Skip to main content
SpringerLink
Log in

4D modelling of fluid mechanics in the zebrafish embryonic heart

  • Original Paper
  • Published:
Biomechanics and Modeling in Mechanobiology Aims and scope Submit manuscript

Abstract

Abnormal blood flow mechanics can result in pathological heart malformation, underlining the importance of understanding embryonic cardiac fluid mechanics. In the current study, we performed image-based computational fluid dynamics simulation of the zebrafish embryonic heart ventricles and characterized flow mechanics, organ dynamics, and energy dynamics in detail. 4D scans of 5 days post-fertilization embryonic hearts with GFP-labelled myocardium were acquired using line-scan focal modulation microscopy. This revealed that the zebrafish hearts exhibited a wave-like contractile/relaxation motion from the inlet to the outlet during both systole and diastole, which we showed to be an energy efficient configuration. No impedance pumping effects of pressure and velocity waves were observed. Due to its tube-like configuration, inflow velocities were higher near the inlet and smaller at the outlet and vice versa for outflow velocities. This resulted in an interesting spatial wall shear stress (WSS) pattern where WSS waveforms near the inlet and those near the outlet were out of phase. There was large spatial variability in WSS magnitudes. Peak WSS was in the range of 47.5–130 dyne/cm2 at the inflow and outflow tracts, but were much smaller, in the range of 4–11 dyne/cm2, in the mid-ventricular segment. Due to very low Reynolds number and the highly viscous environment, intraventricular pressure gradients were high, suggesting substantial energy losses of flow through the heart.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7

Similar content being viewed by others

References

  • Antiga L, Piccinelli M, Botti L, Ene-Iordache B, Remuzzi A, Steinman DA (2008) An image-based modeling framework for patient-specific computational hemodynamics. Med Biol Eng Comput 46:1097–1112

    Article  Google Scholar 

  • Avrahami I, Gharib M (2008) Computational studies of resonance wave pumping in compliant tubes. J Fluid Mech 608:139–160

    Article  Google Scholar 

  • Bark DL Jr, Johnson B, Garrity D, Dasi LP (2017) Valveless pumping mechanics of the embryonic heart during cardiac looping: pressure and flow through micro-PIV. J Biomech 50:50–55. https://doi.org/10.1016/j.jbiomech.2016.11.036

    Article  Google Scholar 

  • Bartman T et al (2004) Early myocardial function affects endocardial cushion development in zebrafish. PLoS Biol 2:e129

    Article  Google Scholar 

  • Chong SP, Pant S, Chen N (2011) Line-scan focal modulation microscopy for rapid imaging of thick biological specimens. In: Asia communications and photonics conference and exhibition. Optical Society of America, p 83111C

  • Feintuch A et al (2007) Hemodynamics in the mouse aortic arch as assessed by MRI, ultrasound, and numerical modeling. Am J Physiol Heart Circ Physiol 292:H884–H892. https://doi.org/10.1152/ajpheart.00796.2006

    Article  Google Scholar 

  • Forouhar AS et al (2006) The embryonic vertebrate heart tube is a dynamic suction pump. Science 312:751–753. https://doi.org/10.1126/science.1123775

    Article  Google Scholar 

  • Geva T, Powell AJ, Crawford EC, Chung T, Colan SD (1998) Evaluation of regional differences in right ventricular systolic function by acoustic quantification echocardiography and cine magnetic resonance imaging. Circulation 98:339–345

    Article  Google Scholar 

  • Groenendijk BC, Hierck BP, Gittenberger-de Groot AC, Poelmann RE (2004) Development-related changes in the expression of shear stress responsive genes KLF-2, ET-1, and NOS-3 in the developing cardiovascular system of chicken embryos. Dev Dyn 230:57–68

    Article  Google Scholar 

  • Haack T, Abdelilah-Seyfried S (2016) The force within: endocardial development, mechanotransduction and signalling during cardiac morphogenesis. Development (Cambridge, England) 143:373–386. https://doi.org/10.1242/dev.131425

    Article  Google Scholar 

  • Ho S, Tan GXY, Foo TJ, Phan-Thien N, Yap CH (2017) Organ dynamics and fluid dynamics of the HH25 chick embryonic cardiac ventricle as revealed by a novel 4D high-frequency ultrasound imaging technique and computational flow simulations. Ann Biomed Eng 45:2309–2323

