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Results: 1 to 8 of 8

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A connexin40 mutation associated with a malignant variant of progressive familial heart block type I.
Makita N, Seki A, Sumitomo N, Chkourko H, Fukuhara S, Watanabe H, Shimizu W, Bezzina CR, Hasdemir C, Mugishima H, Makiyama T, Baruteau A, Baron E, Horie M, Hagiwara N, Wilde AA, Probst V, Le Marec H, Roden DM, Mochizuki N, Schott JJ, Delmar M
(2012) Circ Arrhythm Electrophysiol 5: 163-72
MeSH Terms: Biomarkers, Blotting, Western, Bundle of His, Cardiac Conduction System Disease, Child, Connexins, DNA, Electrocardiography, Electrophysiologic Techniques, Cardiac, Female, Genetic Predisposition to Disease, Heart Block, Heart Rate, Humans, Immunohistochemistry, Male, Mutation, Pedigree, Polymerase Chain Reaction, Prognosis
Show Abstract · Added August 16, 2012
BACKGROUND - Progressive familial heart block type I (PFHBI) is a hereditary arrhythmia characterized by progressive conduction disturbances in the His-Purkinje system. PFHBI has been linked to genes such as SCN5A that influence cardiac excitability but not to genes that influence cell-to-cell communication. Our goal was to explore whether nucleotide substitutions in genes coding for connexin proteins would associate with clinical cases of PFHBI and if so, to establish a genotype-cell phenotype correlation for that mutation.
METHODS AND RESULTS - We screened 156 probands with PFHBI. In addition to 12 sodium channel mutations, we found a germ line GJA5 (connexin40 [Cx40]) mutation (Q58L) in 1 family. Heterologous expression of Cx40-Q58L in connexin-deficient neuroblastoma cells resulted in marked reduction of junctional conductance (Cx40-wild type [WT], 22.2±1.7 nS, n=14; Cx40-Q58L, 0.56±0.34 nS, n=14; P<0.001) and diffuse localization of immunoreactive proteins in the vicinity of the plasma membrane without formation of gap junctions. Heteromeric cotransfection of Cx40-WT and Cx40-Q58L resulted in homogenous distribution of proteins in the plasma membrane rather than in membrane plaques in ≈50% of cells; well-defined gap junctions were observed in other cells. Junctional conductance values correlated with the distribution of gap junction plaques.
CONCLUSIONS - Mutation Cx40-Q58L impairs gap junction formation at cell-cell interfaces. This is the first demonstration of a germ line mutation in a connexin gene that associates with inherited ventricular arrhythmias and emphasizes the importance of Cx40 in normal propagation in the specialized conduction system.
1 Communities
1 Members
0 Resources
20 MeSH Terms
The potential of dual camera systems for multimodal imaging of cardiac electrophysiology and metabolism.
Holcomb MR, Woods MC, Uzelac I, Wikswo JP, Gilligan JM, Sidorov VY
(2009) Exp Biol Med (Maywood) 234: 1355-73
MeSH Terms: Algorithms, Animals, Calcium, Computer Simulation, Electrophysiologic Techniques, Cardiac, Heart Ventricles, Heterocyclic Compounds, 3-Ring, Imaging, Three-Dimensional, In Vitro Techniques, Myocardium, NAD, Pyridinium Compounds, Rabbits, Spectrometry, Fluorescence
Show Abstract · Added May 29, 2014
Fluorescence imaging has become a common modality in cardiac electrodynamics. A single fluorescent parameter is typically measured. Given the growing emphasis on simultaneous imaging of more than one cardiac variable, we present an analysis of the potential of dual camera imaging, using as an example our straightforward dual camera system that allows simultaneous measurement of two dynamic quantities from the same region of the heart. The advantages of our system over others include an optional software camera calibration routine that eliminates the need for precise camera alignment. The system allows for rapid setup, dichroic image separation, dual-rate imaging, and high spatial resolution, and it is generally applicable to any two-camera measurement. This type of imaging system offers the potential for recording simultaneously not only transmembrane potential and intracellular calcium, two frequently measured quantities, but also other signals more directly related to myocardial metabolism, such as [K(+)](e), NADH, and reactive oxygen species, leading to the possibility of correlative multimodal cardiac imaging. We provide a compilation of dye and camera information critical to the design of dual camera systems and experiments.
