0 √ √ 2𝑅0 𝜌 (1 + 2𝐸ℎ ) 2𝑅0 𝜌 + 4𝜌 𝑐= = 𝑝 𝑅 𝑝 𝑅 1− 0 0 1− 0 0 𝐸ℎ 𝐸ℎ (7) 2.3 Wave propagation through an elastic tube filled with a viscous fluid Fluid motion is governed by continuity equation (8) and Navier–Stokes equations (9,10): 𝑑𝜌 + ∇(ρv) = 0 𝑑𝑡 𝜕𝑣𝑧 𝜕𝑣𝑧 𝜕𝑣𝑧 𝜕𝑝 1 𝜕 𝜕𝑣𝑧 𝜕 2 𝑣𝑧 𝜌( + 𝑣𝑟 + 𝑣𝑧 )=− +𝜇( (𝑟 )+ ) + 𝜌𝑔𝑧 𝜕𝑡 𝜕𝑟 𝜕𝑧 𝜕𝑧 𝑟 𝜕𝑟 𝜕𝑟 𝜕𝑧 2 𝜕𝑣𝑟 𝜕𝑣𝑟 𝜕𝑣𝑟 𝜕𝑝 1 𝜕 𝜕𝑣𝑟 𝜕 2 𝑣𝑟 𝑣𝑟 𝜌( + 𝑣𝑟 + 𝑣𝑧 )=− +𝜇( (𝑟 )+ − ) 𝜕𝑡 𝜕𝑟 𝜕𝑧 𝜕𝑟 𝑟 𝜕𝑟 𝜕𝑟 𝜕𝑧 2 𝑟 2 (8) (9) (10) 7 where is density, 𝑣𝑧 is the axial velocity of the fluid, 𝑣𝑟 is the radial velocity of the fluid, is the dynamic viscosity. By solving these equations (Appendix) we obtain pulse wave velocities for the case of small viscosity and high viscosity: 𝐸ℎ 𝑝0 √ 1 𝑡 1 𝜇 𝜎 2 3𝑡 2𝑅0 𝜌 + 4𝜌 𝑐= + − − 𝜎 + − )) (1 (1 √ 2 𝑝 𝑅 4 𝑅0 2𝜔𝜌 4 8 1 − 0 0 (1 + 𝑡 ) 𝐸ℎ 4 And for high viscosity 𝑐= 𝑐0 𝐸ℎ 𝑝0 𝜔𝜌 1 = ±√ + 𝑅0 √ 2𝑅0 𝜌 4𝜌 𝜇 5 − 4𝜎 + 6𝑡 5 − 4𝜎 + 6𝑡 √ 𝑅 2 𝜔𝜌 0 𝜇 (11) (12) The last equation (eq.12) has no application for medical research due to its high viscosity values, so it will not be discussed further in the paper. 2.4 Biophysical model A biophysical model of the cardiovascular system was used for the experimental validation of the equation (Figure 4). A similar model was used in Stojadinović et al. (2015) and Žikić et al. (2019). In the first experiment, pulse wave velocities were measured with increasing initial fluid pressure. The transmural pressure (difference in pressure between two sides of a wall of a tube) was changed from 0 mmHg to 120 mmHg with a step of 20 mmHg. A silicone transparent isotropic tube with an inner diameter of 10 mm and a wall thickness of 1 mm with a modulus of elasticity E = 5.19 MPa was used. The fluid was distilled water with a density of 998 kg/m3 and a viscosity of 0.99 mPa·s at 23 °C. PWV was determined from the equation d/t where d is the distance between the sensors (Figure 4) and t is the propagation time of the pulse wave between the sensors. In all experiments, the distance d between the sensors was 1m. In Stojadinović et al. (2015) and Žikić et al. (2019) is a detailed explanation of the model and the determination of PWV. In another experiment, pulse wave velocities were measured with fluids of different densities and viscosities. The fluid pressure was 0 mmHg. Aqueous alcohol solutions with a concentration