Clinical Cardiac Electrophysiology in the Young - 1st Edition

Visit the link below to download the full version of this book:

https://medipdf.com/product/clinical-cardiac-electrophysiology-in-the-young-1st-
edition/

Click Download Now

 This book was written by all of us
because of our parents and teachers,
with our spouses and partners,
for our and all children.
 Contributors

Mohamad Al-Ahdab, M.D., Lecturer, Uni- Ian H. Law, M.D., Associate Professor of
versity of Michigan Medical School, Ann Pediatrics, University of Iowa Medical
Arbor, Michigan School, Iowa City, Iowa
David Bradley, M.D., Assistant Professor of Sarah Leroy, Clinical Nurse Specialist and
Pediatrics, Pediatric Cardiology, University Nurse Practitioner, Pediatric Electrophysiol-
of Utah Medical School, Salt Lake City, Utah ogy and Anti-Arrhythmia Device Clinics,
University of Michigan Medical School, Ann
Burt Bromberg, M.D., Pediatric Cardiolo-
Arbor, Michigan
gist and Electrophysiologist, St. Louis, MO
Mark Russell, M.D., Associate Professor of
Craig Byrum, M.D., Associate Professor
Pediatrics, University of Michigan Medical
of Pediatrics, Upstate Medical School, New
School, Ann Arbor, Michigan
York University, State University of New
York, Syracuse, New York. Elizabeth V. Saarel, M.D., Assistant Profes-
sor of Pediatrics, Cleveland Clinic Founda-
Robert M. Campbell, M.D., Associate Pro-
tion, Cleveland, Ohio
fessor of Pediatrics, Children’s Heart Center,
Emory University, Atlanta, Georgia William A. Scott, M.D., Professor of Pedi-
atrics, Southwestern Texas Medical School,
Macdonald Dick II, M.D., Professor of
Dallas, Texas
Pediatrics, University of Michigan Medical
School, Ann Arbor, Michigan Gerald Serwer, M.D., Professor of Pe-
diatrics, University of Michigan Medical
Parvin Dorostkar, M.D., Associate Profes-
School, Ann Arbor, Michigan
sor of Pediatrics, Rainbow Babies and Chil-
dren’s Hospital, University Hospitals Health Christopher B. Stefanelli, M.D., Pediatric
Systems, Cleveland, Ohio Cardiologist, Tacoma, Washington
Peter S. Fischbach, M.D., Assistant Profes- Margaret Strieper, D.O., Associate Profes-
sor of Pediatrics and Pharmacology, Univer- sor of Pediatrics, Children’s Heart Center,
sity of Michigan Medical School, Ann Arbor, Emory University, Atlanta, Georgia
Michigan
Stephanie Wechsler, M.D., Associate
Carlen Gomez, M.D., Associate Professor of Professor of Pediatrics, University of
Pediatrics, University of Michigan Medical Michigan Medical School, Ann Arbor,
School, Ann Arbor, Michigan Michigan

