Differences in the Aging-Associated Trends of the Monophasic Action Potential Duration and Effective Refractory Period of the Right and Left Atria of the Rat

Huang, Congxin; Ding, Wei; Li, Lan; Zhao, Dongdong

doi:10.1253/circj.70.352

Cited by 28 publications

(17 citation statements)

References 24 publications

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“…This age-associated enhancement in carbachol-induced hyperpolarization may be due to a greater increase in I KACh (acetylcholine-induced potassium conductance) in aged atria, since the key mechanism for hyperpolarization of MDP is activation of I KACh through stimulation of muscarinic cholinergic receptors in the atria. More recently, Huang et al [5] used Langendorff-perfused rat hearts to record MAPs and ERPs of RA and LA epicardium from rats in 3 age groups: adult (7–8 months), middle-aged (13–15 months) and aged (over 2 years). Both MAPD 90 and ERPs were prolonged with age in RA (S1S1 = 400 ms) (Table 1), but in LA they were shorter in the aged group than in the other 2 groups.…”

Section: Substrate Changesmentioning

confidence: 99%

Aged atria: electrical remodeling conducive to atrial fibrillation

Dun

Boyden

2009

J Interv Card Electrophysiol

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The incidence of atrial fibrillation (AF) increases with age. Alterations in structure and function of atrial ion channels associated with aging provide the substrate for AF. In this review we provide an overview of current knowledge regarding these age-related changes in atria, focusing on intrinsic ion channel function, impulse initiation and conduction. Studies on the action potentials (APs) of atria have shown that the AP contour is altered with age and the dispersion of AP parameters is increased with age. However, studies using human tissues are not completely consistent with experimental animal studies, since specimens from humans have been obtained from hearts with concomitant cardiovascular diseases and/or that are under the influence of pharmacologic agents. Ionic current studies show that while there are no age-related changes in sodium currents in atrial tissue, the calcium current is reduced and the transient outward and sustained potassium currents are increased in aged cells. While sinoatrial node firing is reduced with age, enhanced impulse initiation may occur in aged atrial cells, for example in the pulmonary veins and coronary sinus. Fibrous tissue is increased in aged atria, which is associated with an increased likelihood of abnormal electrical conduction. Thus, age-related AF involves alterations in the substrate as well as in the passive properties of aged atria.

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Section: Substrate Changesmentioning

confidence: 99%

Aged atria: electrical remodeling conducive to atrial fibrillation

Dun

Boyden

2009

J Interv Card Electrophysiol

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“…4 In the MR dogs, regional LA conduction slowing and increased directional dependency, which allowed unidirectional conduction block and preferential pathways of conduction, may have accounted for the increased AF inducibility. 5 There is increasing evidence that AF is a predominantly a disease of the LA 6,7 and the role of the LA posterior wall (LAPW) in the mechanism of AF is well documented. In the chronic atrial pacing model in dogs the shortest AF cycle lengths (CLs) are found in the LAPW, 8 and patients with chronic AF.…”

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confidence: 99%

Alterations in Electrophysiology and Tissue Structure of the Left Atrial Posterior Wall in a Canine Model of Atrial Fibrillation Caused by Chronic Atrial Dilatation

Tang

Zhang

Sun

et al. 2007

Circ J

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Methods AnimalsAdult mongrel dogs weighing 30-35 kg were used for the study: 8 control and 9 CDLA dogs. All studies were performed in accordance with the guidelines specified by the institutional animal care and use committee, and the Public Health Service Policy on Use of Laboratory Animals in Wuhan University. Surgical Procedure for the CDLA ModelThe model has been previously described. 13,14 Preoperative, transthoracic echocardiography (TTE) was performed, the dogs were anesthetized with isoflurane and the procedure was monitored with fluoroscopy and TTE. The carotid artery and jugular vein were isolated by a cutdown procedure and under fluoroscopic guidance, a Swan-Ganz catheter was placed in the pulmonary artery via the femoral vein for measurement of pulmonary wedge pressure (PWP). A biopsy forceps catheter (Cordis 502-302L) was placed in the left ventricle (LV) by means of an introducer (Daig Fast-Cath 406181, 30 cm) inserted into the carotid artery in order to cut or damage the mitral valve chordae and thus produce MR. PWP and regurgitant ratio measurements Circ J 2007; 71: 1636 -1642 (Received April 3, 2007 revised manuscript received June 1, 2007; accepted June 19, 2007 Background Chronic left atrial dilatation (CDLA) is associated with an increased incidence of atrial fibrillation (AF). The electrophysiological functions of the left atrial posterior wall (LAPW) are not well understood. Methods and ResultsEight control dogs and 8 with CDLA (developed 6 months after partial mitral valve avulsion) were studied. An electrophysiological study was performed using the noncontact mapping system. The conduction velocity was significantly decreased in the LAPW in the CDLA group. During atrial extrastimulation, a sharp curvature in the activation wavefront became apparent in the LAPW of 6 CDLA dogs, with unidirectional block in 1 dog. The effective refractory periods increased homogeneously throughout the atrium in the CDLA group. AF was much more easily inducible in the CDLA dogs than in the controls. After the onset of AF, the LAPW exhibited the earliest disorganized activity as compared with other sites in the left atrial. In the CDLA dogs, the most extensive interstitial fibrosis was observed in the LAPW. Conclusions Alterations in the electrophysiologic properties and tissue structure of the LAPW were observed in the CDLA dogs. This study supports the idea that the LAPW may play a role in the mechanism of AF induced by CDLA. (Circ J 2007; 71: 1636 -1642)

