Pulmonary Vein Sleeves Research Articles

Atrial Fibrillation as the Initial Presentation of Lung Cancer

SESSION TITLE: Student/Resident Case Report Poster - Lung Cancer II SESSION TYPE: Student/Resident Case Report Poster PRESENTED ON: Tuesday, October 25, 2016 at 01:30 PM - 02:30 PM INTRODUCTION: Metastases to the heart and pericardium can occur in 18% of patients with an underlying tumors. Such patients may develop arrhythmias, pericarditis, pericardial effusion and heart failure. We report a case of a lung cancer, invading the left atrium, resulting in pericardial effusion and presenting with atrial fibrillation. CASE PRESENTATION: A 59-year-old male with PMH of COPD and tobacco abuse presented with complaints of new-onset palpitations and an unintentional weight loss of 20 lbs. in the last 3 months. He was found to have an irregular-irregular pulse (115/min). The rest of the examination was normal. EKG showed atrial fibrillation with a rapid ventricular rate and chest x-ray showed a left paraspinal mass with emphysematous changes. A CT scan chest showed a left hilar and posterior mediastinal mass occluding the left lower lobe bronchus, narrowing inferior pulmonary veins, with extrinsic mass effect on the left atrium. CT guided FNAc was indicative of squamous cell carcinoma of the lung. A 2D echocardiogram revealed pericardial effusion. DISCUSSION: Lung cancer is the leading cause of cancer-related deaths in the US (27% of all cancer deaths). Squamous cell carcinoma, commonly seen in smokers, arise frequently in the proximal bronchi and tend to cause bronchial obstruction, atelectasis, pneumonia or pericardial effusions. Few cases have documented the occurrence of arrhythmia as the first manifestation of a tumor invading atrial structures. The most dramatic presentation is a sudden conduction abnormality with various degrees of heart block. Atrial fibrillation episodes are triggered by ectopic beats from fibers extending from the left atrium into the pulmonary veins. Tumor cells infiltrate the myocardium creating a pulmonary vein sleeve, which is interdigitated by smooth muscle and fibrous tissue, thus creating a chance for micro-reentry. Mediastinal tumors can also result in mechanical stretching of the pulmonary vein(s) and atrial fibers resulting in tachycardia. In our case enhanced CT revealed the presence of a lesion encircling/narrowing the inferior pulmonary veins. We propose that his presentation could be explained by a reentry, presence of pericardial effusion, and/or as a consequence of the compression of the heart by the growing tumor. CONCLUSIONS: While arrhythmias can be a rare complication of lung tumors, it can rapidly result in hemodynamic instability if not recognized and treated promptly. Physicians are expected to look for lung tumors invading the heart when a patient with a significant smoking history presents with a new onset atrial fibrillation. Reference #1: Mio Tamura, et al. A case of atrial tachycardia originating from pulmonary vein invaded by lung cancer. Journal of Cardiology Cases 2012; 5, 118—121 Reference #2: Parambil JG, Gersh BJ, Knight MZ, Krowka MJ, Ryu JH. Bronchogenic cyst causing atrial fibrillation by impinging the right inferior pulmonary vein. Am J Med Sci 2006;331:336—8 Reference #3: American Cancer Society/Cancer Facts and Figures 2015 DISCLOSURE: The following authors have nothing to disclose: Ahmed Dirweesh, Ritika Zijoo No Product/Research Disclosure Information

A Regional Reduction in Ito and IKACh in the Murine Posterior Left Atrial Myocardium Is Associated with Action Potential Prolongation and Increased Ectopic Activity.

