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Aged atria: electrical remodeling conducive to atrial fibrillation

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Abstract

The incidence of atrial fibrillation (AF) increases with age. Alterations in structure and function of atrial ion channels associated with aging provide the substrate for AF. In this review we provide an overview of current knowledge regarding these age-related changes in atria, focusing on intrinsic ion channel function, impulse initiation and conduction. Studies on the action potentials (APs) of atria have shown that the AP contour is altered with age and the dispersion of AP parameters is increased with age. However, studies using human tissues are not completely consistent with experimental animal studies, since specimens from humans have been obtained from hearts with concomitant cardiovascular diseases and/or that are under the influence of pharmacologic agents. Ionic current studies show that while there are no age-related changes in sodium currents in atrial tissue, the calcium current is reduced and the transient outward and sustained potassium currents are increased in aged cells. While sinoatrial node firing is reduced with age, enhanced impulse initiation may occur in aged atrial cells, for example in the pulmonary veins and coronary sinus. Fibrous tissue is increased in aged atria, which is associated with an increased likelihood of abnormal electrical conduction. Thus, age-related AF involves alterations in the substrate as well as in the passive properties of aged atria.

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References

  1. Brorson, L., & Ollsson, S. B. (1976). Right atrial monophasic action potentials in healthy males, studies during spontaneous sinus rhythm and atrial pacing. Acta Medica Scandinavica, 199(6), 433–446.

    PubMed  CAS  Google Scholar 

  2. Spach, M. S., Dolber, P. C., & Heidlage, J. F. (1988). Influence of the passive anisotropic properties on directional differences in propagation following modification of the sodium conductance in human atrial muscle. A model of reentry based on anisotropic discontinuous propagation. Circulation Research, 62(4), 811–832.

    PubMed  CAS  Google Scholar 

  3. Toda, N. (1980). Age related changes in the transmembrane potential of isolated rabbit sino-atrial nodes and atria. Cardiovascular Research, 14(1), 58–63.

    Article  PubMed  CAS  Google Scholar 

  4. Su, N., Duan, J., Moffat, M. P., & Narayanan, N. (1995). Age related changes in electrophysiological responses to muscarinic receptor stimulation in rat myocardium. Canadian Journal of Physiology and Pharmacology, 73(10), 1430–1436.

    PubMed  CAS  Google Scholar 

  5. Huang, C., Ding, W., Li, L., & Zhao, D. (2006). Differences in the aging associated trends of the monophasic action potential duration and effective refractory period of the right and left atria of the rat. Circulation Journal, 70(3), 352–357.

    Article  PubMed  Google Scholar 

  6. Anyukhovsky, E. P., Sosunov, E. A., Plotnikov, A., Gainullin, R. Z., Jhang, J. S., Marboe, C. C., et al. (2002). Cellular electrophysiologic properties of old canine atria provide a substrate for arrhythmogenesis. Cardiovascular Research, 54(2), 462–469.

    Article  PubMed  CAS  Google Scholar 

  7. Anyukhousky, E. P., Sosunov, E. A., Chandra, P., Rosen, T. S., Boyden, P. A., Danilo Jr, P., et al. (2005). Age-associated changes in electrophysiologic remodeling: a potential contributor to initiation of atrial fibrillation. Cardiovascular Research, 66(2), 353–363.

    Article  Google Scholar 

  8. Baba, S., Dun, W., Hirose, M., & Boyden, P. A. (2006). Sodium current function in adult and aged canine atrial cells. American Journal of Physiology. Heart and Circulatory Physiology, 291(2), H756–H761.

    Article  PubMed  CAS  Google Scholar 

  9. Dun, W., Yagi, T., Rosen, M. R., & Boyden, P. A. (2003). Calcium and Potassium currents in cells from adult and aged canine right atria. Cardiovascular Research, 58(3), 526–534.

    Article  PubMed  CAS  Google Scholar 

  10. Tipparaju, S. M., Kumar, R., Wang, Y., Joyner, R. W., & Wagner, M. B. (2004). Developmental differences in L-type calcium current of human atrial myocytes. American Journal of Physiology. Heart and Circulatory Physiology, 286(5), H1963–H1969.

