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Keibel F. and Mall FP. Manual of Human Embryology II. (1912) J. B. Lippincott Company, Philadelphia.

XVIII. Development of Blood, Vascular System and Spleen: Introduction | Origin of the Angioblast and Development of the Blood | Development of the Heart | The Development of the Vascular System | General | Special Development of the Blood-vessels | Origin of the Blood-vascular System | Blood-vascular System in Series of Human Embryos | Arteries | Veins | Development of the Lymphatic System | Development of the Spleen
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II. The Development of the Heart

Tandler J. The Development of the Heart. (1912) Sect. II, chapt. 18, vol. 2, in Keibel F. and Mall FP. Manual of Human Embryology II. (1912) J. B. Lippincott Company, Philadelphia., pp. 534-570.

Julius Tandler
Julius Tandler (1869 – 1936)

By Julius Tandler.


The earliest developmental processes of the heart, especially in so far as they concern the formation of the endothelium of the heart and vessels, are unknown in the human embryo, but probably one will not be far astray in assuming that the earliest anlage of the human heart is essentially similar to that of the mammalia. The earliest development of the heart is naturally associated with the first appearance of the vessels, but concerning this the following brief statement is all that is necessary here. According to the comprehensive investigations of Mollier, the preliminary to the formation of the heart in all craniote vertebrates is the appearance of a number of cells between the endoderm and mesoderm, at first in the distal portion of the head. These elements, known as vascular cells, are discernible much earlier in the amniota than in the anamnia, and are recognizable in mammalian embryos with two or three primitive somites. From these vascular cells there develops, however, only the cardiac endothelium, the remaining constituents of the heart wall, the myocardium and epicardium, being derivatives of the visceral ccelomic wall. The first aggregation of the vascular cells of the heart is paired and produces a bulging of the visceral lamella into the wide pleuropericardial cavity. This bulging portion of the wall, which, as already stated, gives rise to the entire heart wall with the exception of the endothelium, has been named by Mollier the heart plate or cardiogenic plate. The topical relation of the paired heart anlagen to one another, that is to say, the time when they come into contact, depends on the configuration of the foregut. If this* is spread out flat at the time of the appearance of the heart anlagen, these are widely separated from one another; if, however, there is an early closure of the fore-gut ventrally, as, judging from stages already known, is undoubtedly the case in human embryos, then the paired heart anlagen are very close together from the beginning and their fusion takes place early. In the Spee embryo G-le (Normentafel 1 No. 2, primitive somites not yet visible) some scattered vascular cells occur in the region of the paired heart anlage.


  • 105 Robert Muir : On the Relations of Bone-marrow to Leucocyte Production and Leucocytosis, Journ. Path, and Bacterid., vol. vii, 1901, p. 161.
  • Muir and Drummond : On the Structure of Bone-marrow, etc., Journ. Anat. and Physiol., vol. xxviii, 1893, p. 125.
  • Rindfleisch: Arch. f. mikr. Anat., vol. xvii, 1880, p. 1-11 (describes the circulation).
  • W. H. Howell: On the Life-history of the Formed Elements of the Blood, Journ. of Morphol., vol. iv, 3890, p. 57.
  • E. Neumann : Ueber die Entwickelung rothen Blutkorperchen in neugebildetem Knochenmark, Virehow's Arch., vol. exix, 1890, p. 385-398.
  • Freiberg: Experimentelle Untersuchungen fiber die Regeneration der Blutkorperchen im Knochenmarke, Inaug. Diss., Dorpat, 1892.
  • Bizzozero: Cbl. med. Wiss., 1881, and Moleschott's Unters. z. Nat.-Lehre, vol. xiii, 1888.
  • O. van der Stricht : Archives der Biologie, vol. xii, 1892, p. 199.


Brinkerhoff and Tyzzer: On the Leucocytes of the Circulating Blood of the Rabbit, Journ. Med. Research, vol. vii, 1902, p. 173.



On the closure of the fore-gut ventrally the hitherto symmetrical pleuropericardial cavities come together anteriorly and fuse in this region, the median partition between them, the mesocardium anterius, disappearing, while the mesocardium posterius persists for some time longer. The closely approximated but not yet fused endothelial tubes are now surrounded by a continuous myo-epicardial mantle (Mollier). Finally the two endothelial tubes come into contact, their partition wall disappears, and the unpaired heart cylinder is formed from the paired heart tubes. This stage of the development of the heart occurs in the KromerPfannenstiel embryo, Klb (Normentafel No. 3, five to six primitive somites), a section of which, passing through the heart anlage, is shown in Fig. f 72. The space which is seen between the myo-epicardial mantle and the endothelial tube, and which is probably filled with fluid intra vitam, is perhaps somewhat enlarged in this embryo by the collapse of the endothelial tube during preservation. The fusion of the endothelial tubes is shown only in a few sections: cranially and caudally from the section figured one still sees the paired ends of the endothelial tnbes.


  • By Normentafel is meant Kernel's Normentafel zur EntwicklungsgescmVhte des Menschen.


With the fusion of the. paired anlagen to form an unpaired cylinder there begins a new period in the development of the heart, during which two processes take place simultaneously, namely, (1) the elongation and consecutive bending of the heart cylinder and (2) the differentiation of the heart into its individual parts. There is no doubt that both processes are the result of the functional elaboration of a primarily straight and simply propulsatory portion of the vascular system, that is to say, of the heart anlage. In the description that follows a division of the process into stages will be made; in the first stage the development of the heart wall will be followed from the condition of a simple straight cylinder, to which stage it has now been traced, up to the time of the primary atrial division. The second stage will extend from the development of the primary atrial septum to the degeneration of the septum primum and the development of the septum secundum, the third to the complete division of the heart, and the fourth, finally, to the acquisition of its definitive form.


The development of the mammalian heart from the stage in which it is a simple cylinder to the completion of its development has been made known by the fundamental work of Born. The observations of this author were made principally on the heart of the rabbit, but were frequently extended also to the human heart. Born has modelled some stages of the latter and has pointed out the slight differences that obtain in the development of the two hearts. Recently Hochstetter has written a comparative embryology of the vertebrate heart for Hertwig's Handbuch. The succeeding account of the development of the human heart follows closely the work of Born, yet the endeavor has been made to complete as far as possible our knowledge of the development of the human heart.


The bending of the heart cylinder begins by the portion exactly midway between the two fixed ends being thrown into a loop, which may be termed the ventricular loop and whose apex is towards the right. The cranial end of the heart cylinder is fixed at the point of emergence of the cylinder from the pericardium, that is to say, at the point of division of the truncus arteriosus into the aortic arches; the venous end, to which the umbilical and omphalomesenteric veins converge, is fixed by the septum transversum, developing immediately above the yolk-sack. Since the heart cylinder grows more rapidly than the fixed points separate from one another, its free portion becomes thrown into a loop. The two limbs of this loop are separated by an almost horizontal cleft, the interventricular, or better the bulb o -ventricular cleft (compare Fig. 373 2 ). By this cleft the heart loop is separated into two portions, into a cranial limb, the bulbar limb, and a caudal one, the ventricular. The part situated immediately above the septum transversum widens later to form a cavity whose greatest diameter is transverse and whose left end communicates with the ventricular limb. This cavity represents the atrial portion of the heart, and the somewhat constricted portion by which it communicates with the ventricular limb is the atrial canal. The atrial portion lies dorso-caudal to the ventricular limb, which, on its pari, is overlapped cranially by the bulbar limb. On the caudal wall of the atrium there opens the sinus venosus, which is greatly expanded in the transverse direction and whose cavity receives the blood from both venae umbilicales, venae omphalomesentericse, and ductus Cuvieri. Consequently, simultaneously with its bending, the heart cylinder becomes divided into its four portions. While the delimitation of the atrial portion from the ventricular limb is indicated by the constriction in the region of the atrial canal and that of the ventricular limb from the bulbus cordis by the constriction at the bottom of the bulbo-ventricufar cleft, that of the sinus from the atrium is less distinct. Later, however, this delimitation is made clearer by a groove which constricts the floor of the atrium from the left and delimits the left portion of the sinus venosus from the left portion of the transverse atrial sac. By this the wide connection between the sinus and the atrium is narrowed and the sinus itself is divided into a transverse middle portion and two lateral portions communicating with this — the transverse portion of the sinus and the left and right sinus horns.



  • 2 I am indebted to Professor P. Thompson for the loan of this model.

Keibel Mall 2 372.jpg

Fig. 372. Section through the heart anlage of the Pfannenstiel-Kromer embryo Klb (Normentafel, Xo. 3, 5 to 6 primitive somites). A., dorsal aorta; E., endothelial tube; M., myo-epicardial mantle; P., pericardial cavity; Ph., pharynx. X 100.

Keibel Mall 2 373.jpg

Fig. 373. Model of the heart of a human embryo. No. 300 of Rob. Meyer's collection (Normentafel Xo. 7), 2.5 mm. greatest length. Modelled by P. Thompson. (After Thompson.) A., atrium; Au., region of the atrial canal; B., bulbus cordis; S., sinus venosus; T ., truncus arteriosus; U., vena umbilicalis sinistra; V., ventricular limb. X 50.



