Analysis of action potentials in the canine ventricular septum: No phenotypic expression of M cells
|
|
- Carol Bradley
- 5 years ago
- Views:
Transcription
1 Cardiovascular Research 74 (2007) Abstract Analysis of action potentials in the canine ventricular septum: No phenotypic expression of M cells Shiho T. Morita, Douglas P. Zipes, Hiroshi Morita, Jiashin Wu Krannert Institute of Cardiology, Indiana University School of Medicine, 1800 N. Capitol Ave., Indianapolis, IN 46202, USA Received 30 October 2006; received in revised form 5 January 2007; accepted 5 January 2007 Available online 12 January 2007 Time primary review 27 days Objective: Transmural heterogeneity in the ventricular free wall, enhanced by the midmyocardial long action potential duration (APD) of M cells, plays an important role in the arrhythmogenesis of long QT syndrome. Although we observed dynamic expression of M cell phenotypes in the canine ventricular free wall, it is still unclear whether similar phenomena are present in the interventricular septum. This study evaluated transmural heterogeneity of APD in the septum. Methods: We isolated and perfused 22 canine septal preparations through the septal branch of the anterior descending coronary artery, and optically mapped 256 channels of action potentials on their cut-exposed transseptal surfaces before and after treatment with sotalol (I Kr blocker), anemone toxin II (ATX-II, which slows the inactivation of I Na ), or drug-free state in 6, 9, and 22 preparations, respectively. The preparations were paced from the left ventricular endocardium at cycle lengths of 500, 1000, 2000, and 4000 ms. Results: We observed progressively lengthening of APD across the septum from the right ventricular to the left ventricular endocardium without a midmyocardial maximum under all conditions. All action potentials had minor phase-1 notches, resembling the endocardial action potential in the ventricular free wall. Increasing cycle lengths and concentrations of sotalol and ATX-II prolonged APD without midmyocardial preference and increased the transseptal dispersion of APDs. Conclusions: Canine interventricular septal action potentials are similar in shape to the endocardial action potentials in the ventricular free wall, with smooth transseptal transition in APD. We found no phenotypical expression of M cells in the canine interventricular septum European Society of Cardiology. Published by Elsevier B.V. All rights reserved. Keywords: Arhythmia (mechanisms); Mapping; QT-dispersion; Repolarization 1. Introduction Corresponding author. Tel.: ; fax: address: jiaswu@iupui.edu (J. Wu). Transmural heterogeneity of action potential duration (APD) and repolarization in the ventricular free wall plays an important role in arrhythmogenesis. Under physiological conditions, ventricular APDs are shortest in the epicardium and longest in the subendocardium. However, the longest APDs can appear in the midmyocardium under pathological, pharmacological, or experimental conditions, especially in ventricles having long QT syndrome (LQTS) or reduced repolarization reserve [1,2]. The midmyocardial phenotypical expression of significantly longer APDs than in the endocardium and epicardium is commonly referred to as M cells [3 7], which were observed in the deep subendocardium to midmyocardium in the anterior wall, and in the deep subepicardium to midmyocardium in the lateral wall of canine left ventricle and in the right ventricular outflow tracts [5]. Manifestation of M cells has been suggested to play a major role in the formation of T and U waves in electrocardiogram (ECG) [8,9] and in ventricular arrhythmogenesis [4 6]. Excessive prolongation of M cell APD can trigger ventricular arrhythmias by causing spontaneous early afterdepolarizations, create functional conduction block that facilitates reentry, and increase the dispersion of repolarization. Compared to epicardial and endocardial myocytes, /$ - see front matter 2007 European Society of Cardiology. Published by Elsevier B.V. All rights reserved. doi: /j.cardiores
2 S.T. Morita et al. / Cardiovascular Research 74 (2007) ventricular myocytes expressing M cell phenotypes have lower membrane density of the slowly activating component of the delayed rectifier current (I Ks ) [6], which causes significant APD prolongation when combined with the reduction of other repolarization currents [e.g., the rapid activating component of the delayed rectifier current, I Kr,in type 2 LQTS, (LQT2)] or with the enhancement of inward currents [e.g., the late Na + current, I Na, in type 3 LQTS, (LQT3)]. Although the above studies identified M cells in the ventricular free wall, evidence of M cells was not found in several other investigations in human [10 14] and in dog ventricle without pharmacological QT prolongation [15 17]. We have recently attempted to reconcile these conflicting previous reports by demonstrating that M cell phenotypes were manifested functionally and conditionally in the canine left ventricular free wall [16]. Although the left ventricular free wall has been studied extensively, and the molecular and action potential (AP) differences between the left and right endocardium of interventricular septum (IVS) have been reported [18], the presence of M cell phenotypes and the functional dynamics of AP and its transseptal profile in the IVS are still unclear. We carried out this study to investigate the transseptal profile, heterogeneity, and functional dynamics of APs and to determine the presence of phenotypical expression of M cells in isolated and arterially perfused canine IVS preparations. The presence of intact intercellular coupling is a major advantage of the IVS preparation over isolated cells in studying the mechanisms of arrhythmia. 2. Methods 2.1. Surgical preparation The investigation confirms to the Guide for the Care and Use of Laboratory Animals published by the National Institutes of Health (NIH publication No , revised 1996). We harvested hearts from 22 adult mongrel dogs (25 30 kg), after intravenous injections of heparin sodium (5000 units) and pentobarbital sodium (30 mg/kg body weight), and quickly Langendorff-perfused the hearts with an ice-cold hyperkalemia cardioplegic solution (Tyrode's solution as shown below with 15 mmol/l KCl). The cardioplegic perfusion washed out the blood and pentobarbital sodium and protected the hearts during the subsequent period of tissue isolation. We cannulated and perfused the septal branch of the left anterior descending coronary artery then performed angiography using an iodine containing contrast media to identify the branches of the arterial tree and regions of perfusion (Fig. 1). We isolated a well perfused transseptal section of Fig. 1. The location of transseptal tissue preparations in canine interventricular septum (IVS). Tissues (without papillary muscle) were isolated (dotted rectangular area in Panels A and B) after the branches of the septal artery were located angiographically. Panel C illustrates the recording area on the cut-exposed transeptal surface of an isolated IVS preparation. TV: tricuspid valve. PV: pulmonary valve. LV and RV: left and right ventricles.
3 98 S.T. Morita et al. / Cardiovascular Research 74 (2007) IVS (30 40 mm long by 8 10 mm wide on the endocardium and mm across the septum) containing the cannulated septal artery (diameter: 1 mm) along its length, about mm from the tricuspid valve, washed out the contrast media with sufficient perfusion, inserted a second cannula into the proximal opening of the septal branch for monitoring perfusion pressure, and trimmed off underperfused tissue. Major arterial leaks in the tissues were ligated with silk sutures. The isolated preparations were mounted in a temperature-controlled (37 ± 0.5 C) tissue chamber, perfused with 37±0.5 C Tyrode's solution (in mmol/l: NaCl, 4.0 KCl, 22.0 NaHCO 3, 0.65 NaH 2 PO 4, 0.50 MgCl 2, 11.1 dextrose, and 2.0 CaCl 2, and gassed with 95% O 2 5% CO 2 ) at an arterial pressure of mm Hg, and immersed in the perfusion efflux Transseptal mapping of action potentials Each tissue was stained with di-4-anepps (4-[beta-[2- (di-n-butylamino)-6-naphthyl]vinyl]pyridinium, 4 μmol/ l in perfusate, Biotium, Hayward, CA), a membrane potential sensitive fluorescent dye used widely in optical mapping studies, after N100 min of tissue recovery and equilibration during continued Tyrode's perfusion. We evaluated the health of the tissues according to our published criteria [15,19] and immobilized the verified tissues with cytochalasin D (20 30 μmol/l, Fermentek, Jerusalem, Israel). Cytochalasin D immobilizes tissue by high affinity biding to actin, and also by reducing the Ca 2+ sensitivity of myofilaments in cardiac myocytes [20]. We verified previously that canine ventricular APs were not affected by cytochalasin D at concentrations up to 80 μmol/l using microelectrodes in isolated ventricular trabeculae [21] and up to 40 μmol/l using optical mapping in isolated ventricular wedges [15]. In addition to canine ventricular myocardium, cytochalasin D also had no visible effects on rat ventricular AP [22], although it can affect mouse APs [23] due to significant interspecies differences in the repolarization currents [24]. The tissues were paced (2 ms duration, 2 diastolic current threshold, bipolar electrode) from the left ventricular (LV) endocardium. Two silver electrodes were placed in the chamber, one at the LV side (negative) and the other at the right ventricular (RV) side (positive) of the preparation, to record the transseptal electrogram. An optical mapping system [15] with a 256-element (16 16) photodiode camera Fig. 2. Transseptal electrogram, action potential (AP) recordings, isochronal maps of conduction time (CT), and isochronal maps of action potential duration (APD) in the absence (A and C) and presence of sotalol (100 μmol/l, B) and ATX-II (10 nmol/l, D) at pacing cycle length (CL) of 4000 ms. The action potentials were from five transseptal sites: RV side of the endocardium (RV endo), 25%, 50%, 75% across the IVS from the RV endo, and LV side of the endocardium (LV endo). A and B were from a single tissue. C and D were from another tissue. The longest APDs were always at the LV septal endocardium.