1 Communities
2 Members
0 Resources
14 MeSH Terms
Effects of unipolar stimulation on voltage and calcium distributions in the isolated rabbit heart.
Sidorov VY, Holcomb MR, Woods MC, Gray RA, Wikswo JP
(2008) Basic Res Cardiol 103: 537-51
MeSH Terms: Action Potentials, Animals, Calcium, Electric Stimulation, Electrophysiologic Techniques, Cardiac, Female, Fluorescent Dyes, Heart, In Vitro Techniques, Male, Myocardium, Rabbits, Ventricular Function, Left
Show Abstract · Added May 29, 2014
BACKGROUND - The effect of electric stimulation on the polarization of cardiac tissue (virtual electrode effect) is well known; the corresponding response of intracellular calcium concentration ([Ca(2+)](i)) and its dependence on coupling interval between conditioning stimulus (S1) and test stimulus (S2) has yet to be elucidated.
OBJECTIVE - Because uncovering the transmembrane potential (V(m))-[Ca(2+)](i) relationship during an electric shock is imperative for understanding arrhythmia induction and defibrillation, we aimed to study simultaneous V(m) and [Ca(2+)](i) responses to strong unipolar stimulation.
METHODS - We used a dual-camera optical system to image concurrently V (m) and [Ca(2+)](i) responses to unipolar stimulation (20 ms +/- 20 mA) in Langendorff-perfused rabbit hearts. RH-237 and Rhod-2 fluorescent dyes were used to measure V(m) and [Ca(2+)](i), respectively. The S1-S2 interval ranged from 10 to 170 ms to examine stimulation during the action potential.
RESULTS - The [Ca(2+)](i) deflections were less pronounced than changes in V(m) for all S1-S2 intervals. For cathodal stimulation, [Ca(2+)](i) at the central virtual cathode region increased with prolongation of S1-S2 interval. For anodal stimulation, [Ca(2+)](i) at the central virtual anode area decreased with shortening of the S1-S2 interval. At very short S1-S2 intervals (10-20 ms), when S2 polarization was superimposed on the S1 action potential upstroke, the [Ca(2+)](i) distribution did not follow V(m) and produced a more complex pattern. After S2 termination [Ca(2+)](i) exhibited three outcomes in a manner similar to V(m): non-propagating response, break stimulation, and make stimulation.
CONCLUSIONS - Changes in the [Ca(2+)](i) distribution correlate with the behavior of the V (m) distribution for S1-S2 coupling intervals longer than 20 ms; at shorter intervals S2 creates more heterogeneous [Ca(2+)](i) distribution in comparison with V(m). Stimulation in diastole and at very short coupling intervals caused V(m)-[Ca(2+)](i) uncoupling at the regions of positive polarization (virtual cathode).
1 Communities
2 Members
0 Resources
13 MeSH Terms
Left ventricular cardiac fibroma in a child presenting with ventricular tachycardia.
Stratemann S, Dzurik Y, Fish F, Parra D
(2008) Pediatr Cardiol 29: 223-6
MeSH Terms: Child, Electrophysiologic Techniques, Cardiac, Fibroma, Heart Neoplasms, Heart Ventricles, Humans, Magnetic Resonance Imaging, Male, Tachycardia, Ventricular
Show Abstract · Added January 20, 2015
Cardiac tumors in children are rare. Although most are histologically benign, they can be associated with life-threatening arrhythmias and sudden death. We report a 7-year-old boy, with a first episode of symptomatic tachycardia, who was found to have a left ventricular (LV) fibroma. He had a normal echocardiogram prior to an electrophysiology study, which revealed a sustained monomorphic ventricular tachycardia and a radio-opacity near the LV apex. These findings prompted a cardiac MRI, which demonstrated a discrete mass on his LV apex and free wall. Our case emphasizes that structural heart disease should be aggressively pursued in children presenting with ventricular tachycardia.
