Skip to main content
Biophysical Journal logoLink to Biophysical Journal
. 2001 Jan;80(1):516–530. doi: 10.1016/S0006-3495(01)76034-1

Visualizing excitation waves inside cardiac muscle using transillumination.

W T Baxter 1, S F Mironov 1, A V Zaitsev 1, J Jalife 1, A M Pertsov 1
PMCID: PMC1301253  PMID: 11159422

Abstract

Voltage-sensitive fluorescent dyes have become powerful tools for the visualization of excitation propagation in the heart. However, until recently they were used exclusively for surface recordings. Here we demonstrate the possibility of visualizing the electrical activity from inside cardiac muscle via fluorescence measurements in the transillumination mode (in which the light source and photodetector are on opposite sides of the preparation). This mode enables the detection of light escaping from layers deep within the tissue. Experiments were conducted in perfused (8 mm thick) slabs of sheep right ventricular wall stained with the voltage-sensitive dye di-4-ANEPPS. Although the amplitude and signal-to-noise ratio recorded in the transillumination mode were significantly smaller than those recorded in the epi-illumination mode, they were sufficient to reliably determine the activation sequence. Penetration depths (spatial decay constants) derived from measurements of light attenuation in cardiac muscle were 0.8 mm for excitation (520 +/- 30 nm) and 1.3 mm for emission wavelengths (640 +/- 50 nm). Estimates of emitted fluorescence based on these attenuation values in 8-mm-thick tissue suggest that 90% of the transillumination signal originates from a 4-mm-thick layer near the illuminated surface. A 69% fraction of the recorded signal originates from > or =1 mm below the surface. Transillumination recordings may be combined with endocardial and epicardial surface recordings to obtain information about three-dimensional propagation in the thickness of the myocardial wall. We show an example in which transillumination reveals an intramural reentry, undetectable in surface recordings.

