(Circulation. 2000;101:1049.)
© 2000 American Heart Association, Inc.
Basic Science Reports |
Proximal Atrioventricular Bundle, Atrioventricular Node, and Distal Atrioventricular Bundle Are Distinct Anatomic Structures With Unique Histological Characteristics and Innervation
From the Department of Medicine, Cardiology, The Feinberg Cardiovascular Research Institute, Northwestern University, Chicago, Ill.
Correspondence to Darlene K. Racker, PhD, Northwestern University Medical School, 303 E Chicago Ave, CH-T 233, Chicago, IL 60611. E-mail darkrac{at}nwu.edu
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Abstract |
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Background—Direct 3D analysis (ie, stereotaxic analysis of 3 planes) has shown that the atrioventricular (AV) node (AVN) is continuous with only specialized myocardium of the proximal AV bundle (PAVB) and distal AV bundle (DAVB) or His bundle. The purpose of the present study was to determine whether the PAVB, AVN, and DAVB possess histological features distinct from each other and from the ordinary myocardium.
Methods and Results—A protocol that preserves the cytoplasmic and
interstitial integrity of the tissue and permits serial
sections of the AV junction region to be made in 3 orthogonal planes
showed that the PAVB, AVN, and DAVB are characterized by
myocardium aggregated into fascicles containing 
8
myofibers. Myofibers within the fascicles are coiled or spiraled about
each other; and spiraling is most compact in the PAVB. Collagen encases
individual fascicles and segregates primary fascicles into secondary
fascicles. Fascicles, and not myofibers, are in parallel array in the
PAVB, interwoven in the AVN, and parallel in the DAVB. Narrow junctions
of parallel fascicles separate the AVN from the PAVB and DAVB.
Myocytes, which are largest in DAVB, possess clear perinuclear regions;
thin finger-like end processes, which are most numerous in the AVN;
uniform, delicate cross-striations; and intercalated disks, which are
broader in the PAVB and form short stacks in the AVN. Sheaves of nerve
terminals, including boutons, are as found in skeletal
muscle.
Conclusions—The PAVB, AVN, and DAVB have distinct histological features. Collagen septation of primary and secondary fascicles presents natural barriers within the tissues and to surrounding myocardium and structures. These findings confirm that the AV junction region contains a specialized conduction system that is anatomically isolated from ordinary myocardium.
Key Words: atrium • atrioventricular node • conduction • collagen • myocytes • nervous system
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Introduction |
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The atrioventricular (AV) junction region and the organization of its ordinary and specialized myocardial tissues have assumed great importance as the focus of radiofrequency catheter ablation therapy of common arrhythmias. The proximal AV bundle (PAVB; atrial bundle), AV node (AVN; Knoten), and distal AV bundle (DAVB; AV or His bundle) were described almost a century ago as an AV bridge of specialized myocardium connecting the atria to the ventricles in many species, including sheep, cat, dog, and humans in dissected hearts and in transverse plane serial sections.1 Nevertheless, the existence of this anatomic bridge was only recently confirmed (Figure 1
, top).2 The tissues have
also been demonstrated to form a functional bridge with discrete
lesions at (1) the DAVB that elicited idioventricular
rhythms3 and (2) at both the PAVB-AVN and AVN-DAVB
junctions that evoked hierarchical automaticity of the AVN with respect
to the DAVB, whereas nearby atrial myocardium showed the
sinus rhythm.4 Moreover, although the tissues exhibit
distinguishing anatomic and
electrophysiological
features,1 2 3 4 5 6 the identity of different components of the
AV bridge myocardium remains
controversial.7 8
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This present report represents a continuation of our correlated anatomic and electrophysiological studies.9 10 11 The purpose of the present study was to determine whether histological criteria can be used to distinguish the PAVB, AVN, and DAVB from each other and from the surrounding ordinary myocardium.
