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arrhythmias, calcium homeostasis, diabetic cardiomyopathy, electrophysiology, ketogenic diet, Biology (General), QH301-705.5, Chemistry, and QD1-999

A ketogenic diet (KD) might alleviate patients with diabetic cardiomyopathy. However, the underlying mechanism remains unclear. Myocardial function and arrhythmogenesis are closely linked to calcium (Ca2+) homeostasis. We investigated the effects of a KD on Ca2+ homeostasis and electrophysiology in diabetic cardiomyopathy. Male Wistar rats were created to have diabetes mellitus (DM) using streptozotocin (65 mg/kg, intraperitoneally), and subsequently treated for 6 weeks with either a normal diet (ND) or a KD. Our electrophysiological and Western blot analyses assessed myocardial Ca2+ homeostasis in ventricular preparations in vivo. Unlike those on the KD, DM rats treated with an ND exhibited a prolonged QTc interval and action potential duration. Compared to the control and DM rats on the KD, DM rats treated with an ND also showed lower intracellular Ca2+ transients, sarcoplasmic reticular Ca2+ content, sodium (Na+)-Ca2+ exchanger currents (reverse mode), L-type Ca2+ contents, sarcoplasmic reticulum ATPase contents, Cav1.2 contents. Furthermore, these rats exhibited elevated ratios of phosphorylated to total proteins across multiple Ca2+ handling proteins, including ryanodine receptor 2 (RyR2) at serine 2808, phospholamban (PLB)-Ser16, and calmodulin-dependent protein kinase II (CaMKII). Additionally, DM rats treated with an ND demonstrated a higher frequency and incidence of Ca2+ leak, cytosolic reactive oxygen species, Na+/hydrogen-exchanger currents, and late Na+ currents than the control and DM rats on the KD. KD treatment may attenuate the effects of DM-dysregulated Na+ and Ca2+ homeostasis, contributing to its cardioprotection in DM.

alternans, the maximum calcium transient, IL-17 neutralizer, IL-17, ventricular arrhythmias, Diseases of the circulatory (Cardiovascular) system, and RC666-701

Background: The mechanism of Interleukin-17 (IL-17) induced ventricular arrhythmia (VA) remains unclear. This study aimed to investigate the effect of intracellular calcium (Cai) handling and VA susceptibility by IL-17.Methods: The electrophysiological properties of isolated perfused rabbit hearts under IL-17 (20 ng/ml, N = 6) and the IL-17 with neutralizer (0.4 μg/ml, N = 6) were evaluated using an optical mapping system. The action potential duration (APD) and Cai transient duration (CaiTD) were examined, and semiquantitative reverse transcriptase-polymerase chain reaction analysis of ion channels was performed.Results: There were longer APD80, CaiTD80 and increased thresholds of APD and CaiTD alternans, the maximum slope of APD restitution and induction of VA threshold in IL-17 group compared with those in IL-17 neutralizer and baseline groups. During ventricular fibrillation, the number of phase singularities and dominant frequency were both significantly greater in IL-17 group than in baseline group. The mRNA expressions of the Na+/Ca2+ exchanger, phospholamban, and ryanodine receptor Ca2+ release channel were upregulated, and the subunit of L-type Ca2+ current and sarcoplasmic reticulum Ca2+-ATPase 2a were significantly reduced in IL-17 group compared to baseline and IL-17 neutralizer group.Conclusions: IL-17 enhanced CaiTD and APD alternans through disturbances in calcium handling, which may increase VA susceptibility.

cardiovascular medicine, induced pluripotent stem cell (iPSC), LMNA, ZFHX3, bioengineering, cardiac arrhythmia, Physiology, and QP1-981

BUNDLE-branch block, VENTRICULAR tachycardia, VENTRICULAR arrhythmia, SODIUM, and INTRAVENOUS therapy

Lithium intoxication induces Brugada-pattern ECG, ventricular arrhythmia, and sudden death with the predominant preference for the male over the female gender. This study investigated the mechanisms of gender difference in lithium-induced arrhythmogenesis. The ECG parameters were recorded in male and female rabbits before and after the intravenous administration of lithium chloride (LiCl) (1, 3, 10 mmol/kg). Patch clamps were used to study the sodium current (INa) and late sodium current (INa-late) in the isolated single male and female right ventricular outflow tract (RVOT) cardiomyocytes before and after LiCl. Male rabbits (n = 9) were more prone to developing lithium-induced Brugada-pattern ECG changes (incomplete right bundle branch block, ST elevation and QRS widening) with fatal arrhythmia (66.7% vs. 0%, p = 0.002) than in female (n = 7) rabbits at 10 mmol/kg (but not 1 or 3 mmol/kg). Compared to those in the female RVOT cardiomyocytes, LiCl (100 μM) reduced INa to a greater extent and increased INa-late in the male RVOT cardiomyocytes. Moreover, in the presence of ranolazine (the INa-late inhibitor, 3.6 mg/kg iv loading, followed by a second iv bolus 6.0 mg/kg administered 30 min later, n = 5), LiCl (10 mmol/kg) did not induce Brugada-pattern ECG changes (p < 0.005). The male gender is much predisposed to lithium-induced Brugada-pattern ECG changes with a greater impact on INa and INa-late in RVOT cardiomyocytes. Targeting INa-late may be a potential therapeutic strategy for Brugada syndrome-related ventricular tachyarrhythmia. [ABSTRACT FROM AUTHOR]

PULMONARY arterial hypertension, ATRIAL arrhythmias, SINOATRIAL node, ENDOTHELIN receptors, PREPROENDOTHELIN, RIGHT heart atrium, CONNEXIN 43, and WESTERN immunoblotting

Atrial arrhythmias are considered prominent phenomena in pulmonary arterial hypertension (PAH) resulting from atrial electrical and structural remodeling. Endothelin (ET)-1 levels correlate with PAH severity and are associated with atrial remodeling and arrhythmia. In this study, hemodynamic measurement, western blot analysis, and histopathology were performed in the control and monocrotaline (MCT, 60 mg/kg)-induced PAH rabbits. Conventional microelectrodes were used to simultaneously record the electrical activity in the isolated sinoatrial node (SAN) and right atrium (RA) tissue preparations before and after ET-1 (10 nM) or BQ-485 (an ET-A receptor antagonist, 100 nM) perfusion. MCT-treated rabbits showed an increased relative wall thickness in the pulmonary arterioles, mean cell width, cross-sectional area of RV myocytes, and higher right ventricular systolic pressure, which were deemed to have PAH. Compared to the control, the spontaneous beating rate of SAN–RA preparations was faster in the MCT-induced PAH group, which can be slowed down by ET-1. MCT-induced PAH rabbits had a higher incidence of sinoatrial conduction blocks, and ET-1 can induce atrial premature beats or short runs of intra-atrial reentrant tachycardia. BQ 485 administration can mitigate ET-1-induced RA arrhythmogenesis in MCT-induced PAH. The RA specimens from MCT-induced PAH rabbits had a smaller connexin 43 and larger ROCK1 and phosphorylated Akt than the control, and similar PKG and Akt to the control. In conclusion, ET-1 acts as a trigger factor to interact with the arrhythmogenic substrate to initiate and maintain atrial arrhythmias in PAH. ET-1/ET-A receptor/ROCK signaling may be a target for therapeutic interventions to treat PAH-induced atrial arrhythmias. [ABSTRACT FROM AUTHOR]