0 Communities
1 Members
0 Resources
9 MeSH Terms
AHA/ACCF Scientific Statement on the evaluation of syncope: from the American Heart Association Councils on Clinical Cardiology, Cardiovascular Nursing, Cardiovascular Disease in the Young, and Stroke, and the Quality of Care and Outcomes Research Interdisciplinary Working Group; and the American College of Cardiology Foundation: in collaboration with the Heart Rhythm Society: endorsed by the American Autonomic Society.
Strickberger SA, Benson DW, Biaggioni I, Callans DJ, Cohen MI, Ellenbogen KA, Epstein AE, Friedman P, Goldberger J, Heidenreich PA, Klein GJ, Knight BP, Morillo CA, Myerburg RJ, Sila CA, American Heart Association Councils on Clinical Cardiology, Cardiovascular Nursing, Cardiovascular Disease in the Young, and Stroke, Quality of Care and Outcomes Research Interdisciplinary Working Group, American College of Cardiology Foundation, Heart Rhythm Society, American Autonomic Society
(2006) Circulation 113: 316-27
MeSH Terms: Adult, Aged, Child, Electrocardiography, Electrophysiologic Techniques, Cardiac, Heart Diseases, Humans, Neurologic Examination, Syncope
Added December 10, 2013
0 Communities
1 Members
0 Resources
9 MeSH Terms
AHA/ACCF scientific statement on the evaluation of syncope: from the American Heart Association Councils on Clinical Cardiology, Cardiovascular Nursing, Cardiovascular Disease in the Young, and Stroke, and the Quality of Care and Outcomes Research Interdisciplinary Working Group; and the American College of Cardiology Foundation In Collaboration With the Heart Rhythm Society.
Strickberger SA, Benson DW, Biaggioni I, Callans DJ, Cohen MI, Ellenbogen KA, Epstein AE, Friedman P, Goldberger J, Heidenreich PA, Klein GJ, Knight BP, Morillo CA, Myerburg RJ, Sila CA, American Heart Association Councils on Clinical Cardiology, Cardiovascular Nursing, Cardiovascular Disease in the Young, and Stroke, Quality of Care and Outcomes Research Interdisciplinary Working Group, American College of Cardiology Foundation, Heart Rhythm Society
(2006) J Am Coll Cardiol 47: 473-84
MeSH Terms: Adult, Aged, Child, Electrocardiography, Electrophysiologic Techniques, Cardiac, Heart Diseases, Humans, Neurologic Examination, Syncope
Added December 10, 2013
0 Communities
1 Members
0 Resources
9 MeSH Terms
Myocyte contractile activity modulates norepinephrine cytotoxicity and survival effects of neuregulin-1beta.