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Methods |
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Eleven adult mongrel dogs weighing 9 to 15 kg were anesthetized with sodium pentobarbital (30 mg/kg IV). As previously described,2 9 10 11 prefixation and postfixation 5% sucrose buffer rinses and Karnovsky’s fixative were used to limit osmotic damage,12 and the hearts were flattened naturally through spreading on a paper towel before fixing. The AV junction region yielded 1 to 3 blocks, depending on the orientation used for sectioning and heart size. Paraffin-embedded tissues blocks were serially sectioned at a thickness of 10 to 15 µm in the parallel (n=5), perpendicular (n=4), or transverse (n=2) plane (Figure 1
, bottom). All sections were mounted on glass microscope slides and
stained with Goldner’s trichrome, Masson’s trichrome, Verhoff’s
elastica, or hematoxylin-phloxine-safran and studied in
photomicrographs taken at intervals of 0.5 mm for transverse and
perpendicular sections and of 0.25 mm for parallel sections. At
selected sites, every section was studied. Goldner’s trichrome was
most useful; myocardium stained brick red; nuclei, black;
nerves and ganglia, magenta; red blood cells, orange; and connective
tissue, blue to green.
Data Analysis
The size of structures were determined through direct
measurement with the use of an ocular micrometer and from
photomicrographs, with photographs of the 1-cm or 0.1-mm rulers
enlarged to the same magnification.
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Results |
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Each plane of section provides histological information that is not apparent in the other planes (Table
). This is exemplified in Figure 2, which shows the macroscopic histology
of the PAVB, AVN, and DAVB in the 3 orthogonal planes. We noted that
anatomic landmarks and tissues have a regular relation with each other
that does not vary in different hearts or with the size of the heart;
this is exemplified by a small sinus appearing regularly in the
anteroinferior lip of the coronary sinus ostium, as
shown here in the perpendicular and transverse sections (Figures 2B and 2C1).
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Histology of the PAVB
The PAVB is composed of small parallel myocardial fascicles (not
myofibers as first described in dissected hearts1 ) along
its full length. Parallel fascicles are displayed in long axis in
parallel (Figures 3A and 3D) and
perpendicular (Figures 4A and 4D) and in
cross section in transverse (Figures 5A and 5D) sections.
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Surprisingly, light microscope high-magnification views revealed that
what appear to be small single myofibers are in reality several
myofibers twisted into single strands (Figures 3D and 4D). These are seen in parallel sections (Figure 3D) but
are most distinct in perpendicular sections (Figure 4D). Neither
individual myofibers nor their disposition within the fascicle is
apparent in transverse sections (Figure 5D).
Connective tissue stains show that individual primary fascicles are
encased by collagen. Collagen septa segregates several primary
fascicles into larger secondary fascicles. Collagen encasement of
individual fascicles can be seen in parallel sections at high
magnification (Figure 3D) and in perpendicular sections at low
magnifications (Figure 4A). Figure 4A shows the collagen
investment prevents casual contact among fascicles within the PAVB and
isolates the PAVB fascicles from the myocardium of the
medial atrial wall and ventricular septum. Transverse
sections clearly show secondary fascicles separated by collagen septa
at low magnification (Figures 5A and 5D). In contrast, elastic
fibers are restricted to the walls of larger blood vessels and the
endocardium.
Goldner’s trichrome–stained parallel sections show that unusual
sheaves of nerve endings extending along lengths of myofibers (Figure 3C) terminate perpendicular to the long axis of the myofiber as
fascicles of boutons, tendrils, and varicosities (Figure 3D).
PAVB myocytes exhibit 4 unique features: a clear perinuclear zone
(Figure 4C), delicate evenly dispersed cross-striations (Figures 3B to 3D), thin cytoplasmic finger-like, end processes (Figure 3D, inset), and wide intercalated disks containing a central
density (Figure 3B, inset). The numbers of intercalated disks
may be underestimated, however, because they may be more difficult to
detect in the tightly twisting and spiraling myofibers.
