Irregular rhythm adversely influences calcium handling in ventricular myocardium: implications for the interaction between heart failure and atrial fibrillation

Ling, Liang-han, Khammy, Ouda, Byrne, Melissa, Amirahmadi, Fatemah, Foster, Anna, Li, Gefeng, Zhang, Linda, dos Remedios, Cris, Chen, Chen and Kaye, David M. (2012) Irregular rhythm adversely influences calcium handling in ventricular myocardium: implications for the interaction between heart failure and atrial fibrillation. Circulation: Heart Failure, 5 6: 786-793. doi:10.1161/CIRCHEARTFAILURE.112.968321

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Author Ling, Liang-han
Khammy, Ouda
Byrne, Melissa
Amirahmadi, Fatemah
Foster, Anna
Li, Gefeng
Zhang, Linda
dos Remedios, Cris
Chen, Chen
Kaye, David M.
Title Irregular rhythm adversely influences calcium handling in ventricular myocardium: implications for the interaction between heart failure and atrial fibrillation
Journal name Circulation: Heart Failure   Check publisher's open access policy
ISSN 1941-3289
1941-3297
Publication date 2012-11-01
Year available 2012
Sub-type Article (original research)
DOI 10.1161/CIRCHEARTFAILURE.112.968321
Volume 5
Issue 6
Start page 786
End page 793
Total pages 8
Place of publication Philadelphia, PA., United States
Publisher Lippincott Williams and Wilkins
Language eng
Formatted abstract
Background—Despite adequate rate control, the combination of atrial fibrillation with heart failure (HF) has been shown, in a number of studies, to hasten HF progression. In this context, we aimed to test the hypothesis that an irregular ventricular rhythm causes an alteration in ventricular cardiomyocyte excitation–contraction coupling which contributes to the progression of HF.

Methods and Results—We investigated the effects of electrical field stimulation (average frequency 2 Hz) in an irregular versus regular drive train pattern on the expression of calcium-handling genes and proteins in rat ventricular myocytes. The effect of rhythm on intracellular calcium transients was examined using Fura-2AM fluorescence spectroscopy. In conjunction, calcium-handling protein expression was examined in left ventricular samples obtained from end-stage HF patients, in patients with either persistent atrial fibrillation or sinus rhythm. Compared with regularly paced ventricular cardiomyocytes, in cells paced irregularly for 24 hours, there was a significant reduction in the expression of sarcoplasmic reticulum calcium (Ca2+) ATPase together with reduced serine-16 phosphorylation of phospholamban. These findings were accompanied by a 59% reduction (P<0.01) in the peak Ca2+ transient in irregulary paced myocytes compared with those with regular pacing. Consistent with these observations, we observed a 54% (P<0.05) decrease in sarcoplasmic reticulum Ca2+ ATPase protein expression and an 85% (P<0.01) reduction in the extent of phosphorylation of phospholamban in the left ventricular myocardium of HF patients in atrial fibrillation compared with those in sinus rhythm.

Conclusions—Together, these data demonstrate that ventricular rhythmicity contributes significantly to excitation–contraction coupling by altering the expression and activity of key calcium-handling proteins. These data suggest that control of rhythm may be of benefit in patients with HF.

Keyword Atrial fibrillation
Heart failure
Excitation-contraction coupling
Calcium-handling proteins
Cardiomyocytes
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2013 Collection
School of Biomedical Sciences Publications
 
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