Heart Failure Enhanced Pulmonary Vein Arrhythmogenesis and Dysregulated Sodium and Calcium Homeostasis with Increased Calcium Sparks

被引：40

作者：

Chang, Shih-Lin ^{[2
,3
,4
]}

Chen, Yao-Chang

Yeh, Yung-Hsin ^{[6
]}

Lin, Yung-Kuo ^{[1
,7
]}

Wu, Tsu-Juey ^{[2
,4
,8
]}

Lin, Cheng-I ^{[5
]}

Chen, Shih-Ann ^{[2
,3
,4
]}

Chen, Yi-Jen ^{[1
,7
]}

机构：

[1] Taipei Med Univ, Wan Fang Hosp, Div Cardiovasc Med, Taipei, Taiwan

[2] Natl Yang Ming Univ, Sch Med, Inst Clin Med, Taipei, Taiwan

[3] Natl Yang Ming Univ, Sch Med, Dept Med, Taipei, Taiwan

[4] Taipei Vet Gen Hosp, Div Cardiol, Taipei, Taiwan

[5] Natl Def Med Ctr, Dept Biomed Engn, Taipei, Taiwan

[6] Chang Gung Univ, Chang Gung Mem Hosp, Cardiovasc Div 1, Tao Yuan, Taiwan

[7] Taipei Med Univ, Grad Inst Clin Med, Taipei, Taiwan

[8] Taichung Vet Gen Hosp, Div Cardiol, Taichung, Taiwan

来源：

JOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY | 2011年 / 22卷 / 12期

关键词：

atrial fibrillation; calcium homeostasis; Ca2+ sparks; late sodium; TRANSIENT INWARD CURRENT; CARDIAC CA2+ SPARKS; ATRIAL-FIBRILLATION; SARCOPLASMIC-RETICULUM; TRIGGERED ACTIVITY; SR CA2+; DOGS; MODEL; CARDIOMYOCYTES; CONSEQUENCES;

D O I：

10.1111/j.1540-8167.2011.02126.x

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

HF Enhanced PV Arrhythmogenesis. Introduction: Late sodium currents and intracellular Ca2+ (Ca-i(2+)) dynamics play an important role in arrhythmogenesis of pulmonary vein (PV) and heart failure (HF). It is not clear whether HF enhances PV arrhythmogenesis through modulation of Ca2+ homeostasis and increased late sodium currents. The aim of this study was to investigate the sodium and calcium homeostasis in PV cardiomyocytes with HF. Methods and Results: Whole-cell patch clamp was used to investigate the action potentials and ionic currents in isolated rabbit single PV cardiomyocytes with and without rapid pacing induced HF. The Ca-i(2+) dynamics were evaluated through fluorescence and confocal microscopy. As compared to control PV cardiomyocytes (n = 18), HF PV cardiomyocytes (n = 13) had a higher incidence of delayed afterdepolarization (45% vs 13%, P < 0.05) and faster spontaneous activity (3.0 +/- 0.2 vs 2.1 +/- 0.2 Hz, P < 0.05). HF PV cardiomyocytes had increased late Na+ currents, Na+/Ca2+ exchanger currents, and transient inward currents, but had decreased Na+ currents or L-type calcium currents. HF PV cardiomyocytes with pacemaker activity had larger Ca-i(2+) transients (R410/485, 0.18 +/- 0.04 vs 0.11 +/- 0.02, P < 0.05), and sarcoplasmic reticulum Ca2+ stores. Moreover, HF PV cardiomyocytes with pacemaker activity (n = 18) had higher incidence (95% vs 70%, P < 0.05), frequency (7.8 +/- 3.1 vs 2.3 +/- 1.2 spark/mm/s, P < 0.05), amplitude (F/F-0, 3.2 +/- 0.8 vs 1.9 +/- 0.5, P < 0.05), and longer decay time (65 +/- 3 vs 48 +/- 4 ms, P < 0.05) of Ca2+ sparks than control PV cardiomyocytes with pacemaker activity (n = 18). Conclusions: Dysregulated sodium and calcium homeostasis, and enhanced calcium sparks promote arrhythmogenesis of PV cardiomyocytes in HF, which may play an important role in the development of atrial fibrillation. (J Cardiovasc Electrophysiol, Vol. 22, pp. 1378-1386, December 2011)

引用

页码：1378 / 1386

页数：9

共 38 条

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