P3830Carvedilol treatment diminishes spontaneous calcium release and electrical activity in human atrial myocytes

Autor: Sergi Casabella, A Ginel, V Jimenez-Sabado, Juan Cinca, H Colino, Leif Hove-Madsen, T Lu, Adela Herraiz-Martínez, Carmen Tarifa, Anna Llach
Rok vydání: 2019
Předmět:
Zdroj: European Heart Journal. 40
ISSN: 1522-9645
0195-668X
DOI: 10.1093/eurheartj/ehz745.0672
Popis: Background Atrial fibrillation (AF) has been associated with an increase in spontaneous calcium release induced electrical activity, which could potentially be reversed by carvedilol, a nonselective beta-blocker that also inhibits the cardiac ryanodine receptor (RyR2). Interestingly the enantiomer R-carvedilol inhibits the RyR2 but not beta-adrenergic receptors, allowing it to effectively prevent calcium release-induced spontaneous electrical activity without inducing bradycardia and hypotension. Purpose The purpose of this study was to determine how carvedilol treatment affects calcium release-induced transient inward currents (ITI) in human atrial myocytes from patients with AF; and to test the effects of R-carvedilol on spontaneous calcium release in order to assess its therapeutical utility. Methods Human atrial myocytes were isolated from patients undergoing cardiac surgery and subjected to patch-clamp technique (n=60) or confocal calcium imaging (n=6). Beta-2 adrenergic receptors were activated with the selective agonist fenoterol (3μM) and 1μM R-carvedilol was used to inhibit spontaneous calcium release events. Results Recordings of calcium release-induced transient inward currents (ITI) revealed that carvedilol treatment reduced the ITI frequency in patients with AF from 2.2±0.4 events/min in untreated patients to 0.59±0.35 events/min (p Conclusions Carvedilol treatment reduces the ITI frequency in patients with AF to levels below that observed at baseline in patients without AF. Furthermore, the non-beta-blocking R-carvedilol enantiomer abolishes spontaneous calcium release events induced by beta-2 adrenergic stimulation in human atrial myocytes, proposing a therapeutical utility for this compound in patients with AF linked to excessive spontaneous calcium release. Acknowledgement/Funding SAF2017-88019; Marato2015-20-30; SGR2017-1769; CIBERCV
Databáze: OpenAIRE
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