Based on copper death, this study investigates the effect and mechanism of Shenmai Injection on isoproterenol(ISO)-induced myocardial fibrosis(MF) in rats. SPF-grade male SD rats were randomly divided into a normal group, model group, captopril(5 mg·kg~(-1)) positive control group, and Shenmai Injection low(6 mL·kg~(-1)), medium(9 mL·kg~(-1)), and high(12 mL·kg~(-1)) dose groups. Except for the normal group, the rats in the other groups were subcutaneously injected with ISO(5 mg·kg~(-1)) once a day for 10 consecutive days to establish an MF model. Starting from the second day after successful modeling, intraperitoneal injections of the respective treatments were administered for 28 consecutive days. Hematoxylin-eosin(HE) and Masson staining were used to observe pathological changes and fibrosis levels in the myocardial tissue. Colorimetry was employed to detect serum Cu~(2+) concentration in rats. The levels of inflammatory cytokines interleukin-6(IL-6), interleukin-1β(IL-1β), interleukin-18(IL-18), tumor necrosis factor-α(TNF-α), as well as mitochondrial energy metabolites adenosine triphosphate(ATP), adenosine diphosphate(ADP), and adenosine monophosphate(AMP) in serum were measured using enzyme-linked immunosorbent assay(ELISA). Western blot was performed to detect the expression of collagen Ⅰ(Col-Ⅰ), collagen Ⅲ(Col-Ⅲ), and copper death-related proteins dihydrolipoamide acetyltransferase(DLAT), ferredoxin 1(FDX1), lipoic acid synthetase(LIAS), and heat shock protein 70(HSP70) in myocardial tissue. Immunofluorescence was used to detect the expression of DLAT, FDX1, and HSP70, while immunohistochemistry was conducted to examine the expressions of DLAT, FDX1, LIAS, and HSP70. The results showed that, compared to the model group, the myocardial structure disorder and collagen fiber deposition in the drug treatment groups were significantly improved, the cardiac index level was reduced, serum Cu~(2+), IL-6, IL-1β, IL-18, TNF-α, ADP, and AMP levels were significantly decreased, ATP levels were significantly increased, and the expressions of Col-Ⅰ, Col-Ⅲ, and HSP70 proteins in myocardial tissue were significantly reduced, while the expressions of DLAT, FDX1, and LIAS proteins were significantly elevated. In conclusion, Shenmai Injection effectively alleviates myocardial structure disorder and interstitial collagen fiber deposition in ISO-induced MF rats, promotes copper excretion, and reduces copper death in the ISO-induced rat MF model.
Animals ; Male ; Drugs, Chinese Herbal/administration & dosage* ; Rats, Sprague-Dawley ; Rats ; Myocardium/metabolism* ; Drug Combinations ; Fibrosis/metabolism* ; Copper/blood* ; Cardiomyopathies/genetics* ; Humans

Sepsis constitutes one of the principal causes of death globally, and the mortality rate of patients complicated with sepsis-induced cardiomyopathy (SIC) surges by over 50%. Early identification of patients with sepsis, particularly SIC, and implementing clinical intervention are vital measures to reduce the mortality. In recent years, biomarkers for the diagnosis and prognosis of SIC have emerged rapidly. Among classical myocardial injury biomarkers, cardiac troponin (cTn), brain natriuretic peptide (BNP), and soluble growth stimulation gene 2 protein (sST2) have predictive value for the prognosis of SIC. Meanwhile, heart-type fatty acid-binding protein (h-FABP) possess relatively high value in diagnosis. Moreover, plasma metabolites, microRNA (miRNA), as well as recently identified markers related to sepsis or cardiovascular diseases also demonstrate outstanding predictive value in both the diagnosis and prognosis of SIC. For instance, exosomal miR-150-5p, blood miR-155, blood miR-378a-3p, blood miR-21-3p, blood miR-233, blood miR-23b, blood miR-135, lipocalin (LCN), heme oxygenase-1 (HO-1), fibroblast growth factor-21 (FGF-21), and growth differentiation factor-15 (GDF-15) show varying degrees of predictive value when it comes to diagnosing SIC. S100A8/A9 protein, triglyceride-glucose (TyG) index, angiotensinogen II (Ang II) and lactoferrin are correlated with the prognosis of SIC. Meanwhile, it has been discovered that the combination of multiple biomarkers outperforms a single biomarker, and certain combinations exhibit superior diagnostic performance. However, most of these studies use single-center clinical data, which has certain limitations and still calls for more high-quality evidence support. Therefore, identifying biomarker combinations that are supported by high-quality evidence, have bedside application potential, and possess high sensitivity and specificity is of crucial importance for the prevention, diagnosis, and treatment of SIC. This review is carried out on the current articles that report biomarkers with predictive value and the diagnosis and prediction of multiple biomarkers in combination, in the hope of continuously optimizing the diagnostic strategy for the specific identification of early SIC.
Humans ; Biomarkers/blood* ; Cardiomyopathies/etiology* ; Sepsis/diagnosis* ; MicroRNAs/blood* ; Prognosis ; Fatty Acid-Binding Proteins/blood*

