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 Series on Bioengineering a nd Biomedica l E ngineering – Vol. 9

D Y N A M I C S o f the
VASCULAR SYSTEM
Interaction with the Heart
Second Edition

9807_9789814723749_TP.indd 1 6/8/18 10:23 AM

 SERIES ON BIOENGINEERING AND BIOMEDICAL
ENGINEERING

Series Editor: John K-J Li (Department of Biomedical Engineering,

Rutgers University, USA)

The aims of the book series are to present a publishing forum for established
researchers, educators and professionals in the field of bioengineering and
biomedical engineering to promote in-depth documentation of new scientific
findings, technological advances, and to provide effective teaching tools of the
fundamental aspects of the field. Single or multiple authored or edited books,
research monographs, textbooks, lab manuals and specialized conference pro-
ceedings are welcome. Topics of interest include biosensors, biomedical devices
and instrumentation, physiological modeling and signal processing, medical
imaging, drug delivery systems, clinical monitoring, tissue engineering, sys-
tems biology and bioinformatics, biomechanics and biomaterials, rehabilitation
and prostheses, nano and micro applications to biomedicine, biomedical optics,
biofluid mechanics, artificial organs and assist devices.

Published

Vol. 9: Dynamics of the Vascular System: Interaction with the Heart

(Second Edition)
by John K-J Li (Rutgers University, USA)

Vol. 8: Neuroprosthetics: Theory and Practice (Second Edition)

edited by Kenneth Horch (University of Utah, USA) and
Daryl Kipke (University of Utah, USA)

Vol. 7: Further Understanding of the Human Machine: The Road to

Bioengineering
edited by Max E Valentinuzzi (National Scientific and Technical
Research Council (CONICET), Argentina)

Vol. 6: Cardiac Fibrillation-Defibrillation: Clinical and Engineering Aspects

by Max E Valentinuzzi (University of Buenos Aires, Argentina &
University of Tucumán, Argentina)

Vol. 5: Biomedical Engineering Principles of the Bionic Man

by George K Hung (Department of Biomedical Engineering,
Rutgers University, USA)

For the complete list of volumes in this series, please visit

www.worldscientific.com/series/sbbe

Alex - 9807 - Dynamics of the Vascular System.indd 1 30-07-18 12:30:20 PM

 Series on Bioengineering and Biomedical Engineering – Vol. 9

DYNAMICS of the
VASCULAR SYSTEM
Interaction with the Heart
Second Edition

John K-J Li
Rutgers University, USA

World Scientific
NEW JERSEY • LONDON • SINGAPORE • BEIJING • SHANGHAI • HONG KONG • TAIPEI • CHENNAI • TOKYO

9807_9789814723749_TP.indd 2 6/8/18 10:23 AM

 Published by
World Scientific Publishing Co. Pte. Ltd.
5 Toh Tuck Link, Singapore 596224
USA office: 27 Warren Street, Suite 401-402, Hackensack, NJ 07601
UK office: 57 Shelton Street, Covent Garden, London WC2H 9HE

Library of Congress Cataloging-in-Publication Data

Names: Li, John K-J., 1950– author.
Title: Dynamics of the vascular system : interaction With the heart / by John K-J Li.
Other titles: Series on bioengineering and biomedical engineering ; v. 9.
Description: 2nd edition. | New Jersey : World Scientific, 2018. | Series: Series on bioengineering
and biomedical engineering ; volume 9 | Includes bibliographical references and index.
Identifiers: LCCN 2018010403 | ISBN 9789814723749 (hc : alk. paper)
Subjects: | MESH: Cardiovascular Physiological Phenomena | Models, Cardiovascular
Classification: LCC QP105 | NLM WG 102 | DDC 612.1--dc23
LC record available at https://lccn.loc.gov/2018010403

British Library Cataloguing-in-Publication Data

A catalogue record for this book is available from the British Library.

Copyright © 2019 by World Scientific Publishing Co. Pte. Ltd.

All rights reserved. This book, or parts thereof, may not be reproduced in any form or by any means,
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Alex - 9807 - Dynamics of the Vascular System.indd 2 30-07-18 12:30:20 PM

9in x 6in b3250 Dynamics of the Vascular System: Interaction with the Heart (2nd Edn) b3250-FM

Preface to the First Edition

This book is the first volume of the Bioengineering and Biomedical

Engineering Book Series. As the Series Editor, and to set a good
example, I have taken the task of writing yet another book on the
cardiovascular system.
The contents of this book extends from Arterial System Dynamics,
my first book published some fifteen years ago, to distinctly different
regimes of the microcirculation and the venous system, as well as the
assisted circulation.
The vascular system is indeed so vast, that a binocular vision is often
needed to unravel the mystery of the many concurrent interactions
occurring at different sites of the vascular tree. This becomes more
challenging with the imposition of studying its dynamic phenomena. The
Dynamics of the Vascular System is written employing mathematical
techniques to formulate the physical principles involved in the structural
and functional correlates of the underlying physiology. The intriguing
control and geometric perspectives are also included wherever possible.
The book also serves as a companion text to The Arterial Circulation:
Physical Principles and Clinical Applications.
Selected topics and references are provided, so that I and the readers
are not overwhelmed by the otherwise exhaustive presentations of the
many observed phenomena and the subsequent diverse interpretations of
their origins and mechanisms.
I hope professionals and students in the field of bioengineering and
biomedical engineering, biomathematics, biophysics, cardiovascular

v
9in x 6in b3250 Dynamics of the Vascular System: Interaction with the Heart (2nd Edn) b3250-FM

vi Preface to the First Edition

physiology and medicine will find this book a relevant source of

reference. Much of the work is the culmination of my three decades of
learning, experimenting and investigation. I am aware that there are
other works of notable items and newer advances which I have not yet
included in this book. I will continue to learn more of them. Finally, I
like to thank those who have contributed to the completion of this book.