The changes that now take place consist in a relative change of position of the individual portions of the loop. The sinus with its sinus horns, which up to this time has been the most caudal portion of the loop, comes to lie on the dorsal side of the transverse atrial sack ; at the same time the apex of the ventricular limb, which hitherto has looked towards the right, comes to be directed more caudally. This change of position of the bulboventricular limb becomes clear by a comparison of the position of the bulbo-ventricular cleft of Thompson's embryo (Fig. 373) with that seen in Embryo Hal 2 (Fig. 374) ; in the former it is almost horizontal, in the latter almost vertical. By this change what was formerly the caudal limb of the loop becomes the left limb, and what was formerly the cranial one becomes the right. As this assumption of a vertical position by the ventricular limb progresses, the atrium rises so that it comes to lie in the dorsocranial side of the ventricular limb and a continually increasing portion of it becomes visible in an anterior view. Moreover, by this change the atrium comes into contact with the basal surface of the bulbar limb, which bends backward almost in a horizontal plane, and as the atrium continues to grow forward it becomes slightly constricted by the bulbus. The movement of the sinus venosus in a craniodorsal direction, already described, accompanies this change in the atrium, so that the sinus, which formerly opened at the base of the atrial limb, now opens into the posterior wall of the atrium. At the same time, by the recession of the entire heart, the direction of the sinus horns is altered, these being directed no longer upward and medially, but assuming at first a horizontal direction and finally opening into the transverse portion of the sinus from above and laterally; they form with the transverse portion an arch which is no longer convex upward, but is at first convex anteriorly and later downward. The bulbus cordis participates in the relative change of position of the various parts of the heart to the extent that its distal end becomes more and more pushed toward the median plane as the ventricular limb becomes more vertical, and at the same time its distal bend becomes straightened out. In earlier stages this bend is quite sharp, but later the slightly curved bulbus passes gradually into the truncus arteriosus.


Keibel Mall 2 374.jpg

Fig. 374. Model of the heart of the embryo Hah of 3 mm. greatest length, 15 primitive somites. The property of the First Anatomical Institute, Vienna. Modelled by R. Weintraub. Seen from in front after removal of the anterior pericardial wall. The dotted lines represent the limits of the veins. A., atrium; A. asc, ascending aorta; Aran., amnion; Au., atrial canal; B., bulbus cordis; D., yolk-sack, cut at its margin; D. C, ductus Cuvieri; D. v., anterior communication of intestine with yolk-sack; M. a., anterior mesocardium; P., pericardium; S. 1., left sinus horn; V., ventricular limb; V. om., omphalomesenteric vein. X 150.


Keibel Mall 2 375.jpg

Fig. 375. The model shown in Fig. 374 after removal of the pericardium, seen from behind. A., atrium; A. asc, ascending aorta; Amn., amnion; B., bulbus cordis; D. v., anterior communication of the intestine with the yolk-sack; E., ectoderm; Ph., lateral wall of pharynx; Ph. + Th., impression of the pharynx and the (median) thyreoid anlage on the pericardium; S. I., reflection of the pericardium upon the left sinus horn; S. r., right sinus horn; V., ventricle. Lateral to S. I. the transverse section of the left ductus Cuvieri is to be seen.


This topical modification of the heart is accompanied with changes of form, which consist partly in the progressive delimitation of the four portions of the heart and partly in the further elaboration of each portion. Hand in hand with the change of position of the sinus there goes a diminution of the left sinus horn and a consequent retardation in the growth of the transverse portion of the sinus. The diminution of the horn is chiefly due to the obliteration of the left umbilical vein. The right half of the transverse part of the sinus is not greatly affected by the diminution, since in the meantime a number of hepatic veins have acquired openings into it. By the progressive constriction of the sinus from the posterior wall of the atrium from the left, the greatly narrowed opening of the sinus comes eventually to lie at the right posterior end of the transverse part of the atrium. The formerly transversely oval opening between the sinus and the atrium has been converted, by the developmental processes just described, into a longitudinally oval one, whose greatest diameter is placed sagittally and vertically. Toward the left it is bounded by the constriction described above, while on the right there is formed a vertical fold which, starting on the upper wall of the atrium, passes down the posterior wall beside the sinus opening to reach the lower wall. This fold is the first anlage of the right sinus valve (valvula venosa dextra).


The atrium changes its form to the extent that its two lateral extremities, enlarged in a balloon-like manner, project beyond the bulbar limb anteriorly and above, and it seems as if the right half decidedly surpasses the left in volume, at least the similar results of observations on several embryos of this stage point this way. The first division of the atrial cavity is due to the distal portion of the bulbus becoming lodged in its anterior upper wall. Corresponding with the blunt prominence projecting into the atrial cavity, produced in this manner, there develops, toward the end of the period now under consideration, a sickle-shaped fold, which extends at first over the posterior and later also over the anterior wall of the atrium, then gradually fading out. This is the anlage of the septum primum.


At about this same time the upper end of the right sinus valve thickens and projects into the atrial cavity as the first indication of the septum spurium; a slight groove on the outer surface of the atrium marks its position. Between this and the constriction produced by the lodgement of the distal end of the bulbus cordis, the cranial wall of the atrium is somewhat outpouched, forming the intersepto-valvular space. At the left end of the lower atrial wall is the entrance into the atrial canal, which at the beginning of this stage of development has a somewhat circular form, but at its end is transversely oval. At first this opening lies wholly to the left, associated with the abruptly descending left Avail of the atrium, but later it shifts as a whole to the right, so that its right end i> finally situated at the middle of the atrial wall that is directed toward the ventricle. Corresponding to this change in the interior of the heart cavity a modification of the outer surface is naturally also visible. The atrial canal, which at fit st is visible on the left side of the heart, gradually comes to lie more and more deeply and vanishes towards the right, being overlapped from the left and above by the enlarging left atrium and from the left and below by the enlarging upper part of the ventricular limb. Hereby the atrial canal approaches nearer to the bulbo-ventricular cleft, until, finally, the depression bounding it on the left becomes continuous with the cleft and forms with it the bulbo-auricular groove. The ventricular limb, at this time, broadens in all directions and overlaps, especially on the left side, the circumference of the atrial canal. Its communication with the bulbus cordis, which at the beginning of this period was rather narrow, enlarges by the disappearance of the duplicature of the heart wall which is interposed between the ventricular and bulbar limbs, this duplicature being produced by the deep bulbo-ventricular cleft. In this process there is naturally no degeneration of heart substance, but merely a difference of growth to the disadvantage of the part under consideration. This lagging behind of the portion intervening between the bulbus and the ventricle shows itself on the outer surface of the heart by the bulbo-ventricular cleft becoming gradually shallower and gradually shortened in the caudocranial direction. The enlargement of the communication produces a common ventricular cavity, involving the transition portion, that is to say the caudal part, of the bulbo-ventricular limb. This becomes divided into two portions in its cranial part by the projection of the heart wall into the interior at the bottom of the bulbo-auricular cleft. This ridge-like projection, whose cranial portion was rather plump so long as the auricular canal lay entirely to the left, becomes sharper with the shifting of the atrial canal toward the right, and finally becomes a sharp-edged fold, which, as already stated, subdivides the cranial portion of the ventricular loop in the sagittal direction. To the left of this bulbo-auricular ridge lies the entrance to the atrium in the form of a well-defined atrial canal, to its right is the bulbus cordis, gradually diminishing in size as it is followed away from the ventricle. At the base of the common ventricular cavity there begins at this period the formation of a sagittally placed elevation, the first anlage of the interventricular septum.


The histogenetic processes which take place during the developmental period that has so far been followed are as follows. At first the distance between the endothelial cardiac tube and the myo-epicardial mantle is very great throughout the whole extent of the heart anlage, and during life it seems to be filled with a serous fluid, since it is occupied in sections by a clot-like, fibrous mass, entirely destitute of cells and staining feebly with hematoxylin (Fig. 376). The endocardium consists of a layer of endothelial cells with large nuclei, while the myo-epicardial mantle is composed of several layers of cells, which have more of a syncytial character, at least their boundaries are distinguishable only rarely and sporadically. It is, however, difficult to determine how far this indistinct delimitation of the individual cells is due to the preservation or staining, since none of the embryos I have had for study were stained with iron-hasmatoxylin. The space which at first exists between the endocardium and the myo-epicardium diminishes later in an irregular manner; it disappears first of all in the sinus and then in the atrium, so that in these regions the endocardium is in contact with the muscle mantle in early stages. In the region of the impaired ventricular cavity the apposition of the two layers occurs somewhat later, while throughout the circumference of the atrial canal and in the bulbus the apposition does not take place within the limits of the period now under consideration. In these regions there are formed in the space between the two layers the so-called endocardial thickenings or endocardial cushions. In place of the absolutely cell-free, fibrous coagulum there occur in these regions sporadic stellate cells with relatively small nuclei, the staining with hematoxylin becomes decidedly stronger, and the whole tissue reminds one forcibly of the type of tissue seen in the Whartonian substance.