The PAVB is also characterized by numerous ganglia nestled among its
fascicles (Figures 5A, 5B, and 5D), large blood vessels within
its substance (Figures 4A and 5A) and flanking its
borders (Figures 3A, 4A, and 4D), and fat vacuoles that
bestow a loose appearance on the PAVB in parallel sections (Figure 3A) and are prominent at its ventricular septal
apposition (Figures 5A and 5B). Fat vacuoles are also a
prominent feature of the ordinary atrial myocardium, at
this same level (Figures 5A and 5B).
Histology of the AVN
Several major distinctions exist between the AVN and PAVB. The AVN
is composed of a meshwork of interwoven myocardial fascicles, not
myofibers as previously described.1 3 13 14 15 16 17 18 The
interwoven AVN meshwork immediately follows the PAVB-AVN junction
(Figure 3A), at which point the AVN is also encased within the
central fibrous body (Figures 2B and 2C4). The result of this
massive whorl of fascicles can be appreciated in perpendicular
sections, where primary fascicles displayed in cross-section are
located next to fascicles disposed in the long axis (see Figure 7D). Although the AVN exhibits parallel
fascicles along its periphery (Figures 6A and 7A), thin end processes interlace these fascicles to deeper
ones. In this way, the peripheral myofibers become part and
parcel of the entire meshwork. Intercalated disks, displayed in short
stacks, join myocyte thin processes (Figure 6B). No large blood
vessels or ganglia and few to no fat vacuoles were found.
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The AVN exhibits many anatomic characteristics of the PAVB. Myofibers
are aggregated into fascicles. Collagen encasement of fascicles, which
is discernible in parallel sections at high magnifications (Figure 6D), is most apparent in perpendicular sections (Figures 7A, 7B, and 7D). Transverse sections show
segregation of primary fascicles (Figure 8C) into secondary fascicles by collagen
septa (Figure 8D). Twisted and spiraling myofibers within the
fascicles are apparent in both parallel and perpendicular sections
(Figures 6D and 7D). AVN myocytes display a clear
cytoplasmic perinuclear zone (Figure 6C) and delicate uniform
cross-striations along their full extent, including their fine
finger-like processes (Figures 6C, 6D, and 7C). Sheaves
of myocyte end processes abound in the AVN, where fascicles of thin
processes can be seen (Figures 6B, 6D, and 7C). Fascicles
of nerves pass over thin myocyte processes (Figure 6B) and
terminate on AVN myocytes (Figure 6D, inset). The variety of
fascicles of nerve terminals is especially apparent in the AVN as
varicosities, tendrils, and boutons (Figure 6D).
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Histology of the DAVB
The DAVB is also composed of myocardial fascicles, not single
myofibers as previously described,1 3 13 14 15 16 and differs
from the AVN and PAVB in several major aspects. It is a narrow bundle;
its fascicles are the largest (Figures 9 to 11,
compare Figures 3D, 6D, and 9D) and are disposed
in clusters in transverse sections (Figure 11). DAVB myocytes
display intercalated disks that are longer (Figure 10C) and
thin end processes that are less numerous (Figure 10D). The
fascicles contain tendrils of white nerve fibers that interlace the
myofibers (Figures 11C and 11D), but packets or fascicles of
nerve endings are not apparent (Figure 9D).
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The DAVB exhibits many histological features in common
with the PAVB and AVN, such as the presence of primary fascicles
(Figure 9D) with collagen encasement (Figures 9A and 10A) and secondary fascicle segregation by collagen septa
(Figures 9D, 10D, 11A, 11B, and 11D). Twisted
and spiraling intrafascicular myofibers are apparent in both parallel
and perpendicular sections (Figures 9B, 9D, and 10D).
Myocytes display a clear perinuclear zone (Figure 10B) and
delicate uniform cross-striations along their full extent (Figures 9B to 9D). As in the case of the AVN, no large blood vessels or
ganglia and few to no fat vacuoles are found.