4 S.T. Morita et al. / Cardiovascular Research 74 (2007) Fig. 3. Effects of bradycardia on APDs in 22 IVS preparations. APDs were measured from all recording sites in the parallel rows at the RV endo, 25%, 50%, 75% across the IVS from the RV endo (M1, M2, and M3), and at the LV endo. A: Increasing pacing cycle length (CL) prolonged APDs at all transseptal layers without midmyocardial maxima. Error bars represent SEM. B: Increasing CL expanded the transseptal (LV endo-rv endo) dispersion of APD. Indicates significant (pb0.01) expansion of the transseptal dispersion of APD compared to the corresponding dispersions at CL of 500 ms. Error bars represent SD. (C4675, Hamamatsu, Japan) and a long-pass (N610 nm) optical filter collected the fluorescence (excited by 540 ± 10 nm light) from an area of mm 2 on the cutexposed transseptal surface of the tissue and converted it into 256 channels of electrical signals. Each channel of electrical signal corresponded to a surface area of mm 2.A custom data acquisition system recorded the steady-state baseline APs and transseptal electrogram after more than 20 pacing beats at each of the sequentially increasing pacing cycle lengths (CLs) of 500, 1000, 2000, and 4000 ms (baseline recordings) after the preparations fully recovered, stabilized, and were verified and immobilized, similar to our previous experiments [2,15,16,19,25,26] Canine transseptal tissue models of LQT2 and LQT3 After the completion of baseline recordings, we created the drug-induced model of LQT2 with an I Kr blocker, (+/ )- sotalol (Sigma Chemical, St. Louis, MO) [27] at sequentially increasing concentrations of 0, 12.5, 25, 50, and 100 μmol/ l in 6 septal preparations, and the drug-induced model of LQT3 with an agent that slows inactivation of I Na, anemone toxin II (ATX-II, Calbiochem-Novabiochem, San Diego, CA) [16,27,28] at sequentially increasing concentrations of 0, 1.25, 2.5, 5.0, and 10.0 nmol/l in 9 preparations. Electrophysiological recordings done at baseline were repeated after N20 min of perfusion stabilization at each of the above concentrations of sotalol or ATX-II Data processing and statistical analysis All raw data were processed and analyzed using custom software developed for the optical mapping system. Conduction time (CT) was measured from the interval between the pacing spike and the maximum rate of depolarization. The time of depolarization was determined at the maximum rate of upstroke of AP. The time of repolarization was determined at the peak of the second-order derivative of AP. All depolarization and repolarization measurements were visually inspected and manually corrected when necessary, as we reported previously [15,16,19]. APD was derived from the interval between depolarization and repolarization. Distributions (maps) of CTs and APDs were measured at all recording sites on the cut-exposed transseptal surface. All measurements were from the data recorded during paced activation without interference from ectopic beats. Statistical analysis was performed with Student's t test for paired data or analysis of variance (ANOVA) coupled with Scheffe's test, as appropriate. APDs were statistically analyzed at the same recording row sites. Differences were considered significant if p b Results 3.1. Baseline transseptal distribution of APDs At baseline (Figs. 2A, C, and 3), APDs were CLdependent, and were always significantly longer in the LV endocardium (longest) than in the RV endocardium (shortest) with transseptal monotonic and progressive transition Table 1 Effects of sotalol and ATX-II on the duration and repolarization time of the transseptal electrogram in the perfused interventricular septal preparations Duration of the transseptal electrogram (ms) Repolarization time of the transseptal electrogram (ms) CL=4000 ms CL=500 ms CL=4000 ms CL=500 ms Control (n=15) 72.9± ± ± ±10.7 Sotalol 100 μmol/l (n=6) 73± ± ± ± 16.8 ATX-II 10 nmol/l (n=9) 83.4± ± ± ±24.1 The duration and repolarization time of the transseptal electrogram were measured in similar ways as the QRS and QT in ECG. CL: cycle length. Data are expressed as mean±sd ms and n is the number of preparations. pb0.01 sotalol or ATX-II vs control.
5 100 S.T. Morita et al. / Cardiovascular Research 74 (2007) Fig. 4. Effects of sotalol on APD. Tissues were paced at the LVendo at CLs of 500 (A), 1000 (B), 2000 (C), and 4000 ms (D). The symbols at the top of A indicate the concentrations of sotalol (μmol/l). APDs lengthened progressively from the RV endo (shortest) to LV endo (longest) without midmyocardial (M1, M2, and M3 for 25%, 50%, and 75% transseptum from RVendo) preferential lengthening. Significantly more APD prolongation than at the RVendo are indicated with (pb0.01) and # (pb0.05). Error bars represent SEM (n=6). without midmyocardial maxima at all tested pacing CLs. Increasing the pacing CL from 500 to 4000 ms prolonged APDs significantly, more in the LV endocardium (from 221.4±7.7 to 285.7±15.5 ms, n=22) than in the RV endocardium (from 198.6±6.6 to 248.7±11.5 ms, n=22), thus increasing the transseptal dispersion of APD (from 22.8 ± 5.6 to 37 ± 12.7 ms, n = 22) (Fig. 3), which had clear CLdependency at CL of 2000 ms or less (Fig. 3B). All APs in the IVS had minor phase-1 notch, similar to the endocardial APs in the ventricular free wall. The minor phase-1 notch is most likely a general feature of APs in the IVS, because we previously showed prominent phase-1 notches in the epicardium of similarly prepared canine ventricular free wall wedges under similar conditions using the same mapping system [15,16,2,25]. There was no evidence of M cell-like behavior in any IVS preparation during baseline recordings at CLs 500 to 4000 ms, although APs in the LV endocardium were always longer than in the RV endocardium APDs in the drug-induced models of LQT2 and LQT3 We investigated the functional dynamics of transseptal distribution of APD in the IVS preparations treated with sotalol [27] or ATX-II [16,27,28], which produced druginduced models of LQT2 and LQT3 and were demonstrated to promote the expression of M cells in the canine ventricular free wall [29]. Table 1 summarizes the electrographical findings in the perfused IVS preparations. These data demonstrate that sotalol 100 μmol/l prolonged only the repolarization time, and ATX-II 10 nmol/l prolonged both the duration and repolarization time of the transseptal electrogram. Conduction time patterns were almost the same before and after drugs with little conduction delay produced by drugs. Sotalol and ATX-II prolonged APDs in the IVS (Figs. 4 and 5), with greater prolongation in the LV septal endocardium than in the RV septal endocardium. Increasing the pacing CL also prolonged the APD, more in the LV septal endocardium than in the RV septal endocardium at each concentration of sotalol or ATX-II. Higher concentrations of sotalol and of ATX-II and longer pacing CLs increased the transseptal dispersion of APD (Fig. 6). At the highest sotalol concentration of 100 μmol/l and at a CL of 4000 ms, the LV and RV septal endocardial APDs increased to 1.45±0.04 (n=6) and to 1.26±0.02 (n=6) times their corresponding baseline control values, respectively, without significant differences (p = 0.07) between the relative prolongations in the LVand RV septal endocardium. ATX-II at 10 nmol/l prolonged APD in the LV septal endocardium 3.65± 0.32 (n=9) times and in the RV septal endocardium 3.39±0.33 (n = 9) times the corresponding baseline control values (CL: 4000 ms), but the difference between the relative
