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?-adrenergic stimulation augments transmural dispersion of repolarization via modulation of delayed rectifier currents IKs and IKr in the human ventricle.

ABSTRACT: Long QT syndrome (LQTS) is an inherited or drug induced condition associated with delayed repolarization and sudden cardiac death. The cardiac potassium channel, IKr, and the adrenergic-sensitive cardiac potassium current, IKs, are two primary contributors to cardiac repolarization. This study aimed to elucidate the role of ?-adrenergic (?-AR) stimulation in mediating the contributions of IKr and IKs to repolarizing the human left ventricle (n?=?18). Optical mapping was used to measure action potential durations (APDs) in the presence of the IKs blocker JNJ-303 and the IKr blocker E-4031. We found that JNJ-303 alone did not increase APD. However, under isoprenaline (ISO), both the application of JNJ-303 and additional E-4031 significantly increased APD. With JNJ-303, ISO decreased APD significantly more in the epicardium as compared to the endocardium, with subsequent application E-4031 increasing mid- and endocardial APD80 more significantly than in the epicardium. We found that ?-AR stimulation significantly augmented the effect of IKs blocker JNJ-303, in contrast to the reduced effect of IKr blocker E-4031. We also observed synergistic augmentation of transmural repolarization gradient by the combination of ISO and E-4031. Our results suggest ?-AR-mediated increase of transmural dispersion of repolarization, which could pose arrhythmogenic risk in LQTS patients.

SUBMITTER: Kang C

PROVIDER: S-EPMC5698468 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature

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β-adrenergic stimulation augments transmural dispersion of repolarization via modulation of delayed rectifier currents IKs and IKr in the human ventricle.

Kang C C Badiceanu A A Brennan J A JA Gloschat C C Qiao Y Y Trayanova N A NA Efimov I R IR

Scientific reports 20171121 1

Long QT syndrome (LQTS) is an inherited or drug induced condition associated with delayed repolarization and sudden cardiac death. The cardiac potassium channel, IKr, and the adrenergic-sensitive cardiac potassium current, IKs, are two primary contributors to cardiac repolarization. This study aimed to elucidate the role of β-adrenergic (β-AR) stimulation in mediating the contributions of IKr and IKs to repolarizing the human left ventricle (n = 18). O ...[more]

PMID: 29162896

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Project description:BackgroundThe previous studies have shown that individuals with hypertension and anxiety have a higher mean left ventricular mass index (LVMI) and QTc dispersion. We explored the associations between anxiety and left ventricular hypertrophy (LVH) and between anxiety and transmural dispersion of repolarization (TDR) (as detected by T peak-T end interval/QT interval, Tp-Te/QT ratio) in patients with hypertension.MethodsA total of 353 patients with uncomplicated hypertension from the Shaanxi Provincial People's Hospital were enrolled between 2017 and 2021. Anxiety was defined as a Hamilton Anxiety Scale (HAM-A) score ≥ 14. Logistic regression models were used to estimate the association between HAM-A and LVH. The association between HAM-A score and Tp-Te/QT was estimated using linear regression.ResultsParticipants were divided into two groups based on the presence of anxiety. LVMI was significantly higher in patients with hypertension and anxiety than in those with hypertension without anxiety (no anxiety: 84.36 ± 23.82, anxiety: 105.75 ± 25.45 g/m2, p < 0.001). HAM-A score was positively correlated with LVMI (r = 0.578, p < 0.001) and with Tp-Te/QT (r = 0.252, p < 0.001). Logistic regression models showed that patients with hypertension and anxiety were at higher risk of LVH than were patients with hypertension without anxiety (adjusted OR, 2.44, 95% CI, 1.35-4.43, p = 0.003). The linear regression analysis showed that the HAM-A score was associated with Tp-Te/QT ratio (adjusted β, 0.001, 95% CI, 0.001-0.002, p = 0.013). There was an interaction between sex and anxiety for LVH risk (p for interaction = 0.035) and for increased Tp-Te/QT (p for interaction = 0.014). After stratification by sex, anxiety was associated with increased risk for LVH in men with hypertension (adjusted OR, 5.56, 95% CI, 2.07-14.98, p = 0.001), but not in women (adjusted: OR, 1.44, 95% CI, 0.64-3.26, p = 0.377) with hypertension. The HAM-A score was also positively associated with Tp-Te/QT ratio in male (adjusted β, 0.002, 95% CI, 0.001-0.003, p < 0.001), but not in women (adjusted β, 0.001, 95% CI, -0.0002-0.002, p = 0.165).ConclusionOur results indicated that anxiety was associated with LVH and with increased TDR in men with hypertension, but not in women with hypertension.

Dataset Information

?-adrenergic stimulation augments transmural dispersion of repolarization via modulation of delayed rectifier currents IKs and IKr in the human ventricle.

Publications

β-adrenergic stimulation augments transmural dispersion of repolarization via modulation of delayed rectifier currents I<sub>Ks</sub> and I<sub>Kr</sub> in the human ventricle.

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