The changing morphology of the ventricular walls of mouse and human with increasing gestation.

That the highly trabeculated ventricular walls of the developing embryos transform to the arrangement during the fetal stages, when the mural architecture is dominated by the thickness of the compact myocardium, has been explained by the coalescence of trabeculations, often erroneously described as 'compaction'. Recent data, however, support differential rates of growth of the trabecular and compact layers as the major driver of change. Here, these processes were assessed quantitatively and visualized in standardized views. We used a larger dataset than has previously been available of mouse hearts, covering the period from embryonic day 10.5 to postnatal day 3, supported by images from human hearts. The volume of the trabecular layer increased throughout development, in contrast to what would be expected had there been 'compaction'. During the transition from embryonic to fetal life, the rapid growth of the compact layer diminished the proportion of trabeculations. Similarly, great expansion of the central cavity reduced the proportion of the total cavity made up of intertrabecular recesses. Illustrations of the hearts with the median value of left ventricular trabeculation confirm a pronounced growth of the compact wall, with prominence of the central cavity. This corresponds, in morphological terms, to a reduction in the extent of the trabecular layer. Similar observations were made in the human hearts. We conclude that it is a period of comparatively slow growth of the trabecular layer, rather than so-called compaction, that is the major determinant of the changing morphology of the ventricular walls of both mouse and human hearts.

Evolutionary Aspects of Chamber Formation and Septation.

The formed hearts of vertebrates are widely different in anatomy and performance, yet their embryonic hearts are surprisingly similar. Developmental and molecular biology are making great advances in reconciling these differences by revealing an evolutionarily conserved building plan to the vertebrate heart. This suggests that perspectives from evolution may improve our understanding of the formation of the human heart. Here, we exemplify this approach by discussing atrial and ventricular septation and the associated processes of remodeling of the atrioventricular junction and formation of the atrioventricular insulating plane.

Molecular Pathways and Animal Models of Ebstein's Anomaly.

Ebstein's anomaly is a congenital malformation of the tricuspid valve characterized by abnormal attachment of the valve leaflets, resulting in varying degrees of valve dysfunction. The anatomic hallmarks of this entity are the downward displacement of the attachment of the septal and posterior leaflets of the tricuspid valve. Additional intracardiac malformations are common. From an embryological point of view, the cavity of the future right atrium does not have a direct orifice connected to the developing right ventricle. This chapter provides an overview of current insight into how this connection is formed and how malformations of the tricuspid valve arise from dysregulation of molecular and morphological events involved in this process. Furthermore, mouse models that show features of Ebstein's anomaly and the naturally occurring model of canine tricuspid valve malformation are described and compared to the human model. Although Ebstein's anomaly remains one of the least understood cardiac malformations to date, the studies summarized here provide, in aggregate, evidence for monogenic and oligogenic factors driving pathogenesis.

Trabeculations of the porcine and human cardiac ventricles are different in number but similar in total volume.

An intricate meshwork of trabeculations lines the luminal side of cardiac ventricles. Compaction, a developmental process, is thought to reduce trabeculations by adding them to the neighboring compact wall which is then enlarged. When pig, a plausible cardiac donor for xenotransplantation, is compared to human, the ventricular walls appear to have fewer trabeculations. We hypothesized the trabecular volume is proportionally smaller in pig than in human. Macroscopically, we observed in 16 pig hearts that the ventricular walls harbor few but large trabeculations. Close inspection revealed a high number of tiny trabeculations, a few hundred, within the recesses of the large trabeculations. While tiny, these were still larger than embryonic trabeculations and even when considering their number, the total tally of trabeculations in pig was much fewer than in human. Volumetrics based on high-resolution MRI of additional six pig hearts compared to six human hearts, revealed the left ventricles were not significantly differently trabeculated (21.5 versus 22.8%, respectively), and the porcine right ventricles were only slightly less trabeculated (42.1 vs 49.3%, respectively). We then analyzed volumetrically 10 pig embryonic hearts from gestational day 14-35. The trabecular and compact layer always grew, as did the intertrabecular recesses, in contrast to what compaction predicts. The proportions of the trabecular and compact layers changed substantially, nonetheless, due to differences in their growth rate rather than compaction. In conclusion, processes that affect the trabecular morphology do not necessarily affect the proportion of trabecular-to-compact myocardium and they are then distinct from compaction.