outflow tract provides the scaffold for formation of the arterial valves (see Fig 51.3B) However, at this stage, which occurs during embryonic days 11.5 and 12.5 in the mouse and by Carnegie stage 15 in humans, there has been no formation of the arterial valvar sinuses The walls of the arterial valvar sinuses are formed by still further proximal growth of the nonmyocardial tissues derived from the second heart field This additional growth is accompanied by excavation of the distal margins of the cushions themselves to form the leaflets and their semilunar hinges.5 During the process of endothelial-to-mesenchymal transformation, the cushions themselves have been invaded by cells migrating from the neural crest.1,3 The neural crest cells then form columns of condensed mesenchyme in the central parts of the unfused proximal cushions Some investigators have described these structures as producing an “aortopulmonary septal complex.”2 However, as described in Chapter 3, the columns cannot be identified until after the formation of the intrapericardial arterial trunks The neural crest cells, nonetheless, do play an important role in separating the arterial trunks from each other The protrusion from the dorsal wall of the aortic sac is itself covered by cells derived from the crest, although the core of the protrusion is derived from the second heart field.1 It is the ongoing growth of the tissues from the second heart field that form the walls of the arterial valvar sinuses, with the cells derived from the neural crest being confined to the valvar leaflets and their hinges, albeit with differential contributions to the intercalated cushions Subsequent to fusion of the central parts of the major outflow cushions, the core of the cushion mass attenuates This area becomes converted into the fibroadipose tissue that, in the postnatal heart, separates the aortic and pulmonary roots A similar process takes place in the proximal part of the outflow tract (Fig 51.5) FIG 51.5 Images taken from episcopic datasets prepared from developing mice These sections replicate the oblique subcostal echocardiographic cut and are taken from mice sacrificed at embryonic day 14.5 (A) and 15.5 (B) The images show the changes that take place during remodeling of the outflow cushions into the hinges and leaflets of the arterial valves, along with the freestanding subpulmonary infundibular sleeve Abnormal remodeling of the hinges of the aortic valve can create the potential for channels either leading back into the left ventricle or into the right ventricle Such abnormal remodeling produces the aortoventricular tunnels When the major cushions began their fusion, the outflow tract was supported exclusively by the developing right ventricle As the fusion continues, the caudal part of the proximal outflow tract is transferred across the crest of the muscular ventricular septum to arise from the developing left ventricle This brings the fused cushions themselves into line with the ventricular septal crest At the same time, the surface of the fused cushions begins to muscularize, while the core of the cushions mass begins to attenuate (see Fig 51.5A) By the beginning of embryonic day 14.5 in the mouse and by Carnegie stage 18 in humans, the persisting part of the embryonic interventricular communication has been closed by growth of the so-called tubercles derived from the ventricular surfaces of the major atrioventricular cushions (see Fig 51.5A) During these stages the distal parts of the cushions remodel to form the arterial valvar leaflets, with myocardium derived from the proximal outflow tract incorporated into the basal parts of the developing left ventricular myocardial cone Abnormal development of the cushion mass and its myocardial support gives the potential for abnormal communications around the hinges of the developing aortic valvar leaflets (see Fig 51.5B) Such communications bypassing the valvar leaflets are the essence of the various forms of aortoventricular tunnel.6 It is likely that abnormal development of the junction between the myocardial and nonmyocardial components of the intermediate part of the outflow tract also sets the scene for eventual aneurysmal formation of the valvar sinuses It is unlikely to be a coincidence that such aneurysmal formation is associated both with formation of the tunnels and with doubly committed and juxtaarterial ventricular septal defects (VSDs), the latter defects formed consequent to failure of muscularization of the proximal outflow cushions It is currently much harder to provide a rational explanation as to why there should be formation of three arterial roots or why the right and left PAs should have separate ventricular outlets It should be remembered, nonetheless, that it is a normal finding in reptiles and crocodilians to find three arterial trunks arising from the heart.7,8 Further comparisons between development in mammals and these other phyla may well cast further light on these problems.9 Aortopulmonary Windows AP windows provide communications between the cavities of the intrapericardial arterial trunks but in the presence of separate aortic and pulmonary roots (Fig 51.6).10 They can be found with atresia of one or other arterial valve, then providing access to the otherwise blind-ending circulation The presence of separate aortic and pulmonary roots serves to distinguish the windows from common arterial trunk, as it does from solitary aortic trunk The latter entity is found when there is complete absence of the intrapericardial PAs The separate nature of the walls of the intrapericardial arterial trunks means that it is incorrect to describe the lesions as “aortopulmonary septal defects.” As we have shown, the lesions are due to failure of closure of the embryonic AP foramen.4 Small windows can be found adjacent to the sinutubular junctions (Fig 51.7A)