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Wilhelm His Junior and his bundle
Available online at www.sciencedirect.com
ScienceDirect Journal of Electrocardiology 49 (2016) 637 – 643 www.jecgonline.com
Review
Wilhelm His Junior and his bundle Robert H. Anderson, BSc, MD, a,⁎ Shumpei Mori, MD b b
a Institute of Genetic Medicine, Newcastle University, Newcastle-upon-Tyne, United Kingdom Division of Cardiovascular Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Japan
Abstract
We have reviewed the evidence relative to the initial description of the penetrating atrioventricular bundle, seeking to determine whether Wilhelm His Junior is deserving of his eponym. © 2016 Elsevier Inc. All rights reserved.
Keywords:
Atrioventricular node; Penetrating atrioventricular bundle; Atrioventricular conduction axis; Sunao Tawara; History of medicine
Introduction When one of us was training in medicine, he was encouraged by his Professor of Anatomy not to use eponyms. The medical students, at the time, considered that the Professor probably took this stance because, despite his eminence as an authority on the anatomy of the autonomic nervous system, he had yet to achieve his own eponym. Be that as it may, and despite the fact that anatomists still disapprove of the use of these devices, eponyms have not gone away, nor are they likely to go away. The potential problem with their use, of course, is that we have no certainty that the honoree is worthy of the structure thus named. This is the case with regard to the “bundle of His”. For many years, one of us had doubted the justification for the naming of this important structure. It was fortunate, therefore, that at the time we were preparing this review, we had the opportunity to read a discussion regarding the “history of evidence” [1]. In that review, Clarke points out that the last century is only 15 years behind us. We need to think about the century before last when contemplating the events of the 1800s. It is the events of the century before last that are pertinent to the achievements of Wilhelm His the Junior [2]. Clarke emphasizes the ease with which it is now possible to access the material published in the 19th century medical literature. Even if armed previously with this information, it would have proved difficult for many, if not most, investigators to appreciate the account of the atrioventricular bundle provided by His. In no small part this was because of its publication in the German language [3]. And, as was acknowledged by His himself [2], it ⁎ Corresponding author at: 60 Earlsfield Road, London SW18 3DN, United Kingdom. E-mail address: [email protected] http://dx.doi.org/10.1016/j.jelectrocard.2016.06.003 0022-0736/© 2016 Elsevier Inc. All rights reserved.
appeared in an obscure journal. Access to the modern day search engines, however, directed us to an excellent translation of the original publication, including its illustrations [4]. This translation, furthermore, has been available for very many years, so our own shortcoming is reflected by our ignorance of its existence. Examination of the work in the English language has now prompted a major revision of our opinion of the validity of the original description. There is no doubt that Wilhelm His Junior discovered the bundle that bears his name, and provided illustrations demonstrating its location [3]. We discuss in our review why the entity initially proved to be enigmatic. We then show how its precise location can now be demonstrated in life by means of “living anatomy”, endorsing the accounts provided by previous giants of cardiac anatomy. We begin, however, by discussing the heritage of Wilhelm His Junior [5], since it is arguable that his father was just as deserving of a suitable eponym. The His family Wilhelm His Senior was professor of anatomy and physiology in Basel, Switzerland, where Wilhelm Junior, the third of six children, was born on December 29, 1863 [2,5]. Wilhelm Junior was 9 years old when his father, already recognized as the foremost worldwide exponent of human development, was appointed as professor of anatomy at the University of Leipzig. During his appointment in Basel, His Senior had made formidable discoveries over and above those relating to human development, including the invention of the microtome [2]. Having established himself in Leipzig, he published the most complete account of human embryology as known at the time, including a description of cardiac development which still maintains its currency [6]. Amongst the illustrations to be found in His'
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Atlas is a depiction of a protrusion growing into the atrial cavity from the dorsal wall of the developing atrial chambers, overlapping the developing primary atrial septum (Fig. 1). His Senior named this protrusion the “spina vestibuli”. We now know that this entity, along with a mesenchymal cap carried on the leading edge of the primary atrial septum, is muscularized to form the buttress that binds the atrial septum itself to the insulating tissues of the atrioventricular junctions [7]. The atrioventricular node is formed within this buttress. We also now know, of course, that this node is part of an axis of specialized myocardium that includes the bundle subsequently discovered by his son. The vestibular spine itself was neglected for well over a century, until its importance in separating the atrioventricular junctions was emphasized by Snarr and his colleagues [8]. The latter workers chose to describe the entity as the “dorsal mesenchymal protrusion”. To our minds, this ignores the initial description by His Senior. Our own preference is to describe it as the vestibular spine [7]. It could be argued that the structure is deserving of description as the protuberance of His. Be that as it may, we can be sure that His Senior took pains to share his anatomical and embryological experiences with his son, thus paving the way for the initial discovery of the atrioventricular bundle. As was suggested by Schechter and colleagues [9], nonetheless, the “brief journey” of His Junior into the fields of anatomy and embryology was made
