Phosphodiesterase 2 protects against catecholamine-induced arrhythmia and preserves contractile function after myocardial infarction

• Verfasst von: Vettel, Christiane [VerfasserIn]
• Verfasst von: Dewenter, Matthias [VerfasserIn]
• Verfasst von: Wieland, Thomas [VerfasserIn]
• Titel: Phosphodiesterase 2 protects against catecholamine-induced arrhythmia and preserves contractile function after myocardial infarction
• Verf.angabe: Christiane Vettel, Marta Lindner, Matthias Dewenter, Kristina Lorenz, Constanze Schanbacher, Merle Riedel, Simon Lämmle, Simone Meinecke, Fleur E. Mason, Samuel Sossalla, Andreas Geerts, Michael Hoffmann, Frank Wunder, Fabian J. Brunner, Thomas Wieland, Hind Mehel, Sarah Karam, Patrick Lechêne, Jérôme Leroy, Grégoire Vandecasteele, Michael Wagner, Rodolphe Fischmeister, Ali El-Armouche
• Jahr: 2017
• Jahr des Originals: 2016
• Umfang: 13 S.
• Illustrationen: Illustrationen
• Fussnoten: Originally published 31 Oct 2016 ; Gesehen am 20.09.2018
• Titel Quelle: Enthalten in: Circulation research
• Ort Quelle: New York, NY : Assoc., 1953
• Jahr Quelle: 2017
• Band/Heft Quelle: 120(2017), 1, Seite 120-132
• ISSN Quelle: 1524-4571
• DOI: doi:10.1161/CIRCRESAHA.116.310069
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 1581144733

Abstract

Rationale:Phosphodiesterase 2 is a dual substrate esterase, which has the unique property to be stimulated by cGMP, but primarily hydrolyzes cAMP. Myocardial phosphodiesterase 2 is upregulated in human heart failure, but its role in the heart is unknown. Objective:To explore the role of phosphodiesterase 2 in cardiac function, propensity to arrhythmia, and myocardial infarction. Methods and Results:Pharmacological inhibition of phosphodiesterase 2 (BAY 60-7550, BAY) led to a significant positive chronotropic effect on top of maximal β-adrenoceptor activation in healthy mice. Under pathological conditions induced by chronic catecholamine infusions, BAY reversed both the attenuated β-adrenoceptor-mediated inotropy and chronotropy. Conversely, ECG telemetry in heart-specific phosphodiesterase 2-transgenic (TG) mice showed a marked reduction in resting and in maximal heart rate, whereas cardiac output was completely preserved because of greater cardiac contraction. This well-tolerated phenotype persisted in e...