Heart Rhythm
Volume 6, Issue 11 , Pages 1641-1649 , November 2009

Effects of fibroblast-myocyte coupling on cardiac conduction and vulnerability to reentry: A computational study

  • Yuanfang Xie, PhD

      Affiliations

    • Department of Medicine-Cardiology, David Geffen School of Medicine at University of California, Los Angeles, California
    • ,
  • Alan Garfinkel, PhD

      Affiliations

    • Department of Medicine-Cardiology, David Geffen School of Medicine at University of California, Los Angeles, California
    • Department of Physiological Science, David Geffen School of Medicine at University of California, Los Angeles, California
    • ,
  • Patrizia Camelliti, PhD

      Affiliations

    • Department of Physiology, Anatomy, and Genetics, Oxford, United Kingdom
    • ,
  • Peter Kohl, MD, PhD

      Affiliations

    • Department of Physiology, Anatomy, and Genetics, Oxford, United Kingdom
    • ,
  • James N. Weiss, MD

      Affiliations

    • Department of Medicine-Cardiology, David Geffen School of Medicine at University of California, Los Angeles, California
    • Department of Physiology, David Geffen School of Medicine at University of California, Los Angeles, California
    • ,
  • Zhilin Qu, PhD

      Affiliations

    • Department of Medicine-Cardiology, David Geffen School of Medicine at University of California, Los Angeles, California
    • Corresponding Author InformationAddress reprint requests and correspondence: Zhilin Qu, Ph.D., Department of Medicine-Cardiology, David Geffen School of Medicine at UCLA, A2-237 CHS, 650 Charles E. Young Drive South, Los Angeles, California 90095

Received 12 May 2009 ,Accepted 1 August 2009.