    Article  PubMed  CAS  Google Scholar 

  11. Dun, W., Baba, S., Boyden, P. A. (2003). Aged-related changes in transient outward and sustained currents in canine right atrial freewall cells are not seen in left atrial cells. Keystone Symposia: Molecular Pathology of Cardiac Arrhythmias.

  12. Lakatta, E. G., & Sollott, S. J. (2002). The "Heartbreak" of Older Age. Molecular Interventions, 2(7), 431–446.

    Article  PubMed  CAS  Google Scholar 

  13. Jones, S. A., Boyett, M. R., & Lancaster, M. K. (2007). Declining Into Failure: The Age-Dependent Loss of the L-Type Calcium Channel Within the Sinoatrial Node. Circulation, 115(10), 1183–1190.

    PubMed  CAS  Google Scholar 

  14. Lyashkov, A. E., Juhaszova, M., Dobrzynski, H., Vinogradova, T. M., Maltsev, V. A., Juhasz, O., et al. (2007). Calcium Cycling Protein Density and Functional Importance to Automaticity of Isolated Sinoatrial Nodal Cells Are Independent of Cell Size. Circulation Research, 100(12), 1723–1731.

    Article  PubMed  CAS  Google Scholar 

  15. Jones, S. A., Lancaster, M. K., & Boyett, M. R. (2004). Ageing-related changes in connexins and conduction within the sinoatrial node. The Journal of Physiology, 560(Pt 2), 429–437.

    Article  PubMed  CAS  Google Scholar 

  16. Grammer, J. B., Zeng, X., Bosch, R. F., & Kuhlkamp, V. (2001). Atrial L-type Ca2+-channel, b-adrenoreceptor, and 5-hydroxytrptamine type 4 receptor mRNAs in human atrial fibrillation. Basic Research in Cardiology, 96(1), 82–90.

    Article  PubMed  CAS  Google Scholar 

  17. Hewett, K., Vullimoz, Y., & Rosen, M. R. (1982). Senescence related changes in the responsiveness to ouabain of canine Purkinje fibers. The Journal of Pharmacology and Experimental Therapeutics, 223(1), 153–156.

    PubMed  CAS  Google Scholar 

  18. Ter Keurs, H. E. D. J., & Boyden, P. A. (2007). Calcium and Arrhythmogenesis. Physiological Reviews, 87(2), 457–506.

    Article  PubMed  CAS  Google Scholar 

  19. Cranefield, P. F., & Aronson, R. S. (1988). Cardiac Arrhythmias: The Role of Triggered Activity. 1 ed. Mount Kisco: Futura Publishing Co. Inc.

    Google Scholar 

  20. Wongchareon, W., Chen, Y. C., Chen, Y. J., Lin, C. I., & Chen, S. A. (2007). Effects of aging and ouabain on left atrial arrhythmogenicity. Journal of Cardiovascular Electrophysiology, 18(5), 526–531.

    Article  Google Scholar 

  21. Ono, N., Hayashi, H., Kawase, A., Lin, S. F., Li, H., Weiss, J. N., et al. (2007). Spontaneous atrial fibrillation initiated by triggered activity near the pulmonary veins in aged rats subjected to glycolytic inhibition. American Journal of Physiology. Heart and Circulatory Physiology, 292(1), H639–H648.

    Article  PubMed  CAS  Google Scholar 

  22. Hove-Madsen, L., Llach, A., Bayes-Genis, A., Roura, S., Font, E. R., Aris, A., et al. (2004). Atrial fibrillation is associated with increased spontaneous calcium release from the sarcoplasmic reticulum in human atrial myocytes. Circulation, 110(11), 1358–1363.

    Article  PubMed  CAS  Google Scholar 

  23. Zhu, X., Altschafl, B. A., Hajjar, R. J., Valdivia, H. H., & Schmidt, U. (2005). Altered Ca2+ sparks and gating properties of ryanodine receptors in aging cardiomyocytes. Cell Calcium, 37(6), 583–591.