at the instigation of His Senior. They argued that His Junior “had no particular inclination for his assignment, but nevertheless tackled the chore in earnest” [9]. Discovery of the atrioventricular bundle Thanks to the connections of his father, His Junior had been able to study at the very best universities in Europe as he obtained his medical training, spending periods in Geneva, Bern, Strasbourg, and Leipzig [2,5]. It was in Leipzig that he graduated as a physician in 1889. During the initial years subsequent to his graduation, he remained in Leipzig. It was in Leipzig where, at the instigation of his father, he carried out the researches leading to the discovery of the bundle. At that time, it was still generally believed that conduction between the different components of the heart depended on the cardiac nerves. The extensive work of His, published in the “home” journal of the medical clinic in Leipzig [3], outlined the evidence he had obtained from studies of cardiac development, which showed that the heartbeat was established prior to the onset of cardiac innervation. The experiments conducted on the developing heart, coupled with evidence provided previously by Gaskell [10], led His to examine hearts histologically in search of a muscular connection between the atrial and ventricular myocardial masses. His description of these findings accounts for less than one page in the overall publication. The key passage was translated by Bast and Gardner as follows: “The bundle arises from the posterior wall of the right auricle, near the auricular septum, in the atrioventricular groove, attaches itself along the upper margin of the ventricular septal muscle by means of numerous fiber exchanges; proceeds on top of this toward the front until near the aorta it forks itself into a right and left limb which latter ends in the base of the aortic cusp of the mitral valve.” He illustrated his findings from mouse (Fig. 2) and human (Fig. 3) hearts. With the aid of subsequent knowledge, we are able to appreciate the validity of these illustrations, in particular the image showing the location of the bundle in the mouse (Fig. 2). Even with benefit of the ongoing studies, nonetheless, it must be acknowledged that the findings shown in Fig. 3 are difficult to understand. Thus, we know that the minimalism of the original description, coupled with the paucity of illustrative material, was sufficient to generate skepticism in the eyes of a cardiac anatomist as skilled as Arthur Keith [11–13]. The skepticism of Keith
Fig. 1. The cartoon is re-drawing of the diagram provided by Wilhelm His Senior to show the growth of the so-called “spina vestibili” from the dorsal wall of the developing atrial chambers. Modified from His W. 1885. Das Herz. In: W His (ed.) Anatomie menschlicher Embryonen. Vol. 3: Zür Geschichte der Organe, Vogel, Leipzig, pp. 129–184.
In 1895, as described in his autobiography, Arthur Keith, at the age of 30, was establishing his anatomical credentials. As part of his training, he spent time in Leipzig, hoping to study with His Senior so as to improve his knowledge of cardiac development. He was less than impressed by the training on offer, commenting in his autobiography that “he lost interest in me when he found that I had no theme in embryology on which I proposed making a research” [11]. At the time, Keith had been most interested in anthropological research, although subsequently he was to become the
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Fig. 2. The left hand panel is a reproduction of the drawing provided by His [3] showing the location of the penetrating atrioventricular bundle (asterisk) in the mouse heart as seen in a “four chamber” section. The right hand panel, taken from a comparable section of a human heart, attests to the accuracy of the section prepared by His.
Fig. 3. The upper panel is a reproduction of the section provided by His [3] provided to show the location of the atrioventricular bundle in the human heart. It is very difficult to interpret, even with the benefit of current knowledge. The lower panel, a reproduction of one of the sections prepared by Tawara, shows that the atrioventricular conduction axis does, indeed, occupy the location described by His. The drawing made by Tawara has been re-positioned to match the orientation of the image provided by His.
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Fig. 5. The illustration provided by Keith and Flack [16] confirming the location of atrioventricular bundle as described by Tawara [13]. It is accurately shown as originating from the atrioventricular node (3), running along the base of the membranous septum, and continuing beneath the “great trabecula on the septal wall" (5) as the right bundle branch.
the vemtricular septal surfaces as the bundle branches, and terminates in the Purkinje network. Keith concluded that “with the discovery of the conducting system of Tawara, heart research entered a new epoch” [12]. Fig. 4. The drawing provided by Keith [12] endorsing the location of the bundle of His. The atrial component of the bundle is shown by “e”. It is depicted as continuing into the ventricles as “f”. Keith shows the bundle continuing inferiorly within the vestibule of the tricuspid valve. He also shows the fibrous structures now known as the “tendon of Todaro” as “g” and “h”. These delimit the atrial boundary of the triangle of Koch.