    Article  Google Scholar 

  • Hove JR, Koster RW, Forouhar AS, Acevedo-Bolton G, Fraser SE, Gharib M (2003) Intracardiac fluid forces are an essential epigenetic factor for embryonic cardiogenesis. Nature 421:172–177. https://doi.org/10.1038/nature01282

    Article  Google Scholar 

  • Hu N, Sedmera D, Yost HJ, Clark EB (2000) Structure and function of the developing zebrafish heart. Anat Rec 260:148–157

    Article  Google Scholar 

  • Huisken J, Swoger J, Del Bene F, Wittbrodt J, Stelzer EH (2004) Optical sectioning deep inside live embryos by selective plane illumination microscopy. Science 305:1007–1009. https://doi.org/10.1126/science.1100035

    Article  Google Scholar 

  • Jacob E, Drexel M, Schwerte T, Pelster B (2002) Influence of hypoxia and of hypoxemia on the development of cardiac activity in zebrafish larvae. Am J Physiol Regul Integr Comput Physiol 283:R911–917. https://doi.org/10.1152/ajpregu.00673.2001

    Article  Google Scholar 

  • Jamison RA, Fouras A, Bryson-Richardson RJ (2012) Cardiac-phase filtering in intracardiac particle image velocimetry. J Biomed Opt 17:036007. https://doi.org/10.1117/1.JBO.17.3.036007

    Article  Google Scholar 

  • Keller PJ, Schmidt AD, Wittbrodt J, Stelzer EH (2008) Reconstruction of zebrafish early embryonic development by scanned light sheet microscopy. Science 322:1065–1069

    Article  Google Scholar 

  • Lee J et al (2013) Moving domain computational fluid dynamics to interface with an embryonic model of cardiac morphogenesis. PLoS ONE 8:e72924. https://doi.org/10.1371/journal.pone.0072924

    Article  Google Scholar 

  • Lee J et al (2017) A rapid capillary-pressure driven micro-channel to demonstrate newtonian fluid behavior of zebrafish blood at high shear rate. Sci Rep 7:1980. https://doi.org/10.1038/s41598-017-02253-7

    Article  Google Scholar 

  • Marstal K, Berendsen F, Staring M, Klein S (2016) SimpleElastix: a user-friendly, multi-lingual library for medical image registration. In: Proceedings of the IEEE conference on computer vision and pattern recognition workshops, pp 134–142

  • Mickoleit M, Schmid B, Weber M, Fahrbach FO, Hombach S, Reischauer S, Huisken J (2014) High-resolution reconstruction of the beating zebrafish heart. Nat Methods 11:919–922. https://doi.org/10.1038/nmeth.3037

    Article  Google Scholar 

  • Miller LA (2011) Fluid dynamics of ventricular filling in the embryonic heart. Cell Biochem Biophys 61:33–45. https://doi.org/10.1007/s12013-011-9157-9

    Article  Google Scholar 

  • Mosimann C, Puller AC, Lawson KL, Tschopp P, Amsterdam A, Zon LI (2013) Site-directed zebrafish transgenesis into single landing sites with the phiC31 integrase system. Dev Dyn 242:949–963. https://doi.org/10.1002/dvdy.23989

    Article  Google Scholar 

  • Oslash RB, Weber R (1995) Effects of oxygenation and the stress hormones adrenaline and cortisol on the viscosity of blood from the trout Oncorhynchus mykiss. J Exp Biol 198:953–959

    Google Scholar 

  • Pant S, Duan Y, Xiong F, Chen N (2017a) Augmented line-scan focal modulation microscopy for multi-dimensional imaging of zebrafish heart in vivo. Biomed Opt Express 8:5698–5707

    Article  Google Scholar 

  • Pant S, Li C, Gong Z, Chen N (2017b) Line-scan focal modulation microscopy. J Biomed Opt 22:50502. https://doi.org/10.1117/1.JBO.22.5.050502

    Article  Google Scholar 

  • Pantokratoras A (2016) Steady laminar flow in a 90 bend. Adv Mech Eng 8:1687814016669472

    Google Scholar 

  • Peterson LM, Jenkins MW, Gu S, Barwick L, Watanabe M, Rollins AM (2012) 4D shear stress maps of the developing heart using Doppler optical coherence tomography. Biomed Opt Express 3:3022–3032. https://doi.org/10.1364/boe.3.003022

    Article  Google Scholar 

  • Raines R, LeWinter M, Covell J (1976) Regional shortening patterns in canine right ventricle. Am J Physiol Leg Content 231:1395–1400