6 S.T. Morita et al. / Cardiovascular Research 74 (2007) Fig. 5. Effect of ATX-II on APDs. Tissues were paced at the LV endo at the CL of 500 (A), 1000 (B), 2000 (C), and 4000 ms (D). The symbols at the top of A indicate the concentrations of ATX-II (nmol/l). Similar to the effects of sotalol in Fig. 4, APDs progressively lengthened from the RV endo (shortest) to LV endo (longest) without excessive midmyocardial (M1 3) APDs lengthening. Significantly more APD prolongation than at the RV endo are indicated with (pb0.01) and # (pb0.05). Error bars represent SEM (n=9). prolongations in the LV and RV septal endocardium was not significant (p =0.36). Similar to the baseline recordings, there was no midmyocardial maxima of APD in all preparations treated with sotalol or ATX-II, even at the highest tested concentrations of sotalol (100 μmol/l) and ATX-II (10.0 nmol/l) and at the longest pacing CL (4000 ms). APDs prolonged with increasing CL from 500 to 4000 ms and lengthened progressively from the shortest APDs at the RV septal endocardium (sotalol: 309±36.2 ms, n=6; ATX-II: 857.2± ms, n=9, CL=4000 ms) to the longest APDs at the LV septal endocardium (sotalol: ± 71.5 ms; ATX-II: ± 176 ms) with significant APD differences between the RV and LV septal endocardium (p b ). Therefore, there was no evidence of M cell phenotypes in the IVS druginduced models of LQT2 and LQT3. 4. Discussion lengthening progressively from the right to left ventricular endocardium across the IVS without a midmyocardial maximum under all tested conditions. This occurred during bradycardia, sotalol, and ATX-II, which prolonged APD and increased its transseptal dispersion and were demonstrated previously to promote phenotypical expression of M cells in canine ventricular free wall [4,5,6,7,16,27], in contrast to the absence of M cell expression in IVS in the current study. We conclude that, in this investigation, the studied region of IVS had electrophysiological characteristics similar to the endocardium of ventricular free wall with gradual transseptal AP transition and without phenotypic expression of M cells. The current observations differed from a prior study that reported the presence of M cells in deep subendocardial layers of superfused strips of canine IVS tissue [6]. The different observations might be related to the differences between arterial perfusion (in the current study) and superfusion (in the prior study) New observations We observed on the cut-exposed transseptal surface that all APs lacked a prominent phase-1 notch with APD 4.2. Possible mechanisms The present observations correspond well with a molecular study on the differences between LV and RV septal
7 102 S.T. Morita et al. / Cardiovascular Research 74 (2007) Fig. 6. Dependencies of the transseptal dispersion of APD on pacing CL, sotalol (n=6, A), and ATX-II (n=9, B). Transseptal dispersion of APDs was calculated from the APD differences between the LV endo (the longest) and RVendo (the shortest) in the same tissue. The transseptal dispersions of APD were expanded by increasing concentrations of sotalol (A) and ATX-II (B) and by longer CLs (indicated at the top of A). Statistically significant increase in the transseptal dispersion of APD from the corresponding drug-free controls are indicated with (pb0.01) and # (pb0.05). Error bars represent SD. endocardium in the relevant mrnas encoding major ionic channels in canine IVS. Ramakers et al. [18] found that the levels of KChIP2, NCX, and KCNQ1, which are mrnas encoding the β subunit of I to channel, Na Ca exchanger, and α subunit of I Ks channel, respectively, were significantly higher in the right half than in the left half of IVS. They also observed similar APs and similar levels of KChlP2 and KCNQ1 between the right septal endocardium and the endocardium of right ventricular free wall, and between the left septal endocardium and the endocardium of left ventricular free wall. The present observations are also in agreement with a previous report showing that isolated mid-septal myocytes had APDs midway between those recorded in the isolated LV septal endocardial myocytes (longest APDs) and RV septal endocardial myocytes (shortest APDs) in the basal sections of guinea-pig IVS [30]. Both the above mrna [18] and isolated myocytes [30] studies suggested the absence of M cell phenotypes were the cellular property of the septum, rather than being caused by electrotonic suppression from intercellular coupling, which reduces electrical heterogeneity in cardiac tissue. The current optical mapping and above molecular and isolated cell studies correspond well with the embryonic development of the IVS, formed by expansion of both RV and LV endocardium [31] and support the notion that canine RV and LV septal endocardium have electrophysiological properties similar to the respective endocardium of right and left ventricular free walls Differences between IVS and ventricular free wall We reported previously the presence of M cell phenotypes during ATX-II perfusion and long pacing CL and observed prominent phase-1 notches in the epicardial APs in canine ventricular free wall [2,16,25]. However, in the current study we found no phenotypic expression of M cells and minor phase-1 notches in all AP in the canine IVS, although similar experimental protocols and the same instrument and drugs were used. Therefore, the differences in the manifestation of M cell phenotypes and in the morphology of AP were due to the substrate differences between IVS and ventricular free wall, which can be related to their differences in embryonic development [31]. The observation of M cell phenotypes in the left ventricular free wall indicated that presence of intact intercellular coupling was not the cause of absence of M cell phenotypes in the septum preparations. The absence of M cell phenotypes in the IVS suggests that, unlike the ventricular free wall, the septum has no midmyocardial region having low repolarization reserve [1,2].Our results also suggest that one of the mechanisms of arrhythmogenesis, focal activation by early afterdepolarizations arising from the phase-2 domes of APs in the M cell regions, as demonstrated in ventricular free walls having LQTS [2,25], may play a less important role in the IVS. Instead, the IVS may contribute to arrhythmogenesis by providing pathways for reentry loops [32] and by other mechanisms of focal activation such as delayed afterdepolarizations IKr and INa alterations in the canine septal preparations Transmural heterogeneity in membrane densities of repolarization currents has been reported in the canine ventricular free wall [5], although it is still unclear whether similar heterogeneity exists in the IVS. We manipulated I Kr and I Na with sotalol and ATX-II, two drugs demonstrated previously to promote the expression of M cell phenotypes in canine ventricular free wall [31,33 37]. We observed that both drugs prolonged APD without evoking phenotypical expression of M cells and increased the transseptal dispersion of APD in IVS. At similar APD prolongation, sotalol increased the transseptal dispersion of APD more than ATX-II (Figs. 4D and 5D). The differences suggested that I Kr blockade with sotalol exposed more transseptal
