Living morphogenesis of the ventricles and congenital pathology of their component parts.

Living morphogenetic studies show that each definitive ventricle is constructed from different primitive cardiac segments, and each has its specific anatomical features. These ventricular segments are the atrioventricular junction; the primitive inlet segment, part of the primary heart tube, which initially provides the inlets of each ventricle; the primitive outlet segment, which gives rise to both ventricular outlets; and the apical trabeculated regions of the right and left ventricles which grow from the primary heart tube, respectively. In this review, we describe regional pathology based on the relationship of these primitive ventricular components. We propose that the abnormal morphogenesis of one of these segments gives origin to regional ventricular pathology. For example, abnormal embryogenesis of the atrioventricular canal produces malformations of the atrioventricular junctions, such as double inlet ventricle, absence of one atrioventricular connection, and straddling and overriding atrioventricular valves. Similarly, abnormal morphogenesis of the primitive outlet segment gives rise to malformations of the subarterial region of each ventricle, along with the valves guarding these vessels. The principal anatomical features of these malformations of the ventricular inlets and outlets are described, and their possible morphogenesis is discussed. Due to the fact that the apical trabeculated region of each ventricle arises from a separate primitive segment, each ventricle can be identified according to the pattern of its apical trabeculations. This feature is crucial in the elucidation of complex congenital pathology, such as discordant atrioventricular connections.

Temporal and spatial asymmetries in the initial distribution of mesenchyme cells in the atrioventricular canal cushions of the developing chick heart.

BACKGROUND: We investigated potential early asymmetries in the distribution of mesenchymal cells within the inferior and superior AV cushions in the developing chick heart. METHODS: Chick embryos stages 16-20 HH were fixed, embedded in polyacrylamide, and the cell nuclei stained with propidium iodide. Cells counts were determined within the cardiac jelly of the atrioventricular canal (AV) by laser confocal microscopy in coronal planes spanning its entire length. RESULTS: Our data show at the different stages studied, 16-20 HH, that the inferior AV cushion invariably contains more cells than the superior AV cushion. In the inferior cushion, the cell distribution is bimodal, i.e., the proximal and distal regions have more mesenchymal cells than the middle part of the AV canal. In the superior cushion, there is a increasing gradient of mesenchymal cells along the longitudinal axis from the atrium to the ventricle. CONCLUSIONS: Our findings reveal that the temporal and spatial characteristics of mesenchyme formation in the inferior vs. superior AV cushion are different. This asymmetry suggests several potential hypotheses: (1) the distribution of the inducer molecule or its receptor has a distribution similar to that of mesenchymal cells, (2) the extracellular matrix has a differential composition or regionally-specific physical associations, (3) the endocardium is heterogeneous with respect to transformation capacity, or (4) these patterns result from an earlier inductive event. The potential importance of the observed asymmetries in the distribution of AV mesenchyme is discussed relative to localization patterns of molecules critical to successful cardiac morphogenesis and remodeling.

Primitive interventricular septum, its primordium, and its contribution in the definitive interventricular septum: in vivo labelling study in the chick embryo heart.

BACKGROUND: Because the studies on the embryological development of the primitive interventricular septum have been done with postmortem material, we do not know the site within the cardiac tube and the developmental stage at which the primordium appears and its anatomical manifestation in the mature heart. Consequently, we do not know its real contribution to the constitution of the definitive interventricular septum. METHODS: With this purpose, we selected an adequate biological model, the chick embryo heart and the in vivo labelling technique. We placed a label of gelatin India ink in the ventral fusion line of both cardiac primordia at the level of the interventricular grooves in the straight tube heart (stage 9+HH), and we traced the ink up to the mature heart (stage 36HH). We made histological sections of some hearts, of the zone where the label was found to investigate the first morphological manifestation of the primitive interventricular septum. We also made microdissections and scanning electron microscopic studies. RESULTS: The label placed at stage 9+HH in the ventral fusion line of both cardiac primordia, at the level of the interventricular grooves, was found at stage 14HH in the greater curvature of the looped heart, opposite the left interventricular groove. This label at stage 17HH was found in the apical trabecular region of the first cardiac septum (8-shaped septum) and in the mature heart (stage 36HH) in the definitive interventricular septum at the limit between the basal and the medial third of the definitive interventricular septum. CONCLUSIONS: Firstly, the primordium of the primitive interventricular septum appears at stage 9+HH, in the ventral fusion line of both cardiac primordia at the level of the interventricular grooves. Secondly, its first morphological manifestation takes place at stage 17HH, and it forms the apical trabeculated region of the first cardiac septum (8-shaped septum). Thirdly, the primitive interventricular septum gives origin to the middle and apical third of the definitive interventricular septum.

