Outflow Tract Development Research Articles

Neural crest ablation does not alter pulmonary vein development in the chick embryo.

Cranial neural crest, which extends from the mid-diencephalon to somite five, plays an integral role in development of pharyngeal arch derivatives and supplies mesenchyme to the aortic arch arteries. Neural crest cells in pharyngeal arches three, four, and six migrate to the heart and are involved in aorticopulmonary and conotruncal septation. Ablation of the "cardiac" neural crest cells in chick embryos results in a variety of outflow tract anomalies, including persistent truncus arteriosus. Although other studies have shown the importance of the neural crest in the development of the cardiac outflow tract, the role of neural crest in venous development has not been established. This investigation evaluates the effect of cardiac neural crest ablation on the morphological development of the pulmonary vein. The presence of the pulmonary vein was confirmed initially at early stage 15 using histological sections and computer reconstructions of serially sectioned, normal embryos. India ink injections demonstrated a complete, patent pulmonary circuit at stage 18. Cardiac neural crest was ablated at stages 8-10. Operated, sham-operated, and control embryos were sacrificed at incubation day 11, and acrylic plastic casts prepared of the intravascular compartment. In experimental embryos with persistent truncus arteriosus, there were no morphological differences in the pulmonary veins, compared with shams and controls. These data indicate that the lesions of the cardiac neural crest have little morphological impact on pulmonary vein development. It is concluded that alterations in the cardiac neural crest are not involved in venous anomalies such as cor triatriatum and total or partial anomalous pulmonary venous return.

Congenital cardiac outflow tract anomalies and otitis media

The neural crest is involved in the differentiation of the cardiac outflow tract and branchial arches. Branchial arches one and two give rise to the eustachian tubes. Anatomically different eustachian tubes (e.g., short length) are found in persons prone to otitis media. We hypothesized a relationship between outflow tract anomalies and eustachian tube anomalies. The medical records of 238 children with a catheterization diagnosis of congenital heart disease were reviewed for otitis diagnoses. Children with syndromes known to be associated with recurring otitis media were excluded. Recurrent otitis media was recorded in 32.2% of those with outflow tract anomaly, significantly ( P < 0.03) higher than the 18.9% rate in children with a cardiac anomaly not involving the outflow tract. Neither race, sex, nor cyanosis seemed to account for the differing rates of otitis. These data may support the concept of a field defect arising from neural crest cells that influences the development of the cardiac outflow tract and eustachian tubes.

Morphogenesis of the truncus arteriosus of the chick embryo heart: movements of autoradiographic tattoos during septation.

In order to trace tissue movements during septation of the embryonic truncus arteriosus into aortic and pulmonary cardiac outlets, the cephalic margin of the developing tubular heart of chick embryos was tattooed at Hamilton-Hamburger Stages 20-22 using diffusion micropipettes filled with 0.5% agarose and radioactive macromolecular precursors (tritiated thymidine, uridine, and leucine). Following further incubation for 2, 48, or 96 hours, the locations of such tattoos were determined by autoradiography of sectioned tissue and computer reconstruction of the developing outflow tract. Two hours after tattooing, radiolabeled cells were clustered at the right distal margin of the myocardial tube, as intended. Two days later, during septation of the outflow tract into the two arterial streams, label was concentrated along the posterior margin of the myocardium, between the developing aortic and pulmonary valve anlagen to the embryo's right and left, respectively. Four days following tattooing, as truncal septation neared completion, remaining label was found primarily to the left of the aortic valve ring posterior to the pulmonary outlet. The movements of thymidine tattoos during septation were demonstrated in a series of 31 embryos, 14 fixed at 2 hours, 12 at 2 days, and 5 at 4 days following tattooing; similar results were seen in uridine and leucine labeled hearts. The motion of such tattoos in the developing chick heart suggests that the left side of the definitive semilunar valve ring derives from the right distal margin of the primitive tubular heart and that normal morphogenesis of the great arterial streams involves both retraction and rotation of the embryonic truncus arteriosus.

