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RESUMEN Introducción : La terapia de resincronización cardíaca (TRC) se indica en pacientes que habitualmente presentan remodelado cardíaco generado por dilatación y disincronía contráctil. La TRC contribuye al remodelado reverso, relacionado con menor mortalidad y hospitalizaciones por insuficiencia cardíaca (IC). Se han observado además mejoras en la conducción intraventricular, con reducción del tiempo de activación. La cuantificación del remodelado eléctrico reverso se ha subutilizado como parámetro de respuesta, con escasos reportes sobre su asociación con la respuesta clínica-estructural. Objetivo : Analizar el remodelado eléctrico reverso intraventricular como parámetro de respuesta a la TRC. Métodos: Se incluyeron pacientes con más de 6 meses de implante. Se obtuvo un ECG con estimulación desactivada (QRS intrínseco, QRSi, post TRC), y por ecocardiograma transtorácico se definió la fracción de eyección ventricular izquierda (FEVI), el diámetro de fin de diástole del ventrículo izquierdo (DFDVI) y la presencia de insuficiencia mitral. Se clasificó a los pacientes según la respuesta clínica-estructural. El remodelado eléctrico se caracterizó con la comparación de la duración del QRS pre y post TRC y la valoración de los cambios del QRS (ΔQRSi) entre grupos. Resultados : Se incluyeron 23 pacientes. Un 39% presentó disminución >10 mseg del QRSi. Observamos un QRSi de -9,3 ± 20,7 mseg en respondedores, y 11,25 ± 18,9 mseg en no respondedores (p = 0,027), más acentuada en los hiper respondedores (ΔQRSi: -14,44 ± 17,40 mseg, p = 0,026). Las mujeres con QRS ≥150 mseg pre TRC exhibieron disminución significativa del QRSi (p = 0,0195). Conclusiones : El remodelado eléctrico reverso se comprobó en 39% de los pacientes que recibieron TRC. Observamos una relación significativa del QRSi con la respuesta clínica-estructural, mayor en hiper respondedores. Mujeres con QRS ancho pre-TRC exhiben remodelado eléctrico reverso más acentuado. Este es un parámetro de fácil acceso e interpretación durante los controles ambulatorios.
ABSTRACT Introduction : Cardiac resynchronization therapy (CRT) is indicated in patients who often present cardiac remodeling due to dilatation and contractile dyssynchrony. CRT contributes to reverse remodeling which is associated with reduced mortality and heart failure (HF) hospitalizations. Improvements in intraventricular conduction with decreased ventricular activation time have also been observed. The quantification of reverse electrical remodeling has been underused as a parameter of response, and there are few reports on its association with the clinical-structural response. Objective : To analyze intraventricular reverse electrical remodeling as a parameter of response to CRT in living individuals. Methods : We included patients implanted at least 6 months ago. A deactivated stimulation ECG (post-CRT intrinsic QRS) was obtained, and by means of transthoracic echocardiography (TTE), the left ventricular ejection fraction (LVEF), the left ventricular end-diastolic diameter (LVEDD) and the presence of mitral regurgitation were defined. Patients were classified according to their clinical-structural response. Electrical remodeling was characterized by comparing pre- and post-CRT QRS duration and assessing QRS changes (ΔiQRS) between groups. Results : A total of 23 patients were included, 39% of which showed a >10 ms decrease in iQRS. We observed a iQRS of -9.3±20.7 ms in responders, and of 11.25±18.9 ms in non-responders (p=0.027), more marked in hyper-responders (ΔiQRS: -14.44±17.40 ms, p=0.026). Women with pre-CRT QRS ≥150 ms showed a significant decrease in iQRS (p=0.0195). Conclusion : Reverse electrical remodeling was found in 39% of the patients under CRT. We noted a significant relationship between iQRS and clinical-structural response, higher in hyper-responders. Women with wider pre-CRT QRS showed more marked reverse electrical remodeling. This parameter is accessible and easy to read in outpatient visits.