BackgroundThe left atrial posterior wall (LAPW) is potentially an important area for the development and maintenance of atrial fibrillation. We assessed whether there are regional electrical differences throughout the murine left atrial myocardium that could underlie regional differences in arrhythmia susceptibility.MethodsWe used high-resolution optical mapping and sharp microelectrode recordings to quantify regional differences in electrical activation and repolarisation within the intact, superfused murine left atrium and quantified regional ion channel mRNA expression by Taqman Low Density Array. We also performed selected cellular electrophysiology experiments to validate regional differences in ion channel function.ResultsSpontaneous ectopic activity was observed during sustained 1Hz pacing in 10/19 intact LA and this was abolished following resection of LAPW (0/19 resected LA, P<0.001). The source of the ectopic activity was the LAPW myocardium, distinct from the pulmonary vein sleeve and LAA, determined by optical mapping. Overall, LAPW action potentials (APs) were ca. 40% longer than the LAA and this region displayed more APD heterogeneity. mRNA expression of Kcna4, Kcnj3 and Kcnj5 was lower in the LAPW myocardium than in the LAA. Cardiomyocytes isolated from the LAPW had decreased Ito and a reduced IKACh current density at both positive and negative test potentials.ConclusionsThe murine LAPW myocardium has a different electrical phenotype and ion channel mRNA expression profile compared with other regions of the LA, and this is associated with increased ectopic activity. If similar regional electrical differences are present in the human LA, then the LAPW may be a potential future target for treatment of atrial fibrillation.

Atrial Early Afterdepolarization: An Emerging Property of the Fibrotic Atria?

Introduction: Early afterdepolarizations (EADs) interrupt and delay repolarization of the cardiac action potential. In the ventricular myocardium, EADs are triggers of torsades de pointes, ventricular tachycardia and fibrillation; in the pulmonary vein sleeves of the left atrium, EADs may contribute to the initiation of atrial fibrillation (AF). While EADs can be readily induced in isolated ventricular and pulmonary vein myocytes, EADs are not readily observed in (non-pulmonary-vein) atrial myocytes. Since fibrosis can promote AF at sites remote from the pulmonary veins, we investigated how fibroblast coupling to atrial myocytes affects the emergence of EADs and AF.Methods and Results: When patch-clamped myocytes from young rabbit hearts were exposed to hypokalemia (2.7mmol/L) and isoproterenol (1-2 μmol/L), EADs readily occurred in ventricular myocytes at slow pacing rates but not in atrial myocytes. However, when those patch-clamped myocytes were coupled to virtual fibroblasts using the dynamic clamp technique, the resultant gap junction current promoted EADs in ventricular myocytes at faster pacing rates and in atrial myocytes at both slow and fast pacing rates. While the early Ito-like gap junction current component was important for EAD genesis in ventricular myocytes, the late gap junction current component was critical for EAD genesis in atrial myocytes. In intact rabbit atria exposed to the same stressors and studied with optical mapping of voltage, spontaneous EADs inducing atrial fibrillation arose from non-pulmonary-vein areas when atrial fibrosis exceeded 10% on subsequent trichrome staining.Conclusion: In response to stressors that prolong repolarization, ventricular myocytes readily develop EADs whereas atrial myocytes are resistant. When coupled to fibroblasts, however, atrial myocytes also become susceptible to EADs. Our findings highlight the differences between ventricular and atrial myocytes and provide a potential mechanism linking atrial fibrosis to the emergence of non-pulmonary-vein triggers of AF.

Changes in P-wave morphology after pulmonary vein isolation: insights from computer simulations.

Apparently conflicting clinical measurements of P-wave duration (PWD) pre- vs. post-ablation have been reported. To assist the interpretation of these clinical data, we used a computer model of the atria and torso to simulate P waves before and after pulmonary vein (PV) isolation. Twenty ablation patterns were designed (segmental or ipsilateral ablation; five distances to PV sleeves; addition of a roof line or not). Possible PV reconnections were introduced as gaps in the ablation lines. PWD and area were measured during sinus rhythm in vectorcardiogram (VCG) magnitude signals and on the 16-lead ECG before and after ablation, and after PV reconnection. After PV isolation, biatrial activation time was prolonged by 0-5 ms without and by 48±5 ms with roof line. Yet PWD was shortened in lead V3 and V4 by up to 15 ms. The effect of ablation on P-wave morphology was stronger when larger PV areas were isolated. Segmental and ipsilateral PV isolation led to concordant results. P-wave area increased in V1 and decreased in V6. Changes in PWD and area on the VCG were sensitive to the threshold used for detecting the end of the P wave. The occurrence of PV reconnection was best identified on leads V3, V4, and V9. PV isolation and reconnection induced measurable changes on the 16-lead ECG that might be used to improve patient follow-up after ablation.

