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Proceedings Paper

Altering hemodynamics leads to congenital heart defects (Conference Presentation)
Author(s): Stephanie M. Ford; Matthew T. McPheeters; Yves T. Wang; Shi Gu; Yong Qiu Doughman; James P. Strainic; Andrew M. Rollins; Michiko Watanabe; Michael W. Jenkins
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Paper Abstract

The role of hemodynamics in early heart development is poorly understood. In order to successfully assess the impact of hemodynamics on development, we need to monitor and perturb blood flow, and quantify the resultant effects on morphology. Here, we have utilized cardiac optical pacing to create regurgitant flow in embryonic hearts and OCT to quantify regurgitation percentage and resultant morphology. Embryonic quail in a shell-less culture were optically paced at 3 Hz (well above the intrinsic rate or 1.33-1.67 Hz) on day 2 of development (3-4 weeks human) for 5 minutes. The pacing fatigued the heart and led to a prolonged period (> 1 hour) of increased regurgitant flow. Embryos were kept alive until day 3 (cardiac looping - 4-5 weeks human) or day 8 (4 chambered heart - 8 weeks human) to quantify resultant morphologic changes with OCT. All paced embryos imaged at day 3 displayed cardiac defects. The extent of regurgitant flow immediately after pacing was correlated with cardiac cushion size 24-hours post pacing (p-value < 0.01) with higher regurgitation leading to smaller cushions. Almost all embryos (16/18) surviving to day 8 exhibited congenital heart defects (CHDs) including 11/18 with valve defects, 5/18 with ventricular septal defects and 5/18 with hypoplastic right ventricles. Our data suggests that regurgitant flow leads to smaller cushions, which develop into abnormal valves and septa. Our model produces similar phenotypes as found in our fetal alcohol syndrome and velo-cardio-facial/DiGeorge syndrome models suggesting that hemodynamics plays a role in these syndromes as well. Utilizing OCT and optical pacing to understand hemodynamics in development is an important step towards determining CHD mechanisms and ultimately developing earlier treatments.

Paper Details

Date Published:
PDF: 1 pages
Proc. SPIE 9716, Optical Methods in Developmental Biology IV, 971608; doi: 10.1117/12.2214825
Show Author Affiliations
Stephanie M. Ford, Univ. Hospitals Rainbow Babies & Children's Hospital (United States)
Matthew T. McPheeters, Case Western Reserve Univ. (United States)
Yves T. Wang, Case Western Reserve Univ. (United States)
Shi Gu, Case Western Reserve Univ. (United States)
Yong Qiu Doughman, Case Western Reserve Univ. (United States)
James P. Strainic, Univ. Hospitals Rainbow Babies & Children's Hospital (United States)
Andrew M. Rollins, Case Western Reserve Univ. (United States)
Michiko Watanabe, Case Western Reserve Univ. (United States)
Michael W. Jenkins, Case Western Reserve Univ. (United States)


Published in SPIE Proceedings Vol. 9716:
Optical Methods in Developmental Biology IV
Andrew M. Rollins; Scott E. Fraser; Michael A. Choma, Editor(s)

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