John Kong-Jiann Li
New Jersey, USA
9in x 6in b3250 Dynamics of the Vascular System: Interaction with the Heart (2nd Edn) b3250-FM

Preface to the Second Edition

This book was originally published in 2004 as the first volume of the
Bioengineering and Biomedical Engineering Book Series. A decade has
quickly passed, together with the many advances in the sciences,
medicine and technology. I decided to take up the task to update some of
the materials for this second edition, while preserving the fundamental
concepts of the original text.
The contents of this second edition include explicitly a chapter on the
Interaction of the Heart and the Arterial System. This topic was
supported by the National Science Foundation that I began working on
right after completing my doctorate at the University of Pennsylvania
four decades ago with the late Professor Abraham Noordergraaf. This
chapter includes basic cardiac muscle mechanics, the contractile function
of the heart and its dependence on the operating relations with the
vascular system under normal and heart failure conditions, with emphasis
on their dynamic interaction. Examples of mechanical cardiac assist
devices and drug treatment are also included.
This second edition continues to emphasize on quantitative treatment
of the vascular system by analyzing the structural and functional
correlates of the underlying physiology. This may purposefully overlook
some of the clinical aspects in terms of diagnosis and treatment efficacies
of certain cardiovascular diseases. Similar to the first edition, rather than
being exhaustive, only selected topics and references are provided. In
this regard, worthwhile publications from some investigators may not
have been included.

vii
9in x 6in b3250 Dynamics of the Vascular System: Interaction with the Heart (2nd Edn) b3250-FM

viii Preface to the Second Edition

I hope many of the cardiovascular scientists, researchers and

clinicians, as well as students will continue to find this book a useful
reference. I like to thank those who have contributed to the completion
of this book.

John Kong-Jiann Li
New Jersey, USA
9in x 6in b3250 Dynamics of the Vascular System: Interaction with the Heart (2nd Edn) b3250-FM

About the Author

John K-J. Li obtained his Ph.D. in Bioengineering

from the University of Pennsylvania and has been a
Distinguished Professor of Biomedical Engineering
at Rutgers University since 1998. He has been an
elected Fellow of the American Institute for
Medical and Biological Engineering, the American
Colleges of Cardiology, the American College of
Angiology, and the Academy of Medicine of New
Jersey. He is also the Founding Editor-in-chief of
Springer’s Cardiovascular Engineering and Bioengineering and
Biomedical Engineering Book Series of World Scientific and Imperial
College Press, and is on the editorial boards of numerous journals. His
research has been founded by the NIH, NSF, AHA, and industry grants,
with interest in cardiac and vascular mechanics, modeling, medical
devices, controlled drug delivery, hypertension and heart failure,
neuroengineering, scaling in biology, and comparative physiology. He
has authored several books and published numerous articles and is a
frequently invited speaker at national and international conferences and
universities. He enjoys teaching and has been the adviser to more than 90
Ph.D. and M.S. students and 175 senior design students, and received
teaching excellence awards. He is also a holder of several US patents
and a recipient of the IEEE Millennium Medal.

ix
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9in x 6in b3250 Dynamics of the Vascular System: Interaction with the Heart (2nd Edn) b3250-TOC

Contents

Preface to the First Edition....................................................................... v

Preface to the Second Edition .................................................................vii
About the Author ...................................................................................... ix

Chapter 1. Historical Background and Book Contents ............................ 1

1.1 Discoveries of the Circulation .................................................... 1
1.2 Importance of the Vascular System ............................................ 7
1.3 Newer Concepts .......................................................................... 8
1.4 Book Contents ............................................................................ 9

Chapter 2. Vascular Biology, Structure and Function ........................... 15

2.1 Anatomical Organization of the Vasculature ............................ 15
2.1.1 The Closed-loop Circulatory System............................. 15
2.1.2 The Heart ....................................................................... 15
2.1.3 The Arteries ................................................................... 18
2.1.4 The Veins ....................................................................... 19
2.1.5 The Microvasculature .................................................... 20
2.2 Geometric and Mechanical Properties of Blood Vessels .......... 21
2.2.1 Geometric Nonuniformity of Blood Vessels ................. 21
2.2.2 Elastic Nonuniformity of the Blood Vessels ................. 24
2.2.3 Vascular Stiffness and Elastic Properties ...................... 25
2.3 Functional Properties of Blood ................................................. 31
2.3.1 Blood Plasma and Blood Gas ........................................ 31
2.3.2 Oxygen Saturation Curves and Hemoglobin ................. 32
2.3.3 Red Blood Cells, Hematocrit and Blood Volume.......... 35

xi
9in x 6in b3250 Dynamics of the Vascular System: Interaction with the Heart (2nd Edn) b3250-TOC

xii Contents

2.4 Control Aspects of the Vascular System .................................. 37

2.4.1 Control of the Central Cardiovascular System .............. 38
2.4.2 Functions of the Baroreceptors ...................................... 39
2.4.3 Arterial Chemoreceptors ................................................ 40