vii
 Preface

It takes a certain hubris to come forth with a This book emerges from the clinical
book entitled Clinical Cardiac Electrophys- practice and research of the pediatric cardiac
iology in the Young. There are a number electrophysiology group in the Division of
of excellent texts, monographs, and reviews Pediatric Cardiology at the C.S. Mott Chil-
on cardiac arrhythmias in both adults and dren’s Hospital, the University of Michigan
children—Josephson’s and also Zipes and in Ann Arbor, and the former pediatric elec-
Jalife’s comprehensive texts come to mind, as trophysiology fellows from Michigan, now
well as a number of others, including Deal, established electrophysiologists in their own
Wolff, and Gelband’s, the several volumes right. It represents a compilation of the clini-
from Gillette, and the recent text from Walsh, cal course, electrocardiograms, electrophysi-
Saul, and Triedman, the latter three texts fo- ologic studies, pharmacological management,
cusing on children. and transcatheter ablation therapy in patients
Nonetheless the past three decades have from infancy through young adulthood seen in
witnessed enormous advances in the under- Ann Arbor and at the current clinical sites of
standing and management of human cardiac the former Michigan fellows. Thus, while the
arrhythmias. This development represents the product may be idiosyncratic, it is not provin-
fruits of both basic and clinical investigations cial. We are interested in “how it is done” but
in cardiac impulse formation and propagation not to the exclusion of other approaches. This
at the organ, tissue, and more recently, cel- is only one (or several) way to address the
lular and molecular levels. This information clinical problem of arrhythmias in children,
explosion may result in information overload and surely not the only way, especially as one
and frustrate the student, the young physi- views the future of emerging energy sources
cian in training, as well as the seasoned prac- for ablation, non-ionizing radiation imaging
titioner. This book focuses on the practical techniques, and molecular diagnostic possi-
(and theoretical when applicable) aspects of bilities.
clinical electrophysiology of cardiac arrhyth- The book is divided into two parts.
mias in the young. Our intention is that the The first part, Background (Chapters 1–3),
young house officer or mature physician who discusses the cardiac conduction system—
is faced with a child with a cardiac arrhyth- development, anatomy, and physiology.
mia will find this book useful in increasing Particular attention is directed to the clinical
their understanding, sparking their interest, electrophysiology of the cardiac conduction
and perhaps leading them to a therapeutic system and the techniques of electrophysio-
solution. logic study that are specific to children and

ix
x PREFACE

that have been developed and practiced at the A text or technical book is rarely the
University of Michigan and at other centers. product of a single individual. With that in
The second part, Cardiac Electrophysiology mind, any value or sense that can be made of
in Infants and Children (Chapters 4–23), this work is solely due to the terrific efforts
focuses on the clinical science of cardiac of the authors; any error or fault can be cor-
arrhythmias in infants and children. rectly attributed to me. I am deeply grateful
Chapters 4–12 discuss the mechanism, to all of the authors for their contributions, as
the ECG characteristics, the electrophysio- well as their patience in bringing the project
logic findings, the treatment, and the progno- together. I want to recognize the generosity of
sis of tachyarrhythmias. Chapters 13–16 focus my colleagues at Michigan in providing cov-
on bradyarrhythmias. Chapters 17–20 address erage when I would hide out (including a sab-
certain specialized subjects, including, syn- batical) to work on the text. Thanks also to the
cope, cardiac pacemakers, implantable car- medical electrophysiology group at Michigan
diac defibrillators, genetic disorders of the for encouragement and support for the pedi-
cardiac impulse, fetal arrhythmias, and sud- atric program. I also want to thank my local
den cardiac death as it occurs in the young. editor, Kathryn Clark, for all her efforts in
Chapters 21–22 center on the pharmacology keeping me on task, endlessly and repeatedly
of antiarrhythmic agents, indications for use, formatting the multiple revisions of the text,
doses, side effects and toxicity, as well as and finding and eliminating too many exam-
on transcatheter arrhythmia ablation. Finally, ples of “nonsense” to count. Finally, I want to
what the practitioner can expect to see from thank Melissa Ramondetta at Springer for her
the impact of cardiac arrhythmias on the life great patience, great good humor, and sound
of the patient and family is discussed from the advice throughout the course of the project.
nursing point of view in Chapter 23. Carolin, my wife, graciously permitted me to
The intent of the book is practical and weed the book of its unwanted wordage (prob-
thus the suggested readings are selected and ably missed a bit) rather than our yard of un-
not encyclopedic. They are meant as a starting wanted plant life on numerous weekends.
place for the interested reader. Examples and
tables are included in the anticipation that the Macdonald Dick II, M.D.
reader will rapidly be able to match the clinical Ann Arbor, MI
problem to the examples and the accompany- August, 2005
ing text.
 Foreword