of 10-60% were used. Silicone tube of the same dimensions and properties as in the first experiment was used. 8 3. Results Table 1 shows the densities and viscosities of the fluids used in the experiments. The results of PWV measurements with increasing fluid pressure are shown in Figure 5. The figure also shows the calculated PWV values using the Moens-Korteweg equation, the Morgan-Kiely equation, and the model using equation (11) in both cases: when the parameter is neglected (t = 0) and when used for the calculation (t ≠ 0). The results of measuring PWV with a change in alcohol concentration and calculated PWV using MorganKiely equation, Moens-Korteweg equation and equation (11) are shown in Figure 6. Figure 7 shows the measured values of PWV and calculated PWV using Morgan-Kiely equation and equation (11) for better visibility and comparison. 4. Discussion With age, the wall thickness of blood vessels increases. One of the most frequently observed is an increase in the thickness of the intima-medium of the carotid artery (Homma et al. 2001; Tanaka et al. 2001; van den Munckhof et al. 2012; Engelen et al. 2013; Dinenno et al. 2000; Green et al. 2010). The increase in artery wall thickness was found to be 5m/year in both women and men (Homma et al. 2001; Tanaka et al. 2001; van den Munckhof et al. 2012; Engelen et al. 2013). Increasing the wall thickness leads to a decrease in the lumen and inner radius of the blood vessel, so to compensate, the diameter of the artery gradually increases with age in both the central (van den Munckhof et al. 2012; Engelen et al. 2013; Dinenno et al. 2000; Green et al. 2010; Schmidt-Trucksass et al. 1999) and peripheral vessels (Green et al. 2010; Sandgrenet al. 1998; van der Heijden 2000). An increase of 0.017 mm/year with atherosclerosis and 0.03 mm/year in those with pre-existing disease (Eigenbrodt et al. 2006) or 0.5% per year was observed, despite maintaining a constant body surface area. Therefore, the elastic tube that most closely corresponds to the ratio of the thickness of blood vessels of the radius of arteries in persons aged 40 and over was used in the 9 biophysical model, i.e. the ratio h/R0≈0.2. Also, medical PWV measurements are performed in middle-aged and elderly people, when the structure of the blood