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Heart Rhythm. 2013 Oct;10(10):1533-41. doi: 10.1016/j.hrthm.2013.07.038. Epub 2013 Jul 26.

Spatial correlation of action potential duration and diastolic dysfunction in transgenic and drug-induced LQT2 rabbits.

Author information

1
Department of Cardiology and Angiology I, Heart Center Freiburg University, Freiburg, Germany. Electronic address: katja.odening@uniklinik-freiburg.de.

Abstract

BACKGROUND:

Enhanced dispersion of action potential duration (APD) is a major contributor to long QT syndrome (LQTS)-related arrhythmias.

OBJECTIVE:

To investigate spatial correlations of regional heterogeneities in cardiac repolarization and mechanical function in LQTS.

METHODS:

Female transgenic LQTS type 2 (LQT2; n = 11) and wild-type littermate control (LMC) rabbits (n = 9 without E4031 and n = 10 with E4031) were subjected to phase contrast magnetic resonance imaging to assess regional myocardial velocities. In the same rabbits' hearts, monophasic APDs were assessed in corresponding segments.

RESULTS:

In LQT2 and E4031-treated rabbits, APD was longer in all left ventricular segments (P < .01) and APD dispersion was greater than that in LMC rabbits (P < .01). In diastole, peak radial velocities (Vr) were reduced in LQT2 and E4031-treated compared to LMC rabbits in LV base and mid (LQT2: -3.36 ± 0.4 cm/s, P < .01; E4031-treated: -3.24 ± 0.6 cm/s, P < .0001; LMC: -4.42 ± 0.5 cm/s), indicating an impaired diastolic function. Regionally heterogeneous diastolic Vr correlated with APD (LQT2: correlation coefficient [CC] 0.38, P = .01; E4031-treated: CC 0.42, P < .05). Time-to-diastolic peak Vr were prolonged in LQT2 rabbits (LQT2: 196.8 ± 2.9 ms, P < .001; E4031-treated: 199.5 ± 2.2 ms, P < .0001, LMC 183.1 ± 1.5), indicating a prolonged contraction duration. Moreover, in transgenic LQT2 rabbits, diastolic time-to-diastolic peak Vr correlated with APD (CC 0.47, P = .001). In systole, peak Vr were reduced in LQT2 and E4031-treated rabbits (P < .01) but longitudinal velocities or ejection fraction did not differ. Finally, random forest machine learning algorithms enabled a differentiation between LQT2, E4031-treated, and LMC rabbits solely based on "mechanical" magnetic resonance imaging data.

CONCLUSIONS:

The prolongation of APD led to impaired diastolic and systolic function in transgenic and drug-induced LQT2 rabbits. APD correlated with regional diastolic dysfunction, indicating that LQTS is not purely an electrical but an electromechanical disorder.

KEYWORDS:

APD; APD(75); CC; Cardiac MRI; Cardiac electrophysiology; Diastolic function; ECG; EPS; I(Ca,L); I(Kr); IV; L-type Ca2+ current; LMC; LQT2; LQTS; LV; Long QT syndrome; MAP; MRI; QTc; Rabbits; Repolarization; SD; TTP; Vr; Vr_dia; Vz; Vz_dia; [Ca(2+)](i); action potential duration; action potential duration at 75% of repolarization; correlation coefficient; cytoplasmic Ca(2+) concentration; diastolic peak long-axis velocities; diastolic peak radial velocities; electrocardiogram; electrophysiological study; heart-rate corrected QT; intravenously; left ventricle/ventricular; long QT syndrome; long QT syndrome type 2; long-axis velocities; magnetic resonance imaging; monophasic action potential; pVT; polymorphic ventricular tachycardia; radial velocities; rapid delayed rectifier potassium current; standard deviation; time-to-peak velocities; wild-type littermate control

PMID:
23892340
DOI:
10.1016/j.hrthm.2013.07.038
[Indexed for MEDLINE]

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