Browsing by Author "Sung, Yen-Ling"

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Effects of long-term exercise on arrhythmogenesis in aged hypertensive rats
(2018-11-01)
Sung, Yen-Ling
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Wu, Chih-En
;
Syu, Jhen-Yang
;
Kuo, Terry B. J.
;
Li, Jai-Yi
Chronic hypertension is a multifactorial disease that is highly associated with cardiovascular disorders. Physical activity, such as long-term exercise, is advocated as a treatment for hypertension, but the responses of different age groups to long-term exercise are unknown. We used aged spontaneous hypertensive rats (SHRs, 80 weeks old) to test the hypothesis that long-term exercise compensated for deficient autonomic control and reduced susceptibility to ventricular tachycardia (VT) and ventricular fibrillation (VF) in this animal model. The aged SHRs were divided into control and voluntary exercise groups. Ambulatory electrocardiography was recorded for the heart rate variability (HRV) analysis. Programmed stimulation was applied to exposed hearts to induce ventricular arrhythmia in situ. Then, the hearts were isolated for an optical mapping study. The results showed that increased HRV indices were broadly related to vagal dominance in the high-intensity exercise group. Exercise altered the electrical propagation dynamic properties, such as the action potential duration restitution (APDR). Furthermore, the VF inducibility decreased with increased exercise intensity. Taken together, our results suggest that long-term exercise reduces the risk of arrhythmogenesis in aged SHRs through enhanced vagal control and stabilized electrical dynamics.
Pleiotropic Effects of Myocardial MMP-9 Inhibition to Prevent Ventricular Arrhythmia
(2016-12-14)
Weng, Ching-Hui
;
Chung, Fa-Po
;
Chen, Yao-Chang
;
Lin, Shien-Fong
;
Huang, Po-Hsun
Observational studies have established a strong association between matrix metalloproteinase-9 (MMP-9) and ventricular arrhythmia. However, whether MMP-9 has a causal link to ventricular arrhythmia, as well as the underlying mechanism, remains unclear. Here, we investigated the mechanistic involvement of myocardial MMP-9 in the pathophysiology of ventricular arrhythmia. Increased levels of myocardial MMP-9 are linked to ventricular arrhythmia attacks after angiotensin II (Ang II) treatment. MMP-9-deficient mice were protected from ventricular arrhythmia. Increased expressions of protein kinase A (PKA) and ryanodine receptor phosphorylation at serine 2808 (pS2808) were correlated with inducible ventricular arrhythmia. MMP-9 deficiency consistently prevented PKA and pS2808 increases after Ang II treatment and reduced ventricular arrhythmia. Calcium dynamics were examined via confocal imaging in isolated murine cardiomyocytes. MMP-9 inhibition prevents calcium leakage from the sarcoplasmic reticulum and reduces arrhythmia-like irregular calcium transients via protein kinase A and ryanodine receptor phosphorylation. Human induced pluripotent stem cell-derived cardiomyocytes similarly show that MMP-9 inhibition prevents abnormal calcium leakage. Myocardial MMP-9 inhibition prevents ventricular arrhythmia through pleiotropic effects, including the modulation of calcium homeostasis and reduced calcium leakage.
Proarrhythmic risk and determinants of cardiac autonomic dysfunction in collagen-induced arthritis rats
(2016-11-29)
Lin, Ting-Tse
;
Sung, Yen-Ling
;
Wu, Chih-En
;
Zhang, Hong
;
Liu, Yen-Bin
Backgrounds: Patients with rheumatoid arthritis (RA) have increased risk of sudden cardiac death (SCD), which is two-fold higher than general population. The driving cause of SCD was considered due to lift-threatening arrhythmia where systemic inflammation acts as the pathophysiological basis linking RA to autonomicdysfunction. Methods: To assess the sympathetic over-activity of "inflammatory reflex", we measured heart rate variability (HRV) in a rat collagen-induced arthritis (CIA) model, whose arthritis is induced in Lewis rats by intradermal injection of emulsion of type II collagen. Single-lead electrocardiogram (ECG) was recorded for 30 min every two days. Time and frequency-domain parameters, detrended fluctuation analysis (DFA), deceleration (DC) and acceleration capacity (AC) were analyzed. Results: Compared with 9 control rats, many of HRV parameters of 9 CIA rats revealed significant different. At the beginning of arthritis, LF/HF was significant higher than controls (1st week: 2.41 +/- 0.7 vs. 1.76 +/- 0.6, p < 0.05; 2nd week: 2.24 +/- 0.5 vs. 1.58 +/- 0.5, p < 0.05) indicating intensive inflammatory reflex at the initial phase of inflammation but no significant difference was observed in the following recover phase. The similar trend of DFA parameters was noted. However, the DC appeared progressive lower despite of no significant increase of the LF/HF compared with controls since 4th week. Conclusions: We observed sympathetic over-activation of inflammatory reflex during early stage of arthritis in CIA rats. The ongoing decline of DC indicated advanced cardiac autonomic dysfunction regardless of remission of acute arthritis.
