Ana C. Durán

Bicuspid aortic valves with different spatial orientations of the leaflets are distinct etiological entities.

OBJECTIVES The aim of this study was to decide whether bicuspid aortic valves (BAVs) with fused right and noncoronary leaflets (R-N) and BAVs with fused right and left leaflets (R-L) have different etiologies or are the product of a single diathesis. BACKGROUND The BAV is the most common congenital cardiac malformation. The R-N and R-L BAVs are the most frequent BAV subtypes. METHODS The study was carried out in adult and embryonic hearts of endothelium nitric oxide synthase knock-out mice and inbred Syrian hamsters with a high incidence of R-N and R-L BAVs, respectively. The techniques used were histochemistry, immunohistochemistry, and scanning electron microscopy. RESULTS The R-N BAVs result from a defective development of the cardiac outflow tract (OT) endocardial cushions that generates a morphologically anomalous right leaflet. The left leaflet develops normally. The R-L BAVs are the outcome of an extrafusion of the septal and parietal OT ridges that thereby engenders a sole anterior leaflet. The noncoronary leaflet forms normally. CONCLUSIONS 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.

Fusion of valve cushions as a key factor in the formation of congenital bicuspid aortic valves in Syrian hamsters

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.

Phylogeny informs ontogeny: a proposed common theme in the arterial pole of the vertebrate heart

SUMMARY In chick and mouse embryogenesis, a population of cells described as the secondary heart field (SHF) adds both myocardium and smooth muscle to the developing cardiac outflow tract (OFT). Following this addition, at approximately HH stage 22 in chick embryos, for example, the SHF can be identified architecturally by an overlapping seam at the arterial pole, where beating myocardium forms a junction with the smooth muscle of the arterial system. Previously, using either immunohistochemistry or nitric oxide indicators such as diaminofluorescein 2‐diacetate, we have shown that a similar overlapping architecture also exists in the arterial pole of zebrafish and some shark species. However, although recent work suggests that development of the zebrafish OFT may also proceed by addition of a SHF‐like population of cells, the presence of a true SHF in zebrafish and in many other developmental biological models remains an open question. We performed a comprehensive morphological study of the OFT of a wide range of vertebrates. Our data suggest that all vertebrates possess three fundamental OFT components: a proximal myocardial component, a distal smooth muscle component, and a middle component that contains overlapping myocardium and smooth muscle surrounding and supporting the outflow valves. Because the middle OFT component of avians and mammals is derived from the SHF, our observations suggest that a SHF may be an evolutionarily conserved theme in vertebrate embryogenesis.

Anatomy and Formation of Congenital Bicuspid and Quadricuspid Pulmonary Valves in Syrian Hamsters

Congenital bicuspid and quadricuspid pulmonary valves have received little attention because of their limited clinical relevance. However, knowledge of the mechanisms by which these anomalous valves develop is essential to obtain a more accurate survey of the etiological factors implicated in the malformations of the cardiac outflow tract in mammals. The present study was designed to assess the anatomical features of bicuspid and quadricuspid pulmonary valves in Syrian hamsters as well as to elucidate the mechanisms involved in the formation of these defective valves.

The conus arteriosus of the adult gilthead seabream ( Sparus auratus )

This paper reports on the presence of the conus arteriosus in the heart of the adult gilthead seabream, Sparus auratus (Perciformes, Teleostei). The junctional region between the single ventricle and the bulbus arteriosus has been studied by conventional light microscopy, and by scanning and transmission electron microscopy. In addition, fluorescent phalloidin and antibodies against the muscle myosin heavy chains, laminin and collagen type IV have been used. The conus arteriosus is a distinct muscular segment interposed between the ventricle and the bulbus arteriosus. It is clearly different from the bulbus arteriosus due to its myocardial nature. It can also be distinguished from the ventricular myocardium because: (1) it has a conus shape; (2) it is formed by compact, well‐vascularized myocardium; (3) it is surrounded on its inner and outer faces by fibrous layers rich in collagen and elastin; (4) it constitutes the anatomical support of the so‐termed conus valves; (5) it shows intense staining for laminin and type‐IV collagen; and (6) the myocardial cells located close to the inner fibrous layer are helicoidally arranged. By contrast, the ventricular myocardium is highly trabecular, lacks a compacta, shows no vessels, and presents barely detectable amounts of laminin and collagen type IV. The presence of a distinct conus arteriosus in the heart of an evolutionary advanced teleost species indicates that the conus is not a vestigial segment from the evolutionary or embryological points of view. The characteristic spatial arrangement of the conus myocytes strongly suggests that the conus is implicated in the mechanical performance of the conus valves.