foremost cardiac anatomist and embryologist in the world. It seems likely that he was unaware, when visiting His Senior, of the vital discovery made by His Junior. Keith's interest in cardiac anatomy was spawned by Mackenzie, who was still practicing at the turn of the nineteenth century as a general practioner in Burnley, Lancashire. In his autobiography, Keith describes how Mackenzie had asked him to explore “the state of a muscular connection between the auricles and ventricles — a connection spoken of at that time as the “bundle of His” [12]. He explained that “In all my dissections of the human heart I had never come across the ‘bundle of His’; indeed, I was skeptical of its existence” [12]. His skepticism had reached sufficient heights for him to write to “The Lancet”, expressing his concern [13]. Before the letter was published, Mackenzie had sent him details of the findings of Sunao Tawara [14], a Japanese working with Ludwig Aschoff in Marburg. These findings are now also available in an English translation, along with all the illustrations [15]. On the basis of the descriptions of Tawara, Keith added to his initial letter an explanation of how, in “heart after heart”, he had now been able to find the specialized pathway we now describe as the atrioventricular conduction axis. This commences in the atrioventricular node, crosses the insulating plane as the bundle of His, passes down
What underscored Keith's skepticism? Armed now with sight of the initial illustrations of His [3], reproduced faithfully in the translation provided by Bast and Gardner [4], and in particular the image showing the location of the penetrating atrioventricular bundle in the mouse heart (Figs. 2), it is difficult for us to understand why as excellent an anatomist as Keith should have experienced problems in endorsing the initial description. We should remember, however, that an alternative account had been provided in 1893 to explain electrical conduction across the atrioventricular junctions. In this second account, Kent had suggested that multiple connections were to be found within the junctions, with only one of these corresponding to the bundle described by His [16]. To the best of our knowledge, Kent never illustrated the septal connection. Although Schechter and colleagues [9] put significant faith in the studies of Kent, we are less impressed. Kent had remained convinced, even after Tawara [13] and Keith [16] had unequivocally endorsed the findings of His, that the parietal connections provided the substrate for normal atrioventricular conduction. As Keith explained in his initial letter to Lancet, he had been expecting to find “direct continuity of ordinary auricular and ventricular muscular fibres” [13]. Such “direct continuity” does not exist in otherwise normal hearts, except in the setting of Wolff–Parkinson–White syndrome. For many years, the direct accessory muscular atrioventricular connections which underscore the Wolff– Parkinson–White variant of pre-excitation were described as “Kent fibers” [18]. In reality, apart from the so-called “Mahaim” variant [18], these connections have no relation to the parietal structures illustrated by Kent [19]. The node-like
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structures illustrated by Kent do exist, but they are sequestrated within the atrial myocardium making up the vestibule of the tricuspid valve. In the letter in which he explained his skepticism, Keith provided a figure to illustrate the location of the bundle described by His (Fig. 4). Subsequent to submitting the initial letter to Lancet, Keith continued his researches on the bundle of His in collaboration with Flack. Together, they swiftly published, again in Lancet, a much more detailed account of the location of the bundle [17]. In this second account, Keith and Flack confirmed the bundle to be the penetrating component of the axis of conduction tissues described so elegantly by Tawara [14]. They also provided a more detailed, and more accurate, illustration showing the location of the bundle, its origin from the atrioventricular node, and its continuation as the right bundle branch (Fig. 5). In their expanded account, Keith and Flack also explained how, in some hearts, the bundle, having penetrated the central fibrous body, came to occupy a location below the crest of the muscular ventricular septum. They offered this as a further potential explanation as to why they might have “missed” the bundle in their earlier investigations. When discussing their findings, they opined that lesions of the bundle provided a good explanation for heart block, a term by then introduced by His himself, endorsing the comments made by His in this regard. Having now examined the initial description [3], along with the subsequent studies by Tawara [14], and Keith and Flack [17], it is pertinent to consider a statement, highlighted by Clarke in his review of historical evidence [1]. It was made by Lord Rayleigh in his presidential address to the British Association for the Advancement of Science held in Montreal in 1885 [20]. The Lord Rayleigh stated “The work which deserves, but I am afraid does not always receive, the most credit is that in which discovery and explanation go hand in hand, in which not only are new facts presented, but their relation to old ones is pointed out.” When assessing the discovery of His in this light, we conclude that it is the work of Tawara that is deserving of the greatest credit. It was Tawara [14] who placed the initial findings of His in their appropriate context, permitting Keith and Flack [17] to provide their own subsequent endorsement. By the same token, nonetheless, our assessment shows that His is richly deserving of his eponym as the original discover of the penetrating atrioventricular bundle [3].
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triangle we now name in his honor (Fig. 6). As had Keith and Flack, Koch also illustrated the heart as seen occupying its usual position within the chest (Figs. 4–6). It remains a mystery as to why, for centuries, other anatomists describing the heart have broken the first rule of human anatomy, namely that all structures should be described as they are perceived in the subject standing upright in the so-called “anatomical position” [23]. This convention is the more important for electrocardiographers, since it is the anatomical position that provides the basis for understanding Einthoven's triangle. The question is posed, therefore, as to why cardiologists, along with anatomists, continue to describe components within the heart as if the organ has been removed from the body and positioned on its apex, in so-called “Valentine” position? This convention creates nothing but confusion. On this basis, the triangle of Koch is frequently, if not usually, shown with its apex pointing to the right. Only on this basis can the superior quadrants of the atrioventricular junctions be incorrectly described as being “anterior”, with their opposite inferior quadrants again incorrectly identified as “posterior”. It is the same inappropriate convention that leads to the inferior interventricular
Subsequent endorsements of the findings of Keith and Flack In their endorsement of the findings of His and Tawara, Keith and Flack illustrated the heart in attitudinally appropriate fashion (Fig. 5). Even when expressing his initial skepticism, Keith had illustrated the landmarks of the area we now describe as the triangle of Koch (Fig. 6). Subsequent to their endorsement of the location of the overall axis responsible for atrioventicular conduction [17], Keith and Flack had proceeded to provide the first account of the location of the sinus node [21]. The location of the sinus node was then endorsed by Koch [22]. It was in this publication that Koch illustrated the landmarks of the
Fig. 6. The illustration was provided by Koch to demonstrate the landmarks to the atrial origin of the atrioventricular conduction axis. We now describe the triangle in Koch's name, although Koch had produced the figure to show the location of the sinus node, discovered of course by Keith and Flack. Like Keith and Flack (Fig. 5), Koch illustrates the triangle in attitudinally appropriate fashion, with its apex positioned superiorly. We have re-labeled the original illustration made by Koch.
