Regional prolongation of ARI and altered restitution  properties cause ventricular arrhythmia in heart failure

Watanabe, Tetsu; Yamaki, Michiyasu; Yamauchi, Sou; Minamihaba, Osamu; Miyashita, Takehiko; Tomoike, Hitonobu

doi:10.1152/ajpheart.2002.282.1.h212

Cited by 21 publications

(13 citation statements)

References 30 publications

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“…Nevertheless, the hearts were vulnerable to arrhythmia. Previously, we reported the same phenomenon for induced VF in congestive heart failure [19] and pharmacological LQT2 [20]. In these studies, the slopes were 0.74 and 0.75, respectively; however, the hearts were definitely vulnerable to arrhythmia.…”

Section: Restitution Hypothesis On Vf Induction In Ischemic Heartsupporting

confidence: 61%

Dynamic and not static change in ventricular repolarization is a substrate of ventricular arrhythmia on chronic ischemic myocardium

Yuuki

Hosoya

Yamaki

2004

Cardiovascular Research

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Section: Restitution Hypothesis On Vf Induction In Ischemic Heartsupporting

confidence: 61%

Dynamic and not static change in ventricular repolarization is a substrate of ventricular arrhythmia on chronic ischemic myocardium

Yuuki

Hosoya

Yamaki

2004

Cardiovascular Research

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“…We also tested the hypothesis that changes in APD ss are responsible for reported alterations in the restitution curve in failing hearts, using a guinea pig model of TAC-induced hypertrophy 20 . Intracellular microelectrode recordings (using sharp electrodes) were used to compare restitution relationships in isolated ventricular myocytes from TAC and sham-operated animals.…”

Section: Resultsmentioning

confidence: 99%

“…Dependency on APD ss appears to explain why restitution relationships are steeper in different myocardial regions, 39 between myocyte cell types, 19 with drugs that prolong APD, 13–15 and with structural/molecular remodelling in heart failure 20 . Furthermore, flattening of the restitution curve at rapid heart rates may be explained by the fact that APD ss determines the magnitude of electrical restitution and that APD ss is itself a function of short-term pacing history.…”

Section: Discussionmentioning

confidence: 99%

Restitution slope is principally determined by steady-state action potential duration

Shattock

Park

Yang

et al. 2017

Cardiovascular Research

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AimsThe steepness of the action potential duration (APD) restitution curve and local tissue refractoriness are both thought to play important roles in arrhythmogenesis. Despite this, there has been little recognition of the apparent association between steady-state APD and the slope of the restitution curve. The objective of this study was to test the hypothesis that restitution slope is determined by APD and to examine the relationship between restitution slope, refractoriness and susceptibility to VF.Methods and resultsExperiments were conducted in isolated hearts and ventricular myocytes from adult guinea pigs and rabbits. Restitution curves were measured under control conditions and following intervention to prolong (clofilium, veratridine, bretylium, low [Ca]e, chronic transverse aortic constriction) or shorten (catecholamines, rapid pacing) ventricular APD. Despite markedly differing mechanisms of action, all interventions that prolonged the action potential led to a steepening of the restitution curve (and vice versa). Normalizing the restitution curve as a % of steady-state APD abolished the difference in restitution curves with all interventions. Effects on restitution were preserved when APD was modulated by current injection in myocytes pre-treated with the calcium chelator BAPTA-AM – to abolish the intracellular calcium transient. The non-linear relation between APD and the rate of repolarization of the action potential is shown to underpin the common influence of APD on the slope of the restitution curve. Susceptibility to VF was found to parallel changes in APD/refractoriness, rather than restitution slope.Conclusion(s)Steady-state APD is the principal determinant of the slope of the ventricular electrical restitution curve. In the absence of post-repolarization refractoriness, factors that prolong the action potential would be expected to steepen the restitution curve. However, concomitant changes in tissue refractoriness act to reduce susceptibility to sustained VF. Dependence on steady-state APD may contribute to the failure of restitution slope to predict sudden cardiac death.

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“…Although to a lesser degree than direct sympathetic stimulation, reflex sympathetic stimulation also creates increased heterogeneity in repolarization duration in the various regions of the diseased myocardium that can serve as the substrate for reentry and occurrence of ventricular arrhythmia. Dispersion in repolarization is a requirement for reentry, and dispersion in ARI has been previously linked to ventricular arrhythmias (9,19,22,26). Left cervicothoracic sympathectomy and thoracic epidural anesthesia can decrease the burden of ventricular arrhythmias in patients presenting in VT storm (3,16,20).…”

Section: Discussionmentioning

confidence: 99%

Sympathetic stimulation increases dispersion of repolarization in humans with myocardial infarction

Vaseghi

Lux

Mahajan

et al. 2012

American Journal of Physiology-Heart and Circulatory Physiology

119

113

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The sympathetic nervous system is thought to play a key role in genesis and maintenance of ventricular arrhythmias. The myocardial effect of sympathetic stimulation on myocardial repolarization in humans is poorly understood. The purpose of this study was to evaluate the effects of direct and reflex sympathetic stimulation on ventricular repolarization in patients with postinfarct cardiomyopathy (ICM). The effects of direct sympathetic stimulation were assessed using isoproterenol, while those of reflex sympathetic stimulation were assessed with nitroprusside infusion in ICM patients (n = 5). Five patients without cardiomyopathy were also studied. Local repolarization was measured from intracardiac electrograms that were used to calculate the activation recovery interval (ARI), a surrogate of action potential duration. Isoproterenol significantly increased heterogeneity in repolarization in patients with ICM; the decrease in ARI from baseline was 72.9 ± 9.1 ms in more viable regions, 64.5 ± 8.9 ms in the scar, and 54.9 ± 9.1 ms in border zones (P = 0.0002 and 0.014 comparing normal and scar to border zones, respectively). In response to nitroprusside, the ARI at the border zones decreased significantly more than either scar or surrounding viable myocardium, which showed an increase in ARI (P = 0.014 and 0.08 comparing normal tissue and scar to border zones, respectively). Furthermore, isoproterenol increased ARI dispersion by 70%, while nitroprusside increased ARI dispersion by 230% when ICM patients were compared to those with structurally normal hearts (P = 0.0015 and P < 0.001, respectively). In humans, both direct and reflex sympathetic stimulations increase regional differences in repolarization. The normal tissue surrounding the scar appears denervated. Dispersion of ARI in response to sympathetic stimulation is significantly increased in patients with ICM.

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Regional prolongation of ARI and altered restitution properties cause ventricular arrhythmia in heart failure

Cited by 21 publications

References 30 publications

Dynamic and not static change in ventricular repolarization is a substrate of ventricular arrhythmia on chronic ischemic myocardium

Dynamic and not static change in ventricular repolarization is a substrate of ventricular arrhythmia on chronic ischemic myocardium

Restitution slope is principally determined by steady-state action potential duration

Sympathetic stimulation increases dispersion of repolarization in humans with myocardial infarction

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