Coronary artery anomalies and aortic valve morphology in the Syrian hamster

In the Syrian hamster, anomalies in the origin of the left coronary artery are significantly associated with the bicuspid condition of the aortic valve. In this species, bicuspid aortic valves are expressions of a trait, the variation of which takes the form of a phenotypic continuum, ranging from a tricuspid aortic valve with no commissural fusion to a bicuspid aortic valve with the aortic sinuses located in ventrodorsal orientation and devoid of any raphe. The intermediate stages of the continuum are represented by tricuspid aortic valves with a more or less extensive fusion of the ventral commissure and bicuspid aortic valves with a more or less developed raphe located in the ventral aortic sinus. The present study was designed to decide whether there is a gap between tricuspid and bicuspid aortic valves regarding the incidence of coronary artery anomalies, or whether this incidence varies according to the different tricuspid and bicuspid morpho types of the continuum. The study was carried out in Syrian hamsters belonging to a single inbred family with a high incidence of tricuspid aortic valves with fusion of the ventral commissure, bicuspid aortic valves, and anomalies in the origin of the left coronary artery, i.e. single right coronary artery ostium in aorta, anomalous origin of the left coronary artery from the pulmonary artery, and anomalous origin of the left coronary artery from the dorsal aortic sinus. The specimens were examined by means of a stereomicroscope and, in several cases; scanning electron microscopy was also used. The relationships between anomalous coronary artery patterns and aortic valve morphologies were tested using a logistic regression model. The results obtained indicate that there is no discontinuity between tricuspid and bicuspid aortic valves regarding the incidence of coronary artery anomalies. The probability of occurrence of anomalous coronary artery patterns increases continuously according to the deviation degree of the aortic valve from its normal (tricuspid) design. The present findings suggest that in the Syrian hamster, the morphogenetic mechanisms involved in the formation of congenital anomalous aortic valves and anomalies in the origin of the left coronary artery, respectively, are strongly related from an aetiological viewpoint.

The coronary arteries of the C57BL/6 mouse strains: implications for comparison with mutant models

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.

Coronary artery anomalies and bicuspid aortic valves in the Syrian hamster

Summary:The condition of coronary arteries and aortic valves was studied in 552 Syrian hamsters belonging to a single family subjected to high endogamous pressure. The study was carried out using a corrosion-cast technique. In 178 hamsters the aortic valve was bicuspid. In 138 specimens, 54 of them with normal aortic valves and 84 with bicuspid aortic valves, anomalies in the origin of the coronary arteries could be classified in three morphologic types: left coronary artery from the pulmonary trunk (36 cases); single right coronary artery (84 cases); left coronary artery from the dorsal aortic sinus (18 cases). Results of a ξ2 contingency test show that the frequency of left coronary artery from the pulmonary trunk and single right coronary artery significantly increases when the aortic valve is bicuspid. The present findings suggest that there is a developmental complex consisting of bicuspid aortic valve and anomalous origin of the coronary arteries.

Anatomy and Development of the Sinoatrial Valves in the Dogfish (Scyliorhinus canicula)

ABSTRACT Background: We describe the adult anatomy and the development of the cardiac sinoatrial valves in the dogfish (Scyliorhinus canicula).

The coronary arteries of the Syrian hamster, Mesocricetus auratus (Waterhouse 1839)

Bearing in mind that the Syrian hamster provides an animal model for the study of congenital coronary artery anomalies, we decided to undertake a definition of its normal coronary artery pattern. The sample examined consisted of 1204 specimens. They were studied both histologically and by means of a corrosion-cast technique. The course of the coronary arteries in this species is intramyocardial. The right coronary artery has two principal branches: the right circumflex branch and the dorsal interventricular branch. The conal branch usually originates from the main trunk of the right coronary artery. The main branches of the left coronary artery are the obtuse marginal branch, the left circumflex branch, and usually a dorsal ventricular branch as well. The ventral interventricular branch is often absent. When it is present, it always originates from the left coronary artery and seldom reaches the apex of the heart. The interventricular septum is principally supplied by one, or rarely two, septal arteries arising from the right and/or left coronary arteries. According to the number and origin of these vessels, three septal coronary artery patterns were established; namely, the right, the left, and the right-left septal patterns. In the Syrian hamster, the left septal pattern is the most frequent (70.4%). The right septal pattern occurred in 28.1% of the specimens studied, whereas the right-left septal pattern was only found in 1.5% of them.