Diadenosine tetra- and pentaphosphates affect contractility and bioelectrical activity in the rat heart via P2 purinergic receptors

Diadenosine polyphosphates (Ap(n)As) are endogenously produced molecules which have been identified in various tissues of mammalian organism, including myocardium. Ap(n)As contribute to the blood clotting and are also widely accepted as regulators of blood vascular tone. Physiological role of Ap(n)As in cardiac muscle has not been completely elucidated. The present study aimed to investigate the effects of diadenosine tetra- (Ap4A) and penta- (Ap5A) polyphosphates on contractile function and action potential (AP) waveform in rat supraventricular and ventricular myocardium. We have also demonstrated the effects of A4pA and Ap5A in myocardial sleeves of pulmonary veins (PVs), which play a crucial role in genesis of atrial fibrillation. APs were recorded with glass microelectrodes in multicellular myocardial preparations. Contractile activity was measured in isolated Langendorff-perfused rat hearts. Both Ap4A and Ap5A significantly reduced contractility of isolated Langendorff-perfused heart and produced significant reduction of AP duration in left and right auricle, interatrial septum, and especially in right ventricular wall myocardium. Ap(n)As also shortened APs in rat pulmonary veins and therefore may be considered as potential proarrhythmic factors. Cardiotropic effects of Ap4A and Ap5A were strongly antagonized by selective blockers of P2 purine receptors suramin and pyridoxalphosphate-6-azophenyl-2',4'-disulfonic acid (PPADS), while P1 blocker DPCPX was not effective. We conclude that Ap(n)As may be considered as new class of endogenous cardioinhibitory compounds. P2 purine receptors play the central role in mediation of Ap4A and Ap5A inhibitory effects on electrical and contractile activity in different regions of the rat heart.

The Timing and Frequency of PulmonaryVeins Unexcitability Relative to Completion of a WideArea Circumferential Ablation Line for Pulmonary Vein Isolation.

This study sought to assess loss of pulmonary vein (PV) excitability to pacing relative to the development of entrance block and the anatomic completion of the circumferential radiofrequency ablation (RFA)line. During encircling RFA for PV isolation (PVI), entrance block develops before anatomic completion of encirclement (early) in some patients. We hypothesized that early entrance block may be associated with loss of PV excitability to pacing. In 30 patients undergoing PV isolation (age 61 ± 10 years, 21 men), excitability to pacing was assessed atpredefined PV sites when entrance block developed and after completion of the RFA line. Of 60 PV pairs, 37 developed entrance block early, with a gap≥10 mm in the RFA line. In only 35% of PV pairs in this subgroup, both PV sleeves captured, and all of the capturing PV pairs showed exit block (no conduction from PVtoatrium) despite the presence of an excitable gap. In the remaining 23 PV pairs, entrance block did not occur untilencircling RFA was anatomically complete. In 83% of these PV pairs, both sleeves captured with exit block (p<0.001compared with early block PVs). The majority of PV pairs develops entrance and exit block before complete anatomic encircling by RFAlesions. Early entrance block is frequently associated with loss of PV sleeve excitability, consistent with a spreading waveof injury or edema rather than a permanent conduction barrier. This may help to explain the significant rate of PV conduction recovery associated with the acute endpoints of entrance and exit block.

Pulmonary vein sleeve cell excitation-contraction-coupling becomes dysynchronized by spontaneous calcium transients.