Histology of the PAVB-AVN and AVN-DAVB Junctions
The PAVB and DAVB junctions with the AVN are narrow, which bestows
on the AVN its bulbous shape (Figure 2A). Both junctions are
composed of fascicles in parallel array; abrupt ordering of the
myofibers occurs at the PAVB-AVN junction (Figure 3A) and at the
AVN-DAVB junction (Figure 6A). The PAVB-AVN junction is most
pronounced, in that the rather broad PAVB abruptly narrows (Figure 2A) to a region of <0.25 mm in length and width (Figure 3A). In contrast, the DAVB remains fairly uniform in size after
the abrupt change in fascicle ordering, as seen in both parallel
(Figure 2A) and perpendicular (Figure 2B) sections.
Histology of the Ordinary Myocardium of the AV
Junction Region
Ordinary atrial and ventricular septal
myocardium overlay and underlay the specialized AV bridge
tissues and are arrayed in the well known layers or sheets of myocytes
with little to no collagen separating individual myofibers or tissues.
Only ordinary atrial myocardium contacts the endocardium.
Myocytes exhibit little to no branching and are joined together in an
end-to-end and side-by-side fashion at myocyte step processes by
prominent intercalated disks. No intercalated disk connections were
found between the ordinary atrial or ventricular septal
myocytes and the AV bridge myocytes. No direct appositions were found,
as the latter was segregated by collagen and connective tissue.
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Discussion |
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Morphological features of the PAVB and histology of the AV bridge tissues are demonstrated here for the first time. The PAVB is a relatively extensive structure. It spans the area between the coronary sinus ostium and the posterior half of the medial leaflet and is as long as the AVN and DAVB combined (Figure 2A
).
The PAVB has been overlooked in conventional studies because the PAVB
region is completely (Hudson,3
Figure 2–11; and
Smith et al,17 Figure 2) or partially (Lev et
al,13 Figure 1) excluded, as seen in schematics of AV
junction region tissue blocks. When the PAVB region is schematized,
none of its features appear in the published
histological sections (Becker and
Anderson,16 Figure 1; and Inoue and Becker,19
Figure 1). Fascicular compartmentation of the AV bridge tissues into primary fascicles are similar only to Purkinje fibers, which in fact consist of several myofibers tightly packed into small fascicles (Sommer and Jennings,20 Figure 30) and has been directly demonstrated through the diffusion of iontophoresed Lucifer yellow.10 Secondary fascicles are unique to the AV bridge tissues and provide an anatomic basis for multiple inputs to and through the AVN.8
Connective tissue investment of AV bridge fascicles is the collagen
type and not elastic fibers, as commonly believed.3 13
Collagen septa were shown here to prevent the direct contact of
fascicles within the same tissue and to prevent even casual contact of
the AV bridge tissues with both atrial and ventricular
septal myocardium. This latter factor is an important
consideration because the PAVB, which is subjacent to medial atrial
wall epicardium, is adjacent to the ventricular septum
along its full extent (Figures 2C2 and 2C3).
Spiraling, twisted intrafascicular myofibers are unique to the AV bridge tissues among the organ systems of the body. Myofibers spiraling is most compact in the PAVB and less compact in the DAVB. Thus, the small caliber and compact spiraling myofibers could provide an anatomic basis for different conduction velocities within the tissues. Relative fiber spiraling under basal conditions is PAVB > AVN > DAVB, and relative fiber size is PAVB < AVN < DAVB.
Sheaves of nerve terminals including tendrils (sympathetic),
varicosities (parasympathetic), and boutons (somatic) impinge on AV
bridge myofibers and small blood vessels (Figures 3D and 6D). This is contrary to the current belief that nerves within
the AVN are restricted to single nerve fibers3 13 15 16
and that specialized canine AV junction tissues are devoid of
parasympathetic fibers.16
Clear perinuclear regions were found in the AV bridge myocytes. These represent glycogen storage and are a hallmark of the ventricular conduction system, which uses anaerobic glycogen metabolism, as opposed to the aerobic metabolism preferred by working myocardium, and permits delineation of this system during surgery through the Lugol’s reaction (Sommer and Jennings,20 Figure 29).
