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Arrhythmogenic remodeling of β2 versus β1 adrenergic signaling in the human failing heart.
- Source :
-
Circulation. Arrhythmia and electrophysiology [Circ Arrhythm Electrophysiol] 2015 Apr; Vol. 8 (2), pp. 409-19. Date of Electronic Publication: 2015 Feb 11. - Publication Year :
- 2015
-
Abstract
- Background: Arrhythmia is the major cause of death in patients with heart failure, for which β-adrenergic receptor blockers are a mainstay therapy. But the role of β-adrenergic signaling in electrophysiology and arrhythmias has never been studied in human ventricles.<br />Methods and Results: We used optical imaging of action potentials and [Ca(2+)]i transients to compare the β1- and β2-adrenergic responses in left ventricular wedge preparations of human donor and failing hearts. β1-Stimulation significantly increased conduction velocity, shortened action potential duration, and [Ca(2+)]i transients duration (CaD) in donor but not in failing hearts, because of desensitization of β1-adrenergic receptor in heart failure. In contrast, β2-stimulation increased conduction velocity in both donor and failing hearts but shortened action potential duration only in failing hearts. β2-Stimulation also affected transmural heterogeneity in action potential duration but not in [Ca(2+)]i transients duration. Both β1- and β2-stimulation augmented the vulnerability and frequency of ectopic activity and enhanced substrates for ventricular tachycardia in failing, but not in donor, hearts. Both β1- and β2-stimulation enhanced Purkinje fiber automaticity, whereas only β2-stimulation promoted Ca-mediated premature ventricular contractions in heart failure.<br />Conclusions: During end-stage heart failure, β2-stimulation creates arrhythmogenic substrates via conduction velocity regulation and transmurally heterogeneous repolarization. β2-Stimulation is, therefore, more arrhythmogenic than β1-stimulation. In particular, β2-stimulation increases the transmural difference between [Ca(2+)]i transients duration and action potential duration, which facilitates the formation of delayed afterdepolarizations.<br /> (© 2015 American Heart Association, Inc.)
- Subjects :
- Action Potentials
Adrenergic beta-1 Receptor Agonists pharmacology
Adrenergic beta-2 Receptor Agonists pharmacology
Arrhythmias, Cardiac diagnosis
Arrhythmias, Cardiac metabolism
Arrhythmias, Cardiac physiopathology
Case-Control Studies
Heart Failure diagnosis
Heart Failure metabolism
Heart Failure physiopathology
Heart Failure surgery
Heart Transplantation
Heart Ventricles drug effects
Heart Ventricles pathology
Heart Ventricles physiopathology
Humans
Phosphorylation
Receptors, Adrenergic, beta-1 drug effects
Receptors, Adrenergic, beta-2 drug effects
Risk Factors
Time Factors
Voltage-Sensitive Dye Imaging
Arrhythmias, Cardiac etiology
Calcium Signaling drug effects
Heart Failure complications
Heart Ventricles metabolism
Receptors, Adrenergic, beta-1 metabolism
Receptors, Adrenergic, beta-2 metabolism
Ventricular Function, Left drug effects
Ventricular Remodeling drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 1941-3084
- Volume :
- 8
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Circulation. Arrhythmia and electrophysiology
- Publication Type :
- Academic Journal
- Accession number :
- 25673629
- Full Text :
- https://doi.org/10.1161/CIRCEP.114.002065