ventricular anatomy for the special electrophysiologist (part...

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SPECIAL REVIEW 6 Journal of Cardiac Arrhythmia Ventricular Anatomy for the Electrophysiologist (Part I) 서울대학교 의과대학 병리학교실 서정욱 ABSTRACT Anatomy of the conduction system for electrophysiologists is reviewed in two parts. This first part details the historical sequence of discovery of the morphology of the conduction system, current or past issues on the morphology of conduction system and basic anatomy of the conduction system. Key words: conduction system of heart arrhythmia Purkinje network Introduction Anatomic substrates of normal or abnormal conduction of electrical stimulation in the heart are far less studied compared to electrophysiologic mechanisms. 1 Studies on the pathology of the cardiac conduction system, summarizing key morphologic features of the major conduction axis and the disposition of the conduction system at a macroscopic level, are still important contents for electrophy siologists. 2,3 There is a Korean study on the histological findings of conduction systems. 4 This review illustrates the historical sequence on the understanding of the conduction system and its basic anatomy, after that some questions on the anatomy of the conduction system are formulated. Current understanding of these issues is presented and hypothetical answers are proposed. Historical sequence of discovery of the conduction system of the heart The Czech Jan Evangelista Purkynje discovered a net of gelatinous fiber at the sub-endocardium of ventricles in the ungulate heart and published his discovery in Czech in 1839 and in English in 1845. 5 His finding concerned the heart of an ungulate (horse or cow), not a human heart. Little was known about its functional significance and its histological features were strangely interpreted as a kind of cartilagein the heart. 5 Tawara in 1906 was the first to re-discover the significance of Purkinje cells during cardiac contraction. Till now disagreement remains on how to define Purkinje cells or fibers, but it is generally understood that Purkinje cells are vacuolated cells with fast conducting fibers at the atria or ventricular bundle branches. In 1893, Wilhelm His Jr. from Leipzig discovered the atrio-ventricular bundle (His bundle) and explained the propagation of cardiac contraction through muscle (myogenic conduction) rather than through nerve (neurogenic conduction), which at that time was the dogma. 5 In the same year, A.F. Stanley Kent from Britain also described myogenic conduction independently. Kent described the muscular connection between atria and ventricles as well, but he described several atrioventricular conduction bundles (Kent bundle) in addition to the

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Page 1: Ventricular Anatomy for the SPECIAL Electrophysiologist (Part I)arrhythmia.medimedia.co.kr/archive/archive/32/pdf/32... ·  · 2015-02-12Electrophysiologist (Part I) ... ¥conduction

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6 Journal of Cardiac Arrhythmia

Ventricular Anatomy for theElectrophysiologist (Part I)

서울대학교 의과대학 병리학교실 서 정 욱

ABSTRACTAnatomy of the conduction system for electrophysiologists is reviewed in two parts. This first part details the

historical sequence of discovery of the morphology of the conduction system, current or past issues on the

morphology of conduction system and basic anatomy of the conduction system.

Key words: ■ conduction system of heart ■arrhythmia ■Purkinje network

Introduction

Anatomic substrates of normal or abnormal

conduction of electrical stimulation in the heart are far

less studied compared to electrophysiologic

mechanisms.1 Studies on the pathology of the cardiac

conduction system, summarizing key morphologic

features of the major conduction axis and the

disposition of the conduction system at a macroscopic

level, are still important contents for electrophy

siologists.2,3 There is a Korean study on the histological

findings of conduction systems.4

This review illustrates the historical sequence on the

understanding of the conduction system and its basic

anatomy, after that some questions on the anatomy of

the conduction system are formulated. Current

understanding of these issues is presented and

hypothetical answers are proposed.

Historical sequence of discovery of theconduction system of the heart

The Czech Jan Evangelista Purkynje discovered a

net of gelatinous fiber at the sub-endocardium of

ventricles in the ungulate heart and published his

discovery in Czech in 1839 and in English in 1845.5

His finding concerned the heart of an ungulate (horse

or cow), not a human heart. Little was known about its

functional significance and its histological features

were strangely interpreted as a kind of ‘cartilage’in

the heart.5 Tawara in 1906 was the first to re-discover

the significance of Purkinje cells during cardiac

contraction. Till now disagreement remains on how to

define Purkinje cells or fibers, but it is generally

understood that Purkinje cells are vacuolated cells

with fast conducting fibers at the atria or ventricular

bundle branches.

