Vulnerability of the developing heart to oxygen deprivation as a cause of congenital heart defects.
Bottom Line: The heart develops under reduced and varying oxygen concentrations, yet there is little understanding of oxygen metabolism in the normal and mal-development of the heart.ODD-Luc activity decreased in 2 stages, the first corresponding with the formation of a functional cardiovascular system for oxygen delivery at E15.5, and the second after birth consistent with complete oxygenation of the blood and tissues.Low oxygen concentrations and lack of oxygen reserve during a critical phase of heart organogenesis may provide a basis for vulnerability to the development of common septation and conotruncal heart defects.
Affiliation: Department of Cardiovascular Medicine, University of Maryland School of Medicine, Baltimore, MD (D.K., S.A.F.).Show MeSH
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Mentions: Bioluminescent imaging was used to determine the spatial distribution of ODD‐Luc activity in the E13.5 embryo. The substrate luciferin was administered to the pregnant mice and the embryos removed and imaged as described in Methods. Robust bioluminescent signal was observed in the ODD‐Luc embryos (Figure 2) while no activity was observed in wild type embryos or in ODD‐Luc mice in the absence of luciferin. The activity in the E13.5 heart was ≈200‐fold above background, similar to that measured in tissue homogenates. Within the heart a gradient of bioluminescent signal was observed with the outflow region of the heart exhibiting ≈50% greater signal as compared to the ventricles (Figures 2B, 2C, and 2F; P<0.001).
Affiliation: Department of Cardiovascular Medicine, University of Maryland School of Medicine, Baltimore, MD (D.K., S.A.F.).