Browsing by Author "Tuan, Ta-Chuan"

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Interleukin-17 enhances cardiac ventricular remodeling via activating MAPK pathway in ischemic heart failure
(2018-09-01)
Chang, Shih-Lin
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Hsiao, Ya-Wen
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Tsai, Yung-Nan
;
Lin, Shien-Fong
;
Liu, Shuen-Hsin
Background: We aimed to investigate the impact of interleukin (IL)-17 on ventricular remodeling and the genesis of ventricular arrhythmia (VA) in an ischemic heart failure (HF) model. The expression of the proinflammatory cytokine IL-17 is upregulated during myocardial ischemia and plays a fundamental role in post-infarct inflammation. However, the influence of IL-17 on the genesis of VA has not yet been studied. Methods and results: The level of inflammation and Th17 cell (CD4(+)IL-17(+)) expression in the rabbit model of ischemic HF were studied by flow cytometry, quantitative polymerase chain reaction (qPCR), and enzyme-linked immunosorbent assay (ELISA). The effect of IL-17 on VA induction following acute and chronic administration of IL-17 was determined using electrophysiological techniques and optical mapping. The expression of IL-17 target genes and related cytokines and chemokines in vivo and in vitro were measured using qPCR, ELISA, and immunoblotting. Th17 cells were markedly increased in the ischemic HF rabbit model. IL-17 directly induced VA in vivo and in vitro in a dose-dependent manner. IL-17 decreased conduction velocity, lengthened action potential duration, and increased the slope of the left ventricle (LV) restitution curve. IL-17 treatment led to fibrosis, collagen production and apoptosis in the LV. Furthermore, increased IL-17 signaling activated mitogen-activated protein kinase and increased the expression of downstream target genes, IL-6, TNF, CCL20, and CXCL1. An anti IL -17 neutralizing antibody abolished the effects of IL-17. Conclusions: The expression of IL-17 and its downstream target genes may play fundamental roles in inducing VA in ischemic HF.
Ventricular divergence correlates with epicardial wavebreaks and predicts ventricular arrhythmia in isolated rabbit hearts during therapeutic hypothermia
(2020-02-21)
Hsieh, Yu-Cheng
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Hsieh, Wan-Hsin
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Li, Cheng-Hung
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Liao, Ying-Chieh
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Lin, Jiunn-Cherng
Introduction High beat-to-beat morphological variation (divergence) on the ventricular electrogram during programmed ventricular stimulation (PVS) is associated with increased risk of ventricular fibrillation (VF), with unclear mechanisms. We hypothesized that ventricular divergence is associated with epicardial wavebreaks during PVS, and that it predicts VF occurrence. Method and results Langendorff-perfused rabbit hearts (n = 10) underwent 30-min therapeutic hypothermia (TH, 30 degrees C), followed by a 20-min treatment with rotigaptide (300 nM), a gap junction modifier. VF inducibility was tested using burst ventricular pacing at the shortest pacing cycle length achieving 1:1 ventricular capture. Pseudo-ECG (p-ECG) and epicardial activation maps were simultaneously recorded for divergence and wavebreaks analysis, respectively. A total of 112 optical and p-ECG recordings (62 at TH, 50 at TH treated with rotigaptide) were analyzed. Adding rotigaptide reduced ventricular divergence, from 0.13 +/- 0.10 at TH to 0.09 +/- 0.07 (p = 0.018). Similarly, rotigaptide reduced the number of epicardial wavebreaks, from 0.59 +/- 0.73 at TH to 0.30 +/- 0.49 (p = 0.036). VF inducibility decreased, from 48 +/- 31% at TH to 22 +/- 32% after rotigaptide infusion (p = 0.032). Linear regression models showed that ventricular divergence correlated with epicardial wavebreaks during TH (p<0.001). Conclusion Ventricular divergence correlated with, and might be predictive of epicardial wavebreaks during PVS at TH. Rotigaptide decreased both the ventricular divergence and epicardial wavebreaks, and reduced the probability of pacing-induced VF during TH.