HEART metabolism, DIABETES, ATRIAL fibrillation, ATRIAL arrhythmias, ENERGY metabolism, FATTY acid oxidation, and THERAPEUTICS

Atrial fibrillation (AF) is the most common type of sustained arrhythmia in diabetes mellitus (DM). Its morbidity and mortality rates are high, and its prevalence will increase as the population ages. Despite expanding knowledge on the pathophysiological mechanisms of AF, current pharmacological interventions remain unsatisfactory; therefore, novel findings on the underlying mechanism are required. A growing body of evidence suggests that an altered energy metabolism is closely related to atrial arrhythmogenesis, and this finding engenders novel insights into the pathogenesis of the pathophysiology of AF. In this review, we provide comprehensive information on the mechanistic insights into the cardiac energy metabolic changes, altered substrate oxidation rates, and mitochondrial dysfunctions involved in atrial arrhythmogenesis, and suggest a promising advanced new therapeutic approach to treat patients with AF. [ABSTRACT FROM AUTHOR]

Cardiology, blood circulation, phlebology, Cardiologie, appareil circulatoire, phlébologie, Sciences biologiques et medicales, Biological and medical sciences, Sciences medicales, Medical sciences, Cardiologie. Appareil circulatoire, Cardiology. Vascular system, Coeur, Heart, Insuffisance cardiaque, oedème pulmonaire cardiogène, hypertrophie cardiaque, Heart failure, cardiogenic pulmonary edema, cardiac enlargement, Trouble du rythme et de la conduction, Cardiac dysrhythmias, Cardiopathie, Heart disease, Cardiopatía, Electrodiagnostic, Electrodiagnosis, Electrodiagnóstico, Electrophysiologie, Electrophysiology, Electrofisiología, Trouble de l'excitabilité, Excitability disorder, Trastorno excitabilidad, Trouble du rythme cardiaque, Arrhythmia, Arritmia, Cardiologie, Cardiology, Cardiología, Fibrillation auriculaire, Atrial fibrillation, Fibrilación auricular, Insuffisance cardiaque, Heart failure, Insuficiencia cardíaca, Pathologie de l'appareil circulatoire, Cardiovascular disease, Aparato circulatorio patología, Potentiel action, Action potential, Potencial acción, Protéine choc thermique, Heat shock protein, Proteína choque térmico, Substrat, Substrate, Substrato, GGA, and Monophasic action potential

Background: Geranylgeranylacetone (GGA) has been reported up-regulating heat shock protein (HSP) expression, and protecting against atrial remodeling. This study aimed to investigate the effects of GGA on atrial electrophysiology and inducibility of atrial fibrillation (AF) in heart failure (HF) model. Methods and results: HF rabbits were created 4 weeks after coronary artery ligation. Monophasic action potential recordings and multielectrode array were used to record the electrophysiological characteristics of left atrium (LA) in normal, or HF rabbits with (HF-GGA) and without (HF-control) oral administration of GGA (200 mg/kg, 24 h before experiments). The mRNA and protein expressions of ionic channels were measured by Western blot and PCR. HF-GGA LA (n = 10), similar to normal LA (n = 10) had a shorter action potential duration (APD) and effective refractory period than HF-control LA (n = 10). HF-GGA LA had less triggered activity and APD alternans (20% vs. 100%, P = 0.001), lower maxima slope of restitution curve of APD (0.94 ± 0.04 vs.1.69 ± 0.04, P < 0.001), and less inducibility of AF (50% vs. 100%, P = 0.033) than HF-control LA. HF-GGA LA had a shorter activation time and higher conduction velocity than HF-control LA. HF-GGA LA had a higher mRNA expression of Cav1.2, Nav1.5, Kir2.1, Kv1.4, Kv7.1, Kv11.1, sarcoplasmic reticulum Ca2+-ATPase, and higher phosphorylation of phospholamban than HF-control LA. Conclusions: GGA decreases triggered activity, dispersion of APD and inducibility of AF in failing heart through induction of HSP, and modulation of ionic channels and calcium homeostasis.

Cardiology, blood circulation, phlebology, Cardiologie, appareil circulatoire, phlébologie, Sciences biologiques et medicales, Biological and medical sciences, Sciences biologiques fondamentales et appliquees. Psychologie, Fundamental and applied biological sciences. Psychology, Genetique des eucaryotes. Evolution biologique et moleculaire, Genetics of eukaryotes. Biological and molecular evolution, Génétique classique, génétique quantitative, hybrides, Classical genetics, quantitative genetics, hybrids, Homme, Human, Sciences medicales, Medical sciences, Cardiologie. Appareil circulatoire, Cardiology. Vascular system, Coeur, Heart, Trouble du rythme et de la conduction, Cardiac dysrhythmias, Cardiopathie, Heart disease, Cardiopatía, Pathologie de l'appareil circulatoire, Cardiovascular disease, Aparato circulatorio patología, Trouble de l'excitabilité, Excitability disorder, Trastorno excitabilidad, Trouble du rythme cardiaque, Arrhythmia, Arritmia, Ablation, Ablación, Age, Edad, Analyse, Analysis, Análisis, Caractère dominant, Dominant character, Carácter dominante, Caractéristique, Characteristic, Característica, Caractéristiques, Characteristics, Características, Carte génétique, Genetic mapping, Mapa genético, Cartographie, Cartography, Cartografía, Cathéter, Catheter, Catéter, Complexe, Complexes, Complejo, Donnée, Data, Dato, Electrique, Electric, Eléctrico, Fibrillation auriculaire, Atrial fibrillation, Fibrilación auricular, Fréquence, Frequency, Frecuencia, Homme, Human, Hombre, Intervalle, Interval, Intervalo, Isolement, Isolation, Aislamiento, Malade, Patient, Enfermo, Mécanisme, Mechanism, Mecanismo, Méthode, Method, Método, OMS, WHO, Oreillette gauche, Left atrium, Orejuela izquierda, Organisation, Organization, Organización, Résultat, Result, Resultado, Substrat, Substrate, Substrato, Système, System, Sistema, Technique, Técnica, Veine pulmonaire, Pulmonary vein, Vena pulmonar, atrial fibrillation, electrogram frequency analysis, and left atrium

Background―There is a paucity of data regarding the mechanism of maintaining atrial fibrillation (AF) after pulmonary vein isolation (PVI) in patients with AF. The aim of this study was to examine the impact of circumferential PVI on the left atrial (LA) substrate characteristics. Methods and Results―Seventy-two AF patients (age, 53±11 years) underwent mapping and catheter ablation using an NavX system. The biatrial characteristics such as the complex fractionated atrial electrograms (CFEs; based on fractionated intervals) and frequency analysis (based on dominant frequencies) were mapped before and after PVI. PVI with electric isolation was performed in all patients. In the 45 patients who did not respond to PVI, the continuous CFEs (>8 seconds, 18±18% and 12±17% of the LA sites, before and after PVI, respectively, P=0.02), degree of LA fractionation (mean fractionated interval: 75.6±14.3 msec versus 87.3±16.7 msec, P=0.001), and mean LA dominant frequencies (6.92±0.88 Hz versus 6.58±0.91 Hz, P=0.001) decreased after PVI. Complete PVI altered the distribution of the CFEs toward the LA anteroseptum, mitral annulus, and LA appendage regions. A persistent presence of continuous CFEs in the vicinity of the dominant frequencies sites (observed in 53% patients) correlated with a higher procedural AF termination rate for the CFE ablation (63% versus 23%, P<0.05). Conclusions―Complete PVI eliminated some CFEs in the LA and altered the distribution of the CFEs. The persistent presence of CFEs before and after PVI in the vicinity of the high frequency sites is important for AF maintenance after PVI.