Atrial fibrillation (AF) is the most common form of sustained cardiac arrhythmia. Substantial evidence indicates that cardiomyocytes located in the pulmonary veins [pulmonary vein sleeve cells (PVCs)] cause AF by generating ectopic electrical activity. Electrical ablation, isolating PVCs from their left atrial junctions, is a major treatment for AF. In small rodents, the sleeve of PVCs extends deep inside the lungs and is present in lung slices. Here we present data, using the lung slice preparation, characterizing how spontaneous Ca2+ transients in PVCs affect their capability to respond to electrical pacing. Immediately after a spontaneous Ca2+ transient the cell is in a refractory period and it cannot respond to electrical stimulation. Consequently, we observe that the higher the level of spontaneous activity in an individual PVC, the less likely it is that this PVC responds to electrical field stimulation. The spontaneous activity of neighbouring PVCs can be different from each other. Heterogeneity in the Ca2+ signalling of cells and in their responsiveness to electrical stimuli are known pro-arrhythmic events. The tendency of PVCs to show spontaneous Ca2+ transients and spontaneous action potentials (APs) underlies their potential to cause AF.

Atrial fibrillation electrical remodelling via ablation of the epicardial neural networks and suprathreshold stimulation of vagosympathetic nerve.

BackgroundNumerous studies have shown that the cardiac autonomic nervous system (CANS) is involved in the occurrence and persistence of atrial fibrillation (AF). The CANS is commonly considered to consist of the extrinsic and intrinsic autonomic nerves. The influence of exogenous and endogenous nerve stimulation plexus ablation on pulmonary vein sleeves and atrial myocardium provides important information in understanding the occurrence and persistence of AF. Vagosympathetic nerve stimulation and epicardial neural networks are important participants in atrial electrical remodelling (AER). Elucidation of the changes in the electrophysiological indicators of the atrial and pulmonary veins caused by epicardial neural network ablation and autonomic nerve stimulation may provide a theoretical basis for the clinical treatment of AF.Material/MethodsA total of 13 beagle dogs were randomly divided into 2 groups: the control group (n=6), which was treated with a simple rapid atrial pacing (RAP) for 6 h, and the experimental group (n=7), which was treated with RAP+vagus nerve stimulation (VNS) for 6 h. Both groups were treated with epicardial ganglia plexus (GP) ablation after 6 h. We measured the monophasic action potential (MAP), various parts of the effective refractory period (ERP), and AF induction rate before and after pacing or ablation.ResultsWith the extension of the pacing time, the atrial MAP and ERP of the 2 groups shortened and returned to normal after ablation plexus. After GP ablation, the atrial AF-induced rate did not decrease significantly compared with that of the pulmonary vein.ConclusionsVagus nerve threshold stimulation exacerbated the deterioration of electrical remodelling, whereas the epicardial neural network ablation blocked or reversed the AER.

Depolarization of atrial epicardium near pulmonary veins orifices in hypertensive ISIAH rats.

The formation of early activation regions was demonstrated in the area of the pulmonary vein orifice in hypertensive rats. The appearance of early activation zones on the dorsal side of the left atrium near the pulmonary veins simultaneously with the sinoatrial node in rats with arterial hypertension indicates the possibility of ectopic foci formation in the area of pulmonary vein sleeves.

Spontaneous, Pro-Arrhythmic Calcium Signals Disrupt Electrical Pacing in Mouse Pulmonary Vein Sleeve Cells