In 1893, Wilhelm His Jr. from Leipzig discovered

the atrio-ventricular bundle (His bundle) and

explained the propagation of cardiac contraction

through muscle (myogenic conduction) rather than

through nerve (neurogenic conduction), which at that

time was the dogma.5 In the same year, A.F. Stanley

Kent from Britain also described myogenic

conduction independently. Kent described the

muscular connection between atria and ventricles as

well, but he described several atrioventricular

conduction bundles (Kent bundle) in addition to the

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Figure 1. The septal surface of the right ventricle after removal of the free anterior wall. The his bundle starts from theatrioventricular node (AVN) and runs inferior to the border of the membranous septum (MS) and continues to the rightbundle branch (arrows) underneath the medial papillary muscle (MPM) and the septomaginal trabeculation. CS; orifice of coronary sinus, RCA; right coronary artery, RVO; right ventricular outflow, SEP; septal leaflet of tricuspid valve, VIF; ventriculo-infundibular fold

His bundle. The nodes and bundles observed by Kent

are now understood to be remnants of atrioventricular

ring tissue rather than an aberrant connection in the

Wolff-Parkinson-White syndrome.

In 1906, Sunao Tawara reported his historical

discovery of the AV node in an absolutely perfect

description. He was a Japanese physician, who

graduated from Tokyo University in 1901 and worked

with Ludwig Aschoff in Germany from 1903. His

achievements were appreciated by cardiologists not

only for his AV node discovery, but also for his

integration of previous knowledge about the

conduction system by His and Purkinje. Tawara

explained how the His bundle expands and how it

branches into the left and right bundles as described

by Purkinje. One year after Tawara’s discovery, Sir

Arthur Keith and his young medical student Martin

Flack discovered the sinus node in the heart of several

species at an area that histologically resembled the

Tawara’s node. In 2007, the centennial discovery of

the sinus node by Keith and Flack was celebrated.1,6

Some questions

The historical question "Why does the heart beat?"

was answered by Tawara, Keith and Flack.4,6 The next

question was on the position of the conduction

pathway in a congenitally malformed heart,

particularly in the heart with an abnormal looping

such as a congenitally corrected transposition.7,8 The

expression of ganglion nodosum, which is like an

antigen in the conduction system, was discovered by

the Amsterdam group during immuno-histochemical

studies on the molecular expression of liver.9,10 They

realized that tracing the conduction system at the

embryonic heart could reveal developmental

processes of the human heart. Studies on cell to cell

communication like gap junction proteins and on

functional development of myofilaments followed.11,12

The development of electro-physiologic techniques

to evaluate the mechanism of arrhythmia left the

question on the cellular mechanism of the abnormal

excitation of the heart10 unanswered. This question is

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8 Journal of Cardiac Arrhythmia

Figure 2. Left ventricular septal surface and anterior mitral leaflet (AML) after removal of the free wall of left ventricleand mural leaflet of mitral valve. A wedge of fibroadipose tissue interposes at the atrioventricular junction. ALPM; antero-lateral papillary muscle, CS; coronary sinus, LAD; left anterior descending coronary artery, PMPM; postero-medial papillary muscle

recently studied in the pathology of the cardiac

conduction system in relation to atrial arrhythmia and

some other pathologic heart conditions such as

myocardial infarct with arrhythmia.13

One major group of questions left unanswered is

about the nature and functional significance of the

Purkinje cell.14 Purkinje cells are vacuolated cells at

the ventricular sub-endocardium found in the ungulate

heart. It is agreed upon that they are not seen in the

human heart. Some physicians use the term Purkinje

fibers, but others talk about Purkinje cardiomyocytes

or the Purkinje network. Sometimes, Purkinje cells are

referred to as the left bundle branch, but in other

occasions a vague term is used describing the

peripheral conduction system irrespective of its

morphology.3

Basic Anatomy

The landmark of the right ventricular aspect of the

conduction axis is documented for surgical anatomy

of the heart with ventricular septal defects, which

demonstrates its location at the inferior border of the

membranous septum of a normal heart (Figure 1), and

at the inferior border of hearts with ventricular septal

defects of a peri-membranous type. The location of

the right bundle branch is also localized at the

myocardium underneath the trabecula septo-

marginalis of the right ventricle.

The left ventricular aspect of the conduction system

has a close relation with the anterior mitral leaflet

(Figure 2). The left bundle arises from the inferior

border of the membranous septum, which lies beneath

the non-coronary cusp of the aortic valve and the

anterior mitral leaflet. The medial 3/4 of the anterior

mitral leaflet is in fibrous continuity with the left cusp

and the non-coronary cusp of the aortic valve, but the

lateral 1/4 has a free wall where the left atrial and

ventricular walls are connected, having a potential for

an aberrant connection (Figure 3).

