Pulmonary Vein Myocardium as a Possible Pharmacological Target for the Treatment of Atrial Fibrillation

Takahara, Akira; Hagiwara, Mihoko; Namekata, Iyuki; Tanaka, Hikaru

doi:10.1254/jphs.14r09cp

Cited by 13 publications

(8 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The myocytes which extend up the pulmonary vein sleeves can fire independently (Perez-Lugones et al, 2003 ), potentially due to automaticity, triggered activity, and micro re-entry [as reviewed in Takahara et al ( 2014 )]. These myocytes are electrophysiologically distinct from those in the atria.…”

Section: The Pathophysiology Of Atrial Fibrillationmentioning

confidence: 99%

Calcium in the Pathophysiology of Atrial Fibrillation and Heart Failure

et al. 2018

View full text Add to dashboard Cite

Atrial fibrillation (AF) is commonly associated with heart failure. A bidirectional relationship exists between the two—AF exacerbates heart failure causing a significant increase in heart failure symptoms, admissions to hospital and cardiovascular death, while pathological remodeling of the atria as a result of heart failure increases the risk of AF. A comprehensive understanding of the pathophysiology of AF is essential if we are to break this vicious circle. In this review, the latest evidence will be presented showing a fundamental role for calcium in both the induction and maintenance of AF. After outlining atrial electrophysiology and calcium handling, the role of calcium-dependent afterdepolarizations and atrial repolarization alternans in triggering AF will be considered. The atrial response to rapid stimulation will be discussed, including the short-term protection from calcium overload in the form of calcium signaling silencing and the eventual progression to diastolic calcium leak causing afterdepolarizations and the development of an electrical substrate that perpetuates AF. The role of calcium in the bidirectional relationship between heart failure and AF will then be covered. The effects of heart failure on atrial calcium handling that promote AF will be reviewed, including effects on both atrial myocytes and the pulmonary veins, before the aspects of AF which exacerbate heart failure are discussed. Finally, the limitations of human and animal studies will be explored allowing contextualization of what are sometimes discordant results.

show abstract

Section: The Pathophysiology Of Atrial Fibrillationmentioning

confidence: 99%

Calcium in the Pathophysiology of Atrial Fibrillation and Heart Failure

et al. 2018

View full text Add to dashboard Cite

show abstract

“…Since then, the pulmonary vein myocardium has attracted great attention from researchers as a key player in the generation and maintenance of atrial fibrillation. The electrical activity of the pulmonary vein myocardium has been investigated as a target for pharmacological treatment of atrial fibrillation [6,7,8]. Experiments have been performed in isolated pulmonary vein myocardia from many experimental animal species [9,10,11,12,13], and information on the mechanisms for their automaticity is accumulating.…”

Section: Introductionmentioning

confidence: 99%

Angiotensin II Induces Automatic Activity of the Isolated Guinea Pig Pulmonary Vein Myocardium through Activation of the IP3 Receptor and the Na+-Ca2+ Exchanger

Tanaka

Obata

Ohmori

et al. 2019

IJMS

Self Cite

View full text Add to dashboard Cite

The automaticity of the pulmonary vein myocardium is known to be the major cause of atrial fibrillation. We examined the involvement of angiotensin II in the automatic activity of isolated guinea pig pulmonary vein preparations. In tissue preparations, application of angiotensin II induced an automatic contractile activity; this effect was mimicked by angiotensin I and blocked by losartan, but not by PD123,319 or carvedilol. In cardiomyocytes, application of angiotensin II induced an increase in the frequency of spontaneous Ca2+ sparks and the generation of Ca2+ transients; these effects were inhibited by losartan or xestospongin C. In tissue preparations, angiotensin II caused membrane potential oscillations, which lead to repetitive generation of action potentials. Angiotensin II increased the diastolic depolarization slope of the spontaneous or evoked action potentials. These effects of angiotensin II were inhibited by SEA0400. In tissue preparations showing spontaneous firing of action potentials, losartan, xestospongin C or SEA0400 decreased the slope of the diastolic depolarization and inhibited the firing of action potentials. In conclusion, in the guinea pig pulmonary vein myocardium, angiotensin II induces the generation of automatic activity through activation of the IP3 receptor and the Na+-Ca2+ exchanger.