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This study aimed to investigate the underlying mechanism of Zhenwu Decoction in the treatment of heart failure by regulating electrical remodeling through the transient outward potassium current(I_(to))/voltage-gated potassium(Kv) channels. Five normal SD rats were intragastrically administered with Zhenwu Decoction granules to prepare drug-containing serum, and another seven normal SD rats received an equal amount of distilled water to prepare blank serum. H9c2 cardiomyocytes underwent conventional passage and were treated with angiotensin Ⅱ(AngⅡ) for 24 h. Subsequently, 2%, 4%, and 8% drug-containing serum, simvastatin(SIM), and BaCl_2 were used to interfere in H9c2 cardiomyocytes for 24 h. The cells were divided into a control group [N, 10% blank serum + 90% high-glucose DMEM(DMEM-H)], a model group(M, AngⅡ + 10% blank serum + 90% DMEM-H), a low-dose Zhenwu Decoction-containing serum group(Z1, AngⅡ + 2% drug-containing serum of Zhenwu Decoction + 8% blank serum + 90% DMEM-H), a medium-dose Zhenwu Decoction-containing serum group(Z2, AngⅡ + 4% drug-containing serum of Zhenwu Decoc-tion + 6% blank serum + 90% DMEM-H), a high-dose Zhenwu Decoction-containing serum group(Z3, AngⅡ + 8% drug-containing serum of Zhenwu Decoction + 2% blank serum + 90% DMEM-H), an inducer group(YD, AngⅡ + SIM + 10% blank serum + 90% DMEM-H), and an inhibitor group(YZ, AngⅡ + BaCl_2 + 10% blank serum + 90% DMEM-H). The content of ANP in cell extracts of each group was detected by ELISA. The relative mRNA expression levels of ANP, Kv1.4, Kv4.2, Kv4.3, DPP6, and KChIP2 were detected by real-time quantitative PCR. The protein expression of Kv1.4, Kv4.2, Kv4.3, DPP6, and KChIP2 was detected by Western blot. I_(to) was detected by the whole cell patch-clamp technique. The results showed that Zhenwu Decoction at low, medium, and high doses could effectively reduce the surface area of cardiomyocytes. Compared with the M group, the Z1, Z2, Z3, and YD groups showed decreased ANP content and mRNA level, increased protein and mRNA expression of Kv4.2, Kv4.3, DPP6, and KChIP2, and decreased protein and mRNA expression of Kv1.4, and the aforementioned changes were the most notable in the Z3 group. Compared with the N group, the Z1, Z2, and Z3 groups showed significantly increased peak current and current density of I_(to). The results indicate that Zhenwu Decoction can regulate myocardial remodeling and electrical remodeling by improving the expression trend of Kv1.4, Kv4.2, Kv4.3, KChIP2, and DPP6 proteins and inducing I_(to) to regulate Kv channels, which may be one of the mechanisms of Zhenwu Decoction in treating heart failure and related arrhythmias.
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Rats , Animals , Myocytes, Cardiac , Atrial Remodeling , Rats, Sprague-Dawley , Heart Failure/metabolism , RNA, Messenger/metabolism , PotassiumABSTRACT
Aim To investigate the role of mechano- sensitive ion channel Piezol in regulating electrical re-modeling of atrial myocytes induced by hypertension and to further explore the potential mechanisms.Methods Spontaneously hypertensive rats ( SHR ) aged 30 - 32 weeks treated with or without valsartan (30 mg • kg 1 • d 1 ) were used.Wistar rats were used as control.Western blot was used to detect the protein expression of Piezol , Src and Cavl.2 in atrial appendages of rats and in atrial myocytes ( HL-1 cells) exposed to different levels of high hydrostatic pressure (20 and 40 mmHg) , Piezol inhibitor (GsmTx4) and agonist ( Yodal ) in vitro.Whole-cell patch clamp technique was employed to detect L-tvpe calcium current (ICa, ) and action potential duration ( APD) of atrial myocytes.Results Compared with Wistar rats in control group, the protein expressions of Piezol and Src significantly increased and the expression of Cavl.2 decreased in SHR group (P < 0.05 ), while the a- bove changes could he reversed in SHR treated with valsartan( P < 0.05 ) .Meanwhile, higher hydrostatic pressure (40 mniHg) could increase the expressions of Piezol and Src in HL-1 cells( P <0.05) and decrease the protein expression of Cavl.2 (P <0.05 ) , accompanied by a shortened APD and a decreased ICa,.GsmTx4 could significantly reverse the above changes.In addition, Piezol agonist Yodal could simulate electrical remodeling and related signal molecule changes in atrial myocytes induced by the high hydrostatic pressure.Conclusions Mechanosensitive ion channel Piezol participates in electrical remodeling induced by hypertension via activating Src kinase signaling pathway and then leading to the decrease of ICa ,.