vessel wall begins to change. A comparison of the experimental results and the model shows that the results of the equation presented in this paper, (eq. 11), almost overlap. In addition to the measured values of PWV with pressure change in Figure 5, the calculated values using other models and equations are also shown. If the Moens-Korteweg equation (eq. 4) is used PWV has the same value for any initial fluid pressure. This can be seen from the equation (eq. 4) because PWV does not depend on pressure. If the equation derived by Morgan and Kiely (eq. A16 for t = 0 and p0 = 0) is used, the same PWV value is obtained again for all initial pressure values, but the values will be less since the equation depends on the viscosity of the fluid than the values of the Moens-Korteweg equation. The slope of the measured PWV values is 0.00388 m/s•mmHg while the slope of the values from equation (11) is 0.00342 m/s•mmHg. If t in equation (11) is neglected (t = 0), then higher values of PWV are obtained, and for the value of the initial transmural pressure of 0 mmHg it has the same value as the Morgan and Kiely model (eq. A16), so they start from the same point on the graph. The lower values obtained by equation (11) compared to the experimental ones are most likely due to the increase in fluid temperature, as a result of which the viscosity and density of the fluid changed. Figure 6 shows the measured PWV values for fluids of different viscosities and densities with the same initial pressure. The figure also shows the values obtained by the Morgan Kiely model (eq. A16) and the model shown in the paper (eq. 11). If equation (eq. 4) is used (Figure 7), increasing values of PWV are obtained, since only the density value changes in the equation. The measured values of PWV have the same form of change as calculated by the Morgan Kiely model and with equation (11). The measured PWV values at 60% alcohol are slightly lower compared to the models, which is most likely either due to alcohol evaporation, so the viscosity value has changed or due to a change in fluid temperature. The values of equation (11) and the measured values in this case also almost overlap, while the Morgan Kiely model has higher PWV values and a larger range of values. In equation (11), the coefficient t was used, so