Reproducible termination of ventricular tachycardia by a single extrastimulus within the reentry circuit during the ventricular effective refractory period

Ranolazine has been found to prevent ventricular arrhythmias (VAs) during acute myocardial infarction (AMI). This study aimed to investigate its efficacy on VAs induced several days post-MI. For this purpose, 13 anesthetized rabbits underwent coronary artery ligation. Ten of these animals that survived AMI were reanesthetized 3 to 7 days later for electrophysiologic testing. An endocardial monophasic action potential combination catheter was placed in the right ventricle for simultaneous pacing and recording. Monophasic action potential duration, ventricular effective refractory period (VERP), and VAs induced by programmed stimulation were assessed. Measurements were performed during control pacing, and following an intravenous infusion of either a low-dose ranolazine (2.4 mg/kg, R1) or a higher dose ranolazine (4.8 mg/kg cumulative dose, R2). During control stimulation, 2 animals developed primary ventricular fibrillation (VF), 6 sustained ventricular tachycardia (sVT), and 2 nonsustained VT (nsVT). R1 did not prevent the appearance of VAs in any of the experiments; in contrast, it aggravated nsVT into sVT and complicated sVT termination in 2 of 6 animals. Sustained ventricular tachycardia cycle length and VERP were only slightly decreased after R1 (112 ± 5 vs 110 ± 6 ms and 101 ± 11 vs 98 ± 10 ms, respectively). R2 suppressed inducibility of control nsVT, VF, and sVT in 2 animals. In 4 animals with still inducible sVT, R2 significantly prolonged VT cycle length by 150 ± 23 ms ( P < .01), and VERP by 120 ± 7 ms ( P < .001) versus control. In conclusion, R2 exerted antiarrhythmic efficacy against subacute-MI VAs, whereas R1 rather aggravated than prevented these arrhythmias. Ventricular effective refractory period prolongation could partially explain the antiarrhythmic action of R2 in this rabbit model.

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Termination of ventricular tachycardia by single extrastimulation during the ventricular effective refractory period.

Circulation ◽

10.1161/01.cir.67.2.457 ◽

1983 ◽

Vol 67 (2) ◽

pp. 457-459 ◽

Cited By ~ 29

Author(s):

R Ruffy ◽

K J Friday ◽

W F Southworth

Keyword(s):

Ventricular Tachycardia ◽

Refractory Period ◽

Effective Refractory Period

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Discrepant effects of mexiletine on cycle length of ventricular tachycardia and on the effective refractory period in the area of slow conduction.

Heart ◽

10.1136/hrt.75.3.281 ◽

1996 ◽

Vol 75 (3) ◽

pp. 281-286

Author(s):

Y. Aizawa ◽

M. Chinushi ◽

H. Kitazawa ◽

T. Washizuka ◽

A. Abe ◽

...

Keyword(s):

Ventricular Tachycardia ◽

Refractory Period ◽

Cycle Length ◽

Effective Refractory Period ◽

Slow Conduction

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Cardiac contractility modulation regulates the structural and electrical remolding in chronic heart failure rabbit model

10.21203/rs.2.11761/v1 ◽

2019 ◽

Author(s):

FEIFEI ZHANG ◽

Yi Dang ◽

Qingqing Hao ◽

Yingxiao Li ◽

Rong Li ◽

...

Keyword(s):

Heart Failure ◽

Ventricular Tachycardia ◽

Chronic Heart Failure ◽

Refractory Period ◽

Cardiac Contractility ◽

Rabbit Model ◽

Effective Refractory Period ◽

Cardiac Contractility Modulation ◽

Failure Group ◽

Protein Levels

Abstract Background Chronic heart failure (CHF) is accompanied by complex changes in cardiac electrophysiology and functional properties of cardiomyocytes which cause the structural and electrical remodeling process. Cardiac contractility modulation (CCM) is a novel therapeutic method and has proven to be effective in improving cardiac function. This study evaluated the effects of CCM on structural and electrical remolding in a rabbit model of CHF. Methods Thirty rabbits were randomly divided into sham group, heart failure group and CCM group. CHF model was induced 12 weeks after trans aortic constriction by pressure unloading. Then cardiac contractility modulation was delivered to the myocardium lasting six hours per day for 4 weeks. Structural changes were assessed by hydroxyproline assay and picrosirius red staining. The QTc intervals, ventricular effective refractory period and the inducibility of ventricular tachycardia were measured by electrophysiological examination. Protein levels of CTGF, Gal-3, Kv4.3, KCNQ1, KCNH2 and CX43 were measured by western blot analysis. Results Our study revealed that CHF rabbits developed significant prolonged QTc, ventricular effective refractory period and increased inducibility of ventricular tachycardia. Prominent myocardial fibrosis and increased levels of hydroxyproline content were observed in the heart failure group. Changes mentioned above can be suppressed with CCM therapy in CHF rabbits. The protein levels of CTGF, Gal-3, Kv4.3, KCNQ1, KCNH2 and CX43 significantly increased in the heart failure group, but these changes were prevented in the CCM group. Conclusions The present study demonstrated that CCM treatment prevented myocardial structural and electrical remolding in a rabbit model of CHF. The beneficial effect of CCM may be related to prevention of downregulation of the CTGF, Gal-3, Kv4.3, KCNQ1, KCNH2 and CX43. These findings provide experimental evidence for the clinical use of CCM in the treatment of HF.

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Effects of Increased Extracellular Potassium Concentration Induced by Ischemia on the Vulnerability of Ventricular Arrhythmias and the Regularity of Related Ventricular Tachycardia

Applied Sciences ◽

10.3390/app11052189 ◽

2021 ◽

Vol 11 (5) ◽

pp. 2189

Author(s):

Zihui Geng ◽

Lian Jin ◽

Honglei Zhu ◽

Jianfei Wang ◽

Xiaomei Wu

Keyword(s):

Ventricular Tachycardia ◽

Myocardial Ischemia ◽

Refractory Period ◽

Ventricular Arrhythmias ◽

Potassium Concentration ◽

Simulation Method ◽

Effective Refractory Period ◽

Extracellular Potassium ◽

Extracellular Potassium Concentration ◽

Dispersion Of Repolarization

Myocardial ischemia could induce arrhythmias such as ventricular tachycardia and ventricular fibrillation, leading to sudden death and other serious consequences. This manuscript adopted the cardiac modeling and simulation method to study the activity pattern of myocardial ischemia-related ventricular tachycardia and the effect of increased extracellular potassium concentration on arrhythmia vulnerability. A whole ventricular electrophysiological model of endocardial ischemia caused by distal occlusion of left anterior descending coronary artery was established. The simulation results suggested that the relationship between the vulnerability of ventricular arrhythmias and extracellular potassium concentration was bell shaped with a peak in susceptibility at 12 mM. This result was caused by the effect of extracellular potassium concentration on the dispersion of repolarization and the effective refractory period of cardiomyocytes. The extension of the effective refractory period was due to the electrical remodeling of the ventricle. Specifically, it was because of the delayed recovery of the INa current. In addition, the regularity of endocardial/epicardial reentrant pattern during non-transmural ischemia was also analyzed. The endocardium formed micro-reentrant, while the epicardium established macro-reentrant rotating around the ischemic regions provided a new idea for the determination of clinical ablation targets.

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