The R-N and R-L BAVs are different etiological entities. The R-N BAVs are the product of a morphogenetic defect that happens before the OT septation and that probably relies on an exacerbated nitric oxide-dependent epithelial-to-mesenchymal transformation. The R-L BAVs result from the anomalous septation of the proximal portion of the OT, likely caused by a distorted behavior of neural crest cells. Care should be taken in further work on BAV genetics because R-N and R-L BAVs might rely on different genotypes. Detailed screening for R-N and R-L BAVs should be performed for a better understanding of the relationships between these BAV morphologic phenotypes and other heart disease.

Background: Bicuspid aortic valve is the most frequent congenital cardiac malformation in humans. However, the morphogenesis of the defect is still unknown. Previous work showed that, in the Syrian hamster, congenital bicuspid aortic valves with the aortic sinuses arranged in ventrodorsal orientation are expressions of a trait the variation of which takes the form of a continuous phenotypic spectrum, ranging from a tricuspid aortic valve with no fusion of the ventral commissure to a bicuspid aortic valve devoid of any raphe. The present study was designed to elucidate the mechanism involved in the formation of bicuspid aortic valves in Syrian hamsters as a possible starting point for further investigation of this process in humans.Methods: The sample examined consisted of 80 embryos, aged between 10 days, 16 hours and 13 days, 1 hour postcoitum. Most (n = 59) of the embryos belonged to a laboratory-inbred family of Syrian hamsters with a high incidence of bicuspid aortic valves. The study was carried out using scanning electron microscopy and histological techniques for light microscopy.Results: Twenty-three embryos showed a still undivided conotruncus. In all of these cases there were six mesenchymal semilunar valve primordia protruding into the lumen of the conotruncus. In a further 29 embryos, the conotruncus had just divided into the aortic and pulmonary channels; the embryos were at the beginning of the valvulogenesis. In 13 of these 29 embryos there were three well-defined aortic valve cushions, right, left, and dorsal, whereas in the other 16, the right and left valve cushions were more or less fused toward the lumen of the aorta; when they were completely fused, only two aortic valve cushions, a ventral and a dorsal, could be identified. In the remaining 28 embryos, the aortic valve cushions showed a marked degree of excavation. In 23 of these cases, the valve exhibited a basically tricuspid architecture, whereas it was unequivocally bicuspid in the other five.Conclusions: All variants of the aortic valve morphologic spectrum occurring in the Syrian hamster develop from three mesenchymal valve cushions, right, left, and dorsal, after normal septation of the conotruncus. The bicuspid condition of the aortic valve is not the consequence of improper development of the conotruncal ridges, conotruncal malseptation, valve cushion agenesis, or lesions acquired after a normal valvulogenesis. Fusion of the right and left valve cushions at the beginning of the valvulogenesis appears to be a key factor in the formation of bicuspid aortic valves. Each aortic valve acquires its specific morphology prior to the end of the valvulogenetic process.

There are few detailed descriptions of the coronary arterial patterns in the mouse. Some recent reports on coronary anomalies in mutant mouse models have uncovered the importance of several genes (i.e. iv and connexin43 ) in coronary morphogenesis. These mutations spontaneously appeared ( iv ) or were generated ( connexin43 ) in a C57BL /6 background, which is widely used for the development of mutant mice. We have studied the origin and course of the main coronary arteries of two C57BL/6 mouse strains. Unusual anatomical coronary arterial patterns were found, including: solitary ostium in aorta, accessory ostium, high take-off, aortic intramural course, slit-like ostium, sinus-like ostium and origin of a septal artery from the left coronary artery. In humans, some of these conditions are clinically relevant. Most of these patterns, which differ from those observed in wild mice and Swiss albino mice, coincide with those previously found in iv / iv and connexin43 knockout mice. The results indicate that there is variability in the coronary arterial arrangement of the laboratory mouse. Care should be taken when analysing coronary phenotypes of mutant mouse models.

The morphology of the aortic valve was studied in 1,022 heart specimens belonging to the collection of the Institute of Pathological Anatomy, University of Padua. Twenty specimens were found to have a unicommissural aortic valve, characterized by the presence of a single leaflet with only one functional commissure; however, the presence of two raphes enabled the recognition of a basically three-sinus arrangement. Age and gender were known in 19 cases: 14 male and five female, mean age nine days. In 19 cases, the unicommissural valve was dysplastic and resulted in a severe congenital aortic valvar stenosis. Only in two hearts was the unicommissural nature of the aortic valve an isolated finding; among the remaining 18, left ventricular fibroelastosis in 11, malformation of the mitral valve in 11, hypoplasia of the left ventricle in eight, ventricular septal defect in four, mitral atresia in three, and subaortic fibrous diaphragm in one. Furthermore, seven (35%) of these 20 unicommissural aortic valves were associated with coarctation of the aorta. Statistical analysis shows that this association is not a random event. Our findings support the hypothesis that the unicommissural aortic valve originates from the early fusion of the three mesenchymal valvar cushions or leaflet primordia. Although the present data do not exclude the possibility that reduction of the blood flow through the aorta during fetal life may play a role in the formation of the unicommissural aortic valve, they rather point in the direction that another etiologic factor, such as an anomalous migration of neural crest cells, may be responsible for the fusion of the valvar cushions.