Chapter 3. Physical Concepts and Basic Fluid Mechanics .................... 43

3.1 Basic Mechanics and Dimensional Analysis ............................ 43
3.1.1 Mass, Length and Time System and the Pi-theorem
of Buckingham .............................................................. 43
3.1.2 Dimensional Matrix ....................................................... 45
3.1.3 Biological Scaling and Dynamics Similitude in
Vascular Biology ........................................................... 46
3.1.4 Elastic and Viscoelastic Properties of Blood
Vessels ........................................................................... 49
3.2 Frequency Domain and Fourier Analysis ................................. 56
3.2.1 Blood Pressure as a Periodic Function .......................... 56
3.2.2 Trigonometric Fourier Series ......................................... 57
3.2.3 Complex Form of Fourier Series ................................... 59
3.2.4 Other Aspects of Frequency Domain Analysis.............. 62
3.2.4.1 Dirichlet Conditions ........................................ 62
3.2.4.2 Line Spectrum and Nyquist Criterion.............. 63
3.2.4.3 Correlation, Coherence and Power
Spectrum .......................................................... 64
3.3 Fluid Mechanics and Rheology ................................................ 65
3.3.1 Steady Flow, the Poiseuille Equation and Flow
Velocity Profile.............................................................. 65
3.3.2 Bernoulli’s Equation and Narrowing Vessel Lumen
or Stenosis...................................................................... 70
3.3.3 Orifice Flow and Torricelli’s Equation.......................... 71
3.3.4 Valvular Cross-section and the Gorlin Equation ........... 72
3.3.5 Flow and Flow Acceleration .......................................... 72
3.3.6 Newtonian Fluid, No-Slip, Boundary Conditions
and Entry Length ........................................................... 75
3.3.6.1 Newtonian Fluid .............................................. 75
3.3.6.2 No-Slip Boundary Conditions ......................... 76
3.3.6.3 Laminar and Turbulent Flow ........................... 77
3.3.6.4 Entry Length .................................................... 78
9in x 6in b3250 Dynamics of the Vascular System: Interaction with the Heart (2nd Edn) b3250-TOC

Contents xiii

Chapter 4. Hemodynamics of Arteries ................................................... 79

4.1 Blood Pressure and Flow Relations .......................................... 79
4.1.1 Pulsatile Pressure and Flow Waveforms
in Arteries ...................................................................... 79
4.1.2 Pressure-flow Relations in the Aorta ............................. 82
4.2 Vascular Impedance to Blood Flow.......................................... 84
4.2.1 The Impedance Concept and Formulation ..................... 84
4.2.2 Input Impedance and Characteristic Impedance ............ 86
4.3 Pulse Wave Propagation Phenomena........................................ 90
4.3.1 The Pulse Wave Propagation Constant.......................... 90
4.3.2 Pulse Wave Velocity and the Foot-to-Foot
Velocity ......................................................................... 91
4.3.3 Apparent Propagation Constant and Transfer
Function ......................................................................... 94
4.3.4 Determination of the Propagation Constant
and Frequency Dependent Pulse Wave Velocity ........... 98
4.4 Pulse Wave Reflection Phenomena ........................................ 102
4.4.1 Influence of Wave Reflections on Pressure
and Flow Waveforms................................................... 102
4.4.2 The Reflection Coefficients ......................................... 108
4.4.3 The Augmentation Index ............................................. 111
4.4.4 Wave Reflection Sites and Multiple Reflections ......... 112
4.5 Modeling Aspects of the Arterial Circulation ......................... 114
4.5.1 Mathematical Formulations of Pulse Wave
Propagation .................................................................. 114
4.5.2 Linear Theories of Oscillatory Blood Flow in
Arteries ........................................................................ 118
4.5.3 The Lumped Model of the Arterial System and the
Windkessel Model ....................................................... 124
4.5.4 Nonlinear Aspects and Pressure-Dependent
Arterial Compliance..................................................... 130

Chapter 5. Vascular Branching ............................................................ 137

5.1 Branching Geometry ............................................................... 137
5.1.1 Complexity of Vascular Branching ............................. 137
5.1.2 Nonuniform Branching and 3-D Branching
Structures ..................................................................... 139
5.1.3 Space-Filling Properties and Modeling ....................... 141
9in x 6in b3250 Dynamics of the Vascular System: Interaction with the Heart (2nd Edn) b3250-TOC

xiv Contents

5.2 Fluid Mechanics of Vascular Branching................................. 144

5.2.1 Branching Geometry and Fluid Dynamic
Considerations ............................................................. 144
5.2.2 Fluid Mechanics Associated with Atherosclerosis
and Stenosis ................................................................. 149
5.3 Pulse Transmission Characteristics at Vascular
Branching ................................................................................ 151
5.3.1 Impedance Matching and Wave Reflections ............... 151
5.3.2 Area Ratio Concept...................................................... 154
5.3.3 Minimum Local Reflections at Vascular Branching
Junctions ...................................................................... 158
5.4 Optimization Aspects Applicable to Vascular Branching ...... 161
5.4.1 Optimizing Vessel Radius and the Cube Law ............. 161
5.4.2 Optimizing Branching Radii and Angles ..................... 164

Chapter 6. The Venous System ............................................................ 167

6.1 The Reservoir Properties and Venous Return ......................... 167
6.1.1 Venous Compliance and Reservoir Characteristics ..... 167
6.1.2 Structural Properties of Veins ...................................... 168
6.1.3 Venous Return ............................................................. 169
6.2 Pressure and Flow Waveforms in Veins ................................. 170
6.2.1 The Normal Pressure and Flow Waveforms
in Veins ....................................................................... 170
6.2.2 Respiration Effects on Venous Pressure and Flow
Waveforms................................................................... 172
6.2.3 Abnormal Venous Pressure and Flow Waveforms ...... 173
6.3 Modeling and Collapsible Vessel Properties .......................... 173
6.3.1 Steady Flow in Collapsible Tubes ............................... 173
6.3.2 Flow Limitation and Model Experiments .................... 175
6.3.3 Pulse Wave Transmission Characteristics in Veins ..... 180