the PWV values are more similar to those measured compared to the Morgan Kiely model. And this proves, as with 10 measurements with a change in initial pressure, that the density of the tube wall plays an important role in the propagation of waves. In this case, too, slightly lower PWV values were obtained by equation (11) compared to the measured ones. One of the reasons is that the temperature affected the experimental setup. These experimental results and the results obtained by the presented model in the paper show that when analyzing the values of PWV measurements in medicine, blood viscosity, artery wall density and especially diastolic arterial pressure should be taken into account. If the effect of fluid pressure on PWV were neglected, then the age of the cardiovascular vessel wall in persons with hypertension would be incorrectly estimated. Also, in people whose blood viscosity is increased due to diabetes, medications, cytostatic therapy and other conditions already mentioned, the medical diagnosis will be errorness and may slow down therapy and recovery. Since the diameter of the artery narrows from proximal to distal, the mean radius of the artery and the value of diastolic pressure when the person is lying down should be used to calculate PWV. 5. Conclusion The solution of Navier-Stokes equations for pulse propagation of waves through an elastic tube filled with viscous fluid is presented. Derivation of equations for calculating the pulse wave velocities depending on the viscosity, density and initial fluid pressure, density and elasticity of the pipe wall as well as the geometry of the tube itself is presented. The results of the equation were compared with the measured experimental values of pulse wave velocities on a biophysical model using fluids of different viscosities, densities and at different values of initial pressure. The comparison shows that the model presented in this paper agrees with the measured values in both cases: when the initial fluid pressure changes and when the viscosity and density of the fluid change. Compared to other models used in medical research today, the presented model uses all variables that affect the result. Using the equation for calculating the pulse wave velocities presented in this paper, the age of the blood vessel wall will be more accurately estimated. 