Atrial selectivity in Na+channel blockade by acute amiodarone.
Cardiovasc Res
; 98(1): 136-44, 2013 Apr 01.
Article
in En
| MEDLINE
| ID: mdl-23341577
ABSTRACT
AIMS:
Na(+) channel blockers are often used to treat atrial fibrillation (AF), but may sometimes cause ventricular contractile dysfunction. However, amiodarone, a multi-channel blocker with Na(+) channel block, causes less contractile dysfunction. In this study, we tested the hypothesis that Na(+) channel block by amiodarone is selective in atrial myocytes (AM) compared with ventricular myocytes (VM). METHODS ANDRESULTS:
Na(+) currents (INa) were measured using whole-cell patch-clamp technique in isolated rabbit AM and VM. Amiodarone inhibited INa in AM (IC50 1.8 ± 1.1 µM; n = 8) much more than in VM (40.4 ± 11.9 µM; n = 7, P < 0.01). Amiodarone at 10 µM shifted the steady-state inactivation relationship in AM (-16.2 ± 1.7 mV shift, n = 12) compared with VM (-5.9 ± 0.7 mV shift; n = 13; P < 0.01). For mexiletine, the inhibition of INa and inactivation curve shifts were comparable for AM and VM. The effects of amiodarone and mexiletine on conduction velocity (CV) in Langendorff-perfused rabbit hearts were evaluated using an optical mapping system. The decrease of CV by 3 µM amiodarone was significantly larger in the atrium (-18.9 ± 3.8% change; n = 5) compared with the ventricle (-3.7 ± 3.7%; n = 5; P < 0.01). In contrast, mexiletine reduced CV equally in the atrium and the ventricle.CONCLUSION:
Amiodarone preferentially inhibits INa of AM compared with VM. Atrial selective Na(+) channel block by amiodarone may contribute to treating AF with less effect on ventricular contractility than other Na(+) channel blockers.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Sodium Channel Blockers
/
Heart Atria
/
Amiodarone
Limits:
Animals
Language:
En
Journal:
Cardiovasc Res
Year:
2013
Document type:
Article
Affiliation country:
Japan