The text of Clinical Cardiac Electrophysiol- professionals. The rapid advances in the field
ogy in the Young provides a systematic ap- in such areas as interventional and surgical
proach to the anatomy, pathophysiology, ba- cryoablation techniques, complexity of rhy-
sic electrophysiology, diagnosis and therapy thm disturbances, new monitoring devices and
of atrial and ventricular arrhythmias as well pharmaceuticals make it an invaluable text.
as conduction abnormalities in the young. It Dr. Macdonald Dick as an author and edi-
elucidates the broad spectrum of rhythm dis- tor of the book is an internationally recognized
turbances that may occur from the fetus to scholar and clinical pediatric electrophysiol-
young adult, as an isolated abnormality, in the ogist. A superb teacher and role model for
presence of underlying congenital heart dis- trainees and faculty his affability and diligent
ease, both prior to and subsequent to surgical effort have brought about the compilation and
repair. The clinical manifestations, diagnosis publication of the book. The majority of the
and appropriate pharmacologic and interven- knowledgeable and experienced contributors
tional therapy by a trained healthcare team are have received their training in pediatric car-
fully discussed. Science is consistently used diology at the University of Michigan. The
to explain the electrophysiologic diagnoses, authors are indebted to their medical and sur-
pharmacologic, interventional and surgical gical colleagues, fellows, family members and
treatment. Some prior knowledge and under- respective institutions for the support and en-
standing of electrophysiology and rhythm dis- couragement in the endeavor.
turbances is helpful and the information pro-
vided here may be utilized as a guidebook, Amnon Rosenthal, MD
resource and reference for residents, cardiol- Professor of Pediatrics
ogy fellows, trained cardiologists and elec- University of Michigan Medical School
trophysiologists as well as other allied health Ann Arbor, MI