The pulmonary vein, which returns oxygenated blood to the left atrium, is ensheathed by a population of unique, myocyte-like cells called pulmonary vein sleeve cells (PVCs). These cells autonomously generate action potentials that propagate into the left atrial chamber and cause arrhythmias resulting in atrial fibrillation; the most common, often sustained, form of cardiac arrhythmia. In mice, PVCs extend along the pulmonary vein into the lungs, and are accessible in a lung slice preparation. We exploited this model to study how aberrant Ca2+ signaling alters the ability of PVC networks to follow electrical pacing. Cellular responses were investigated using real-time 2-photon imaging of lung slices loaded with a Ca2+-sensitive fluorescent indicator (Ca2+ measurements) and phase contrast microscopy (contraction measurements). PVCs displayed global Ca2+ signals and coordinated contraction in response to electrical field stimulation (EFS). The effects of EFS relied on both Ca2+ influx and Ca2+ release, and could be inhibited by nifedipine, ryanodine or caffeine. Moreover, PVCs had a high propensity to show spontaneous Ca2+ signals that arose via stochastic activation of ryanodine receptors (RyRs). The ability of electrical pacing to entrain Ca2+ signals and contractile responses was dramatically influenced by inherent spontaneous Ca2+ activity. In PVCs with relatively low spontaneous Ca2+ activity (<1 Hz), entrainment with electrical pacing was good. However, in PVCs with higher frequencies of spontaneous Ca2+ activity (>1.5 Hz), electrical pacing was less effective; PVCs became unpaced, only partially-paced or displayed alternans. Because spontaneous Ca2+ activity varied between cells, neighboring PVCs often had different responses to electrical pacing. Our data indicate that the ability of PVCs to respond to electrical stimulation depends on their intrinsic Ca2+ cycling properties. Heterogeneous spontaneous Ca2+ activity arising from stochastic RyR opening can disengage them from sinus rhythm and lead to autonomous, pro-arrhythmic activity.

Mechanical function of left atrium and pulmonary vein sleeves before and after their antrum isolation

Background and objectivePulmonary vein (PV) sleeves are established as the main substrate taking part in the mechanisms of atrial fibrillation (AF) initiation. However, we have extremely few data concerning their physiological role in the heart contractility. The aim of the study was to estimate the mechanical function of the left atrium (LA) and PV sleeves before and early after their isolation. Materials and methodsA total of 17 patients with a mean age of 57.4±8.3 years who underwent PVs isolation due to AF were enrolled in the study. A day before the procedure a computed tomography (CT) of the LA and PVs and dopplerography of transmitral flow were performed. During the procedure the mechanical function of the LA and PV sleeves were estimated by transesophageal echocardiography and manometry in the left heart chambers. ResultsDuring the invasive study the patterns of the heart chambers and PV sleeves pressure were identified. These patterns confirmed the active role of the PV sleeves in LA filling and active LA relaxation during left ventricular systole. After PV isolation an alteration of transmitral blood flow and increase of LA pressure were registered. However, diastolic dysfunction was ruled out by LV manometry, thereby testifying LA mechanical function disturbance. The change in PV hemodynamics also occurred as a result of the decrease in PV sleeves contractility, revealed by manometry and paired CT scans. ConclusionsThe PVs take an active part in left atrial filling by contraction of their sleeves. Antrum isolation of the PVs leads to the deterioration of their contractility and LA reservoir function.

Defragmentation in ablative AF treatment: is our knowledge too fragmented?

Defragmentation in ablative AF treatment: is our knowledge too fragmented?

Experimental Evaluation of the Cardiac Rhythm Originating in Myocardial Sleeves of Pulmonary Veins Using a Monophasic Action Potential

Spontaneous depolarization similar to that from the sinus node was documented from the myocardial sleeves of pulmonary veins (PV) after isolation procedures. It was then hypothesized that sinus node-like tissue is present in the PVs of humans. Based on a number of features, the myocardium of myocardial sleeves (MS) is highly arrhythmogenic. Membrane potentials originating from MS are invariably recordable at the PVs ostia in patients with atrial fibrillation (AF) and delayed conduction around the PVs ostia may play a role in re-entry process responsible for the initiation and maintenance of AF. Diagnostic and therapeutic evidence of premature atrial beats induced in MS of PVs and resulting in launch of AF was detected by 3D electroanatomic method of monophasic action potential (MAP). MAP recording plays an important role in a direct view of human myocardial electrophysiology under both physiological and pathological conditions. Its crucial importance lies in the fact that it enables the study of the action potential of myocardial cell in vivo and, therefore, the study of the dynamic relation of this potential with all the organism variables. The knowledge of pathological MAPs from PV myocardial sleeves can help us to confirm a diagnosis when finding the similar action potential morphology. MAP can be also used to evaluate the therapeutic efficiency of vagal nerves suppression, radiofrequency ablation or other treatment procedures in PVs myocardial sleeves as well as for post-treatment following up.