Muscle dissection

Conduction starts from the base of the ventricles

and spreads down to the apex, but the contraction

starts from the apex so that the ventricles squeeze

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Figure 3. Close up of the specimen Fig 2. after lifting up the anterior mitral leaflet to show the aortic valve and theventricular surface of the mitral anterior leaflet seen from the apex of the left ventricular cavity. Mitral-aortic fibrouscontinuity is observed between the left and non-coronary cusps and the anterior part of mitral anterior leaflet (dottedline). The posterior part of the mitral leaflet is attached both to the left atrium and left ventricle (line). Arrows indicatethe anterior and posterior sub-branches of the left bundle branch. LC; left coronary cusp, MS; membranous septum, NC; non-coronary cusp, RC; right coronary cusp

Figure 4. After removal of the epicardium and fatty tissue, we can see the direction of cardiac muscle fiber bundles,which make whorls in the apex. LAD; left anterior descending coronary artery, LV; left ventricle, RV; right ventricle.

LV Septum

cs

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10 Journal of Cardiac Arrhythmia

from the apex. Dissection of the cardiac muscle at

macroscopic level confirms this principle (Figure 4).

Then the question arises if the left and right bundle

branches form a U-turn at the apex through a counter

current of the septal area’s bundle branch and the

Purkinje network (Figure 5).

Conclusion

The cardiac conduction system of ventricles

consists of the Atrioventricular node, the His bundle

and right and left bundle branches. They run to the

apex to connect to the peripheral conduction system

called ‘Purkinje network’. The histological details

and functional molecular nature of the conduction

system and Purkinje network will be discussed in part

II.

References

1. Boyett MR, Dobrzynski H. The sinoatrial node is still setting the

pace 100 years after its discovery. Circ Res. 2007;100:1543-

1545.

2. Davies MJ. Pathology of conducting tissue of the heart. London:

Butterworths, 1971.

3. Davies MJ, Anderson RH, Becker AE. The conduction system of

the heart. London: Butterworths, 1983.

4. Seo JW, Chi JG, Lee SK. Cardiac conduction system-

Morphological observations on the autopsy cases. Korean JPathol. 1983;17:127-137.

5. James TN. The development of ideas concerning the conduction

system of the heart. Ulster Med J. 1982;51:81-97.

6. Silverman ME, Hollman A. Discovery of the sinus node by Keith

and Flack: on the centennial of their 1907 publication. Heart.2007;93:1184-1187.

7 .Lev M, Fielding RT, Zaeske D. Mixed Levocardia with Ventricular

Inversion (Corrected Transposition) with Complete Atrioventricular

Block. A Histopathologic Study of the Conduction System. Am JCardiol. 1963;12:875-883.

8. Anderson RH. The conduction tissues in congenitally corrected

transposition. Ann Thorac Surg. 2004;77:1881-1882.

9. Wessels A, Vermeulen JL, Verbeek FJ, Viragh S, Kalman F, Lamers

WH, Moorman AF. Spatial distribution of "tissue-specific"

antigens in the developing human heart and skeletal muscle. III.

An immunohistochemical analysis of the distribution of the neural

tissue antigen G1N2 in the embryonic heart; implications for the

development of the atrioventricular conduction system. Anat Rec.

1992;232:97-111.

10. Moorman AF, Christoffels VM, Anderson RH. Anatomic

substrates for cardiac conduction. Heart Rhythm. 2005;2:875-

886.

Figure 5. Further dissection of the ventricular septum shows gradual change of their direction. The free wall of the leftventricle has a fiber direction in parallel to the long axis of heart.

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11 .Davis LM, Rodefeld ME, Green K, Beyer EC, Saffitz JE. Gap

junction protein phenotypes of the human heart and conduction

system. J Cardiovasc Electrophysiol. 1995;6:813-822.

12. van Kempen MJ, Fromaget C, Gros D, Moorman AF, Lamers

WH. Spatial distribution of connexin43, the major cardiac gap

junction protein, in the developing and adult rat heart. Circ Res.1991;68:1638-1651.

13. de Bakker JM, van Rijen HV. Electrocardiographic manifestation

of anatomical substrates underlying post-myocardial infarction

tachycardias. J Electrocardiol. 2007;40:S21-25.

14. Di Maio A, Ter Keurs HE, Franzini-Armstrong C. T-tubule profiles

in Purkinje fibres of mammalian myocardium. J Muscle Res CellMotil. 2007;28:115-121.