Non-β-Blocking Carvedilol Analog, VK-II-86, Prevents Ouabain-Induced Cardiotoxicity.
Background It has been shown that carvedilol and its non β-blocking analog, VK-II-86, inhibit spontaneous Ca2+ release from the sarcoplasmic reticulum (SR). The aim of this study is to determine whether carvedilol and VK-II-86 suppress ouabain-induced arrhythmogenic Ca2+ waves and apoptosis in cardi...
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| Autores principales: | , , , , , , , , , , , , , , |
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| Formato: | Articulo |
| Lenguaje: | Inglés |
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2018
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| Acceso en línea: | http://sedici.unlp.edu.ar/handle/10915/124179 |
| Aporte de: |
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I19-R120-10915-124179 |
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dspace |
| institution |
Universidad Nacional de La Plata |
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I-19 |
| repository_str |
R-120 |
| collection |
SEDICI (UNLP) |
| language |
Inglés |
| topic |
Ciencias Médicas Apoptosis Arrhythmias Carvedilol Digitalis VK-II-86 |
| spellingShingle |
Ciencias Médicas Apoptosis Arrhythmias Carvedilol Digitalis VK-II-86 Gonano, Luis Alberto Sepúlveda, Marisa Noemí Morell, Malena Toteff, Tamara Racioppi, María Florencia Lascano, Elena Catalina Negroni, Jorge Antonio Fernández Ruocco, Maria Julieta Medei, Emiliano Neiman, Gabriel Miriuka, Santiago Gabriel Back, Thomas G. Chen, S. R. Wayne Mattiazzi, Alicia Ramona Vila Petroff, Martín Gerardo Non-β-Blocking Carvedilol Analog, VK-II-86, Prevents Ouabain-Induced Cardiotoxicity. |
| topic_facet |
Ciencias Médicas Apoptosis Arrhythmias Carvedilol Digitalis VK-II-86 |
| description |
Background It has been shown that carvedilol and its non β-blocking analog, VK-II-86, inhibit spontaneous Ca2+ release from the sarcoplasmic reticulum (SR). The aim of this study is to determine whether carvedilol and VK-II-86 suppress ouabain-induced arrhythmogenic Ca2+ waves and apoptosis in cardiac myocytes. Methods and Results: Rat cardiac myocytes were exposed to toxic doses of ouabain (50 µmol/L). Cell length (contraction) was monitored in electrically stimulated and non-stimulated conditions. Ouabain treatment increased contractility, frequency of spontaneous contractions and apoptosis compared to control cells. Carvedilol (1 µmol/L) or VK-II-86 (1 µmol/L) did not affect ouabain-induced inotropy, but significantly reduced the frequency of Ca2+ waves, spontaneous contractions and cell death evoked by ouabain treatment. This antiarrhythmic effect was not associated with a reduction in Ca2+ calmodulin-dependent protein kinase II (CaMKII) activity, phospholamban and ryanodine receptor phosphorylation or SR Ca2+ load. Similar results could be replicated in human cardiomyocytes derived from stem cells and in a mathematical model of human myocytes. Conclusions Carvedilol and VK-II-86 are effective to prevent ouabain-induced apoptosis and spontaneous contractions indicative of arrhythmogenic activity without affecting inotropy and demonstrated to be effective in human models, thus emerging as a therapeutic tool for the prevention of digitalis-induced arrhythmias and cardiac toxicity. |
| format |
Articulo Articulo |
| author |
Gonano, Luis Alberto Sepúlveda, Marisa Noemí Morell, Malena Toteff, Tamara Racioppi, María Florencia Lascano, Elena Catalina Negroni, Jorge Antonio Fernández Ruocco, Maria Julieta Medei, Emiliano Neiman, Gabriel Miriuka, Santiago Gabriel Back, Thomas G. Chen, S. R. Wayne Mattiazzi, Alicia Ramona Vila Petroff, Martín Gerardo |
| author_facet |
Gonano, Luis Alberto Sepúlveda, Marisa Noemí Morell, Malena Toteff, Tamara Racioppi, María Florencia Lascano, Elena Catalina Negroni, Jorge Antonio Fernández Ruocco, Maria Julieta Medei, Emiliano Neiman, Gabriel Miriuka, Santiago Gabriel Back, Thomas G. Chen, S. R. Wayne Mattiazzi, Alicia Ramona Vila Petroff, Martín Gerardo |
| author_sort |
Gonano, Luis Alberto |
| title |
Non-β-Blocking Carvedilol Analog, VK-II-86, Prevents Ouabain-Induced Cardiotoxicity. |
| title_short |
Non-β-Blocking Carvedilol Analog, VK-II-86, Prevents Ouabain-Induced Cardiotoxicity. |
| title_full |
Non-β-Blocking Carvedilol Analog, VK-II-86, Prevents Ouabain-Induced Cardiotoxicity. |
| title_fullStr |
Non-β-Blocking Carvedilol Analog, VK-II-86, Prevents Ouabain-Induced Cardiotoxicity. |
| title_full_unstemmed |
Non-β-Blocking Carvedilol Analog, VK-II-86, Prevents Ouabain-Induced Cardiotoxicity. |
| title_sort |
non-β-blocking carvedilol analog, vk-ii-86, prevents ouabain-induced cardiotoxicity. |
| publishDate |
2018 |
| url |
http://sedici.unlp.edu.ar/handle/10915/124179 |
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