Coronary arteries in transposition of the great arteries.

The topic of coronary arteries in transposition of the great arteries (TGA) is complex and confusing despite having been the subject of several recently published reports. One hundred thirty-three autopsy specimens of uncomplicated TGA were studied, with special attention to methodologic issues in anatomic description and classification. Uncomplicated TGA was defined as congenital anomaly involving origin of the aorta from the right ventricle and of the pulmonary artery from the left ventricle. Three types of transposition were recognized ("anterior aorta," "side-by-side," and "posterior aorta") depending on the aortopulmonary relations, which were intrinsically defined by the relation of the valvular orifices of the great arteries with respect to the atrioventricular orifices. The frequency of distribution of individual coronary patterns differs substantially in the first 2 types of TGA. As in normal hearts, coronary arteries in TGA tend to originate from the facing sinuses (adjacent to the pulmonary valve); in TGA, however, variations in further distal anatomy are much more frequent. It is suggested that individual coronary patterns be described in terms of number of ostia, exact ostial location within or outside the aortic sinuses, and proximal course and distribution. The use of strict, simplified classifications of coronary patterns is discouraging because of the relevance of each individual anatomic parameter to clinical aims. Because of the aortopulmonary switch repair for TGA, this study emphasizes the surgical implications of the different coronary features.

The right atrioventricular valvular apparatus in the chick heart.

The purpose of this study was to describe the detailed anatomy and histology of the right atrioventricular valve apparatus in the chicken. Newborn and adult chicken hearts were studied by anatomic description, light and scanning electron microscopy, and histologic (Masson's trichrome stain) and histochemical (Sirius Red stain) techniques. Our findings indicate the presence of an incomplete fibrous annulus, a great mural leaflet, and multiple microleaflets in the right atrioventricular apparatus of the chicken heart. The great mural leaflet, essentially muscular in structure, extended from the anterior and posterior juxtaseptal commissures and was subdivided into an anterior and a posterolateral region by the attachment of the anterolateral papillary muscle. The posterolateral region presented an intermediate cleft, subdividing this region into an anterior and a posterior portion. Multiple microleaflets, which adhered to the upper right side of the ventricular septum adjacent to the right atrioventricular orifice, inserted directly into the ventricular septum via short chordae tendineae, without papillary muscles. The microleaflets were composed of smooth subendocardial connective tissue, with varying amounts of type I, II and III collagen. In addition, we observed a central fibrous body, leading to fibrous continuity between the mitral and aortic valves and the mitral and right atrioventricular valves. An atrioventricular septum was also present.(ABSTRACT TRUNCATED AT 250 WORDS)

[Teratology and epidemiology in the study of environmental teratogens]. / La teratología y la epidemiología en el estudio de los teratógenos ambientales.

The processes of cellular migration, cellular differentiation and cellular multiplication are studied, since these are the basic developmental processes upon which teratogenic agents act resulting in congenital malformations. We also carefully analyze the interactions between teratogen-embryo in order to establish adequate parameters for analysis of environmental teratogens, as well as experimental teratogenesis and epidemiology. Information on the pathogenesis of congenital malformations obtained from experimental teratology in an adequate biological model, can be extrapolated to the human. The etiology of congenital malformations resulting from environmental teratogens can only be elucidated through epidemiology, since there is species specificity. Such a study must fulfill the following prerequisites: diagnosis of the congenital malformation, ruling out genetic factors in the family tree and determination of the exact time of exposure to the possible teratogen during the pregnancy.

