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Start Over Author "N. Doisne" Topic cardiology and cardiovascular medicine
12 results on '"N. Doisne"'

1. P3483Diet governs metabolic and electrical properties of the atrial myocardium in mice

Author

N Suffee-Mosbah, W. Le Goff, V Galand, N Mougeneot, Marie Lhomme, Jérôme Piquereau, M Meriskay, N Doisne, Stéphane N. Hatem, F Ichou, E Baptista, and C Pichard

Subjects
medicine.medical_specialty, business.industry, Internal medicine, medicine, Cardiology, Atrial myocardium, Cardiology and Cardiovascular Medicine, business
Abstract

Background Obesity is associated with an increased risk of atrial fibrillation. This epidemiologic observation may not only be due to shared co-morbidities but also from direct impacts of metabolic disorders on myocardium Here, we examined the impact of high fat diet (HFD) induced obesity on atrial properties in mice. Methods Eight weeks old C57Bl/6J mice were subjected to 2 or 4 months of HFD (60% fat) or normal diet (ND, 4% fat). Rapid burst atrial pacing were delivered using a trans-esophageal probe to induced AF in anesthetized animals. Action potential (AP) were recorded in left atrial trabeculae using glass microelectrode technique. Potassium currents were recorded in isolated atrial myocytes using the whole cell or perforated patch clamp configurations. Metabolomic and lipidomic analysis were performed on whole left atria. Mitochondrial respiration was studied in situ in saponin-permeabilized atrial muscle fibres using a Clarke electrode and oxygen consumption was measured after successive addition of ADP (2 mM), malate (4 mM), palmitoyl-CoA and carnitine (pCoA-Ca) (100 μM and 2 mM), pyruvate (1 mM), glutamate (10 mM), succinate (15 mM), amytal (1 mM) and tetramethyl-paraphenylenediamine (TMPD)/ascorbate (0.5/0.5 mM). Results HFD mice showed a higher atrial vulnerability to AF as indicated by longer AF episodes compared to ND mice. APs were shorter in HFD versus ND mice (AP duration measured at 90% of repolarization: 47.9±2.4 msec in HFD vs 58.2±1.4 msec in ND, P Conclusions High fat diet induces a shift from carbon hydrate to a beta oxidation of the atrial myocardium metabolism together with an enhanced use of fatty acids by mitochondria. These metabolic changes could result in an enhanced activity of K-ATP channels and AP shortening that might contribute to AF vulnerability in this clinical setting. Acknowledgement/Funding ANR-10-IAHU-05

Published
2019
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3. A new SCN5A mutation responsible for Multifocal Ectopic Purkinje-Related Premature Contractions

Author

Xavier Waintraub, Estelle Gandjbakhch, Nathalie Neyroud, F. Hidden-Lucet, Victor Waldmann, N Doisne, L Fosse, Véronique Fressart, and Alban Redheuil

Subjects
medicine.medical_specialty, business.industry, Sodium channel, Mutant, HEK 293 cells, Dilated cardiomyopathy, Transfection, medicine.disease, Exon, Endocrinology, Internal medicine, medicine, Missense mutation, Patch clamp, Cardiology and Cardiovascular Medicine, business
Abstract

Introduction Recently, SCN5A mutations have been associated with Multifocal Ectopic Purkinje-Related Premature Contractions (MEPPC), a cardiac syndrome associating polymorphic ventricular arrhythmia with dilated cardiomyopathy. Methods and Results A new SCN5A mutation was identified in a young woman presenting with polymorphic PVCs and dilated cardiomyopathy since the age of 12. Radiofrequency catheter ablation showed at least three exit sites of purkinje-PVCs. A treatment by hydroquinidine was tried, leading to an immediate and spectacular disappearance of all PVCs. A new heterozygous missense mutation was identified in exon 5 of SCN5A (c.611C > A, pAla204Glu) in the DI-S3 domain. We investigated the functional consequences of NaV1.5-A204E expressed in HEK cells by recording the sodium current using the whole-cell configuration of the patch clamp technique. The NaV1.5-A204E mutant channels exhibited a significant leftward shift of the activation curve of 8 mV (V0.5 of activation = −42.9 ± 1.3 mV in A204E transfected cells (n = 24) compared to −34.8 ± 1.9 mV in cells transfected with the wild-type (WT) channel (n = 20), P Conclusion The functional consequences of this new SCN5A mutation associated with MEPPC revealed a pattern of abnormal voltage dependence of activation leading to a larger hyperpolarized window current as a shared biophysical mechanism of the syndrome. These features of the mutant sodium channel are likely to be responsible for hyperexcitability of the fascicular-Purkinje system.

Published
2019
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4. Poster session 3

