OSA's Digital Library

Biomedical Optics Express

Biomedical Optics Express

  • Editor: Joseph A. Izatt
  • Vol. 5, Iss. 5 — May. 1, 2014
  • pp: 1616–1625

Optical assessment of the cardiac rhythm of contracting cardiomyocytes in vitro and a pulsating heart in vivo for pharmacological screening

Yu-Cheng Lai, Wei-Tien Chang, Kuen-You Lin, and Ian Liau  »View Author Affiliations

Biomedical Optics Express, Vol. 5, Issue 5, pp. 1616-1625 (2014)

View Full Text Article

Enhanced HTML    Acrobat PDF (1458 KB)

Browse Journals / Lookup Meetings

Browse by Journal and Year


Lookup Conference Papers

Close Browse Journals / Lookup Meetings

Article Tools



Our quest in the pathogenesis and therapies targeting human heart diseases requires assessment of the contractile dynamics of cardiac models of varied complexity, such as isolated cardiomyocytes and the heart of a model animal. It is hence beneficial to have an integral means that can interrogate both cardiomyocytes in vitro and a heart in vivo. Herein we report an application of dual-beam optical reflectometry to determine noninvasively the rhythm of two representative cardiac models–chick embryonic cardiomyocytes and the heart of zebrafish. We probed self-beating cardiomyocytes and revealed the temporally varying contractile frequency with a short-time Fourier transform. Our unique dual-beam setup uniquely records the atrial and ventricular pulsations of zebrafish simultaneously. To minimize the cross talk between signals associated with atrial and ventricular chambers, we particularly modulated the two probe beams at distinct frequencies and extracted the signals specific to individual cardiac chambers with phase-sensitive detection. With this setup, we determined the atrio-ventricular interval, a parameter that is manifested by the electrical conduction from the atrium to the ventricle. To demonstrate pharmacological applications, we characterized zebrafish treated with various cardioactive and cardiotoxic drugs, and identified abnormal cardiac rhythms and atrioventricular (AV) blocks of varied degree. In light of its potential capability to assess cardiac models both in vitro and in vivo and to screen drugs with cardioactivity or toxicity, we expect this approach to have broad applications ranging from cardiopharmacology to developmental biology.

© 2014 Optical Society of America

OCIS Codes
(170.0170) Medical optics and biotechnology : Medical optics and biotechnology
(170.2655) Medical optics and biotechnology : Functional monitoring and imaging

ToC Category:
Cardiovascular Applications

Original Manuscript: February 10, 2014
Revised Manuscript: April 15, 2014
Manuscript Accepted: April 15, 2014
Published: April 23, 2014

Yu-Cheng Lai, Wei-Tien Chang, Kuen-You Lin, and Ian Liau, "Optical assessment of the cardiac rhythm of contracting cardiomyocytes in vitro and a pulsating heart in vivo for pharmacological screening," Biomed. Opt. Express 5, 1616-1625 (2014)

