Regular Articles
Time Course of Atrial Fibrillation-induced Cellular Structural Remodeling in Atria of the Goat

https://doi.org/10.1006/jmcc.2001.1472Get rights and content

Abstract

Background: Previously we documented cellular structural changes of a non-degenerative nature in atrial myocytes after atrial fibrillation (AF) in the goat. The time course of these changes was not studied. Methods and Results: Cellular structural changes were studied by light- and electron microscopy and immunohistochemistry in goat atria after 0–16 weeks AF. The first sign of cellular structural remodeling was a more homogeneous chromatin distribution, at 1 week of AF. Sub-structural changes in mitochondria and sarcoplasmic reticulum occurred gradually. Cellular degeneration was absent. The degree of myolysis and glycogen accumulation increased till 8 weeks of AF and did not increase further from thereon. After 16 weeks of AF, 42% of the myocytes in the right atrial free wall were affected by myolysis. The diameter of the atrial myocytes increased. Dedifferentiation of the atrial myocytes was suggested by altered expression patterns of structural proteins, such as the disappearance of cardiotin (1 week), the A–I junctional part of titin (4 weeks), desmin at the intercalated disk (ID) (8 weeks) and a gradual re-expression of α -smooth muscle actin. Conclusion: Remodeling of the cellular ultrastructure in atrial myocardium of the goat develops progressively during AF. Re-expression of fetal proteins indicate dedifferentiation of atrial myocytes, analogous to observations in hibernating myocardium of the ventricle.

References (35)

  • L Mary-Rabine et al.

    The relationship of human atrial cellular electrophysiology to clinical function and ultrastructure

    Circ Res

    (1983)
  • MCEF Wijffels et al.

    Atrial fibrillation begets atrial fibrillation. A study in awake chronically instrumented goats

    Circulation

    (1995)
  • CA Morillo et al.

    Chronic rapid atrial pacing: Structural, functional and electrophysiological characteristics of a new model of sustained atrial fibrillation

    Circulation

    (1995)
  • J Ausma et al.

    Structural changes of atrial myocardium due to sustained atrial fibrillation in the goat

    Circulation

    (1997)
  • GD Dispersyn et al.

    Chronic hibernating myocardium and chronic atrial fibrillation; a prelude to apoptosis?

    Cardiovasc Res

    (1999)
  • J Ausma et al.

    Dedifferentiation of atrial cardiomyocytes as a result of chronic atrial fibrillation

    Am J Pathol

    (1997)
  • Verbeke, G, Molenberghs, G, Linear mixed models in practice. A SAS-oriented approach. Springer Verlag, New York,...
  • Cited by (176)

    • Correlation of Histopathological Changes in the Left Atrium and Left Atrial Appendage with the Degree of Dilation in Cats

      2021, Journal of Comparative Pathology
      Citation Excerpt :

      Further studies with proliferation markers will be required in order to address this issue. Various studies conducted in dogs (Goette et al, 1996; Li et al, 1999), goats (Ausma et al, 2001) and humans (Sanders et al, 2003) have revealed that acute LA remodelling (within 1 week of stressor exposure) is often reversible, whereas alterations occurring over longer periods of time are often irreversible. According to Thomas and Abhayaratna (2017), there are limited treatment options when assessing reversal of human LA fibrosis.

    View all citing articles on Scopus
    View full text