Author

O. Nanka, E. Krejci, Z. Pesevski, D. Sedmera, N. Smart, A. Rossdeutsch, K. N. Dube, J. Riegler, A. N. Price, A. Taylor, V. Muthurangu, M. Turner, M. F. Lythgoe, P. R. Riley, S. Kryvorot, T. Vladimirskaya, I. Shved, M. Schwarzl, S. Seiler, S. Huber, P. Steendijk, H. Maechler, M. Truschnig-Wilders, B. Pieske, H. Post, C. Caprio, A. Baldini, E. Chiavacci, L. Dolfi, L. Verduci, F. Meghini, F. Cremisi, L. Pitto, T.-C. Kuan, M.-C. Chen, T.-H. Yang, W.-T. Wu, C. S. Lin, H. Rai, S. Kumar, A. K. Sharma, S. Mastana, A. Kapoor, C. M. Pandey, S. Agrawal, N. Sinha, E. H. Orlowska-Baranowska, G. Placha, J. Gora, R. Baranowski, E. Abramczuk, T. Hryniewiecki, Z. Gaciong, J. J. W. Verschuren, J. A. M. Wessels, S. Trompet, D. J. Stott, N. Sattar, B. Buckley, H. J. Guchelaar, J. W. Jukema, M. Gharanei, A. Hussain, C. J. Mee, H. L. Maddock, W. J. Wijnen, S. Van Den Oever, I. Van Der Made, M. Hiller, A. J. Tijsen, Y. M. Pinto, E. E. Creemers, S. U. Y. Nikulina, A. Chernova, A. Petry, T. Rzymski, D. Kracun, F. Riess, L. Pike, A. L. Harris, A. Gorlach, R. Katare, A. Oikawa, F. Riu, A. P. Beltrami, D. Cesseli, C. Emanueli, P. Madeddu, T. Zaglia, G. Milan, M. Franzoso, P. Pesce, C. Sarais, M. Sandri, M. Mongillo, T. J. Butler, A.-M. L. Seymour, D. Ashford, F. Jaffre, M. Bussen, I. Flohrschutz, G. R. Martin, S. Engelhardt, G. Kararigas, B. T. Nguyen, H. Jarry, V. Regitz-Zagrosek, M. Van Bilsen, A. Daniels, C. Munts, B. J. A. Janssen, G. J. Van Der Vusse, F. A. Van Nieuwenhoven, C. Montalvo, A. V. Villar, D. Merino, R. Garcia, M. Llano, M. Ares, M. A. Hurle, J. F. Nistal, A. Dembinska-Kiec, B. K. W. Beata Kiec-Wilk, A. P. Anna Polus, U. C. Urszula Czech, T. K. Tatiana Konovaleva, G. S. Gerd Schmitz, L. Bertrand, M. Balteau, A. Timmermans, B. Viollet, K. Sakamoto, O. Feron, S. Horman, J. L. Vanoverschelde, C. Beauloye, C. De Meester, E. Martinez, R. Martin, M. Miana, R. Jurado, N. Gomez-Hurtado, M. V. Bartolome, J. A. San Roman, V. Lahera, M. L. Nieto, V. Cachofeiro, F. Rochais, R. Sturny, K. Mesbah, L. Miquerol, R. G. Kelly, S. Messaoudi, B. Gravez, A. Tarjus, V. Pelloux, J. L. Samuel, C. Delcayre, J. M. Launay, K. Clement, N. Farman, F. Jaisser, L. Hadyanto, C. Castellani, G. Vescovo, B. Ravara, R. Tavano, M. Pozzobon, P. De Coppi, E. Papini, R. Vettor, G. Thiene, A. Angelini, M. Meloni, A. Caporali, D. Cesselli, O. Fortunato, E. Avolio, R. Schindler, S. Simrick, T. Brand, N. S. Smart, A. Herman, S. Roura Ferrer, J. Rodriguez Bago, C. Soler-Botija, J. M. Pujal, C. Galvez-Monton, C. Prat-Vidal, A. Llucia-Valldeperas, J. Blanco, A. Bayes-Genis, G. Foldes, M. Maxime, N. N. Ali, M. D. Schneider, S. E. Harding, C. Reni, G. Mangialardi, A. De Pauw, B. Sekkali, A. Friart, H. Ding, A. Graffeuil, D. Catalucci, J. L. Balligand, F. Azibani, F. Tournoux, S. Schlossarek, E. Polidano, L. Fazal, R. Merval, L. Carrier, C. Chatziantoniou, B. Buyandelger, W. Linke, P. Zou, S. Kostin, C. Ku, L. Felkin, E. Birks, P. Barton, M. Sattler, R. Knoell, K. Schroder, S. Benkhoff, H. Shimokawa, O. Grisk, R. P. Brandes, I. R. Parepa, L. Mazilu, A. I. Suceveanu, A. Suceveanu, L. Rusali, L. Cojocaru, L. Matei, M. Toringhibel, E. Craiu, A. L. Pires, M. Pinho, S. Pinho, C. Sena, R. Seica, A. Leite-Moreira, F. Dabroi, S. Schiaffino, E. Kiseleva, N. Krukov, O. Nikitin, L. Ardatova, I. Mourouzis, C. Pantos, A. D. Kokkinos, D. V. Cokkinos, E. Scoditti, M. Massaro, M. A. Carluccio, M. Pellegrino, N. Calabriso, A. Gastaldelli, C. Storelli, R. De Caterina, D. Lindner, C. Zietsch, H.-P. Schultheiss, C. Tschope, D. Westermann, B. R. Everaert, V. J. Nijenhuis, F. C. M. Reith, V. Y. Hoymans, J. P. Timmermans, C. J. Vrints, I. Simova, H. Mateev, T. Katova, L. Haralanov, N. Dimitrov, N. Mironov, S. P. Golitsyn, S. F. Sokolov, Y. U. A. Yuricheva, E. B. Maikov, N. B. Shlevkov, L. V. Rosenstraukh, E. I. Chazov, J. Radosinska, V. Knezl, T. Benova, J. Slezak, L. Urban, N. Tribulova, L. Virag, A. Kristof, Z. S. Kohajda, T. Szel, Z. Husti, I. Baczko, N. Jost, A. Varro, A. Sarusi, A. S. Farkas, S. Z. Orosz, T. Forster, A. Farkas, O. M. Zakhrabova-Zwiauer, M. Hardziyenka, R. Nieuwland, H. L. Tan, A. J. A. Raaijmakers, V. J. A. Bourgonje, G. J. M. Kok, A. A. B. Van Veen, M. E. Anderson, M. A. Vos, M. F. A. Bierhuizen, J. Benes, B. Sebestova, I. A. Ghouri, O. J. Kemi, A. Kelly, F. L. Burton, G. L. Smith, S. Ozdemir, K. Acsai, N. Doisne, R. Van Der Nagel, H. D. M. Beekman, T. A. B. Van Veen, K. R. Sipido, G. Antoons, S. C. Harmer, J. S. Mohal, D. Kemp, A. Tinker, D. Beech, D. S. Burley, C. D. Cox, K. T. Wann, G. F. Baxter, R. Wilders, A. Verkerk, P. Fragkiadaki, G. Germanakis, K. Tsarouchas, C. Tsitsimpikou, M. Tsardi, D. George, A. Tsatsakis, P. Rodrigues, C. Barros, A. K. Najmi, V. Khan, M. Akhtar, K. K. Pillai, M. Mujeeb, M. Aqil, C. R. Bayliss, A. E. Messer, M.-C. Leung, D. Ward, J. Van Der Velden, C. Poggesi, C. S. Redwood, S. Marston, A. Vite, E. Gandjbakhch, F. Gary, V. Fressart, P. Leprince, G. Fontaine, M. Komajda, P. Charron, E. Villard, I. Falcao-Pires, C. Gavina, N. Hamdani, G. J. M. Stienen, H. W. M. Niessens, A. F. Leite-Moreira, W. J. Paulus, M. Memo, S. B. Marston, E. Vafiadaki, J. Qian, D. A. Arvanitis, D. Sanoudou, E. G. Kranias, N. Elmstedt, B. Lind, K. Ferm-Widlund, M. Westgren, L.-A. Brodin, C. Mansfield, T. West, M. Ferenczi, P. J. M. Wijnker, D. B. Foster, A. Coulter, A. Frazier, A. M. Murphy, M. Shah, M. B. Sikkel, T. Desplantez, T. P. Collins, P. O' Gara, A. R. Lyon, K. T. Macleod, A. H. Ottesen, W. E. Louch, C. Carlson, O. J. B. Landsverk, M. Stridsberg, I. Sjaastad, E. Oie, T. Omland, G. Christensen, H. Rosjo, J. Cartledge, L. A. Clark, M. Ibrahim, U. Siedlecka, M. Navaratnarajah, M. H. Yacoub, P. Camelliti, C. M. Terracciano, A. Chester, A. Gonzalez-Tendero, I. Torre, F. Garcia-Garcia, J. Dopazo, E. Gratacos, D. Taylor, S. Bhandari, A.-M. Seymour, D. Fliegner, J. Jost, H. Bugger, R. Ventura-Clapier, A. Carpi, M. Campesan, M. Canton, R. Menabo, P. G. Pelicci, M. Giorgio, F. Di Lisa, M. Hancock, A. Venturini, N. Al-Shanti, C. Stewart, R. Ascione, G. Angelini, M.