Cardiology, blood circulation, phlebology, Cardiologie, appareil circulatoire, phlébologie, Sciences biologiques et medicales, Biological and medical sciences, Sciences medicales, Medical sciences, Cardiologie. Appareil circulatoire, Cardiology. Vascular system, Coeur, Heart, Trouble du rythme et de la conduction, Cardiac dysrhythmias, Cardiopathie, Heart disease, Cardiopatía, Pathologie de l'appareil circulatoire, Cardiovascular disease, Aparato circulatorio patología, Trouble de l'excitabilité, Excitability disorder, Trastorno excitabilidad, Trouble du rythme cardiaque, Arrhythmia, Arritmia, Appareil circulatoire, Circulatory system, Aparato circulatorio, Caractéristique, Characteristic, Característica, Caractéristiques, Characteristics, Características, Cardiologie, Cardiology, Cardiología, Etude comparative, Comparative study, Estudio comparativo, Sexe, Sex, Sexo, Tachycardie auriculaire, Atrial tachycardia, and Taquicardia auricular

Gender differences of supraventricular tachycardias such as atrioventricular nodal re-entry, atrioventricular re-entry, and atrial fibrillation have been reported. There is little evidence of the effect of gender on focal atrial tachycardia (FAT). The study consisted of 298 patients who were referred to this institution for radiofrequency catheter ablation of FAT from October 1992 to April 2008 and included 156 men (52%) and 142 women (48%). Men were significantly older than women (57.9 ± 18.2 vs 47.2 ± 19.0 years old, p <0.001). Women had more associated arrhythmias (17.0% vs 28.9%, p = 0.01), mostly due to an increased incidence of atrioventricular nodal re-entrant tachycardia. Men had more cardiovascular co-morbidities (19.9% vs 9.9%, p = 0.02), a mechanism of increased automaticity (19.1% vs 8.1%, p = 0.01), and nonparoxysmal tachycardia (14.7% vs 4.4%, p = 0.01). No gender differences were noted among FAT number, left atrial involvement, shortest tachycardia cycle, success rate of catheter ablation, or recurrence rate of FAT. Mean duration of follow-up was 63.2 ± 47.5 months. Premenopausal women had a lesser cardiovascular co-morbidity (15.3% vs 4.3%, p = 0.04) and a greater incidence of a mechanism of increased automaticity (13.4% vs 2.9%, p = 0.03). In conclusion, gender differences in electrophysiologic characteristics were noted in FAT.

Brugada syndrome, gender, lithium intoxication, sodium current dysregulation, right ventricular outflow tract, Biology (General), and QH301-705.5

Lithium intoxication induces Brugada-pattern ECG, ventricular arrhythmia, and sudden death with the predominant preference for the male over the female gender. This study investigated the mechanisms of gender difference in lithium-induced arrhythmogenesis. The ECG parameters were recorded in male and female rabbits before and after the intravenous administration of lithium chloride (LiCl) (1, 3, 10 mmol/kg). Patch clamps were used to study the sodium current (INa) and late sodium current (INa-late) in the isolated single male and female right ventricular outflow tract (RVOT) cardiomyocytes before and after LiCl. Male rabbits (n = 9) were more prone to developing lithium-induced Brugada-pattern ECG changes (incomplete right bundle branch block, ST elevation and QRS widening) with fatal arrhythmia (66.7% vs. 0%, p = 0.002) than in female (n = 7) rabbits at 10 mmol/kg (but not 1 or 3 mmol/kg). Compared to those in the female RVOT cardiomyocytes, LiCl (100 μM) reduced INa to a greater extent and increased INa-late in the male RVOT cardiomyocytes. Moreover, in the presence of ranolazine (the INa-late inhibitor, 3.6 mg/kg iv loading, followed by a second iv bolus 6.0 mg/kg administered 30 min later, n = 5), LiCl (10 mmol/kg) did not induce Brugada-pattern ECG changes (p < 0.005). The male gender is much predisposed to lithium-induced Brugada-pattern ECG changes with a greater impact on INa and INa-late in RVOT cardiomyocytes. Targeting INa-late may be a potential therapeutic strategy for Brugada syndrome-related ventricular tachyarrhythmia.

Cardiology, blood circulation, phlebology, Cardiologie, appareil circulatoire, phlébologie, Sciences biologiques et medicales, Biological and medical sciences, Sciences medicales, Medical sciences, Cardiologie. Appareil circulatoire, Cardiology. Vascular system, Coeur, Heart, Trouble du rythme et de la conduction, Cardiac dysrhythmias, Trouble excitabilité, Excitability disorder, Trastorno excitabilidad, Trouble rythme cardiaque, Arrhythmia, Arritmia, Ablation, Ablación, Appareil circulatoire pathologie, Cardiovascular disease, Aparato circulatorio patología, Caractérisation, Characterization, Caracterización, Cardiopathie, Heart disease, Cardiopatía, Flutter auriculaire, Atrial flutter, Flutter auricular, Homme, Human, Hombre, Radiofréquence, Radiofrequency, and Radiofrecuencia

OBJECTIVES The aim of the study was to investigate the conduction properties and anisotropy of the crista terminalis (CT) in patients with atrial flutter (AFL) using non-contact mapping. BACKGROUND The CT is a posterior barrier during typical AFL. However, the CT has transverse conduction capabilities in patients with upper loop re-entry (ULR). METHODS Twenty-two patients (16 males, 63 ± 15 years) with typical AFL and ULR were included. Non-contact mapping of the right atrium during AFL and pacing from coronary sinus (CS) and low anterolateral right atrium (LARA) was performed to evaluate transverse conduction across the CT. During ULR, the longitudinal (CVL) and transverse (CVT) conduction velocity along and across the CT were measured. The width of the CT conduction gap was evaluated to guide radiofrequency ablation (RFA). RESULTS No transverse CT gap conduction was found during typical AFL. Transverse CT gap conduction was found in three patients during CS pacing and in three patients during LARA pacing. During ULR, CVL was greater than CVT (1.28 ± 0.43 vs. 0.73 ± 0.30 m/s, p < 0.001). The CVL/CVT ratio was 1.95 ± 0.77, which was inversely related to the CT gap width (15.7 ± 6.8 mm) (p < 0.001). The RFA of the CT gap was successful in 18 patients. Four patients had recurrence of arrhythmias during the follow-up of 11 ± 3 months. CONCLUSIONS Most of the CT conduction gaps were functional and only appeared during ULR. The width of the CT gap was inversely related to the anisotropic ratio of the CT. The RFA of the CT gap was effective in eliminating ULR.