Proarrhythmic risk and determinants of cardiac autonomic dysfunction in collagen-induced arthritis rats
(2016-11-29)
Lin, Ting-Tse
;
Sung, Yen-Ling
;
Wu, Chih-En
;
Zhang, Hong
;
Liu, Yen-Bin
Backgrounds: Patients with rheumatoid arthritis (RA) have increased risk of sudden cardiac death (SCD), which is two-fold higher than general population. The driving cause of SCD was considered due to lift-threatening arrhythmia where systemic inflammation acts as the pathophysiological basis linking RA to autonomicdysfunction. Methods: To assess the sympathetic over-activity of "inflammatory reflex", we measured heart rate variability (HRV) in a rat collagen-induced arthritis (CIA) model, whose arthritis is induced in Lewis rats by intradermal injection of emulsion of type II collagen. Single-lead electrocardiogram (ECG) was recorded for 30 min every two days. Time and frequency-domain parameters, detrended fluctuation analysis (DFA), deceleration (DC) and acceleration capacity (AC) were analyzed. Results: Compared with 9 control rats, many of HRV parameters of 9 CIA rats revealed significant different. At the beginning of arthritis, LF/HF was significant higher than controls (1st week: 2.41 +/- 0.7 vs. 1.76 +/- 0.6, p < 0.05; 2nd week: 2.24 +/- 0.5 vs. 1.58 +/- 0.5, p < 0.05) indicating intensive inflammatory reflex at the initial phase of inflammation but no significant difference was observed in the following recover phase. The similar trend of DFA parameters was noted. However, the DC appeared progressive lower despite of no significant increase of the LF/HF compared with controls since 4th week. Conclusions: We observed sympathetic over-activation of inflammatory reflex during early stage of arthritis in CIA rats. The ongoing decline of DC indicated advanced cardiac autonomic dysfunction regardless of remission of acute arthritis.
Risk of ischemic stroke in patients with hypertrophic cardiomyopathy in the absence of atrial fibrillation - a nationwide cohort study
(2019-12-15)
Lin, Ting-Tse
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Sung, Yen-Ling
;
Ko, Tsung-Yu
;
Lee, Chih-Kuo
;
Lin, Lian-Yu
Ischemic stroke (IS) is a catastrophic complication of hypertrophic cardiomyopathy (HCM) with aging. We investigated the incidence of IS in HCM patients without atrial fibrillation (AF) and compared the relative risk of IS with matched general population with AF. This study identified 17,371 HCM patients without AF and utilized propensity-score-matching to identify one-to-one matched control of general population with AF receiving oral anti-coagulants (OACs). During a median follow-up of 7.3 years, 847 (4.9%) subjects experienced IS with the incidence of 0.589/100 person-years. The corresponding matched controls experienced 788 (4.5%) events with the incidence of 0.494/100 person-years. Compared with control, HCM patients had similar risk of IS (Hazard ratios [HRs] 0.965, 95% confidence interval [CI] 0.854-1.091). HCM patients with age above 65 years had a significantly increased risk of IS (age 65-74 years, HR 1.278, 95% CI 1.070-1.335; age >= 75 years, HR 1.757, 95% CI 1.435-2.152). Stratified by CHA(2)DS(2)-VASc score, HCM subjects with score 0, 1 and 2 had significantly increased risk of IS than control while those with score >= 2 had similar risk as control. Compared with general population with AF, HCM patients without AF had similar risk of IS, suggesting OACs might be necessary in HCM patient without AF.
Unique Localization of Phospholamban in Perinuclear Membranes of Cardiomyocytes from Several Species
(2016-02-16)
Chiou, Yu-An
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Sung, Yen-Ling
;
Chen, Peng-Sheng
;
Lin, Shien-Fong
;
Chen, Zhenhui