-S. Suleiman, E. Kravchuk, E. Grineva, M. Galagudza, A. Kostareva, A. Bairamov, K. A. Krychtiuk, L. Watzke, C. Kaun, S. Demyanets, J. Pisoni, S. P. Kastl, K. Huber, G. Maurer, J. Wojta, W. S. Speidl, Z. V. Varga, N. Farago, A. Zvara, G. F. Kocsis, M. Pipicz, C. Csonka, T. Csont, G. L. Puskas, P. Ferdinandy, M. Klevstigova, J. Silhavy, D. Manakov, F. Papousek, J. Novotny, M. Pravenec, F. Kolar, O. Novakova, F. Novak, J. Neckar, J. Barallobre-Barreiro, A. Didangelos, X. Yin, M. Fernandez-Caggiano, I. Drozdov, P. Willeit, N. Domenech, M. Mayr, S. Lemoine, S. Allouche, L. Coulbault, P. Galera, J. L. Gerard, J. L. Hanouz, E. Suveren, M. Whiteman, I. M. Studneva, O. Pisarenko, V. Shulzhenko, L. Serebryakova, O. Tskitishvili, A. Timoshin, J. Fauconnier, A. C. Meli, J. Thireau, S. Roberge, A. M. Lompre, E. Jacotot, A. M. Marks, A. Lacampagne, B. Dietel, R. Altendorf, W. G. Daniel, R. Kollmar, C. D. Garlichs, V. Parente, S. Balasso, G. Pompilio, G. Colombo, G. Milano, L. Squadroni, F. Cotelli, O. Pozzoli, M. C. Capogrossi, Y. Ajiro, N. Saegusa, K. Iwade, W. R. Giles, D. M. Stafforini, K. W. Spitzer, R. Sirohi, L. Candilio, G. Babu, N. Roberts, D. Lawrence, A. Sheikh, S. Kolvekar, J. Yap, D. J. Hausenloy, D. M. Yellon, M. Aslam, S. Rohrbach, K.-D. Schlueter, H. M. Piper, T. Noll, D. Guenduez, L. Malinova, V. P. Ryabukho, D. V. Lyakin, T. P. Denisova, S. Montoro-Garcia, E. Shantsila, G. Y. H. Lip, B. Kalaska, E. Sokolowska, K. Kaminski, K. Szczubialka, K. Kramkowski, A. Mogielnicki, M. Nowakowska, W. Buczko, N. Stancheva, E. Mekenyan, K. Gospodinov, S. Tisheva, A. Darago, I. Rutkai, J. Kalasz, A. Czikora, P. Orosz, H. D. Bjornson, I. Edes, Z. Papp, A. Toth, K. Riches, P. Warburton, D. J. O'regan, S. G. Ball, N. A. Turner, I. C. Wood, K. E. Porter, S. Kogaki, H. Ishida, N. Nawa, K. Takahashi, H. Baden, H. Ichimori, T. Uchikawa, S. Mihara, K. Miura, K. Ozono, R. Lugano, T. Padro, M. Garcia-Arguinzonis, L. Badimon, F. Ferraro, R. Viner, J. Ho, D. Cutler, V. Matchkov, C. Aalkjaer, P. A. J. Krijnen, N. E. Hahn, I. Kholova, J. A. Sipkens, F. P. Van Alphen, S. Simsek, C. G. Schalkwijk, J. D. Van Buul, V. W. M. Van Hinsbergh, H. W. M. Niessen, C. G. Caro, A. Seneviratne, C. Monaco, D. Hou, J. Singh, P. Gilson, M. G. Burke, K. B. Heraty, R. Krams, G. Coppola, K. Albrecht, W. Schgoer, D. Wiedemann, N. Bonaros, C. Steger, M. Theurl, U. Stanzl, R. Kirchmair, S. Amadesi, G. Spinetti, E. Cangiano, M. Valgimigli, A. M. Miller, A. Cardinali, K. Vierlinger, G. Pagano, D. Liccardo, C. Zincarelli, G. D. Femminella, A. Lymperopoulos, C. De Lucia, W. J. Koch, D. Leosco, G. Rengo, R. Hinkel, W. Husada, T. Trenkwalder, Q. Di, S. Lee, B. Petersen, I. Bock-Marquette, H. Niemann, M. Di Maio, C. Kupatt, M. Nourian, Z. Yassin, R. Kelishadi, S. H. Memarian, A. Heidari, A. Leuner, D. M. Poitz, C. Brunssen, U. Ravens, R. H. Strasser, H. Morawietz, F. Vogt, A. Grahl, C. Flege, N. Marx, M. Borinski, B. De Geest, F. Jacobs, I. Muthuramu, S. C. Gordts, E. Van Craeyveld, P. Herijgers, S. Weinert, S. Medunjanin, J. Herold, A. Schmeisser, R. C. Braun-Dullaeus, A. H. Wagner, K. Moeller, O. Adolph, M. Schwarz, C. Schwale, C. Bruehl, R. Nobiling, T. Wieland, S. W. Schneider, M. Hecker, A. Cross, A. Strom, J. Cole, M. Goddard, A. Hultgardh-Nilsson, J. Nilsson, C. Mauri, N. P. Mitkovskaya, T. A. Kurak, E. G. Oganova, E. I. Shkrebneva, Z. H. N. Kot, T. V. Statkevich, F. Molica, F. Burger, C. M. Matter, A. Thomas, C. Staub, A. Zimmer, B. Cravatt, P. Pacher, S. Steffens, R. Blanco, R. Sarmiento, C. Parisi, S. Fandino, F. Blanco, G. Gigena, J. Szarfer, A. Rodriguez, A. Garcia Escudero, M. A. Riccitelli, S. Wantha, S. Simsekyilmaz, R. T. Megens, M. A. Van Zandvoort, E. Liehn, A. Zernecke, D. Klee, C. Weber, O. Soehnlein, L. M. Lima, M. G. Carvalho, K. B. Gomes, I. R. Santos, M. O. Sousa, C. A. S. Morais, S. H. V. Oliveira, I. F. Gomes, F. C. Brandao, M. R. A. Lamego, L. Fornai, A. Kiss, F. Giskes, G. Eijkel, M. Fedrigo, M. L. Valente, R. M. A. Heeren, A. Grdinic, D. Vojvodic, N. Djukanovic, A. G. Grdinic, S. Obradovic, I. Majstorovic, S. Rusovic, Z. Vucinic, D. Tavciovski, M. Ostojic, S.-C. Lai, M.-Y. Chen, H.-T. Wu, L. Gouweleeuw, S. U. Oberdorf-Maass, R. A. De Boer, W. H. Van Gilst, A. H. Maass, I. C. Van Gelder, L. Benard, C. Li, D. Warren, C. M. Shanahan, Q. P. Zhang, A. Bye, R. Vettukattil, S. T. Aspenes, G. Giskeodegaard, I. S. Gribbestad, U. Wisloff, T. F. Bathen, J. Cubedo, R. Alonso, P. Mata, I. Ivic, Z. Vamos, P. Cseplo, D. Kosa, O. Torok, J. Hamar, A. Koller, K. Norita, S. V. De Noronha, M. N. Sheppard, I. Amat-Roldan, I. Iruretagoiena, S. Psilodimitrakopoulos, F. Crispi, D. Artigas, P. Loza-Alvarez, J. C. Harrison, S. D. Smart, E. H. Besely, J. R. Kelly, Y. Yao, I. A. Sammut, M. Hoepfner, W. Kuzyniak, E. Sekhosana, B. Hoffmann, C. Litwinski, A. Pries, E. Ermilov, D. Fontoura, A. P. Lourenco, F. Vasques-Novoa, J. P. Pinto, R. Roncon-Albuquerque, I. P. Oyeyipo, L. A. Olatunji, T. O. Usman, V. A. Olatunji, B. Bacova, C. Viczenczova, V. Dosenko, E. Goncalvesova, J. Vanrooyen, S. K. Maulik, S. Seth, A. K. Dinda, A. Jaiswal, G. Mearini, D. Khajetoorians, E. Kraemer, C. Gedicke-Hornung, G. Precigout, T. Eschenhagen, T. Voit, L. Garcia, S. Lorain, P. Mendes-Ferreira, C. Maia-Rocha, R. Adao, R. J. Cerqueira, M. J. Mendes, P. Castro-Chaves, G. W. De Keulenaer, C. Bras-Silva, G. Ruiter, Y. Y. Wong, M. Lubberink, P. Knaapen, P. Raijmakers, A. A. Lammertsma, J. T. Marcus, N. Westerhof, W. J. Van Der Laarse, A. Vonk-Noordegraaf, N. Steinbronn, E. Koch, G. Steiner, A. Berezin, O. A. Lisovaya, A. M. Soldatova, V. A. Kuznetcov, T. N. Yenina, A. Y. U. Rychkov, P. V. Shebeko, R. Altara, M. H. M. Hessel, J. J. R. Hermans, W. M. Blankesteijn, T. A. Berezina, V. Seden, C. Bonanad, J. Nunez, D. Navarro, M. F. Chilet, F. Sanchis, V. Bodi, G. Minana, F. Chaustre, M. J. Forteza, A. Llacer, G. Galasso, N. Ferrara, A. Akhmedov, R. Klingenberg, C. Brokopp, D. Hof, S. Zoller, R. Corti, S. Gay, A. Von Eckardstein, S. P. Hoerstrup, T. F. Luescher, J. Heijman, A. Zaza, D. M. Johnson, Y. Rudy, R. L. M. Peeters, P. G. A. Volders, R. L. Westra, S. Fujita, R. Okamoto, M. Taniguchi, K. Konishi, I. Goto, K. Sugimoto, M. Nakamura, K. Shiraki, C. Buechler, and M. Ito