Cardiology, blood circulation, phlebology, Cardiologie, appareil circulatoire, phlébologie, Sciences biologiques et medicales, Biological and medical sciences, Sciences medicales, Medical sciences, Cardiologie. Appareil circulatoire, Cardiology. Vascular system, Coeur, Heart, Trouble du rythme et de la conduction, Cardiac dysrhythmias, Appareil circulatoire pathologie, Cardiovascular disease, Aparato circulatorio patología, Cardiopathie, Heart disease, Cardiopatía, Trouble excitabilité, Excitability disorder, Trastorno excitabilidad, Trouble rythme cardiaque, Arrhythmia, Arritmia, Appareil circulatoire, Circulatory system, Aparato circulatorio, Atypique, Atypical, Atípico, Cardiologie, Cardiology, Cardiología, Carte génétique, Genetic mapping, Mapa genético, Cartographie, Cartography, Cartografía, Conduction, Conducción, Endocarde, Endocardium, Endocardio, Flutter auriculaire, Atrial flutter, Flutter auricular, Homme, Human, Hombre, Oreillette droite, Right atrium, Orejuela derecha, Phlébologie, Phlebology, Flebología, Substrat, Substrate, and Substrato

OBJECTIVES The purpose of this study was to investigate the relationship between the abnormal substrate and peak negative voltage (PNV) in the right atrium (RA) with atypical flutter. BACKGROUND The impact of a local abnormally low voltage electrogram on the local activation pattern and velocity of atrial flutter (AFL) remains unclear. METHODS Twelve patients with clinically documented AFL were included to undergo noncontact mapping of the RA. The atrial substrate was characterized by the: 1) activation mapping; 2) high-density voltage mapping; and 3) conduction velocity along the flutter re-entrant circuit. The normalized PNV (i.e., the relative ratio to the maximal PNV) in each virtual electrode recording was used to produce the voltage maps of the entire chamber. The protected isthmus was bordered by low voltage zones. RESULTS Atypical AFL of the RA was induced by atrial pacing in 12 patients, including 10 upper loop re-entry and 2 RA free wall re-entry flutter. These protected isthmuses were located near the crista terminalis. The mean width of the protected isthmus was 1.7 ± 0.3 cm and mean voltage at the isthmus was -0.91 ± 0.39 mV. The conduction velocities within these paths were significantly slower than outside the path (0.30 ± 0.18 m/s vs. 1.14 ± 0.41 m/s, respectively; p = 0.004). The ratiometric PNV of 37.6% of the maximal PNV had the best cut-off value to predict slow conduction, with a high sensitivity (92.3%) and specificity (85.7%). CONCLUSIONS Characterization of the RA substrate in terms of the unipolar PNV is an effective predictor of the slow conduction path within the critical isthmus of the re-entrant circuit.

Cardiology, blood circulation, phlebology, Cardiologie, appareil circulatoire, phlébologie, Sciences biologiques et medicales, Biological and medical sciences, Sciences medicales, Medical sciences, Cardiologie. Appareil circulatoire, Cardiology. Vascular system, Coeur, Heart, Trouble du rythme et de la conduction, Cardiac dysrhythmias, Appareil circulatoire pathologie, Cardiovascular disease, Aparato circulatorio patología, Cardiopathie, Heart disease, Cardiopatía, Trouble excitabilité, Excitability disorder, Trastorno excitabilidad, Trouble rythme cardiaque, Arrhythmia, Arritmia, Analyse, Analysis, Análisis, Appareil circulatoire, Circulatory system, Aparato circulatorio, Cardiologie, Cardiology, Cardiología, Fibrillation auriculaire, Atrial fibrillation, Fibrilación auricular, Fréquence, Frequency, Frecuencia, Phlébologie, Phlebology, Flebología, Type, and Tipo

OBJECTIVES This study sought to investigate the regional frequency distribution from multiple bi-atrial sites in different types of paroxysmal atrial fibrillation (AF). BACKGROUND A previous study showed a left atrium (LA) to right atrium (RA) frequency gradient in patients with paroxysmal AF. METHODS Forty-four patients (age = 60 ± 16, male patients = 27) with paroxysmal AF originating from the pulmonary veins (PVs) (n = 31) or superior vena cava (SVC) (n = 13) were included. Frequency analysis was performed on the intracardiac electrograms (7 s, 1 kHz/channel) recorded from PV, posterior LA, coronary sinus (CS), posterolateral RA, and SVC. The largest peak frequency was identified as the dominant frequency (DF). RESULTS In the PV-AF patients, there was a frequency gradient from the PV ostium to the LA, RA, and SVC (8.5 ± 3.3 Hz vs. 5.9 ± 1.1 Hz vs. 5.2 ± 0.85 Hz vs. 5.5 ± 0.48 Hz, respectively, p < 0.001). The highest DFs were mostly located at the arrhythmogenic PV ostium (58%). The DFs of the arrhythmogenic PV and PV ostium were significantly higher than those of the non-arrhythmogenic PVs and PV ostia (p < 0.05). In the SVC-AF patients, there was a frequency gradient from the SVC to the RA, LA, and PV (8.0 ± 2.4 Hz vs. 5.9 ± 1.1 Hz vs. 5.9 ± 0.7 Hz vs. 5.8 ± 0.7 Hz, respectively, p = 0.001). The highest DFs were mostly located inside the SVC (77%) instead of the SVC ostium (as compared with PV-AF patients, p = 0.035). CONCLUSIONS The location of the highest DF depended on the arrhythmogenic PV or SVC. A frequency gradient was present between the arrhythmogenic thoracic vein and atrium in all patients.

Cardiology, blood circulation, phlebology, Cardiologie, appareil circulatoire, phlébologie, Sciences biologiques et medicales, Biological and medical sciences, Sciences medicales, Medical sciences, Pharmacologie. Traitements medicamenteux, Pharmacology. Drug treatments, Système cardiovasculaire, Cardiovascular system, Vasodilatateurs périphériques. Vasorégulateurs cérébraux, Vasodilator agents. Cerebral vasodilators, Métabolisme général et cellulaire. Vitamines, General and cellular metabolism. Vitamins, Cardiologie. Appareil circulatoire, Cardiology. Vascular system, Vaisseaux sanguins et lymphatiques, Blood and lymphatic vessels, Maladies vasculaires des membres. Pathologie de la veine cave. Maladies vasculaires diverses, Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous, Cardiopathie, Heart disease, Cardiopatía, Trouble excitabilité, Excitability disorder, Trastorno excitabilidad, Trouble rythme cardiaque, Arrhythmia, Arritmia, Ablation, Ablación, Appareil circulatoire pathologie, Cardiovascular disease, Aparato circulatorio patología, Cathéter, Catheter, Catéter, Fibrillation auriculaire, Atrial fibrillation, Fibrilación auricular, Homme, Human, Hombre, Oreillette droite, Right atrium, Orejuela derecha, ablation, atrial fibrillation, and atrium

Background-Catheter ablation of the right atrial (RA) substrate has had variable efficacy in curing paroxysmal atrial fibrillation (PAF), suggesting that RA substrate ablation can play an important role in the treatment of atrial fibrillation (AF) in some patients. The aim of this study was to investigate the electrophysiological characteristics and ablation strategy and its results in a specific group of patients with paroxysmal RA-AF. Methods and Results-The study population consisted of 13 patients (8 men; age, 64± 15 years) with drug-refractory (2± 1 drugs), frequent episodes of PAF. Provocation maneuvers did not reveal any ectopic beat-initiating AF. However, rapid atrial pacing easily induced AF. Activation mapping during sinus rhythm, atrial pacing, and AF was visualized by using a noncontact mapping system. Noncontact mapping revealed RA reentry (6 patients with single-loop circuits and 7 with double-loop circuits) with conduction through channels between lines of block, crista terminalis gaps, and the cavotricuspid isthmus, which could be identified during sinus rhythm and atrial pacing, resulting in fibrillatory conduction in other parts of the RA. The consistency of wavefront activation was confirmed by frequency analysis from equally distributed mapping sites in the RA. Short lines of ablation lesions were aimed at the conduction channels between the lines of block, crista terminalis gaps, and the cavotricuspid isthmus, resulting in bidirectional block. AF was eliminated in 11 (85%) of 13 patients, and those 11 patients with acute success were free of AF without any antiarrhythmic drugs during the long-term follow-up period (16±6 months). Conclusions-RA ablation still can cure selected patients with PAF. Linear ablation of the RA substrate guided by the electrophysiological characteristics of RA-AF is an effective approach for treating this specific group of patients with AF.