    Article  Google Scholar 

  • Schenkel T, Malve M, Reik M, Markl M, Jung B, Oertel H (2009) MRI-based CFD analysis of flow in a human left ventricle: methodology and application to a healthy heart. Ann Biomed Eng 37:503–515. https://doi.org/10.1007/s10439-008-9627-4

    Article  Google Scholar 

  • Scherz PJ, Huisken J, Sahai-Hernandez P, Stainier DY (2008) High-speed imaging of developing heart valves reveals interplay of morphogenesis and function. Development (Cambridge, England) 135:1179–1187. https://doi.org/10.1242/dev.010694

    Article  Google Scholar 

  • Sedmera D, Pexieder T, Rychterova V, Hu N, Clark EB (1999) Remodeling of chick embryonic ventricular myoarchitecture under experimentally changed loading conditions. Anat Rec 254:238–252

    Article  Google Scholar 

  • Staudt DW, Liu J, Thorn KS, Stuurman N, Liebling M, Stainier DY (2014) High-resolution imaging of cardiomyocyte behavior reveals two distinct steps in ventricular trabeculation. Development (Cambridge, England) 141:585–593. https://doi.org/10.1242/dev.098632

    Article  Google Scholar 

  • Steed E, Boselli F, Vermot J (2016a) Hemodynamics driven cardiac valve morphogenesis. Biochim Biophys Acta 1863:1760–1766. https://doi.org/10.1016/j.bbamcr.2015.11.014

    Article  Google Scholar 

  • Steed E, Faggianelli N, Roth S, Ramspacher C, Concordet J-P, Vermot J (2016b) klf2a couples mechanotransduction and zebrafish valve morphogenesis through fibronectin synthesis. Nat Commun 7:11646

    Article  Google Scholar 

  • Tobita K, Keller BB (2000) Right and left ventricular wall deformation patterns in normal and left heart hypoplasia chick embryos. Am J Physiol Heart Circ Physiol 279:H959–969

    Article  Google Scholar 

  • Topper JN, Gimbrone MA (1999) Blood flow and vascular gene expression: fluid shear stress as a modulator of endothelial phenotype. Mol Med Today 5:40–46. https://doi.org/10.1016/S1357-4310(98)01372-0

    Article  Google Scholar 

  • Tu S, Chi NC (2012) Zebrafish models in cardiac development and congenital heart birth defects. Differentiation 84:4–16. https://doi.org/10.1016/j.diff.2012.05.005

    Article  Google Scholar 

  • Vedula V, Lee J, Xu H, Kuo C-CJ, Hsiai TK, Marsden AL (2017) A method to quantify mechanobiologic forces during zebrafish cardiac development using 4-D light sheet imaging and computational modeling. PLoS Comput Biol 13:e1005828

    Article  Google Scholar 

  • Wiputra H et al (2016) Fluid mechanics of human fetal right ventricles from image-based computational fluid dynamics using 4D clinical ultrasound scans. Am J Physiol Heart Circ Physiol 311:H1498–H1508. https://doi.org/10.1152/ajpheart.00400.2016

    Article  Google Scholar 

  • Yotti R et al (2005) Doppler-derived ejection intraventricular pressure gradients provide a reliable assessment of left ventricular systolic chamber function. Circulation 112:1771–1779. https://doi.org/10.1161/CIRCULATIONAHA.104.485128

    Article  Google Scholar 

Download references

Acknowledgement

This study was supported by the National University of Singapore 2015 Young Investigator Award (PI:Yap). All authors have no conflict of interest to declare. We thank Christian Mosimann and Suresh Jesuthasan for providing the transgenic zebrafish line.

Author information

Authors and Affiliations

  1. Department of Biomedical Engineering, National University of Singapore, Singapore, Singapore

    Yoke Yin Foo, Shilpa Pant, Nanguang Chen & Choon Hwai Yap

  2. Department of Biological Science, National University of Singapore, Singapore, Singapore

    Huiping Shermaine Tay, Nurgul Imangali & Christoph Winkler

Authors
  1. Yoke Yin Foo
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Shilpa Pant
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Huiping Shermaine Tay
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Nurgul Imangali
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Nanguang Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Christoph Winkler
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Choon Hwai Yap
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Choon Hwai Yap.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Electronic supplementary material

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Foo, Y.Y., Pant, S., Tay, H. et al. 4D modelling of fluid mechanics in the zebrafish embryonic heart. Biomech Model Mechanobiol 19, 221–232 (2020). https://doi.org/10.1007/s10237-019-01205-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10237-019-01205-6

Keywords

Search

Navigation