Chapter 7. The Microcirculation .......................................................... 183

7.1 Structure of the Microcirculation ............................................ 183
7.1.1 Functional Organization of the Microvasculature ....... 183
7.1.2 The Capillary Circulation ............................................ 188
7.2 Pressure-Flow Relation and Microcirculatory Mechanics ...... 191
7.2.1 Flow-Related Mechanical Characteristics of the
Microcirculation .......................................................... 191
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Contents xv

7.2.2 Some Pressure-Related Mechanical Characteristics

of the Microcirculation ................................................ 193
7.3 Pulse Transmission and Modeling Aspects ............................ 196
7.3.1 Pressure and Flow Waveforms in Arterioles
and Capillaries ............................................................. 196
7.3.2 Pulse Transmission Characteristics in the
Microcirculation .......................................................... 198
7.3.3 Modeling Aspects of the Microcirculation .................. 201

Chapter 8. Hemodynamic Measurements: Invasive and

Noninvasive Monitoring ................................................... 205
8.1 Catheterization for Blood Pressure Measurement .................. 205
8.1.1 Fluid-filled Blood Pressure Measurement
Systems ........................................................................ 205
8.1.2 Experimental Evaluation of the Frequency
Response of Catheter-Pressure Transducer
Systems ........................................................................ 208
8.2 Noninvasive Blood Pressure Measurements ........................... 213
8.2.1 Auscultation Measurement of Blood Pressure............. 213
8.2.2 Blood Pressure Measurement with the Oscillometric
Method ......................................................................... 215
8.2.3 Noninvasive Blood Pressure Monitoring with
Tonometer .................................................................... 217
8.2.4 The Photoplethysmograph (PPG) ................................ 219
8.3 Blood Flow Measurement ....................................................... 219
8.3.1 Electromagnetic Flowmeter ......................................... 219
8.3.2 Ultrasound and Doppler Flow Velocity
Measurement ............................................................... 221
8.3.3 Cardiac Output Measurement with Indicator
Dilution Methods and Thermodilution ........................ 224
8.4 Measurement of Vascular Dimensions ................................... 227

Chapter 9. Interaction of the Heart and the Arterial System ................ 229
9.1 Ventricular Outflow and the Aorta ......................................... 229
9.1.1 Ventricular Ejection ..................................................... 229
9in x 6in b3250 Dynamics of the Vascular System: Interaction with the Heart (2nd Edn) b3250-TOC

xvi Contents

9.2 Cardiac Muscle Mechanics and the Force-Velocity-Length

Relation ................................................................................... 232
9.2.1 Structure of Myocardial Fibers and the Sliding
Filament Theory .......................................................... 232
9.2.2 Hill Model of Muscle Contraction ............................... 234
9.3 The Pressure-Volume Curve and Contractility
of the Heart ............................................................................. 235
9.3.1 Variables Defining the Pressure-Volume Loop ........... 235
9.3.2 Frank-Starling Mechanism and Ejection Fraction ....... 237
9.3.3 Cardiac Contractility and Indices of Cardiac
Performance ................................................................. 239
9.4 Heart and the Arterial System Interaction .............................. 241
9.4.1 The Concept of Ventricular and Arterial
Elastances .................................................................... 241
9.4.2 Dynamic Heart-Arterial System Interaction ................ 246
9.4.3 Left Ventricle-Arterial System Interaction
in Heart Failure ............................................................ 248
9.5 Heart-Arterial System Interaction in the Assisted
Circulation .............................................................................. 250
9.5.1 Mechanical Assist Devices and the Intra-Aortic
Balloon Pump .............................................................. 250
9.5.2 Optimization of Intra-Aortic Balloon Pumping:
Physiological Considerations....................................... 254
9.5.3 Optimization of Intra-Aortic Balloon Pumping:
Modeling Aspects ........................................................ 258
9.5.4 Optimization of Intra-Aortic Balloon Pumping:
Control Aspects ........................................................... 259

Bibliography ......................................................................................... 261

Index...................................................................................................... 273
9in x 6in b3250 Dynamics of the Vascular System: Interaction with the Heart (2nd Edn) b3250-ch01

Chapter 1

Historical Background and Book Contents

1.1 Discoveries of the Circulation

That “blood moves in closed circle” was apparently known in the Far
East, several millennia ago, about 2,650 B.C., as recorded in the book by
the Yellow Emperor of China written in the Canon of Medicine (Nei
Ching). Ancient Chinese practitioners customarily felt palpable wrist
artery (radial artery) pulsations as a means of diagnosing the cardiac state
of their patients. In this approach, the practitioners were able to obtain
both the strength of the pulsation to infer the vigor of contraction of the
heart, and the interval duration of the pulses, hence heart rate. This
seemingly indicates that the importance of the rate-pressure product, now
a popular clinical index of myocardial oxygen consumption, might even
have been considered pertinent at that time. The supply and demand of
oxygenation, as well as its proper utilization in terms of energy balance,
or ying-yang, is center to achieving body harmony. Thus, this suggestion
of an intrinsic transfer of the energy (Chi) generated by the heart to the
peripheral arteries may have been known since antiquity, although the
theoretical foundation was not established until much later.
In the West, the observation that man must inspire air to sustain life
led ancient scientists and philosophers to toy with the idea that arteries
contained air rather than blood. This was the notion originally attributed
to Erasistratus in the third century B.C., following the teaching of
Aristotle. Aristotle and later Herophilus performed numerous anatomical
studies and the latter discovered the connecting arteries to the contracting
heart. That arteries themselves contract and relax thus was known in
Aristotle’s time. Arterial properties in terms of elastic stiffness,
distensibility and compliance, as we know now, were not fully described.
Galen’s (130-200) description of the ebb and flow of blood in arteries,

