ABSTRACT
OBJECTIVE@#To investigate the effect of Chinese compound Shensong Yangxin Capsule ( , SSYX) on myocardial microcirculation in myocardial-infarcted rabbits.@*METHODS@#Myocardial infarction (MI) was established in rabbits by ligation of the left circumflex coronary. Thirty rabbits were randomly divided into the control group, the MI group (model), and the MI treated with SSYX group (MI+SSYX) by a random number table method. After 4 weeks of administration, low-energy real-time myocardial contrast echocardiography (RT-MCE) was conducted to assess the microcirculatory perfusion. Immunofluorescence double staining was used to detect the capillary density. The endothelial ultrastructure was observed with a transmission electron microscope. The mRNA expression levels of vascular endothelial growth factor (VEGF), endothelin 1 (ET-1), prostaglandin I2 (PGI2) and endothelial nitric oxide synthase (eNOS) were measured by real-time quantitative polymerase chain reaction (Real-time PCR). The plasmic levels of ET-1, thromboxane A2 (TXA2), nitric oxide (NO) and von willebrand factor (vWF) were examined with enzyme-linked immunosorbent assays (ELISA).@*RESULTS@#SSYX significantly improved the myocardial blood volume, myocardial micro bubble velocity, and myocardial inflow according to the examination of RT-MCE, and it visibly ameliorated the capillary endothelial structure. Furthermore, compared with the MI group, the plasma levels of TXA2, ET-1 and vWF contents significantly decreased in the MI+SSYX group, and the ET-1 mRNA expression levels of myocardium in the border zone significantly decreased, and the VEGF, PGI2 and eNOS mRNA expression levels significantly increased (all P<0.05).@*CONCLUSIONS@#SSYX has favorable advantages in ameliorating the impaired myocardial microcirculation following MI. The mechanisms of the effect are related to the ability of SSYX in balancing the endothelial-derived vasodilators and vasoconstrictors, and up-regulating the expression of VEGF and eNOS.
ABSTRACT
Objective To explore the protective effect of neuregulin-1 (NRG-1) on heart function and myocardium in rats with sepsis and its mechanism . Methods Healthy male Sprague-Dawly (SD) rats were divided into three groups according to random number table method, with 6 rats in each group. Sepsis model was established by cecal ligation and puncture (CLP group); rats in sham operation group (sham group) underwent the same procedure except ligation. Rats in NRG-1 pre-treatment group (NRG group) were intravenously injected with recombinant human NGR-1 (rhNRG-1) at the dose of 10 μg/kg through tail vein; rats in CLP group and sham group were treated with the same amount of saline. At 24 hours after CLP, hemodynamic method was used to evaluate the cardiac function, and myocardial morphology was observed with hematoxylin and eosin (HE) staining, enzyme linked immunosorbent assay (ELISA) was used to detect the levels of cardiac troponin T (cTnT), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) in serum and macrophage migration inhibitor factor (MIF) in myocardial tissue. Results ① heart function: compared with the sham group, the mean arterial pressure (MAP), left ventricular systolic pressure (LVSP) and left ventricular pressure maximal rate of rise and fall (±dp/dt max) were significantly decreased in CLP group and NRG group, while the MAP, LVSP and ±dp/dt max in NRG group were significantly higher than those in CLP group [MAP (mmHg, 1 mmHg = 0.133 kPa): 125.78±8.15 vs. 113.05±5.85, LVSP (mmHg): 151.27±6.79 vs. 139.39±8.05, +dp/dt max (kPa/s): 4 389.59±332.38 vs. 3 706.85±451.31, -dp/dt max (kPa/s): 4 291.42±323.72 vs. 3 691.17±515.44, all 1 <0.05]. ②Myocardial injury: compared with the sham group, the levels of serum cTnT in CLP group and NRG group were significantly increased, while the levels of serum cTnT in NRG group were significantly lower than those in CLP group (ng/L: 206.37±67.28 vs. 344.13±80.95, 1 < 0.05), and the HE staining showed that myocardial pathological changes in NRG group were improved compared with the CLP group. ③Inflammatory mediators level: compared with the sham group, the levels of serum TNF-α, IL-1β and myocardial MIF were significantly increased in CLP group and NRG group, while the indicators in NRG group were lower than those in CLP group [TNF-α(ng/L): 52.77±3.43 vs. 97.19±13.98, IL-1β (ng/L): 40.25±5.48 vs. 56.05±6.88, MIF (μg/L): 1.92±0.16 vs. 2.87±0.10, all 1 <0.05]. Conclusion NRG-1 can reduce circulating levels of inflammatory factors in rats with sepsis, adjust myocardial MIF level, and alleviate myocardial cell injury, thereby improving cardiac function, and play a role in myocardial protection.