Heterogeneous and anisotropic integrative model of pulmonary veins: computational study of arrhythmogenic substrate for atrial fibrillation

Mechanisms underlying the genesis of re-entrant substrate for the most common cardiac arrhythmia, atrial fibrillation (AF), are not well understood. In this study, we develop a multi-scale three-dimensional computational model that integrates cellular electrophysiology of the left atrium (LA) and pulmonary veins (PVs) with the respective tissue geometry and fibre orientation. The latter is reconstructed in unique detail from high-resolution (approx. 70 μm) contrast micro-computed tomography data. The model is used to explore the mechanisms of re-entry initiation and sustenance in the PV region, regarded as the primary source of high-frequency electrical activity in AF. Simulations of the three-dimensional model demonstrate that an initial break-down of normal electrical excitation wave-fronts can be caused by the electrical heterogeneity between the PVs and LA. High tissue anisotropy is then responsible for the slow conduction and generation of a re-entrant circuit near the PVs. Evidence of such circuits has been seen clinically in AF patients. Our computational study suggests that primarily the combination of electrical heterogeneity and conduction anisotropy between the PVs and LA tissues leads to the generation of a high-frequency (approx. 10 Hz) re-entrant source near the PV sleeves, thus providing new insights into the arrhythmogenic mechanisms of excitation waves underlying AF.

Hyperpolarization activated cation current (&lt;I&gt;I&lt;/I&gt;&lt;SUB&gt;f&lt;/SUB&gt;) in cardiac myocytes from pulmonary vein sleeves in the canine with atrial fibrillation

ObjectiveTo investigate the characteristics of ectopic automaticity and cation current (If) of cardiac myocytes from pulmonary vein sleeves (PVs) in canines with atrial fibrillation.MethodsThe canines (8–10 years old) were subjected to long-term, rapid atrial pacing (RAP) for 10 weeks, which induced the atrial fibrillation model. Disassociation of PVs of canines yielded single cardiac myocytes from a Landengorff column. Action potential, If and hyperpolarisation activated cyclic nucleotide-gated (HCN) currents were measured with the patch-clamp technique.ResultsCompared with the control group, cardiac myocytes from the RAP canine PVs had spontaneous diastolic depolarization, shorter action potential duration, and larger If densities. In the group of RAP cells, the half maximal activation potential (V1/2) was found to be less negative (−105.5 ± 5.2 mV) compared to control cells (−87.3 ± 4.9 mV). Current densities of If were increased significantly by β-adrenergic receptor stimulation with isoproterenol and caused an acceleration of current activation. In contrast, If currents in the RAP were reduced by carvedilol, a selective beta-adrenergic receptor. Another important finding is that HCN4-based channels may make a significant contribution to If in PVs cells, but not HCN2. Meanwhile, HCN4 current significantly increases in canine PVs cardiac myocytes with RAP.ConclusionsThe spontaneous action potential and larger If current were observed in the PVs cardiac myocytes using RAP, which may contribute to more ectopic activity events to trigger and maintain atrial fibrillation.

