Regional ?-adrenergic regulation of action potential duration and arrhythmias in the pig right ventricle - 26/03/18
Résumé |
Introduction |
The right ventricular outflow tract (RVOT) is the main origin of idiopathic ventricular tachycardia (VT). Although these arrhythmias appear to be cAMP-dependent, the actual mechanisms leading to VT remain uncertain. Here we studied β-adrenergic regulation of action potential duration (APD) in the healthy pig right ventricle (RV).
Objective |
To determine regional β-adrenergic regulation of APD and arrhythmias in the RVOT.
Methods |
The RV of 4 pig hearts were isolated and perfused via both the coronary arteries. Epicardial electrical activity was optically mapped (di-4-ANEPPS 20μM) and APD measured at 80% repolarization (APD80) in the RVOT and posterior RV free wall region (RVFW). Regional mRNA and protein expression of β-adrenergic receptors was determined respectively by RT-PCR and Western-Blot.
Results |
The expression of β1-adrenergic receptor (β1-AR) was lower in the RVOT at the mRNA level (P<0.05) but remained unchanged at the protein level compared to the RVFW while β2-adrenergic receptor (β2-AR) expression remained similar in both regions. At lower concentrations (0.6–10nM), isoprenaline (ISO) led to a prolongation of APD80 in the RVOT and the RVFW. Higher ISO concentrations (500nM–1μM) led to a larger APD80 shortening in the RVOT than in the RVFW and triggered VT episodes that originated from the RVOT or the anterior RV. β2-AR blockade (ICI 118,551 100nM) accelerated while β1-AR blocker Metoprolol (4μM) slowed or abolished VT. Similar ISO concentrations triggered bursts of Ca2+ transients in RVOT myocytes that stopped upon ISO washout while these events remained rare in RVFW myocytes.
Conlcusion |
β-adrenergic stimulation differentially regulates APD80 in the RVOT and RVFW. Although β1-AR expression was similar in the 2 regions, ISO preferentially shortened APD and triggered arrhythmia in the RVOT. These results suggest the presence of a high sensitivity of RVOT electrophysiology to β-adrenergic stimulation.
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Vol 10 - N° 2
P. 240 - avril 2018 Retour au numéroBienvenue sur EM-consulte, la référence des professionnels de santé.
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