1
9in x 6in b3250 Dynamics of the Vascular System: Interaction with the Heart (2nd Edn) b3250-ch01

2 Dynamics of the Vascular System (2nd Edition)

though lasted for centuries, was grossly inaccurate. Additionally, in the

Galenic view, blood was passed from the right side of the heart to the left
side through pores, which was later shown to be incorrect as they do not
exist within the inter-ventricular septum, as demonstrated by Columbus
(1516-1559), a Belgian anatomist. Otherwise, this would be known as
the septal defect. Columbus, during his many dissections, confirmed that
venous blood of the right ventricle passed into the left ventricle through
the lungs. This was concluded a few years earlier by Servetus (1511-
1553), a Spanish theologian and physician. Thus, the open-circuit
interpretation of the circulation by Galen cannot accurately describe the
“circulation of blood”.
In his many teachings, though some aspects were later known to be
erroneous, Galen was nevertheless the first to recognize that the walls of
arteries are thicker than those of the veins, and that arteries were
connected to veins. It was the Persian physician Ibn al-Nafis (1210-
1288) who claimed that venous blood of the right ventricle is carried by
the artery-like vein into the lungs, where it mixes with the air and then
into the left ventricle through vein-like artery.
Galileo Galilei (1564-1642) in his “Dialogue of the Two Sciences”,
which appeared in 1637, suggested the circulation of blood in a closed
system. Centuries later today, the idea of the circulation of blood was
credited to William Harvey (1578-1657), a contemporary of Galileo, in
his now famous “De Motu Cordis and De Circulatione Sanguinis” (1628)
presented to King Charles of England. He described in his “Anatomical
Exercises” that “blood does continually passes through the heart” and
that “blood flow continually out the arteries and into the veins”. Harvey’s
work indicated the pulsatile nature of blood as a consequence of
intermittent inflow, during roughly one-third of the heart cycle, now
known as systole, in combination with essentially steady outflow through
the periphery during the remaining cardiac period, the diastole.
Harvey’s work was completed before Malphighi who worked with the
aid of a compound microscope. He reported in 1661 the discovery of the
capillaries linking the arterial circulation to the venous circulation, while
he was working with the microscopic anatomy of the pulmonary
parenchyma in the frog, an uni-ventricular amphibian. Dutch anatomist
Van Leeuwenhoek (1632-1723) confirmed the capillaries in different
9in x 6in b3250 Dynamics of the Vascular System: Interaction with the Heart (2nd Edn) b3250-ch01

Historical Background and Book Contents 3

organs of several animal species and established the concept of the

capillary bed. Bypassing the capillaries are the arterio-venous
anastomoses, which are now known to perform the function of
controlling blood flow.
German anatomist Henle discovered the smooth muscle cells in small
arteries in 1841. Thus, this provided the first evidence that smooth
muscle contributes to arterial contraction. But it is not until almost a
century later in 1937 that Zweifach showed that active contractility of the
micro-vessels is confined to those vessels with smooth muscle cells.
In the investigation of the microcirculation, credit was given to Hall,
an English physiologist, first to differentiate the capillaries from
arterioles. The fact that capillaries transfer water and water-soluble
substances from the blood stream to the surrounding tissues, were shown
by Starling (1866-1927) and is now known as the Starling’s hypothesis
governing fluid exchange. The measurement of capillary blood pressure
by cannulation was first performed in 1930, by Landis, in the nail
microvascular bed (Mayrovitz, 1998). The ultra-structure of the
microcirculation has now been established from electron microscope
studies.
French physiologist Claude Bernard in 1852 showed that stimulation of
sympathetic nerves induces vasoconstriction and the concept of
controlling blood flow by vasomotor nerves. Neural control of the
circulation is recognized as an important aspect in the regulation of
vascular function.
Fascinated by anatomic structure of the vascular tree, as an art,
Leonardo da Vinci (1452-1519) made many detailed drawings of the
constituent parts of the circulatory system. He apparently already knew
that both the contraction and resting periods are necessary for the heart to
function with a normal rhythm. His anatomic drawings of the heart and
the perfusing arteries are, to a large extent, amazingly accurate. This
includes drawings of the heart and the great vessels, together with the
main, anterior descending and circumflex coronary arteries and their
major branches. Several drawings of the heart valves, demonstrating
how well the leaflets are arranged when the valves are closed, as well as
the detailed anatomic drawing of the neck arteries in man with
its branching morphology were also shown (Li, 2000). In these, both the
9in x 6in b3250 Dynamics of the Vascular System: Interaction with the Heart (2nd Edn) b3250-ch01

4 Dynamics of the Vascular System (2nd Edition)

Fig. 1.1.1: Anatomic drawings by Vesalius. The extensiveness of the vascular tree is well
appreciated.
9in x 6in b3250 Dynamics of the Vascular System: Interaction with the Heart (2nd Edn) b3250-ch01