xi
 Contents

I. BACKGROUND

1 Development and Structure of the Cardiac Conduction System 1

Parvin Dorostkar

2 Physiology of the Cardiac Conduction System 17

Peter S. Fischbach

3 Clinical Electrophysiology of the Cardiac Conduction System 33

Macdonald Dick II, Peter S. Fischbach, Ian H. Law, and William A. Scott

II. CLINICAL ELECTROPHYSIOLOGY IN INFANTS AND CHILDREN

4 Atrioventricular Reentry Tachycardia 51

Ian H. Law

5 Atrioventricular Nodal Reentrant Tachycardia 69

David J. Bradley

6 Persistent Junctional Reciprocating Tachycardia 83

Parvin C. Dorostkar

7 Sinoatrial Reentrant Tachycardia 91

Macdonald Dick II

8 Intra-atrial Reentrant Tachycardia—Atrial Flutter 95

Ian H. Law and Macdonald Dick II

9 Atrial Fibrillation 115

Peter S. Fischbach

10 Atrial Ectopic Tachycardias/Atrial Automatic Tachycardia 119

Burt Bromberg

xiii
xiv CONTENTS

11 Multifocal Atrial Tachycardia 135

David J. Bradley

12 Ventricular Tachycardia 139

Craig Byrum

13 Sick Sinus Syndrome 153

William A. Scott

14 First- and Second-Degree Atrioventricular Block 163

William A. Scott

15 Complete Heart Block—Third-Degree Heart Block 173

Mohamad Al-Ahdab

16 Syncope 183
Margaret Strieper, Robert M. Campbell, William A. Scott

17 Cardiac Pacemakers and Implantable Cardioverter-Defibrillators 195

Gerald S. Serwer and Ian H. Law

18 Genetic Disorders of the Cardiac Impulse 217

Mark W.W. Russell and Stephanie Wechsler

19 Fetal Arrhythmia 241

Elizabeth V. Saarel and Carlen Gomez

20 Sudden Cardiac Death in the Young 257

Christopher B. Stefanelli

21 Pharmacology of Antiarrhythmic Agents 267

Peter S. Fischbach

22 Transcatheter Ablation of Cardiac Arrhythmias in the Young 289

Macdonald Dick II, Peter S. Fischbach and Ian H. Law

23 Nursing Management of Arrhythmias in the Young 315

Sarah Leroy

Index 327
 I

Background
 1

Development and Structure of the

Cardiac Conduction System
Parvin Dorostkar

In the adult mammalian heart, the primary car- in characteristics make a focused study of
diac impulse is ultimately driven by the sinoa- the specialized conduction system very dif-
trial (SA) node, which contains the leading ficult. However, the conduction system cells,
pacemaker cells of the mature human heart. once matured, exhibit subcellular elements
The generated impulse then travels through that differentiate these cells from other work-
the atrial myocardium to the atrioventricular ing myocytes, such as connexins (in the my-
(AV) node. Here a delay in conduction occurs, ocardial cell membrane), and contractile and
after which the impulse is rapidly transmitted cytoskeletal proteins (intramyocardial).
from the AV node through the His-Purkinje A number of investigators have stud-
system to the ventricular myocardium. It is the ied the embryologic formation and develop-
peripheral His-Purkinje system that transmits ment of the heart. Animal models have been
the impulse to the ventricular myocardium, used extensively to study the development of
which, in conjunction with electromechani- the heart and the cardiac conduction system.
cal coupling, results in myocardial contraction However, interspecies variability and multi-
from the apex of the heart toward the base of ple challenges associated with the study of
the heart, generating cardiac output with each the early embryo have made the quest to un-
beat. ravel the many interrelated factors of cardiac
Even though the cardiac conduction sys- development difficult.
tem in its function and anatomy is considered In the chick embryo, which has been
quite separate from the working myocardium studied in detail, the earliest development of
of the heart, it is virtually indistinguishable the heart occurs in the cardiac progenitor cells
from adjacent myocardial tissue by gross visu- originating from the embryonic mesoderm.
alization. Even on a cellular and microscopic There are specific “heart-forming fields”
level the cells are indistinguishable. Cells of where the cells will develop and produce beat-
the conduction system as well as all other my- ing tissue. In chicks, cells designated to form
ocardial cells are capable of contraction, au- the heart arise lateral to the primitive streak,
tomaticity, intercellular conduction, and elec- which can be identified during Hamburger
tromechanical coupling. These similarities Hamilton (HH) stage 3 of chick embryo