Keibel Mall 2 376.jpg

Fig. 376. Transverse section through the embryo Hah. A. d., descending aorta; B., bulbus cordis; E., endothelium of the cardiac tube; H., auditory pit; M., myo-epicardial mantle; Ph., pharynx; V., ventricle. X 100.

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Fig. 377. Section through the ventricular wall of the heart of embryo Hah, 3.5 mm. greatest length, in the collection of the I. Anatomical Institute, Vienna. E., endothelial cells; Ep., epicardium; M., myocardium; Mc, cortical and Ms., spongy portion. X 150.

The myo-epicardial mantle differentiates to the extent that in the region of the ventricular loop and in that of the bulbus its superficial layer is formed by a continuous row of cells, the epicardium, while on the atrium and sinus, so far as the latter has a free surface, no such differentiation can as yet be said to occur. But the ventricular limb takes precedence over the atrium in the differentiation of the myocardium itself, as well as in that of the epicardium. In the ventricle one sees not only an increase of volume in the myocardium, but also its further differentiation and finally the appearance of trabecular These first appear at the base of the common ventricular cavity as projecting elevations, which gradually become more and more undermined, until finally, surrounded on all sides by the closely apposed endocardium, they traverse the ventricle more or less free. The elaboration of the trabecular network proceeds from the base toward the atrial canal on the one hand and toward the bulbus on the other, and at the close of this period one can speak of two portions in the cardiac musculature, an outer cortical and an inner trabecular or spongy portion (Fig. 397). The latter is of considerable thickness, but the corticalis forms only a thin layer and a difference in the degree of differentiation of the two portions is also perceptible. At the beginning of the period under consideration the entire myocardium stained deeply with eosin and the individual cells were rich in protoplasm, but at this stage the spongy portion is composed of cells poor in protoplasm; at least these cells in well-preserved embryos stain feebly with eosin. On account of their poverty of protoplasm the boundaries of the individual myoblasts are more distinct than formerly. In the region of the trabecular myocardium there now appear in the otherwise feebly-stained cell-bodies fine, strongly eosinophile muscle fibrils, which do not confine themselves to individual cell territories, but traverse several cells. None of this fibrillar structure is yet to be seen in the cortical layer. The atrial myocardium, which, so far as its differentiation is concerned, behaves like the cortical layer of the ventricle, shows a discontinuity along the line of attachment of the posterior mesocardium, muscle substance being completely wanting in early stages along this narrow zone (area interposita of His). The right sinus valve in its early stages is a duplicative of the myocardium, at least it may be seen that embryonic connective tissue occurs between the two muscle lamellae. No boundary exists between the atrial and ventricular musculature, the former passing into the latter on all sides at the atrial canal. The myocardium is continued distally to the line of attachment of the pericardium, that is to say, to the region of transition from the bulbus to the truncus. Later this limit becomes less definite, as the distal portion of the bulbar myocardium apparently vanishes, a process by which the truncus arteriosus undergoes an elongation at the expense of the bulbus, and this at the time when the myoepicardial mantle is not yet differentiated at the distal end of the cardiac tube. This explains the difficulty which exists in determining the limits of these two portions of the efferent tube.


The endocardial thickenings in the atrial canal, mentioned above, may be described, in accordance with the form of the atrial canal itself, as an anterior endocardial cushion, situated on the anterior wall, and a posterior one on the posterior wall. On the small lateral borders of atrial canal the endocardium lies fairly close upon the myocardium. In the region of the bulbus a ring of endocardial tissue, at first of almost uniform thickness, replaces the space filled with fluid that is present in the earlier stages, and in this ring the following changes take place. In the proximal part of the bulb, the ventricular part, the endocardial thickening becomes especially strong along two spirally arranged regions, while in the intervals between these its development is retarded, and there are thus formed the proximal bulbar swellings, which, according to Born's method of nomenclature, may be termed the proximal bulbar swellings A and B. The distal portion of the swelling A lies on the left side of the bulbus, and as it descends it passes more and more toward the front, until, finally, at the proximal end of the bulb, it extends down toward the common ventricular cavity on the anterior wall. The proximal swelling B in its distal part lies on the right wall of the bulb and passes thence downward on the posterior wall to disappear in the posterior wall of the ventricular cavity, just as the swelling A does in the anterior wall. In the oldest embryos belonging to this period of development one sees already that the most proximal parts of both bulbar swellings are undermined by trabecular musculature ascending from the apex of the ventricle. In the distal or truncus portion of the bulb the endocardial ring is also in process of differentiation to the extent that in a series of sections one sees endocardial thickenings projecting toward the lumen to form the distal bulbar swellings. Distally the endocardial thickenings become gradually lower, until finally they pass over into the closely apposed endothelium of the truncus at the region where externally the indistinct boundary between the bulbus and truncus may be perceived. The projecting spur, the future septum aorto-pulmonale, which projects between the two halves of the system of aortic arches, i. e., between the • future systemic and pulmonary aortas, does not at this stage reach the line at which the pericardium is attracted to the truncus arteriosus.


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Fig. 378. Model of the heart of the embryo Hah of 5.2 mm. greatest length. In the collection of the I. Anatomical Institute, Vienna. Modelled by W. von Wieser. Seen from in front. A. d., right atrium; A. «., left atrium; An., region of the atrial canal; B., bulbus cordis; Bv., bulbo-ventricular cleft; T., truncus arteriosus; V., ventricle. X 100.


In the second stage of development of the heart there is an approximation of the external form to the final condition, but the more important part of the progress is in connection with parts in the interior of the heart. As regards the external form, the change in the relative position of the various parts proceeds, the atrium gradually reaching a higher position, while the apex of the heart is carried so far caudally that, as is shown by a side view, it comes to lie caudal to the atrium. At the same time the opening of the sinus shifts completely to the dorsal wall of the atrium. The formerly slight constriction of the cranial wall of the atrium, produced by the bulb and the truncus arteriosus, now becomes a deep groove, and the lateral parts of the atrium on either side of this groove have enlarged so much that they begin to embrace the bulb as the anlagen of the auricular appendages (Fig. 378).

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Fig. 379. Model of the heart of embryo £U of 6.5 mm. greatest length. In the collection of the I. AnatomicalJInBtitute, Vienna (Normentafel No. 27). Modelled by J. Tandler. The lower half of the model divided transversely, seen from above. A. d., right atrium; A. «., left atrium; Ek. h., posterior endocardial cushion! of the atrial canal; P., pericardium; p.Bw. A, proximal bulbar swelling A; p.Bw.B, proximal bulbar [swelling B; S., sinus venosus; <S. /., septum primum; V., ventricle; V.p., vena pulmonalis (with sound inserted); V.v.d., right valvula venosa; V.v.s., left valvula venosa. X 100.


The posterior surface of the atrium also shows a shallow furrow, which corresponds to the oesophagus. To the right of the broad deep atrial furrow for the reception of the bulbus cordis, the groove corresponding to the attachment of the septum spurium, already described, has greatly deepened, so that a portion of the posterior wall of the right atrium projects in a dome-like manner, forming the spatium intersepto-valvulare. This is bounded below by a short transverse furrow, which separates it distinctly from the region in which the right sinus horn opens. The left sinus horn has emancipated itself from the pericardium to the extent that at first it remains in connection with it only by a small band, resembling a mesentery, but in later stages this also vanishes and all connection between the sinus horn and the pericardium disappears. Similar conditions occur also in the transverse part of the sinus, except that in this region they occur somewhat later. The right sinus horn continues to enlarge without interruption and at the same time gradually ascends on the posterior atrial wall and is absorbed into the atrium, with the exception of its caudal portion, into which the transverse part of the sinus opens, and of its blind cranial end which is elevated in a dome-like manner and is separated from the spatium interseptovalvulare by the groove already described (compare Fig. 380).


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Fig. 380. Model of [thejjheart of embryo La of 9 mm. greatest length. In the collection of the I. Anatomical Institute, Vienna (Normentafel No. 37). Modelled by J. Tandler. The atrial portion of the model has been divided frontally and the whole is viewed from in front. A.d., right atrium; A.s., left atrium; Ek.h., posterior endocardial cushion of the atrial canal; S.I, septum primum; S.I I, septum secundum; S.i., spatium interseptovalvulare ; S.iv., sulcus interventricularis; S.a., septum spurium; V.p. vena pulmonalis; V.v., right and left valvula venosa. X 75.