Sort:  Author  |  Year  |  Journal  |  Reset  


  1. A. S. Go, D. Mozaffarian, V. L. Roger, E. J. Benjamin, J. D. Berry, W. B. Borden, D. M. Bravata, S. Dai, E. S. Ford, C. S. Fox, S. Franco, H. J. Fullerton, C. Gillespie, S. M. Hailpern, J. A. Heit, V. J. Howard, M. D. Huffman, B. M. Kissela, S. J. Kittner, D. T. Lackland, J. H. Lichtman, L. D. Lisabeth, D. Magid, G. M. Marcus, A. Marelli, D. B. Matchar, D. K. McGuire, E. R. Mohler, C. S. Moy, M. E. Mussolino, G. Nichol, N. P. Paynter, P. J. Schreiner, P. D. Sorlie, J. Stein, T. N. Turan, S. S. Virani, N. D. Wong, D. Woo, M. B. Turner, and American Heart Association Statistics Committee and Stroke Statistics Subcommittee, “Heart disease and stroke statistics--2013 update: a report from the American Heart Association,” Circulation127(1), e6–e245 (2013). [CrossRef] [PubMed]
  2. G. Iribe, M. Helmes, and P. Kohl, “Force-length relations in isolated intact cardiomyocytes subjected to dynamic changes in mechanical load,” Am. J. Physiol. Heart. C.292, H1487–H1497 (2007).
  3. N. Klauke, G. Smith, and J. M. Cooper, “Local regional stimulation of single isolated ventricular myocytes using microfluidics,” Anal. Chem.81(15), 6390–6398 (2009). [CrossRef] [PubMed]
  4. G. J. Lieschke and P. D. Currie, “Animal models of human disease: zebrafish swim into view,” Nat. Rev. Genet.8(5), 353–367 (2007). [CrossRef] [PubMed]
  5. N. C. Chi, R. M. Shaw, B. Jungblut, J. Huisken, T. Ferrer, R. Arnaout, I. Scott, D. Beis, T. Xiao, H. Baier, L. Y. Jan, M. Tristani-Firouzi, and D. Y. Stainier, “Genetic and physiologic dissection of the vertebrate cardiac conduction system,” PLoS Biol.6(5), e109 (2008). [CrossRef] [PubMed]
  6. J. Gao, J. A. Lyon, D. P. Szeto, and J. Chen, “In vivo imaging and quantitative analysis of zebrafish embryos by digital holographic microscopy,” Biomed. Opt. Express3(10), 2623–2635 (2012). [CrossRef] [PubMed]
  7. T. J. A. Chico, P. W. Ingham, and D. C. Crossman, “Modeling cardiovascular disease in the zebrafish,” Trends Cardiovasc. Med.18(4), 150–155 (2008). [CrossRef] [PubMed]
  8. J. Bakkers, “Zebrafish as a model to study cardiac development and human cardiac disease,” Cardiovasc. Res.91(2), 279–288 (2011). [CrossRef] [PubMed]
  9. D. S. Peal, R. W. Mills, S. N. Lynch, J. M. Mosley, E. Lim, P. T. Ellinor, C. T. January, R. T. Peterson, and D. J. Milan, “Novel chemical suppressors of long QT syndrome identified by an in vivo functional screen,” Circulation123(1), 23–30 (2011). [CrossRef] [PubMed]
  10. C.-K. Sun, S.-W. Chu, S.-Y. Chen, T.-H. Tsai, T.-M. Liu, C.-Y. Lin, and H.-J. Tsai, “Higher harmonic generation microscopy for developmental biology,” J. Struct. Biol.147(1), 19–30 (2004). [CrossRef] [PubMed]
  11. C. G. Burns, D. J. Milan, E. J. Grande, W. Rottbauer, C. A. MacRae, and M. C. Fishman, “High-throughput assay for small molecules that modulate zebrafish embryonic heart rate,” Nat. Chem. Biol.1(5), 263–264 (2005). [CrossRef] [PubMed]
  12. S.-H. Huang, C.-D. Hsiao, D.-S. Lin, C.-Y. Chow, C.-J. Chang, and I. Liau, “Imaging of zebrafish in vivo with second-harmonic generation reveals shortened sarcomeres associated with myopathy induced by statin,” PLoS ONE6(9), e24764 (2011). [CrossRef] [PubMed]
  13. M. Brodsky, D. Wu, P. Denes, C. Kanakis, and K. M. Rosen, “Arrhythmias documented by 24 hour continuous electrocardiographic monitoring in 50 male medical students without apparent heart disease,” Am. J. Cardiol.39(3), 390–395 (1977). [CrossRef] [PubMed]