Full Text

The Full Text of this article is available as a PDF (639.8 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Baxter W. T., Davidenko J. M., Loew L. M., Wuskell J. P., Jalife J. Technical features of a CCD video camera system to record cardiac fluorescence data. Ann Biomed Eng. 1997 Jul-Aug;25(4):713–725. doi: 10.1007/BF02684848. [DOI] [PubMed] [Google Scholar]
  2. Davidenko J. M. Spiral wave activity: a possible common mechanism for polymorphic and monomorphic ventricular tachycardias. J Cardiovasc Electrophysiol. 1993 Dec;4(6):730–746. doi: 10.1111/j.1540-8167.1993.tb01258.x. [DOI] [PubMed] [Google Scholar]
  3. Dillon S. M., Kerner T. E., Hoffman J., Menz V., Li K. S., Michele J. J. A system for in-vivo cardiac optical mapping. IEEE Eng Med Biol Mag. 1998 Jan-Feb;17(1):95–108. doi: 10.1109/51.646226. [DOI] [PubMed] [Google Scholar]
  4. Efimov I. R., Sidorov V., Cheng Y., Wollenzier B. Evidence of three-dimensional scroll waves with ribbon-shaped filament as a mechanism of ventricular tachycardia in the isolated rabbit heart. J Cardiovasc Electrophysiol. 1999 Nov;10(11):1452–1462. doi: 10.1111/j.1540-8167.1999.tb00204.x. [DOI] [PubMed] [Google Scholar]
  5. El-Sherif N., Chinushi M., Caref E. B., Restivo M. Electrophysiological mechanism of the characteristic electrocardiographic morphology of torsade de pointes tachyarrhythmias in the long-QT syndrome: detailed analysis of ventricular tridimensional activation patterns. Circulation. 1997 Dec 16;96(12):4392–4399. doi: 10.1161/01.cir.96.12.4392. [DOI] [PubMed] [Google Scholar]
  6. El-Sherif N., Smith R. A., Evans K. Canine ventricular arrhythmias in the late myocardial infarction period. 8. Epicardial mapping of reentrant circuits. Circ Res. 1981 Jul;49(1):255–265. doi: 10.1161/01.res.49.1.255. [DOI] [PubMed] [Google Scholar]
  7. Fast V. G., Kléber A. G. Microscopic conduction in cultured strands of neonatal rat heart cells measured with voltage-sensitive dyes. Circ Res. 1993 Nov;73(5):914–925. doi: 10.1161/01.res.73.5.914. [DOI] [PubMed] [Google Scholar]
  8. Flock S. T., Patterson M. S., Wilson B. C., Wyman D. R. Monte Carlo modeling of light propagation in highly scattering tissue--I: Model predictions and comparison with diffusion theory. IEEE Trans Biomed Eng. 1989 Dec;36(12):1162–1168. doi: 10.1109/tbme.1989.1173624. [DOI] [PubMed] [Google Scholar]
  9. Frazier D. W., Wolf P. D., Wharton J. M., Tang A. S., Smith W. M., Ideker R. E. Stimulus-induced critical point. Mechanism for electrical initiation of reentry in normal canine myocardium. J Clin Invest. 1989 Mar;83(3):1039–1052. doi: 10.1172/JCI113945. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Gardner C. M., Jacques S. L., Welch A. J. Light transport in tissue: Accurate expressions for one-dimensional fluence rate and escape function based upon monte carlo simulation. Lasers Surg Med. 1996;18(2):129–138. doi: 10.1002/(SICI)1096-9101(1996)18:2<129::AID-LSM2>3.0.CO;2-U. [DOI] [PubMed] [Google Scholar]
  11. Girouard S. D., Laurita K. R., Rosenbaum D. S. Unique properties of cardiac action potentials recorded with voltage-sensitive dyes. J Cardiovasc Electrophysiol. 1996 Nov;7(11):1024–1038. doi: 10.1111/j.1540-8167.1996.tb00478.x. [DOI] [PubMed] [Google Scholar]
  12. Jacques S. L. Light distributions from point, line and plane sources for photochemical reactions and fluorescence in turbid biological tissues. Photochem Photobiol. 1998 Jan;67(1):23–32. [PubMed] [Google Scholar]
  13. Knisley S. B. Transmembrane voltage changes during unipolar stimulation of rabbit ventricle. Circ Res. 1995 Dec;77(6):1229–1239. doi: 10.1161/01.res.77.6.1229. [DOI] [PubMed] [Google Scholar]
  14. Lenfant C. NHLBI funding policies. Enhancing stability, predictability, and cost control. Circulation. 1994 Jul;90(1):1–1. doi: 10.1161/01.cir.90.1.1. [DOI] [PubMed] [Google Scholar]
  15. Marynissen J. P., Star W. M. Phantom measurements for light dosimetry using isotropic and small aperture detectors. Prog Clin Biol Res. 1984;170:133–148. [PubMed] [Google Scholar]
  16. Pertsov A. M., Davidenko J. M., Salomonsz R., Baxter W. T., Jalife J. Spiral waves of excitation underlie reentrant activity in isolated cardiac muscle. Circ Res. 1993 Mar;72(3):631–650. doi: 10.1161/01.res.72.3.631. [DOI] [PubMed] [Google Scholar]
  17. Pogwizd S. M., Corr P. B. Reentrant and nonreentrant mechanisms contribute to arrhythmogenesis during early myocardial ischemia: results using three-dimensional mapping. Circ Res. 1987 Sep;61(3):352–371. doi: 10.1161/01.res.61.3.352. [DOI] [PubMed] [Google Scholar]
  18. Preuss L. E., Bolin F. P., Cain B. W. A comment on spectral transmittance in mammalian skeletal muscle. Photochem Photobiol. 1983 Jan;37(1):113–116. doi: 10.1111/j.1751-1097.1983.tb04443.x. [DOI] [PubMed] [Google Scholar]
  19. Profio A. E., Doiron D. R. Transport of light in tissue in photodynamic therapy. Photochem Photobiol. 1987 Nov;46(5):591–599. doi: 10.1111/j.1751-1097.1987.tb04819.x. [DOI] [PubMed] [Google Scholar]
  20. Rohr S., Salzberg B. M. Multiple site optical recording of transmembrane voltage (MSORTV) in patterned growth heart cell cultures: assessing electrical behavior, with microsecond resolution, on a cellular and subcellular scale. Biophys J. 1994 Sep;67(3):1301–1315. doi: 10.1016/S0006-3495(94)80602-2. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Salama G., Kanai A., Efimov I. R. Subthreshold stimulation of Purkinje fibers interrupts ventricular tachycardia in intact hearts. Experimental study with voltage-sensitive dyes and imaging techniques. Circ Res. 1994 Apr;74(4):604–619. doi: 10.1161/01.res.74.4.604. [DOI] [PubMed] [Google Scholar]
  22. Salama G., Lombardi R., Elson J. Maps of optical action potentials and NADH fluorescence in intact working hearts. Am J Physiol. 1987 Feb;252(2 Pt 2):H384–H394. doi: 10.1152/ajpheart.1987.252.2.H384. [DOI] [PubMed] [Google Scholar]
  23. Star W. M., Marijnissen J. P., van Gemert M. J. Light dosimetry in optical phantoms and in tissues: I. Multiple flux and transport theory. Phys Med Biol. 1988 Apr;33(4):437–454. doi: 10.1088/0031-9155/33/4/004. [DOI] [PubMed] [Google Scholar]
  24. Svaasand L. O. Optical dosimetry for direct and interstitial photoradiation therapy of malignant tumors. Prog Clin Biol Res. 1984;170:91–114. [PubMed] [Google Scholar]
  25. Wikswo J. P., Jr, Lin S. F., Abbas R. A. Virtual electrodes in cardiac tissue: a common mechanism for anodal and cathodal stimulation. Biophys J. 1995 Dec;69(6):2195–2210. doi: 10.1016/S0006-3495(95)80115-3. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Wilson B. C., Jeeves W. P., Lowe D. M. In vivo and post mortem measurements of the attenuation spectra of light in mammalian tissues. Photochem Photobiol. 1985 Aug;42(2):153–162. doi: 10.1111/j.1751-1097.1985.tb01554.x. [DOI] [PubMed] [Google Scholar]
  27. Winfree A. T. Scroll-shaped waves of chemical activity in three dimensions. Science. 1973 Sep 7;181(4103):937–939. doi: 10.1126/science.181.4103.937. [DOI] [PubMed] [Google Scholar]
  28. Witkowski F. X., Leon L. J., Penkoske P. A., Giles W. R., Spano M. L., Ditto W. L., Winfree A. T. Spatiotemporal evolution of ventricular fibrillation. Nature. 1998 Mar 5;392(6671):78–82. doi: 10.1038/32170. [DOI] [PubMed] [Google Scholar]

Articles from Biophysical Journal are provided here courtesy of The Biophysical Society

RESOURCES