Developmental Fetal Cardiovascular Biomechanics in the 21st Century: Another Tipping Point

The relationships between structure and function during cardiovascular morphogenesis have fascinated biologists, anatomists, and clinicians for centuries due to the observable and carefully orchestrated transformation of simple cellular structures into highly ordered and dynamically functioned organs and the broad spectrum of malformations that occur and produce congenital cardiovascular defects. For example, in 1932 Harvard anatomist Bremer described two spiral flow streams within the primitive, unseptated heart based on observations of moving blood cells.3 For many years, it was thought that the paths of these streams predetermined the formation of the spiral aortopulmonary septum, the asymmetric mature aortic arch and pulmonary arteries, and a subset of congenital cardiac defects. Contemporary studies using fluorescent dye injections to map intracardiac flow streams have shown that this relationship is much more complex25 and involves the interactions between migrating, extracardiac neural crest cells, cell–matrix,21 and 33 paracrine regulation