11 Appendix Equations of fluid motion As already mentioned, fluid motion is governed by continuity equation (8) and Navier – Stokes equations (9,10). We will assume that the fluid is incompressible and viscous and that the fluid propagates pulsatingly through a cylindrical tube of thin elastic walls. We will also assume that the motion is axisymmetric without tangential velocity 𝑣𝜃 = 0, as well as that the fluid is not affected by gravity, i.e. that the z axis is in a horizontal position, so the last term in eq. 9 can be ignored. Next, we describe the movement of the tube wall with two equations: longitudinal and radial 𝜌0 ℎ 𝜕2𝜂 𝐸ℎ 𝜂 𝜕𝜁 =𝑝− ( +𝜎 ) 2 2 (1 − 𝜎 )𝑅0 𝑅0 𝜕𝑡 𝜕𝑧 (A1) 𝜌0 ℎ 𝜕2𝜁 𝐸ℎ 𝜕 2 𝜁 𝜎 𝜕𝜂 𝜕𝑣𝑧 𝜕𝑣𝑟 = + + ) ( )−𝜇( 2 2 2 (1 − 𝜎 ) 𝜕𝑧 𝜕𝑡 𝑅0 𝜕𝑧 𝜕𝑟 𝜕𝑧 (A2) where 𝜂 and 𝜁 are the components of the displacement of the point on the tube wall in the axial and radial directions, respectively, E – Young's modulus of elasticity, ρ0 –the density of the tube wall. The assumption is that the pulse wave has a sinusoidal shape and that 𝜂, 𝜁, 𝑣𝑟 𝑎𝑛𝑑 𝑣𝑧 change in the same way. Let them be 𝑝 = 𝑃𝑒 𝑖(𝐾𝑧−𝜔𝑡) , 𝜂 = Ω𝑒 𝑖(𝐾𝑧−𝜔𝑡) , 𝜁 = Λ𝑒 𝑖(𝐾𝑧−𝜔𝑡) , 𝑣𝑧 = 𝑢(𝑟)𝑒 𝑖(𝐾𝑧−𝜔𝑡) 𝑖 𝑣𝑟 = 𝑤(𝑟)𝑒 𝑖(𝐾𝑧−𝜔𝑡) (𝑤, 𝑢 – functions of 𝑟, 𝑃, Ω, Λ – constants). After substitution in equations (9), (10), (A1) and (A2) and 𝑖𝜔𝜌 𝜇 differentiation ( = 𝛼2, 𝜕2 𝑣𝑟 𝜕𝑧 2 𝜕2 𝑢 ≈ 0, 𝜕𝑧2 ≈ 0 ) follows: 𝜕 2 𝑢 1 𝜕𝑢 𝑖𝐾 + + 𝛼2𝑢 = 𝑃 2 𝜕𝑟 𝑟 𝜕𝑟 𝜇 𝜕 2 𝑤 1 𝜕𝑤 1 1 𝜕𝑝 + + (𝛼 2 − 2 ) 𝑤 = 2 𝜕𝑟 𝑟 𝜕𝑟 𝑟 𝜇 𝜕𝑟 𝐸ℎ Ω 𝑖𝐾𝜎 −𝜌0 ℎ𝜔2 Ω = 𝑃 − Λ) ( 2+ 2 (1 − 𝜎 ) 𝑅0 𝑅0 𝐸ℎ 𝑖𝐾𝜎 𝜕𝑢 −𝜌0 ℎ𝜔2 Λ = (−𝐾 2 Λ + Ω) − 𝜇 ( |𝑟=𝑅0 + 𝑖𝐾𝑤) 2 (1 − 𝜎 ) 𝑅0 𝜕𝑟 (A3) (A4) (A5) (A6) Equations (A3) and (A4) are partial Bessel equations. 12 Assuming that P is in the form: 𝑃 = 𝐴1 ∙ 𝐽0 (𝑦𝑟), where 𝐴1 is a constant and a non-homogeneous solution in the form 𝑢(𝑟) = 𝐵1 ∙ 𝐽0 (𝑦𝑟), by substituting in equation (A3) and differentiating, a particular solution is obtained 𝑖𝐾𝐴1 1 ∙ 𝐽 (𝑦𝑟) 2 𝜇 (𝛼 − 𝑦 2 ) 0 𝑢(𝑟) = Assumption that a homogeneous solution in the form 𝑢(𝑟) = 𝐶1 𝐽0 (𝛼𝑟) , 𝐽0 (𝛼) where C1 is a constant to be determined and in the final form: 𝑢(𝑟) = 𝐶1 𝐽0 (𝛼𝑟) 𝑖𝐾𝐴1 1 + ∙ 𝐽 (𝑦𝑟) 2 𝐽0 (𝛼) 𝜇 (𝛼 − 𝑦 2 ) 0 (A7) Similar mathematical operations are repeated to solve equation (A4). Let non-homogeneous solution be in the form 𝑤 = 𝐷1 ∙ 𝐽1 (𝑦𝑟), and by changing to equation (A4) and differentiating, a particular solution is obtained 𝑤=− 𝑦𝐴1 1 ∙ 𝐽 (𝑦𝑟) 2 𝜇 (𝛼 − 𝑦 2 ) 1 Here, too, the assumption is that the homogeneous solution is in the form 𝑤 = 𝐶2 𝐽1 (𝛼𝑟) , 𝐽0 (𝛼) where C2 is a constant, so it is in the final form: 𝐽1 (𝛼𝑟) 𝑦𝐴1 1 − ∙ 𝐽 (𝑦𝑟) 𝐽0 (𝛼) 𝜇 (𝛼 2 − 𝑦 2 ) 1 From the equation of continuity (8) => (A8) 𝜕𝑤 𝑤 + + 𝑖𝐾𝑢 = 0 𝜕𝑟 𝑟 By substituting equations (A7) and (A8) into equation (A9) and arranging it, we get (A9) 𝑤(𝑟) = 𝐶2 − (𝑖𝐾𝐶1 𝐽0 (𝛼𝑟) 𝑖 2 𝐾 2 𝐴1 1 + ∙ 𝐽 (𝑦𝑟)) 2 𝐽0 (𝛼) 𝜇 (𝛼 − 𝑦 2 ) 0 = 𝛼𝐶2 𝐽0 (𝛼𝑟) 𝑦 2 𝐴1 1 𝐶2 𝐽1 (𝛼𝑟) 1 𝑦𝐴1 1 − ∙ 𝐽0 (𝑦𝑟) + − ∙ 𝐽 (𝑦𝑟) 2 2 2 𝐽0 (𝛼) 𝜇 (𝛼 − 𝑦 ) 𝑟 𝐽0 (𝛼) 𝑟 𝜇 (𝛼 − 𝑦 2 ) 1 By solving we get 𝐶2 = − 𝑖𝐾 𝐶 𝛼 1 and after series expansion of Bessel coefficients: 13 𝑦𝑟 2 𝑦𝑟 4 (2) (2) 𝐽0 (𝑦𝑟) = 1 − + 2 2 +⋯ ≈ 1 (12 ) (1 )(2 ) 𝑦𝑟 1 𝑦𝑟 3 𝑦𝑟 5 (2) (2) (2) 𝑦𝑟 𝐽1 (𝑦𝑟) = − + +⋯ ≈ 1 2 12 ∙ 3 22 2 𝑖𝜔𝜌 𝑖𝜔𝜌 𝑖 𝜔 2 2 2 2 As well as (𝛼 − 𝑦 ) = 𝜇 − 𝑖 𝐾 = 𝜇 − 𝑐 2 ≈ 𝛼 2 Due to the viscosity the velocities of the fluid along the inner wall of the vessel (when r = R0) are 𝑢|𝑟=𝑅0 = 𝐶1 𝐽0 (𝛼𝑟) 𝑖𝐾𝐴1 1 𝐽0 (𝛼𝑟) 𝐴1 + ∙ 𝐽0 (𝑦𝑟) = 𝐶1 + 2 2 𝐽0 (𝛼) 𝜇 (𝛼 − 𝑦 ) 𝐽0 (𝛼) 𝜌𝑐 𝑤|𝑟=𝑅0 = 𝐶2 𝐽1 (𝛼𝑟) 𝑦𝐴1 1 𝑖𝐾 2 𝐽1 (𝛼𝑟) 𝐴1 − ∙ 𝐽1 (𝑦𝑟) = − (𝐶1 + ∙𝑅 ) 2 2 𝐽0 (𝛼) 𝜇 (𝛼 − 𝑦 ) 2 𝛼 𝐽0 (𝛼) 𝜌𝑐 0 and we have 𝑑𝑢 𝐽1 (𝛼𝑅0 ) 𝑖𝐾𝐴1 1 𝐽1 (𝛼𝑅0 ) 𝐴1 𝐾 2 𝑅0 (−𝑦)𝐽 (𝑦𝑅 ) |𝑟=𝑅0 = −𝐶1 𝛼 + ∙ = −𝐶 𝛼 + 1 0 1 𝑑𝑟 𝐽0 (𝛼) 𝜇 (𝛼 2 − 𝑦 2 ) 𝐽0 (𝛼) 𝜌𝑐 2 𝐸ℎ With substitutions: 𝐵 = (1−𝜎2 ) , 𝑃 = 𝐴1 ∙ 𝐽0 (𝑦𝑟) and 𝐽0 (𝑦𝑟) ≈ 1 in equation (A5) we have 1 𝐵 𝑖𝐾𝜎𝐵 𝐴1 + (𝜔2 − Λ=0 )Ω − 2 𝜌0 ℎ 𝜌0 𝑅0 𝜌0 𝑅0 (A10) Since the velocity of the wall is equal to the velocity of the fluid along the wall of the vessel, equalizing the equations 𝑢= 𝑑𝜁 𝐽0 (𝛼𝑟) 𝐴1 𝑖(𝐾𝑥−𝜔𝑡) |𝑟=𝑅0 = −𝑖𝜔Λ𝑒 𝑖(𝐾𝑥−𝜔𝑡) = (𝐶1 + )𝑒 𝑑𝑡 𝐽0 (𝛼) 𝜌𝑐 𝐴1 𝐽0 (𝛼𝑅0 ) + 𝐶1 + 𝑖𝜔Λ = 0 𝜌𝑐 𝐽0 (𝛼) 𝑑𝜂 𝑖𝐾 2 𝐽1 (𝛼𝑅0 ) 𝐴1 𝑤= |𝑟=𝑅0 = −𝑖𝜔Ω𝑒 𝑖(𝐾𝑥−𝜔𝑡) = − (𝐶1 + ∙ 𝑅 ) 𝑒 𝑖(𝐾𝑥−𝜔𝑡) 𝑑𝑡 2 𝛼 𝐽0 (𝛼) 𝜌𝑐 0 𝑖𝐾𝑅0 𝑖𝐾 𝐽1 (𝛼𝑅0 ) 𝐴1 + 𝐶1 − 𝑖𝜔Ω = 0 2𝜌𝑐 𝛼 𝐽0 (𝛼) And the last equation, with substitutions in (A6) => (A11) (A12) −𝜔2 Λ = −𝐾 2 𝐵ℎ 𝑖𝐾𝜎 𝐵ℎ 𝜇 𝐽1 (𝛼𝑅0 ) 𝐴1 𝐾 2 𝑅0 𝑖 2 𝐾 2 2 𝐽1 (𝛼𝑅0 ) 𝐴1 Λ+ Ω− (−𝐶1 𝛼 + − + ∙ 𝑅 )) (𝐶1 𝜌0 ℎ 𝑅0 𝜌0 ℎ 𝜌0 ℎ 𝐽0 (𝛼) 𝜌𝑐 2 2 𝛼 𝐽0 (𝛼) 𝜌𝑐 0 𝜔2 𝑐2 ≪ 1 , 𝛼 𝐾2 2 𝐽1 (𝛼𝑅0 ) 𝐴1 + ∙𝑅 )≪1 (𝐶1 2 𝛼 𝐽0 (𝛼) 𝜌𝑐 0 14 We obtain 𝜇 𝐾 2 𝑅0 𝜇𝛼 𝐽1 (𝛼𝑅0 ) 𝐵ℎ 𝑖𝐾𝜎 𝐵ℎ − ∙ 𝐴1 + 𝐶1 + (𝜔2 − 𝐾 2 )Λ + Ω=0 𝜌0 ℎ𝜌𝑐 2 𝜌0 ℎ 𝐽0 (𝛼) 𝜌0 ℎ 𝑅0 𝜌0 ℎ (A13 - 23) The