Subjects
AMP-activated protein kinase, biology, Physiology, Chemistry, Physiology (medical), Mesenchymal stem cell, biology.protein, Cardiology and Cardiovascular Medicine, Cell biology
Published
2012
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5. P128Recovery of Scn5a-deficient mice cardiac conduction using AAVs

Author

L Fosse, Michel Clergue, Alain Coulombe, Nathalie Mougenot, N Doisne, Flavien Charpentier, M Grauso-Culetto, Pascale Guicheney, and Nathalie Neyroud

Subjects
medicine.medical_specialty, Endocrinology, Physiology, business.industry, Physiology (medical), Internal medicine, Cardiac conduction, medicine, Deficient mouse, Cardiology and Cardiovascular Medicine, business
Published
2018
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6. P133Atrial fibrillation vulnerability and action potential shortening in high fat diet-induced obesity in mice

Author

V Galand, Alain Coulombe, Stéphane N. Hatem, Nathalie Mougenot, N Suffee-Mosbah, and N Doisne

Subjects
Fibrillation, medicine.medical_specialty, Physiology, business.industry, Vulnerability, High fat diet induced obesity, Endocrinology, Action (philosophy), Physiology (medical), Internal medicine, Medicine, medicine.symptom, Cardiology and Cardiovascular Medicine, business
Published
2018
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9. Control of Rhythm and Rate278Cx43 hemichannels in ventricular cardiomyocytes can be activated by an elevation of cytoplasmic Ca2+ through a CaM-dependent signaling cascade and are a potent contributor to cardiac arrhythmogenesis279Exploration of the dominant-negative effect of a SCN5A mutation in mice using adeno-associated viruses280Modeling susceptibility to drug-induced long qt syndrome with a panel of subject-specific induced pluripotent stem cells

Author

Christian Funck-Brentano, Michel Clergue, Dorota Jeziorowska, Alessio Lissoni, Noël Zahr, Nathalie Mougenot, Pascale Guicheney, Jens Hansen, Nathalie Neyroud, Alain Coulombe, M. De Smet, Chi-Wing Kong, Nan Wang, N Doisne, Marta Grauso, Ravi Iyengar, Luc Leybaert, Roger J. Hajjar, Francesca Stillitano, Jean-Sébastien Hulot, and Ronald A. Li

Subjects
medicine.medical_specialty, biology, Calmodulin, Physiology, Long QT syndrome, hERG, Sotalol, Depolarization, KCNE4, medicine.disease, QT interval, Endocrinology, Physiology (medical), Internal medicine, Ventricular fibrillation, medicine, biology.protein, Cardiology and Cardiovascular Medicine, medicine.drug
Abstract

