Biomechanics and Modeling in Mechanobiology

, Volume 14, Issue 6, pp 1379–1389 | Cite as

Altered mechanical state in the embryonic heart results in time-dependent decreases in cardiac function

  • Brennan Johnson
  • David BarkJr
  • Ilse Van Herck
  • Deborah Garrity
  • Lakshmi Prasad DasiEmail author
Original Paper


Proper blood flow patterns are critical for normal cardiac morphogenesis, a process that occurs rapidly in order to support further development of all tissue and organs. Previously, intracardiac fluid forces have been shown to play a critical role in cardiac morphogenesis. Altered blood flow in early development can result in an array of cardiac defects including ventricular septal defects, valve malformations, and impaired cardiac looping. However, given the dynamic and highly transient nature of cardiac morphogenesis, time dependency of the mechanical environment as an epigenetic factor in relation to intracardiac forces must be significant. Here, we show that abnormal cardiac loading adversely influences cardiac morphology only during certain time windows, thus confirming that mechanical factors are a time-dependent epigenetic factor. To illustrate this, groups of zebrafish embryos were spaced at 6-h increments from 24 to 48 h post-fertilization (hpf) in which embryos were centrifuged to generate a noninvasive alteration of cardiac preload in addition to an overall hypergravity environment. We found that earlier and later treatment groups responded with altered morphology and function, while the group with altered preload from 30 to 36 hpf had no effect. These results demonstrate the inherently time-dependent nature of epigenetic factors as pertaining to intracardiac forces and external mechanical factors. Further, it underscores the highly coupled nature of programmed biology and mechanical forces during cardiac morphogenesis. Future studies with respect to surgical correction during cardiac morphogenesis must consider timing to optimize therapeutic impact.


Epigenetics Morphogenesis Mechanobiology Heart tube Peristalsis Pumping Zebrafish Congenital defects 



We acknowledge funding from the National Science Foundation (Award # 1235305).

Supplementary material

Supplementary material 1 (wmv 7177 KB)

Supplementary material 2 (wmv 7083 KB)


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Copyright information

© Springer-Verlag Berlin Heidelberg 2015

Authors and Affiliations

  • Brennan Johnson
    • 1
  • David BarkJr
    • 1
  • Ilse Van Herck
    • 2
  • Deborah Garrity
    • 2
  • Lakshmi Prasad Dasi
    • 1
    Email author
  1. 1.Department of Mechanical EngineeringColorado State UniversityFort CollinsUSA
  2. 2.Department of BiologyColorado State UniversityFort CollinsUSA

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