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Heat shock protein inducer modifies arrhythmogenic substrate and inhibits atrial fibrillation in the failing heart.

Abstract：

BACKGROUND:Geranylgeranylacetone (GGA) has been reported up-regulating heat shock protein (HSP) expression, and protecting against atrial remodeling. This study aimed to investigate the effects of GGA on atrial electrophysiology and inducibility of atrial fibrillation (AF) in heart failure (HF) model. METHODS AND RESULTS:HF rabbits were created 4 weeks after coronary artery ligation. Monophasic action potential recordings and multielectrode array were used to record the electrophysiological characteristics of left atrium (LA) in normal, or HF rabbits with (HF-GGA) and without (HF-control) oral administration of GGA (200 mg/kg, 24 h before experiments). The mRNA and protein expressions of ionic channels were measured by Western blot and PCR. HF-GGA LA (n = 10), similar to normal LA (n = 10) had a shorter action potential duration (APD) and effective refractory period than HF-control LA (n = 10). HF-GGA LA had less triggered activity and APD alternans (20% vs. 100%, P = 0.001), lower maxima slope of restitution curve of APD (0.94 ± 0.04 vs.1.69 ± 0.04, P < 0.001), and less inducibility of AF (50% vs. 100%, P = 0.033) than HF-control LA. HF-GGA LA had a shorter activation time and higher conduction velocity than HF-control LA. HF-GGA LA had a higher mRNA expression of Cav1.2, Nav1.5, Kir2.1, Kv1.4, Kv7.1, Kv11.1, sarcoplasmic reticulum Ca(2+)-ATPase, and higher phosphorylation of phospholamban than HF-control LA. CONCLUSIONS:GGA decreases triggered activity, dispersion of APD and inducibility of AF in failing heart through induction of HSP, and modulation of ionic channels and calcium homeostasis.

journal_name

Int J Cardiol

journal_title

International journal of cardiology

authors

Chang SL,Chen YC,Hsu CP,Kao YH,Lin YK,Lai YJ,Yeh HI,Higa S,Chen SA,Chen YJ

doi

10.1016/j.ijcard.2013.06.072

subject

Has Abstract

pub_date

2013-10-09 00:00:00

pages

4019-26

issue

4

eissn

0167-5273

issn

1874-1754

pii

S0167-5273(13)01127-3

journal_volume

168

pub_type

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