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Aim To explore type 1 diabetes mice and the advance glycation end products (AGE) involved in electrical remodeling of atrial myocytes. Methods The diabetic mouse model was induced by intraperitoneal injection of STZ; action potential duration, and the current density of I
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Objective@#To investigate the effects and mechanism of digoxin on atrium electrical remodeling and susceptibility of atrial fibrillation (AF) in aged rabbits.@*Methods@#Twenty aged male New Zealand rabbits were divided into aged group and aged plus digoxin group (n=10 each). Electrical parameters including heart rate (HR), RR and QT interval, ST segment and P wave dispersion from normal Ⅱ electrocardiogram, and the maximum upstroke velocity (Maxdv/dt), plateau potential (plateau P), action potential duration of 10%, 20% and 90% (APD10, APD20, APD90) from recording of monophasic action potential (MAP), as well as atrial effective refractory period (AERP200) and dispersion (dERP200) with 200 ms of basic cycle length (BCL), and frequency self adaptation of AERP with 300 ms and 150 ms of BCLs (fERP) were recorded and compared between the 2 groups. BCLs and inducibility of AF post programmed electrical stimulation and Burst-pacing in left atrium tissue of rabbits in vivo were also analyzed. The L-type calcium current (ICa-L) in 2 groups were recorded via whole-cell patch clamp technique, and the fluorescence intensity of intracellular free Ca2+ was detected with Flup-3/AM loading by the laser scanning confocal microscope in enzymatically dissociated single rabbit atrial myocytes.@*Results@#Compared with aged group, the heart rate was faster, RR and QT interval were obvious shorter, ST segment was raised and P wave dispersion was significantly increased in aged plus digoxin group (all P<0.05). Moreover, compared with aged group, the Maxdv/dt and plateau P were obviously increased, APD10 and APD20 were significantly prolongated, and APD90 was significantly shorter in aged plus digoxin group (all P<0.01). Otherwise, the fERP was markedly increased (0.81±0.15 vs. 0.67±0.05), and the induced rate of AF was obviously higher in aged plus digoxin group than in aged group (6/8 vs. 4/9) (all P<0.01). With voltage clamp model, digoxin significantly increased ICa-L of atrial myocytes of aged rabbits, When command potential was 10 mV, the current densities of ICa-L were significantly higher in digoxin group than that in aged group ((15.45±2.38) pA/pF vs. (7.03±1.69) pA/pF, P<0.01). Otherwise, the I-V curve of ICa-L was downward shifted of all I-V curves in digoxin perfused aged atrial cells of rabbits. Moreover, the fluorescence intensities of intracellular free Ca2+ was significantly higher in aged plus digoxin group than in aged group ((1 748±173) μmol/L vs. (478.13±87.63) μmol/L, P<0.01).@*Conclusion@#Digoxin could aggravate the atrial electrical remodeling in atrium of aged rabbits, facilitate susceptibility of atrial fibrillation in aged rabbit, increased current density of ICa-L and concentration of intracellular free Ca2+, followed Ca2+ overload and oscillations might be part of the underlying mechanisms.
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AIM:To evaluate the effects of atorvastatin (ATO) on atrial electrical remodeling in a rabbit mo-del of chronic atrial fibrillation (AF) produced by 3 weeks of rapid atrial pacing (RAP). METHODS:The sternotomy was performed and the pacing and testing electrodes were fixed to the left atria of 24 New Zealand white rabbits. The ani-mals were randomly divided into 3 groups. The rabbits in model group and ATO group were subjected to RAP for 3 weeks, and then were treated with placebo and ATO(2.5 mg·kg-1·d-1),respectively. The rabbits in sham group did not re-ceive RAP and drugs. Electrophysiological examination was performed to test heart rate, P-wave duration, atrial effective refractory period (AERP) and AF inducibility. The protein expression levels of Cav1.2, Kv4.3 and myeloperoxidase (MPO) were detected by Western blot. RESULTS:Sustained AF was induced in 5 and 4 rabbilts in model group and atorvastatin group and no rabbits in sham group was found. After 3 weeks of RAP, compared with sham group, heart rate and P-wave duration were increased and AERP was shortened in model group and ATO group(P<0.05). Compared with model group,AERP was increased in ATO group(P<0.05),while heart rate and P-wave duration had no difference be-tween these 2 groups. Compared with sham group, the protein levels of Cav1.2 and Kv4.3 were decreased, and protein level of MPO was increased in model group and ATO group (P<0.05). Compared with model group, Cav1.2 was in-creased and MPO was decreased in ATO group(P<0.05),while Kv4.3 had no difference between these 2 groups. CON-CLUSION:Atorvastatin suppresses the down-regulation of atrial Cav1.2 protein level and the shortening of AERP, thus preventing atrial electrical remodeling in a rabbit model of chronic AF. The effect of atrovastatin on reducing atrial MPO level may be the potential mechanism.