278 Cx43 hemichannels in ventricular cardiomyocytes can be activated by an elevation of cytoplasmic Ca2+ through a CaM-dependent signaling cascade and are a potent contributor to cardiac arrhythmogenesis {#article-title-2} Introduction and purpose: Cx43, most abundantly expressed in the ventricles, is engaged in forming both gap junctions that electrically couple the cardiac tissue and unapposed hemichannels (HCs) that function as a non-selective transmembrane conduit. The latter are typically closed but open in response to electrical or chemical triggers such as pro-inflammatory cytokines or elevation of cytoplasmic Ca2+ ([Ca2+]i). Evidence for hemichannel opening by [Ca2+]i elevation is based on indirect ATP/dye uptake measurements, but conclusive electrophysiological evidence is lacking. Here, we studied [Ca2+]i-dependent activation of cardiac Cx43 HCs with the use of single-channel recordings and further proposed their arrhythmogenic potential. Methods: Left ventricular cardiomyocytes were acutely isolated from C57/Bl6 and inducible Cx43 knockdown mice (Cx43Cre-ER(T)/Fl). We provoked Ca2+ release from the sarcoplasmic reticulum by local application of caffeine (10 mM) under voltage-clamp conditions (Vm = -70 mV) and studied the effect on HC unitary currents using whole-cell patch-clamp techniques. Involvement of Cx43 HCs was verified by the biophysical properties, intracellular application of Gap19 (100 µM) and CT9 (100 µM) (a selective Cx43 HC blocker and positive modulator respectively) and Cx43 knockdown. Involvement of [Ca2+]i was assessed by applying the Ca2+-chelator EGTA (10 mM) intracellularly. Calmodulin (CaM) antagonist W7 (50 µM) was used to investigate the contribution of CaM signaling. Results and conclusions: Applying caffeine pulses (8 s) at resting membrane potential activated an inward current carried by the Na+/Ca2+ exchanger (NCX). Superimposed on this macroscopic current, there appeared microscopic current spiking activity characterized by a unitary conductance of ~210 pS. Unitary currents were inhibited by EGTA, by conditional Cx43 knockdown (Cx43Cre-ER(T)/Fl) and by the Cx43 HC blocking peptide Gap19. Additionally, CT9 peptide promoted the HC currents activated by caffeine-induced Ca2+-release while delivery of W7 into the cell completely abolished HC currents. The results indicate that Cx43 HCs can be opened by Ca2+-stimulation without any associated electrical stimulus through a CaM-dependent signaling cascade. The kinetics of Ca2+-triggered opening activity were very different from voltage-triggered activity (fast spiking versus prolonged opening respectively) indicating a distinct gating mechanism. Computational modeling of the impact of electrically/chemically-triggered Cx43 HC opening on cardiomyocyte excitability indicates that this may contribute to arrhythmogenesis in the heart by providing depolarizing inward currents with potential for generating delayed afterdepolarizations and subsequent focal excitation. # 279 Exploration of the dominant-negative effect of a SCN5A mutation in mice using adeno-associated viruses {#article-title-3} Introduction: Loss-of-function mutations in the cardiac sodium (Na+) channel α-subunit gene, SCN5A, cause Brugada syndrome (BrS), a hereditary disease with an autosomal dominant transmission and variable penetrance, characterized by ventricular fibrillation and sudden cardiac death. We previously evidenced in HEK293 cells, the dominant-negative effect of the R104W BrS mutation in the N-terminal region of the cardiac Na+ channel, inducing the retention of the wild-type (WT) channel and the proteasomal degradation of the mutant protein, leading to a drastic reduction of the resulting Na+ current. Our goal was to further study the effects of this mutation in vivo in mice, taking advantage of adeno-associated viruses (AAV) and pre-mRNA trans-splicing strategy. Methods: Because of the large size of the SCN5A gene, we used a dual AAV vector strategy combining viral DNA recombination and trans-splicing. Mice were injected with two AAV-9: one, AAV-SCN5A-5', packaging the cardiac troponin-T promoter, the 5' half of hSCN5A, the 5' donor site of a synthetic intron and a highly recombinogenic part of the human alkaline phosphatase (AP); and another, AAV-SCN5A-3', packaging the same AP sequence, the 3' acceptor site of the intron, the 3' half of hSCN5A fused to the gfp gene as a reporter and the SV40 polyA signal. Six weeks after systemic injection, the hSCN5A-GFP full-gene expression was assessed by RT-qPCR, western blot and immunohistochemistry on transduced heart tissues. The Na+ current was recorded by the patch-clamp technique in isolated adult trasduced cardiomyocytes. Results: Almost 40% of cells were transduced in injected mice hearts. Overexpression of the R104W mutant channel induced a dilatation of the left vendtricle (+21% in systole, P

Published
2016
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10. G015 Adrenergic regulation of the resting membrane potential in the left atrium and thoracic veins of the rat

Author

Ian Findlay, N. Doisne, N. Zannad, Véronique Maupoil, and Pierre Cosnay

Subjects
Membrane potential, medicine.medical_specialty, business.industry, Thoracic Vein, Cardiac muscle, Adrenergic, Depolarization, General Medicine, Cirazoline, Pulmonary vein, chemistry.chemical_compound, Endocrinology, medicine.anatomical_structure, chemistry, Internal medicine, Isoprenaline, medicine, Cardiology, business, Cardiology and Cardiovascular Medicine, medicine.drug
Abstract

The physiology of cardiac muscle in thoracic veins is of interest as a source of ectopic activity which can lead to paroxystic atrial fibrillation (Haissaguerre et al. 1998 N Engl J Med 339: 659-666 ; Chen et al. 1999 Circulation 100:1879-1886). We have shown that noradrenalin can induce automatic ectopic activity in the pulmonary vein of the rat (Maupoil et al. 2007 Br J Pharmacol 150:899-905). Here we describe the effects of adrenergic agonists upon the resting membrane potential recorded with intracellular microelectrodes from cardiac muscle in the left atrium (LA), pulmonary veins (PV) and superior vena cava (SVC) of the rat. Isolated tissues were continuously perfused with Krebs-Heinseleit solution aerated with 95 % O2, 5 % CO2 and maintained at 36-37 °C. The quiescent resting membrane potentials were: LA −84±1 mV (n=14), SVC −74±1 mV (n=14), PV −69±1 mV (n=17). In each tissue noradrenalin (10-5M) induced a biphasic response with an initial hyperpolarisation (LA −3±1 mV, SVC −9±1 mV, PV −8±1 mV) followed by a depolarisation (LA +1±2 mV, SVC +15±2 mV, PV +34±1 mV). Only in PV did noradrenalin induce automatic electrical activity when the membrane potential reached ∼−50 mV. The α-adrenergic agonist cirazoline (10-6M) induced a monophasic depolarisation of the resting membrane potential in each tissue: to −80±2 mV in LA, to −49±1 mV in SVC and to −34±1 mV in PV. In no case did cirazoline induce automatic electrical activity. The β-adrenergic agonist isoprenaline (10-7M) induced a monophasic hyperpolarisation of the resting membrane potential in each tissue: to −87±1 mV in LA, to −79±2 mV in SVC and to −80±2 mV in PV. Conclusions 1. There are significant differences between the resting membrane potentials of the left atrium and both thoracic veins. 2. The responses of the resting membrane potential to adrenergic stimulation are qualitatively similar but quantitatively different with LA 3. Depolarisation is not sufficient to induce automatic electrical activity.