An Image-Based Model of Atrial Muscular Architecture

Background— Computer models that capture key features of the heterogeneous myofiber architecture of right and left atria and interatrial septum provide a means of investigating the mechanisms responsible for atrial arrhythmia. The data necessary to implement such models have not previously been available. The aims of this study were to characterize surface geometry and myofiber architecture throughout the atrial chambers and to investigate the effects of this structure on atrial activation. Methods and Results— Atrial surface geometry and myofiber orientations were reconstructed in 3D at 50×50×50-μm 3 resolution from serial images acquired throughout the sheep atrial chambers. Myofiber orientations were determined by Eigen-analysis of the structure tensor. These data have been incorporated into an anatomic model that provides the first quantitative representation of myofiber architecture throughout the atrial chambers. By simulating activation on this 3D structure, we have confirmed the roles of specialized myofiber tracts such as the crista terminalis, pectinate muscles, and the Bachman bundle on the spread of activation from the sinus node. We also demonstrate how the complex myocyte arrangement in the posterior left atrium contributes to activation time dispersion adjacent to the pulmonary veins and increased vulnerability to rhythm disturbance generated by ectopic stimuli originating in the pulmonary vein sleeves. Conclusions— We have developed a structurally detailed, image-based model of atrial anatomy that provides deeper understanding of the role that myocyte architecture plays in normal and abnormal atrial electric function.

Electrophysiological Characteristics of Canine Superior Vena Cava Sleeve Preparations

Background— In addition to extrasystoles of pulmonary vein (PV) origin, those arising from the superior vena cava (SVC) can precipitate atrial fibrillation (AF). The present study evaluates the electrophysiological properties of canine SVC sleeve preparations and the effect of ranolazine on late phase 3 early and delayed afterdepolarization (EAD and DAD)-induced triggered activity in SVC sleeves and compares SVC and PV sleeve electrophysiological properties. Methods and Results— Action potentials (APs) were recorded from superfused SVC and PV sleeves using microelectrode techniques. Acetylcholine (1 μmol/L), isoproterenol (1 μmol/L), high calcium ([Ca 2+ ] o =5.4 mmol/L), or a combination were used to induce EADs, DADs, and triggered activity. A marked diversity of action potential characteristics was observed in the SVC sleeve, including action potentials with short and long APs, with and without phase 4 depolarization. Rapid pacing induced hyperpolarization, accentuating the slope of phase 4 depolarization. Phase 4 depolarization and rapid pacing-induced hyperpolarization were reduced or eliminated after atropine (10 μmol/L) or ranolazine (10 μmol/L). APs displaying phase 4 depolarization (n=19) had longer APDs, smaller amplitude and V max , and a more positive take-off potential than APs lacking phase 4 depolarization (n=15). Ranolazine (5–10 μmol/L) eliminated late phase 3 EAD- and DAD-induced triggered activity as well as isoproterenol-induced automaticity elicited in SVC sleeves. Compared with PV, SVC sleeves display phase 4 depolarization, smaller V max , and longer APs. Conclusions— Autonomic influences promote spontaneous automaticity and triggered activity in SVC sleeves, thus generating extrasystolic activity capable of initiating atrial arrhythmias. Ranolazine can effectively suppress these triggers.

Comparison of propagation of atrial excitation with the cardiopotential distribution on the body surface of hypertensive rats

Arterial hypertension is associated with the risk of developing atrial arrhythmia. This research was aimed at studying the sequence of depolarization along the atrial epicardium and formation of the cardioelectric field on the body surface of hypertensive rats. The study was carried out on eleven ISIAH rats (with hereditary stress-induced hypertension). We analyzed spatial-temporal characteristics of body surface potential map (BSPM), time characteristics of electrocardiogram during atrial depolarization, sequence of atrial epicardial depolarization of rats. Statistical analysis was performed using independent samples t-test. The results indicated that in 27% of hypertensive rats in the pulmonary vein (PV) sleeves, early excitation areas are formed 2.0 ± 0.5 ms after the beginning of depolarization of the sino-atrial node area, in 73% of animals, the area of the PV sleeves is excited 6.5 ± 0.4 ms after the beginning of depolarization. In experimental animals, the beginning of inversion of areas of positive and negative cardioelectric potentials on BSPM does not differ. In 73% of rats, duration of inversion on BSPM was 7.7 ± 1.9 ms, and in 27% - 3.9 ± 0.1 ms (p=0.011). The formation of early activation zones in PV of rats with arterial hypertension testifies to possible wandering focus in the myocardium of PV sleeves. Stress-induced hypertension results in actual risk of atrial arrhythmias, which originate at the base of the PV. In rats with arterial hypertension, two early depolarization zones are revealed in the sinus node area and in the PV return to the left atrium, projected on BSPM by mutual positions of negative and positive potential zones.