Anesthesia, intensive care, Anesthésie, réanimation, Cardiology, blood circulation, phlebology, Cardiologie, appareil circulatoire, phlébologie, Pneumology, Pneumologie, Sciences biologiques et medicales, Biological and medical sciences, Sciences medicales, Medical sciences, Pneumologie, Pneumology, Cardiologie. Appareil circulatoire, Cardiology. Vascular system, Coeur, Heart, Trouble du rythme et de la conduction, Cardiac dysrhythmias, Cardiopathie, Heart disease, Cardiopatía, Trouble excitabilité, Excitability disorder, Trastorno excitabilidad, Trouble rythme cardiaque, Arrhythmia, Arritmia, Ablation, Ablación, Anatomie, Anatomy, Anatomía, Appareil circulatoire pathologie, Cardiovascular disease, Aparato circulatorio patología, Appareil respiratoire pathologie, Respiratory disease, Aparato respiratorio patología, Cathéter, Catheter, Catéter, Fibrillation auriculaire, Atrial fibrillation, Fibrilación auricular, Oesophage, Esophagus, Esófago, Oreillette gauche, Left atrium, Orejuela izquierda, ablation, esophagus, and left atrium

Study objectives: Atrioesophageal fistulas have been reported to be a lethal complication following catheter ablation of atrial fibrillation (AF). The purpose of this study was to investigate the relationship between the esophagus and posterior left atrium (LA) and provide the anatomic information necessary to minimize the risk of esophageal injury during AF ablation. Methods and results: Forty-eight patients (43 men; mean ± SD age, 59 ± 12 years) with drug-refractory paroxysmal AF and 32 control subjects (26 men; mean age, 60 ± 9 years) were included. All underwent a CT scan for delineation of the relationship between the esophagus and posterior LA. In the paroxysmal AF group, two major types of esophageal routes were demonstrated. Type 1 routes were found in 42 patients with the lower portion of esophagus close to the ostium of the left inferior pulmonary vein (LIPV), including three subtypes of courses according to the proximity to the left superior pulmonary vein (PV) and LIPV. Type 2 routes were found in six patients with the lower portion of esophagus close to the ostium of the right inferior pulmonary vein (RIPV), including three subtypes of courses according to the proximity to the right superior PV and RIPVs. The mean shortest distance of the esophagus to the four individual PVs significantly differed between type 1 and type 2: 28.4 ± 6.1 mm vs 10.5 ± 5.7 mm (to the right superior), 19.6 ± 7.0 mm vs 3.7 ± 3.4 mm (to the right inferior), 10.1 ± 3.4 mm vs 22.8 ± 4.2 mm (to the left superior), and 2.8 ± 2.5 mm vs 18.7 ± 5.2 mm (to the left inferior), respectively (p < 0.001 for all). Contact of the esophagus and middle part of posterior LA was observed in each patient. However, direct contact of the aorta with the posterior LA wall was more frequent in type 2 than in type 1 (p = 0.001). The clinical characteristics, type of esophageal routes, distance from the esophagus to the four PVs, and diameter of the thoracic cage, LA, and aorta in the control group were similar to those in the AF group (p > 0.05 for all). Conclusion: Although the anatomic relationship between the esophagus and LA posterior wall varied widely, two major patterns of esophageal routes could be depicted. This information is important for deciding the location of the ablation lesions around the PV ostia and LA and for avoiding the potential risk of esophageal injury.

Cardiology, blood circulation, phlebology, Cardiologie, appareil circulatoire, phlébologie, Sciences biologiques et medicales, Biological and medical sciences, Sciences medicales, Medical sciences, Cardiologie. Appareil circulatoire, Cardiology. Vascular system, Coeur, Heart, Trouble du rythme et de la conduction, Cardiac dysrhythmias, Appareil circulatoire pathologie, Cardiovascular disease, Aparato circulatorio patología, Cardiopathie, Heart disease, Cardiopatía, Electrodiagnostic, Electrodiagnosis, Electrodiagnóstico, Trouble excitabilité, Excitability disorder, Trastorno excitabilidad, Trouble rythme cardiaque, Arrhythmia, Arritmia, Algorithme, Algorithm, Algoritmo, Appareil circulatoire, Circulatory system, Aparato circulatorio, Cardiologie, Cardiology, Cardiología, Electrocardiographie, Electrocardiography, Electrocardiografía, Flutter auriculaire, Atrial flutter, Flutter auricular, Phlébologie, Phlebology, and Flebología

OBJECTIVES This study was performed to differentiate upper loop re-entry (ULR) from reverse typical atrial flutter (AFL). BACKGROUND Right atrial ULR and reverse typical AFL have different mechanisms and ablation strategies, but similar electrocardiographic characteristics. METHODS This study included 26 patients with reverse typical AFL and 20 patients with ULR. The noncontact mapping system (EnSite-3000, Endocardial Solutions, St. Paul, Minnesota) was used to confirm diagnosis and guide successful radiofrequency ablation. Flutter wave polarity and amplitude in the 12-lead surface electrocardiogram were determined by two independent electrophysiologists. RESULTS The flutter wave polarity in leads I and aVL was significantly different between the reverse typical AFL and ULR groups (p £ 0.001). Voltage measurement revealed significant differences between reverse typical AFL and ULR in leads I, II, aVR, aVF, V1, and V2 (p < 0.001). A new diagnostic algorithm based on negative or isoelectric/flat flutter wave polarity and amplitude ≤0.07 mV in lead I was useful for diagnosis of ULR, with an accuracy of 90% to 97%, a sensitivity of 82% to 100%, and a specificity of 95%. CONCLUSIONS Polarity and voltage measurement of flutter wave in lead I can differentiate reverse typical AFL from ULR.