8 S.T. Morita et al. / Cardiovascular Research 74 (2007) heterogeneity in the remaining repolarization currents than enhancing the late I Na with ATX-II. Acknowledgements This research was supported by award Z from American Heart Association Midwest Affiliation and by the Herman C. Krannert Fund, Indianapolis. References [1] Roden DM. Taking the idio out of idiosyncratic : predicting torsades de pointes. Pacing Clin Electrophysiol 1998;21: [2] Ueda N, Zipes DP, Wu J. Prior ischemia enhances arrhythmogenicity in isolated canine ventricular wedge model of long QT 3. Cardiovasc Res 2004;63: [3] van Dam R, Durrer D. Experimental study on the intramural distribution of the excitability cycle and on the form of the epicardial T wave in the dog heart in situ. Am Heart J 1961;61: [4] Sicouri S, Antzelevitch C. A subpopulation of cells with unique electrophysiological properties in the deep subepicardium of the canine ventricle: the M cell. Circ Res 1991;68: [5] Antzelevitch C. Modulation of transmural repolarization. Ann N Y Acad Sci 2005;1047: [6] Sicouri S, Fish J, Antzelevitch C. Distribution of M cells in the canine ventricle. J Cardiovasc Electrophysiol 1994;5: [7] Antzelevitch C, Shimizu W, Yan GX, Sicouri S, Weissenburger J, Nesterenko VV, et al. The M cell: its contribution to the ECG and to normal and abnormal electrical function of the heart. J Cardiovasc Electrophysiol 1999;10: [8] Yan GX, Antzelevitch C. Cellular basis for the normal T wave and the electrocardiographic manifestations of the long-qt syndrome. Circulation 1998;98: [9] Antzelevitch C, Sicouri S. Clinical relevance of cardiac arrhythmias generated by afterdepolarizations: the role of M cells in the generation of U waves, triggered activity and torsade de pointes. J Am Coll Cardiol 1994;23: [10] Sosunov EA, Anyukhovsky EP, Rosen MR. Effects of quinidine on repolarization in canine epicardium, midmyocardium, and endocardium: I. in vitro study. Circulation 1997;96(11): [11] Taggart P, Sutton PM, Opthof T, Coronel R, Trimlett R, Pugsley W, et al. Transmural repolarisation in the left ventricle in humans during normoxia and ischaemia. Cardiovasc Res 2001;50: [12] Anyukhovsky EP, Sosunov EA, Rosen MR. Regional differences in electrophysiological properties of epicardium, midmyocardium, and endocardium. In vitro and in vivo correlations. Circulation 1996;94: [13] Anyukhovsky EP, Sosunov EA, Gainullin RZ, Rosen MR. The controversial M cell. J Cardiovasc Electrophysiol 1999;10: [14] Taggart P, Sutton P, Opthof T, Coronel R, Kallis P. Electrotonic cancellation of transmural electrical gradients in the left ventricle in man. Prog Biophys Mol Biol 2003;82: [15] Wu J, Biermann M, Rubart M, Zipes DP. Cytochalasin D as excitation contraction uncoupler for optically mapping action potentials in wedges of ventricular myocardium. J Cardiovasc Electrophysiol 1998;9: [16] Ueda N, Zipes DP, Wu J. Functional and transmural modulation of M cell behavior in canine ventricular wall. Am J Physiol Heart Circ Physiol 2004;287:H [17] Akar FG, Yan GX, Antzelevitch C, Rosenbaum DS. Unique topographical distribution of M cells underlies reentrant mechanism of torsade de pointes in the long-qt syndrome. Circulation 2002;105 (10): [18] Ramakers C, Stengl M, Spatjens RL, Moorman AF, Vos MA. Molecular and electrical characterization of the canine cardiac ventricular septum. J Mol Cell Cardiol 2005;38(1): [19] Wu J, Zipes DP. Transmural reentry during acute global ischemia and reperfusion in canine ventricular muscle. Am J Physiol Heart Circ Physiol 2001;280:H [20] Calaghan SC, White E, Bedut S, Le Guennec JY. Cytochalasin D reduces Ca 2+ sensitivity and maximum tension via interactions with myofilaments in skinned rat cardiac myocytes. J Physiol (Lond) 2000;529: [21] Biermann M, Rubart M, Moreno A, Wu J, Josiah-Durant A, Zipes DP. Differential effects of cytochalasin D and 2,3 butanedione monoxime on isometric twitch force and transmembrane action potential in isolated ventricular muscle: implications for optical measurements of cardiac repolarization. J Cardiovasc Electrophysiol 1998;9: [22] Yang X, Salas PJ, Pham TV, Wasserlauf BJ, Smets MJ, Myerburg RJ, et al. Cytoskeletal actin microfilaments and the transient outward potassium current in hypertrophied rat ventriculocytes. J Physiol (Lond) 2002;541: [23] Jalife J, Morley GE, Tallini NY, Vaidya D. A fungal metabolite that eliminates motion artifacts. J Cardiovasc Electrophysiol 1998;9: [24] Zicha S, Moss I, Allen B, Varro A, Papp J, Dumaine R, et al. Molecular basis of species-specific expression of repolarizing K+currents in the heart. Am J Physiol Heart Circ Physiol 2003;285:H [25] Ueda N, Zipes DP, Wu J. Coronary occlusion and reperfusion promote early afterdepolarizations and ventricular tachycardia in a canine tissue model of type 3 long QT syndrome. Am J Physiol Heart Circ Physiol 2006;290:H [26] Morita H, Zipes DP, Lopshire J, Morita ST, Wu J. T wave alternans in an in vitro canine tissue model of Brugada syndrome. Am J Physiol Heart Circ Physiol 2006;291:H [27] Shimizu W, Antzelevitch C. Differential effects of beta-adrenergic agonists and antagonists in LQT1, LQT2 and LQT3 models of the long QT syndrome. J Am Coll Cardiol 2000;35: [28] Boutjdir M, el-sherif N. Phamacological evaluation of early afterdepolarisations induced by sea anemone toxin (ATX II) in dog heart. Cardiovasc Res 1991;25: [29] Sicouri S, Antzelevitch D, Heilmann C, Antzelevitch C. Effects of sodium channel block with mexiletine to reverse action potential prolongation in in vitro models of the long term QT syndrome. J Cardiovasc Electrophysiol 1997;8: [30] Wan X, Bryant SM, Hart G. A topographical study of mechanical and electrical properties of single myocytes isolated from normal guineapig ventricular muscle. J Anat 2003;202: [31] Keller BB, Wessels A, Roger R. Markwald Foundations of cardiovascular medicine: mechanisms of cardiac septation. Hurst's The Heart11th ed.. McGraw-Hill Co, Inc.; 2004 [32] El-Sherif N, Chinushi M, Caref EB, Restivo M. Electrophysiological mechanism of the characteristic electrocardiographic morphology of torsade de pointes tachyarrhythmias in the long-qt syndrome: detailed analysis of ventricular tridimensional activation patterns. Circulation 1997;96(12): [33] Curran ME, Splawski I, Timothy KW, Vincent GM, Green ED, Keating MT. A molecular basis for cardiac arrhythmia: HERG mutations cause long QT syndrome. Cell 1995;80: [34] Sanguinetti MC, Curran ME, Spector PS, Keating MT. Spectrum of HERG K+-channel dysfunction in an inherited cardiac arrhythmia. Proc Natl Acad Sci 1996;93: [35] Wang Q, Shen J, Splawski I, Atkinson D, Li Z, Robinson JL, et al. SCN5A mutations associated with an inherited cardiac arrhythmia, long QT syndrome. Cell 1995;80: [36] Bennett PB, Yazawa K, Makita N, George Jr AL. Molecular mechanism for an inherited cardiac arrhythmia. Nature 2002;376: [37] Priori SG, Napolitano C, Cantu F, Brown AM, Schwartz PJ. Differential response to Na + channel blockade, beta-adrenergic stimulation, and rapid pacing in a cellular model mimicking the SCN5A and HERG defects present in the long-qt syndrome. Circ Res 1996;78:
Phase 2 Early Afterdepolarization as a Trigger of Polymorphic Ventricular Tachycardia in Acquired Long-QT Syndrome
Phase 2 Early Afterdepolarization as a Trigger of Polymorphic Ventricular Tachycardia in Acquired Long-QT Syndrome Direct Evidence From Intracellular Recordings in the Intact Left Ventricular Wall Gan-Xin
More informationTriggers of Ventricular Tachyarrhythmias and Therapeutic Effects of Nicorandil in Canine Models of LQT2 and LQT3 Syndromes
Journal of the American College of Cardiology Vol. 40, No. 3, 2002 2002 by the American College of Cardiology Foundation ISSN 0735-1097/02/$22.00 Published by Elsevier Science Inc. PII S0735-1097(02)01975-7
More informationBody surface electrocardiograms and electrograms recorded
Ionic Current Basis of Electrocardiographic Waveforms A Model Study Kazutaka Gima, Yoram Rudy Abstract Body surface electrocardiograms and electrograms recorded from the surfaces of the heart are the basis
More informationEffect of an Increase in Coronary Perfusion on Transmural Ventricular Repolarization
Physiol. Res. 56: 285-290, 2007 Effect of an Increase in Coronary Perfusion on Transmural Ventricular Repolarization Y.-Z. ZHANG 1, B. HE 1, L.-X. WANG 2 1 Department of Cardiology, Renji Hospital, Medical
More informationEffect of an increase in coronary perfusion on transmural. ventricular repolarization
Effect of an increase in coronary perfusion on transmural ventricular repolarization Yan-Zhou Zhang 1, MD, PhD, Ben He 1, MD, Le-Xin Wang 2, MD, PhD. From: 1 Department of Cardiology, Renji Hospital, Medical
More informationJ Wave Syndromes. Osama Diab Lecturer of Cardiology Ain Shams University
J Wave Syndromes Osama Diab Lecturer of Cardiology Ain Shams University J Wave Syndromes Group of electric disorders characterized by > 1 mm elevation of the J point or prominent J wave with or without
More informationSympathetic modulation of the long QT syndrome
European Heart Journal (2002) 23, 1246 1252 doi:10.1053/euhj.2002.3287, available online at http://www.idealibrary.com on Sympathetic modulation of the long QT syndrome See Eur Heart J 2002; 23: 975 93
More informationAsyndrome of sudden death characterized by ST-segment
Ionic and Cellular Basis for the Predominance of the Brugada Syndrome Phenotype in Males José M. Di Diego, MD; Jonathan M. Cordeiro, PhD; Robert J. Goodrow, BS; Jeffrey M. Fish, DVM; Andrew C. Zygmunt,
More informationT-wave alternans (TWA), an ECG phenomenon characterized. Cellular and Ionic Basis for T-Wave Alternans Under Long-QT Conditions
Cellular and Ionic Basis for T-Wave Alternans Under Long-QT Conditions Wataru Shimizu, MD, PhD; Charles Antzelevitch, PhD Background T-wave alternans (TWA), an ECG phenomenon characterized by beat-to-beat
More informationCME Article Brugada pattern masking anterior myocardial infarction
Electrocardiography Series Singapore Med J 2011; 52(9) : 647 CME Article Brugada pattern masking anterior myocardial infarction Seow S C, Omar A R, Hong E C T Cardiology Department, National University
More informationElectrophysiological Mechanism of Enhanced Susceptibility of Hypertrophied Heart to Acquired Torsade de Pointes Arrhythmias
Electrophysiological Mechanism of Enhanced Susceptibility of Hypertrophied Heart to Acquired Torsade de Pointes Arrhythmias Tridimensional Mapping of Activation and Recovery Patterns Dmitry O. Kozhevnikov,
More informationEffects of I Kr and I Ks Heterogeneity on Action Potential Duration and Its Rate Dependence
Effects of I Kr and I Ks Heterogeneity on Action Potential Duration and Its Rate Dependence A Simulation Study Prakash C. Viswanathan, BE; Robin M. Shaw, PhD; Yoram Rudy, PhD Background A growing body
More informationBrugada syndrome is characterized by peculiar ST elevation
Mechanism of ST Elevation and Ventricular Arrhythmias in an Experimental Brugada Syndrome Model Masaomi Kimura, MD; Takao Kobayashi, MD; Shingen Owada, MD; Keiichi Ashikaga, MD; Takumi Higuma, MD; Shingo
More informationCOPYRIGHTED MATERIAL. The role of spatial dispersion of repolarization and intramural reentry in inherited and acquired sudden cardiac death syndromes
1 CHAPTER Abstract 1 The role of spatial dispersion of repolarization and intramural reentry in inherited and acquired sudden cardiac death syndromes Charles Antzelevitch The cellular basis for intramural
More informationHeterogeneous Ventricular Repolarization Provides a Substrate for Arrhythmias in a German Shepherd Model of Spontaneous Arrhythmic Death
Heterogeneous Ventricular Repolarization Provides a Substrate for Arrhythmias in a German Shepherd Model of Spontaneous Arrhythmic Death Maria N. Obreztchikova, PhD; Eugene A. Sosunov, PhD; Evgeny P. Anyukhovsky,
More informationTorsadedepointesarrhythmiasariseatthesiteof maximal heterogeneity of repolarization in the chronic complete atrioventricular block dog
Europace (217) 19, 858 865 doi:1.193/europace/euw87 BASIC SCIENCE Torsadedepointesarrhythmiasariseatthesiteof maximal heterogeneity of repolarization in the chronic complete atrioventricular block dog
More informationClinical and Electrocardiographic Characteristics of Patients with Brugada Syndrome: Report of Five Cases of Documented Ventricular Fibrillation
J Arrhythmia Vol 25 No 1 2009 Original Article Clinical and Electrocardiographic Characteristics of Patients with Brugada Syndrome: Report of Five Cases of Documented Ventricular Fibrillation Seiji Takashio
More informationJ-wave syndromes: update on ventricular fibrillation mechanisms
J-wave syndromes: update on ventricular fibrillation mechanisms Michael Nabauer University of Munich, Germany 28.8.2011 I have no conflicts of interest ECG labelling by Einthoven Circ 1998 Osborn wave
More informationThe Electrophysiologic Mechanism of ST-Segment Elevation in Brugada Syndrome
Journal of the American College of Cardiology Vol. 40, No. 2, 2002 2002 by the American College of Cardiology Foundation ISSN 0735-1097/02/$22.00 Published by Elsevier Science Inc. PII S0735-1097(02)01964-2
More informationCLINICAL INVESTIGATIONS. Methods
CLINICAL INVESTIGATIONS Jpn Circ J 2001; 65: 702 706 Correlation Between the Effective Refractory Period and Activation-Recovery Interval Calculated From the Intracardiac Unipolar Electrogram of Humans
More informationMicrostructural Basis of Conduction II Introduction to Experimental Studies
Bioeng 6460 Electrophysiology and Bioelectricity Microstructural Basis of Conduction II Introduction to Experimental Studies Frank B. Sachse fs@cvrti.utah.edu Overview Microstructural Basis of Conduction
More informationBasics of Structure/Function of Sodium and Potassium Channels Barry London, MD PhD
Basics of Structure/Function of Sodium and Potassium Channels Barry London, MD PhD University of Pittsburgh Medical Center Pittsburgh, PA International Symposium of Inherited Arrhythmia Disorders and Hypertrophic
More informationΦαρμακεσηική αγωγή ζηις ιδιοπαθείς κοιλιακές αρρσθμίες. Άννα Κωζηοπούλοσ Επιμελήηρια Α Ωνάζειο Καρδιοτειροσργικό Κένηρο
Φαρμακεσηική αγωγή ζηις ιδιοπαθείς κοιλιακές αρρσθμίες Άννα Κωζηοπούλοσ Επιμελήηρια Α Ωνάζειο Καρδιοτειροσργικό Κένηρο Όλες οι κοιλιακές αρρσθμίες δεν είναι ίδιες Υπάρτοσν διαθορές ζηον πληθυσμό, ηον μηχανισμό