Absence of Gender-based Differences in Pulmonary Vein or Left Atrial Electrophysiology in Patients Undergoing SVT Ablation

Introduction: There are recognised differences in the prevalence of various forms of paroxysmal SVT between male and female populations. Gender-based differences in left atrial (LA) and pulmonary vein (PV) electrophysiology have been demonstrated in animal studies but there are few data regarding such differences in human electrophysiology. Methods: Detailed studies of LA and PV electrophysiology were undertaken in 39 patients undergoing SVT ablation, matching a cohort of patients undergoing AF ablation. The SVT cohort had no history of AF, in order to eliminate potential confounding effects on atrial remodelling. ERP was measured at three LA and two PV sites at two cycle lengths. The LA was divided into six regions (appendage, roof, floor, septum, lateral and posterior). Activation time (AT) and voltage were analysed globally and regionally. PV sleeve length was measured from PV electrogram extent and AT was corrected for length as a marker of conduction. Data were analysed for the presence of systematic differences between male and female patients. Results: Male and female groups were well matched for age (51 vs 49 years, p = ns), LA diameter (3.8 vs 3.4 cm, p = ns) and LVEF (61 vs 59%, p = ns). No consistent differences were observed in any parameter. Representative data are presented:Tabled 1Male (n = 25)Female (n = 14)pRSPV ERP @ 600 ms (ms)267 ± 26267 ± 28NS (0.95)LIPV voltage (mV)1.58 ± 0.511.67 ± 0.87NS (0.75)LIPV AT (ms)24 ± 925 ± 4NS (0.77)LAA ERP @ 450 ms (ms)239 ± 23258 ± 10NS (0.18)LAA voltage (mV)3.11 ± 1.133.02 ± 1.38NS (0.88)LA floor AT (ms)31 ± 930 ± 11NS (0.73) Open table in a new tab Conclusion: There are no systematic gender-based differences in either PV or LA electrophysiology in patients with no history of AF who are undergoing SVT ablation.

Absence of Gender-based Differences in Pulmonary Vein or Left Atrial Electrophysiology in Patients Undergoing AF Ablation

266 Absence of Gender-based Differences in Pulmonary Vein or Left Atrial Electrophysiology in Patients Undergoing AF Ablation T. Walters 1,2,∗, A. Teh1,2, S. Spence1,2, P. Kistler 2,3, J. Morton1,2, J. Kalman1,2 1 Royal Melbourne Hospital, Department of Cardiology, Australia 2 University of Melbourne, Department of Medicine, Australia 3 Alfred Hospital and Baker IDI, Australia Introduction:Atrialfibrillation (AF) is significantlymore prevalent inmen than inwomen. Significant differences in left atrial (LA) and pulmonary vein (PV) electrophysiology thatmaypredispose toAFhave beendemonstrated in animal studies but there are fewdata regardinggender-based differences in human electrophysiology. Methods: Detailed studies of LA and PV electrophysiology were undertaken in 66 consecutive patients with AF undergoing ablation. ERP was measured at 3 LA and 2 PV sites at two cycle lengths. The LA was divided into six anatomic regions (appendage, roof, floor, septum, lateral and posterior). Activation time (AT) and voltage were analysed globally and regionally. PV sleeve length was measured from PV electrogram extent and AT was corrected for length as a marker of conduction. Data were analysed for the presence of systematic differences b