Published
2009
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11. 0235 : In vivo overexpression of a cardiac sodium channel mutant in mice

Author

Pascale Guicheney, Nathalie Mougenot, Nathalie Neyroud, Alain Coulombe, Marta Grauso, Michel Clergue, and N Doisne

Subjects
Mutation, medicine.diagnostic_test, business.industry, Sodium channel, Mutant, HEK 293 cells, medicine.disease_cause, Virology, Molecular biology, Green fluorescent protein, Western blot, In vivo, Mutant protein, medicine, Cardiology and Cardiovascular Medicine, business
Abstract

Loss-of-function mutations in the cardiac Na+ channel α-subunit gene, SCN5A, cause Brugada syndrome (BrS), a hereditary disease characterized by ventricular fibrillation and sudden cardiac death. We previously evidenced, in HEK cells, the dominant-negative effect of the R104W BrS mutation in Nav1.5, inducing the retention of the wild-type (WT) channel and the proteasomal degradation of the mutant protein. To explore this dominant-negative effect in vivo, we created a murine model using adeno-associated viruses (AAV). We used a dual AAV vector strategy combining viral DNA recombination and trans-splicing. One-week old mice were injected with two AAV serotypes capsid 9: one, packaging the cardiac specific troponin-T promoter, the 5’ half of hSCN5A, the 5’ donor site of a synthetic intron and a highly recombinogenic sequence; and another, packaging the same recombinogenic sequence, the 3’ acceptor site of the synthetic intron, the 3’ half of hSCN5A, the gfp gene as a reporter, and the SV40 polyA signal. Six weeks after injection, the hSCN5A full-gene expression and the percentage of transduced cardiac cells were assessed by qPCR, western blot (WB) analysis and immunohistochemistry on transduced heart tissues. The Na+ current was recorded by the patchclamp technique in isolated cardiomyocytes. Both WT and mutant human Nav1.5 transcripts and proteins were observed by RT-qPCR, WB and immunohistochemistry on injected-mice heart tissues. Patch-clamp recordings in WT-channel injected mice evidenced a two-fold increase of the Na+ current. In contrast, the cardiac Na+ current of R104Winjected mice was impaired (i.e. the current density was decreased by 45% and the activation was shifted by -4mV). Our data suggest that the trans-splicing and viral DNA recombination strategy using AAV9 serotype and a cardiac-specific promoter is successful to overexpress WT or mutant Na+ channels in mouse hearts. This approach allowed us to modulate the cardiac Na+ current in adult mice.

Published
2015
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12. Poster Session 4