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artery being described as a posterior and descending entity, despite the fact that all cardiologists are aware that blockage of the artery produces inferior myocardial infarction. The advent of new imaging techniques, such as three-dimensional echocardiography, magnetic resonance imaging, or multi-detector computed tomography, now demonstrates the obvious flaws in using descriptions dependent on the Valentine approach. These new techniques illustrate the cardiac components as they are seen in the heart within the body, this also being the view obtained by the cardiac interventionist. Use of these techniques now permits us to reveal living anatomy with just as much detail (Fig. 7) as when the heart is examined in the dissecting room (Fig. 6). The reconstructions show how the ventricular septum forms the rightward wall of the subaortic left ventricular outflow tract. As well described by Keith and Flack, the axis responsible for atrioventricular conduction, having penetrated through the central fibrous body, branches on or just below the crest of the muscular ventricular septum. The left bundle branch ramifies on the septal surface on the left ventricular outflow tract, while the right bundle branch passes through the substance of the ventricular septum, emerging on the right ventricular septal surface beneath the medial papillary muscle (Fig. 7).
Conclusions As was emphasized by Clarke in his incisive review regarding the history of evidence, the availability of evidential material through the internet is now remarkable. Use of the Google search engine has greatly enhanced our own understanding, not only of the history of the discovery of the atrioventricular bundle, but also the excellence of the initial studies that clarified its location. It could be argued that our current understanding is little different, with regard to this anatomical location, from that of Tawara [14], and subsequently of Keith and Flack [17]. Thanks to our ongoing researches, we now have a greater understanding of the reason for the initial skepticism of Keith regarding the very existence of the bundle. The evidence already available in 1949, of which to our chagrin we had been unaware, is sufficient to show that His Junior is more than worthy of his eponym. Our own studies using modern imaging techniques do no more than validate the excellence of the original descriptions. They do serve to emphasize the importance of attitudinally appropriate nomenclature [23]. We submit that it is only in this way that the anatomic information can be presented to clinicians in optimal fashion.
Fig. 7. The image is a reconstruction made from a multi-detector computed tomographic dataset obtained from a patient undergoing investigation for suspected coronary arterial disease. It shows the landmarks of the triangle of Koch, and the location of the medial papillary muscle. The membranous septum has been reconstructed in blue. The virtual dissection shows well the location of the atrioventricular conduction axis (red dotted line), with its origin from the atrioventricular node at the apex of the triangle of Koch (white star with red borders). The virtual dissection validates the accuracy of the dissection provided by Keith and Flack (Fig. 5). Further virtual dissection then permits demonstration of the short distance required for the penetrating bundle as described by His to traverse from the apex of the triangle of Koch to reach the crest of the muscular ventricular septum (see Fig. 8).
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Fig. 8. The virtual dissection of the computed tomographic dataset also shown in Fig. 7 reveals the course and location of the atrioventricular conduction axis as seen in the short axis of the cardiac base. The membranous septum in this image has been reconstructed in green.
References [1] Clarke M. History of evidence synthesis to assess treatment effects: personal reflections on something that is very much alive. J Royal Soc Med 2016;109:154–63. [2] Roguin A. Wilhelm His Jr (1863–1934) — the man behind the bundle. Heart Rhythm 2006;3:480–3. [3] His Jr W. Die Tätigkeit des embryonalen herzens und deren bedeutung für die Lehre von der Hezebewegung beim menschen. Arbeiten aus der medidizinischen Klinik zu Leipzig 1893;14-49. [4] His Jr W. The activity of the embryonic human heart and its significance for understanding of the heart movement in the adult. Translated from the original German by TH Bast and WD Gardner. J Hiest Med 1949;4:289–318. [5] Loukas M, Clarke P, Tubbs RS, Kapos T, Trotz M. The His family and their contributions to cardiology. Cardiol 2008;123:75–8. [6] His W. Das Herz. In: His W, editor. Anatomie menschlicher Embryonen. Zür geschichte der OrganeLeipzig: Vogel; 1885. p. 129–84. [7] Anderson RH, Mohun TJ, Brown NA. Clarifying the morphology of the ostium primum defect. J Anat 2015;226:244–57. [8] Snarr BS, O'Neal JL, Chintalapudi MR, Wirrig EE, Phelps AL, Kubalek SW, et al. Isl1 expression at the venous pole identifies a novel role for the second heart field in cardiac development. Circ Res 2007;101:971–4. [9] Schechter DC, Lillehei CW, Soffer A. History of sphygmology and of heart block. Dis Chest 1969;55(Suppl 1):535–79. [10] Gaskell WH. On the innervation of the heart, with special reference to the heart of the tortoise. J Physiol 1883;4:43–127.
