Development of the coronary vasculature and its implications for coronary abnormalities in general and specifically in pulmonary atresia without ventricular septal defect

Aim: Coronary vascular anomalies are an important factor in congenital heart disease in the neonate. However, our knowledge of the pathomorphogenesis is still defective. Material and methods: 1) Study of coronary anomaly variations in congenital heart disease using specimens and 2) study of the role of epicardium-derived cells (EPDC) and neural crest cells in coronary vascular formation using quail-chicken chimeras. Results: The clinical and pathological data revealed the existence of ventriculo-coronary arterial communications during fetal life before pulmonary atresia was established. This supported a primary coronary developmental anomaly as the origin of some cases of pulmonary atresia as opposed to other cases in which the pulmonary orifice atresia was the primary anomaly. Our experimental work showed the high relevance of the development of the epicardium and epicardium-derived cells for the formation of the coronary vasculature, and showed the coronary vascular ingrowth into the myocardium and subsequently into the aorta and the right atrium. The absence of epicardium-derived cells leads to embryonic death, while delayed outgrowth could result in the absence of the main coronary arteries to pinpoint orifice formation. In these cases, the circulation was maintained through ventriculo-coronary arterial communications. Neural crest cells were important for the patterning of the coronary vasculature. We have extended this knowledge to a number of other heart malformations. Conclusions: Coronary vascular anomalies are highly linked to the development of extracardiac contributors like the epicardium and the neural crest. A proper interaction between these cell types and the myocardium and aortic arterial wall are important for normal vascular development.