A computer graphic study of cardiac truncal septation

AbstractSeptation of the cardiac truncus arteriosus in the normal rat embryo was described and illustrated by three‐dimensional reconstruction from serial sections through the developing outflow tract. Tracings of selected structures were digitized on an Apple II‐plus microcomputer, relayed through a central computer facility, and displayed on a Hewlett‐Packard 9845C graphics computer. Rotation and dissection of the color images allowed a kinetic description of the principal features of truncal septation and comparison with analogous events in the chick.A complex of tissue structures appeared in the downstream, distal truncus at 13 days of gestation and moved toward the ventricle(s) through the following day. As in the chick, the forming semilunar valves remained within 200 μm of the cephalic margin of the myocardial sleeve as they rotated and descended toward their definitive position against the heart. Mesenchymal condensations formed within the intervening aorticopulmonary (AP) septum and remained in close association with the principal bifurcation of the spiralling blood lumens, passing between the valves and descending along the conus septum. As the conus septum fused at 15 days of gestation, three outlets for cardiac outflow were seen: the major left and right streams to the aortic and pulmonary valves, respectively, and an apparently dwindling stream which crossed from the right ventricle behind the conus septum to exit through the aorta. In the chick, but not in the rat, nerve bundles invaded the distal truncus during septation to form the cardiac plexus.

The development of the arterial outflow tract in the chick embryo heart

AbstractBloodstream flow patterns have been outlined in the arterial outflow tract (ventricular outflow tract and bulbus arteriosus) of the chick embryo heart during the period in which septation takes place, Hemodynamic factors underlying flow changes during this period are discussed.The mapping of flow patterns did not support the concept of a conoventricular flange reported previously. Septation was found to take place between two separate and discrete bloodstreams.The cellular nature of the aorticopulmonary septum has been described. The spiral ridges that form this septum expand by cellular growth, explaining the ability of this septum to develop against the direction of blood flow. The aorticopulmonary septum divides about two‐thirds of the arterial outflow tract; the final partitioning of the most proximal portion of the outflow tract was found to take place by means of the apposition of endocardial cushion tissue masses.Failure of aorticopulmonary septum development (truncus arteriosus communis persistens) was found to follow fusion of the bloodstreams in experimental studies. In experimental aortic stenosis the appearance of a small left stream was found to be followed by the development of a stenotic aorta. Thus in the first instance the septum apparently cannot develop unless the streams remain separate and in the second case the size of the prhnordial bloodstreams appears to determine the diameter of the vessel.

Acute Abdominal Pain of Female Genital Origin: Diagnosis and Management

The Sonic hedgehog (Shh)-null mouse was initially described as a phenotypic mimic of Tetralogy of Fallot with pulmonary atresia (Washington Smoak, I., Byrd, N.A., Abu-Issa, R., Goddeeris, M.M., Anderson, R., Morris, J., Yamamura, K., Klingensmith, J., and Meyers, E.N. 2005. Sonic hedgehog is required for cardiac outflow tract and neural crest cell development. Dev. Biol. 283, 357–372.); however, subsequent reports describe only a single outflow tract, leaving the phenotype and its developmental mechanism unclear. We hypothesized that the phenotype that occurs in response to Shh knockdown is pulmonary atresia and is directly related to the abnormal development of the secondary heart field. We found that Shh was expressed by the pharyngeal endoderm adjacent to the secondary heart field and that its receptor Ptc2 was expressed in a gradient in the secondary heart field, with the most robust expression in the caudal secondary heart field, closest to the Shh expression. In vitro culture of secondary heart field with the hedgehog inhibitor cyclopamine significantly reduced proliferation. In ovo, cyclopamine treatment before the secondary heart field adds to the outflow tract reduced proliferation only in the caudal secondary heart field, which coincided with the region of high Ptc2 expression. After outflow tract septation should occur, embryos treated with cyclopamine exhibited pulmonary atresia, pulmonary stenosis, and persistent truncus arteriosus. In hearts with pulmonary atresia, cardiac neural crest-derived cells, which form the outflow tract septum, migrated into the outflow tract and formed a septum. However, this septum divided the outflow tract into two unequal sized vessels and effectively closed off the pulmonary outlet. These experiments show that Shh is necessary for secondary heart field proliferation, which is required for normal pulmonary trunk formation, and that embryos with pulmonary atresia have an outflow tract septum.