Cardiology, blood circulation, phlebology, Cardiologie, appareil circulatoire, phlébologie, Sciences biologiques et medicales, Biological and medical sciences, Sciences medicales, Medical sciences, Cardiologie. Appareil circulatoire, Cardiology. Vascular system, Vaisseaux sanguins et lymphatiques, Blood and lymphatic vessels, Maladies vasculaires des membres. Pathologie de la veine cave. Maladies vasculaires diverses, Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous, Cardiopathie, Heart disease, Cardiopatía, Trouble excitabilité, Excitability disorder, Trastorno excitabilidad, Trouble rythme cardiaque, Arrhythmia, Arritmia, Ablation, Ablación, Appareil circulatoire pathologie, Cardiovascular disease, Aparato circulatorio patología, Cartographie, Cartography, Cartografía, Cathéter, Catheter, Catéter, Tachycardie auriculaire, Atrial tachycardia, and Taquicardia auricular

Background-This study investigated the electrophysiologic characteristics, atrial activation pattern, and effects of radiofrequency (RF) catheter ablation guided by noncontact mapping system in patients with focal atrial tachycardia (AT). Methods and Results-In 13 patients with 14 focal ATs, noncontact mapping system was used to map and guide ablation of AT. AT origins were in the crista terminalis (n=8), right atrial (RA) free wall (n=3), Koch triangle (n=1), anterior portion of RA-inferior vena cava junction (n= 1), and superior portion of tricuspid annulus (n=1); breakout sites were in the crista terminalis (n=5), RA free wall (n=5), middle cavotricuspid isthmus (n=2), and RA-superior vena cava junction (n=2). ATs arose from the focal origins (11 ATs inside or at the border of low-voltage zone), with preferential conduction, breakout, and spread to the whole atrium. After applications of RF energy on the earliest activation site or the proximal portion of preferential conduction from AT origin, 13 ATs were eliminated without complication. During the follow-up period (8±5 months), 11 (91.7%) of the 12 patients with successful ablation were free of focal ATs. Conclusions-Focal AT originates from a small area and spreads out to the whole atrium through a preferential conduction. Application of RF energy guided by noncontact mapping system was effective and safe in eliminating focal AT.

anti‐tachycardia pacing therapy, implantable cardioverter defibrillator, RR interval variability, shock therapy, ventricular tachycardia, Diseases of the circulatory (Cardiovascular) system, and RC666-701

Abstract Background An implantable cardioverter defibrillator (ICD) is the most reliable therapeutic device for preventing sudden cardiac death in patients with sustained ventricular tachycardia (VT). Regarding its effectiveness, targeted VT is defined based on the tachyarrhythmia cycle length. However, variations in RR interval variability of VTs may occur. Few studies have reported on VT characteristics and effects of ICD therapy according to the RR interval variability. We aimed to identify the clinical characteristics of VTs and ICD therapy effects according to the RR interval variability. Methods We analyzed 821 VT episodes in 69 patients with ICDs or cardiac resynchronization therapy defibrillators. VTs were classified as irregular when the difference between two successive beats was >20 ms in at least one of 10 RR intervals; otherwise, they were classified as regular. We evaluated successful termination using anti‐tachycardia pacing (ATP)/shock therapy, spontaneous termination, and acceleration between regular and irregular VTs. The RR interval variability reproducibility rates were evaluated. Results Regular VT was significantly more successfully terminated than irregular VT by ATP. No significant difference was found in shock therapy or VT acceleration between the regular and irregular VTs. Spontaneous termination occurred significantly more often in irregular than in regular VT cases. The reproducibility rates of RR interval variability in each episode and in all episodes were 89% and 73%, respectively. Conclusions ATP therapy showed greater effectiveness for regular than for irregular VT. Spontaneous termination was more common in irregular than in regular VT. RR interval variability of VTs seems to be reproducible.

atrial arrhythmogenesis, mitochondria, energy metabolism, glucose oxidation, fatty acid oxidation, ketone body, Cytology, and QH573-671

Atrial fibrillation (AF) is the most common type of sustained arrhythmia in diabetes mellitus (DM). Its morbidity and mortality rates are high, and its prevalence will increase as the population ages. Despite expanding knowledge on the pathophysiological mechanisms of AF, current pharmacological interventions remain unsatisfactory; therefore, novel findings on the underlying mechanism are required. A growing body of evidence suggests that an altered energy metabolism is closely related to atrial arrhythmogenesis, and this finding engenders novel insights into the pathogenesis of the pathophysiology of AF. In this review, we provide comprehensive information on the mechanistic insights into the cardiac energy metabolic changes, altered substrate oxidation rates, and mitochondrial dysfunctions involved in atrial arrhythmogenesis, and suggest a promising advanced new therapeutic approach to treat patients with AF.

Diseases of the circulatory (Cardiovascular) system and RC666-701

DIABETIC cardiomyopathy, KETOGENIC diet, CALCIUM-dependent protein kinase, HOMEOSTASIS, ACTION potentials, RYANODINE receptors, and SODIUM channels

A ketogenic diet (KD) might alleviate patients with diabetic cardiomyopathy. However, the underlying mechanism remains unclear. Myocardial function and arrhythmogenesis are closely linked to calcium (Ca2+) homeostasis. We investigated the effects of a KD on Ca2+ homeostasis and electrophysiology in diabetic cardiomyopathy. Male Wistar rats were created to have diabetes mellitus (DM) using streptozotocin (65 mg/kg, intraperitoneally), and subsequently treated for 6 weeks with either a normal diet (ND) or a KD. Our electrophysiological and Western blot analyses assessed myocardial Ca2+ homeostasis in ventricular preparations in vivo. Unlike those on the KD, DM rats treated with an ND exhibited a prolonged QTc interval and action potential duration. Compared to the control and DM rats on the KD, DM rats treated with an ND also showed lower intracellular Ca2+ transients, sarcoplasmic reticular Ca2+ content, sodium (Na+)-Ca2+ exchanger currents (reverse mode), L-type Ca2+ contents, sarcoplasmic reticulum ATPase contents, Cav1.2 contents. Furthermore, these rats exhibited elevated ratios of phosphorylated to total proteins across multiple Ca2+ handling proteins, including ryanodine receptor 2 (RyR2) at serine 2808, phospholamban (PLB)-Ser16, and calmodulin-dependent protein kinase II (CaMKII). Additionally, DM rats treated with an ND demonstrated a higher frequency and incidence of Ca2+ leak, cytosolic reactive oxygen species, Na+/hydrogen-exchanger currents, and late Na+ currents than the control and DM rats on the KD. KD treatment may attenuate the effects of DM-dysregulated Na+ and Ca2+ homeostasis, contributing to its cardioprotection in DM. [ABSTRACT FROM AUTHOR]

ATRIAL fibrillation, STATINS (Cardiovascular agents), PULMONARY veins, MICROELECTRODES, ATRIAL arrhythmias, and WESTERN immunoblotting

Introduction: Pulmonary veins (PVs) are the most important focus for the generation of atrial fibrillation. The HMG-CoA reductase inhibitors (statins) can reduce the occurrence of atrial fibrillation. The purposes of this study were to evaluate whether statins may inhibit the PV arrhythmogenic activity to prevent atrial arrhythmias from PVs and to investigate the link between fluvastatin, nitric oxide synthase (NOS) activity, mechanical activity, and electrical activity. Methods: Conventional microelectrodes and Western blot were used to record the electrical activity, diastolic tension, contractility and expression of Akt, endothelial nitric oxide synthase (eNOS), neuronal nitric oxide synthase (nNOS), and phosphorylated Akt and eNOS before and after the administration of fluvastatin in rabbit PVs or atria. Results: Fluvastatin decreased the PV spontaneous activity, diastolic tension, and contractility, but did not change the action potential duration or resting membrane potential. The effects of fluvastatin on the PV firing rate and diastolic tension were attenuated in the presence of L-NAME (100 μM), wortmannin (100 nM), and ODQ (3 μM). Fluvastatin (1 μM) increased the phosphorylated Akt and eNOS, but did not change the total Akt or eNOS in the PVs and atria. In contrast, fluvastatin (1 μM) decreased the total nNOS in the PVs and atria. Conclusions and implications: Fluvastatin produced nitric oxide through the PI3kinase/Akt pathway, thus reducing the PV vascular diastolic tension and PV spontaneous activity. These results may contribute to the beneficial effects of statins. [ABSTRACT FROM AUTHOR]