ABSTRACT
<p><b>BACKGROUND</b>Pharmacological therapy for congestive heart failure (CHF) with ventricular arrhythmia is limited. In the study, our aim was to evaluate the effects of Chinese traditional medicine Shensong Yangxin capsules (SSYX) on heart rhythm and function in CHF patients with frequent ventricular premature complexes (VPCs).</p><p><b>METHODS</b>This double-blind, placebo-controlled, multicenter study randomized 465 CHF patients with frequent VPCs to the SSYX (n = 232) and placebo groups (n = 233) for 12 weeks of treatment. The primary endpoint was the VPCs monitored by a 24-h ambulatory electrocardiogram. The secondary endpoints included the left ventricular ejection fraction (LVEF), left ventricular end-diastolic diameter, N-terminal pro-brain natriuretic peptide (NT-proBNP), New York Heart Association (NYHA) classification, 6-min walking distance (6MWD), Minnesota Living with Heart Failure Questionnaire (MLHFQ) scores, and composite cardiac events (CCEs).</p><p><b>RESULTS</b>The clinical characteristics were similar at baseline. SSYX caused a significantly greater decline in the total number of VPCs than the placebo did (-2145 ± 2848 vs. -841 ± 3411, P < 0.05). The secondary endpoints of the LVEF, NYHA classification, NT-proBNP, 6MWD, and MLHFQ scores showed a greater improvements in the SSYX group than in the placebo group (ΔLVEF at 12th week: 4.75 ± 7.13 vs. 3.30 ± 6.53; NYHA improvement rate at the 8th and 12th week: 32.6% vs. 21.8%, 40.5% vs. 25.7%; mean level of NT-proBNP in patients with NT-proBNP ≥125 pg/ml at 12th week: -122 [Q1, Q3: -524, 0] vs. -75 [Q1, Q3: -245, 0]; Δ6MWD at 12th week: 35.1 ± 38.6 vs. 17.2 ± 45.6; ΔMLHFQ at the 4th, 8th, and 12th week: -4.24 ± 6.15 vs. -2.31 ± 6.96, -8.19 ± 8.41 vs. -3.25 ± 9.40, -10.60 ± 9.41 vs. -4.83 ± 11.23, all P < 0.05). CCEs were not different between the groups during the study period.</p><p><b>CONCLUSIONS</b>In this 12-week pilot study, SSYX was demonstrated to have the benefits of VPCs suppression and cardiac function improvement with good compliance on a background of standard treatment for CHF.</p><p><b>TRIAL REGISTRATION</b>www.chictr.org.cn, ChiCTR-TRC-12002061 (http://www.chictr.org.cn/showproj.aspx?proj=7487) and Clinicaltrials.gov, NCT01612260 (https://clinicaltrials.gov/ct2/show/NCT01612260).</p>
ABSTRACT
The traditional Chinese medicine Shensong Yangxin (SSYX) can improve the clinical symptoms of arrhythmia in an integrated manner. This study aimed to investigate the electrophysiological effect of SSYX on the hearts of myocardial-infarcted rabbits and further explore the mechanism by which SSYX alleviates myocardial fibrosis. Myocardial infarction (MI) was established in rabbits by ligation of the left circumflex coronary. The rabbits were treated with SSYX (0.5 g/kg/d) or saline for 8 weeks by oral administration. Microelectrode array (MEA) technology was used in vivo for extracellular electrophysiological recordings of the infarct border zone. Masson's trichrome staining was used to observe myocardial fibrosis. Western blotting was performed to evaluate the protein expression levels of collagen I (COL I) and collagen III (COL III). Quantitative real-time polymerase chain reaction (real-time PCR) was performed to evaluate the TGF-β1 and MMP-2 mRNA expression levels. The results showed that the total activation time (TAT) and the dispersion of TAT were significantly increased and the excitation propagation markedly disordered after MI. SSYX could significantly decrease TAT and the dispersion of TAT, and significantly ameliorate the chaotic spread pattern of excitation. Furthermore, SSYX treatment could significantly decrease COL I and COL III protein levels and down-regulate TGF-β1 and MMP-2 mRNA expression levels in MI rabbits. It was concluded that SSYX may ameliorate cardiac electrophysiological abnormalities in infarcted hearts by decreasing the protein levels of COL I and COL III, down-regulating the mRNA expression levels of TGF-β1 and MMP2, and thereby reducing adverse cardiac remodeling.
Subject(s)
Animals , Female , Male , Rabbits , Collagen Type I , Genetics , Metabolism , Collagen Type III , Genetics , Metabolism , Drugs, Chinese Herbal , Pharmacology , Therapeutic Uses , Heart Rate , Hyperplasia , Matrix Metalloproteinase 2 , Genetics , Metabolism , Myocardial Infarction , Drug Therapy , Pathology , Myocardium , Metabolism , Pathology , Transforming Growth Factor beta , Genetics , MetabolismABSTRACT
The traditional Chinese medicine Shensong Yangxin (SSYX) can improve the clinical symptoms of arrhythmia in an integrated manner. This study aimed to investigate the electrophysiological effect of SSYX on the hearts of myocardial-infarcted rabbits and further explore the mechanism by which SSYX alleviates myocardial fibrosis. Myocardial infarction (MI) was established in rabbits by ligation of the left circumflex coronary. The rabbits were treated with SSYX (0.5 g/kg/d) or saline for 8 weeks by oral administration. Microelectrode array (MEA) technology was used in vivo for extracellular electrophysiological recordings of the infarct border zone. Masson's trichrome staining was used to observe myocardial fibrosis. Western blotting was performed to evaluate the protein expression levels of collagen I (COL I) and collagen III (COL III). Quantitative real-time polymerase chain reaction (real-time PCR) was performed to evaluate the TGF-β1 and MMP-2 mRNA expression levels. The results showed that the total activation time (TAT) and the dispersion of TAT were significantly increased and the excitation propagation markedly disordered after MI. SSYX could significantly decrease TAT and the dispersion of TAT, and significantly ameliorate the chaotic spread pattern of excitation. Furthermore, SSYX treatment could significantly decrease COL I and COL III protein levels and down-regulate TGF-β1 and MMP-2 mRNA expression levels in MI rabbits. It was concluded that SSYX may ameliorate cardiac electrophysiological abnormalities in infarcted hearts by decreasing the protein levels of COL I and COL III, down-regulating the mRNA expression levels of TGF-β1 and MMP2, and thereby reducing adverse cardiac remodeling.