Myocyte finger-like end processes (Figures 3D, inset, and
7C) explain the knobby protrusions from the body of the myocytes
displayed in 3-D electron micrograph reconstructions of AVN myocytes by
Thaemert.21 The latter study was limited to 11-µm
lengths. We show the processes are multiples of 10 µm in length
(Figures 3D, inset, and 7C).
Points of Controversy
A number of investigators have examined the AV junction
histologically. Although the same plane of section was
used, major discrepancies are still apparent in schematics of the AV
junction region14 15 16 18 19 22 and in different studies by
the same workers.16 19 23 24 The real AV junction region
tissues were revealed by (1) preservation of the hearts with a protocol
that maintains the ultrastructural integrity of paraffin-embedded
tissues (Racker,12 Figures 1-8 to 1-11), (2)
natural flattening of the hearts so that structures could be viewed in
orthogonal planes at right angles to each other in 360 degrees, and (3)
systematic study of the histological details of the
entire AV junction region in 3 orthogonal planes in photomicrographs. A
comparison of our data with that generated with conventional protocols
reveals that the latter resulted in osmotic damage with a loss of
cytoplasmic (eg, Hudson,3 Figures 2-12C and 2-13C;
James,14 Figures 3B and 3D; and Becker and
Anderson,16 Figure 10) and interstitial (eg,
James,14 Figure 3; McGuire et al,25 Figures 12 and 13;
and Medkour et al,24 Figure 2) details. In
addition, sectioning of the heart in its curved state precludes the
visualization of many histological attributes, as well
as linear relations within and among structures.
Histological details of myocytes, myofibers, and
tissues are also not apparent in orthogonal transverse sections
(Table), which are similar to the classic conventional
transverse or frontal plane sections.3 13 14 15 16 17 18 19 22 23 25
What Is the Atrial or Posterior Input to the AVN?
A comparison of histological data for the atrial
or posterior input identified by other workers with
histological data presented here identifies
these structures as ordinary myocardium of the medial
atrial wall and, by and large, as various parts of its annular
myocardium: terminals of internodal tracts
(James,14 Figures 2B, 6, 7, and 9;
James,23 Figures 6C and 6D), the rightward component of
the compact AVN (Becker and Anderson,16 Figure 8A; Inoue
and Becker,19 Figures 2B, 3, and 5 to 7), the overlay and
transitional myofibers (James,14 Figures 2A and 3B; Becker
and Anderson,16 Figure 2A), with the posterior nodal
extension and compact AVN (Medkour et al,24 Figure 2) and
the AV nodal ring input being analogous to part or all of the
circumferential lamina encircling the tricuspid valve (McGuire et
al,25 Figures 11 and 12) and all of the ordinary atrial
myocardium of the AV junction region (Sanchez-Quintana et
al,18 Figure 2). Moreover, the PAVB is aligned with the
medial or upper leg of Koch’s triangle (Figure 2A).
Importantly, the circumferential lamina runs parallel to the annulus,
aligned with the lower leg of Koch’s triangle; these myofibers are
referred to as the posterior nodal extension (Medkour et
al,24 Figure 2) and the AV nodal ring myofibers (McGuire
et al,25 Figures 11 and 12). Because the ordinary
myocardium is physically isolated from the AVN and PAVB by
connective tissue and collagen ensheathment, this connective tissue
isolation prevents even casual contact of the 2 classes of
myocardium.
What Are the AV Junction Region Transitional Cells?
Transitional cells are envisioned as connecting ordinary atrial
myocardium to the AVN as listed above (eg, Ho et
al22 ) and are in fact ordinary atrial
myocardium that appear to be contiguous with the AV bridge
tissues when not carefully viewed in 3 planes.
What Is the AVN or the Compact AVN?
