Congenital heart malformations induced by hemodynamic altering surgical interventions

Abstract

Embryonic heart formation results from a dynamic interplay between genetic and environmental factors. Blood flow during early embryonic stages plays a critical role in heart development, as interactions between flow and cardiac tissues generate biomechanical forces that modulate cardiac growth and remodeling. Normal hemodynamic conditions are essential for proper cardiac development, while altered blood flow induced by surgical manipulations in animal models result in heart defects similar to those seen in humans with congenital heart disease. This review compares the altered hemodynamics, changes in tissue properties, and cardiac defects reported after common surgical interventions that alter hemodynamics in the early chick embryo, and shows that interventions produce a wide spectrum of cardiac defects. Vitelline vein ligation and left atrial ligation decrease blood pressure and flow; and outflow tract banding increases blood pressure and flow velocities. These three surgical interventions result in many of the same cardiac defects, which indicate that the altered hemodynamics interfere with common looping, septation and valve formation processes that occur after intervention and that shape the four-chambered heart. While many similar defects develop after the interventions, the varying degrees of hemodynamic load alteration among the three interventions also result in varying incidence and severity of cardiac defects, indicating that the hemodynamic modulation of cardiac developmental processes is strongly dependent on hemodynamic load.

Reduced embryonic blood flow impacts extracellular matrix deposition in the maturing aorta

“…B–C). These ECM changes are likely to result in a stiffer DA and also limit radial distension due to pressure, which is unaffected by ligation (Midgett and Rugonyi, ). Since vascular resistance is inversely proportional to the fourth power of radius (Thurston, ), we expect that the reduction in DA radius at HH36 (Fig.…”

Cardiovascular shunting in vertebrates: a practical integration of competing hypotheses

“…Ventricular septal defects have been described in a juvenile houbara bustard (Chlamydotis undulata macqueenii) (Bailey & Kinne, 2001) and for penguins as well as various species of caged birds (Laughlin et al, 2016). Experimental manipulation of the circulation of chicken embryos has been used to investigate causal mechanisms for mammalian cardiac defects (Aranega et al, 1985;Broekhuizen et al, 1999;Ward et al, 2005;Midgett & Rugonyi, 2014), so presumably some, if not all, of the cardiovascular defects that occur in adult mammals also can appear in adult birds.…”

The force within: endocardial development, mechanotransduction and signalling during cardiac morphogenesis

“…The endocardium is a specialised endothelium, and the mechanosensation and transduction mechanisms that it uses are thus likely to be similar to those used by other endothelial cells. Alterations to these hemodynamic forces, for example by surgical interventions in animal models, cause cardiac abnormalities that resemble human congenital heart defects (Midgett and Rugonyi, 2014). Numerous important mechanosensory pathways have been identified in endothelial cells, but if and exactly how some of them function specifically in endocardial cells remains unclear.…”

“…In mice and humans, disturbed blood flow frequently manifests in cardiac cushion and valve defects (Midgett and Rugonyi, 2014). Hence, hemodynamic forces apparently induce mechanosensitive responses within endocardial cells that control morphogenetic changes in higher vertebrates (Culver and Dickinson, 2010).…”