Mounting Evidence That Fibrosis Generates a Major Mechanism for Atrial Fibrillation

Spach, Madison S.

doi:10.1161/circresaha.107.163956

Cited by 55 publications

(42 citation statements)

References 27 publications

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“…Atrial fibrosis impairs cell-to-cell coupling, causing inhomogeneities in intra-atrial and interstitial conduction, thus increasing atrial susceptibility to AF and providing a discontinuous and branching morphological substrate susceptible for multiple wavelet reentry. Thus, advanced atrial fibrosis would predict an impairment of atrial conduction and create a vulnerable substrate to promote AF (Spach, 2004;Everett and Olgin, 2007).…”

Section: Effects Of Spironolactone On Atrial Fibrosis and Dilatationmentioning

confidence: 99%

Effects of spironolactone on atrial structural remodelling in a canine model of atrial fibrillation produced by prolonged atrial pacing

Zhao

et al. 2010

British J Pharmacology

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Background and purpose: Suppression of the renin-angiotensin-aldosterone system can prevent atrial fibrillation (AF) by attenuating atrial structural remodelling but the role of aldosterone in AF prevention has not been investigated thoroughly. We explored whether the aldosterone antagonist, spironolactone, could improve atrial structural remodelling in long-term rapid pacing-induced AF. Experimental approach: Three groups of dogs were used, sham-operated, control and spironolactone-treated groups. Dogs in the control and spironolactone groups had right atrial pacing for 6 weeks. The spironolactone group was given spironolactone 1 week before and during the atrial pacing. After 6 weeks of pacing, atrial structural and functional changes were assessed by echocardiography, haemodynamic parameters by cardiac catheterization, histopathological changes by light and electron microscopy and cardiomyocyte apoptosis by TUNEL. Caspase-3, Bcl-2, bax, calpain I, calpastatin, matrix metalloproteinase (MMP)-9 and tissue inhibitors of metalloproteinase (TIMP)-1 were analysed by immunohistochemistry and Western blotting. The inducibility and duration of AF were measured by atrial burst pacing. Key results: After atrial pacing, the proportion of TUNEL positive cells, myolysis, atrial fibrosis and dilatation were all significantly increased and these changes were inhibited by spironolactone. Spironolactone treatment reversed the increased expression of caspase-3, bax, calpain I and MMP-9 and the decreased level of Bcl-2, calpastatin and TIMP-1, induced by chronic atrial pacing. Also spironolactone prevented the increased inducibility and duration of AF, induced by tachypacing. Conclusions and implications: Treatment with spironolactone prevented myocardial apoptosis, myolysis, atrial fibrosis and dilatation, suggesting a possible beneficial effect of aldosterone antagonism on atrial structural remodelling in AF.

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Section: Effects Of Spironolactone On Atrial Fibrosis and Dilatationmentioning

confidence: 99%

Effects of spironolactone on atrial structural remodelling in a canine model of atrial fibrillation produced by prolonged atrial pacing

Zhao

et al. 2010

British J Pharmacology

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“…Alternatively, the substrate may have spatially inhomogeneous excitability, and this structural heterogeneity (see section 1.3) can cause a partial block under stress conditions. For both possibilities, a number of underlying reasons have been identified, including, but not limited to, genetic mutations altering the dynamics of ion channels or receptors [46,47,48], remodeling after myocardial infarction [49,50], electrical shocks during the vulnerable phase of a normal heart beat [51,52,53,54] or fibrosis [55,56,57]. A case which is difficult to classify is idiopathic ventricular fibrillation, which is thought to be responsible for a considerable percentage of sudden cardiac deaths and occurs in seemingly healthy patients [58].…”

Section: Arrhythmiasmentioning

confidence: 99%

Complex Structure and Dynamics of the Heart

Bittihn

2015

Springer Theses

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“…[51][52][53] Histology marked by interstitial fibrosis, [54][55][56] uncoupling of muscle bundle, 57 altered distribution of gap junction, 58,59 and inflammation 60 underlies slow conduction, giving rise to P wave prolongation. Several studies [61][62][63][64][65][66][67][68] determined P-wave duration.…”

Section: Atrial Conduction Delay and Afmentioning

confidence: 99%