Mechanoelectrical feedback regulates the arrhythmogenic activity of pulmonary veins

Chang, Shih‐Lin; Chen, Yao‐Chang; Chen, Yi‐Jen; Wangcharoen, Wanwarang; Lee, Shih‐Huang; Lin, Cheng‐I; Chen, Shih‐Ann

doi:10.1136/hrt.2006.089359

Cited by 110 publications

(102 citation statements)

References 31 publications

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“…release inhibitor (ryanodine, 0.3 or 3 µM), sodium current inhibitor [tetrodotoxin (TTX), 1, 3 or 10 µM in 0.01% acetic acid) and late sodium current inhibitor (ranolazine, 10 µM). Details of this method were described in previous studies by our group (22,23). One end of the preparation was pinned to the bottom of a tissue bath, while the other end was connected to a Grass FT03C force transducer (Natus Medical, Inc., Pleasanton, CA, USA) with silk thread.…”

Section: Methodsmentioning

confidence: 99%

Heart failure modulates electropharmacological characteristics of sinoatrial nodes

Chang

Chuang

Chen

et al. 2016

Experimental and Therapeutic Medicine

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Abstract. The impact of heart failure (HF) on sinoatrial node (SAN) channel regulation and electropharmacological responses has remained elusive. The present study aimed to investigate the effects of HF on the electrical activity of SANs with and without pharmacological interventions. Action potentials (APs) were recorded in isolated SANs from normal rabbits (control) and those with HF (rapid ventricular pacing for 4 weeks) prior to and after administration of a funny current blocker (ivabradine; 0.1, 0.3, 3 or 10 µM), a calmodulin kinase II inhibitor (KN-93; 0.3 or 3 µM), a sarcoplasmic reticulum Ca 2+ release inhibitor (ryanodine; 0.3 or 3 µM), a sodium current inhibitor (tetrodotoxin; 1, 3 or 10 µM) and a late sodium current inhibitor (ranolazine; 10 µM). Western blot analysis was used to investigate the protein expression in SANs from normal rabbits and those with HF. Control SANs had a higher beating rate than SANs from rabbits with HF (2.3±0.1 vs. 1.5±0.1 Hz; P<0.001). Similarly, ivabradine (10 µM), KN-93 (3 µM), ranolazine (10 µM) and ryanodine (3 µM) decreased the beating rates of SANs in the control (n=6) and HF (n=6) groups. Ivabradine treatment resulted in a higher incidence of AP block in HF vs. control SANs (66.7 vs. 0%; P<0.05). Tetrodotoxin (1, 3 or 10 µM) decreased the beating rate to a higher extent in SANs from rabbits with HF than in those from control rabbits and induced a higher incidence of AP block (66.7 vs. 0%; P<0.05). Furthermore, SANs from rabbits with HF had higher protein levels of phospholamban (PLB) and lower levels of hyperpolarization-activated cyclic nucleotide-gated potassium channel 4, ryanodine receptor and phosphorylated PLB than control SANs. In conclusion, HF modulates electropharmacological responses in the SAN by channel regulation, which may result in SAN dysfunction.

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Section: Methodsmentioning

confidence: 99%

Heart failure modulates electropharmacological characteristics of sinoatrial nodes

Chang

Chuang

Chen

et al. 2016

Experimental and Therapeutic Medicine

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“…2,31, 47 An animal study revealed that stretch force dependently increased the incidence of spontaneous activity, early afterdepolarization (EAD) and DAD in the PVs. 46 Moreover, stretch-activated channels blockers, gadolinium and streptomycin, decreased the incidence of spontaneous activity and firing rates in PVs. These findings indicate that stretch-induced arrhythmogenic activity of the PVs may contribute to the genesis of AF.…”

Section: Aging-related Disorder: Endothelial Dysfunctionmentioning

confidence: 99%

“…Mechano-electrical feedback is the critical link in structural and electrical remodeling. 46 A dilated atrium or PV not only provides substrate support for reentry, but also significantly changes the atrial (or PV) electrical properties. 2,31, 47 An animal study revealed that stretch force dependently increased the incidence of spontaneous activity, early afterdepolarization (EAD) and DAD in the PVs.…”

