MODELING THE EFFECT OF HEMODYNAMICS ON CARDIAC GROWTH DURING EMBRYONIC DEVELOPMENT

摘要

Congenital heart disease (CHD) affects about 1% of newborn babies in the US, and is the leading cause of noninfectious death in children. Abnormal blood flow dynamics during early development can lead to CHD. Although the effect of hemodynamic conditions on cardiac development - even under normal conditions - has been widely accepted, the mechanisms by which blood flow influences cardiac cell responses are only starting to emerge. Mathematical models of cardiac growth could then help elucidate key aspects of cardiac development. During early embryonic development, the heart is a looped tube that functions as a peristaltic pump. Hemodynamic conditions (blood pressure and wall shear stress) modulate the response of cardiac cells, leading to growth as well as changes in the microstructure and composition of the cardiac wall. Cardiac walls are composed of three layers: 1) the endocardium, a monolayer of endothelial cells, known to respond to wall shear stresses; 2) the cardiac jelly, composed of extracellular matrix; and 3) the myocardium, composed of cardiomyocytes that respond to wall stresses (or strains). Because during development intracardiac blood pressure increases with developmental time, if cardiac growth is modeled in response to wall stresses (which increase with pressure), growth-law parameters must change with developmental time (see e.g. [1]). In contrast, by considering strain-induced growth, growth laws that apply throughout development are feasible. Here, we present a model of cardiac development in which growth is induced by wall shear stresses and wall strains.