What has been termed by many investigators the AVN
(Hudson,3 Figure 2-12; Lev et al,13 Figure 4;
Truex and Smythe,15 Figure 3; James,23 Figure 8) or the compact AVN (Becker and Anderson,16 Figures 2 and 4; Inoue and Becker,19 Figure 2A; Ho et
al,22 Figure 2) is in fact restricted to the PAVB-AVN
junction, which is composed of fine-caliber parallel fascicles. Because
the PAVB-AVN junction is outside of the central fibrous body and not
even protected by Todaro’s tendon (Figure 2A), as is the PAVB
(Figures 2C2 and 2C3) and because of its minute size (Figure 3A), it is more sensitive to heat, and discrete lesions are more
likely to cause complete AVN block. On the basis of the present
results, the area anterior to the PAVB-AVN junction is an interwoven
mass of myocardium (Figures 2A and 3A), is
coincident with the appearance of the central fibrous body (sleeve of
connective tissue separating AVN from the medial atrial wall (Figure 2B), and should be defined as the AVN.
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Acknowledgments |
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This work was supported by the Northwestern Memorial Foundation, Jadwiga Roguska-Kytes (grant NMH 572), and NIH grants HL-40667 and HL-30557 (to Dr Brian F. Hoffman). We thank Dr Brian F. Hoffman for leading the way. The photographic assistance of Vanessa Jones and Gail Alfred is gratefully acknowledged. We are indebted to Dr Hsueh-Hwa Wang for dedication to this body of work, for careful reading of the manuscript, and for helpful discussion and suggestions.
Received April 20, 1999; revision received August 30, 1999; accepted September 7, 1999.
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References |
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TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
1. Tawara S. Die topographie und histologie der bruckenfasern: ein beitrag zur lehre von der bedeutung der Purkinjeschen faden. Zentralbl Physiol. 1906;19:70–76.
2. Racker DK. The atrioventricular node and input pathways: a correlated gross anatomical and histological study of the canine AV junctional region. Anat Rec. 1989;224:336–354.[Medline] [Order article via Infotrieve]
3. Hudson RE. The conduction system. In: Hudson RE, ed. Cardiovascular Pathology. Vol 1. Baltimore, Md: Williams & Wilkins; 1965.
4.
Racker DK. Sinoventricular
transmission in 10 mM K+ by canine
atrioventricular nodal inputs: superior atrionodal
bundle and proximal atrioventricular bundle.
Circulation. 1991;83:1738–1753.
5. Hoffman BF, Paes de Carvalho A, DeMello WC. Transmembrane potentials of single fibres of the atrio-ventricular node. Nature. 1958;181:66–67.
6. Scher AM, Rodriquez MI, Liikane J, Young AC. The mechanism of atrioventricular conduction. Circ Res. 1959;54–61.
7. Racker DK. Transmission and reentrant activity in the sinoventricular conducting system and in the circumferential lamina of the tricuspid valve. J Cardiovasc Electrophysiol. 1993;4:513–525.[Medline] [Order article via Infotrieve]
8. Sung RJ, Lauer MR, Chun H. Atrioventricular reentry: current concepts and new perspectives. Pacing Clin Electrophysiol. 1994;17:1413–1430.[Medline] [Order article via Infotrieve]
9.
Racker DK, Ursell PC, Hoffman BF.
Anatomy of the tricuspid annulus circumferential myofibers as
the structural basis for atrial flutter in a canine model.
Circulation. 1991;84:841–851.
10. Racker DK. The demonstration of intercellular coupling between cells of the canine distal AV bundle using Lucifer yellow-CH and histological sections. J Mol Cell Cardiol. 1989;21:479–493.[Medline] [Order article via Infotrieve]
11. Racker DK. The AV junction region of the heart: a comprehensive study correlating gross anatomy and direct three-dimensional analysis, part I: architecture and topography. Anat Rec. 1999;256:49–63.[Medline] [Order article via Infotrieve]
12. Racker DK. Principles of specimen preparation. In: Transmission Electron Microscopy: Methods of Application. Springfield, Ill: Charles C. Thomas; 1983.