[11] [12] [13] [14] [15]
[16] [17] [18]
[19] [20]
[21]
[22] [23]
Keith A. An autobiography. London: Watts & Co.; 1950176. Keith A. An autobiography. London: Watts & Co.; 1950255. Keith A. The auriculo-ventricular bundle of his. Lancet 1906;623-625. Tawara S. Das Reizleitungssystem des Sa¨ugetierherzens Jena. Germany: Gustav Fischer; 1906. Suma K, Shimada M. The conduction system of the mammalian heart. An anatomico-histological study of the atrioventricular bundle and the Purkinje fibres. S. Tawara. London: Imperial College Press; 2000. Kent AFS. Researches on the structure and function of the mammalian heart. J Physiol 1893;14:233–54. Keith A, Flack MW. The auriculo-ventricular bundle of the human heart. Lancet 1906;11:359–64. Anderson RH, Ho SY, Gillette PC, Becker AE. Mahaim, Kent and abnormal atrioventricular conduction. Cardiovasc Res 1996;31:480–91. Kent AFS. The structure of the cardiac tissues at the auricular– ventricular junction. J Physiol 1913;47:xvii–xviii. Rayleigh L. Address by the Rt. hon. Lord Rayleigh. Report of the fiftyfourth meeting of the British Association for the Advancement of Science. Montreal, QC, Canada. August and September. London: John Murray; 1885. Keith A, Flack M. The form and nature of the muscular connections between the primary divisions of the vertebrate heart. J Anat Physiol 1907;41:172–89. Koch W. Weiter Mitteilungen uber den Sinusknoten der herzens. Verh Dtsch Pathol Ges 1909;13:85–92. Loukas M, Aly I, Tubbs RS, Anderson RH. The naming game: a discrepancy amongst the medical community. Clin Anat 2016;29:285–9.
ScienceDirect Journal of Electrocardiology 49 (2016) 637 – 643 www.jecgonline.com
Review
Wilhelm His Junior and his bundle Robert H. Anderson, BSc, MD, a,⁎ Shumpei Mori, MD b b
a Institute of Genetic Medicine, Newcastle University, Newcastle-upon-Tyne, United Kingdom Division of Cardiovascular Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Japan
Abstract
We have reviewed the evidence relative to the initial description of the penetrating atrioventricular bundle, seeking to determine whether Wilhelm His Junior is deserving of his eponym. © 2016 Elsevier Inc. All rights reserved.
Keywords:
Atrioventricular node; Penetrating atrioventricular bundle; Atrioventricular conduction axis; Sunao Tawara; History of medicine
Introduction When one of us was training in medicine, he was encouraged by his Professor of Anatomy not to use eponyms. The medical students, at the time, considered that the Professor probably took this stance because, despite his eminence as an authority on the anatomy of the autonomic nervous system, he had yet to achieve his own eponym. Be that as it may, and despite the fact that anatomists still disapprove of the use of these devices, eponyms have not gone away, nor are they likely to go away. The potential problem with their use, of course, is that we have no certainty that the honoree is worthy of the structure thus named. This is the case with regard to the “bundle of His”. For many years, one of us had doubted the justification for the naming of this important structure. It was fortunate, therefore, that at the time we were preparing this review, we had the opportunity to read a discussion regarding the “history of evidence” [1]. In that review, Clarke points out that the last century is only 15 years behind us. We need to think about the century before last when contemplating the events of the 1800s. It is the events of the century before last that are pertinent to the achievements of Wilhelm His the Junior [2]. Clarke emphasizes the ease with which it is now possible to access the material published in the 19th century medical literature. Even if armed previously with this information, it would have proved difficult for many, if not most, investigators to appreciate the account of the atrioventricular bundle provided by His. In no small part this was because of its publication in the German language [3]. And, as was acknowledged by His himself [2], it ⁎ Corresponding author at: 60 Earlsfield Road, London SW18 3DN, United Kingdom. E-mail address: [email protected] http://dx.doi.org/10.1016/j.jelectrocard.2016.06.003 0022-0736/© 2016 Elsevier Inc. All rights reserved.