The changes taking place in the interior of the atrium may be described as follows (Fig. 379). The septum I, which grows downward from the posterior upper wall of the atrium and is at first quite low, becomes higher, and its ends, drawn out in a sickleshaped fashion, extend so far forward along the lower and upper walls of the atrium that they reach the margin of the atrial canal. At the same time the free edge of the septum becomes remarkably thickened and bounds, together with the plane of entrance of the atrial canal, the primary narrowed opening of communication between the two atria, the foramen ovale I. Its line of origin, however, becomes gradually thinner and thinner, and finally there is formed, either directly at the line of origin of the septum on the posterior upper wall of the atrium or immediately below it, a dehiscence, the foramen ovale II, which rapidly enlarges. The septum I then gradually separates from its line of attachment and becomes a ribbon-like structure with fluted margins, traversing the atrium from behind and below forward and upward. In such hearts (compare embryo La, "Wal, Figs. 380, 381, 382) the original line of attachment of the septum I appears as a slight elevation on the dorsal wall of the atrium, and immediately to the right of this the elevation of the septum II begins; the further history of this may conveniently be described in the third period of development. In the first period the right sinus valve was the only one present, the left (valvula venosa sinistra) being scarcely indicated, but now the latter is strongly developed. The two valves lie one on either side of the slit-like opening of the sinus, which is directed from above and outward, inward and downward (Fig. 379). The left one unites on the cranial wall of the atrium with the thickening* of the right valve, which has already been described, and forms with it a large distinct septum-like structure which passes over the cranial wall of the atrium on to the anterior wall and is the septum spurium of His (Fig. 380). Caudally the two valves behave differently, in that the right one gradually flattens ont on the floor of the atrium, while the left one extendi toward the sicklelike end of the septum II, which is growing backward on the floor of the atrium, and later unites with it. 3 The space between the left valvula venosa and the anlage of the septum II is outpouched dorsocranially to form the spatium intersepto-valvulare. To the left of the septum I, in the angle between the posterior and lower walls of the atrium and in the region where externally the posterior mesocardium is still attached, is the opening of a. vessel coming from the lungs, the single vena pulmonalis (Figs. 379, 380). In a section through the model of a heart at this stage (Fig. 380) one sees how distinctly the atrium has become separated from the ventricle by the deepening of the atrioventricular groove, — that is to say, how greatly the atrium and ventricle have become expanded beyond the outline of the atrial canal. Changes in the position and form of this canal have also taken place. As regards its position it is to be" noted that it has made such progress in its shifting toward the right that it has already come to lie in the centre of the floor of the atrium. If in the model of a heart at this stage one looks from the ventricle into the atrium through the atrial canal, one sees that the septum I is directed exactly toward the centre of the transverse diameter of the canal (Figs. 379, 380). As the result of this further shifting toward the right the bulbo-atrial ridge, already described, becomes still more prominent and simultaneously with the shifting other changes take place in the canal. In correspondence with the bulging of the ventricle beyond the circumference of the canal, which has already been noted, and, further, in correspondence with the continued undermining of the endocardial cushions by the musculature, the endothelial swellings project freely some distance further into the ventricular cavity. Both the anterior and the posterior swellings become modified in such a way that their lateral extremities become more elevated, while their central parts remain somewhat flatter; consequently one may distinguish in each endocardial cushion a middle straight portion and two lateral elevations or tubercles. The shape of the atrial canal in transverse section thus comes to resemble the figure formed by two T's placed base to base ( I— H). This peculiar modification of the atrial canal is completed relatively quickly; small endocardial thickenings also appear on the lateral margins of the canal in later stages.

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Fig. 381. Sagittal section through the model shown in Fig. 380, the section passing to the left of the septum I. Seen from the left. Au., atrial canal; B., bulbus; F.o.II, foramen ovale II; S., sinus venosus ; S.I, septum primum; S.II, septum secundum; V., ventricle. Below the septum primum and above the atrial canal is the foramen ovale I.

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Fig. 382. Transverse section through the heart region of the embryo Wal of 8 mm. greatest length. In the collection of the I. Anatomical Institute, Vienna. A.d., descending aorta; Au., atrial canal;!"S., sinus; S.I, septum primum; V.v., valvule venos».



3 The details of this process will be described with the next period of development.


In the ventricular limb on the convexity of the common ventricular cavity, — that is to say, at the point where in the earlier stage the ventricular limb passed into the bulbus, — a constriction appears, extending over the ventricular surface of the heart and gradually becoming shallower as it is traced upward. This interventricular groove (Fig. 380) marks externally the separation between the right and left ventricle and divides the blunt apex of the heart into two portions, so that at this stage the right and left ventricle each has its own apex. The portion belonging to the left ventricle is, however, greater than that pertaining to the right one. Corresponding to this external groove, the interventricular septum, already seen in the earlier period as a rounded ridge, becomes more prominent, but just as there is externally an asymmetry in the two ventricles, so too in the interior the subdivisions of the ventricular cavity are by no means equal at first. This inequality of the ventricles is later partly compensated for by a broadening of the right one, but a slight asymmetry persists in that the interventricular septum is so placed that its prolongation would not cut the middle of the atrial canal but the right tubercules of the endothelial cushions.


The most proximal portion of the bulbus has enlarged considerably and has been taken up into the ventricle, and at the same time the greater part of the bulbo-ventricular cleft has disappeared. Processes having an important bearing on the entire subdivision of the heart take place in the bulb during this period of development. Attention has been called to the fact that already in the first period endocardial thickenings develop in the bulbus ; these were termed the proximal bulbar swellings A and B, and, as their name indicates, they are situated in the proximal half of the bulbus. They have, as has also been stated, a spiral course around the inner surface of the bulbus, yet they have grown more distally, so that the swelling A, beginning distally on the left posterior wall, passes thence to the left, to finally disappear proximally on the right anterior bulbar wall, as this ascends from the d.Bw.2 mil mf

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Fig. 383. Section through the bulbus cordis of the embryo H6. The section cute the bulbus obliquely to its long axis, and consequently the line of attachment of the pericardium is also cut. d.Bw. 1-4, distal bulbar swellings 1-4.


common ventricular chamber without any sharp delimitation from it. The swelling B begins distally on the anterior wall of the bulbus and passes thence over the right wall to the posterior one, where it disappears at about the same level as swelling A, at the junction of the bulbus and ventricle. The conditions at the proximal ends of the bulbar swellings will be described in detail later on. In earlier stages an endocardial thickening occurred around the whole circumference of- the bulb in its distal portion, and a differentiation of the distal bulbar swellings had not yet taken place. In the period now under consideration these are developed ; but it may be said that they do not present the regularity of form and occurrence that obtains in the birds and reptiles. To demonstrate the extent of the proximal and distal bulbar swellings it is convenient to divide the bulbus into a proximal ventricular and a distal truncus portion; these subdivisions can only be temporary, however, since the bulbus during this period of development undergoes a continuous and rather rapid shortening at both ends. Its central end is gradually taken up into the right ventricle, while the truncus arteriosus elongates heart-ward at the expense of its distal end. In this shortening bulbus the proximal bulbar swellings occupy the proximal half and the distal swellings the distal half ; yet this delimitation is not quite accurate, at least for the distal bulbar swellings 1 and 3, to be described below, since these gradually pass over into the proximal swellings A and B. Four distal bulbar swellings can be distinguished, and starting with the right distal one and proceeding to the left and backward they may be denoted by the numbers 1-4. When followed proximally they are seen to run downward on the bulbus walls in a clock-wise spiral. They do not project equally into the lumen of the bulbus, but swellings 1 and 3 are strongly developed while 2 and 4 are weaker. Swelling 1 lies distally on the right wall of the bulb and passes gradually backward and to the left, swelling 3 begins above on the left wall and passes to the right anterior one as it descends; thus it is possible for them to pass over into the proximal swellings A and B in later stages, since swelling A passes distally on to the left posterior and swelling B on to the right anterior wall of the bulbus. The swellings 2 and 4 have a position between swellings 1 and 3, swelling 2 passing from above and behind downward and to the left and swelling 4 from above and in front downward and to the right.

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Fig. 384. Model of the bulbus cordis of the embryo H6, divided longitudinally. The left half of the model is shown. -4., aorta (4th aortic arch); d.Bw. 1-3, distal bulbar swellings 1-3; P., attachment of pericardium; p. Bw. A, B, proximal bulbar swellings A, B; PL, pulmonary artery (6th aortic aroh); S.a.p., septum aorto-pulmonale; *, point at which the sound in the lumen of the pulmonary artery disappears, being covered by the fusion of the distal bulbar swellings 1 and 3, forming the distal bulbar septum; **, point at which the sound again appears in the common lumen. Proximally the aorta and pulmonary artery are separated by the two proximal bulbar swellings coming into contact to form the proximal bulbar septum. The subdivision of the common efferent tube is produced distally by the septum aorto-pulmonale, in the middle region by the distal bulbar septum and proximally by the proximal bulbar septum. Between these three portions of the partition there are two points of communication, in which the ends of the sound are visible.


