Normal development of the pulmonary veins in human embryos and formulation of a morphogenetic concept for sinus venosus defects

A sinus venosus defect is a form of interatrial communication associated with abnormal drainage of the right pulmonary veins. Its morphogenesis still remains unclear. We therefore studied the normal development of pulmonary veins in human embryos in relation to the sinus venosus and the dorsal mesocardium using graphic reconstructions and HNK-1 immunohistochemistry. Twenty embryos, ranging from 4 to 7 weeks’ gestation, were examined. At 4 weeks, the orifice of the nonlumenized common pulmonary vein is visible as an endothelial invagination within the sinus venosus segment. Development of the muscular septum primum and the ventral proliferation of extracardiac mesenchyme from the dorsal mesocardium positions the common pulmonary vein (CPV) eventually into the left atrium. The right wall of the CPV contributes to the posterior part of the atrial septum and is continuous with the dorsal sinuatrial fold (the future left venous valve). With the use of HNK-1 antigen expression as a marker for sinus venosus myocardium, this common wall between the right-sided sinus venosus and the CPV is demonstrated, and at 7 weeks the proximal part of the right upper pulmonary vein also becomes part of this common wall. This study demonstrates that the CPV develops within the sinus venosus segment and that later a common myocardial wall is present between the sinus venosus in the right atrium and the CPV. A deficiency of this wall explains the development of sinus venosus defects.