HLHS: Power of the Chick Model

Abstract

Background: Hypoplastic left heart syndrome (HLHS) is a rare but deadly form of human congenital heart disease, most likely of diverse etiologies. Hemodynamic alterations such as those resulting from premature foramen ovale closure or aortic stenosis are among the possible pathways.

Methods: The information gained from studies performed in the chick model of HLHS is reviewed. Altered hemodynamics leads to a decrease in myocyte proliferation causing hypoplasia of the left heart structures and their functional changes.

Conclusions: Although the chick phenocopy of HLHS caused by left atrial ligation is certainly not representative of all the possible etiologies, it provides many useful hints regarding the plasticity of the genetically normal developing myocardium under altered hemodynamic loading leading to the HLHS phenotype, and even suggestions on some potential strategies for prenatal repair.

Keywords: embryonic myocardium; hemodynamic alteration; left atrial ligation; left ventricular hypoplasia; myocyte proliferation.

Figure 1

Scheme of the workflow for creating the chick model of HLHS and examples of phenotypic findings (below the time axis in days) and rescue attempts (top right). From references [1,6,8,9,10]. The time axis shows embryonic days; the heart starts to beat before ED2, develops trabeculae at ED3, completes ventricular septation at ED8, and completes functional coronary vasculature by ED9. The panels above the axis show the appearance of the chick embryo at ED4 and ED8 [8], rescued ED9 heart with a silver microclip on the right atrium, green fluorescence protein expression in the embryonic left ventricle confirming successful injection of the adenovirus [1], and the graph shows the increased myocardial volumes in the right atrial clip rescue experiment [9]. The bottom panels show the phenotype on transverse sections in the scanning electron microscopy 48 h after ligation (left) [6], and decreased myocyte proliferation demonstrated by increased retention of radiolabeled [3H]-thymidine [10] (green grains over the hypoplastic left ventricle).