    Article  PubMed  CAS  Google Scholar 

  24. Vest, J. A., Wehrens, X. H., Reiken, S., Lehnart, S. E., Dobrev, D., Chandra, P., et al. (2005). Defective cardiac ryanodine receptor regualtion during atrial fibrillation. Circulation, 111(16), 2025–2032.

    Article  PubMed  CAS  Google Scholar 

  25. Schmidt, U., del Monte, F., Miyamoto, M. I., Matsui, T., Gwathmey, J. K., Rosenzweig, A., et al. (2000). Restoration of Diastolic Function in Senescent Rat Hearts Through Adenoviral Gene Transfer of Sarcoplasmic Reticulum Ca2+-ATPase. Circulation, 101(7), 790–796.

    PubMed  CAS  Google Scholar 

  26. El-Armouche, A., Boknik, P., Eschenhagen, T., Carrier, L., Knaut, M., Ravens, U., et al. (2006). Molecular Determinants of Altered Ca2+ Handling in Human Chronic Atrial Fibrillation. Circulation, 114(7), 670–680.

    Article  PubMed  CAS  Google Scholar 

  27. Spach, M. S., & Dolber, P. C. (1986). Relating extracellular Potentials and their derivatives to anisotropic Propagation at a Microscopic level in Human cardiac muscle. Evidence for electrical uncoupling of side-to-side fiber connections with increasing age. Circulation Research, 58(3), 356–371.

    PubMed  CAS  Google Scholar 

  28. Spach, M. S., Miller 3rd, W. T., Dolber, P. C., Kootsey, J. M., Sommer, J. R., & Mosher Jr., C. E. (1982). The functional role of structural complexities in the propagation of depolarization in the atrium of the dog. Cardiac conduction disturbances due to discontinuities of effective axial resistivity. Circulation Research, 50(2), 175–191.

    PubMed  CAS  Google Scholar 

  29. Spach, M. S., Heidlage, J. F., Dolber, P. C., & Barr, R. C. (2000). Electrophysiological effects of remodeling cardiac gap junctions and cell size and model studies of normal cardiac growth. Circulation Research, 86(3), 302–311.

    PubMed  CAS  Google Scholar 

  30. Spach, M. S., Heidlage, J. F., Barr, R. C., & Dolber, P. C. (2004). Cell size and communication: role in structural and electrical development and remodeling of the heart. Heart Rhythm, 1(4), 500–515.

    Article  PubMed  Google Scholar 

  31. Spach, M. S., Heidlage, J. F., Dolber, P. C., & Barr, R. C. (2007). Mechanism of origin of conduction disturbances in aging human atrial bundles: Experimental and model study. Heart Rhythm, 4(2), 175–185.

    Article  PubMed  Google Scholar 

  32. Kojodjojo, P., Kanagaratnam, P., Markides, V., Davies, D. W., & Peters, N. (2006). Age related changes in human left and right atrial conduction. Journal of Cardiovascular Electrophysiology, 17(2), 120–127.

    Article  PubMed  Google Scholar 

  33. Koura, T., Hara, M., Takeuchi, S., Ota, K., Okada, Y., Miyoshi, S., et al. (2002). Anisotropic conduction properties in canine atria analyzed by high-resolution optical mapping: preferential direction of conduction block changes from longitudinal to transverse with increasing age. Circulation, 105(17), 2092–2098.

    Article  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Pharmacology, Center for Molecular Therapeutics, Columbia University, New York, NY, USA

    Wen Dun & Penelope A. Boyden

  2. Department of Pharmacology, Columbia College of Physicians and Surgeons, 630 West 168th ST., New York, NY, 10032, USA

    Penelope A. Boyden

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  1. Wen Dun
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  2. Penelope A. Boyden
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Correspondence to Penelope A. Boyden.

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Supported by grant HL58860 and HL66140 from the National Heart Lung and Blood Institute Bethesda, Maryland

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Dun, W., Boyden, P.A. Aged atria: electrical remodeling conducive to atrial fibrillation. J Interv Card Electrophysiol 25, 9–18 (2009). https://doi.org/10.1007/s10840-008-9358-3

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  • DOI: https://doi.org/10.1007/s10840-008-9358-3

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