title: Homocysteine exposure affects early hemodynamic parameters of embryonic chicken heart function.
abstract: Maternal hyperhomocysteinemia has been associated with an increased risk of newborns with a congenital heart defect. This has been substantiated in the chicken embryo, as congenital heart defects have been induced after homocysteine treatment. Comparable heart defects are observed in venous clipping studies, a model of altered embryonic blood flow. Because of this overlap in heart defects, our aim was to test the hypothesis that homocysteine would cause alterations in embryonic heart function that precede the structural malformations previously described. Therefore, Doppler flow velocity waveforms were recorded in both primitive ventricles and the outflow tract of the embryonic heart of homocysteine treated and control chicken embryos at embryonic day 3.5. Homocysteine treatment consisted of 50 μL 0.05 M L-homocysteine thiolactone at 24, 48, and 72 hr. Homocysteine-treated embryos displayed significantly lower mean heart rates of 134 (SD 22) bpm, compared to 150 (14) bpm in control embryos. Homocysteine treatment caused an inhibiting effect on hemodynamic parameters, and altered heart function was presented by a shift in the proportions of the different wave times in percentage of total cycle time. Homocysteine induces changes in hemodynamic parameters of early embryonic chicken heart function. These changes may precede morphological changes and contribute to the development of CHD defects through alterations in shear stress and shear stress related genes, as seen before in venous clipping studies.
authors.affiliation: Department of Obstetrics and Gynecology, Division of Obstetrics and Prenatal Medicine, Erasmus MC, University Medical Center, Rotterdam, The Netherlands.
authors.forename: Annelien M
authors.initials: AM
authors.lastname: Oosterbaan
authors.forename: Els
authors.initials: E
authors.lastname: Bon
authors.forename: Regine P M
authors.initials: RP
authors.lastname: Steegers-Theunissen
authors.forename: Anton F W
authors.initials: AF
authors.lastname: Van Der Steen
authors.forename: Nicolette T C
authors.initials: NT
authors.lastname: Ursem
mesh_terms: D000014:Abnormalities, Drug-Induced / Q000473:pathology* / Q000503:physiopathology; D000818:Animals; D001783:Blood Flow Velocity / Q000187:drug effects / Q000502:physiology; D002642:Chick Embryo; D004625:Embryo, Nonmammalian / Q000187:drug effects* / Q000196:embryology; D006321:Heart / Q000187:drug effects* / Q000196:embryology / Q000503:physiopathology; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D006710:Homocysteine / Q000494:pharmacology*; D017078:Laser-Doppler Flowmetry
chemical_list: D006710:Homocysteine