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

Abstract

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.

Quantitative volumetric analysis of cardiac morphogenesis assessed through micro‐computed tomography

“…This expansion is also concomitant with a dextral translation of the venous inflow. Previous research suggests that the AV canal is initially a large contributor to early cardiac volume, and similar to our quantitative measurements disappears as the valves form out of the primitive AV cushions (de la Cruz et al, 2001). It has been postulated that the slow conducting AV region loses mechanical stimulation with the development of the valves and, therefore, atrophies (Knaapen et al, 1995), but increased expansion and remodeling of the atria and ventricles is also a possible explanation (Oosthoek et al, 1998).…”

“…This process involves several key events that happen in three dimensions, including linear heart tube looping, septation of the ventricles, and development of the atrioventricular (AV) valve apparatus, defects in which result in a myriad of clinically relevant congenital heart defects (Collins-Nakai and McLaughlin, 2002;Gittenberger-de Groot et al, 2005). Although the initial heart tube only contains portions of the primitive right ventricle (de la Cruz et al, 2001), eventually all of the chambers are derived from the growing linear heart tube, with smaller contributions from sources such as the anterior heart field and proepicardium. During cardiogenesis, the sizes of these chambers change significantly, but few studies have attempted to quantify them.…”

The living aortic valve: From molecules to function

“…The presumptive cardiac segments are arranged with the putative atria most caudal, through a singular contractile ventricular segment, and then finally the outflow most cranial. Shortly after the initiation of a rudimentary linear conduction sequence, the heart bends rightward into a characteristic “C” loop and through differential growth of the ventricular segment arrives at a figure of eight shape with the ventricular segment now caudal to the atrial segment 20 . It is in this configuration that the cardiac valves originate (Figure 4).…”

Required, tissue-specific roles for Fgf8 in outflow tract formation and remodeling

“…Inductive interactions between these populations and regionally-specific transcription factor hierarchies regulate distinct morphogenetic events during heart development; their disruption by mutation or environmental insult usually results in malformations that affect discrete cardiac substructures, leaving the rest of the organ intact (de la Cruz et al, 2001;Harvey, 2002). Given the duration and complexity of heart development, it is not surprising that nearly one percent of humans are born with congenital cardiovascular defects (Creazzo et al, 1998;Harvey, 2002;Olson and Schneider, 2003).…”