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...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2018-02-01
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| Series: | Journal of Cardiovascular Development and Disease |
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| Online Access: | http://www.mdpi.com/2308-3425/5/1/13 |
| _version_ | 1818083941272256512 |
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| author | Taylor B. Lawson Devon E. Scott-Drechsel Venkat Keshav Chivukula Sandra Rugonyi Kent L. Thornburg Monica T. Hinds |
| author_facet | Taylor B. Lawson Devon E. Scott-Drechsel Venkat Keshav Chivukula Sandra Rugonyi Kent L. Thornburg Monica T. Hinds |
| author_sort | Taylor B. Lawson |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-10T19:45:59Z |
| format | Article |
| id | doaj.art-d69716ca41814798b8a62f29837eb620 |
| institution | Directory Open Access Journal |
| issn | 2308-3425 |
| language | English |
| last_indexed | 2024-12-10T19:45:59Z |
| publishDate | 2018-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Journal of Cardiovascular Development and Disease |
| spelling | doaj.art-d69716ca41814798b8a62f29837eb6202022-12-22T01:35:53ZengMDPI AGJournal of Cardiovascular Development and Disease2308-34252018-02-01511310.3390/jcdd5010013jcdd5010013Hyperglycemia Alters the Structure and Hemodynamics of the Developing Embryonic HeartTaylor B. Lawson0Devon E. Scott-Drechsel1Venkat Keshav Chivukula2Sandra Rugonyi3Kent L. Thornburg4Monica T. Hinds5Biomedical Engineering Department, Oregon Health & Science University, Portland, OR 97239, USABiomedical Engineering Department, Oregon Health & Science University, Portland, OR 97239, USABiomedical Engineering Department, Oregon Health & Science University, Portland, OR 97239, USABiomedical Engineering Department, Oregon Health & Science University, Portland, OR 97239, USAKnight Cardiovascular Institute, Oregon Health & Science University, Portland, OR 97239, USABiomedical Engineering Department, Oregon Health & Science University, Portland, OR 97239, USACongenital 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.http://www.mdpi.com/2308-3425/5/1/13diabetesdevelopmentcongenital heart defecthemodynamics |
| spellingShingle | Taylor B. Lawson Devon E. Scott-Drechsel Venkat Keshav Chivukula Sandra Rugonyi Kent L. Thornburg Monica T. Hinds Hyperglycemia Alters the Structure and Hemodynamics of the Developing Embryonic Heart Journal of Cardiovascular Development and Disease diabetes development congenital heart defect hemodynamics |
| 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 | diabetes development congenital heart defect hemodynamics |
| url | http://www.mdpi.com/2308-3425/5/1/13 |
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