appeared in an obscure journal. Access to the modern day search engines, however, directed us to an excellent translation of the original publication, including its illustrations [4]. This translation, furthermore, has been available for very many years, so our own shortcoming is reflected by our ignorance of its existence. Examination of the work in the English language has now prompted a major revision of our opinion of the validity of the original description. There is no doubt that Wilhelm His Junior discovered the bundle that bears his name, and provided illustrations demonstrating its location [3]. We discuss in our review why the entity initially proved to be enigmatic. We then show how its precise location can now be demonstrated in life by means of “living anatomy”, endorsing the accounts provided by previous giants of cardiac anatomy. We begin, however, by discussing the heritage of Wilhelm His Junior [5], since it is arguable that his father was just as deserving of a suitable eponym. The His family Wilhelm His Senior was professor of anatomy and physiology in Basel, Switzerland, where Wilhelm Junior, the third of six children, was born on December 29, 1863 [2,5]. Wilhelm Junior was 9 years old when his father, already recognized as the foremost worldwide exponent of human development, was appointed as professor of anatomy at the University of Leipzig. During his appointment in Basel, His Senior had made formidable discoveries over and above those relating to human development, including the invention of the microtome [2]. Having established himself in Leipzig, he published the most complete account of human embryology as known at the time, including a description of cardiac development which still maintains its currency [6]. Amongst the illustrations to be found in His'
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Atlas is a depiction of a protrusion growing into the atrial cavity from the dorsal wall of the developing atrial chambers, overlapping the developing primary atrial septum (Fig. 1). His Senior named this protrusion the “spina vestibuli”. We now know that this entity, along with a mesenchymal cap carried on the leading edge of the primary atrial septum, is muscularized to form the buttress that binds the atrial septum itself to the insulating tissues of the atrioventricular junctions [7]. The atrioventricular node is formed within this buttress. We also now know, of course, that this node is part of an axis of specialized myocardium that includes the bundle subsequently discovered by his son. The vestibular spine itself was neglected for well over a century, until its importance in separating the atrioventricular junctions was emphasized by Snarr and his colleagues [8]. The latter workers chose to describe the entity as the “dorsal mesenchymal protrusion”. To our minds, this ignores the initial description by His Senior. Our own preference is to describe it as the vestibular spine [7]. It could be argued that the structure is deserving of description as the protuberance of His. Be that as it may, we can be sure that His Senior took pains to share his anatomical and embryological experiences with his son, thus paving the way for the initial discovery of the atrioventricular bundle. As was suggested by Schechter and colleagues [9], nonetheless, the “brief journey” of His Junior into the fields of anatomy and embryology was made
at the instigation of His Senior. They argued that His Junior “had no particular inclination for his assignment, but nevertheless tackled the chore in earnest” [9]. Discovery of the atrioventricular bundle Thanks to the connections of his father, His Junior had been able to study at the very best universities in Europe as he obtained his medical training, spending periods in Geneva, Bern, Strasbourg, and Leipzig [2,5]. It was in Leipzig that he graduated as a physician in 1889. During the initial years subsequent to his graduation, he remained in Leipzig. It was in Leipzig where, at the instigation of his father, he carried out the researches leading to the discovery of the bundle. At that time, it was still generally believed that conduction between the different components of the heart depended on the cardiac nerves. The extensive work of His, published in the “home” journal of the medical clinic in Leipzig [3], outlined the evidence he had obtained from studies of cardiac development, which showed that the heartbeat was established prior to the onset of cardiac innervation. The experiments conducted on the developing heart, coupled with evidence provided previously by Gaskell [10], led His to examine hearts histologically in search of a muscular connection between the atrial and ventricular myocardial masses. His description of these findings accounts for less than one page in the overall publication. The key passage was translated by Bast and Gardner as follows: “The bundle arises from the posterior wall of the right auricle, near the auricular septum, in the atrioventricular groove, attaches itself along the upper margin of the ventricular septal muscle by means of numerous fiber exchanges; proceeds on top of this toward the front until near the aorta it forks itself into a right and left limb which latter ends in the base of the aortic cusp of the mitral valve.” He illustrated his findings from mouse (Fig. 2) and human (Fig. 3) hearts. With the aid of subsequent knowledge, we are able to appreciate the validity of these illustrations, in particular the image showing the location of the bundle in the mouse (Fig. 2). Even with benefit of the ongoing studies, nonetheless, it must be acknowledged that the findings shown in Fig. 3 are difficult to understand. Thus, we know that the minimalism of the original description, coupled with the paucity of illustrative material, was sufficient to generate skepticism in the eyes of a cardiac anatomist as skilled as Arthur Keith [11–13]. The skepticism of Keith
Fig. 1. The cartoon is re-drawing of the diagram provided by Wilhelm His Senior to show the growth of the so-called “spina vestibili” from the dorsal wall of the developing atrial chambers. Modified from His W. 1885. Das Herz. In: W His (ed.) Anatomie menschlicher Embryonen. Vol. 3: Zür Geschichte der Organe, Vogel, Leipzig, pp. 129–184.
In 1895, as described in his autobiography, Arthur Keith, at the age of 30, was establishing his anatomical credentials. As part of his training, he spent time in Leipzig, hoping to study with His Senior so as to improve his knowledge of cardiac development. He was less than impressed by the training on offer, commenting in his autobiography that “he lost interest in me when he found that I had no theme in embryology on which I proposed making a research” [11]. At the time, Keith had been most interested in anthropological research, although subsequently he was to become the
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Fig. 2. The left hand panel is a reproduction of the drawing provided by His [3] showing the location of the penetrating atrioventricular bundle (asterisk) in the mouse heart as seen in a “four chamber” section. The right hand panel, taken from a comparable section of a human heart, attests to the accuracy of the section prepared by His.
Fig. 3. The upper panel is a reproduction of the section provided by His [3] provided to show the location of the atrioventricular bundle in the human heart. It is very difficult to interpret, even with the benefit of current knowledge. The lower panel, a reproduction of one of the sections prepared by Tawara, shows that the atrioventricular conduction axis does, indeed, occupy the location described by His. The drawing made by Tawara has been re-positioned to match the orientation of the image provided by His.