3
4 DEVELOPMENT AND STRUCTURE OF THE CARDIAC CONDUCTION SYSTEM

sors. By HH stage 10, the chick heart primor-

a
dia fuse to form a tubular heart with the ante-
d rior most region of the cardiac tube giving rise
to an outflow region or conotruncus or bulbus
cordis. In the chick embryo, the most cau-
dal portion contributes to the most posterior
b
end of the heart and will result in the inflow
region or the sinoatrial region. This primary
e
heart tube undergoes peristalsis-like contrac-
c tions that support unidirectional flow. In the
mammalian heart, the formation of the cardiac
tube occurs in six, similar, successive stages,
AP which support transformation of a flat cardio-
genic crest into a cardiac tube. During this
process the outer contour of the myocardial
crescent folds around the fusing endocardial
v
vesicles. This primitive heart tube consists of
the endocardium with adjacent myocardium
and has slowly conducting contractions that
f
support peristaltic movements. Within this
primitive heart tube fast-conducting atrial
and ventricular myocytes develop. The fast-
VP VP conducting atrial and ventricular myocytes,
however, remain next to the slowly conduct-
FIGURE 1. Formation of the cardiac tube. Transforma-
tion of the flat cardiogenic crescent into a cardiac tube
ing tissue, which eventually gives rise to the
is displayed. During this process the red outer contour inflow tract, AV canal area, and outflow tract.
of the myocardial crescent (grey) folds around the fusing As development proceeds, the slow conduct-
endocardial vesicles (yellow) and passes the blue inner ing areas give rise to the SA node (around
contour of the crescent, thereby forming the cardiac tube. the inflow area), the AV node, and the slowly
AP = anterior pole, VP = venous pole, V = future ven-
tricle. Reprinted with permission from AFN Moorman
conducting outflow tract, whereas the fast
et al., Development of the cardiac conduction system, conducting atrial and ventricular cells give
Circulation Research 1998; 82:629–644. rise to the His-Purkinje system and its ramifi-
cations. During development, alternating slow
and fast conducting segments support unidi-
development (Figure 1). These cells migrate rectional flow and are responsible for the em-
rostrolaterally to form the lateral plate. Color bryonic ECG. Alternating fast and slow con-
patterns in Figure 1 show the region of the duction also prevent relaxation of the atrial
embryo that gives rise to precardiac cells, or ventricular segments before contraction of
which will eventually contribute to the devel- a downstream segment, therefore, minimiz-
opment of myocardium. The relative anterior– ing regurgitating blood. As polarity develops
posterior positions of precardiac cells in the in the vertebrate heart, there is an increase in
primitive streak is maintained in the heart phenotypic atrial cells posteriorly and an in-
field in the mesoderm and continues during crease of phenotypic ventricular cells anteri-
HH stage 5 through 7 of development. At HH orly. Highest pacemaker activity (highest beat
stage 8, the embryo folds ventrally, generat- frequency) can then be observed in cells as-
ing the foregut and somatic and splanchnic sociated with the intake portion of the cardiac
layers of the mesoderm. The splanchnic layer tube (atrial cells); this phenomenon occurs at
of the mesoderm contains myocardial precur- the human embryonic age of about 20 days.
 DEVELOPMENT AND STRUCTURE OF THE CARDIAC CONDUCTION SYSTEM 5

DEVELOPMENT OF IMPULSE develop into an anatomically distinct SA node

GENERATION is still unclear.

The early cardiac mesoderm arises from

ectodermal tissue and subsequently forms the DEVELOPMENT OF IMPULSE
cardiac tube, which has polarity along its ante- PROPAGATION
rior posterior axis. As mentioned previously,
a straight heart tube is present at about day The primary myocardium is character-
20 of human embryonic life, while cardiac ized by action potentials that are primarily
looping occurs at about day 21. The polarity supported by slow voltage-gated calcium ion
of the mammalian heart is characterized by channels. As embryonic atrial and ventricular
the predominance of an atrial tissue pheno- chambers develop, synchronous contractions
type posteriorly at the inflow region of the of these chambers are characterized by higher
heart or upstream side of the heart and of conduction velocities, which are more likely
the ventricular tissue phenotype anteriorly at associated with fast voltage-gated sodium
the outflow or downstream region of the heart. channels. These variations in conduction are
Dominant pacemaker activity and highest beat accompanied by the development of an adult
frequency are found at the intake of the heart type ECG that reflects the sequential activa-
tube. Here an efficient contraction wave is tion of the atrial and ventricular chambers
generated. Cells of the primary cardiac tube rather than the presence of a morphologically
and the future sinus node region show action recognizable conduction system. For exam-
potentials resembling those of the adult pace- ple, a noted AV delay is present before the de-
maker cells. These action potentials display velopment of a morphologically identifiable
slow depolarization and are similar to those of AV node. This AV delay occurs in the region
pacemaker cells that are associated with slow of the AV canal, which is recognized as an
voltage-gated calcium ion channels. Cells of area of slow conduction. Segments of slowly
the future ventricles, however, show action conducting primary myocardium also persist
potential behavior similar to that of adult ven- at both the inflow and outflow area of the heart.
tricles exhibiting action potentials that have Several theories exist regarding the de-
high amplitudes similar to action potentials velopment of the specialized conduction sys-
associated with fast voltage-gated sodium tem (i.e., the AV node and its penetrating
channels. bundles and bundle branches). Using a mon-
As the heart develops, the frequency of oclonal antibody against a specific neural
the intrinsic beat rate increases along the in- marker (G1N2), several investigators have
flow tract of the heart. In both birds and mam- suggested that there is a process of differ-
mals, the leading pacemaker area is initially entiation that supports the development of a
found on the left side but as soon as the sinus myocardial ring that encircles the presump-
venosus has formed (at approximately 25 days tive foramen between the developing right
in the human), the right side becomes more and left ventricles. These investigators sug-
dominant. Both right and left inflow tracts will gest that the dorsal portion of this ring will
become incorporated into the future, mature develop the AV bundle whereas parts cover-
right atrium. “Node-like cells” develop in the ing the septum will give rise to the right and
right atrium. Such cells have also been found left bundles (Figures 2 and 3). However, sev-
in the myocardium surrounding the distal por- eral investigators suggest that ventricular de-
tion of the pulmonary veins in adult rats and polarization undergoes a transition, where the
appear to play a role in preventing regurgita- myocardium undergoes a switch from base-
tion of blood into the pulmonary veins from to-apex depolarization of the ventricular my-
the left atrium. How leading pacemaker cells ocardium to an apex-to-base depolarization
6 DEVELOPMENT AND STRUCTURE OF THE CARDIAC CONDUCTION SYSTEM