More informationModulation of the late sodium current by ATX-II and ranolazine affects the reverse use-dependence and proarrhythmic liability of I Kr blockade
308..316 British Journal of Pharmacology DOI:10.1111/j.1476-5381.2010.01181.x www.brjpharmacol.org RESEARCH PAPERbph_1181 Modulation of the late sodium current by ATX-II and ranolazine affects the reverse
More informationModeling of Anatomy, Electrophysiology and Tension Development in the Human Heart
European Functional Cardiac Modeling Meeting Modeling of Anatomy, Electrophysiology and Tension Development in the Human Heart Dr.-Ing. Gunnar Seemann Overview Electrophysiology Tension development Anatomy
More informationIntroduction. Circulation
Introduction Circulation 1- Systemic (general) circulation 2- Pulmonary circulation carries oxygenated blood to all parts of the body carries deoxygenated blood to the lungs From Lt. ventricle aorta From
More informationLeft cardiac sympathectomy to manage beta-blocker resistant LQT patients
Left cardiac sympathectomy to manage beta-blocker resistant LQT patients Lexin Wang, M.D., Ph.D. Introduction Congenital long QT syndrome (LQTS) is a disorder of prolonged cardiac repolarization, manifested
More informationIn vivo studies of Scn5a+/ mice modeling Brugada syndrome demonstrate both conduction and repolarization abnormalities
Available online at www.sciencedirect.com Journal of Electrocardiology 43 (2010) 433 439 www.jecgonline.com In vivo studies of Scn5a+/ mice modeling Brugada syndrome demonstrate both conduction and repolarization
More informationBlocking the Late Sodium Current
Non-classical Targets in Antiarrhythmic Therapy Blocking the Late Sodium Current Luiz Belardinelli, MD SVP, Cardiovascular Therapeutics Gilead Sciences, CA, USA Madrid June 28, 2011 Disclosures: Full time
More informationCase Report. Faculty of Medicine, Oita University 2 Department of Cardiology, Hakuaikai Hospital
Case Report Manifestation of ST-Segment Elevation in Right Precordial Leads during schemia at a Right Ventricular Outflow Tract rea in a Patient with rugada Syndrome Naohiko Takahashi MD 1, Tetsuji Shinohara
More informationClinical observations have shown that conduction abnormalities
Arrhythmia/Electrophysiology Fragmented QRS as a Marker of Conduction Abnormality and a Predictor of Prognosis of Brugada Syndrome Hiroshi Morita, MD; Kengo F. Kusano, MD; Daiji Miura, PhD; Satoshi Nagase,
More informationCardiac physiology. b. myocardium -- cardiac muscle and fibrous skeleton of heart
I. Heart anatomy -- general gross. A. Size/orientation - base/apex B. Coverings D. Chambers 1. parietal pericardium 2. visceral pericardium 3. Layers of heart wall a. epicardium Cardiac physiology b. myocardium
More informationEffects of adrenergic activation to the action potentials and ionic currents of cardiac cells. by Ferenc Ruzsnavszky MD
SHORT THESIS FOR THE DEGREE OF DOCTOR OF PHILOSOPHY (PhD) Effects of adrenergic activation to the action potentials and ionic currents of cardiac cells by Ferenc Ruzsnavszky MD Supervisor: Prof. János
More informationCytosolic calcium accumulation and delayed repolarization associated with ventricular arrhythmias in a guinea pig model of Andersen-Tawil syndrome
Cytosolic calcium accumulation and delayed repolarization associated with ventricular arrhythmias in a guinea pig model of Andersen-Tawil syndrome Przemysław B. Radwański, PharmD,* Rengasayee Veeraraghavan,*
More informationRate- and Site-Dependent Effects of Propafenone, Dofetilide, and the New I
Rate- and Site-Dependent Effects of Propafenone, Dofetilide, and the New I Ks -Blocking Agent Chromanol 293b on Individual Muscle Layers of the Intact Canine Heart Alexander Bauer, MD; Ruediger Becker,
More informationThe effect of acidosis on the ECG of the rat heart
The effect of acidosis on the ECG of the rat heart A. Aberra*, K. Komukai, F. C. Howarth and C. H. Orchard School of Biomedical Sciences, University of Leeds, Leeds LS2 9NL, UK, * Faculty of Medicine,
More informationDimethyl Lithospermate B, an Extract of Danshen, Suppresses Arrhythmogenesis Associated With the Brugada Syndrome
Dimethyl Lithospermate B, an Extract of Danshen, Suppresses Arrhythmogenesis Associated With the Brugada Syndrome Jeffrey M. Fish, DVM; Daniel R. Welchons; Young-Sup Kim, PhD; Suk-Ho Lee, MD, PhD; Won-Kyung
More informationMutations to the cardiac potassium channel gene KCNQ1
Arrhythmia/Electrophysiology Subunit Interaction Determines I Ks Participation in Cardiac Repolarization and Repolarization Reserve Jonathan Silva, MS; Yoram Rudy, PhD Background The role of I Ks, the
More informationName of Presenter: Marwan Refaat, MD
NAAMA s 24 th International Medical Convention Medicine in the Next Decade: Challenges and Opportunities Beirut, Lebanon June 26 July 2, 2010 I have no actual or potential conflict of interest in relation
More informationAmiodarone Reduces Transmural Heterogeneity of Repolarization in the Human Heart
1063 Amiodarone Reduces Transmural Heterogeneity of Repolarization in the Human Heart EMMANUEL DROUIN, PHD,* GILLES LANDE, MD, FLAVIEN CHARPENTIER, PHD Nantes, France Objectives. The present work was designed
More informationTdP Mechanisms and CiPA
TdP Mechanisms and CiPA Craig T. January, MD, PhD Division of Cardiovascular Medicine University of Wisconsin-Madison Cardiac Safety Research Consortium Hilton Washington DC December 6, 2016 Disclosures
More informationShort QT Syndrome: Pharmacological Treatment
Journal of the American College of Cardiology Vol. 43, No. 8, 2004 2004 by the American College of Cardiology Foundation ISSN 0735-1097/04/$30.00 Published by Elsevier Inc. doi:10.1016/j.jacc.2004.02.034
More informationIncreased Short-Term Variability of Repolarization Predicts d-sotalol Induced Torsades de Pointes in Dogs
Increased Short-Term Variability of Repolarization Predicts d-sotalol Induced Torsades de Pointes in Dogs Morten B. Thomsen, MSc; S. Cora Verduyn, PhD; Milan Stengl, PhD; Jet D.M. Beekman; Geert de Pater,
More informationDispersion of myocardial repolarization contributes to arrhythmia
Imaging Dispersion of Myocardial Repolarization, I Comparison of Body-Surface and Epicardial Measures John E. Burnes, PhD; Raja N. Ghanem, MS; Albert L. Waldo, MD; Yoram Rudy, PhD Background Body-surface
More informationInstability in action potential morphology underlies phase 2 reentry: A mathematical modeling study
Instability in action potential morphology underlies phase 2 reentry: A mathematical modeling study Anat Maoz, BS,* Trine Krogh-Madsen, PhD,* David J. Christini, PhD* From the *Greenberg Division of Cardiology,
More informationAntiarrhythmic Effects of Ranolazine in a Guinea Pig in Vitro Model of Long-QT Syndrome
0022-3565/04/3102-599 605$20.00 THE JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS Vol. 310, No. 2 Copyright 2004 by The American Society for Pharmacology and Experimental Therapeutics 66100/1155498
More informationMapping Cardiac Pacemaker Circuits: Methodological puzzles of SAN optical mapping
Mapping Cardiac Pacemaker Circuits: Methodological puzzles of SAN optical mapping Igor R. Efimov, Vadim V. Fedorov, Boyoung Joung, and Shien-Fong Lin Journal of American College of Cardiology, 66(18):1976-86,
More informationArrhythmias. Simple-dysfunction cause abnormalities in impulse formation and conduction in the myocardium.
