期刊
HEART RHYTHM
卷 12, 期 1, 页码 220-228出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.hrthm.2014.10.003
关键词
Long QT syndrome; Early afterdepolarization; Ventricular tachycardia; Polymorphic ventricular tachycardia; Action potential duration dispersion; Optical mapping; Bi-excitability
资金
- National Heart, Lung, and Blood Institute [R01-HL-096669-04, R01-HL-046005-18A1, R01 HL110791-01A1]
BACKGROUND Long QT syndrome type 1 (LQT1) is a congenital disease arising from a loss of function in the slowly activating delayed potassium current I-Ks which causes early afterdepolarizabons (EADs) and polymorphic ventricular tachycardia (pVT). OBJECTIVE The purpose of this study was to investigate the mechanisms underlying pVT using a transgenic rabbit model of LQT1. METHODS Hearts were perfused retrogradely, and action potentials were recorded using a voltage-sensitive dye and CMOS cameras. RESULTS Bolus injection of isoproterenol (140 nM) induced pVT initiated by focal excitations from the right ventricle (RV; n = 15 of 18 pVTs). After the pVT was initiated, complex focal excitations occurred in both the RV and the left ventricle, which caused oscillations of the QRS complexes on ECG, consistent with the recent proposal of multiple shifting foci caused by EAD chaos. Moreover, the action potential upstroke in pVT showed a bimodal distribution, demonstrating the coexistence of 2 types of excitation that interacted to produce complex pVT: Na+ current (I-Na)-mediated fast conduction and L-type Ca2+ current (I-ca)-mediated slow conduction coexist, manifesting as pVT. Addition of 2 mu M tetrodotoxin to reduce I-Na converted pVT into monomorphic VT. Reducing late I-Na in computer simulation converted pVT into a single dominant reentry, agreeing with experimental results. CONCLUSION Our study demonstrates that pVT in LQT1 rabbits is initiated by focal excitations from the RV and is maintained by multiple shifting foci in both ventricles. Moreover, wave conduction in pVT exhibits bi-excitability, that is, fast wavefronts driven by I-Na and slow wavefronts driven by I-ca co-exist during pVT.
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