In addition to these two sets of bulbar swellings the septum aorto-pulmonale, in so far as it is a derivative of the truncus wall, must be considered in connection with the subdivision of the efferent tube. The partition between the sixth and fourth pairs of aortic arches, which in earlier stages reached to the line of attachment of the pericardium, grows proximally in this period of development and extends into the portion of the efferent tube that is already intrapericardial. At the same time a continually increasing portion of that part of the truncus which was originally outside the pericardium is brought within its territory by the elongation of its walls at the expense of those of the bulbus. The processes by which this change of the walls is brought about will be described later. Three factors, accordingly, take part in the subdivision of the efferent tube, the septum aorto-pulmonale and the distal and proximal bulbar swellings. At the beginning of the second period of development — in embryro H G (Fig. 384), for example — these three portions are still distinctly separated. The septum aorto-pulmonale ends bluntly, and with its prolongations are associated the distal bulbar swellings 1 and 3, which for a certain distance still project but little into the lumen, so that in this region the aorta and pulmonary artery still remain in communication ; more proximally the two swellings are in contact and consequently separate the two arterial tubes. They terminate immediately below this region of contact and are still distinctly separated from the proximal swellings A and B. At this point the more or less broad, single lumen of the proximal half of the bulb begins, and the proximal swellings, which project extensively into the lumen of the bulb, gradually flatten out. In the succeeding stages of this period the septum aorto-pulmonale reaches the point of union of the distal bulbar swellings 1 and 3, so that the aorta and pulmonary artery become separate throughout the entire extent of the distal half of the bulb; yet even in this stage the limit between the septum aorto-pulmonale and the distal bulbar septum, as the union of the distal bulbar swellings 1 and 3 may be termed, may be recognized by the differences in the histological structure of the two partitions and of the walls of the truncus and bulbus.


As regards the tissue differentiation in this period two distinct processes may be recognized : first, the differentiation of the mvocardium. and, second, the continued development of the endocardial thickenings. The differentiation of the muscular tissue proceeds more rapidly in the ventricle than in the atrium. In the latter the tissue occurs in the septum T and also in the two sinus valves, the myocardium of these latter being a single structure and no longer appearing as a duplicating projecting into the atrial cavity. It is continued as a strong bundle into the septum spurium, and. in addition, there are present some muscular ridges projecting into the lumen of the atrium, the first anlagen of the musculi pectinati. The right sinus horn, the transverse portion of the sinus, and even the left horn possess a musculature, and in the walls of the atrial canal the atrial musculature at all points is continuous with that of the ventricle. In this two portions may again be recognized, a peripheral cortical and a central trabecular layer, the latter being everywhere more differentiated than the former. In sections in which the trabecular musculature is cut longitudinally (Fig. 385) it may be seen that the fibrillar have become quite long and occupy the entire breadth of the prismatic cells ; correspondingly the boundaries between individual cells are still quite distinct where they are in contact by their lateral surfaces, while in those places where their bases are in contact the boundaries have vanished, at least it is impossible to say, on account of the extensive development of the fibrillar, to what extent these belong to one cell or the other. In transverse sections through trabecular the cell boundaries are therefore plainly visible, but at the same time the greater part of the cell body is already occupied by fibrillae. In sections of the cortical portion one can see that only the peripheral portions of the cells are occupied by very fine fibrils, the central portions being free from them and poor in protoplasm. While the development of the cortical substance in the proximal part of the bulbus keeps pace with that of the ventricle, the musculature of the distal part is less differentiated. The myocardium of this portion surrounds the bulbus tube as a distinct muscle layer and extends peripherally as far as the distal bulbar swellings can be traced, the layer, however, gradually becoming thinner distally and the differentiation of the myo-epicardial mantle less pronounced, until finally it appears not only as if a further differentiation of it had not occurred, but even as if degeneration had taken place. All those parts of the efferent tube in whose lumen the partition is formed by the septum aorto-pulmonale are destitute of myocardium.


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Fig. 385. Section through the wall of the ventricle of embryo EU (Normentafel No. 27). Mc, cortical substance; Ms., spongy substance. Muscle fibrilte are distinctly visible in the spongy substance. X 150.


The cardiac endothelium rests smoothly on the subjacent tissue in all parts of the heart and, as in earlier stages, consists of a single layer of flat cells with relatively large nuclei. The endocardial thickenings have the following distribution: in the atrium the free, thickened edge of the septum I is provided throughout its entire length with a small endocardial thickening, whose anterior and posterior prolongations extend as far as the corresponding endothelial cushions of the atrial canal and fuse with them. Consequently the foramen ovale primum is completely surrounded by an endocardial thickening. The shape of the endothelial cushions of the atrial canal has already been described, but it may be remarked that the masses of tissue now stain more deeply with hematoxylin and their nuclei are more abundant. The endocardial swellings on the narrow sides of the atrial canal have also been described already. The most important change that occurs in the atrial endothelial cushions is their undermining by the trabecular musculature of the ventricle. In earlier stages- the slope of the endothelial swellings toward the ventricular cavity was a gradual one and they did not overhang the ventricle; but now, partly by the downgrowth of the endocardial cushions and partly by the undermining of their attachment, they project freely into the lumen of the ventricle with sharp edges. The undermining is brought about by the continued extension of the trabecular network, which may be followed as far as the attachment of the anterior and posterior endocardial swellings. In the atrial canal itself the cortical and spongy substances are not yet differentiated and as a single sheet pass over into the atrial musculature. The lateral endocardial thickenings have not yet been affected by the undermining process.


The proximal bulbar swellings are bounded externally in their upper parts by the muscle ring of cortical substance ; if, however, they are traced proximally they show a change at about the level of the atrial canal, in that there develops between the endocardial thickenings and the cortical substance of the bulb a system of trabecular musculature, which is at first thin and composed of scattered trabecular, but increases gradually in thickness toward the ventricle. Here also the endocardial swellings become undermined by trabecular, and in places where the bulbar swellings have ceased for some time to be distinguishable in the model as elevations directed toward the ventricle, one sees as final prolongations of them, endocardial thickenings on the surface of the trabecular network which looks toward the lumen of the ventricle. These conditions show, moreover, the extent to which the progressive absorption of the bulbus into the ventricle has advanced in given cases. Histologically the bulbar swellings differ from the endocardial cushions principally by being somewhat poorer in cells. The distal bulbar swellings are similar in structure to the proximal ones, but the septum aorto-pulmonale is quite different. Here one finds a connective tissue which is very rich in cells with large nuclei and which does not differ from that of the rest of the wall of the aorta and pulmonary artery. This tissue also does not stain diffusely with hematoxylin. Where the septum aorto-pulmonale ends — that is to say, where it passes over into the distal bulbar swellings 1 and 3 — the histological character of the wall alters, a very delicate ring of but slightly differentiated myocardium making its appearance.


At the conclusion of the period of development just described the subdivision of the heart into the right and left halves has advanced so far that the anlagen of almost all portions of the cardiac septum have appeared and the individual cardiac cavities communicate only by more or less wide openings. In the succeeding third period of development the subdivision is completed, with the exception of that of the atria, which, as is well known, only becomes perfect post partum. But this period, which includes embryos from about 10 to 20 mm. vertex-breech measurement, and extends from the fifth to the eighth week of fetal life, shows not only the completion of the subdivision of the heart but also the almost complete development of the valve apparatus. At the close of the period the outer form of the heart and the subdivision of the ventricular cavity and bulbus are complete, but only in the next and last period is the final development of the interior of the atrium accomplished and the histological differentiation of the heart then reaches its completion. This period extends to the close of fetal life and, indeed, is not quite completed at birth.


Beginning with the changes that take place in the sinus during this period, it is seen that simultaneously with the gradual retrogression of the left sinus horn, the right one sinks more and more to the level of the posterior wall of the atrium, until finally it no longer is seen rising above the posterior surface of the atrium when the right atrium is viewed from behind. This, however, is not due to a fusion of the atrial and sinus walls, but to the absorption of the sinus walls into the posterior atrial wall by the flattening out of the furrows bounding the sinus and by the passive stretching of the sinus wall, which lags behind the rapidly growing atrium, so that both the transverse and vertical diameters of the sinus are enlarged. Thereby the opening of the superior vena cava (ductus Cuvieri), which has appeared in the meantime, is shifted from the posterior to the upper atrial wall, and similarly the inferior cava is shifted to the inferior wall. The portion of the sinus wall situated between these two vessels becomes at the same time part of the posterior wall of the atrium, and this exogenous portion of the atrial wall is delimited from the parts in its neighborhood by the line of attachment of the two sinus valves. While the right sinus valve is still very high at the close of this period, the left one lags behind in its development and undergoes a modification to be described later.


With this absorption of the sinus wall into the posterior wall of the atrium there occurs a change in the opening of the transverse portion of the sinus into the right sinus horn. This transverse portion, the continuation of the left horn, opened hitherto into the left lower angle of the right sinus horn immediately beside the opening of the inferior vena cava. By the absorption of the sinus the opening is brought to the level of the posterior atrial wall, and with it the spur-like elevation between it and the right hom, representing the former bend of the transverse portion toward the right horn. This sinus septum, that seems to arise from the posterior wall of the atrium, now grows so far toward the right that it reaches the valvula venosa dextra and divides this into two portions, — a shorter portion in front of and below the line of meeting of the two structures, and a longer portion behind and above, passing upward over the posterior wall of the atrium and disappearing in the septum spurium. When the last period of development is being considered it will be seen that from the former portion the valvula Thebesii is formed and from the lower part of the latter portion the valvula Eustachii.