The infundibular interrelationships and the ventriculoarterial connection in double outlet right ventricle. Clinical and surgical implications.

Fifty specimens of double outlet right ventricle were studied. The insertion of the outlet (infundibular) septum determines two types of infundibular interrelationships. In the first type, with anterior and posterior infundibulums, the outlet septum is inserted to the anterior limb of the septomarginal trabeculation; the posterior infundibulum is related with the atrioventricular orifices and the interventricular septum forms exclusively one of the walls of the posterior infundibulum. Therefore, the artery connected with the posterior infundibulum may be related with a subarterial ventricular septal defect. Of our material, 35 cases (70% of 50) had anterior and posterior infundibulums and, in 32, the aorta was connected with the posterior infundibulum (91.4% of 35). The ventricular septal defect was subaortic in 26 cases (81.2% of 32). In the second type, with side-by-side infundibulums, the outlet septum is inserted in to the ventriculo-infundibular fold in the proximity of the posterior limb of the septomarginal trabeculation. Both infundibulums are related with the atrioventricular orifices and the interventricular septum forms exclusively one of the walls of the medial infundibulum. Therefore, the artery connected with the medial infundibulum has the possibility of being related with a subarterial ventricular septal defect. Of our material, 13 cases (26% of 50) had side-by-side infundibulums. In all of these (100% of 13), the pulmonary trunk was connected with the medial infundibulum and the ventricular septal defect was subpulmonary in 12 cases (92.3% of 13). There were two cases (4% of 50) with a doubly committed ventricular septal defect. The insertion of the outlet septum permits one to determine the infundibular interrelationships, information which cannot be attained by taking into account the relationship of the great arteries with each other. Once the infundibular interrelationship is established, one must determine if the aorta is connected with the posterior or with the medial infundibulum, since, depending on the anatomical constitution of these infundibulums, there is the possibility of a ventricular septal defect being related with this artery. This information is indispensable before attempting the surgical correction of the double outlet right ventricle and it may be obtained by echocardiography or by angiocardiography.

Coronary arteries in truncus arteriosus.

The origin and distribution of the coronary arteries was described in 39 autopsy specimens of truncus arteriosus (TA). The specimens were classified according to the number and the patterns of the truncal cusps. The position of the truncal cusps was defined in relation to intracardiac structures, namely, the atrioventricular orifices. Bicuspid truncal valves were observed in 8 cases (21%), tricuspid in 22 cases (56%) and quadricuspid in 9 cases (23%). All tricuspid valves had 2 anterior and 1 posterior cusp. Great variability in the origin of the coronary arteries was observed, with a tendency for the right coronary artery to arise from the anterior right quadrant and for the left coronary artery to arise from the anterior and left quadrant. Such a tendency was observed in 50% of the bicuspid, in 59% of the tricuspid and in 66% of the quadricuspid valves. The anatomic right ventricle was always observed to be vascularized by a right coronary artery, and the anatomic left ventricle by a left coronary artery, even in cases in which there was a single coronary trunk. The anterior surface of the right ventricle was crossed by a right coronary artery in 5 cases. A single coronary artery was observed in 7 cases (18%). Embryologic considerations are offered, especially regarding the relation between the observed variability in coronary artery patterns in TA and the absence of the truncal septation.

[Embryologic and anatomic considerations on normal and pathologic heart separation. II. Atrioventricular and interventricular septum]. / Consideraciones embriológicas y anatómicas sobre la septación cardiaca normal y patológica. II. Septum atrioventricular e interventricular.

The atrioventricular septum is defined and its anatomical features are described. This consists of two regions, a muscular and a membranous region. Isolated atrioventricular types of defect are described. The normal and the pathological embryogenesis of the atrioventricular septum are discussed. A definition of the interventricular septum is given and its anatomical features are described. This septum is divided into two regions, a membranous and muscular region. The muscular region is divided into three regions: inflow region or inlet, trabeculated region and outflow region or outlet. Interventricular defects are classified according to the septal regions in which they are located. The anatomical features which characterize each type of interventricular septal defect are established. A brief comment on the normal and pathological morphogenesis of the interventricular septum is made.