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AAIM:To investigate the effect of atorvastatin ( ATO) on electrical remodeling, atrial ion channel protein expression and cardiac function in atrial tachypacing rabbits, and to explore the potential electrical mechanism of ATO in the prevention of atrial fibrillation.METHODS:The rabbits were subjected to atrial tachypacing at 600 min-1 in the absence or presence of treatment with atorvastatin (ATP and ATO groups) for 48 h, and the other 10 as sham group without pacing ( NP group) .The tachypacing model was performed by attaching pacing and testing electrodes to left atrial and connecting with custom animal cardiac pacemaker in the open-chest situation.The animals in ATO group were pretrea-ted with ATO for 7 d and continued during tachypacing.Serial atrial effective refractory period ( AERP) was measured in each rabbit at baseline, 8 h, 16 h, 24 h, 32 h, 40 h and 48 h with different cycle lengths.The changes of cardiac func-tions and cardiac structure were observed by cardiac ultrasonic cardiogram before and after atrial tachypacing.The expres-sion of atrial ion channel proteins CaLα1 and Kv4.3 was detected by Western blotting.RESULTS:Compared with NP group, AERP at cycle lengths of 150 and 200 ms, the adaption of AERP, and the levels of CaLα1 and Kv4.3 expression were all decreased in ATP and ATO group, especially in ATP group.Left atrial dimension ( LAD) was increased in pacing groups as compared with NP group (P<0.05) after pacing delivery for 48 h, while no difference between the formers was observed.No significant change of the left ventricular dimension ( LVD) and ejection fraction ( LVEF) among groups be-fore and after pacing was found.CONCLUSION:Atrial tachypacing significantly shorten AERP, resulting in poor adap-tion of AERP, while ATO pretreatment significantly attenuates the atrial electrical remodeling in rabbits, but had no effect on cardiac structure.ATO suppresses the down-regulation of atrial ion channel proteins CaLα1 and Kv4.3 expression after 48 h, which may be the potential ionic mechanism of atrial electrical remodeling for ATO.
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AIM:To investigate whether the association of connexin 43 ( Cx43 ) and L-type calcium channel involved in the pathogenesis of atrial fibrillation ( AF) .METHODS:The biochemical assays and whole-cell patch-clamp technique were used to study the expression of Cx43 in human atrial tissue.The co-localization of Cx43 and L-type calcium channel, and the regulation of L-type calcium current in atrial myocytes were investigated.RESULTS:The expression of Cx43 at mRNA and protein levels was decreased in human atrial tissues of AF patients.In cultured atrium-derived myocytes ( HL-1 cells) , knockdown of Cx43 significantly inhibited the mRNA expression of L-type calcium channelα1c subunit, as well as L-type calcium current.Co-localization of Cx43 with L-type calcium channel α1c subunit in mouse atrial myocytes was observed.CONCLUSION:The decrease in Cx43 is involved in the pathogenesis of AF, probably through reducing the L-type calcium current in atrial myoctyes by co-localization with L-type calcium channel, thus representing the potential pathogenesis in atrial fibrillation.
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Objective In this research we established rapid atrial pacing rabbit models, to investigate the effects of simvastatin on changes of early atrial effective refractory period (AERP) and protein expression of atrial α1c sub-unit of L-type calcium channel on atrial remodeling. Methods 42 rabbits were randomly divided into 3 groups:control group,rapid pacing group and simvastatin group,simvastatin 5 mg/( kg·d) was given intragastrically daily for two weeks before electrophysiology study in simvastatin group, normal saline was given intragastrically in control and rapid pacing group instead. Control group with no pacing, in simvastatin group and rapid pacing group, right atrium was paced at 800 beats/min for 8 hours to establish acute atrial fibrillation models, right atrial effective re-fractory period(AERP)was measured at the basic cycle length of 200 ms and 150 ms before pacing and 1,2,4,6, and 8 hours after the onset of the pacing, the changes of rate adaptation of AERP (AERP200-AERP150) were ana-lyzed . Right atrium tissue was obtained for measurement of protein expression of atrialα1 c subunit of L-type calcium channel by Western blot. Simultaneously,lipid levels in each group was examined. Results No significant differ-ence in lipid levels among three groups was observed. The AERP was shortened and the rate adaptation of AERP (AERP200-AERP150) disappeared during pacing compared with those before pacing(P<0.05). The shortening of AERP was reversed and AERP200-AERP150 was maintained in simvastatin group. Compared with the control group,the protein expression levels of atrial α1c subunit of L-type calcium channel decreased significantly after 8 hours pacing in rapid pacing group(P<0.01). The protein expression levels of simvastatin group decreased insig-nificantly . Conclusion Atrial rapid pacing can induce the shortening of the AERP and the losing of adaptability to the frequency of AERP,pretreatment with simvastatin can improve the degree significantly and maintain the adapta-bility to frequence basically. The protein expression levels of atrial α1c subunit of L-type calcium channel de-creased significantly after 8 hours pacing,pretreatment with simvastatin can prevent this change without lowering the lipid levels,thus contributing to the ionic mechanism of simvastatin for antiarrhythmia.