The foramen ovale I closes at the end of the preceding period by the fusion of the free edge of the septum I with the endocardial cushions of the atrial canal, but the foramen ovale II still forms a wide communication between the two atria on account of the feeble height of the septum II. Later this septum increases in height and there is in consequence a narrowing of the foramen ovale II. But in addition another change occurs in the circumference of the foramen, dependent upon a change in the direction of growth of the two septa. This change is as follows: at the beginning of this period the free edge of the septum I, directed toward the foramen ovale II, in the natural position of the heart (the plane of the foramina atrio-ventricnlaria almost frontal), looks backward and upward ; gradually, however, its lower prolongation extends backward and upward, at first over the posterior wall of the atrium and finally over the upper wall, while the upper prolongation lags behind in its growth, so that now, with the heart in the same position, the free edge of the septum looks forward and upward. At the beginning of this period the septum II is still low, and its free edge, directed toward the foramen ovale II, looks forward and downward in the natural position of the heart. Later the septum becomes higher and at the same time its anterior prolongation grows forward and downward over the upper wall of the atrium, until finally the free edge of the septum looks backward and downward. The two septa have thus altered their relative positions to the extent that the posterior prolongation of the septum I on the left side has grown past the line of attachment of the septum II, and the anterior prolongation of the septum II has similarly on the right side grown past the line of attachment of the septum I. The left sinus valve now also takes part in the formation of the circumference of the foramen ovale II in the following manner : the outpouching of the right atrium, the spatium inter septo-valvulare, described in the preceding period of development and situated between the left sinus valve or the septum spurium and the septum atriorum, continually lags behind in its growth. Consequently the prominence produced by the spatium on the posterior wall of the atrium also disappears and the valvula venosa sinistra gradually approaches the septum atriorum, and, finally, there remains of the once extensive spatium intersepto-valvulare only a small cleft-like recess, which is closed below by the fusion of the lower end of the left sinus valve with the lower prolongation of the septum secundum. Later, while the destruction of the spatium intersepto-valvulare is taking place by the fusion of the valvula venosa sinistra with the septum I, the upper and middle portions of the left sinus valve vanish more or less completely, but the lower part, persisting on account of its union with the septum II as described above, elongates its free border backward and upward, and so completes later the limbus Vieussenii, which is formed from this free border.


In the earlier period of development the single quite short pulmonary vein trunk opens close to the line of attachment of the septum atriorum. Later there is an absorption of this short trunk into the posterior wall of the atrium, so that the right and left pulmonary veins open into the left atrium by two separate openings. The portion of the atrial wall between the two openings has therefore been formed by an originally extracardial portion of the pulmonary veins, and later it increases rather rapidly in breadth, so that the two pulmonary veins become separated more and more.


The changes in the form of the atrial canal have been followed to the time when the canal is a slit so narrow in the frontal direction that its central portion is a mere cleft, while its lateral extremities represent the places in which the atrio-ventricular valves will develop. At the beginning of the present period of development the opposed edges of the slit fuse throughout their whole extent, where the marginal tubercles, that have already been described, occur. In this way the single atrial canal is divided to form the two atrio-ventricular orifices, which are separated by the entire width of the zone of fusion. The septum primum rests upon this zone of fusion.


The subdivision of the ventricular cavity has progressed by the ventricular septum becoming higher, so that only a small opening, the remains of the foramen interventricular e, exists between its upwardly concave margin and the under surfaces of the endocardial cushions, which, in the meantime, have fused. The anterior end of the ventricular septum, which if prolonged would come into relation with the two right tubercles of the endothelial swelling, passes without interruption into the remains of the bulbo-atrial ridge, while the posterior prolongation applies itself directly to the right tubercle of the posterior endocardial cushion.


Before the processes which lead to the final closure of the foramen interventriculare are described it will be necessary to consider in detail the subdivision of the bulb, since the two sets of processes not only take place simultaneously but also show a causal dependence. After the fusion of the distal bulbar swellings 1 and 3 the lumen of the aorta contains one half of each bulbar swelling 1 and 3 and the whole of the swelling 4, while the pulmonary artery has the other halves of swellings 1 and 3 and the entire swelling 2. The external groove between the aorta and pulmonary artery, which was present in earlier stages only in the distal portion, has now become prolonged proximally and has deepened, so that the two vessels have almost circular lumina.


While the peripheral portions of the distal bulbar swellings flatten out and finally disappear, their most proximal portions, which have come into relation with the proximal swellings A and B, not only retain their former height but increase in size and begin to be hollowed out in their distal slopes. Thus there are formed in each vessel three plump folds directed distally, the first anlagen of the semilunar valves. The pouch-like cavities between these folds and the walls of the vessels gradually increase in size, partly by the folds becoming thinner and partly by the outpouching of the corresponding portions of the walls of the vessels, and the evaginations so formed are the anlagen of the sinus Valsalva. A complete separation of the aorta and pulmonary artery has thus been accomplished, and the semilunar valves develop, as has just been described, from the lower end<= of the distal bulbar swellings. Proximally the proximal bulbar swellings A and B, which have increased in height in the mean time, fuse to form a short septum, the proximal septum bulbi, which extends toward the ventricle from the line of the semilunar valves. This septum lies in the same plane as the septum between the aorta and pulmonary artery, which was formed by the fusion of the two distal swellings 1 and 3, but it becomes replaced by the tissue of the septum aorto-pulmonale as the wall of the truncus arteriosus elongates proximally at the expense of the wall of the bulbus. The proximal septum thins out rapidly as it is traced downward, and, in the natural position of the heart, it extends from the right above and behind to the left down and forward, and consequently does not lie in line with the sagittally placed septum interventriculare, but forms with it a sharp angle, open upward and backward (Fig. 386). The proximal septum bulbi has a free border that is concave downward, and its anterior prolongation, the bulbar swelling A, becomes continuous with the anterior prolongation of the upwardly concave septum interventriculare, while its posterior prolongation, the swelling B, deviates to the right of the right tubercle of the anterior endocardial cushion and becomes greatly broadened and flattened; the posterior prolongation of the septum interventriculare, however, runs toward the right tubercle of the posterior endocardial cushion. If one follows the margin of the foramen hiterventriculare, beginning with the posterior prolongation of the septum bulbi, it is found to be a spiral ridge, that runs first upward along the free concave border of the proximal septum bulbi, passing anteriorly into the edge of the septum interventriculare, then along this downward and backward and finally upward again, to terminate at the right tubercle of the posterior endocardial cushion. The opening so bounded unites not only the two ventricles, but also leads upward and to the right into the pulmonary artery and to the left and upward into the aorta. It becomes closed in the following manner: the proximal septum bulbi grows downward and reaches the septum interventriculare. The right ends of the endocardial cushions, which have fused in the meantime, undoubtedly participate in the fusion of the two septa, but the extent of their participation cannot be exactly determined, since the entire circumference of the foramen interventriculare is surrounded by endocardial growths which pass into one another. Since from the very beginning the septum interventriculare tends toward the right tubercles of the endocardial cushions, and since the final closure of the foramen interventriculare takes place in the region where they occur, it follows that the right atrio-ventricular orifice lies immediately adjacent to the point of closure, while the left one is separated from it by the entire breadth of the fused endocardial cushions. A further complication is introduced by the fact that the closure of the foramen takes place with the aid of the prolonged septum aorto-pulmonale, so that the right portion of the circumference of the aorta comes to lie at the very point of closure. Consequently the septum membranaceum, which is formed at the point of closure, forms a constituent of the wall of the conus arteriosus aortce.

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Fig. 386. Model of the heart of embryo S2 of 14.5 mm. greatest length (Normentafel No. 58). In the collection of the I. Anatomical Institute, Vienna. Modelled by J. Tandler. The model has been divided transversely midway between the atrio-ventricular groove and the apex of the ventricle and the upper half is shown from below. E.r., the two endocardial cushions fused; l.H.h.E., left tubercle of the posterior cushion; l.H.v.E., left tubercle of the anterior cushion; O.v.d., right ostium venosum; O.v.s., left ostium venosum; PL, pulmonary artery; p.S.B., proximal septum bulbi; r.H.t.e., right tubercle of the anterior endocardial cushion; S.v., septum ventricularum; Y.b.l.Z., lateral cusp of bicuspid valve. The arrow points to the orifice of the aorta. X 44.


Since the septum atriorum is attached to the endocardial cushions much further to the left than the septum interventriclare. the portion of the fused cushions between the attachments of the two septa, when it later comes to lie in the planes of the septa, does not separate ventricle from ventricle, but the sinus arteriosus aortae, i. e., the left ventricle, from the right auricle, and it may therefore be termed the septum atrio-ventriculare (Hochstetter). The distance between the semilunar valves and the point of final closure of the foramen interventriculare is still relatively great, so that the aorta, and especially the pulmonary artery, arise from the ventricles as elongated cones. The inner surfaces of the cones are smooth, trabecular musculature not having yet developed in their walls. "With the closure of the foramen interventriculare the final subdivision of the ventricular portion of the heart is completed.


