Effect of Zhenwu Decoction on electrical remodeling of cardiomyocytes in heart failure via I_(to)/Kv channels / 中国中药杂志

This study aimed to investigate the underlying mechanism of Zhenwu Decoction in the treatment of heart failure by regulating electrical remodeling through the transient outward potassium current(I_(to))/voltage-gated potassium(Kv) channels. Five normal SD rats were intragastrically administered with Zhenwu Decoction granules to prepare drug-containing serum, and another seven normal SD rats received an equal amount of distilled water to prepare blank serum. H9c2 cardiomyocytes underwent conventional passage and were treated with angiotensin Ⅱ(AngⅡ) for 24 h. Subsequently, 2%, 4%, and 8% drug-containing serum, simvastatin(SIM), and BaCl_2 were used to interfere in H9c2 cardiomyocytes for 24 h. The cells were divided into a control group [N, 10% blank serum + 90% high-glucose DMEM(DMEM-H)], a model group(M, AngⅡ + 10% blank serum + 90% DMEM-H), a low-dose Zhenwu Decoction-containing serum group(Z1, AngⅡ + 2% drug-containing serum of Zhenwu Decoction + 8% blank serum + 90% DMEM-H), a medium-dose Zhenwu Decoction-containing serum group(Z2, AngⅡ + 4% drug-containing serum of Zhenwu Decoc-tion + 6% blank serum + 90% DMEM-H), a high-dose Zhenwu Decoction-containing serum group(Z3, AngⅡ + 8% drug-containing serum of Zhenwu Decoction + 2% blank serum + 90% DMEM-H), an inducer group(YD, AngⅡ + SIM + 10% blank serum + 90% DMEM-H), and an inhibitor group(YZ, AngⅡ + BaCl_2 + 10% blank serum + 90% DMEM-H). The content of ANP in cell extracts of each group was detected by ELISA. The relative mRNA expression levels of ANP, Kv1.4, Kv4.2, Kv4.3, DPP6, and KChIP2 were detected by real-time quantitative PCR. The protein expression of Kv1.4, Kv4.2, Kv4.3, DPP6, and KChIP2 was detected by Western blot. I_(to) was detected by the whole cell patch-clamp technique. The results showed that Zhenwu Decoction at low, medium, and high doses could effectively reduce the surface area of cardiomyocytes. Compared with the M group, the Z1, Z2, Z3, and YD groups showed decreased ANP content and mRNA level, increased protein and mRNA expression of Kv4.2, Kv4.3, DPP6, and KChIP2, and decreased protein and mRNA expression of Kv1.4, and the aforementioned changes were the most notable in the Z3 group. Compared with the N group, the Z1, Z2, and Z3 groups showed significantly increased peak current and current density of I_(to). The results indicate that Zhenwu Decoction can regulate myocardial remodeling and electrical remodeling by improving the expression trend of Kv1.4, Kv4.2, Kv4.3, KChIP2, and DPP6 proteins and inducing I_(to) to regulate Kv channels, which may be one of the mechanisms of Zhenwu Decoction in treating heart failure and related arrhythmias.

Comparison of Short- and Long-term Hearing Outcomes of Successful Inlay Cartilage Tympanoplasty Between Small and Large Eardrum Perforations

OBJECTIVES: To compare the short- and long-term hearing outcomes after successful inlay cartilage tympanoplasty between patients with small ( or =50%) eardrums perforations. METHODS: This is a retrospective case series study conducted in a tertiary referral center. Twenty-five patients who underwent 27 procedures were enrolled. Their mean age was 60.26 years (range, 42 to 76 years). The mean follow-up time was 18.86 months (range, 12.30 to 35.83 months). The preoperative, initial postoperative, and long-term hearing results in patients with total repair of the eardrum were analyzed. RESULTS: In the small size group, the average (+/-standard deviation) air-bone gap (ABG) closure was 1.08+/-7.53 dB in the short-term and 2.33+/-11.56 dB in the long-term hearing examinations. There was no difference between short- and long-term ABG closure (P=0.689). In the large size group, the average ABG closure was 9.77+/-9.40 dB in the short-term and 16.25+/-6.01 dB in the long-term hearing examinations. There was a significant difference between short- and long-term ABG closure (P=0.029). CONCLUSION: Patients with large perforations have continuous hearing improvement and ABG closure for more than one year. In contrast, the short- and long-term postoperative ABGs are almost the same in patients with small perforations. More long-term postoperative follow-up of hearing results is necessary for large perforations.