system of equations (A10), (A11), (A12) and (A13) is solved by setting the coefficients A1, C1, Λ and Ω to be equal to 0: 1 𝜌𝑐 | 𝑖𝜔𝑅0 2𝜌𝑐 2 | 1 𝜌0 ℎ | 𝜇 𝜔2 𝑅0 − ∙ 𝜌0 ℎ𝜌𝑐 3 2 𝐽0 (𝛼𝑅0 ) 𝐽0 (𝛼) 𝑖𝜔 𝐽1 (𝛼𝑅0 ) 𝛼𝑐 𝐽0 (𝛼) 0 𝑖𝜔 −𝑖𝜔 0 𝐵 𝜌0 𝑅02 𝑖𝜔𝜎 𝐵 𝑅0 𝑐 𝜌0 𝜔2 − 0 𝜇𝛼 𝐽1 (𝛼𝑅0 ) 𝜌0 ℎ 𝐽0 (𝛼) | 𝑖𝜔𝜎𝐵 | = 0 𝜌0 𝑅0 𝑐 𝜔2 𝐵 | 𝜔2 − 2 𝑐 𝜌0 − By simplifying this determinant, we obtain | 1− 2 𝐽1 (𝛼𝑅0 ) 𝛼𝑅0 𝐽0 (𝛼𝑅0 ) 1 | − 1 𝐽1 (𝛼𝑅0 ) 𝛼𝑅0 𝐽0 (𝛼𝑅0 ) 2 𝐵ℎ 𝜌𝑐 2 𝑅0 𝜎𝐵 − 2 𝜌𝑐 𝑅0 1 | 𝜎𝐵ℎ 1+ 2 =0 𝜌𝑐 𝑅0 𝜌0 ℎ 𝐵ℎ | − 𝜌𝑅0 𝜌𝑐 2 𝑅0 Using substitutions 𝐸ℎ 𝜌0 ℎ = 𝑥, =𝑡 2 (A14) 2𝜌𝑐 𝑅0 𝜌𝑅0 and after solving the determinant, the so-called frequency equation in term of variable x was obtained (4 − 2𝛼𝑅0 𝐽0 (𝛼𝑅0 ) 2 𝛼𝑅0 𝐽0 (𝛼𝑅0 ) 𝐽0 (𝛼𝑅0 ) − 1) − 4𝜎 + 1 + 2𝛼𝑅0 ]𝑥 ) 𝑥 + [2𝑡 ( 𝐽1 (𝛼𝑅0 ) 2 𝐽1 (𝛼𝑅0 ) 𝐽1 (𝛼𝑅0 ) 𝛼𝑅0 𝐽0 (𝛼𝑅0 ) − 2𝑡(1 − 𝜎 2 ) − (1 − 𝜎 2 ) = 0 2 𝐽1 (𝛼𝑅0 ) Using the values for viscosity of blood, diameter of aorta or main arteries, blood density and density of artery wall, we obtained that |𝛼𝑅0 | ≫ 1, ie that they are in the ranges of 𝛼𝑅0 = 3 − 12 and 𝑡 = 0.1 − 0.4. After asymptotic expansion of the Bessel function 𝐽0 (𝛼𝑅0 ) 1 ~−𝑖+ 𝐽1 (𝛼𝑅0 ) 2𝛼𝑅0 15 and by substituting in the frequency equation and arranging, the quadratic equation is obtained (−2𝛼𝑅0 𝑖 − 3)𝑥 2 + [4𝜎 − 2 + 2𝛼𝑅0 𝑖 + 𝑡𝛼𝑅0 𝑖 + 3𝑡 𝑡 ] 𝑥 + (1 − 𝜎 2 ) (1 + − 𝑡𝛼𝑅0 𝑖) = 0 2 2 1 This quadratic equation can be solved for 𝜎 = 0, 𝜎 = 2 and 𝜎 = 1. For an artery 𝜎 = 0.49, so the roots of 1 quadratic equation for 𝜎 = 2, are: 𝑡 𝑖 𝜎 2 3𝑡 𝑖(1 − 𝜎 2 ) 𝑥1 = 1 + + − ) and 𝑥2 = (2 − 2𝜎 + 2 𝛼𝑅0 2 4 2𝛼𝑅0 Substituting in (24) 𝐾 2 𝐸ℎ 𝐾2 2 = 𝑐 =𝑥 𝜔 2 2𝜌𝑅0 𝜔 2 0 We look for solutions in the following form and only for x1 (for 𝜇 → 0, 𝑥2 → ∞) 𝐾 𝐾1 + 𝑖𝐾2 𝑐0 = 𝑐0 = √𝑥1 𝜔 𝜔 After substitution √𝑖 = √2 (1 + 2 𝑖) and solving the root of a complex number 𝜎 2 3𝑡 𝜎 2 3𝑡 2 (1 − 𝜎 + − ) 2𝑖 (1 − 𝜎 + 𝑡 4 8 4 − 8 ) 𝐾1 + 𝑖𝐾2 + = 𝑐0 √𝑥1 = √1 + + 2 𝜔 2𝜔𝜌 2𝜔𝜌 √ √ 𝜇 𝑅0 𝜇 𝑅0 𝜎 2 3𝑡 𝐾1 𝑡 (1 − 𝜎 + 4 − 8 ) 𝑐 =1+ + , 𝜔 0 4 2𝜔𝜌 √ 𝜇 𝑅0 𝜎 2 3𝑡 (1 − 𝜎 + 4 − 8 ) 2𝜔𝜌 √ 𝐾2 𝜇 𝑅0 𝑐0 = 𝜎 2 3𝑡 𝜔 (1 − 𝜎 + 𝑡 4 − 8) 1+4+ 2𝜔𝜌 √ 𝜇 𝑅0 By substituting c0 with equation (7) which is a function of the initial pressure and arranging, we obtain the final equation (A15) for the pulse wave velocity 𝐸ℎ 𝑝 √ + 0 𝜔 1 𝑡 1 𝜇 𝜎 2 3𝑡 2𝑅0 𝜌 4𝜌 𝑐= =± + − − 𝜎 + − )) (1 (1 √ 2 𝑝0 𝑅0 𝐾1 4 𝑅 2𝜔𝜌 4 8 𝑡 0 1− 𝐸ℎ (1 + 4) And (A15) 