Cilia and Nodal Flow in Asymmetry: An Engineering Perspective.

Over the past several years, cilia in the primitive node have become recognized more and more for their contribution to development, and more specifically, for their role in axis determination. Although many of the mechanisms behind their influence remain undocumented, it is known that their presence and motion in the primitive node of developing embryos is the determinant of the left-right axis. Studies on cilial mechanics and nodal fluid dynamics have provided clues as to how this asymmetry mechanism works, and more importantly, have shown that direct manipulation of the flow field in the node can directly influence physiology. Although relatively uncommon, cilial disorders have been shown to have a variety of impacts on individuals from chronic respiratory infections to infertility, as well as situs inversus which is linked to congenital heart disease. After first providing background information pertinent to understanding nodal flow and information on why this discussion is important, this paper aims to give a review of the history of nodal cilia investigations, an overview of cilia mechanics and nodal flow dynamics, as well as a review of research studies current and past that sought to understand the mechanisms behind nodal cilia's involvement in symmetry-breaking pathways through a biomedical engineering perspective. This discussion has the additional intention to compile interdisciplinary knowledge on asymmetry and development such that it may encourage more collaborative efforts between the sciences on this topic, as well as provide insight on potential paths forward in the field.

Computational Investigation of a Self-Powered Fontan Circulation.

Children born with anatomic or functional "single ventricle" must progress through two or more major operations to sustain life. This management sequence culminates in the total cavopulmonary connection, or "Fontan" operation. A consequence of the "Fontan circulation", however, is elevated central venous pressure and inadequate ventricular preload, which contribute to continued morbidity. We propose a solution to these problems by increasing pulmonary blood flow using an "injection jet" (IJS) in which the source of blood flow and energy is the ventricle itself. The IJS has the unique property of lowering venous pressure while enhancing pulmonary blood flow and ventricular preload. We report preliminary results of an analysis of this circulation using a tightly-coupled, multi-scale computational fluid dynamics model. Our calculations show that, constraining the excess volume load to the ventricle at 50% (pulmonary to systemic flow ratio of 1.5), an optimally configured IJS can lower venous pressure by 3 mmHg while increasing systemic oxygen delivery. Even this small decrease in venous pressure may have substantial clinical impact on the Fontan patient. These findings support the potential for a straightforward surgical modification to decrease venous pressure, and perhaps improve clinical outcome in selected patients.