ERA ELA

OFT
IFT AVC

ERV ELV
a b
ERA ELA

OFT
IFT AVC

FIGURE 3. Development of the ventricular conduction

system. a. Drawing of a prototypical heart, in which the
ERV position of the ventricular conduction system is indicated,
ELV
including those parts that are only present in the fetal
C d mammalian heart. The entire system persists in the adult
chicken heart. b. Section of a 5-week human heart im-
FIGURE 2. Formation of the cardiac chambers. Scan- munostained for the presence of GlN2 in which the posi-
ning electron photomicrographs (a and c) and schematic tion of the developing conduction system is represented
representations (b and d) of a 3-day embryonic chicken in brick red. c–e. Drawings representing the development
heart, where the first signs of the ventricles emerge (a of the ventricular conduction system based on reconstruc-
and b), and of a 37-day embryonic human heart with tions of GlN2 expression in developing hearts at ≈5 (c),
clearly developed ventricles (c and d). ERA = indicates ≈6 (d), and ≈7 (e) weeks of development. See text for
embryonic right atrium; ELA = embryonic left atrium; explanation. RAORB = retro-aortic root branch; SB =
ELV = embryonic left ventricle; and ERV = embryonic septal branch; RAVRB = right atrioventricular ring bun-
right ventricle. The atrial segment is indicated in blue; dle; LBB and RBB = left and right bundle branches,
the ventricular segment, in red; and the primary heart respectively; LA = left atrium; LV = left ventricle;
tube, encompassing the flanking segments, IFT, AVC, RA = right atrium; RV = right ventricle; AO = aorta;
and OFT, as well as the atrial and ventricular parts, in and PT = pulmonary trunk. Reprinted with permission
purple. Reprinted with permission from AFN Moorman from AFN Moorman et al., Development of the cardiac
et al., Development of the cardiac conduction system, conduction system, Circulation Research 1998; 82:629–
Circulation Research 1998; 82:629–644. 644.