Historical Background and Book Contents 5

length and angle of branching arteries are incredibly accurate. Vesalius

(1514-1564), an anatomist, later provided a detailed drawing of the entire
human vascular tree (Fig. 1.1.1).
Italian physician Caesalpinus apparently identified the pulmonary
circulation and its associated two types of blood vessels: vena cava and
pulmonary vein and pulmonary artery and aorta. Hooke (1635-1703; of
Hooke’s law of elasticity), an assistant of the English chemist Boyle
(1627-1692; of Boyle’s law of gases), recognized that respiration was
necessary. But it was the English physiologist Lower (1631-1691) who
continued the investigation to show the importance of ventilation-
perfusion, i.e. exchange of gases between the lungs and blood. Gas
transport in blood was reported by Magnus in 1837. He demonstrated
that there was greater oxygen content in arterial blood and greater carbon
dioxide content in the venous blood. Other formed elements, such as
hemoglobin (Hb) were discovered by Funke in 1851 and has been shown
as an important oxygen transporter. Neural effect was shown by Haldane
(1860-1936), that carbon dioxide is a normal physiologic stimulus for the
respiratory centers. The Haldane effect is now well appreciated in
respiratory function and in oxygen therapy applications.
Lack of instrumentation, the measurements of the magnitudes of
blood pressure and flow took considerably longer than the interpretation
of the circulatory function. Hales in 1733 had incidentally already
registered the magnitude of the blood pressure level about which blood
oscillates. His initial measurement of blood pressure with a glass tube in
a horse has been well illustrated in many publications. Thus, the
magnitude of the mean arterial pressure and the amplitude of oscillation,
or pulse pressure, were already known at that time. This forms the basis
of modern day oscillometric measurement of blood pressure. Hales’
measurements however, did not induce recognition of the great
importance of blood pressure magnitude for many decades. We now
know that significantly increased magnitudes of mean blood pressure and
pulse pressure, the difference between systolic pressure and diastolic
pressure, are major contributors to hypertension and many forms of
cardiovascular diseases.
The shape of the pressure pulse became known only in the 19th
century when Ludwig came up with the kymograph which inscribed
blood pressure waveforms. His instrument provided information within
a single beat which was a truly a technological advance at the time. Its
9in x 6in b3250 Dynamics of the Vascular System: Interaction with the Heart (2nd Edn) b3250-ch01

6 Dynamics of the Vascular System (2nd Edition)

accuracy was not comparable to present day instrument, although not an

issue at the time. Blood pressure recording with the sphygmographs by
Marey and his contemporary Mahomed has led to the clinical assessment
of arterial diseases, such as hypertension. Incidentally, Chaveau and
Marey (1863) also recorded cardiac chamber pressures. Both, shortly
later, measured blood flow with an instrument they developed, now
known as the bristle flowmeter.
Modern understanding of pressure-flow relationships came with the
inventions of fluid-filled catheter-manometer system and the
electromagnetic flowmeter. The simultaneous measurements of blood
pressure and flow have led to considerable advancement of
hemodynamics, or the studies of blood flow. The catheter was introduced
in man by Forssmann in 1929, and later advanced for catheterization of
the right heart for pressure measurement by Cournand and Range in 1941
(Li et al., 1976). Cournand and Forssmann (together with Richards)
shared the Nobel prize for medicine in 1956 for the invention leading to
the advancement of modern day catheterization for visualization of blood
pressure waveforms in various anatomical sites throughout the
circulation. The electromagnetic flowmeter was introduced by Kolin in
1936. But ultrasonic transit-time and Doppler flow velocity probes have
taken center stage in modern research and routine clinical measurements,
mostly for their noninvasive monitoring capabilities.
In an attempt to understand the function of the arterial system as a
whole, Hales (1733) concluded that in order for the arteries to accept the
large amount of blood ejected, or the stroke volume, the arteries must
behave like a temporary storage reservoir. Since the size of the aorta is
considerably smaller than that of the ventricle, the receiving aorta must
be elastic in order to perform the function as a reservoir. This
interpretation of the reservoir function of arteries became known later as
the Windkessel theory which was vigorously pursued a century later by a
German physician Frank towards the end of the 19th century. The
emphasis on the storage properties of the arteries modeled by Frank as a
single elastic tube implied that all pressure fluctuations in the arterial tree
should occur synchronously. In other words, the blood pressure pulse
should propagate with infinite velocity. The peripheral vessels, on the
other hand, are assumed rigid as stiff tubes. This gives rise to the lumped
9in x 6in b3250 Dynamics of the Vascular System: Interaction with the Heart (2nd Edn) b3250-ch01

Historical Background and Book Contents 7

compliance-resistance model of the arterial circulation. This Windkessel

model lacks the description of the propagation characteristics of the
pressure pulse, but has remained the most popular model describing the
arterial system and interpreting its physiological properties even until
this day.
Blood pressure pulse propagation with finite wave velocity in a blood
vessel was considered over two centuries ago by Euler in 1775. He
attempted to develop a formula for its calculation. The well-known
physicist Young in 1816, and also the Weber brothers in 1866,
apparently solved for the propagation velocity in an elastic tube
(Noordergraaf, 1969). Incorporating the elastic properties and geometry
of the blood vessel, Moens (1878) and Korteweg (1878) separately
developed what is now known as the Moens-Korteweg formula for the
pulse wave velocity, or PWV:

Eh
c0  (1.1.1)
2r

where E is, appropriately at the time, defined as the Young’s modulus of

elasticity of the blood vessel, h and r are the wall thickness and inner
radius of the uniform cylindrical vessel, respectively, and  is the density
of blood. Pulse propagation velocity is seen to be related to the
mechanical and geometrical properties of the blood vessel.