References 

  1. Brown RD, Ambler SK, Mitchell MD, et al. The cardiac fibroblast: therapeutic target in myocardial remodeling and failure. Ann Rev Pharmacol Toxicol. 2005;45:657–687
  2. Burstein B, Nattel S. Atrial fibrosis: mechanisms and clinical relevance in atrial fibrillation. J Am Coll Cardiol. 2008;51:802–809
  3. de Bakker JMT, van Rijen HMV. Continuous and discontinuous propagation in heart muscle. J Cardiovasc Electrophysiol. 2006;17:567–573
  4. Spach MS, Heidlage JF, Dolber PC, et al. Mechanism of origin of conduction disturbances in aging human atrial bundles: experimental and model study. Heart Rhythm. 2007;4:175–185
  5. Goshima K. Formation of nexuses and electrotonic transmission between myocardial and FL cells in monolayer culture. Exp Cell Res. 1970;63:124–130
  6. Gaudesius G, Miragoli M, Thomas SP, et al. Coupling of cardiac electrical activity over extended distances by fibroblasts of cardiac origin. Circ Res. 2003;93:421–428
  7. Chilton L, Giles WR, Smith GL. Evidence of intercellular coupling between co-cultured adult rabbit ventricular myocytes and myofibroblasts. J Physiol. 2007;583:225–236
  8. Camelliti P, Borg TK, Kohl P. Structural and functional characterisation of cardiac fibroblasts. Cardiovasc Res. 2005;65:40–51
  9. Camelliti P, Green CR, LeGrice I, et al. Fibroblast network in rabbit sinoatrial node: structural and functional identification of homogeneous and heterogeneous cell coupling. Circ Res. 2004;94:828–835
  10. Walker NL, Burton FL, Kettlewell S, et al. Mapping of epicardial activation in a rabbit model of chronic myocardial infarction. J Cardiovasc Electrophysiol. 2007;18:862–868
  11. Rook MB, Jongsma HJ, de Jonge B. Single channel currents of homo- and heterologous gap junctions between cardiac fibroblasts and myocytes. Pflugers Arch. 1989;414:95–98
  12. Rook MB, van Ginneken AC, de Jonge B, et al. Differences in gap junction channels between cardiac myocytes, fibroblasts, and heterologous pairs. Am J Physiol Cell Physiol. 1992;263:C959–C977
  13. Miragoli M, Gaudesius G, Rohr S. Electrotonic modulation of cardiac impulse conduction by myofibroblasts. Circ Res. 2006;98:801–810
  14. Zlochiver S, Munoz V, Vikstrom KL, et al. Electrotonic myofibroblast-to-myocyte coupling increases propensity to reentrant arrhythmias in two-dimensional cardiac monolayers. Biophys J. 2008;95:4469–4480
  15. Miragoli M, Salvarani N, Rohr S. Myofibroblasts induce ectopic activity in cardiac tissue. Circ Res. 2007;101:755–758
  16. Fahrenbach JP, Mejia-Alvarez R, Banach K. The relevance of non-excitable cells for cardiac pacemaker function. J Physiol. 2007;585:565–578
  17. Baudino TA, McFadden A, Fix C, et al. Cell patterning: interaction of cardiac myocytes and fibroblasts in three-dimensional culture. Microsc Microanal. 2008;14:117–125
  18. Jacquemet V, Henriquez CS. Modelling cardiac fibroblasts: interactions with myocytes and their impact on impulse propagation. Europace. 2007;9(Suppl 6):29–37
  19. Jacquemet V, Henriquez CS. Loading effect of fibroblast-myocyte coupling on resting potential, impulse propagation, and repolarization: insights from a microstructure model. Am J Physiol Heart Circ Physiol. 2008;294:H2040–H2052
  20. Sachse FB, Moreno AP, Abildskov JA. Electrophysiological modeling of fibroblasts and their interaction with myocytes. Ann Biomed Eng. 2008;36:41–56
  21. Sachse F, Moreno A, Seemann G, et al. A model of electrical conduction in cardiac tissue including fibroblasts. Ann Biomed Eng. 2009;37:874–889
  22. Tanaka K, Zlochiver S, Vikstrom KL, et al. Spatial distribution of fibrosis governs fibrillation wave dynamics in the posterior left atrium during heart failure. Circ Res. 2007;101:839–847
  23. MacCannell KA, Bazzazi H, Chilton L, et al. A mathematical model of electrotonic interactions between ventricular myocytes and fibroblasts. Biophys J. 2007;92:4121–4132
  24. Maleckar MM, Greenstein JL, Trayanova NA, et al. Mathematical simulations of ligand-gated and cell-type specific effects on the action potential of human atrium. Prog Biophys Mol Biol. 2008;98:161–170
  25. Jacquemet V, Henriquez CS. Modulation of conduction velocity by nonmyocytes in the low coupling regime. IEEE Trans Biomed Eng. 2009;56:893–896
  26. Kohl P, Noble D. Mechanosensitive connective tissue: potential influence on heart rhythm. Cardiovasc Res. 1996;32:62–68
  27. Xie Y, Garfinkel A, Weiss JN, et al. Cardiac alternans induced by fibroblast-myocyte coupling: mechanistic insights from computational models. Am J Physiol Heart Circ Physiol. 2009;297:H775–H784
  28. Kagiyama Y, Hill JL, Gettes LS. Interaction of acidosis and increased extracellular potassium on action potential characteristics and conduction in guinea pig ventricular muscle. Circ Res. 1982;51:614–623
  29. Shaw RM, Rudy Y. Electrophysiologic effects of acute myocardial ischemia: a mechanistic investigation of action potential conduction and conduction failure. Circ Res. 1997;80:124–138
  30. Kohl P, Camelliti P. Cardiac myocyte-nonmyocyte electrotonic coupling: implications for ventricular arrhythmogenesis. Heart Rhythm. 2007;4:233–235
  31. Luo CH, Rudy Y. A model of the ventricular cardiac action potential: depolarization, repolarization, and their interaction. Circ Res. 1991;68:1501–1526
  32. Kohl P, Kamkin AG, Kiseleva IS, et al. Mechanosensitive fibroblasts in the sino-atrial node region of rat heart: interaction with cardiomyocytes and possible role. Exp Physiol. 1994;79:943–956
  33. Vasquez C, Moreno AP, Berbari EJ. Modeling fibroblast-mediated conduction in the ventricle. Computers Cardiol. 2004;31:349–352
  34. Hyde A, Blondel B, Matter A, et al. Homo- and heterocellular junctions in cell cultures: an electrophysiological and morphological study. Prog Brain Res. 1969;31:283–311
  35. Kohl P. Heterogeneous cell coupling in the heart: an electrophysiological role for fibroblasts. Circ Res. 2003;93:381–383
  36. Kamkin A, Kiseleva I, Wagner KD, et al. Mechanically induced potentials in fibroblasts from human right atrium. Exp Physiol. 1999;84:347–356
  37. Hubbard ML, Ying W, Henriquez CS. Effect of gap junction distribution on impulse propagation in a monolayer of myocytes: a model study. Europace. 2007;9(Suppl 6):20–28
  38. Kucera JP, Rudy Y. Mechanistic insights into very slow conduction in branching cardiac tissue: a model study. Circ Res. 2001;89:799–806
  39. Pope AJ, Sands GB, Smaill BH, et al. Three-dimensional transmural organization of perimysial collagen in the heart. Am J Physiol Heart Circ Physiol. 2008;295:H1243–H1252
  40. Qu Z, Karagueuzian HS, Garfinkel A, et al. Effects of Na+ channel and cell coupling abnormalities on vulnerability to reentry: a simulation study. Am J Physiol Heart Circ Physiol. 2004;286:H1310–H1321
  41. Baudino TA, Carver W, Giles W, et al. Cardiac fibroblasts: friend or foe?. Am J Physiol Heart Circ Physiol. 2006;291:H1015–H1026
  42. Vasquez C, Feig JE, Mohandas P, et al. Arrhythmogenic potential of activated fibroblasts. Biophys J. 2009;96:562a–563a
  43. Camelliti P, Devlin GP, Matthews KG, et al. Spatially and temporally distinct expression of fibroblast connexins after sheep ventricular infarction. Cardiovasc Res. 2004;62:415–425

 This work was supported by National Institutes of Health/National Heart, Lung and Blood Institute grant no. P01 HL078931 and by the Laubisch and Kawata Endowments. PK is a Senior Research Fellow of the British Heart Foundation.

PII: S1547-5271(09)00833-9

doi: 10.1016/j.hrthm.2009.08.003

Heart Rhythm
Volume 6, Issue 11 , Pages 1641-1649 , November 2009

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