Display options
Cite
de Oliveira BL, Pfeiffer ER, Sundnes J, et al. Increased cell membrane capacitance is the dominant mechanism of stretch-dependent conduction slowing in the rabbit heart: a computational study. Cell Mol Bioeng. 2015;8(2):237-246doi: 10.1007/s12195-015-0384-9.
de Oliveira, B. L., Pfeiffer, E. R., Sundnes, J., Wall, S. T., & McCulloch, A. D. (2015). Increased cell membrane capacitance is the dominant mechanism of stretch-dependent conduction slowing in the rabbit heart: a computational study. Cellular and molecular bioengineering, 8(2), 237-246. https://doi.org/10.1007/s12195-015-0384-9
de Oliveira, Bernardo L, et al. "Increased cell membrane capacitance is the dominant mechanism of stretch-dependent conduction slowing in the rabbit heart: a computational study." Cellular and molecular bioengineering vol. 8,2 (2015): 237-246. doi: https://doi.org/10.1007/s12195-015-0384-9
de Oliveira BL, Pfeiffer ER, Sundnes J, Wall ST, McCulloch AD. Increased cell membrane capacitance is the dominant mechanism of stretch-dependent conduction slowing in the rabbit heart: a computational study. Cell Mol Bioeng. 2015 Jun 01;8(2):237-246. doi: 10.1007/s12195-015-0384-9. Epub 2015 Mar 24. PMID: 27087858; PMCID: PMC4830494.
Copy Download .nbib Format: NLM
Share it on

Cell Mol Bioeng. 2015 Jun 01;8(2):237-246. doi: 10.1007/s12195-015-0384-9. Epub 2015 Mar 24.

Increased cell membrane capacitance is the dominant mechanism of stretch-dependent conduction slowing in the rabbit heart: a computational study.

Cellular and molecular bioengineering

Bernardo L de Oliveira, Emily R Pfeiffer, Joakim Sundnes, Samuel T Wall, Andrew D McCulloch

Affiliations

  1. Simula Research Laboratory, Lysaker, Norway.
  2. Bioengineering Department, University of California, San Diego.
  3. Simula Research Laboratory, Lysaker, Norway; Department of Informatics, University of Oslo, Norway.

PMID: 27087858 PMCID: PMC4830494 DOI: 10.1007/s12195-015-0384-9

Abstract

Volume loading of the cardiac ventricles is known to slow electrical conduction in the rabbit heart, but the mechanisms remain unclear. Previous experimental and modeling studies have investigated some of these mechanisms, including stretch-activated membrane currents, reduced gap junctional conductance, and altered cell membrane capacitance. In order to quantify the relative contributions of these mechanisms, we combined a monomain model of rabbit ventricular electrophysiology with a hyperelastic model of passive ventricular mechanics. First, a simplified geometric model with prescribed homogeneous deformation was used to fit model parameters and characterize individual MEF mechanisms, and showed good qualitative agreement with experimentally measured strain-CV relations. A 3D model of the rabbit left and right ventricles was then compared with experimental measurements from optical electrical mapping studies in the isolated rabbit heart. The model was inflated to an end-diastolic pressure of 30 mmHg, resulting in epicardial strains comparable to those measured in the anterior left ventricular free wall. While the effects of stretch activated channels did alter epicardial conduction velocity, an increase in cellular capacitance was required to explain previously reported experimental results. The new results suggest that for large strains, various mechanisms can combine and produce a biphasic relationship between strain and conduction velocity. However, at the moderate strains generated by high end-diastolic pressure, a stretch-induced increase in myocyte membrane capacitance is the dominant driver of conduction slowing during ventricular volume loading.

Keywords: Mechano-electric feedback; bidomain model; cell membrane; multiscale model; pressure loaded heart; stretch-activated currents; tissue conductivity

References

  1. Cell. 2011 Feb 4;144(3):402-13 - PubMed
  2. Biophys J. 1991 Mar;59(3):722-8 - PubMed
  3. Cardiovasc Res. 1996 Jul;32(1):15-24 - PubMed
  4. Am J Physiol. 1996 Oct;271(4 Pt 1):C1400-8 - PubMed
  5. Ann Biomed Eng. 2001 May;29(5):414-26 - PubMed
  6. Prog Biophys Mol Biol. 1999;71(1):139-54 - PubMed
  7. IEEE Trans Biomed Eng. 1997 Apr;44(4):326-8 - PubMed
  8. J Electrocardiol. 1972;5(1):15-24 - PubMed
  9. J Mol Cell Cardiol. 2014 Nov;76:265-74 - PubMed
  10. Nat Protoc. 2006;1(3):1379-91 - PubMed
  11. In Vitro Cell Dev Biol Anim. 2008 Mar-Apr;44(3-4):45-50 - PubMed
  12. Biophys J. 2008 Jan 15;94(2):392-410 - PubMed
  13. J Cardiovasc Electrophysiol. 2003 Jul;14(7):739-49 - PubMed
  14. J Physiol. 2003 Jan 15;546(Pt 2):501-9 - PubMed
  15. Am J Physiol Heart Circ Physiol. 2012 Jan 1;302(1):H206-14 - PubMed
  16. Prog Biophys Mol Biol. 2008 Jun-Jul;97(2-3):461-78 - PubMed
  17. Front Physiol. 2011 Apr 09;2:14 - PubMed
  18. Br J Pharmacol. 1996 May;118(2):407-13 - PubMed
  19. Math Biosci. 2005 Apr;194(2):233-48 - PubMed
  20. Prog Biophys Mol Biol. 2003 May-Jul;82(1-3):221-7 - PubMed
  21. Am J Physiol Heart Circ Physiol. 2008 Sep;295(3):H1270-H1278 - PubMed
  22. Conf Proc IEEE Eng Med Biol Soc. 2004;5:3593-6 - PubMed
  23. J Am Coll Cardiol. 1997 Sep;30(3):825-33 - PubMed
  24. Am J Physiol Heart Circ Physiol. 2007 Jun;292(6):H2832-53 - PubMed
  25. Glob Cardiol Sci Pract. 2014 Jun 18;2014(2):9-25 - PubMed
  26. Microsc Microanal. 2005 Jun;11(3):249-59 - PubMed
  27. Europace. 2005 Sep;7 Suppl 2:128-34 - PubMed
  28. Ann Biomed Eng. 2012 Oct;40(10 ):2243-54 - PubMed
  29. Prog Biophys Mol Biol. 2008 Jun-Jul;97(2-3):367-82 - PubMed
  30. Philos Trans A Math Phys Eng Sci. 2011 Nov 13;369(1954):4331-51 - PubMed
  31. J Mol Cell Cardiol. 1997 Jun;29(6):1511-23 - PubMed
  32. IEEE Trans Biomed Eng. 1998 May;45(5):563-71 - PubMed
  33. Prog Biophys Mol Biol. 2008 Jun-Jul;97(2-3):383-400 - PubMed
  34. Comput Methods Biomech Biomed Engin. 2014;17 (6):604-15 - PubMed

Publication Types

Grant support