Atrial Remodeling and Novel Pharmacological Strategies for Antiarrhythmic Therapy in Atrial Fibrillation

Jost, Norbert; Kohajda, Zsófia; Kristóf, Attila; Kovács, P.; Husti, Zoltán; Juhász, Viktor; Kiss, Lóránd; Varró, András; Virág, László; Baczkó, István

doi:10.2174/092986711796642373

Cited by 14 publications

(14 citation statements)

References 174 publications

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“…Consequently, blockade of this combined basal I K,ACh and CC_I K,ACh current may prevent AF. Indeed, in a series of recent experiments we have clearly demonstrated the presence of CI-I K,ACh in atrial cardiomyocytes isolated from ATR dogs, near of a clear presence of cholinergic activated I K,ACh currents [9]. Selective blockade of combined I K,ACh current with low nanomolar concentrations of Tertiapin Q (Figure 3) successfully prevented experimentally induced AF in conscious ATR dogs [9,96,97].…”

Section: Constitutively Active I Kach Channels (Ci-i Kach )mentioning

confidence: 93%

“…The changes are due to the downregulation of the plateau currents and upregulation of several repolarizing currents ( Figure 2). In this respect, three major changes have been described in the past decade to underlie the AP triangularization: (i) downregulation of inward current I Ca,L , (ii) upregulation of the inward rectifier current IK1, and (iii) activation of I K,Ach , respectively [7][8][9][10].…”

Section: Mechanisms Of Atrial Remodelingmentioning

confidence: 99%

“…Indeed, in a experimentally induced tachypaced dog model of permanent AF (ATR), we have revealed that the real magnitude of the outward repolarizing CI_I K,Ach does not seem to be large enough to substantially contribute to the atrial ERP shortening and thus to the APD shortening [9,96,97]. Therefore, in this study [9] we have proposed the following new concept: in normal in vivo physiological condition a "background" vagal stimulation is always present, thereby, consequently it is probable that a acetylcholine-dependent IK,ACh exists in atrial myocytes either in SR or AF. In permanent AF the CI-I K,ACh can also be activated, and its effect will add to the vagally stimulated I KA,Ch , so the resulting net outward current may become large enough to contribute to the atrial ERP/APD shortening.…”

Section: Constitutively Active I Kach Channels (Ci-i Kach )mentioning

confidence: 99%

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Atrial Remodeling in Permanent Atrial Fibrillation: Mechanisms and Pharmacological Implications

Muntean¹,

Kohajda²,

Fazekas

et al. 2013

J Clin Exp Cardiolog

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Atrial fibrillation (AF), the most prevalent rhythm disorder in clinical practice, is currently significantly contributing to morbidity and mortality of the ageing population. In the past decades, a tremendous amount of research resulted in valuable insights into AF pathophysiology, with a primary focus on atrial remodeling. Defined as a persistent change in atrial function and structure, remodeling has the intrinsic properties to enhance the probability of focal (ectopic) and/or re-entrant pursuits, thus supporting AF persistence. The hallmark of structural remodeling is represented by atrial fibrosis, a multifactorial process involving an interaction between neurohormonal and cellular mediators. This paper provides a brief summary of the recent knowledge with respect to electrical and structural remodeling and novel insights into the pathogenesis of atrial fibrosis. Since current drug options for AF treatment are far from being optimal we also discuss the therapeutic principles and current alternatives for counteracting atrial fibrosis, and thus preventing arrhythmia recurrence.

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Section: Constitutively Active I Kach Channels (Ci-i Kach )mentioning

confidence: 93%

Section: Mechanisms Of Atrial Remodelingmentioning

confidence: 99%

Section: Constitutively Active I Kach Channels (Ci-i Kach )mentioning

confidence: 99%

See 1 more Smart Citation

Atrial Remodeling in Permanent Atrial Fibrillation: Mechanisms and Pharmacological Implications

Muntean¹,

Kohajda²,

Fazekas

et al. 2013

J Clin Exp Cardiolog

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“…Namely, these CCAs effectively reduce the atrioventricular (AV) conduction leading to a negative dromotropic effect. For a recent review on AF see ref [100]. 4.…”

