Sick sinus syndrome (SSS) is a disease with bradycardia or arrhythmia. The pathological mechanism of SSS is mainly due to the abnormal conduction function of the sinoatrial node (SAN) caused by interstitial lesions or fibrosis of the SAN or surrounding tissues, SAN pacing dysfunction, and SAN impulse conduction accompanied by SAN fibrosis. Tongyang Huoxue Decoction (TYHX) is widely used in SSS treatment and amelioration of SAN fibrosis. It has a variety of active ingredients to regulate the redox balance and mitochondrial quality control. This study mainly discusses the mechanism of TYHX in ameliorating calcium homeostasis disorder and redox imbalance of sinoatrial node cells (SANCs) and clarifies the protective mechanism of TYHX on the activity of SANCs. The activity of SANCs was determined by CCK-8 and the TUNEL method. The levels of apoptosis, ROS, and calcium release were analyzed by flow cytometry and immunofluorescence. The mRNA and protein levels of calcium channel regulatory molecules and mitochondrial quality control-related molecules were detected by real-time quantitative PCR and Western Blot. The level of calcium release was detected by laser confocal. It was found that after H/R treatment, the viability of SANCs decreased significantly, the levels of apoptosis and ROS increased, and the cells showed calcium overload, redox imbalance, and mitochondrial dysfunction. After treatment with TYHX, the cell survival level was improved, calcium overload and oxidative stress were inhibited, and mitochondrial energy metabolism and mitochondrial function were restored. However, after the SANCs were treated with siRNA (si-β-tubulin), the regulation of TYHX on calcium homeostasis and redox balance was counteracted. These results suggest that β-tubulin interacts with the regulation of mitochondrial function and calcium release. TYHX may regulate mitochondrial quality control, maintain calcium homeostasis and redox balance, and protect SANCs through β-tubulin. The regulation mechanism of TYHX on mitochondrial quality control may also become a new target for SSS treatment.
Background. The transient outward potassium current (Ito) and the ultrarapid delayed rectifier potassium current (IKur) are major potassium currents involved in the repolarization process of sinoatrial node cells (SNCs). Methods and Results. The SNCs of neonatal rats were divided into control, ischemia/reperfusion (I/R), I/R+blank serum, and Tongyang Huoxue recipe (TYHX) serum groups. Ito and IKur were recorded using the whole cell patch-clamp technique, and the current-voltage (I-V), steady-state activation (SSA), steady-state inactivation (SSI), and recovery from inactivation (RFI) curves were plotted, respectively. Compared to the control group, both the peak current density and the current density at the voltage of Ito and IKur decreased obviously in SNCs after simulated I/R, the SSA curves moved right, and the SSI curves moved left. After TYHX was added to the extracellular solution of SNCs, both the peak current density and the current density at the voltage of Ito and IKur increased significantly, the SSA curves moved left, and the SSI curves moved right with a significant difference of
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. The recovery from the IKur RFI curves was slightly restored, and the Ito curves did not change. Conclusions. TYHX increases the peak current density, accelerates the activation, and decreases the inactivation of the Ito and IKur. This may be the mechanism of TYHX in shortening the action potential duration of repolarization, which accelerates spontaneous pulsation.
Patients with sick sinus syndrome (SSS) experience a decrease in health-related quality of life (HRQoL), but there is currently no scale available to measure their unpleasant symptoms. The Short Form 36 Health Survey (SF-36) is a commonly used scale to assess HRQoL. In this study, we aimed to evaluate the reliability, validity, and sensitivity of SF-36 in patients with SSS. The sample included 199 eligible participants. We estimated the reliability through test-retest reliability, internal consistency, and split-half reliability. To examine the validity of the questionnaire, confirmatory factor analysis, convergent validity, and discriminant validity were conducted. Sensitivity was determined by the differences in age (cutoff 65 years) and New York Heart Association class. The intraclass correlational coefficients scores showed high test-retest reliability (intraclass correlational coefficients > 0.7). The overall Cronbach α was 0.87 (8 scales range: 0.85–0.87), showing good internal consistency reliability. The split-half reliability coefficient of the SF-36 is 0.814, indicating good reliability. Factor analysis showed that SF-36 subscales could be drawn into 6 components that explain 61% of the total variance. Results of model fit indicate comparative fit index = 0.9, incremental fit index = 0.92, Turker–Lewis index = 0.90, approximate root mean square error = 0.07, and normalized root mean square residual = 0.06. Convergent validity and discriminative validity showed adequate results. Comparison of different ages and New York Heart Association class groups showed statistical significance on most SF-36 subscales. We confirmed the SF-36 as a valid instrument for evaluating HRQoL patients with SSS. The reliability, validity, and sensitivity of SF-36 are acceptable for patients with SSS.
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