16 2 𝑝0 𝑅0 (1 − 𝜎 + 𝜎 − 3𝑡) 4 8 𝐸ℎ 𝐾2 = ±𝜔 𝐸ℎ 𝑝0 𝑡 2𝜔𝜌 √ √ 2𝑅0 𝜌 + 4𝜌 (1 + 4) 𝜇 𝑅0 1− If we assume that t is very small it can be neglected (𝑡 = 0) 𝑎𝑛𝑑 the initial fluid is zero (𝑝0 = 0) we get the same equation derived by Morgan and Kiely for small viscosity 𝑐= 𝜔 𝐸ℎ 1 𝜇 𝜎2 = ±√ (1 + − √ (1 − 𝜎 + )) 𝐾1 2𝑅0 𝜌 𝑅0 2𝜔𝜌 4 (A16) And if we neglect both σ and μ we get the Moens-Korteweg equation (4) for PWV. In case of high viscosity, or |𝛼𝑅0 | ≪ 1, we use serial expansions 𝐽0 (𝛼𝑅0 ) ≈ 1 − 𝛼 2 𝑅02 , 4 𝐽1 (𝛼𝑅0 ) ≈ 𝛼𝑅0 𝛼 2 𝑅02 (1 − ) 2 8 After substituting in the frequency equation and solving the quadratic equations we obtain 𝑐= 𝜔 = 𝐾1 𝑐0 𝐸ℎ 𝑝0 𝜔𝜌 1 = ±√ + 𝑅0 √ 2𝑅0 𝜌 4𝜌 𝜇 5 − 4𝜎 + 6𝑡 5 − 4𝜎 + 6𝑡 √ 𝑅 2 𝜔𝜌 0 𝜇 (A17) and 𝐾2 = ±𝜔√ 1 𝜇 √5 − 4𝜎 + 6𝑡 √ 𝐸ℎ 𝑝 𝑅0 + 0 𝜔𝜌 2𝑅0 𝜌 4𝜌 Conflict of interest statement No conflicts of interest, financial or otherwise, are declared by the authors. Acknowledgments This work was supported by Serbian Ministry of Education, Science and Technological Development Grants 32040 and 41022. 17 Fig. 1. Increase in disk radius and width due to pulse wave: du/dz - the narrowing of the disk, u - disk shift, ∆𝑅0 - radius change Fig. 2. The propagation of the pulse wave increases the pressure on one side of the disk by ∆p Fig. 3. Stresses in a circular cylindrical pressure vessel a - hoop stress, b - longitudinal stress Fig. 4. 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Žikić D, Stojadinović B and Nestorović Z (2019) Biophysical modeling of wave propagation phenomena: experimental determination of pulse wave velocity in viscous fluid-filled elastic tubes in a gravitation field Eur Biophys J 48:407-411 20 Figure 1 Click here to access/download;Images;Figure 1.tif Figure 2 Click here to access/download;Images;Figure 2.tif Figure 3 Click here to access/download;Images;Figure 3.tif Figure 4 Click here to access/download;Images;Figure 4.tif Figure 5 Click here to access/download;Images;Figure 5.tif Figure 6 Click here to access/download;Images;Figure 6.tif Figure 7 Click here to access/download;Images;Figure 7.tif Table Click here to access/download Supplemental Files Table 1.docx Statement by authors Click here to access/download Supplemental Files Statement by authors.pdf Cover letter Click here to access/download Supplemental Files Cover letter.docx