1.2 Importance of the Vascular System

In terms of the dynamics of the vascular system, the function of the heart
is to provide energy and perfuse organ vascular beds. For the heart to
accomplish this efficiently, the vascular system plays a central role as the
distributing conduits. As such, both the distributing arteries and the
peripheral vascular beds present the load to the pumping heart.
Peripheral resistance has been popularly viewed in the clinical setting as
the principal vascular load to the heart. This applies mainly to steady
flow conditions. This description is naturally inadequate, because of the
pulsatile nature of blood flow which remains throughout the
microcirculation. Pulsatility implies that there is an oscillatory or
pulsatile contribution to the vascular load to the heart. The significance
9in x 6in b3250 Dynamics of the Vascular System: Interaction with the Heart (2nd Edn) b3250-ch01

8 Dynamics of the Vascular System (2nd Edition)

of pulsations has been a popularly debated topic in the clinical settings

where perfusion to organs is considered pertinent.
The vascular system provides a seamless illustration of an efficient
transport system. This can be seen from the function of, for instances, the
coronary circulation in perfusing the heart, the renal circulation in
perfusing the kidneys, the cerebral circulation in perfusing the brain and
the pulmonary circulation in perfusing the lungs. By virtue of the
distributing arterial trees, oxygen, humoral agents, and nutrients be
transported to the vital parts of the body, and at the same time, removal
of biological waste materials is also accomplished.

1.3 Newer Concepts

Modern development of the theory related to blood flow in the vascular

system has included multi-faceted aspects, such as, fluid mechanics,
fluid-vessel interface, vascular tissue engineering, pulse wave trans-
mission and mathematical modeling.
The mathematical formulations of blood flow through visoelastic
arteries have been well established and documented in many texts (e.g.
Noordergraaf, 1978, 2011; Li, 1987, 2000, 2004; Nichols and O’Rourke,
1998). These texts also provided experimental measurement methods and
quantitative approaches to the assessments of the state of the arterial
circulation. There are also several texts in describing the microcirculation
and associated biomechanical behavior in greater detail (e.g. Lee and
Skalak, 1989; Fung, 1997).
In the application to clinical situations, the interpretation of the
morphology of blood pressure and flow waveforms in relation to
underlying diseased conditions has attracted the most attention. The
introduction of new groups of drugs beyond vasodilators, beta adrenergic
blockers, calcium channel blockers and angiotensin-converting enzyme
inhibitors that includes local targeted vascular drug delivery, as well as
the introduction of gene therapy and regenerative medicine, to improve
vascular perfusion and in the treatment of diseases, has become more
avant garde.
Not only the arteries, the microcirculatory vessels are no longer
viewed merely as resistance vessels, but are compliant with viscoelastic
9in x 6in b3250 Dynamics of the Vascular System: Interaction with the Heart (2nd Edn) b3250-ch01

Historical Background and Book Contents 9

properties that vary with frequency. The classical elastic description of

blood vessels has been modified to include viscosities of the blood and
the vessel wall. The viscosities give rise to energy dissipation. Thus, the
energy utilization and dissipation in relation to blood flow is now
considered pertinent. Regarding Chi, or energy, the amount of the work
that the heart has to generate during each beat has generated considerable
attention. This included the steady energy dissipation through peripheral
resistance vessels in different parts of the body, as well as energy
required to overcome pulsations which persist even in the
microcirculation.
Clinical applications of modern development of dynamics of the
vascular system have initiated both invasive and noninvasive
technological development and improvement in the accuracy of assessing
the vascular structure and function. These include laser-Doppler
velocimeter, multi-sensor pressure-velocity catheter, phase contrast
magnetic resonance imaging (PC-MRI) and intravascular ultrasonic
system (IVUS). There are also advancements in the development of
interventional devices, such as local drug delivery catheter, laser- or
balloon-angioplasty catheter, vascular stents and grafts. Many of these
have been used for the assessment and treatment of vascular
hypertrophy, stenosis and aneurysm, hypertension and atherosclerosis.

1.4 Book Contents

This book deals primarily with the dynamic behavior of the components
of the vascular system and methods and techniques for their quantitative
measurements. The book is written applying fundamental physical
principles in conjunction with physiological measurements to the
analysis of the structural and functional aspects of the vascular tree that
includes the arterial circulation, the venous circulation, and the
microcirculation, inclusive of arterioles, capillaries and venules. In
addition, the constituent components, such as collagen, elastin, smooth
muscle, and endothelial and red blood cells as well as transport
phenomena are also discussed. An additional chapter on the interaction
of the heart and the arterial system is also included in this second edition.
Quantitative approaches are emphasized in the overall treatment.
9in x 6in b3250 Dynamics of the Vascular System: Interaction with the Heart (2nd Edn) b3250-ch01

10 Dynamics of the Vascular System (2nd Edition)

In Chapter 2, modern concepts of vascular biology are illustrated.