in the mature, intact His-Purkinje system. A The authors suggest that the switch may occur
transition in the ventricular myocardial de- because the His-Purkinje system has matured,
polarization pattern was demonstrated using and the muscular AV junction is then able to
monoclonal antibodies to the polysialylated support and limit the avenue of AV conduction
neural cell adhesion molecule and the HNK-1 to the His-Purkinje system, allowing rapid im-
sulfated carbohydrate epitope. In the chick pulse propagation to the apical myocardium.
embryo, HH stage 30 appears to represent a The mature AV node as a nodal structure
critical period in the morphogenesis of the becomes only gradually identifiable after
heart. The primitive myocardium has slow about Carnegie stage 15 (5 weeks of human
conduction; however, faster conduction along development).
ventricular myocardium has been observed as In summary, during the process of cham-
early as HH stage 23. This fast conduction ber formation, fast conducting atrial and ven-
is functionally distinct from slow conduction tricular segments are being formed within
around HH stage 28, just before the transi- slowly conducting primary myocardium of
tion period. Because activation of the ventri- the embryonic heart tube so that the car-
cles occurs base-to-apex, the developing His- diac tube becomes a composite of alternating
Purkinje system is still thought to be relatively slow and fast conducting segments that persist
immature at this stage. At HH stage 30, this in a more specialized fashion in the mature
sequence reverses and becomes apex-to-base. heart. The molecular basis underlining such
 DEVELOPMENT AND STRUCTURE OF THE CARDIAC CONDUCTION SYSTEM 7

compartmentalization is still poorly under- the absence of fast sodium currents. The poor
stood and continues to be studied. coupling of nodal cells appears to be a require-
ment for the expression of an action potential
by these nodal myocytes, which differenti-
CELLULAR DEVELOPMENT ates itself from the much more abundant atrial
OF “NODAL” PHENOTYPE and/or ventricular working myocardium. This
difference in connexin concentration has been
In the mature heart, the nodal myocytes an important marker for nodal-specific tissue.
display a number of embryonic characteris- An abrupt rather than gradual increase in the
tics. Nodal cells are poorly distinguishable number of gap junctions is found at the transi-
from surrounding myocardium in the early tion of nodal tissue to working myocardium.
embryonic heart as they exhibit many of the This boundary is thought to be due to a de-
same characteristics as the surrounding my- crease in the number of nodal cells towards the
ocardium. However, with development, it ap- atrial working myocardium rather than a gra-
pears that nodal cells retain some of the same dient due to a change in molecular phenotype.
characteristics as early embryonic myocytes
such as organized actin and myosin filaments Cytoskeletal Proteins
and poorly developed sarcoplasmic reticu-
lum. In addition, nodal cells express differ- Nodal-specific developmental expres-
ent structural and cellular markers which are sion of contractile proteins such as myosin
species-specific. Several classes of markers heavy chain and its isoforms, desmin and
have been identified including connexins, spe- neurofilament, has been used to delineate
cific contractile proteins, desmin, and neuro- the sinoatrial and AV nodes. However, inter-
filament that provide specific markers for the species variability in the staining of these
study of conduction system development. In markers does not allow enough consistent data
addition, antibodies to carbohydrate markers to draw a definitive global conclusion in rela-
such as the polysialylated neural cell adhe- tion to development or morphologic changes
sion molecule and HNK1 have been used to that are specific to the conduction system or
study the development of specific regions of its development and differentiation.
the specialized conduction tissue.
Cell Markers
Connexins
Nodal tissue seems to acquire unique
The transmission of the electrical action characteristics during development, including
potential is thought to be primarily associ- the expression of higher amounts of calcium-
ated with gap junctions. Gap junctions are release channel/type-1 inositol triphosphate
aggregates of membrane channels, composed receptor, gamma enolase, alpha 1 and alpha
of protein subunits named connexins that are 2 of the sodium pump, G-protein alpha sub-
encoded by a multi-gene family. Five dif- unit, and angiotensin II receptor. The role of
ferent connexins are expressed in the mam- these differences remains to be studied.
malian heart including connexin 37, 40, 43,
45, and 46. In the early myocardium, both
number and size of gap junctions are small ANATOMIC DEVELOPMENT
but they increase during development. The OF THE SPECIALIZED
number of gap junctions remains scarce in the CONDUCTION TISSUE
developing SA node and the AV node. The
low abundance of connexin expression in the The AV node structure appears to arise
nodes corresponds with both the slow con- from “primordia cells” that originate from the
duction velocities observed in the nodes and myocardium of the posterior wall of the AV