[Embryologic and anatomic considerations on the normal and pathologic formation of the cardiac septum. I. Interauricular septum]. / Consideraciones embriológicas y anatómicas sobre la septación cardiaca normal y patológica. I. Septum interauricular.

A brief presentation of the normal embryological development of the human interatrial septum is made. The anatomical expression of each of its embryological components is described. Our classification of interatrial septal defect is enriched by their more precise anatomical description and by making a more correct morphogenetic interpretation, based on new information obtained by means of experimental embryology. Emphasis is made that absence of the interatrial septum does not preclude the diagnosis of viscero-atrial situs.

The contribution of the inferior endocardial cushion of the atrioventricular canal to cardiac septation and to the development of the atrioventricular valves: study in the chick embryo.

The contribution of the inferior endocardial cushion of the atrioventricular canal to cardiac septation and to the development of the atrioventricular valves was studied in the chick embryo by in vivo labelling techniques. The study was performed in White Leghorn chick embryos in which the dorsal cushion was labelled at stage 20-21 (Hamburger and Hamilton, 1951), when the endocardial cushions were not yet fused. The embryos were sacrificed at stage 35 (mature heart). These experiments allow us to conclude that the inferior atrioventricular cushion gives origin to: a) that part of the cardiac septum between the septal insertion of the antero-septal leaflet of the mitral valve and the fibrous ridge which is the equivalent to the human septal leaflet of the tricuspid valve (atrioventricular septum); b) the region of the interatrial and the interventricular septa adjacent to the atrioventricular septum; c) the portion of the antero-septal leaflet of the mitral valve which inserts into the septum; d) the fibrous ridge corresponding to the septal leaflet of the tricuspid valve. Microdissection shows that, when they appear at stage 18, the superior and inferior endocardial cushions of the atrioventricular canal are in continuity, without boundaries, with both the interatrial and interventricular septa. Therefore, each atrioventricular orifice opens into its corresponding ventricle, there being no stage in the development of the chick embryo heart in which the atrioventricular orifices are connected to the left ventricle at the same time. The development of the atrioventricular canal is similar in the chick and human.

Double outlet right ventricle: experimental morphogenesis in the chick embryo heart.

Double outlet right ventricle (DORV) was produced experimentally in the chick embryo by preventing the incorporation of the posteromedial conus into the left ventricle. This was accomplished by placing a ligature around the caudal end of the conus at a stage in which it is exclusively continuous with the right ventricle. The embryos were divided into two groups according to the stage of development of the conal ridge. In one group, the conal ridges had not appeared (stages 17-18); in the other they had begun to develop (stage 22). Both groups were divided into two subgroups; in one the ligature was left in place up to the mature heart stage and in the other it remained for only 24 hours. In all the embryos where the ligature remained until the mature heart stage a DORV was obtained, while in the embryos where the ligature remained in place for only 24 hours a DORV was obtained in only two-thirds of the cases. Two different types of DORV were produced: 1) with anterior and posterior infundibula in which the subpulmonary infundibulum was anterior to the subaortic infundibulum and there was a subaortic infracristal ventricular septal defect (VSD); 2) with side-by-side infundibula in which the subpulmonary infundibulum was on the left side and the subaortic infundibulum on the right side; the VSD was far from both infundibula. Our experiments show that DORV is an essentially infundibular malformation. In DORV there are two types of infundibular relationships: a) with anterior and posterior infundibula, and b) with side-by-side infundibula. The crista supraventricularis in the normal heart and the infundibular septum in DORV are two different anatomic and embryologic structures.

Different concepts of univentricular heart. Experimental embryological approach.