show abstract

“…The blood pressure of the pulmonary circulation as well as the level of autonomic and hormonal influence are known to be altered under various pathological conditions. 4,5,13) Whether blockers of SACs are effective against various models of atrial fibrillation is a matter of great interest.…”

Section: Discussionmentioning

confidence: 99%

Enhancement of Automaticity by Mechanical Stretch of the Isolated Guinea Pig Pulmonary Vein Myocardium

Hamaguchi

Hikita

Tanaka

et al. 2016

Biological & Pharmaceutical Bulletin

Self Cite

View full text Add to dashboard Cite

The effects of mechanical stretch on the automaticity of the guinea pig isolated pulmonary vein preparations were studied in microelectrode experiments. The application of cumulative mechanical stretch to the preparations resulted in increases in the firing rate of spontaneous electrical activity in the myocardial layer. This effect was significantly inhibited by stretch-activated channel blockers such as gadolinium or streptomycin. These results suggest that acute mechanical stretch enhances the automaticity of the guinea pig pulmonary vein myocardium through the opening of the stretch-activated channels.Key words pulmonary vein; spontaneous activity; mechanical stretchThe pulmonary vein contains a myocardial layer which is connected to the left atrial myocardium and is capable of generating spontaneous or triggered action potentials.1) The finding that paroxysmal atrial fibrillation is initiated by trains of rapid discharges from the pulmonary veins, 2) has attracted great attention to the electrical activity of the pulmonary vein myocardium as a key player in the generation and maintenance of atrial fibrillation.3,4) Microelectrode recordings from the myocardial layer have been performed in isolated pulmonary vein preparations from several experimental species, and difference in the firing pattern and frequency was observed.5) Studies including those from our laboratory have clarified that factors such as reduced repolarizing power and elevated intracellular calcium ion are involved in the manifestation of automaticity in the pulmonary vein myocardium. 6)The electrical activity of the pulmonary vein myocardium was also shown to be affected by various neuronal and hormonal factors. However, less information is available concerning the relation between pathological condition and pulmonary vein automaticity.The major risk factors of atrial fibrillation include highblood pressure, heart failure and valvular dysfunction; conditions which are accompanied by mechanical stretch of the heart. Chronic mechanical stretch of the heart induces histological remodeling of the heart such as eccentric hypertrophy and atrial enlargement. 7) Based on the understanding that the pulmonary vein automaticity serves as a trigger for the initiation of atrial fibrillation, it is probable that chronic mechanical stretch of the atrial region including the pulmonary vein increases the tendency to generate atrial fibrillation through long-term enhancement of the automaticity of the pulmonary vein myocardium. On the other hand, mechanical stretch may acutely affect cardiomyocytes through the opening of stretch-activated channels (SACs) and lead to the generation the trigger for atrial fibrillation. It was indeed reported in the isolated sheep heart that acute application of intra-atrial pressure increases the rate and organization of excitation waves emanating from the pulmonary veins.8) It was also reported that the stretch-induced atrial fibrillation in perfused rabbit hearts was successfully inhibited by venom of the tarantula Grammosto...

show abstract

Pulmonary Vein Myocardium as a Possible Pharmacological Target for the Treatment of Atrial Fibrillation

Cited by 13 publications

References 34 publications

Calcium in the Pathophysiology of Atrial Fibrillation and Heart Failure

Calcium in the Pathophysiology of Atrial Fibrillation and Heart Failure

Angiotensin II Induces Automatic Activity of the Isolated Guinea Pig Pulmonary Vein Myocardium through Activation of the IP3 Receptor and the Na+-Ca2+ Exchanger

Enhancement of Automaticity by Mechanical Stretch of the Isolated Guinea Pig Pulmonary Vein Myocardium

Contact Info

Product

Resources

About