The Impact of Mechanical Forces in Heart Morphogenesis

Congenital heart disease (CHD) is the most common birth defect in humans and results from deficient cardiac development, a complex process that is not completely understood. The heart starts to function before its morphogenesis is complete and the increasing needs of the growing embryo for oxygen and nutrients demand a proportional increase in the performance of the organ. We review recent findings supporting the hypothesis that the activity of the developing heart influences its morphogenesis and that internal or external factors, which significantly modify its functional capability, can in turn, induce anatomic cardiac defects. We propose that a role for early cardiac contraction in heart development is supported by recent experimental evidence and that the Notch pathway acts as a key transducer between hemodynamic stimuli and cardiogenesis. Cardiac Contraction Begins Before Convective Transport Is NecessarySeveral pieces of evidence suggest that heart primordium contraction starts well before the active transport of oxygen and nutrients by the circulation is required to meet the needs of the embryonic tissues. For example, rhythmic action potentials can be detected in the chick heart primordium as early as Hamburger-Hamilton stage 9 (HH9, 7-somite stage, 29–33 hours after laying).1 The chick heart tube starts showing contraction as early as HH10 (10-somite, 33–38 hours), whereas effective blood flow starts during looping at HH12 (16-somite, 45–49 hours).2 By days 3 to 4 (HH20-23), vigorous circulation is established.3 However, total elimination of cardiac ejection by complete ligation of the cardiac outflow tract in 3- or 4-day chick embryos has no significant effect on O2 consumption or eye growth in the 4 hours after the procedure4 and no correlation between cardiac output and eye, vessel growth, or body mass accumulation was observed in 24 hours after partial conotruncal ligation.5 Moreover, chick embryos show no hemoglobin-mediated transport of oxygen up to about 3 …