Author

H. Tada, H. Yamasaki, Y. Sekiguchi, M. Igarashi, K. Kuroki, T. Machino, K. Yoshida, K. Aonuma, F. R. Heinzel, H. Forstner, P. Lercher, E. Bisping, B. Rotman, F. M. Fruhwald, B. M. Pieske, R. Dabrowski, I. Kowalik, A. Borowiec, E. Smolis-Bak, A. Trybuch, C. Sosnowski, H. Szwed, M. A. Baturova, A. Lindgren, Y. V. Shubik, B. Olsson, P. G. Platonov, K. C. Van Den Broek, J. Denollet, J. Widdershoven, N. Kupper, R. Allam, R. A. G. A. B. Allam, W. A. G. D. Y. Galal, H. A. Y. A. M. El-Damnhoury, A. Y. M. A. N. Mortada, J. Jimenez-Candil, A. Martin, J. Hernandez, F. Martin, M. Gallego, C. Martin-Luengo, J. G. Quintanilla, J. Moreno Planas, R. Molina-Morua, T. Archondo, M. J. Garcia-Torrent, N. Perez-Castellano, C. Macaya, J. Perez-Villacastin, J. Saiz, C. Tobon, J. F. Rodriguez, F. Hornero, J. M. Ferrero, K. Ito, T. Date, M. Kawai, M. Hioki, R. Narui, S. Matsuo, M. Yoshimura, T. Yamane, N. Tabatabaei, G. Lin, B. D. Powell, R. Smairat, J. F. Glockner, P. A. Brady, S. Fichtner, U. Czudnochowsky, H. Estner, T. Reents, C. Jilek, S. Ammar, G. Hessling, I. Deisenhofer, D. C. Shah, J. Kautzner, N. Saoudi, C. Herrera, P. Jais, G. Hindricks, P. Neuzil, K. H. Kuck, K. C. K. Wong, M. Jones, N. Qureshi, A. Muthumala, T. R. Betts, Y. Bashir, K. Rajappan, T. Vogtmann, M. Wagner, J. Schurig, P. Hein, B. Hamm, G. Baumann, A. Lembcke, B. Saad, C. Slater, L. A. Oliveira, R. Elias, A. Camiletti, D. Moura, P. Maldonado, L. E. Camanho, A. Bulava, J. Hanis, D. Sitek, A. Novotny, W. B. Chik, T. W. Lim, H. K. Choon, V. A. See, R. Mccall, L. Thomas, D. L. Ross, S. P. Thomas, J. Chen, A. De Bortoli, O. Rossvoll, P. I. Hoff, E. Solheim, L. Z. Sun, P. Schuster, O. J. Ohm, A. V. Ardashev, E. Zhelyakov, M. S. Rybachenko, A. V. Konev, Y. U. N. Belenkov, M. Gunawardene, K. R. J. Chun, B. Schulte-Hahn, V. Windhorst, M. Kulikoglu, B. Nowak, B. Schmidt, G. A. Albina, R. S. Rivera, F. Scazzuso, R. L. Laino, G. A. Giniger, E. Arbelo, N. Calvo, D. Tamborero, D. Andreu, R. Borras, A. Berruezo, J. Brugada, L. Mont, L. Stefan, M. Eisenberger, E. Celentano, P. Peytchev, O. Bodea, P. Geelen, T. De Potter, M. M. Oliveira, N. Silva, P. S. Cunha, J. Feliciano, A. Lousinha, A. Toste, S. Santos, R. C. Ferreira, H. Matsuda, T. Harada, K. Soejima, Y. Ishikawa, K. Mizukoshi, T. Sasaki, K. Mizuno, F. Miyake, P. P. Adragao, D. Cavaco, R. Miranda, M. Santos, F. Morgado, K. Reis Santos, R. Candeias, S. Marcelino, F. Zoppo, G. Grandolino, F. Zerbo, E. Bertaglia, S. M. Schlueter, O. Grebe, E. G. Vester, A. L. Miracle Blanco, A. Arenal Maiz, F. Atienza Fernandez, T. Datino Romaniega, E. Gonzalez Torrecilla, G. Eidelman, J. Hernandez Hernandez, F. Fernandez Aviles, K. Fukumoto, S. Takatsuki, T. Kimura, N. Nishiyama, Y. Aizawa, T. Sato, S. Miyoshi, K. Fukuda, B. Richter, M. Gwechenberger, A. Socas, G. Zorn, S. Albinni, M. Marx, J. Wojta, H. Goessinger, T. Deneke, O. Balta, M. Paesler, K. Buenz, H. Anders, M. Horlitz, A. Muegge, D.- I. Shin, K. Natsuyama, K. M. Yamaguchi, Y. N. Nishida, J. Kosiuk, K. Bode, A. Arya, C. Piorkowski, T. Gaspar, P. Sommer, A. Bollmann, D. Wichterle, P. Peichl, J. Simek, S. Havranek, V. Bulkova, R. Cihak, A. Jurado Roman, R. Salguero Bodes, M. Lopez Gil, A. Fontenla Cerezuela, M. De Riva Silva, F. Arribas Ynsaurriaga, A. I. Fernandez Herranz, S. De Dios Perez, A. S. Revishvili, M. Dishekov, Z. Tembotova, S. Barsamyan, D. Vaccari, C. Alvarenga, I. Jesus, J. Layher, A. Takahashi, N. Singh, P. Siot, J. P. Elkaim, I. Savelieva, L. Mcclelland, A. Lovegrove, S. Jones, J. Camm, A. F. Folino, R. Breda, P. Calzavara, J. Comisso, F. Borghetti, S. Iliceto, G. Buja, R. Mlynarski, A. Mlynarska, M. Sosnowski, J. Wilczek, P. Mabo, G. Carrault, P. Bordachar, A. Makdissi, L. Duchemin, C. Alonso, G. Neri, G. Masaro, S. Vittadello, A. Gardin, A. Barbetta, F. Di Gregorio, E. Sciaraffia, M. R. Ginks, J. S. Gustafsson, M. C. Hollmark, C. A. Rinaldi, C. Blomstrom Lundqvist, S. Brusich, D. Tomasic, B. Ferek-Petric, Z. Mavric, A. Kutarski, B. Malecka, A. Kolodzinska, M. Grabowski, E. V. Dovellini, L. Giurlani, G. Cerisano, N. Carrabba, R. Valenti, D. Antoniucci, G. Opolski, G. Tomassoni, J. Baker, R. Corbisiero, D. Martin, I. Niazi, R. Sheppard, J. Sperzel, K. Gutleben, J. Petru, L. Sediva, J. Skoda, P. Mazzone, G. Ciconte, P. Vergara, A. Marzi, G. Paglino, N. Sora, S. Gulletta, P. Della Bella, R. Pietura, M. Czajkowski, N. Cabanelas, V. P. Martins, M. Alves, F. X. Valente, L. Marta, A. Francisco, R. Silva, G. Ferreira Da Silva, Y. Huo, F. Holmqvist, J. Carlson, U. Wetzel, P. Platonov, E. Nof, R. Abu Shama, R. Kuperstein, M. S. Feinberg, M. Eldar, M. Glikson, D. Luria, P. Kubus, O. Materna, R. A. Gebauer, T. Matejka, R. Gebauer, T. Tlaskal, J. Janousek, A. Muessigbrodt, S. Richter, M. Stockburger, S. Boveda, P. Defaye, P. Stancak Branislav, G. Kaliska, M. Rolando, J. Moreno, M.- A. G. Ohlow, B. Lauer, B. Buchter, M. Schreiber, J. C. Geller, J. E. Val-Mejias, S. Ouali, S. Azzez, S. Kacem, H. Ben Salem, S. Hammas, E. Neffeti, F. Remedi, E. Boughzela, H. Miyazaki, S. Miyanaga, K. Shibayama, M. Tokuda, T. Kudo, B. Coppola, R. E. N. Shehada, P. Costandi, J. Healey, S. H. Hohnloser, M. R. Gold, A. Capucci, I. C. Van Gelder, M. Carlson, C. P. Lau, S. J. Connolly, M. D. Bogaard, G. E. Leenders, B. Maskara, A. E. Tuinenburg, P. Loh, R. N. Hauer, P. A. Doevendans, M. Meine, B. Thibault, M. Dubuc, E. Karst, K. Ryu, P. Paiement, T. Farazi, V. Puetz, C. Berndt, J. Buchholz, A. Dorszewski, C. Mornos, D. Cozma, A. Ionac, L. Petrescu, A. Mornos, S. Pescariu, M. Benser, G. Roscoe, S. De Jong, G. Roberts, P. Boileau, A. Rec, C. Folman, A. Morttada, M. Abd El Kader, R. Samir, R. Roushdy, S. Khaled, M. Abo El Maaty, B. Van Gelder, P. Houthuizen, F. A. Bracke, J. Osca Asensi, D. Tejada, J. M. Sanchez, B. Munoz, O. Cano, M. Rodriguez, M. J. Sancho-Tello, J. Olague, W. Hou, S. Rosenberg, S. Koh, J. Poore, J. Snell, M. Yang, D. Nirav, G. Bornzin, T. Deering, D. Dan, A. C. Wickliffe, S. Cazeau, K. Karimzadeh, S. Mukerji, C. Loghin, B. Kantharia, M. A. Jones, J. Lamba, C. S. Simpson, D. P. Redfearn, K. A. Michael, M. Fitzpatrick, A. Baranchuk, M. Heinke, B. Ismer, H. Kuehnert, R. Surber, A. M. Haltenberger, D. Prochnau, H. R. Figulla, N. Delarche, O. Bizeau, P. Couderc, A. Chapelet, W. Amara, A. Lazarus, S. Krupickova, C. J. M. Van