13. Lev M, Widran J, Erickson EE. A method for the histopathologic study of the atrioventricular node, bundle and branches. Arch Pathol. 1951;52:73–83.
14. James TN. Morphology of the human atrioventricular node, with remarks pertinent to its electrophysiology. Am Heart J. 1961;62:756–771.[Medline] [Order article via Infotrieve]
15. Truex RC, Smythe MQ. Reconstruction of the human atrioventricular node. Anat Rec. 1967;158:11–20.[Medline] [Order article via Infotrieve]
16. Becker AE, Anderson RH. Morphology of the human atrioventricular junctional area. In: Wellens HJ, Lee KI, Janse MJ, eds. Conduction System of the Heart. Philadelphia, Pa: Lea & Febiger; 1976.
17. Smith A, Ho SY, Anderson RH. Histological study of the cardiac conduction system as a routine procedure. Med Lab Sci. 1977;34:223–229.[Medline] [Order article via Infotrieve]
18. Sanchez-Quintana D, Davies W, Ho SY, Oslizlok PO, Anderson RH. Architecture of the atrial musculature in and around the triangle of Koch: its potential relevance to atrioventricular nodal reentry. J Cardiovasc Electrophysiol. 1997;8:1396–1407.[Medline] [Order article via Infotrieve]
19.
Inoue S, Becker AE. Posterior extensions of the
human compact atrioventricular node: a neglected
anatomic feature of potential clinical significance.
Circulation. 1998;97:188–193.
20. Sommer JR, Jennings RB. Ultrastructure of cardiac muscle. In: Fozzard HA, Haber E, Jennings RB, Katz AM, Morgan HE, eds. The Heart and Cardiovascular System. Vol 1. New York, NY: Raven Press; 1986.
21. Thaemert JC. Atrioventricular node innervation in ultrastructural three dimensions. Am J Anat. 1970;128:239–264.[Medline] [Order article via Infotrieve]
22. Ho SY, Kilpatrick L, Kanai T, Germroth PG, Thompson RP, Anderson RH. The architecture of the atrioventricular conduction axis in dog compared to man: its significance to ablation of the atrioventricular nodal approaches. J Cardiovasc Electrophysiol. 1995;6:26–39.[Medline] [Order article via Infotrieve]
23. James TN. The connecting pathways between the sinus node and the A-V node and between the right and the left atrium in the human heart. Am Heart J. 1963;66:498–508.[Medline] [Order article via Infotrieve]
24.
Medkour D, Becker AE, Khalife K, Billette J.
Anatomic and functional characteristics of a slow pathway role in dual
pathway physiology and reentry. Circulation. 1998;98:164–174.
25.
McGuire MA, deBakker JMT, Vermeulen J, Ophthof T,
Becker AE, Janse MJ. Origin and significance of double potentials near
the atrioventricular node correlation of extracellular
potentials, intracellular potentials, and histology.
Circulation. 1994;89:2351–2360.
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A. E. Becker, R. H. Anderson, D. K. Racker, and A. H. Kadish Proximal Atrioventricular Bundle, Atrioventricular Node, and Distal Atrioventricular Bundle Are Distinct Anatomic Structures With Unique Histological Characteristics and Innervation Response Circulation, February 13, 2001; 103 (6): 30e - e31. [Full Text] [PDF]
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D. Franco and J. M. Icardo Molecular characterization of the ventricular conduction system in the developing mouse heart: topographical correlation in normal and congenitally malformed hearts Cardiovasc Res, February 1, 2001; 49(2): 417 - 429. [Abstract] [Full Text] [PDF]
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J. P. Kucera and Y. Rudy Mechanistic Insights Into Very Slow Conduction in Branching Cardiac Tissue: A Model Study Circ. Res., October 26, 2001; 89(9): 799 - 806. [Abstract] [Full Text] [PDF]
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