This begins with the anatomical organization of the vascular tree. Major
branches of the aorta and some arteries at similar anatomic sites in some
mammalian species, such as human, dog and rats, are described. These
latter are common mammalian species where experimental
measurements and data are most frequently collected. Geometric
nonuniformities in terms of tapering and branching of the vessels are
quantified. The fractal nature of the vascular tree can be well
appreciated from some of the illustrations. The distributing channels and
networking environment are illustrated.
Examination of structural properties allows us to differentiate the
mechanical and functional characteristics of various vessels. This
includes the nonuniformities in elasticity reflected in the content and
organization of the walls of the various blood vessels. Constituent
structural components of the arterial and venous wall are examined in
rheological terms. In particular, the physical properties of elastin,
collagen, and smooth muscle. The relative contents of the wall materials
differentiate arteries from veins, arterioles and capillaries.
Oxygen is perhaps the most important component to be transported in the
blood. The formed elements of blood are dealt with, that includes
hemoglobin, red blood cells and plasma. Functional properties of blood
are therefore included in this chapter. Some aspects of the circulating
catacholamines and hormones, as well as neural control of the vascular
system are equally important.
Chapter 3 deals with some fundamental concepts for analysis of the
vascular system. The differences in their mechanical properties in large
and small arteries and veins are examined. Their collective contributions
to the overall function are analyzed. The arterial wall does not merely
behave as an elastic vessel, therefore viscoelastic behavior becomes
important. In this context, the viscous and elastic behavior of the
composite, i.e. the arterial wall, is discussed. This includes the
characteristics of a viscoelastic material, i.e. creep phenomenon, stress
relaxation, and hysteresis. These aspects are also applied to veins, except
the differences in distending pressures and collapsibility come into play.
Fundamental principles of fluid mechanics that includes classical laws
and governing equations are provided. This includes Poiseuille’s
9in x 6in b3250 Dynamics of the Vascular System: Interaction with the Heart (2nd Edn) b3250-ch01

Historical Background and Book Contents 11

equation, Bernouilli’s equation and the determining laminar and

turbulent behavior in terms of Reynolds number. This is examined in
terms of the rheology of blood flow to the containing vessel properties.
Engineering methods of basic analysis in the time domain, the Fourier
analysis in the frequency domain are also included with examples that
apply to the vascular system.
Chapter 4 deals with the hemodynamics of large arteries. Aorta is the
largest artery whose distensibility and compliance facilitates ventricular
ejection in systole. The pulsatile wave transmission characteristics of
blood pressure and flow and simplified mathematical description, and
fundamentals of modeling are included. The description classic of the
windkessel model of the arterial system is first introduced. The
windkessel is the mostly used lumped model and its analysis is
elaborated in terms of total arterial system compliance and peripheral
resistance. Extension of this model to more sophisticated later models
include those that vary from a linear rigid tube model to a freely moving
or constrained thin- or thick-walled, viscoelastic tube model. Some of
these utilize Navier-Stokes equations describing fluid motion, Navier
equations describing wall movement, and the equation of continuity
describing the incompressibility of the blood. Experimental deviations
from linear models are compared to nonlinear theories, so as to identify
the regimes of nonlinearities.
Distributed model provide more precise descriptions of the pressure
and flow behavior under varied conditions. However, they are generally
complex and time-consuming in identify individual parameters, and less
useful in daily clinical settings. Reduced models that are useful for
practical and clinical applications are discussed. A recently introduced
model to analyze the arterial wall behavior subject to varying pressure
amplitudes in terms of pressure-dependent compliance is elaborated.
This helps to explain the cyclical stress placed on the arterial wall and
how the arterial wall adjust to rapidly changing pressure amplitudes.
Once models of the arterial system have been developed, it is
necessary to verify the validity and limitations of these models. Such
verifications depend often critically on the specific design of the
experiments for measuring relevant hemodynamic parameters. For all
9in x 6in b3250 Dynamics of the Vascular System: Interaction with the Heart (2nd Edn) b3250-ch01

12 Dynamics of the Vascular System (2nd Edition)

practical purposes, these are pressure, flow, velocity, and vessel

dimensions.
Pulsatile pressure and flow and their transmission characteristics are
also the centerpoints of this chapter. Here, the peculiarities and features
associated with pressure and flow waveforms measured in their
respective anatomical sites are explained. How the vascular beds present
as load to impede blood flow is quantitatively described in terms of the
vascular impedance concept. Impedance, unlike resistance, which
remains constant, is complex with its magnitude changes with frequency.
Its usefulness is in its ability to include alterations in compliance,
resistance and inertance. This provides a useful description of the
changing arterial tree and individual vascular bed behavior. The manner
by which pressure and flow pulses propagate and reflect can also be
quantified.
Chapter 5 addresses the vascular branching aspects of the circulation,
whether of arterial, venous or capillary, except the latter two are dealt in
more detail in subsequent chapters. Branching geometry is examined in
terms of morphological measurements. The basic fluid mechanic aspects
of vascular branching in terms of pressure and flow transmission, shear
stresses are explained, best with illustrations and mathematical
formulations.
How efficient the pressure and flow pulses transmit depends on the
propagation and reflection characteristics through different arteries and
vascular branching junctions. Pulse wave velocity, a popularly used
index to describe the vascular stiffness, is dependent on the geometric
and elastic properties of the local arterial wall. Its measurement is
therefore, elaborated.
With differing vascular impedances, wave reflections arise, because
of the mismatching in impedances. The large peripheral resistances in
the arterioles are the principal sites contributing to reflections. Increased
wave reflection increases blood pressure amplitude and thus decreases
flow. This reduces the pulse transmission efficiency for the propagating
pulse. Pulse transmission through vascular branching junctions is
dictated by the local blood vessel properties. For forward traveling wave,
it is practically impedance-matched, resulting in optimal transmission.
For the backward traveling wave towards the heart, it is greatly
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