ATRIAL fibrillation, DISEASE mapping, ELECTRIC properties of hearts, ELECTROPHYSIOLOGY, and ARRHYTHMIA treatment

Unipolar Characteristics of CFAEs. Background: The noncontact mapping (NCM) system possesses the merit of global endocardial recording for unipolar and activation mapping. Objective: We aimed to evaluate the unipolar electrogram characteristics and activation pattern over the bipolar complex fractionated atrial electrogram (CFAE) sites during atrial fibrillation (AF). Methods: Twenty patients (age 55 ± 11 years old, 15 males) who underwent NCM and ablation of AF (paroxysmal/persistent = 13/7) were included. Both contact bipolar (32–300 Hz) and NCM virtual unipolar electrograms (0.5–300 Hz) were simultaneously recorded along with the activation pattern (total 223 sites, 11 ± 4 sites/patient). A CFAE was defined as a mean bipolar cycle length of ≤ 120 ms with an intervening isoelectric interval of more than 50 ms (Group 1A, n = 63, rapid repetitive CFAEs) or continuous fractionated activity (Group 1B, n = 59, continuous fractionated CFAEs), measured over a 7.2-second duration. Group 2 consisted of those with a bipolar cycle length of more than 120 ms (n = 101). Results: The Group 1A CFAE sites exhibited a shorter unipolar electrogram cycle length (129 ± 11 vs 164 ± 20 ms, P < 0.001), and higher percentage of an S-wave predominant pattern (QS or rS wave, 63 ± 13% vs 35 ± 13%, P < 0.001) than the Group 2 non-CFAE sites. There was a linear correlation between the bipolar and unipolar cycle lengths (P < 0.001, R = 0.87). Most of the Group 1A CFAEs were located over arrhythmogenic pulmonary vein ostia or nonpulmonary vein ectopy with repetitive activations from those ectopies (62%) or the pivot points of the turning wavefronts (21%), whereas the Group 1B CFAEs exhibited a passive activation (44%) or slow conduction (31%). Conclusions: The bipolar repetitive and continuous fractionated CFAEs represented different activation patterns. The former was associated with an S wave predominant unipolar morphology which may represent an important focus for maintaining AF. (J Cardiovasc Electrophysiol, Vol. 21, pp. 640-648, June 2010) [ABSTRACT FROM AUTHOR]

ATRIAL fibrillation, CATHETER ablation, PULMONARY veins, ELECTRIC countershock, ATRIAL arrhythmias, and THERAPEUTICS

Background: The left atrial (LA) size is an important predictor of atrial fibrillation (AF) procedural termination and the long-term outcome. We sought to evaluate the long-term outcome in regard to the LA size and procedural termination. Methods: Eighty-seven consecutive chronic AF patients (72 males, 53 ± 10 years) underwent 3D mapping (NavX) and ablation. A stepwise approach including circumferential pulmonary vein (PV) isolation, linear ablation, and continuous complex-fractionated electrogram (CFE) ablation (targeting fractionation intervals of < 50 ms). Electrical cardioversion was applied to those without any procedural termination. The freedom from AF was defined as the maintenance of sinus rhythm without the use of any class I or III antiarrhythmic drugs after the blanking period. Results: Among the 87 patients, all received a circumferential PV isolation, 93% a linear ablation, and 59% a continuous CFE ablation. Those with AF procedural termination (n = 30) had a better long-term outcome when compared with those without termination during a follow-up of 21 ± 12 months. Moreover, a Kaplan-Meier analysis showed that in those with an LA diameter of less than 45 mm (n = 49), the freedom from AF rate was higher when procedural termination was achieved (P = 0.004). On the contrary, the outcome was comparable in those with an LA diameter of ≥ 45 mm (n = 38), whether AF procedural termination occurred or not (P = 0.658). Conclusions: AF procedural termination was related to the long-term success during chronic AF ablation, especially in those with an LA diameter of less than 45 mm. The favorable effect of termination decreased when the LA diameter was ≥ 45 mm. [ABSTRACT FROM AUTHOR]

TACHYCARDIA, ADENOSINES, ADENINE, ARRHYTHMIA, CATHETER ablation, and ELECTROSURGERY

Focal Atrial Tachycardia. Introduction:Adenosine can terminate most focal atrial tachycardias (ATs). However, information about the termination mechanism is limited. This study investigated the effects and mechanism of adenosine on terminating focal AT using a three-dimensional noncontact mapping system.Methods and Results:The study consisted of 7 patients (4 men and 3 women; age 44± 29 years) with focal AT. Cycle length variation and atrial activation pattern at baseline and just before AT termination by adenosine (3–12mg) were analyzed. Noncontact mapping demonstrated focal AT propagated from the origin (O) with preferential conduction and spread away from the breakout sites to the whole atrium. Compared to baseline AT, termination episodes revealed higher mean beat-to-beat variation of AT cycle length (11.7± 11.7 msec vs 4.7± 4.5 msec, P<0.001) and standard deviation of normalized AT cycle length (0.033± 0.014 vs 0.011± 0.005, P<0.001). In termination episodes, adenosine significantly decreased the peak negative voltage of AT-O (–27.2± 15.3%, P<0.01), preferential conduction (proximal:–32.1± 18.7, mid:–28.4± 22.8, distal portion:–29.6± 21.4%, P<0.01), and breakout (–31.4± 12.5%, P<0.01). However, adenosine did not affect voltage in nontermination episodes. Adenosine shifted the locations of AT-O in 5 of 10 AT episodes with termination. Mean number of shifting AT-O was 2.4± 1.5 (range 1–4), with maximum shifting distance of 15.0± 3.1 (range 10–19) mm. Focal activation at AT-O simply disappeared in all termination episodes and therefore was not due to conduction block within preferential conduction or breakout site. Catheter ablation lesions covered 50% of total shifting origins, without late recurrence.Conclusion:Adenosine-induced AT termination was associated with significantly decreased electrogram voltage, shifting AT-O locations, and disappearance of focal activation.(J Cardiovasc Electrophysiol, Vol. 15, pp. 1-7, December 2004) [ABSTRACT FROM AUTHOR]

ENZYMES, HEART atrium, ATRIOVENTRICULAR node, VENTRICULAR tachycardia, ARRHYTHMIA, ELECTRIC properties of heart cells, and CARDIOMYOPATHIES