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[ABSTRACT]AIM:TodeterminetheeffectsofShensongyangxincapsule(SSYX)ontheventricularelectrical properties, structural remodeling and cardiac function in the rats with diabetes mellitus (DM).METHODS:Male SD rats (n=45) were randomly divided into control group (n=15), DM group (n=15) and SSYX group (n=15).The rats in DM group and SSYX group were injected with streptozotocin (60 mg/kg, ip), while the rats in control group were given normal saline (1 mL/kg, ip).The blood samples were collected 72 h after treatment for determining the blood glucose lev-els in DM group and SSYX group .The model rats in SSYX group were administered with SSYX (1 g· kg-1 · d-1 , ig) for 6 weeks, while the other rats received normal saline (2 mL· kg-1· d-1, ig).The echocardiography was used to assess the cardiac function , and the lead II electrocardiogram was also recorded in all the animals .The radioimmunoassay and Masson trichrome staining were used to measure the plasma levels of endothelin -1 (ET-1) and the collagen deposition in the ventricles, respectively.A whole Langendorff-perfused heart model was used to conduct the electrophysiologic study .The monophasic action potential ( MAP) and the ventricular effective refractory period ( VERP) were recorded in the left anteri-or free wall ( LAF) , and the burst pacing was used to induce ventricular arrhythmia ( VA) .RESULTS: Compared with control group, the VERP, action potential duration (APD), QT interval, incidence of VA, degree of myocardial fibrosis and plasma level of ET-1 were increased , while the cardiac function was declined in DM group .Compared with DM group , the VERP, APD, QT interval, incidence of VA, degree of myocardial fibrosis and plasma level of ET-1 were all de-creased, while the cardiac function was improved in SSYX group .CONCLUSION: SSYX attenuates the electrical and structural remodeling and improves the cardiac function in DM rats .
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Objective To investigate the impact and significance of the vagus nerve intervention on the atrial electrical emodeling.Methods 30 mongrel dogs were given metoprolol in order to eliminate the effects of sympathetic nerve on atrial electrical remodeling;observe the atrial effective refractory period (ERP) and atrial fibrillation susceptible window(VW) in the high right atrial(SA) and coronary sinus (CS) by the vagus nerve stimulation(VS) or vagus nerve stimulation(Non-VS) before and after using atropine and after atrial electrical remodeling was observed.Results Before using vagus nerve blocking agents atropine,ERP shortened significantly [(54.83 ± 46.23) ms] and VW increased significantly [(19.86±13.23) ms] after VS,this time with atrial fibrillation-prone ; After using atropine,ERP increased significantly [(112.33 ± 9.63) ms] under VS,did not induce atrial fibrillation; After atrial electrical remodeling,the value of ERP was no significant difference under basis and VS (t =2.116,0.853,all P ＞0.05).Conclusion VS can increase the atrial electrical remodeling,an increase of atrial fibrillation susceptibility;vagus nerve block can reduce atrial electrical remodeling and atrial fibrillation susceptibility decreased.
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Introducción: la fibrilación auricular (AF), es la más común de la arritmia cardiaca sostenida y un factor de riesgo para el accidente cerebro vascular y otras morbilidades, si no es tratada. Estudios epidemiológicos muestran que la AF tiende a perpetuarse con el tiempo, generando cambios electrofisiológicos y anatómicos denominados: remodelados auriculares. Se ha demostrado que estos cambios provocan variaciones de la velocidad de conducción (CV), en el tejido auricular. Objetivo: estudiar el efecto del remodelado de gap junctions en la propagación del potencial de acción, implementando un modelo 3D de aurícula humana altamente realista. Materiales y Métodos: se incorporaron los cambios generados por el remodelado eléctrico a un modelo de potencial de acción (AP) de miocito auricular, acoplado con un modelo tridimensional anatómicamente realista de aurícula humana dilatada. Mediante simulaciones de la propagación del AP en condiciones de remodelado eléctrico y anatómico, y de remodelado de gap junctions, se midieron las ventanas vulnerables de generación de reentradas en la base de las venas pulmonares izquierdas de la aurícula. Resultados: los resultados obtenidos indican que la ventana vulnerable en el remodelado de gap junctions, se desplazó 38 ms con relación al modelo dilatado, lo que nos muestra el impacto de la dilatación con remodelado de gap junction. Conclusiones: el remodelado eléctrico generó una disminución del 70 % en la duración del potencial de acción y una disminución de las velocidades de conducción entre un 14.6 y un 26 %, que fueron medidas en diferentes regiones de la aurícula dilatada. El foco disparado en la base de las venas pulmonares izquierdas, generó un frente de onda que mantiene una actividad reentrante debido a la anatomía subyacente de las venas pulmonares.