A brief historical review of the main descriptions, definitions, classifications and nomenclatures of the univentricular heart within the historical context of the evolution of the technical and scientific knowledge, is made. The development of the ventricles and particularly the posterior interventricular septum (posterior smooth plus posterior trabeculated septa), were studied experimentally in the chick embryo, by the vivo labelling technics, since they are very important for the definition of the univentricular heart. It was demonstrated: 1. In the apical region of the embryonic heart only a primitive interventricular septum develops and this gives origin to the posterior interventricular septum. 2. The walls of the bulbus cordis and the primitive ventricle adjacent to the primitive interventricular septum contribute to the development of this septum. 3. Cell division and cell movement are the basic processes of development which seem to take part in the development of the posterior interventricular septum.

Experimental study of the development of the truncus and the conus in the chick embryo.

The development of the truncus and the conus was studied in the chick embryo by in vivo labelling techniques. The earliest labels were placed at the stage of fusion of the myocardial troughs (stage 9-) and they were traced until the mature heart stage (stage 35). Microdissections and light microscopic studies were also carried out. The results are discussed in relation to the human heart. Our experiments permit the following conclusions: (1) At stage 9- fusion of the myocardial troughs takes place at the level of the primordium of the trabeculated portion of the right ventricle, when neither the conus nor the truncus are present. (2) At stage 12 (loop stage) there appears the caudal portion of the conus, which constitutes the cephalic end of the cardiac tube. (3) The truncus appears between stages 13 and 22. (4) At stage 22 angular junction between the conus and the truncus is the area where the semilunar valve cusps of the great arteries will develop and that, at this same stage, the junction between the conus and the trabeculated portion of the right ventricle seen from the right surface corresponds to the inferior edge of the crista supraventricularis. (5) It was confirmed that the pulmonary semilunar valve cusps originate from the walls of the truncus. (6) The development of the conus and truncus are similar in chick and man. (7) Histologically, in the chick, the wall of the truncus and the conus contain cardiac muscle as late as stage 28, but from then on the walls of the truncus are transformed into connective tissue and plain muscle.

Rules for diagnosis of arterioventricular discordances and spatial identification of ventricles. Crossed great arteries and transposition of the great arteries.

Rules are presented for the diagnosis of arterioventricular discordances and the spatial position of the ventricles in these cardiopathies by means of angiocardiography and the position of cardiac catheters. Because these rules are based on previous anatomo-embryological findings, the normal development of the conus and the truncus is briefly analysed. The probable morphogenesis of this group of truncoconal cardiopathies is discussed. The fundamental process required to establish the diagnosis of these cardiopathies is as follows: 1) The truncoconal morphology is identified in the lateral projection. a) The anterior position of the pulmonary artery and its infundibulum with respect to the aorta and its infundibulum is characteristic of crossed great arteries with arterioventricular concordance or discordance. b) The anterior position of the aorta and its infundibulum with respect to the pulmonary artery and its infundibulum is characteristic of transposition of the great arteries with arterioventricular concordance or discordance. 2) Once the truncoconal morphology is identified, the use of the anteroposterior projection allows the establishment of the differential diagnosis between arterioventricular concordances and discordances, and of the spatial location of the ventricles in these entities. a) An anterior pulmonary artery directed from right to left, emerging from an infundibulum placed on the left side (anatomically right ventricle on the left) or an anterior pulmonary artery directed from left to right, arising from an infundibulum located to the right (anatomically right ventricular placed on the right), is the specific image of discordant crossed great arteries. b) An anterior pulmonary artery directed from right to left emerging from an infundibulum placed on the right side (anatomically right ventricle on the right side) or the anterior pulmonary artery directed from left to right arising from a left-sided infundibulum (anatomically right ventricle placed on the left side) is characteristic of concordant crossed great arteries. c) An anterior aorta placed to the right of the pulmonary artery and emerging from a left-sided infundibulum (anatomically right ventricle placed on the left side) or an anterior aorta placed to the left of the pulmonary artery and arising from an infundibulum placed on the right side (anatomically right ventricle placed on the right) is characteristic of discordant transposition of the great arteries. d) An anterior aorta placed to the right of the pulmonary artery emerging from a right-sided infundibulum (anatomically right ventricle placed on the right) or an anterior aorta placed to the left of the pulmonary artery arising from an infundibulum placed on the left (anatomically right ventricle placed on the left) is the specific picture of concordant transposition of the great arteries...