Section: Aging-related Disorder: Endothelial Dysfunctionmentioning

confidence: 99%

Aging Modulates the Substrate and Triggers Remodeling in Atrial Fibrillation

Lin

Chen

Lee

et al. 2018

Circ J

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how aging and AF are connected and highlight the potential role of aging in AF substrate and triggered remodeling. Effects of Aging on Structural RemodelingStructural remodeling is characterized by histopathological changes, such as cellular hypertrophy, apoptosis, or myocardial fibrosis, and anatomical changes, such as chamber dilatation. 5 Anatomical Changes With Dilation of PV and Atria in AgingThe left atrium (LA) anteroposterior diameter and wall thickness increase with aging, and the 4 PVs become dilated in patients older than 50 years (Figure 1), 3 which suggests mechanical effects of aging on AF triggers and substrates. 3 Clinical data indicate that PV size correlates with PV arrhythmogenesis. Therefore, larger PVs may correlate with a higher PV arrhythmogenesis resulting in AF. Histopathological Changes With AgingBoth animal and human studies had shown that loss of cardiomyocytes by apoptosis and necrosis produces compensatory cellular hypertrophy, which may represent the structural basis of the aged heart, and contribute to cardiac dysfunction in the elderly. 5 Aging increases the rate of ventricular cardiomyocyte death caused by enhanced vulnerability to stress such as oxidative stress. 6 These histopathological changes at the microscopic level potentially T he prevalence and severity of arrhythmias increase with age. Advancing age is independently associated with the prevalence of atrial fibrillation (AF). 1 Aging and aging-related underlying diseases frequently result in structural remodeling as cardiac morphological changes either grossly or at the histological and ultrastructural levels, or they induce electrophysiological remodeling with changes in cardiac electrical properties in response to a functional insult, or as a result of a structural alteration. Aging-associated cardiac anatomical and functional remodeling may enhance the occurrence or the persistence of AF.Ectopic impulses generated from the pulmonary veins (PVs) play a key role in the genesis and maintenances of AF. 2 Elimination of PV arrhythmogenic foci or targeting atrial substrate abnormalities reduces the AF burden or cures AF. 2 PVs contain complex electrical activity because of their distinctive anatomical and physiological characteristics. 3 Aging-associated electrophysiological or structural changes in the atria or PVs may facilitate AF occurrence. 3 Age is an independent predictor of AF recurrence in lone AF patients after undergoing the first circumferential PV isolation. 4 AF may coexist with cardiovascular disorders, which may potentiate its occurrence, and these are also more prevalent with increased age. Together with agingrelated myocardial degeneration or anatomical changes, both inflammation and oxidative stress, as consequences of aging, enhance the occurrence and maintenance of AF. The aim of this review is to update the understanding of Aging plays a critical role in the genesis of atrial fibrillation (AF) and also increases the risks of cardiac dysfunction and stroke in AF patients. AF is caused by increased AF t...

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“…For LA experiments, the LA appendage (approximately 10×5×0.5 mm) was isolated and prepared as described previously. 25 The PV and LA tissue strips were superfused at a constant rate (3 ml/min) with Tyrode's solution saturated with a 97% O2-3% CO2 gas mixture. The temperature was maintained at 37 o C, and the preparations were allowed to equilibrate for 1 h before electrophysiology assessment.…”

Section: Oxidative Stress On Pulmonary Veinsmentioning

confidence: 99%

Oxidative Stress on Pulmonary Vein and Left Atrium Arrhythmogenesis

Lin

Chen

et al. 2010

Circ J

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Mechanoelectrical feedback regulates the arrhythmogenic activity of pulmonary veins

Abstract: Stretch is an important factor in the electrical activity of the pulmonary vein. Stretch-induced arrhythmogenic activity of the pulmonary vein may contribute to the genesis of atrial fibrillation.

Cited by 110 publications

References 31 publications

Heart failure modulates electropharmacological characteristics of sinoatrial nodes

Heart failure modulates electropharmacological characteristics of sinoatrial nodes

Aging Modulates the Substrate and Triggers Remodeling in Atrial Fibrillation

Oxidative Stress on Pulmonary Vein and Left Atrium Arrhythmogenesis

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