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

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

Authors :
Odening KE
Jung BA
Lang CN
Cabrera Lozoya R
Ziupa D
Menza M
Relan J
Franke G
Perez Feliz S
Koren G
Zehender M
Bode C
Brunner M
Sermesant M
Föll D
Source :
Heart rhythm [Heart Rhythm] 2013 Oct; Vol. 10 (10), pp. 1533-41. Date of Electronic Publication: 2013 Jul 26.
Publication Year :
2013

Abstract

Background: Enhanced dispersion of action potential duration (APD) is a major contributor to long QT syndrome (LQTS)-related arrhythmias.<br />Objective: To investigate spatial correlations of regional heterogeneities in cardiac repolarization and mechanical function in LQTS.<br />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.<br />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.<br />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.<br /> (© 2013 Heart Rhythm Society. All rights reserved.)

Details

Language :
English
ISSN :
1556-3871
Volume :
10
Issue :
10
Database :
MEDLINE
Journal :
Heart rhythm
Publication Type :
Academic Journal
Accession number :
23892340
Full Text :
https://doi.org/10.1016/j.hrthm.2013.07.038