Introduction: Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia and a significant risk factor for cerebrovascular accident and other morbidities if left untreated. Epidemiological studies show that AF tends to persist over time, creating electrophysiological and anatomical changes called atrial remodeling. It has been shown that these changes result in variations in conduction velocity (CV) in the atrial tissue. Objective: to study the effect of remodeling of gap junctions in the propagation of the action potential by implementing a highly realistic 3D human atrial model. Materials and methods: the changes caused by electrical remodeling were incorporated in an atrial myocyte action potential (AP) model coupled with an anatomically realistic three-dimensional model of dilated human atria. Through simulations of the AP spread in variations of anatomical and electrical remodeling and of gap junctions remodeling, vulnerable windows of reentry generation were measured at the base of the atrium left pulmonary veins. Results: the results obtained indicate that vulnerable window in the gap junctions remodeling moved 38 ms in relation with the expanded model which shows the impact of the dilatation gap junction remodeling. Conclusions: the electrical remodeling produced 70% decrease in action potential duration and decreased conduction velocities between 14.6 and 26 %, which were measured in different regions of the dilated atrium. The focus shot at the base of the left pulmonary veins created a wave which maintains a reentering activity due to the underlying anatomy of the pulmonary veins.
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Autonomic nervous system activation can result in significant changes of atrial electrophysiology and facilitate induction of atrial fibrillation.By recording influence of different concentrations of acetylcholine (ACh) on atrial fibers (AF),we investigated the role of the increased vagal tone in electrical remodeling in atrial fibrillation.Parameters of action potentials and force contraction (Fc) in atrial fibers were recorded by using standard intracellular microelectrode technique and force transducer.It was found that:(1) ACh at 0.1 μmol/L had no significant influence on spontaneous action potentials (SAPs) and Fc (n=6,P＞0.05); ACh at both 1.0 and 10.0 μmol/L shortened action potential duration (APD) and Fc of human AF from right atrium (n=6,P＜0.05); there was no significant difference in shortening APD between 10.0 and 1.0 μmol/L of ACh; (2) ACh at 0.1 μmol/L had no significant desensitization (n=6,P＞0.05),but ACh at 1.0 and 10.0 μmol/L had desensitization (n=6,P＜0.05) to SAPs and Fc.The desensitization of ACh on APD in AF was concentration- and time-dependent.It was shown that APD was longer than the control along with extending time of continuous Tyrode's solution perfusion after desensitization.It is concluded that ACh changes the electrophysiological characteristics of human AF,indicating that increased vagal tone plays a role in the development of a vulnerable substrate for atrial electrical remodeling in atrial fibrillation.
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BACKGROUND/AIMS: Underlying cardiac pathology and atrial fibrillation (AF) affect the molecular remodeling of ion channels in the atria. Changes in the expression of these molecules have not been demonstrated in Korean patients with mitral valvular heart disease. Thus, the purpose of this study was to analyze ion channel expression in patients with chronic AF and mitral valvular heart disease. METHODS: A total of 17 patients (eight males and nine females; mean age, 57 +/- 14 years [range, 19 to 77]) undergoing open-heart surgery were included in the study. Twelve patients (seven with coronary artery disease and five with aortic valvular disease) had sinus rhythm, and five patients (all with mitral valvular disease) had chronic, permanent AF. A piece of right atrial appendage tissue (0.5 g) was obtained during surgery. RT-PCR was used to evaluate the expression of L-type Ca2+ channels, ryanodine receptor (RyR2), sarcoplasmic reticular Ca2+-ATPase (SERCA2), gene encoding the rapid component of the delayed rectifier Ikr (HERG), gene encoding calcium-independent transient outward current I(to1) (Kv4.3), gene encoding the ultrarapid component of the delayed rectifier Iku (Kv1.5), K+ channel-interacting protein 2 (KChIP2), hyperpolarization-activated cation channel 2 associated with the pacemaker current If (HCN2), and gene encoding Na+ channel (SCN5A). RESULTS: Reduced L-type Ca2+ channel, RyR2, SERCA2, Kv1.5, and KChIP2 expression and borderline increased HCN2 expression were observed in the patients with AF and mitral valvular heart disease. Left atrial diameter was negatively correlated with RyR2 and KChIP2 expression. Fractional area shortening of the left atrium was positively correlated with RyR2 and KChIP2 expression. CONCLUSIONS: Alterations in ion channel expression and the anatomical substrate may favor the initiation and maintenance of AF in patients with mitral valvular heart disease.