Arrhythmias Simple-dysfunction cause abnormalities in impulse formation and conduction in the myocardium. However, in clinic it present as a complex family of disorders that show variety of symptoms, for
More informationThe action potential and the underlying ionic currents. Norbert Jost, PhD
The action potential and the underlying ionic currents Norbert Jost, PhD The propagation of the stimulation in the heart Sinus node Left atria His Bundle Conduction velocity in m/s Time to arrive from
More informationLong-term cardiac memory in canine heart is associated with the evolution of a transmural repolarization gradient
Cardiovascular Research 74 (2007) 416 425 www.elsevier.com/locate/cardiores Long-term cardiac memory in canine heart is associated with the evolution of a transmural repolarization gradient Ruben Coronel
More informationAntiarrhythmic Drugs
Antiarrhythmic Drugs DR ATIF ALQUBBANY A S S I S T A N T P R O F E S S O R O F M E D I C I N E / C A R D I O L O G Y C O N S U L T A N T C A R D I O L O G Y & I N T E R V E N T I O N A L E P A C H D /
More informationAlthough reduced repolarization reserve of the myocardium
Fever Accentuates Transmural Dispersion of Repolarization and Facilitates Development of Early Afterdepolarizations and Torsade de Pointes Under Long-QT Conditions Alexander Burashnikov, PhD; Wataru Shimizu,
More informationoptical mapping analysis Tyrode connexin43 Sprague Dawley male 8 weeks old g n 64 ketamine hydrochloride 5 mg/kg
14 Symposium 39 optical mapping SD 1 4 1 2 4 Tyrode Na channel di 4 ANEPPS action potential duration dispersion APDd VTVF 1 2 4 APDd VT/VF 30 1,2 3 optical mapping analysis connexin43 1 Sprague Dawley
More informationCase Report Suppression of Frequent Ventricular Ectopy in a Patient with Hypertrophic Heart Disease with Ranolazine: A Case Report
www.ipej.org 84 Case Report Suppression of Frequent Ventricular Ectopy in a Patient with Hypertrophic Heart Disease with Ranolazine: A Case Report David K. Murdock, MD 1,2 and Jeffrey W. Kaliebe, MT(ASCP),
More informationArrhythmias. 1. beat too slowly (sinus bradycardia). Like in heart block
Arrhythmias It is a simple-dysfunction caused by abnormalities in impulse formation and conduction in the myocardium. The heart is designed in such a way that allows it to generate from the SA node electrical
More informationEHRA Accreditation Exam - Sample MCQs Invasive cardiac electrophysiology
EHRA Accreditation Exam - Sample MCQs Invasive cardiac electrophysiology Dear EHRA Member, Dear Colleague, As you know, the EHRA Accreditation Process is becoming increasingly recognised as an important
More informationDifferences in cardiac atrial and ventricular ion channels
Differences in cardiac atrial and ventricular ion channels Norbert Jost, PhD Department of Pharmacology & Pharmacotherapy, University of Szeged Division for Cardiovascular Pharmacology, Hungarian Academy
More informationA tale of two dogs: analyzing two models of canine ventricular electrophysiology
Am J Physiol Heart Circ Physiol 292: H43 H55, 2007. First published September 22, 2006; doi:10.1152/ajpheart.00955.2006. CALL FOR PAPERS Computational Analyses in Ion Channelopathies A tale of two dogs:
More informationEffects of Ectopic Pacing on Repolarization of the Chicken Left Ventricle
Physiol. Res. 58: 351-361, 2009 Effects of Ectopic Pacing on Repolarization of the Chicken Left Ventricle S. N. KHARIN, D. N. SHMAKOV, N. A. ANTONOVA Laboratory of Cardiac Physiology, Institute of Physiology,
More informationExtensive evidence supports the concept that dual atrioventricular
Mechanisms Underlying the Reentrant Circuit of Atrioventricular Nodal Reentrant Tachycardia in Isolated Canine Atrioventricular Nodal Preparation Using Optical Mapping Jianyi Wu, Jiashin Wu, Jeffrey Olgin,
More informationPolymorphic ventricular tachycardia (VT) has been reported
Polymorphic Reentrant Ventricular Tachycardia in the Isolated Rabbit Heart Studied by High-Density Mapping Lucas Boersma, MD, PhD; Zoltan Zetelaki, MSc; Josep Brugada, MD, PhD; Maurits Allessie, MD, PhD
More informationThe duration of the canine ventricular action potential
Contribution of I Kr to Rate-Dependent Action Potential Dynamics in Canine Endocardium Fei Hua, Robert F. Gilmour, Jr Abstract Previous modeling studies have suggested that the rapid component of the delayed
More informationIdiopathic Long QT Syndrome With Early Afterdepolarization Induced by Epinephrine
CASE REPORTS Circ J 2004; 68: 587 591 Idiopathic Long QT Syndrome With Early Afterdepolarization Induced by Epinephrine A Case Report Norifumi Urao, MD; Hirokazu Shiraishi, MD; Kazuya Ishibashi, MD; Masayuki
More informationCONGENITAL LONG QT SYNDROME(CLQTS) ASSOCIATED WITH COMPLETE ATRIOVENTRICULAR BLOCK. A CASE REPORT.
CONGENITAL LONG QT SYNDROME(CLQTS) ASSOCIATED WITH COMPLETE ATRIOVENTRICULAR BLOCK. A CASE REPORT. SAHA Annual Congress 2017. Samkelo Jiyana, Adele Greyling, Andile Nxele, ZM,Makrexeni,L.Pepeta. BACKGROUND
More informationChapter 12: Cardiovascular Physiology System Overview
Chapter 12: Cardiovascular Physiology System Overview Components of the cardiovascular system: Heart Vascular system Blood Figure 12-1 Plasma includes water, ions, proteins, nutrients, hormones, wastes,
More informationBrugada Syndrome: An Update
Brugada Syndrome: An Update Osama Diab Associate professor of Cardiology Ain Shams university, Cairo, Egypt Updates Mechanism and Genetics Risk stratification Treatment 1 Brugada syndrome causes 4 12%
More informationMechanisms Underlying Conduction Slowing and Arrhythmogenesis in Nonischemic Dilated Cardiomyopathy
Mechanisms Underlying Conduction Slowing and Arrhythmogenesis in Nonischemic Dilated Cardiomyopathy Fadi G. Akar, David D. Spragg, Richard S. Tunin, David A. Kass, Gordon F. Tomaselli Abstract Heart Failure
More informationSEMINAIRES IRIS. Sudden cardiac death in the adult. Gian Battista Chierchia. Heart Rhythm Management Center, UZ Brussel. 20% 25% Cancers !
Sudden cardiac death in the adult Gian Battista Chierchia. Heart Rhythm Management Center, UZ Brussel.! " # $ % Cancers National Vital Statistics Report, Vol 49 (11), Oct. 12, 2001. 20% 25% State-specific
More informationDr Wilde, could you please begin by describing the strongest key evidence in support of the depolarisation hypothesis?
Welcome to the Journal of Molecular and Cellular Cardiology Podcast on the Pathophysiological Mechanism of the Brugada Syndrome. My name is from the Department of Pharmacology at the University of California
More informationMontreal, Quebec, Canada H1T 1C8 b Aventis Pharmaceuticals, Frankfurt, Germany
Cardiovascular Research 61 (2004) 705 714 www.elsevier.com/locate/cardiores In vivo electrophysiological effects of a selective slow delayed-rectifier potassium channel blocker in anesthetized dogs: potential
More informationQuinidine for Brugada syndrome: Panacea or poison?
Quinidine for Brugada syndrome: Panacea or poison? Jo-Jo Hai, MBBS, * Chun-Ka Wong, MBBS, * Pak-Hei Chan, MBBS, * Hung-Fat Tse, MD, PhD, * Tak-Cheung Yung, MBBS, Chung-Wah Siu, MD From the * Division of
More informationTransmural Dispersion of Myofiber Mechanics
Journal of the American College of Cardiology Vol. 49, No. 8, 2007 2007 by the American College of Cardiology Foundation ISSN 0735-1097/07/$32.00 Published by Elsevier Inc. doi:10.1016/j.jacc.2006.07.074
More informationHeart. Heart 2-Tunica media: middle layer (media ='middle') muscle fibers (smooth or cardiac).