Right Atrial Substrate of Supraventricular Tachyarrhythmias. Background:Voltage mapping has been used to detect diseased myocardium. However, accurate determination of the local atrial voltage at the same site, and simultaneous recordings from multiple mapping sites were limited. The purpose of this study was to investigate the right atrial (RA) substrate properties in patients with supraventricular tachyarrhythmias (SVT).Methods and Results:Forty patients (aged 55± 20 years) undergoing noncontact mapping and ablation of SVT constituted the study population. There were eight patients with atrioventricular node reentrant tachycardia (AVNRT), eight patients with focal atrial tachycardia (AT), 14 patients with atrial flutter (AFL), and 10 patients with atrial fibrillation (AF). The mean peak negative voltage (PNV) was analyzed in virtual unipolar electrograms, which were obtained from 256 equally distributed RA endocardial sites during sinus rhythm (SR), atrial pacing, and tachycardia. The mean PNV of global RA during SR (−1.34± 0.22 vs.−0.90± 0.40 vs.−1.00± 0.36 vs.−0.85± 0.35 mV, P= 0.04), atrial pacing at cycle lengths of 500 ms (−1.30± 0.29 vs.−0.70± 0.35 vs.−0.76± 0.25 vs.−0.64± 0.26 mV, P= 0.02), and 300 ms (−1.54± 0.47 vs.−0.94± 0.21 vs.−0.75± 0.27 vs.−0.57± 0.22 mV, P<0.01) were significantly greater in patients with AVNRT compared to AT, AFL, and AF. Furthermore, the mean PNV decreased during atrial pacing with shorter pacing cycle length was demonstrated only in patients with AFL and AF.Conclusion:Negative unipolar voltage analysis of global RA showed different RA substrate characteristics during various SVT. The substrate property of activation and cycle length-dependent voltage reduction may be related to the development of AFL and AF.(J Cardiovasc Electrophysiol, Vol. 16, pp. 1-8, March 2005) [ABSTRACT FROM AUTHOR]

Cardiology, blood circulation, phlebology, Cardiologie, appareil circulatoire, phlébologie, Sciences biologiques et medicales, Biological and medical sciences, Sciences biologiques fondamentales et appliquees. Psychologie, Fundamental and applied biological sciences. Psychology, Genetique des eucaryotes. Evolution biologique et moleculaire, Genetics of eukaryotes. Biological and molecular evolution, Génétique classique, génétique quantitative, hybrides, Classical genetics, quantitative genetics, hybrids, Homme, Human, Sciences medicales, Medical sciences, Cardiologie. Appareil circulatoire, Cardiology. Vascular system, Ablation, Ablación, Appareil circulatoire, Circulatory system, Aparato circulatorio, Cardiologie, Cardiology, Cardiología, Carte génétique, Genetic mapping, Mapa genético, Cartographie, Cartography, Cartografía, Cathéter, Catheter, Catéter, Ganglion lymphatique, Lymph node, Ganglio linfático, Guide, Guía, Image tridimensionnelle, Tridimensional image, Imagen tridimensional, Phlébologie, Phlebology, Flebología, Système 3 dimensions, Three dimensional system, Sistema 3 dimensiones, Tachycardie, Tachycardia, Taquicardia, Atrioventricular nodal reentrant tachycardia, Catheter ablation, and Noncontact three-dimensional mapping system

Background: Atrioventricular nodal reentrant tachycardia (AVNRT) is the most common supraventricular tachycardia in adulthood. Although selective ablation of the slow AV nodal pathway can cure AVNRT, accidental AV block may occur. The details on the electrophysiologic characteristics, quantitative data on the voltage inside Koch's triangle, and the use of three-dimensional noncontact mapping to facilitate the catheter ablation of AVNRT associated with a high-risk for AV block or other arrhythmias have been limited. Methods and results: Nine patients (MF=5/4, 34±23 years, range 17-76) with clinically documented AVNRT were included. All patients had undergone previous sessions for slow AV nodal pathway ablation but they had failed, because of repetitive episodes of complete AV block during the RF energy applications. Further, one patient had a complex anatomy and 4 patients were associated with other tachycardias, respectively. The electrophysiologic studies revealed that 4 patients had the slow-fast, 4 the slow-intermediate and one the fast-intermediate form of AVNRT. Noncontact mapping demonstrated two types of antegrade AV nodal conduction, markedly differing sites of the earliest atrial activation during retrograde VA conduction, and a lower range of voltage within Koch's triangle. The lowest border of the retrograde conduction region was defined on the map, and the application of the RF energy was delivered below that border to prevent the occurrence of AV block. The distance between the successful ablation lesions and the lowest border of the retrograde conduction region was significantly shorter in the patients with the slow-intermediate form of AVNRT than in those with the slow-fast form (5.5±3.4 vs. 15±7.6 mm; p<0.05). After the ablation procedure, either rapid pacing or extrastimulation could not induce any tachycardia, and there was no recurrence during the follow-up (10.3±5.4, 2 to 22 months). Conclusions: Noncontact mapping could effectively demonstrate the antegrade and retrograde atrionodal conduction patterns, electrophysiologic characteristics of Koch's triangle, and guide the successful catheter ablation in difficult AVNRT cases.

Background Resveratrol has shown benefits in reducing ventricular remodeling and arrhythmias. Objective This study aimed to assess the therapeutic efficacy of resveratrol in reducing atrial fibrillation (AF) in a heart failure (HF) model and to explore the underlying mechanisms. Methods HF rabbits were created 4 weeks after undergoing coronary ligation. Group 1 (n = 6) was divided into subgroups of (a) normal rabbits, (b) HF sham rabbits, and (c) HF rabbits treated for 1 week with intraperitoneal injections of resveratrol, (d) resveratrol plus wortmannin, or (e) resveratrol plus diphenyleneiodonium chloride (DPI). All rabbits underwent epicardial catheter stimulation. Collagen content, messenger RNA and protein expression in ion channels, and phosphoinositide 3-kinase (PI3K)/AKT/endothelial nitric oxide synthase (eNOS) signaling pathways were studied in left atrial appendage (LAA) preparations. To investigate acute drug effects on left atrial electrophysiology, groups 2 a through 2e (n = 6 per group) were subjected to Langendorff perfusion. Results Higher AF inducibility was found in the HF group and groups that were given PI3K and eNOS inhibitors than in the normal and resveratrol-treated groups ( P < .001). Histologic analysis of the LAA revealed a decrease in fibrosis in resveratrol-treated groups compared with the HF group (8.95% ± 1.53% vs 26.62% ± 2.19%, P < .001). In real-time polymerase chain reaction analysis, ion channels including Kv1.4, Kv1.5, KvLQT1, Kir2.1, Nav1.5, Cav1.2, NCX, SERCA2a, and phospholamban were upregulated by resveratrol. PI3K, AKT, and eNOS messenger RNA and protein expression were upregulated by resveratrol but were inhibited by the coadministration of wortmannin and DPI. Conclusion Resveratrol decreases left atrial fibrosis and regulates variation in ion channels to reduce AF through the PI3K/AKT/eNOS signaling pathway. [ABSTRACT FROM AUTHOR]

MUSCLE cells, HAMSTERS as laboratory animals, ION channels, SARCOPLASMIC reticulum, CELLS, and ACTIVE biological transport

1. The present experiments were performed in order to study abnormal action potential configuration and ion channel activity in ventricular myocytes obtained from 23 male myopathic Syrian hamsters (Biobreeders strain 14.6, 32–52 weeks old) compared with 10 age-matched healthy control hamsters (Biobreeders F1B) by means of whole-cell patch-clamp techniques.2. The results show that the myopathic myocytes had a longer action potential duration, a reduced transient outward K+ current on depolarization and a smaller transient inward current on repolarization after prolonged depolarizing pulses (> 500 msec). However, the L-type Ca2+ current and the inwardly rectifing K+ current were not significantly different from those of healthy myocytes.3. The oscillatory transient inward currents could be diminished by treatment with ryanodine (0.01–1 µmol/L), a sarcoplasmic reticulum (SR) Ca2+ release channel blocker, or with Na+-free superfusate.4. We conclude that the hereditary myopathic hamsters are less likely to develop delayed afterdepolarization-related transient inward currents and triggered arrhythmias owing to a smaller SR Ca2+ content. [ABSTRACT FROM AUTHOR]