Triggers of ventricular tachyarrhythmias and therapeutic effects of nicorandil in canine models of LQT2 and LQT3 syndromes
Masaomi Chinushi, MD*,*,
Hidehiro Kasai, MD ,
Minoru Tagawa, MD,
Takashi Washizuka, MD,
Yukio Hosaka, MD,
Yuko Chinushi, MD and
Yoshifusa Aizawa, MD
* School of Health Science,Niigata, Japan
First Department of Internal Medicine, Niigata University School of Medicine, Niigata, Japan
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Figure 1 Inducibility of ventricular tachyarrhythmia before and after administration of nicorandil. Each bar represents the number of experiments during which ventricular tachyarrhythmias were induced. BRADY = bradycardia produced by atrioventricular block; LQT2 and LQT3 = long QT syndrome, types 2 and 3, respectively; LSS = left stellate (ganglion) stimulation; PVS = programmed ventricular stimulation.
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Figure 2 Induction of ventricular tachyarrhythmias (VTAs) in the long QT syndrome type 2 (LQT2) (A) and long QT syndrome type 3 (LQT3) (B and C) models. During 600-ms basic cycle length pacing, VTA was initiated by a premature beat during left stellate (ganglion) stimulation (LSS) in LQT2 (A). In the LQT3 model, LSS induced multiple premature ventricular complexes and initiated VTA (B). (C) Bradycardia produced by atrioventricular block-dependent VTA. A premature ventricular beat (#) infringed on spatial dispersion of repolarization and created functional conduction block or delayed conduction at the mid-myocardial site (Mid). Endo = endocardial site; Epi = epicardial site.
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Figure 3 Transmural unipolar recording of the left ventricle in the long QT syndrome type 2 (LQT2) model. The activation-recovery interval (ARI) and its transmural dispersion are presented during pacing at basic cycle lengths (BCLs) of 600 ms (A), 400 ms (B) and 600 ms after nicorandil (C). The ARI measurements are shown with each electrogram. The thin vertical line in each electrogram represents the point of the maximal derivative of the T-wave. (A) The mid-myocardial (Mid) site shows greater ARI prolongation than the epicardial (Epi) or endocardial (Endo) sites, resulting in a 43- to 44-ms ARI dispersion across the ventricular wall. Faster pacing at a 400-ms BCL shortened ARI at all sites, and transmural ARI dispersion was reduced to 30 to 31 ms (B). Compared with faster pacing, the magnitude of ARI shortening was significantly greater when nicorandil was administrated during 600-ms BCL pacing, and transmural ARI dispersion decreased to 25 to 26 ms (C).
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Figure 4 Mean transmural activation-recovery interval (ARI) dispersion in the long QT syndrome type 2 (LQT2) and long QT syndrome type 3 (LQT3) models. See text for details. N.S. = not significant.
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Figure 5 Transmural unipolar recordings of the left ventricle in the long QT syndrome type 3 (LQT3) model, as presented in Figure 3. (A) Pacing at 600-ms basic cycle length (BCL). The activation-recovery interval (ARI) at the mid-myocardial (Mid) site was longer than that at the epicardial (Epi) and endocardial (Endo) sites, and marked ARI dispersion of 69 ms was observed across the ventricular wall. Faster pacing at 400-ms BCL (B) shortened ARI at all sites, and transmural ARI dispersion was decreased to 30 to 33 ms. Intravenous administration of nicorandil slightly shortened all ARIs at 600-ms BCL pacing (C), and prominent transmural ARI dispersion of 54 to 56 ms persisted across the ventricular wall.
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