The histological changes occurring during this period may be described as follows : The left sinus horn possesses far distally a muscle mantle that is interrupted by the openings of certain cardiac veins. The differentiation of this musculature, as well as of that in the region of the atrial wall which has been formed by the absorption of the right sinus horn, lags far behind that of the rest of the atrium. In the regions of the septum I and the septum II, as well as in the sinus valves, musculature is present, but it has made no especial progress in differentiation. In the portions of the atrium which represent the auricular appendages trabecular have developed, more apparently on the right side than on the left. In the small area of the left atrium, which was formed by the absorption of the pulmonary trunk, no musculature is evident at this period. As to the ventricular musculature it may be noted in the first place that the wall of the left ventricle undoubtedly surpasses that of the right in thickness. The difference depends, however, especially on the cortical substance. The trabecule are exceedingly numerous and almost fill the entire cavities, yet they are not so uniform in thickness and differentiation as in the earlier stages, but trabecular conspicuous by their strength and advanced differentiation occur in both ventricles. These trabecule, from their topography and from their relation to the valves, are to be identified as anlagen of the musculi papillares. While, at the beginning of the period under consideration, the cortical substance was relatively thin, at the end of the period it has become greatly developed and its fibrillar structure has made further progress.

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Fig. 387. Section through the heart of embryo Mi of 16.75 mm. greatest length. In the collection of the I. Anatomical Institute, Vienna. Semidiagrammatic. S.a., septum atriorum; S.a.v., septum atrioventriculare; S.v., septum ventriculorum; V.d., right ventricle; V.s., left ventricle; V.v., valvule venosse.


In longitudinal and transverse sections through the cardiac musculature the individual muscle-cells show distinct cell boundaries on their long sides, but pass into one another on their short sides without any delimitation, a condition that was present to some extent in the earlier period of development, but has now become general. To this extent it is proper to speak of a cardiac syncytium at the end of this period. 4 At the same time the myocardium shows a further differentiation in that the individual rows of muscle-cells have already become arranged to form muscle bands, just as one sees them in the adult heart.


While up to the present the atrial and ventricular musculatures were continuous around the atrial canal, one now sees these two portions of the musculature lose their continuity. In earlier stages there was along the line of the atrio-ventricular groove an aggregation of embryonic connective tissue, which was wedgeshaped in section, the edge of the wedge being directed inward. In later stages this wedge gradually becomes prolonged toward the cavity of the heart and cuts so deeply in between the atrial and ventricular musculature throughout the entire circumference of the atrio-ventricular groove that the direct continuity of the atrial and ventricular cortical substance is interrupted. Thus the original continuous cortical musculature is divided into two portions, a sinus-atrial portion and a ventricular portion, while the trabecular parts are still in continuity at the anlagen of the valves.


The changes in the form of the endocardial thickenings occurring in the atrial canal and in the bulbus have already been described. The following points may be noted as regards their texture. The plump semilunar valves, formed from the proximal ends of the distal bulbar swellings, do not yet show any special differentiation of their tissue, at least their diffuse staining has not appreciably diminished, although the nuclei of these portions of the endocardial swellings are perhaps somewhat more closely set than formerly. The part of the septum aorto-pulmonale that follows, i e., the proximal septum bulbi, still shows all the characteristics of endocardial growths, as do also its prolongations, the remains of the bulbar swellings A and B. If one follows the bulbar swelling A, one sees the tissue characteristic of such swellings fade out at the free edge of the septum interventriculare and pass posteriorly without interruption into the fused endothelial swelling. The tissue of the posterior bulbar swelling becomes


4 The old discussion concerning the boundaries of the cardiac muscle-cells cannot be considered here. As has already been described, the fibrillas pass beyond the cell territories, a condition which may justify the term syncytium. The condition described above is not, however, sufficient for the settlement of the question, since the staining of the objects (haematoxylin-eosin) is not suitable for final conclusions.


greatly broadened and in part passes medially into the tissue of the endocardial cushions and into the endocardial thickening on the free edge of the interventricular septum, and in part it passes laterally toward the lateral circumference of the right atrio-ventricular orifice and may be followed for some distance toward the apex in the posterior wall of the ventricle.


When the closure of the interventricular foramen is completed, nothing can be determined as to the origin of the various parts contributing to the closure from their texture, the entire region being occupied by an endocardial tissue, relatively poor in cells and staining diffusely with hsematoxylin, and which at the very spot of the future septum membranaceum undergoes rather soon a further development ; it loses its diffuse staining with haematoxylin and at the same time becomes richer in cells. The anlagen of the valve cusps, which arise from the anterior and posterior endocardial cushions, as well as from the endocardial thickenings at the lateral ends of the atrial canal, lag behind the region just described in their differentiation (Fig. 387). These anlagen are plump and their undermined borders are connected with the trabecule of the ventricles. This connection is quite distinct where especially strong Irabeculae, the anlagen of the musculi papillares, come into connection with definite portions of the valves. In such places it is possible to follow muscle bundles ascending from the cortical substance through the entire length of the papillary anlage to the valve. The muscle bundles on the atrial surface of the valve anlagen which have been described as passing toward the ventricles are apparently continuous with the ventricular bundles just described; at least no boundaries between the two could be made out. Thus the valve cusps are for a time a series of plump elevations, consisting partly of endocardial growths and partly of musculature; a differentiation into actual musculi papillares, chordas tendinese, and valve flaps cannot be distinguished at this stage.


In addition, the degenerated processes which occur in the region of the bulbus cordis are of interest. At the beginning of the period under consideration the undermining of the proximal bulbar swellings by the trabecular myocardium has not extended verv far. The older the embryo, the more the trabecular tissue grows toward the line of attachment of the semilunar valves. On the other hand, one sees the cortical substance, which formerly surrounded the bulbus far distally, gradually receding, the recession being accompanied by a simultaneous change in the structure of walls of the derivatives of the distal part of the bulbus, the aorta and pulmonary artery. The typical wall of the two arteries extends gradually proximally, until finally this typically layered wall, destitute of myocardium, mav be followed to near the semilunar valves. The part of the bulb immediately distal to- the valve zone thus becomes surrounded by a common myocardial layer, so that in this stage of development the future bulbus aortae is surrounded for a considerable distance by cardiac musculature. Toward the end of the period this portion of the musculature is so far degenerated that the relation of the aorta to the musculature is almost that which obtains in the heart of the child.


In the following period of development the parts of the heart that have been already elaborated undergo a further modelling and are slightly altered, but one sees nowhere any extensive transformations of the constituent parts of the heart. The same is true also with regard to the further histological differentiation.


As regards, first of all, the sinus portion of the heart, one sees that, in consequence of the apposition of the left sinus valve to the septum atriorum, the latter comes to represent the medial boundary of the sinus area, while the lateral boundary is formed by the derivatives of the right sinus valve or of the septum spurium. It is therefore necessary to consider first the extensive modifications of the right sinus valve (Fig. 388). As was noted in the account of the preceding period of development, this broad valve, which projects markedly into the lumen of the atrium, is divided by the apposition of the sinus septum into two parts, an anterior inferior (ventral) and a posterior superior (dorsal). The dorsal portion of the valve is continued without interruption into the septum spurium, which formerly served as a common stay for the two valvular venosae, and later it undergoes further modifications. The portion of valve corresponding to the posterior wall of the atrium, which was also originally high, gradually flattens and forms a prolongation of the ridge-like elevation of the septum spurium on the upper wall of the atrium, carrying it over this wall backward and downward. This small ridge, which forms the persistent lateral boundary of the original sinus area, consists in its upper portion of the rudiment of the septum spurium and in its posterior inferior portion of the rudiment of the right sinus valve, the crista terminalis of His.


The lower part of the dorsal portion of the sinus valve remains high and bounds the opening of the inferior vena cava laterally, as the valvula vence cavce Evstachii. Frequently one may actually speak of an increase in the surface of this portion, but the valve presents great variation in its height, development, and form. In accordance with its development the valvula Eustachii is continuous above and behind with the crista terminalis and in front and below it ends at the border of the transverse portion of the sinus, i. e., the sinus coronarius cordis.


The ventral, much smaller portion of the right sinus valve bounds the opening of the sinus coronarius, that has been formed from the transverse portion of the sinus, and eventually becomes the valvula Thebesii.


Since the atrial septum must furnish until birth a means of communication between the two atria, a final closure of this portion of the heart cannot occur during embryonic life. In the developmental period under consideration the septum I increases in height more rapidly than its surrounding parts increase in extent ; the communication between the two atria thus becomes somewhat narrowed, but, on account of the oblique position of the septum I, it continues to be wide enough to allow free passage of the blood from the right atrium into the left. The oblique position of the septum I is not determined by any special mode of growth of the septum, but is produced mechanically by the greater pressure of the blood in the right atrium. The septum I, i. e., the valvula f oraminis ovalis Vetteri, only attains its definitive position when the blood pressure becomes equal in the two atria, and then only does it have an opportunity for fusing with the septum II and so bringing about the final separation of the two atria.


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Fig. 388. Model of the heart of an embryo of 310 mm. greatest length. Modelled by Born. C. i., vena cava inferior, in which a sound is placed; C. t., crista terminalis; S.I, septum primum; S. II, septum secundum; S. c, opening of coronary sinus; S. s., sinus septum; Y. E., valvula Eustachii; V.Th., valvula Thebesii.