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Fig. 5. The illustration provided by Keith and Flack [16] confirming the location of atrioventricular bundle as described by Tawara [13]. It is accurately shown as originating from the atrioventricular node (3), running along the base of the membranous septum, and continuing beneath the “great trabecula on the septal wall" (5) as the right bundle branch.
the vemtricular septal surfaces as the bundle branches, and terminates in the Purkinje network. Keith concluded that “with the discovery of the conducting system of Tawara, heart research entered a new epoch” [12]. Fig. 4. The drawing provided by Keith [12] endorsing the location of the bundle of His. The atrial component of the bundle is shown by “e”. It is depicted as continuing into the ventricles as “f”. Keith shows the bundle continuing inferiorly within the vestibule of the tricuspid valve. He also shows the fibrous structures now known as the “tendon of Todaro” as “g” and “h”. These delimit the atrial boundary of the triangle of Koch.
foremost cardiac anatomist and embryologist in the world. It seems likely that he was unaware, when visiting His Senior, of the vital discovery made by His Junior. Keith's interest in cardiac anatomy was spawned by Mackenzie, who was still practicing at the turn of the nineteenth century as a general practioner in Burnley, Lancashire. In his autobiography, Keith describes how Mackenzie had asked him to explore “the state of a muscular connection between the auricles and ventricles — a connection spoken of at that time as the “bundle of His” [12]. He explained that “In all my dissections of the human heart I had never come across the ‘bundle of His’; indeed, I was skeptical of its existence” [12]. His skepticism had reached sufficient heights for him to write to “The Lancet”, expressing his concern [13]. Before the letter was published, Mackenzie had sent him details of the findings of Sunao Tawara [14], a Japanese working with Ludwig Aschoff in Marburg. These findings are now also available in an English translation, along with all the illustrations [15]. On the basis of the descriptions of Tawara, Keith added to his initial letter an explanation of how, in “heart after heart”, he had now been able to find the specialized pathway we now describe as the atrioventricular conduction axis. This commences in the atrioventricular node, crosses the insulating plane as the bundle of His, passes down
What underscored Keith's skepticism? Armed now with sight of the initial illustrations of His [3], reproduced faithfully in the translation provided by Bast and Gardner [4], and in particular the image showing the location of the penetrating atrioventricular bundle in the mouse heart (Figs. 2), it is difficult for us to understand why as excellent an anatomist as Keith should have experienced problems in endorsing the initial description. We should remember, however, that an alternative account had been provided in 1893 to explain electrical conduction across the atrioventricular junctions. In this second account, Kent had suggested that multiple connections were to be found within the junctions, with only one of these corresponding to the bundle described by His [16]. To the best of our knowledge, Kent never illustrated the septal connection. Although Schechter and colleagues [9] put significant faith in the studies of Kent, we are less impressed. Kent had remained convinced, even after Tawara [13] and Keith [16] had unequivocally endorsed the findings of His, that the parietal connections provided the substrate for normal atrioventricular conduction. As Keith explained in his initial letter to Lancet, he had been expecting to find “direct continuity of ordinary auricular and ventricular muscular fibres” [13]. Such “direct continuity” does not exist in otherwise normal hearts, except in the setting of Wolff–Parkinson–White syndrome. For many years, the direct accessory muscular atrioventricular connections which underscore the Wolff– Parkinson–White variant of pre-excitation were described as “Kent fibers” [18]. In reality, apart from the so-called “Mahaim” variant [18], these connections have no relation to the parietal structures illustrated by Kent [19]. The node-like
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structures illustrated by Kent do exist, but they are sequestrated within the atrial myocardium making up the vestibule of the tricuspid valve. In the letter in which he explained his skepticism, Keith provided a figure to illustrate the location of the bundle described by His (Fig. 4). Subsequent to submitting the initial letter to Lancet, Keith continued his researches on the bundle of His in collaboration with Flack. Together, they swiftly published, again in Lancet, a much more detailed account of the location of the bundle [17]. In this second account, Keith and Flack confirmed the bundle to be the penetrating component of the axis of conduction tissues described so elegantly by Tawara [14]. They also provided a more detailed, and more accurate, illustration showing the location of the bundle, its origin from the atrioventricular node, and its continuation as the right bundle branch (Fig. 5). In their expanded account, Keith and Flack also explained how, in some hearts, the bundle, having penetrated the central fibrous body, came to occupy a location below the crest of the muscular ventricular septum. They offered this as a further potential explanation as to why they might have “missed” the bundle in their earlier investigations. When discussing their findings, they opined that lesions of the bundle provided a good explanation for heart block, a term by then introduced by His himself, endorsing the comments made by His in this regard. Having now examined the initial description [3], along with the subsequent studies by Tawara [14], and Keith and Flack [17], it is pertinent to consider a statement, highlighted by Clarke in his review of historical evidence [1]. It was made by Lord Rayleigh in his presidential address to the British Association for the Advancement of Science held in Montreal in 1885 [20]. The Lord Rayleigh stated “The work which deserves, but I am afraid does not always receive, the most credit is that in which discovery and explanation go hand in hand, in which not only are new facts presented, but their relation to old ones is pointed out.” When assessing the discovery of His in this light, we conclude that it is the work of Tawara that is deserving of the greatest credit. It was Tawara [14] who placed the initial findings of His in their appropriate context, permitting Keith and Flack [17] to provide their own subsequent endorsement. By the same token, nonetheless, our assessment shows that His is richly deserving of his eponym as the original discover of the penetrating atrioventricular bundle [3].