Deursen, M. Strik, K. Vernooy, A. Van Hunnik, M. Kuiper, H. J. G. M. Crijns, F. W. Prinzen, N. Islam, D. Gras, W. Abraham, L. Calo, U. Birgersdotter-Green, C. Clyne, J. Herre, N. Klein, O. Kowalski, R. Lenarczyk, P. Pruszkowska, A. Sokal, T. Kukulski, T. Zielinska, S. Pluta, Z. Kalarus, J. O. Schwab, M. Gasparini, F. Anselme, J. Clementy, M. Santini, J. Martinez Ferrer, V. Burrone, E. Santi, R. Nevzorov, A. Porter, J. Kusniec, G. Golovchiner, T. Ben-Gal, B. Strasberg, M. Haim, R. Rordorf, S. Savastano, A. Sanzo, A. Vicentini, B. Petracci, M. De Amici, L. Striuli, M. Landolina, J. M. Tolosana, A. M. Martin, A. Hernandez-Madrid, A. Macias, I. Fernandez-Lozano, J. Osca, A. Quesada, Y. Noguchi, S. Shahrzad, N. Karim Soleiman, A. Tavoosi, S. Taban, Z. Emkanjoo, M. Fukunaga, M. Goya, K. Hiroshima, M. Ohe, K. Hayashi, M. Iwabuchi, H. Nosaka, M. Nobuyoshi, D. Doiny, A. Perez-Silva, S. Castrejon Castrejon, A. Estrada, M. Ortega, J. L. Lopez-Sendon, J. L. Merino, F. J. Garcia Fernandez, R. Gallardo, M. Pachon, J. Almendral, J. Martin, D. Yahya, B. Al-Mogheer, S. Gouda, E. Eweis, M. El Ramly, A. Abdelwahab, W. Kassenberg, F. H. M. Wittkampf, I. E. Hof, J. H. Heijden, K. G. E. J. Neven, R. N. W. Hauer, F. Baratto, E. Bignami, F. Pappalardo, G. Maccabelli, D. Nicolotti, A. Zangrillo, M. Nagashima, Y. An, A. Okreglicki, C. Russouw, R. Tilz, Y. Yoshiga, S. Mathew, A. Fuernkranz, A. Rillig, E. Wissner, F. Ouyang, A. De Sisti, J. Tonet, F. Gueffaf, F. Touil, P. Aouate, F. Hidden-Lucet, H. Makimoto, K. Satomi, Y. Yamada, H. Okamura, T. Noda, W. Shimizu, N. Aihara, S. Kamakura, A. Perez Silva, S. Castrejon, M. Gonzalez Vasserot, J. Senges, J. Brachmann, D. Andresen, E. Hoffmann, B. Schumacher, S. Willems, B. Springer, C. Kolb, F. Akca, T. Bauernfeind, N. M. S. De Groot, B. Schwagten, M. Witsenburg, L. Jordaens, T. Szili-Torok, Y. Hata, R. Nakagami, T. Watanabe, A. Sato, H. Watanabe, T. Kabutoya, T. Mituhashi, D. A. M. J. Theuns, T. Smith, S. S. Pedersen, L. Dabiri-Abkenari, M. W. Prull, S. Unverricht, A. Bittlinsky, H. Wirdemann, B. Sasko, S. Wirdeier, H. J. Trappe, E. Zorio Grima, J. Rueda, P. Medina, T. Jaijo, T. Sevilla, M. A. Arnau, A. Salvador, A. H. Starrenburg, K. Kraaier, M. F. Scholten, J. Van Der Palen, S. De Haan, J. Commandeur, K. De Boer, A. M. Beek, A. C. Van Rossum, C. P. Allaart, P. Berne, J. M. Porres, J. A. Arnaiz, R. Brugada, S. Man, A. C. Maan, J. Thijssen, E. E. Van Der Wall, M. J. Schalij, L. Burattini, R. Burattini, C. A. Swenne, A. Bonny, I. Ditah, F. Larrazet, R. Frank, G. Fontaine, P. H. Van Der Voort, M. Alings, A. Shimane, K. Okajima, G. Kanda, K. Yokoi, S. Yamada, Y. Taniguchi, T. Hayashi, T. Kajiya, M. C. Santos, J. Wright, J. Betts, R. Denman, L. Dominguez-Perez, M. A. Arias Palomares, J. Toquero, E. Diaz-Infante, L. Tercedor, I. Valverde, A. Napp, S. Joosten, D. Stunder, M. Zink, N. Marx, P. Schauerte, J. Silny, M. E. Trucco, M. Arce, J. Palazzolo, F. Femenia, J. M. Glad, S. J. Szymkiewicz, J. Fernandez-Armenta, O. Camara, L. L. Mont, E. Diaz, E. Silva, A. Frangi, B. Brembilla-Perrot, F. Laporte, J. Morinigo, C. Ledesma, C. Hadid, M. Ortiz, C. Wolpert, E. Cobo, X. Navarro, F. Arribas, Y. Miki, S. Naitoh, K. Kumagai, K. Goto, K. Kaseno, S. Oshima, K. Taniguchi, S. Rivera, G. Albina, A. Klein, R. Laino, V. Sammartino, A. Giniger, M. Muggenthaler, H. Raju, M. Papadakis, N. Chandra, R. Bastiaenen, E. R. Behr, S. Sharma, N. Samniah, Y. Radezishvsky, H. Omari, U. Rosenschein, A. R. Perez Riera, M. Ferreira, W. M. Hopman, W. F. Mcintyre, A. R. Baranchuk, W. Wongcharoen, K. Keanprasit, A. Phrommintikul, R. Chaiwarith, A. Yagishita, H. Hachiya, T. Nakamura, Y. Tanaka, K. Higuchi, M. Kawabata, K. Hirao, M. Isobe, V. Stoickov, S. Ilic, M. Deljanin Ilic, P. Aagaard, A. Sahlen, L. Bergfeldt, F. Braunschweig, A. Sousa, A. Lebreiro, C. Sousa, S. Oliveira, A. S. Correia, I. Rangel, J. Freitas, M. J. Maciel, E. Asensio Lafuente, A. A. C. Aguilera, M. A. C. C. Corral, K. L. M. C. Mendoza, P. E. N. D. Nava, A. L. R. C. Rendon, L. V. C. Villegas, L. C. M. Castillo, R. Schaerf, R. Develle, C. Oliver, P. Y. Zinzius, R. A. Providencia, A. Botelho, J. Trigo, J. Nascimento, N. Quintal, P. Mota, A. M. Leitao-Marques, J. Borbola, P. Abraham, C. S. Foldesi, A. Kardos, S. Almeida, M. B. Santos, R. Quaresma, F. B. Morgado, P. Adragao, M. Fatemi, R. Didier, G. Le Gal, Y. Etienne, Y. Jobic, M. Gilard, J. Boschat, J. Mansourati, M. Zubaid, W. Rashed, A. Alsheikh-Ali, W. Almahmeed, A. Shehab, K. Sulaiman, N. Asaad, H. Amin, L. V. A. Boersma, M. Swaans, M. Post, B. Rensing, K. Jarverud, M. Broome, K. Noren, T. Svensson, S. Hjelm, M. Hollmark, A. Bjorling, K. Maeda, M. Takagi, K. Suzuki, H. Tatsumi, M. Yoshiyama, E. Simeonidou, C. Michalakeas, S. Kastellanos, C. Varounis, A. Nikolopoulou, C. Koniari, M. Anastasiou-Nana, T. Furukawa, R. Maggi, C. Bertolone, D. Fontana, M. Brignole, A. Z. Pietrucha, M. Wnuk, I. Bzukala, D. Mroczek-Czernecka, E. Konduracka, O. Kruszelnicka, W. Piwowarska, J. Nessler, N. Edvardsson, G. Rieger, C. Garutti, N. Linker, C. Jorge, J. Silva Marques, A. Veiga, J. Cruz, M. J. Correia, J. Sousa, G. Miltenberger-Miltenyi, A. Nunes Diogo, D. Matic, I. Mrdovic, G. Stankovic, M. Asanin, N. Antonijevic, M. Matic, N. Kocev, Z. Vasiljevic, M. A. Ramirez-Marrero, B. Perez-Villardon, J. L. Delgado-Prieto, M. Jimenez-Navarro, E. De Teresa-Galvan, M. De Mora-Martin, K. Sztefko, A. Malek, N. De Groot, T. Shalganov, M. Schalij, N. Rivas, J. Casaldaliga, I. Roca, A. Pijuan, J. Perez-Rodon, L. Dos, D. Garcia-Dorado, A. Moya, A.- E. Baruteau, A. Behaghel, S. Chatel, J. J. Schott, J. C. Daubert, H. Le Marec, V. Probst, J. Navarro-Manchon, P. Molina, B. Igual, M. Bermejo, J. 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Subjects
medicine.medical_specialty, business.industry, Physiology (medical), Internal medicine, Diastole, medicine, Cardiology, Cardiology and Cardiovascular Medicine, business
Abstract

spectively), (p

Published
2011
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