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506 results on '"LEE, KUN‐TAI"'

20. The Arrhythmogenic Effect of Protein-Bound Uremic Toxin p-Cresylsulfate: An In Vitro Study

Author

Tsai, I-Ting, Hsu, Chia-Chang, Hung, Wei-Chin, Wang, Chao-Ping, Yu, Teng-Hung, Houng, Jer-Yiing, Lee, Kun-Tai, and Tang, Wei-Hua

Subjects
cardiovascular system, Original Article, humanities
Abstract

BACKGROUND: p-Cresylsulfate (PCS) is a protein-bound uremic toxin that accumulates in patients with chronic kidney disease. Previous studies have indicated that serum total PCS levels are significantly increased in the presence of abnormal corrected QT (QTc) intervals, and that they are associated with QTc prolongation. However, the QTc prolongation effect of PCS remains unclear. The current study aimed to investigate the arrhythmogenic effect of PCS using in vitro experiments and computer simulation. METHODS: The arrhythmogenic effect of PCS was evaluated by incubating H9c2 rat ventricular cardiomyocytes in vitro with increasing concentrations of PCS. Electrophysiological studies and mathematical computer simulations were performed. RESULTS: in vitro, the delayed rectifier potassium current (I(K)) was significantly decreased in a dose-dependent manner after treatment with PCS. The modulation of PCS on I(K) was through regulation of the phosphorylation of the major potassium ion channel protein Kv2.1. In computer simulations, the decrease in I(K) induced by PCS prolonged the action potential duration (APD) and sped up the re-entrant wave, which is known to be a trigger mechanism for lethal ventricular arrhythmias. CONCLUSIONS: PCS significantly downregulated the phosphorylation of the I(K) channel protein Kv2.1 and I(K) current activity, which increased the cardiomyocyte APD. This was observed both in vitro and in the computer O'Hara-Rudy dynamic human ventricular model. These findings suggest that PCS may play a key role in the development of cardiac arrhythmias.

Published
2019

32. The Impact of Urate‐Lowering Therapy in Post‐Myocardial Infarction Patients: Insights From a Population‐Based, Propensity Score‐Matched Analysis.

Author

Tai, Chi‐Jung, Wu, Chin‐Chung, Lee, Kun‐Tai, Tseng, Tzyy‐Guey, Wang, Hui‐Chun, Chang, Fang‐Rong, and Yang, Yi‐Hsin

Subjects
MYOCARDIAL infarction, CORONARY artery bypass, MOTIVATIONAL interviewing, PERCUTANEOUS coronary intervention, XANTHINE oxidase, NATIONAL health insurance, ARRHYTHMIA
Abstract

The role of urate‐lowering therapy (ULT) for the primary prevention of cardiovascular (CV) events has been widely discussed, but its evidence for the secondary prevention of myocardial infarction (MI) is limited. Therefore, we conduct a population‐based, propensity score‐matched cohort study to investigate the CV outcomes among patients with post‐MI with and without ULT. A total of 19,042 newly diagnosed in‐hospital patients with MI were selected using the Taiwan National Health Insurance Database between January 1, 2005, and December 31, 2016. After 1:1 propensity score matching with covariates, patients with MI with (n = 963) and without (n = 963) ULT were selected for further analysis. The primary outcome was the all‐cause mortality and the secondary outcomes were composite CV outcomes, including hospitalization for recurrent MI, stroke, heart failure, and cardiac arrhythmias. ULT users were associated with lower all‐cause mortality (adjusted hazard ratio (adjHR), 0.67; 95% confidence interval (CI), 0.51–0.87) compared to the ULT nonusers. In addition, ULT users had a significantly lower risk of recurrent MI, which needed revascularization by percutaneous coronary intervention or coronary artery bypass grafting (adjHR, 0.67; 95% CI, 0.53–0.86) than the ULT nonusers. The primary and secondary outcomes were not different between patients with post‐MI who received uricosuric agents and xanthine oxidase inhibitors. The anti‐inflammatory effect of ULT plays an essential role in MI management. From a real‐world setting, this study shows that ULT is associated with the lower risk of all‐cause mortality in patients with post‐MI. In addition, the result shows the possible lower incidence of repeat revascularization procedures in the ULT users. [ABSTRACT FROM AUTHOR]

Published
2022
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