Section: Potential Mechanisms Behind the Antiarrhythmic Actions Of Ccasmentioning

confidence: 99%

Class IV Antiarrhythmic Agents: New Compounds Using an Old Strategy

Szentandrássy

Nagy²,

Hegyi³

et al. 2014

CPD

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Cardiac arrhythmias are a major cause of morbidity and mortality in the industrialized world. Among their treatment regimens one can find the calcium channel antagonists (CCAs), the class IV agents. In the cardiovascular system Land T-type calcium channels are found on vascular smooth muscle cells and cardiac myocytes with well defined physiological roles. Inhibition of calcium channels by CCAs has widely been used in clinical practice for several decades. Cardiovascular disorders are one of the many fields of medicine in which CCAs are used for various reasons and conditions. The three main indications of them are hypertension, angina and various cardiac arrhythmias. The most important classes of CCAs are dihydropyridines, phenylalkylamines and benzothiazepines but some newer compounds do not fall into any of these major classes. Dihydropyridines are not used in the antiarrhythmic therapy but are good vasodilators and antianginal agents. In contrast, phenylalkylamines and benzothiazepines exert cardiac actions in vivo and therefore these are one choice of antiarrhythmic drugs. This review focuses on phenylalkylamines, benzothiazepines and on new drugs with potential antiarrhythmic action in the heart as well as the mechanisms how calcium channels antagonism can lead to an antiarrhythmic action.

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“…These alterations are partly adaptive in nature, however, when maintained for longer periods they can lead to further deterioration of cardiac function, and importantly, can significantly contribute to arrhythmia development and maintenance. This review mainly focuses on the arrhythmogenic consequences of electrical remodeling and their possible exploitation for therapy, thus the reader is recommended to refer to previous articles discussing structural remodeling [109][110]. The following sections will deal with three main areas of electrical remodeling in HF and AF: aspects of myocardial repolarization, conduction and impulse generation remodeling.…”

Section: Myocardial Remodeling: Creating Ar-rhythmia Substrate Anmentioning

confidence: 99%

Future Perspectives in the Pharmacological Treatment of Atrial Fibrillation and Ventricular Arrhythmias in Heart Failure

Baczkó

Leprán

Kiss

et al. 2014

CPD

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Heart failure (HF) is a clinical syndrome characterized by significant impairment of cardiac ventricular function. Atrial fibrillation (AF) is the most commonly observed sustained arrhythmia in clinical practice. Both HF and AF are associated with increased morbidity and mortality and their prevalence increases with age. Approximately 50% of patients with moderate HF die due to ventricular fibrillation that leads to sudden cardiac death. Patients with AF exhibit increased mortality due to HF and stroke. HF and AF often co-exist, and the development of the other condition further deteriorates prognosis. Both chronic HF and AF lead to structural and electrophysiological changes in the heart called remodeling, modifying therapeutic targets including those for antiarrhythmic intervention. Current pharmacological treatment of arrhythmias has major limitations due to low efficacy and serious adverse effects. In this review, the main aspects of electrical remodeling in HF and AF are discussed along with possible novel targets identified for future pharmacological antiarrhythmic therapy.Keywords: Heart failure, atrial fibrillation, cardiac arrhythmias, electrical remodeling, potassium channel expression, multi-channel blocking drugs. I. OVERVIEW AND CURRENT STATUS Epidemiology of Heart Failure, Atrial Fibrillation and their CombinationHeart failure (HF) is a clinical syndrome resulting from a wide range of cardiovascular disorders, featuring significant impairment of cardiac function that leads to reduced ventricular filling or ejection of blood. HF markedly reduces health-related quality of life [1], causes significant morbidity and high mortality and represents an enormous economic burden for the health care system [2]. The incidence of HF is increasing with age, with 20 per 1000 persons 65-69 years old and more than 80 per 1000 persons older than 85 [3] and its prevalence is increasing in a continuously aging population [2]. In spite of the significant advances in the treatment of HF, mortality rates remain poor at approximately 50% of patients dying within 5 years of diagnosis [4]. Serious ventricular arrhythmias are common in HF [5] and approximately 50% of HF patients die due to ventricular fibrillation leading to sudden cardiac death (SCD), the rate of which is several times higher in HF patients compared to the general population [6]. In addition to severe ventricular arrhythmias, atrial arrhythmias often develop in heart failure. Bradycardia can develop due to sinoatrial function impairment [7] that can exacerbate cardiac dysfunction [8], can lead to syncope and haemodynamic collapse and can be resolved by application of implantable devices [9].Atrial fibrillation (AF) is the most common sustained arrhythmia and it is associated with significant morbidity and mortality, especially due to the increased risk of heart failure and stroke [10][11][12]. The prevalence of AF increases with age, with 0.5% of patients affected in the 50 year old range, ~10% over the age of 80 [13] and the prediction is that it...

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Atrial Remodeling and Novel Pharmacological Strategies for Antiarrhythmic Therapy in Atrial Fibrillation

Cited by 14 publications

References 174 publications

Atrial Remodeling in Permanent Atrial Fibrillation: Mechanisms and Pharmacological Implications

Atrial Remodeling in Permanent Atrial Fibrillation: Mechanisms and Pharmacological Implications

Class IV Antiarrhythmic Agents: New Compounds Using an Old Strategy

Future Perspectives in the Pharmacological Treatment of Atrial Fibrillation and Ventricular Arrhythmias in Heart Failure

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