BACKGROUND: The relationship between changes in endocardial cushion and resultant @entity299 ( @entity299 ) has yet to be established. It has been shown that increased regurgitant flow early in embryonic heart development leads to @entity4007 , but it remains unclear how abnormal endocardial cushions during the looping stages might affect the fully septated heart. The goal of this study was to reproducibly alter blood flow in vivo and then quantify the resultant effects on morphology of endocardial cushions in the looping heart and on CHDs in the septated heart. METHODS: Optical pacing was applied to create regurgitant flow in @entity299 , and optical coherence tomography (OCT) was utilized to quantify regurgitation and morphology. Embryonic quail hearts were optically paced at 3 Hz (180 bpm, well above intrinsic rate 60-110 bpm) at stage 13 of development (3-4 weeks @entity1 ) for 5 min. Pacing fatigued the heart and led to at least 1 h of increased regurgitant flow. Resultant morphological changes were quantified with OCT imaging at stage 19 (cardiac looping-4-5 weeks @entity1 ) or stage 35 (4 chambered heart-8 weeks @entity1 ). RESULTS: All paced embryos imaged at stage 19 displayed structural changes in cardiac cushions. The amount of regurgitant flow immediately after pacing was inversely correlated with cardiac cushion size 24-h post pacing (P value   <   .01). The embryos with the most regurgitant flow and smallest cushions after pacing had a decreased survival rate at 8 days (P < .05), indicating that those most severe @entity4007 were lethal. Of the embryos that survived to stage 35, 17/18 exhibited CHDs including @entity340 , @entity1757 , hypoplastic ventricles, and common AV canal. CONCLUSION: The data illustrate a strong inverse relationship in which regurgitant flow precedes abnormal and smaller cardiac cushions, resulting in the development of CHDs.

Increased regurgitant flow causes @entity4007 in an avian embryonic model of XXXX .

@entity1 :: ('9606', 'Species') :: ['human'] @entity4007 :: ('MESH:D004694', 'Disease') :: ['endocardial cushion defects'] @entity1757 :: ('MESH:D006345', 'Disease') :: ['ventricular septal defects'] @entity299 :: ('MESH:D006331', 'Disease') :: ['embryonic hearts', 'CHD', 'congenital heart diseases'] @entity340 :: ('MESH:D006349', 'Disease') :: ['valve defects']
@entity299 :: (MESH:D006331,Disease) :: ['congenital heart disease']