Subject(s)
Adult , Aged , Female , Humans , Male , Middle Aged , Aortic Valve Stenosis/metabolism , Atrial Fibrillation/metabolism , Calcium/metabolism , Chronic Disease , Coronary Artery Disease/metabolism , Heart Valve Diseases/metabolism , Ion Channels/genetics , Mitral Valve , Potassium Channels/genetics , Ryanodine Receptor Calcium Release Channel/genetics , Sodium Channels/geneticsABSTRACT
Fundamentos: A fibrilação atrial (FA) apresenta alta taxa de recorrência que pode ser explicada por dois mecanismos: o primeiro diz respeito à capacidade dessa arritmia se perpetuar através da autoindução de alterações eletrofisiológicas, denominadas de remodelagem elétrica. O segundo mecanismo está relacionado a condições cardiovasculares subjacentes que podem estar presentes com alterações estruturais do coração, mesmo que de forma subclínica, por um longo período de tempo até o primeiro episódio de FA. Objetivo: Investigar a importância do eletrocardiograma de alta resolução da onda P (ECGAR-P) na avaliação da remodelagem elétrica atrial e na predição de recorrência da fibrilação atrial. Métodos: Foram realizados dois estudos, o ECGAR-P foi aplicado em ambos. No primeiro avaliaram-se os padrões evolutivos da ativação elétrica atrial durante um mês em 31 pacientes com FA idiopática de longa duração e submetidos à cardioversão. No segundo, investigou-se o ECGAR-P e outros preditores clínicos de não resposta à amiodarona em baixa dose, após a cardioversão do primeiro episódio persistente e altamente sintomático de FA não valvar. O segundo estudo incluiu 87 pacientes e teve seguimento mínimo de 24 meses. Ao final do seguimento, a resposta à terapia antiarrítmica (TA) foi considerada como não responsiva quando ocorreram duas ou mais recorrências de FA ou insucesso em nova cardioversão. Obteve-se de todos os participantes, de ambos os estudos, o Consentimento Livre e Esclarecido, tendo sido o estudo aprovado pelo Comitê de Ética da instituição. Resultados: O primeiro estudo mostrou que entre 31 indivíduos, 9 tiveram recorrência precoce da arritmia, todos nos primeiros sete dias após a cardioversão, e 22 permaneceram em ritmo sinusal por pelo menos um mês. Nesses pacientes a duração da onda P diminuiu progressivamente do primeiro para o terceiro ECGAR. Na análise no domínio da frequência, a turbulência espectral se mostrou inaparente no ECGAR imediato...
Background: Atrial fibrillation is frequently disabling and drug resistant. The high rate of recurrence of AF is represented by two separate mechanisms: the first can be summarized as atrial fibrillation (AF) itself promotes electrophysiological changes, termed "electrical remodeling", facilitationg its recurrence and maintenance. There are evidences that the remodeling process is reversible after restoration of sinus rhythm. However, the timing for recovery of electrophysiological properties is characterized by marked vulnerability to early recurrence of the arrhythmia and still undefined. The second mechanism relates to underlying cardiovascular conditions and cardiac structural changes, which may be hidden for a long time until AF emerges. Objective: In the first article we evaluated the atrial electrical activation by using P-wave signal-averaged electrocardiogram (P-SAECG) post-cardioversion of long-standing lone AF, focusing on the reversal remodeling process to identify the timing of stabilization of the process. The objective of the second article was evaluated the follow-up of patients after cardioversion of the first persistent AF episode, with poorly symptoms and without structural cardiopathy. Methods: In the first study with 31 patients, P-SAECG was performed immediately after cardioversion and repeated on days seven and thirty. The second article included 87 patients with highly symptomatic first-detected persistent AF. After successful electrical cardioversion, echocardiogram and P-SAECG were obtained. During the segment, for all patients were prescribed low-dose of amiodarone and each one were followed-up at least for 24 months. At the end of the follow-up, antiarrythmic therapy (AT) outcome was defined as nonresponse if there were >- 2 recurrences of symptomatic AF or unsuccessful in sequential cardioversion. Results: the results of the first study shows that among 31 subjets, nine underwent early recurrence of AF, all of then...
Subject(s)
Humans , Male , Female , Amiodarone/therapeutic use , Anti-Arrhythmia Agents/therapeutic use , Electric Countershock , Electrophysiologic Techniques, Cardiac , Electrocardiography/methods , Atrial Fibrillation/diagnosis , Atrial Fibrillation/physiopathology , Atrial Fibrillation/therapy , Recurrence/prevention & control , Signal Processing, Computer-Assisted , Age FactorsABSTRACT
Objective To investigate the effects of ciyelosporine-A(CsA).a calcinenrin(CAN)inhibitor,on electrophysiological propertiesof atria in canine tachycardia-induced model of AF.Methods Eighteen healthy adult mongrel canines weighing 17.0 to 23.2 kg(rangedfrom 2 to 4 years old)were randomized to 3 groups,Sham group(no pacemaker was implanted),atrial tachypacing group(ATP group)each group at baseline and after 8 weeks' tachypacing.Measurements included atrial effective refractory period(AERP),conductionvelocity(CV),wave length(WE),atrial fibrillation load and rate-adaptability. Results After 8 weeks' atrial tachypacing,ATP andCsA groups showed significant longer duration of the P wave,shorter AERP,decreased adaptation of AERE slower CV,shorter Wland longer AF duration compared to the shamg roup (all P＜0.05).AERP of the CsA group was longer than that of ATP group (P＜0.05),but there were no differences in rate-adaptability,CV,incidence of induced AF and AF duration between CsA group and ATP group.Conclusions Our results suggest that calcineurin pathway intervention by CsA have a positive effect on tachycardia-inducedelectrical remodeling of atria,but can not prevent or reverse AF.