Before mentioning the changes that take place in the ventricles and the valve apparatus, a few words are necessary as to the modifications that now occur in the left atrium. By the absorption of the originally single pulmonary vein trunk, these veins are now represented by two stems, and at the same time a new portion, corresponding to the distance between the two pulmonary orifices, has been added to the atrial wall. This portion continues to increase in breadth, and at the same time the absorption of the two pulmonary vein stems progresses until these have been taken up into the atrial wall as far as their first division. As a result the originally single openings of the right and left venae pulmonales become again divided, so that on either side there is an upper and a lower pulmonary vein orifice. The portion of the atrial wall between each pair of pulmonary veins was likewise originally a part of the wall of the veins. It will thus be seen that the participation of the pulmonary veins in the formation of the wall of the left atrium is quite extensive.


The anatomical changes occurring in the ventricular portion of the heart during this period can be briefly described. The valve apparatus alone undergoes further elaboration in that the differentiation of the valve cusps, the chorda tendinece, and the musculi papillares makes further progress and the formal differentiation of the semilunar valves increases.


The histological differentiation of the heart approaches its conclusion during this period. The principal changes occur in connection with the valve apparatus, but before this is described it will be necessary to consider briefly the remaining portions of the heart. And, first of all, it may be noted that even in the latest fetal stages the development of the sinus musculature lags behind that of the rest of the atrium.


While the part of the right sinus valve which becomes the valvula Eustachii continues to lose its musculature, that of the crista terminalis continually increases. The rudiment of the left sinus valve still shows traces of musculature in later stages of fetal life, as, for instance, in a fetus of 150 mm. vertex-breech length. The originally thin margin of the limbus Vieussenii thickens by the development of strong muscle bundles in it.


The portion of the left atrial wall lying between the openings of the pulmonary veins was destitute of musculature in the earlier period of development, but in this period it acquires a complete muscle layer. The differentiation of the musculi pectinati takes place more rapidly than that of the remaining portions of the atria.


The greater thickness of the cortical substance of the left ventricle continually increases (Fig. 389), and the fibrillar of this layer become more and more abundant until the difference between the cortical and spongy substances which obtained at the beginning of the period now under consideration gradually disappears. In this period also loose subepicardial connective tissue appears on the surface of the heart along the lines of the vessels and nerves.


The semilunar valves become thinner, their connective tissue loses its succulent character, becoming fibrous and tendinous, and finally presents the characteristic appearance seen in the child.


While in the earlier period the endocardial portion of the atrio-ventricular valves greatly surpassed the muscular, at the beginning of the present period the trabecular which pass from the spongy substance of the ventricle toward the valves increase greatly, and at the same time the central portions of the valves come to project further into the lumen, owing to the growth of their peripheral portions. In accordance with this process the trabecular of the spongy substance, which originally were almost immediately in contact with the cortical substance in the neghborhood of the atrio-ventricular orifices, separate from the corticalis more and more and pass centrally. In this stage also not one free-ending trabecula could be found as an indication of a secondary union between the valves and the papillary muscles. At this time also the musculature on the atrial surfaces of the valves becomes greatly developed, so that, in comparison with later stages, it actually seems as if the valves were exclusively muscular in structure, with the exception of the purely endocardial marginal portions which are directed toward the lumen. Later the musculature degenerates, at first in the valve areas, and connective tissue takes its place, standing in intimate connection with the connective-tissue wedge which was described as occurring in the earlier stage of development and which separates the cortical substance of the atria from that of the ventricles. Still later one sees that the peripheral portion of the ventricular valve musculature degenerates, at first at the surface and then more deeply, giving place to connective tissue and so becoming transformed into chordce tendinece. In later stages accordingly one must distinguish between a connectivetissue valve (the secondary valve of Bernays), chordce tendinece, and papillary muscles. The free margins of the valves at certain points retain for a longer time the characteristic structure of the endocardial thickenings, while in other points they are converted into typical connective tissue. These thickenings represent the noduli Albini.

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Fig. 389. Section through the heart of an embryo of 165 mm. greatest length. V. d., right ventricle; V. s., left ventricle. The difference in the thickness of the two ventricles is apparent.


Appendix

The developmental history of the atrio-ventricular system is at present practically unknown. The time allowed for the completion of the present article did not permit a thorough study of the question and a satisfactory solution of it, and I shall therefore state the results of my observations briefly.


In a human embryo of 19.75 mm. one sees at the upper border of the septum inusculare, close to the lower surface of the not yet completely differentiated endothelial swelling, a triangular area, which occupies the tip of the muscular septum and is distinguishable even under a low magnification by its special staining properties. Its nuclei are dark and the cell bodies stain faintly with eosin. It is not unlike a sympathetic ganglion, but its cells are less numerous. This structure corresponds in position with the stem of the His bundle, and it already possesses a right and left prolongation, which are the right and left limbs of the atrio-ventricular system.


An embryo of 28.5 mm. shows a similar condition at the same region, but the two limbs have become longer and the cells larger. A similar aggregation of cells is to be seen in the region of the septum atriorum, immediately above the septum membranaceum.


In the study of the development of the bundle of His the following point is of importance.


The conducting system may either be a persistent connection between the atrial and ventricular musculatures situated in the posterior wall of the heart, in which case it would represent an ancient connection between the two parts of the heart, or it may be a new development which has been formed only after the completion of the septum, in other words only secondarily. If the latter be the case, the conducting apparatus of hearts without a septum is quite a different affair from that of hearts which possess a septum. Furthermore the conduction of stimuli in hearts which possess a septum must be a different affair before the development of the septum — that is to say, before the development of the bundle of His — from what it is later on.


So far as my observations go, I incline to the view that the His bundle does not represent the persistence of an ancient atrioventricular connection. This view has also been expressed by Retzer, who has supplied some data as to the development of the atrio-ventricular system of the pig.




Literature

Bernats, A. C. : Entwicklungsgeschichte der Atrioventrikularklappen. Morphol. Jahrbuch. Vol. 2. 1876.

Born, G. : Ueber die Bildung der Klappen, Ostien und Seheidewande in Saugetierherzen. Anat. Anz. Vol. 3. 1888.

Beitrage zur Entwicklungsgeschichte des Saugetierherzens. Arch, fiir mikr. Anat. Vol. 33. 1889.

His, W. : Anatoniie mensehlieher Embryoneu. Leipzig. 1880-1885.

Mitteilungen zur Embryologie der Saugetiere und des Menschen. Arch. fur Anat. u. Phys. 1881.
Ueber die Entwieklung der Form und der Abteilungen des Herzens. Comptes Rendus Congres period, intemat. des sci. med. 1884.
I. Section d' Anatomie. Copenhagen. 1886.
Beitrage zur Anatomie des menschlichen Herzens. Leipzig. 1886.

Hochstetter, F. : Ueber die pars membranaeea septi. Vortrag gehalten in der wissenschaftlichen Aerztegesellsehaft zu Innsbruck. Wiener klin. Wochen schr. 1898.

Die Entwieklung des Blutgefasssystems. Hertwig's Handb. der vergl. und experim. Entwicklungsgesch. d. Wirbeltiere. Vol. 3. 1906. (Published 1901 and 1903.)

Keibel, F., and Elze, C. : Normentafel zur Entwicklungsgeschiehte des Menschen. Jena. 1908.

Mollier: Die erste Anlage des Herzens bei den Wirbeltieren. Hertwig's Hand. d. vergl. u. exper. Entwicklungsgesch. d. Wirbeltiere. Vol. I. 1906.

Retzer: Some Results of Recent Investigations on the Mammalian Heart. Anat. Record. Vol. 2. 1908.

Spee, Graf F. : Beobachtungen an einer menschlichen Keimscheibe mit offener Medularrinne und eanalis neurentericus. Arch, fiir Anat. u. Physiol. Anat. Abth. 1889.

Thompson P. Description of a human embryo of twenty-three paired somites. (1907) J Anat Physiol, 41(3):159-71. PMID 17232726



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XVIII. Development of Blood, Vascular System and Spleen: Introduction | Origin of the Angioblast and Development of the Blood | Development of the Heart | The Development of the Vascular System | General | Special Development of the Blood-vessels | Origin of the Blood-vascular System | Blood-vascular System in Series of Human Embryos | Arteries | Veins | Development of the Lymphatic System | Development of the Spleen
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العربية | català | 中文 | 中國傳統的 | français | Deutsche | עִברִית | हिंदी | bahasa Indonesia | italiano | 日本語 | 한국어 | မြန်မာ | Pilipino | Polskie | português | ਪੰਜਾਬੀ ਦੇ | Română | русский | Español | Swahili | Svensk | ไทย | Türkçe | اردو | ייִדיש | Tiếng Việt    These external translations are automated and may not be accurate. (More? About Translations)

Keibel F. and Mall FP. Manual of Human Embryology II. (1912) J. B. Lippincott Company, Philadelphia.

Manual of Human Embryology II: Nervous System | Chromaffin Organs and Suprarenal Bodies | Sense-Organs | Digestive Tract and Respiration | Vascular System | Urinogenital Organs | Figures 2 | Manual of Human Embryology 1 | Figures 1 | Manual of Human Embryology 2 | Figures 2 | Franz Keibel | Franklin Mall | Embryology History