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“…Therefore, it might be suitable to use older mice with a higher baseline AF inducibility in order to determine a possible protective effect of genetic manipulations presumed to cause a decreased inducibility rate. Because of the fact that a heterogeneously-slowed conduction velocity has been observed in the atria of the older animals, 30 and that atrial electrical remodeling is described as associated with age, 33 parasympathetic stimulation as a trigger for facilitating AF might not be necessarily needed to induce AF in older animals. However, additional parasympathetic stimulation seems to influence the stability of the induced AF episodes, because in the present study the duration of the AF episodes was longer after parasympathetic stimulation compared with baseline.…”

Section: Discussionmentioning

confidence: 99%

In Vivo Effect of a Dominant Negative Kv4.2 Loss-of-Function Mutation Eliminating Ito,f on Atrial Refractoriness and Atrial Fibrillation in Mice

Odening

Nerbonne²,

Bode

et al. 2009

Circ J

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he most common arrhythmia in humans is atrial fibrillation (AF), with increasing prevalence and incidence with aging. 1 Electrical remodeling resulting in a shortening of the atrial action potential duration (APD) and of the atrial effective refractory period (AERP) is known to promote AF, 2 whereas drug-induced prolongation of APD and the AERP reduces its occurrence. [3][4][5] Recent evidence suggests that mutations in the genes responsible for voltage-gated K + -channels play an important role in the subset of human patients with familial AF. 6-8 These mutations lead to a shortening of the APD and AERP by a gain of function in IKs or IK1 and thereby facilitate AF.In line with these findings in humans with familial AF, transgenic mice overexpressing Kir2.1, which leads to augmentation of the IK1 current, show a shortening of APD and AERP, as well as an increase in the occurrence of spontaneous AF. 9 Spontaneous AF was also demonstrated in transgenic mouse models with atrial fibrosis because of either the expression of a constitutively-active form of transforming growth factor (TGF)-β1 10 or an overexpression of tumor necrosis factor (TNF)-α, 11 even in the absence of changes in the APD. 10 Similarly, targeted deletion of connexin40 (Cx40 -/-) slowed atrial and atrioventricular (AV) conduction, and increased vulnerability to AF 12 after transesophageal stimulation.Interestingly, in the TNF-α heart failure mouse model, the incidence of spontaneous and inducible AF increases with age, predominantly in males, 11 indicating a similar influence of age and gender as seen in human patients.In experimental studies, the feasibility of inducing AF using in vivo programmed stimulation has been demonstrated in mice; in wild-type (WT) animals, transvenous electrophysiological (EP) studies showed that after administration of the parasympathetic drug carbachol, which is known to facilitate AF and hence is used as standard model for AF induction, the majority (>70%) of animals had AF induced. 13 Several mutations protect against pacing-induced AF: in an IKACh knock-out mouse model, AF was inducible after carbachol only in WT animals, but not in knock-out mice. 14 In another mouse model, the overexpression of HERG markedly reduced AF inducibility after carbachol administration, despite shortening of the APD, predominantly at slow heart rates, presumably because of a prolonged post-repolarization refractoriness, an increased repolarization reserve and the lack of electrical alternans. 15 Genetic alterations of the atria that either shorten the APD and AERP (eg, by augmenting potassium currents such as IKs or IK1) or manipulations that slow atrial conduction (Cx40 -/-or TGF-β1/TNF-α overexpression) lead to increased vulnerability for AF in mice, and both the elimi-

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Differences in the Aging-Associated Trends of the Monophasic Action Potential Duration and Effective Refractory Period of the Right and Left Atria of the Rat

Cited by 28 publications

References 24 publications

Aged atria: electrical remodeling conducive to atrial fibrillation

Aged atria: electrical remodeling conducive to atrial fibrillation

Alterations in Electrophysiology and Tissue Structure of the Left Atrial Posterior Wall in a Canine Model of Atrial Fibrillation Caused by Chronic Atrial Dilatation

In Vivo Effect of a Dominant Negative Kv4.2 Loss-of-Function Mutation Eliminating Ito,f on Atrial Refractoriness and Atrial Fibrillation in Mice

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