  14. D. J. Milan, I. L. Jones, P. T. Ellinor, and C. A. MacRae, “In vivo recording of adult zebrafish electrocardiogram and assessment of drug-induced QT prolongation,” Am. J. Physiol. Heart. C.291, H269–H273 (2006).
  15. P. Sun, Y. Zhang, F. Yu, E. Parks, A. Lyman, Q. Wu, L. S. Ai, C. H. Hu, Q. F. Zhou, K. Shung, C. L. Lien, and T. K. Hsiai, “Micro-electrocardiograms to study post-ventricular amputation of zebrafish heart,” Ann. Biomed. Eng.37(5), 890–901 (2009). [CrossRef] [PubMed]
  16. C. T. Tsai, C. K. Wu, F. T. Chiang, C. D. Tseng, J. K. Lee, C. C. Yu, Y. C. Wang, L. P. Lai, J. L. Lin, and J. J. Hwang, “In-vitro recording of adult zebrafish heart electrocardiogram - A platform for pharmacological testing,” Clin. Chim. Acta412(21-22), 1963–1967 (2011). [CrossRef] [PubMed]
  17. T. Schwerte, C. Prem, A. Mairösl, and B. Pelster, “Development of the sympatho-vagal balance in the cardiovascular system in zebrafish (Danio rerio) characterized by power spectrum and classical signal analysis,” J. Exp. Biol.209(6), 1093–1100 (2006). [CrossRef] [PubMed]
  18. S. S. Dhillon, É. Dóró, I. Magyary, S. Egginton, A. Sík, and F. Müller, “Optimisation of embryonic and larval ECG measurement in zebrafish for quantifying the effect of QT prolonging drugs,” PLoS ONE8(4), e60552 (2013). [CrossRef] [PubMed]
  19. P. A. Ritto, J. G. Contreras, and J. J. Alvarado-Gil, “Monitoring of heartbeat by laser beam reflection,” Meas. Sci. Technol.14(3), 317–322 (2003). [CrossRef]
  20. M. Yoshida, R. Hirano, and T. Shima, “Photocardiography: A novel method for monitoring cardiac activity in fish,” Zoolog. Sci.26(5), 356–361 (2009). [CrossRef] [PubMed]
  21. W. T. Chang, D. Yu, Y. C. Lai, K. Y. Lin, and I. Liau, “Characterization of the mechanodynamic response of cardiomyocytes with atomic force microscopy,” Anal. Chem.85(3), 1395–1400 (2013). [CrossRef] [PubMed]
  22. W. C. Huang, Y. S. Hsieh, I. H. Chen, C. H. Wang, H. W. Chang, C. C. Yang, T. H. Ku, S. R. Yeh, and Y. J. Chuang, “Combined use of MS-222 (Tricaine) and isoflurane extends anesthesia time and minimizes cardiac rhythm side effects in adult zebrafish,” Zebrafish7(3), 297–304 (2010). [CrossRef] [PubMed]
  23. D. J. Milan, T. A. Peterson, J. N. Ruskin, R. T. Peterson, and C. A. MacRae, “Drugs that induce repolarization abnormalities cause bradycardia in zebrafish,” Circulation107(10), 1355–1358 (2003). [CrossRef] [PubMed]
  24. M. Gheorghiade, K. F. Adams, and W. S. Colucci, “Digoxin in the management of cardiovascular disorders,” Circulation109(24), 2959–2964 (2004). [CrossRef] [PubMed]
  25. S. Kinlay and N. A. Buckley, “Magnesium sulfate in the treatment of ventricular arrhythmias due to digoxin toxicity,” J. Toxicol. Clin. Toxicol.33(1), 55–59 (1995). [CrossRef] [PubMed]
  26. G. Ma, W. J. Brady, M. Pollack, and T. C. Chan, “Electrocardiographic manifestations: digitalis toxicity,” J. Emerg. Med.20(2), 145–152 (2001). [CrossRef] [PubMed]

Cited By

Alert me when this paper is cited

OSA is able to provide readers links to articles that cite this paper by participating in CrossRef's Cited-By Linking service. CrossRef includes content from more than 3000 publishers and societies. In addition to listing OSA journal articles that cite this paper, citing articles from other participating publishers will also be listed.

« Previous Article  |  Next Article »

OSA is a member of CrossRef.

CrossCheck Deposited