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triangle we now name in his honor (Fig. 6). As had Keith and Flack, Koch also illustrated the heart as seen occupying its usual position within the chest (Figs. 4–6). It remains a mystery as to why, for centuries, other anatomists describing the heart have broken the first rule of human anatomy, namely that all structures should be described as they are perceived in the subject standing upright in the so-called “anatomical position” [23]. This convention is the more important for electrocardiographers, since it is the anatomical position that provides the basis for understanding Einthoven's triangle. The question is posed, therefore, as to why cardiologists, along with anatomists, continue to describe components within the heart as if the organ has been removed from the body and positioned on its apex, in so-called “Valentine” position? This convention creates nothing but confusion. On this basis, the triangle of Koch is frequently, if not usually, shown with its apex pointing to the right. Only on this basis can the superior quadrants of the atrioventricular junctions be incorrectly described as being “anterior”, with their opposite inferior quadrants again incorrectly identified as “posterior”. It is the same inappropriate convention that leads to the inferior interventricular
Subsequent endorsements of the findings of Keith and Flack In their endorsement of the findings of His and Tawara, Keith and Flack illustrated the heart in attitudinally appropriate fashion (Fig. 5). Even when expressing his initial skepticism, Keith had illustrated the landmarks of the area we now describe as the triangle of Koch (Fig. 6). Subsequent to their endorsement of the location of the overall axis responsible for atrioventicular conduction [17], Keith and Flack had proceeded to provide the first account of the location of the sinus node [21]. The location of the sinus node was then endorsed by Koch [22]. It was in this publication that Koch illustrated the landmarks of the
Fig. 6. The illustration was provided by Koch to demonstrate the landmarks to the atrial origin of the atrioventricular conduction axis. We now describe the triangle in Koch's name, although Koch had produced the figure to show the location of the sinus node, discovered of course by Keith and Flack. Like Keith and Flack (Fig. 5), Koch illustrates the triangle in attitudinally appropriate fashion, with its apex positioned superiorly. We have re-labeled the original illustration made by Koch.
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artery being described as a posterior and descending entity, despite the fact that all cardiologists are aware that blockage of the artery produces inferior myocardial infarction. The advent of new imaging techniques, such as three-dimensional echocardiography, magnetic resonance imaging, or multi-detector computed tomography, now demonstrates the obvious flaws in using descriptions dependent on the Valentine approach. These new techniques illustrate the cardiac components as they are seen in the heart within the body, this also being the view obtained by the cardiac interventionist. Use of these techniques now permits us to reveal living anatomy with just as much detail (Fig. 7) as when the heart is examined in the dissecting room (Fig. 6). The reconstructions show how the ventricular septum forms the rightward wall of the subaortic left ventricular outflow tract. As well described by Keith and Flack, the axis responsible for atrioventricular conduction, having penetrated through the central fibrous body, branches on or just below the crest of the muscular ventricular septum. The left bundle branch ramifies on the septal surface on the left ventricular outflow tract, while the right bundle branch passes through the substance of the ventricular septum, emerging on the right ventricular septal surface beneath the medial papillary muscle (Fig. 7).
Conclusions As was emphasized by Clarke in his incisive review regarding the history of evidence, the availability of evidential material through the internet is now remarkable. Use of the Google search engine has greatly enhanced our own understanding, not only of the history of the discovery of the atrioventricular bundle, but also the excellence of the initial studies that clarified its location. It could be argued that our current understanding is little different, with regard to this anatomical location, from that of Tawara [14], and subsequently of Keith and Flack [17]. Thanks to our ongoing researches, we now have a greater understanding of the reason for the initial skepticism of Keith regarding the very existence of the bundle. The evidence already available in 1949, of which to our chagrin we had been unaware, is sufficient to show that His Junior is more than worthy of his eponym. Our own studies using modern imaging techniques do no more than validate the excellence of the original descriptions. They do serve to emphasize the importance of attitudinally appropriate nomenclature [23]. We submit that it is only in this way that the anatomic information can be presented to clinicians in optimal fashion.
Fig. 7. The image is a reconstruction made from a multi-detector computed tomographic dataset obtained from a patient undergoing investigation for suspected coronary arterial disease. It shows the landmarks of the triangle of Koch, and the location of the medial papillary muscle. The membranous septum has been reconstructed in blue. The virtual dissection shows well the location of the atrioventricular conduction axis (red dotted line), with its origin from the atrioventricular node at the apex of the triangle of Koch (white star with red borders). The virtual dissection validates the accuracy of the dissection provided by Keith and Flack (Fig. 5). Further virtual dissection then permits demonstration of the short distance required for the penetrating bundle as described by His to traverse from the apex of the triangle of Koch to reach the crest of the muscular ventricular septum (see Fig. 8).
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Fig. 8. The virtual dissection of the computed tomographic dataset also shown in Fig. 7 reveals the course and location of the atrioventricular conduction axis as seen in the short axis of the cardiac base. The membranous septum in this image has been reconstructed in green.
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