Kuramochi Y, Lim CC, Guo X, Colucci WS, Liao R, Sawyer DB
(2004) Am J Physiol Cell Physiol 286: C222-9
MeSH Terms: Animals, Apoptosis, Cell Survival, Electric Stimulation, Electrophysiologic Techniques, Cardiac, Enzyme Activation, HSP70 Heat-Shock Proteins, HSP90 Heat-Shock Proteins, Heart Ventricles, JNK Mitogen-Activated Protein Kinases, Mitochondria, Heart, Mitogen-Activated Protein Kinases, Myocardial Contraction, Myocytes, Cardiac, Neuregulin-1, Norepinephrine, Phosphatidylinositol 3-Kinases, Phosphorylation, Protein Isoforms, Rats, Time Factors
Show Abstract · Added March 5, 2014
The purpose of this study is to test the hypothesis that mechanical and electrical activity in adult rat ventricular myocytes (ARVM) alters responses to proapoptotic and prosurvival ligands. The effects of electrical stimulation on myocyte survival, stress signaling, response to beta-adrenergic receptor (beta-AR)-stimulated apoptosis, and neuregulin-1beta (NRG) were examined. Electrical stimulation (6.6 V/cm; 0, 2, and 5 Hz; 2-ms duration; alternating polarity) of ARVM resulted in more than 70% capture. Although ARVM paced for 48 h showed higher mitochondrial uptake of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (P < 0.05, 0 vs. 2 and 5 Hz), electrical stimulation had little effect on cell survival assessed by trypan blue uptake, CPK release, and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling staining. Electrical stimulation for 24 h did not induce stress response (heat shock protein 70, 90) nor stress kinase (Erk, JNK, p38) activation. NRG stimulation of Erk and Akt was similar between paced and quiescent cells. Pacing sensitized myocytes to beta-AR-stimulated JNK phosphorylation and cell death with 0.1 microM norepinephrine (NE) in paced myocytes causing equivalent cytotoxicity to 10 microM NE in quiescent cells. NRG suppressed beta-AR-induced apoptosis through a phosphatidylinositol-3-kinase-dependent pathway in both paced and quiescent cells, although it is overwhelmed by high-NE concentration in paced cells. Thus myocyte contractility modulates both NE cytotoxicity as well as the cytoprotective effect of NRG. These results demonstrate the feasibility and importance of using electrically paced cardiomyocytes in primary culture when examining the signaling pathways of cell survival.
0 Communities
1 Members
0 Resources
21 MeSH Terms
Transgenic mice overexpressing mutant PRKAG2 define the cause of Wolff-Parkinson-White syndrome in glycogen storage cardiomyopathy.
Arad M, Moskowitz IP, Patel VV, Ahmad F, Perez-Atayde AR, Sawyer DB, Walter M, Li GH, Burgon PG, Maguire CT, Stapleton D, Schmitt JP, Guo XX, Pizard A, Kupershmidt S, Roden DM, Berul CI, Seidman CE, Seidman JG
(2003) Circulation 107: 2850-6
MeSH Terms: AMP-Activated Protein Kinases, Animals, Cardiomyopathies, Disease Models, Animal, Electrocardiography, Electrophysiologic Techniques, Cardiac, Glycogen Storage Disease, Heart Conduction System, Humans, Mice, Mice, Transgenic, Multienzyme Complexes, Mutation, Myocardium, Protein-Serine-Threonine Kinases, Survival Rate, Wolff-Parkinson-White Syndrome
Show Abstract · Added March 5, 2014
BACKGROUND - Mutations in the gamma2 subunit (PRKAG2) of AMP-activated protein kinase produce an unusual human cardiomyopathy characterized by ventricular hypertrophy and electrophysiological abnormalities: Wolff-Parkinson-White syndrome (WPW) and progressive degenerative conduction system disease. Pathological examinations of affected human hearts reveal vacuoles containing amylopectin, a glycogen-related substance.
METHODS AND RESULTS - To elucidate the mechanism by which PRKAG2 mutations produce hypertrophy with electrophysiological abnormalities, we constructed transgenic mice overexpressing the PRKAG2 cDNA with or without a missense N488I human mutation. Transgenic mutant mice showed elevated AMP-activated protein kinase activity, accumulated large amounts of cardiac glycogen (30-fold above normal), developed dramatic left ventricular hypertrophy, and exhibited ventricular preexcitation and sinus node dysfunction. Electrophysiological testing demonstrated alternative atrioventricular conduction pathways consistent with WPW. Cardiac histopathology revealed that the annulus fibrosis, which normally insulates the ventricles from inappropriate excitation by the atria, was disrupted by glycogen-filled myocytes. These anomalous microscopic atrioventricular connections, rather than morphologically distinct bypass tracts, appeared to provide the anatomic substrate for ventricular preexcitation.
CONCLUSIONS - Our data establish PRKAG2 mutations as a glycogen storage cardiomyopathy, provide an anatomic explanation for electrophysiological findings, and implicate disruption of the annulus fibrosis by glycogen-engorged myocytes as the cause of preexcitation in Pompe, Danon, and other glycogen storage diseases.
0 Communities
1 Members
0 Resources
17 MeSH Terms