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: To determine how O2 deprivation might affect heart development in this critical developmental window, pregnant mice were subjected to O2 deprivation (0.5 atmospheres [ATM], one‐half of normal) from E10.5 to 13.5 and heart morphology examined at E15.5 when the circulation has matured. Of 15 embryos examined the most common defect was isolated VSD associated with increased AV cushion mesenchyme (Table 3). Two of these embryos also had atrial septal defect (ASD). In 2 of the 15 embryos, the VSD was associated with mal‐position of the aorta partly originating from the RVOT and described as DORV (Figures 8B and 8D). VSD and ASD associated with increased AV cushion mesenchyme were present more posteriorly (Figures 8F and 8H). There was also thinning of the ventricular myocardium. In contrast the same regimen of O2 deprivation beginning at E13.5 resulted in no observable structural heart defects in embryos examined at E17.5 (n=21, Table 3), consistent with measures of ODD‐Luc activity and hypoxia‐inducible gene expression, establishing E10.5 to 13.5 as a critical developmental window for vulnerability of the embryo to O2 deprivation.
Affiliation: Department of Cardiovascular Medicine, University of Maryland School of Medicine, Baltimore, MD (D.K., S.A.F.).