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Hyperglycemia Alters the Structure and Hemodynamics of the Developing Embryonic Heart

Congenital heart defects (CHDs) represent the most common form of human birth defects; approximately one-third of heart defects involve malformations of the outflow tract (OFT). Maternal diabetes increases the risk of CHD by 3–5 fold. During heart organogenesis, little is known about the effects of...

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Autores principales: Lawson, Taylor B., Scott-Drechsel, Devon E., Chivukula, Venkat Keshav, Rugonyi, Sandra, Thornburg, Kent L., Hinds, Monica T.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5872361/
https://www.ncbi.nlm.nih.gov/pubmed/29439517
http://dx.doi.org/10.3390/jcdd5010013
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author Lawson, Taylor B.
Scott-Drechsel, Devon E.
Chivukula, Venkat Keshav
Rugonyi, Sandra
Thornburg, Kent L.
Hinds, Monica T.
author_facet Lawson, Taylor B.
Scott-Drechsel, Devon E.
Chivukula, Venkat Keshav
Rugonyi, Sandra
Thornburg, Kent L.
Hinds, Monica T.
author_sort Lawson, Taylor B.
collection PubMed
description Congenital heart defects (CHDs) represent the most common form of human birth defects; approximately one-third of heart defects involve malformations of the outflow tract (OFT). Maternal diabetes increases the risk of CHD by 3–5 fold. During heart organogenesis, little is known about the effects of hyperglycemia on hemodynamics, which are critical to normal heart development. Heart development prior to septation in the chick embryo was studied under hyperglycemic conditions. Sustained hyperglycemic conditions were induced, raising the average plasma glucose concentration from 70 mg/dL to 180 mg/dL, akin to the fasting plasma glucose of a patient with diabetes. The OFTs were assessed for structural and hemodynamic alterations using optical coherence tomography (OCT), confocal microscopy, and microcomputed tomography. In hyperglycemic embryos, the endocardial cushions of the proximal OFT were asymmetric, and the OFTs curvature and torsion were significantly altered. The blood flow velocity through the OFT of hyperglycemic embryos was significantly decreased, including flow reversal in 30% of the cardiac cycle. Thus, hyperglycemia at the onset of gestation results in asymmetric proximal endocardial cushions, abnormal OFT curvature, and altered hemodynamics in the developing heart. If present in humans, these results may identify early developmental alterations that contribute to the increased risk for cardiac malformations in babies from diabetic mothers.
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spelling pubmed-58723612018-03-30 Hyperglycemia Alters the Structure and Hemodynamics of the Developing Embryonic Heart Lawson, Taylor B. Scott-Drechsel, Devon E. Chivukula, Venkat Keshav Rugonyi, Sandra Thornburg, Kent L. Hinds, Monica T. J Cardiovasc Dev Dis Article Congenital heart defects (CHDs) represent the most common form of human birth defects; approximately one-third of heart defects involve malformations of the outflow tract (OFT). Maternal diabetes increases the risk of CHD by 3–5 fold. During heart organogenesis, little is known about the effects of hyperglycemia on hemodynamics, which are critical to normal heart development. Heart development prior to septation in the chick embryo was studied under hyperglycemic conditions. Sustained hyperglycemic conditions were induced, raising the average plasma glucose concentration from 70 mg/dL to 180 mg/dL, akin to the fasting plasma glucose of a patient with diabetes. The OFTs were assessed for structural and hemodynamic alterations using optical coherence tomography (OCT), confocal microscopy, and microcomputed tomography. In hyperglycemic embryos, the endocardial cushions of the proximal OFT were asymmetric, and the OFTs curvature and torsion were significantly altered. The blood flow velocity through the OFT of hyperglycemic embryos was significantly decreased, including flow reversal in 30% of the cardiac cycle. Thus, hyperglycemia at the onset of gestation results in asymmetric proximal endocardial cushions, abnormal OFT curvature, and altered hemodynamics in the developing heart. If present in humans, these results may identify early developmental alterations that contribute to the increased risk for cardiac malformations in babies from diabetic mothers. MDPI 2018-02-12 /pmc/articles/PMC5872361/ /pubmed/29439517 http://dx.doi.org/10.3390/jcdd5010013 Text en © 2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Lawson, Taylor B.
Scott-Drechsel, Devon E.
Chivukula, Venkat Keshav
Rugonyi, Sandra
Thornburg, Kent L.
Hinds, Monica T.
Hyperglycemia Alters the Structure and Hemodynamics of the Developing Embryonic Heart
title Hyperglycemia Alters the Structure and Hemodynamics of the Developing Embryonic Heart
title_full Hyperglycemia Alters the Structure and Hemodynamics of the Developing Embryonic Heart
title_fullStr Hyperglycemia Alters the Structure and Hemodynamics of the Developing Embryonic Heart
title_full_unstemmed Hyperglycemia Alters the Structure and Hemodynamics of the Developing Embryonic Heart
title_short Hyperglycemia Alters the Structure and Hemodynamics of the Developing Embryonic Heart
title_sort hyperglycemia alters the structure and hemodynamics of the developing embryonic heart
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5872361/
https://www.ncbi.nlm.nih.gov/pubmed/29439517
http://dx.doi.org/10.3390/jcdd5010013
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