t. innermost lumenal General Circulatory system heart and blood vessels walls have 3 layers (inside to outside) 1-Tunica interna: aka tunica intima layer--lumenal layer epithelium--endothelium simple squamous
More informationAssessment of pro-arrhythmic effects using Pluricyte Cardiomyocytes. on the ACEA xcelligence RTCA CardioECR
Assessment of pro-arrhythmic effects using Pluricyte Cardiomyocytes on the ACEA xcelligence RTCA CardioECR Application Note Version 2.1 / March 2018 Contents 1. Introduction 1 2. Assessment of pro-arrhythmic
More informationEffect of Simulated I to on Guinea Pig and Canine Ventricular Action Potential Morphology
Page 1 of Articles 31 in PresS. Am J Physiol Heart Circ Physiol (March 24, 2006). doi:10.1152/ajpheart.00084.2006 Effect of Simulated I to on Guinea Pig and Canine Ventricular Action Potential Morphology
More informationUvA-DARE (Digital Academic Repository) The T wave: physiology and pathophysiology Meijborg, V.M.F. Link to publication
UvA-DARE (Digital Academic Repository) The T wave: physiology and pathophysiology Meijborg, V.M.F. Link to publication Citation for published version (APA): Meijborg, V. M. F. (2015). The T wave: physiology
More informationCardiac repolarization. The long and short of it *
Europace (2005) 7, S3eS9 Cardiac repolarization. The long and short of it * Charles Antzelevitch* Gordon K. Moe Scholar, Masonic Medical Research Laboratory, 2150 Bleecker Street, Utica, NY 13501-1787,
More informationCARDIOVASCULAR SYSTEM
CARDIOVASCULAR SYSTEM Overview Heart and Vessels 2 Major Divisions Pulmonary Circuit Systemic Circuit Closed and Continuous Loop Location Aorta Superior vena cava Right lung Pulmonary trunk Base of heart
More informationGene annotation for heart rhythm. 1. Control of heart rate 2. Action Potential 3. Ion channels and transporters 4. Arrhythmia 5.
Gene annotation for heart rhythm 1. Control of heart rate 2. Action Potential 3. Ion channels and transporters 4. Arrhythmia 5. EC coupling Control of heart rate Autonomic regulation of heart function
More informationECG CONVENTIONS AND INTERVALS
1 ECG Waveforms and Intervals ECG waveforms labeled alphabetically P wave== represents atrial depolarization QRS complex=ventricular depolarization ST-T-U complex (ST segment, T wave, and U wave)== V repolarization.
More informationPotassium channel activators differentially modulate the effect of sodium channel blockade on cardiac conduction
Acta Physiol 212 Potassium channel activators differentially modulate the effect of sodium channel blockade on cardiac conduction R. Veeraraghavan, 1 A. P. Larsen, 1 N. S. Torres, 1 M. Grunnet 2 and S.
More informationCarvedilol analogue inhibits triggered activities evoked by both early and delayed afterdepolarizations
1 Carvedilol analogue inhibits triggered activities evoked by both early and delayed afterdepolarizations Mitsunori Maruyama, MD, PhD, * Jianmin Xiao, MD, PhD, Qiang Zhou, MD, PhD, Kannan Vembaiyan, PhD,
More informationAlterations in electrical coupling between ventricular
Pharmacological Modulation of Cardiac Gap Junctions to Enhance Cardiac Conduction Evidence Supporting a Novel Target for Antiarrhythmic Therapy Benjamin C. Eloff, MS*; Eran Gilat, DSc*; Xiaoping Wan, MD,
More informationINSTABILITY IN ACTION POTENTIAL MORPHOLOGY UNDERLIES PHASE 2 REENTRY INITIATION
INSTABILITY IN ACTION POTENTIAL MORPHOLOGY UNDERLIES PHASE 2 REENTRY INITIATION by Anat Maoz This thesis/dissertation document has been electronically approved by the following individuals: Christini,David
More informationSudden cardiac death: Primary and secondary prevention
Sudden cardiac death: Primary and secondary prevention By Kai Chi Chan Penultimate Year Medical Student St George s University of London at UNic Sheba Medical Centre Definition Sudden cardiac arrest (SCA)
More informationSPLITTING OF HEART SOUNDS FROM VENTRICULAR
Brit. Heart J., 1965, 27, 691. SPLITTING OF HEART SOUNDS FROM VENTRICULAR ASYNCHRONY IN BUNDLE-BRANCH BLOCK, VENTRICULAR ECTOPIC BEATS, AND ARTIFICIAL PACING* BY EDGAR HABER AND AUBREY LEATHAM From the
More informationMechanisms of Arrhythmogenesis: Focus on Long QT Syndrome (LQTS)
Mechanisms of Arrhythmogenesis: Focus on Long QT Syndrome (LQTS) Craig T. January, MD, PhD Division of Cardiovascular Medicine University of Wisconsin-Madison CSRC-HESI-FDA Rechanneling the Current Cardiac
More informationAblative Therapy for Ventricular Tachycardia
Ablative Therapy for Ventricular Tachycardia Nitish Badhwar, MD, FACC, FHRS 2 nd Annual UC Davis Heart and Vascular Center Cardiovascular Nurse / Technologist Symposium May 5, 2012 Disclosures Research
More informationIs There a Genomic Basis to Acquired Channelopathic disease
Is There a Genomic Basis to Acquired Channelopathic disease Yaniv Bar-Cohen, M.D. Associate Professor of Pediatrics Division of Cardiology / Electrophysiology Children s Hospital Los Angeles Keck School
More informationRepolarisation and refractoriness during early ischaemia in humans
Heart 000;84:65 69 65 The Hatter Institute, Cardiology, Cardiothoracic Surgery, University College London Hospitals, Grafton Way, London WCE 6DB, UK P M I Sutton P Taggart R Trimlett W Pugsley P Kallis
More informationECG Cases and Questions. Ashish Sadhu, MD, FHRS, FACC Electrophysiology/Cardiology
ECG Cases and Questions Ashish Sadhu, MD, FHRS, FACC Electrophysiology/Cardiology 32 yo female Life Insurance Physical 56 yo male with chest pain Terminology Injury ST elevation Ischemia T wave inversion
More informationIntraoperative and Postoperative Arrhythmias: Diagnosis and Treatment
Intraoperative and Postoperative Arrhythmias: Diagnosis and Treatment Karen L. Booth, MD, Lucile Packard Children s Hospital Arrhythmias are common after congenital heart surgery [1]. Postoperative electrolyte
More informationElectrocardiographic Markers Associated with Sotalol-induced Torsades de Pointes
Electrocardiographic Markers Associated with Sotalol-induced Torsades de Pointes Based on Data from the Telemetric and Holter ECG Warehouse (THEW) Initiative Jean-PhiIippe Couderc, PhD Center for Quantitative
More informationQTU Prolongation and Polymorphic Ventricular Tachyarrhythmias Due to Bradycardia-Dependent Early Afterdepolarizations
286 QTU Prolongation and Polymorphic Ventricular Tachyarrhythmias Due to Bradycardia-Dependent Early Afterdepolarizations Afterdepolarizations and Ventricular Arrhythmias Nabil El-Sherif, Robert H. Zeiler,
More informationVentricular Arrhythmias
Presenting your most challenging cases Venice Arrhythmias Ventricular Arrhythmias Gioia Turitto, MD Presenter Disclosure Information A questionable indication for CRT-D in a patient with VT after successful
More informationCardiac Telemetry Self Study: Part One Cardiovascular Review 2017 THINGS TO REMEMBER
Please review the above anatomy of the heart. THINGS TO REMEMBER There are 3 electrolytes that affect cardiac function o Sodium, Potassium, and Calcium When any of these electrolytes are out of the normal
More informationGenetics of Sudden Cardiac Death. Geoffrey Pitt Ion Channel Research Unit Duke University. Disclosures: Grant funding from Medtronic.
Genetics of Sudden Cardiac Death Geoffrey Pitt Ion Channel Research Unit Duke University Disclosures: Grant funding from Medtronic Duke U N I V E R S I T Y Sudden Cardiac Death High incidence 50-100 per
More informationNcardia. Assessment of pro-arrhythmic effects in Pluricyte Cardiomyocytes. using the Axion BioSystems Maestro TM MEA system
Ncardia Stem cell experts Assessment of pro-arrhythmic effects in Pluricyte Cardiomyocytes using the Axion BioSystems Maestro TM MEA system Application note Version 2.0 Contents 1. Introduction 1 2. Assessment
More information