scholarly journals Lingguizhugan decoction attenuates doxorubicin-induced heart failure in rats by improving TT-SR microstructural remodeling

Author(s):  
Xueping Li ◽  
Guangmin Xu ◽  
Shujun Wei ◽  
Baocheng Zhang ◽  
Huan Yao ◽  
...  

Abstract Background Lingguizhugan decoction (LGZG), an ancient Chinese herbal formula, has been used to treat cardiovascular diseases in eastern Asia. We investigated whether LGZG has protective activity and the mechanism underlying its effect in an animal model of heart failure (HF). Methods A rat model of HF was established by administering eight intraperitoneal injections of doxorubicin (DOX) (cumulative dose of 16 mg/kg) over a 4-week period. Subsequently, LGZG at 5, 10, and 15 mL/kg/d was administered to the rats intragastrically once daily for 4 weeks. The body weight, heart weight index (HWI), heart weight/tibia length ratio (HW/TL), and serum BNP level were investigated to assess the effect of LGZG on HF. Echocardiography was performed to investigate cardiac function, and H&E staining to visualize myocardial morphology. Myocardial ultrastructure and T-tubule-sarcoplasmic reticulum (TT-SR) junctions were observed by transmission electron microscopy. The JP-2 protein level was determined by Western blotting. The mRNA level of CACNA1S and RyR2 and the microRNA-24 (miR-24) level were assayed by quantitative RT-PCR. Results Four weeks after DOX treatment, rats developed cardiac damage and exhibited a significantly increased BNP level compared with the control rats (169.6 ± 29.6 pg/mL versus 80.1 ± 9.8 pg/mL, P < 0.001). Conversely, LGZG, especially at the highest dose, markedly reduced the BNP level (93.8 ± 17.9 pg/mL, P < 0.001). Rats treated with DOX developed cardiac dysfunction, characterized by a strong decrease in left ventricular ejection fraction compared with the control (58.5 ± 8.7% versus 88.7 ± 4.0%; P < 0.001). Digoxin and LGZG improved cardiac dysfunction (79.6 ± 6.1%, 69.2 ± 2.5%, respectively) and preserved the left ventricular ejection fraction (77.9 ± 5.1, and 80.5 ± 4.9, respectively, P < 0.01). LGZG also improved the LVEDD, LVESD, and FS and eliminated ventricular hypertrophy, as indicated by decreased HWI and HW/TL ratio. LGZG attenuated morphological abnormalities and mitochondrial damage in the myocardium. In addition, a high dose of LGZG significantly downregulated the expression of miR-24 compared with that in DOX-treated rats (fold change 1.4 versus 3.4, P < 0.001), but upregulated the expression of JP-2 and antagonized DOX-induced T-tubule TT-SR microstructural remodeling. These activities improved periodic Ca2+ transients and cell contraction, which may underly the beneficial effect of LGZG on HF. Conclusions LGZG exerted beneficial effects on DOX-induced HF in rats, which were mediated in part by improved TT-SR microstructural remodeling.

2011 ◽  
pp. 62-70
Author(s):  
Lien Nhut Nguyen ◽  
Anh Vu Nguyen

Background: The prognostic importance of right ventricular (RV) dysfunction has been suggested in patients with systolic heart failure (due to primary or secondary dilated cardiomyopathy - DCM). Tricuspid annular plane systolic excursion (TAPSE) is a simple, feasible, reality, non-invasive measurement by transthoracic echocardiography for evaluating RV systolic function. Objectives: To evaluate TAPSE in patients with primary or secondary DCM who have left ventricular ejection fraction ≤ 40% and to find the relation between TAPSE and LVEF, LVDd, RVDd, RVDd/LVDd, RA size, severity of TR and PAPs. Materials and Methods: 61 patients (36 males, 59%) mean age 58.6 ± 14.4 years old with clinical signs and symtomps of chronic heart failure which caused by primary or secondary DCM and LVEF ≤ 40% and 30 healthy subject (15 males, 50%) mean age 57.1 ± 16.8 were included in this study. All patients and controls were underwent echocardiographic examination by M-mode, two dimentional, convensional Dopler and TAPSE. Results: TAPSE is significant low in patients compare with the controls (13.93±2.78 mm vs 23.57± 1.60mm, p<0.001). TAPSE is linearly positive correlate with echocardiographic left ventricular ejection fraction (r= 0,43; p<0,001) and linearly negative correlate with RVDd (r= -0.39; p<0.01), RVDd/LVDd (r=-0.33; p<0.01), RA size (r=-0.35; p<0.01), TR (r=-0.26; p<0.05); however, no correlation was found with LVDd and PAPs. Conclusions: 1. Decreased RV systolic function as estimated by TAPSE in patients with systolic heart failure primary and secondary DCM) compare with controls. 2. TAPSE is linearly positive correlate with LVEF (r= 0.43; p<0.001) and linearly negative correlate with RVDd (r= -0.39; p<0.01), RVDd/LVDd (r=-0.33; p<0.01), RA size (r=-0.35; p<0.01), TR (r=-0.26; p<0.05); however, no correlation is found with LVDd and PAPs. 3. TAPSE should be used routinely as a simple, feasible, reality method of estimating RV function in the patients systolic heart failure DCM (primary and secondary).


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