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Background Atrial electrical remodeling(AER)plays an important role in the pathogenesis and maintenance of atrialfibrillation.However,little is known about modulation of vagal activilty to AER.This study aimed to investigate the relationshipbetween vagal moduation and AER. Methods Twenty four adult mongrel dogs under general anesthesia were randomized into 3groups.Sympathetic activity was blocked by administration of metoprolol in 3 groups.The changes in vagal modulation to atria afterAER were observed in 10 dogs without vagal interruption in group A.The effects of vagal intervention on AER were investigated in 8dogs with administration of atropine in group B.The impact of aggressively vagal activity on AER was studied in 6 dogs with bilateralcervical vag sympathetic trunLks stimulation during AER in group C.Bilateral cervicall vagosympathetic trunks were decentralized.Multipolar catheters wereplaced into high right atria(RA),coronary sinus(CS)and rightventricle(RV).AER was induced by 600 bpmpacing through RA catheter for 30 minutes.Attial effective refractory period(ERP)and vulnerability window (VW)of atrial fibrillationwere measured with and without vagal stimulation before and after AER.Results In group A,ERP decreased significantly at baselineand during vagal stimulation after AER compared with that beforeAER(all P＜0.05).In group B,ERP remaind unchanged at baselineand vagal stimulation after AER compared with tbat before AER (all P＞0.05).In group C,ERP shortened significantly at baseline andvagal stimulation after AER compared with that before AER(all P＜0.05).ERP shortening after AER in Groups A and C increasedsignificantly than that in group B (all P＜0.05).Atrial fibrillation could not be induced at baseline(VW close to 0) before and after AERin three groups.VW became widen significantly during vagal stimulation after AER compared with that before AER in Groups A and C(all P＜0.05),while VW remained unchanged in group B (VW close to 0).Conclusions Short-term AER results in the decrease inERP.AER is accompanied by the increases in atrial vagal modulation.The increased vagal activity and vagal stimulation promote AER,thereby increase the susceptibility to atrial fibrillation.The interrupted vagal activity attenuates AER.thereby suppresses the atriaIfibrillation mediated by vagal stimutlation.
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The expression of stretch-activated potassium channel TREK-1 mRNA and protein of hypertrophic myocardium was measured. Using a model of hypertrophy induced by coarctation of abdominal aorta in male Wistar rats, the expression of TREK-1 mRNA and protein was detected by using semi quantitative RT PCR and Western blot respectively. At 4th and 8th week after constriction of the abdominal aorta, rats developed significant left ventricular hypertrophy. As compared to sham operated group, stretch activated potassium channel TREK-1 mRNA was strongly expressed and protein was up regulated in operation groups (P＜0.05). It was concluded that the expression of TREK 1 was up regulated in hypertrophic myocardium induced by chronic pressure overload in Wistar rats.
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Myocardial hypertrophy is the complication of many cardiovascular diseases that induce cardiac remodeling.The molecular mechanism of cardiac remodeling involves abnormal changes in various transmembrane ionic currents in the heart.Recent studies suggest the potential involvement of volume-regulated Cl-current(ICl.Vol)in cardiac hypertrophy.Although the molecular basis of ICl.Vol remains to be elucidated,recent progress is reviewed in the potential role of ICl.Vol in cardiac remodeling.
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Aim To determine the effects of sodium tashinoneⅡA sulfonate(TSN) on monophasic action potential(MAP) and tachycardia-induced electrical remodeling of rabbit atria in vivo.Methods Twenty-four rabbits were equally divided into two groups randomly: control group and TSN group.Electrical catheters were localized in the right atrium through right internal jugular vein.Right atrial MAP was recorded by multiple channel recording. ERP of right atrial(AERP) was assessed by programmed electrical stimulation before pacing and from 0～8 hours after the onset of the pacing.Results The AERP_(200 ms) of control group was shortened from (105.9?3.8) ms to(114.7?7.2) ms and the rate-dependent of control group's atrium was lost through the pacing process compared with TSN group before pacing(P