There is a close relationship between diabetes mellitus and heart failure, both of which are known to increase morbidity and mortality. Diabetes can cause or aggravate heart failure, and heart failure can precipitate diabetes. Diabetes mellitus causes structural and functional changes in the heart, such as fibrosis of the myocardium and left ventricular dysfunction. The mechanisms of diabetic cardiomyopathy are metabolic disturbance, myocardial fibrosis, microvascular disease, and autonomic dysfunction. Improper blood glucose control leads to deterioration of heart failure, but the role of strict glycemic control in reducing heart failure is unclear. The role of SGLT2 inhibitors in reducing the incidence of heart failure is of great importance in the treatment of diabetic patients. However, further long-term follow-up and safety studies are needed.
Blood Glucose ; Diabetes Complications ; Diabetes Mellitus ; Diabetic Cardiomyopathies ; Fibrosis ; Follow-Up Studies ; Heart Failure ; Heart ; Humans ; Incidence ; Mortality ; Myocardium ; Ventricular Dysfunction, Left

OBJECTIVE: To investigate the inhibitory effect of Zhenwu Decoction on ventricular hypertrophy in rats with uremic cardiomyopathy and explore the mechanism. METHODS: Cardiocytes isolated from suckling rats were divided into control group and indoxyl sulfate (IS) group, and the protein synthesis was assayed with [H]- leucine incorporation and cellular protein expressions were detected using Western blotting. Fifty SD rats were randomly divided into sham operation group, model group, and low- and high-dose Zhenwu Decoction treatment groups, and except for those in the sham operation group, all the rats underwent 5/6 nephrectomy. Four weeks after the operation, the rats in low- and high-dose treatment groups were given Zhenwu Decoction gavage at the dose of 4.5 g/kg and 13.5 g/kg, respectively; the rats in the sham-operated and model groups were given an equal volume of distilled water. After 4 weeks of treatment, serum levels of IS were determined, and cardiac and ventricular mass indexes were measured in the rats; cardiac ultrasound was performed and Western blotting was used to measure the expressions of BNP, p-ERK1/2, p-p38 and p-JNK in the myocardium. RESULTS: Rat cardiomyocytes treated with IS showed significantly enhanced protein synthesis and increased expression levels of BNP, p-erk1/2, and p-p38 as compared with the control cells ( < 0.01), but the expression of p-jnk was comparable between the two groups. In the animal experiment, the rats in the model group showed significantly increased serum creatinine (SCr) and urea nitrogen (BUN) levels, 24-h urine protein (24 hUpro), plasma IS level, left ventricular mass index (LVMI) and whole heart mass index (HMI) compared with those in the sham group ( < 0.01); Both LVESD and LVEDD were significantly reduced and LVAWS, LVAWD, LVPWS and LVPWD were significantly increased in the model rat, which also presented with obvious cardiomyocyte hypertrophy and increased myocardial expressions of BNP, p-ERK1/2, p-p38 and p-jnk ( < 0.01). Compared with the rats in the model group, the rats treated with low-dose and high-dose Zhenwu Decoction had significantly lowered levels of SCr, BUN, 24 hUpro and IS ( < 0.05) and decreased LVMI and HMI; LVESD, LVEDD, LVPWS, LVAWS, and LVAWD were improved more obviously in the high-dose group, and the myocardial expressions of BNP, p-ERK1/2, p-p38 and p-JNK was significantly downregulated after the treatment. CONCLUSIONS Zhenwu Decoctin can reduce plasma IS levels and inhibit ventricular hypertrophy to delay ventricular remodeling in rats with uremic cardiomyopathy.
Animals ; Blood Urea Nitrogen ; Cardiomegaly ; prevention & control ; Cardiomyopathies ; complications ; Creatinine ; blood ; Drugs, Chinese Herbal ; pharmacology ; Heart Ventricles ; Indican ; blood ; pharmacology ; Myocytes, Cardiac ; drug effects ; metabolism ; Nephrectomy ; Random Allocation ; Rats ; Rats, Sprague-Dawley

Diabetic cardiomyopathy( DCM) is one of the major cardiovascular complications of diabetes mellitus. Based on the clinical efficacy of Danzhi Jiangtang Capsules( DJC) in the prevention and treatment of diabetes and its cardiovascular complications,both in vivo and in vitro methods were adopted to investigate its effect and underlying mechanism of protecting myocardial injury induced by diabetes. The type 2 diabetic rats were prepared by feeding high-energy food combined with streptozotin( STZ) injection,and the effects of DJC were observed by blood sugar,blood lipid,hemodynamic index,cardiac weight index and the change of cardiac pathological morphology. The protein expressions of TLR4,MyD88 and NF-κB p65 in myocardial tissue were detected and the possible mechanism was preliminarily analyzed. Besides this,DJC containing serum was prepared,H9 c2 cardiomyocyte induced by high sugar were studied to investigate the mechanism of TLR4/MyD88/NF-κB signaling pathway regulating cardiomyocyte injury and the therapeutic effect of DJC. The results demonstrated that fasting blood sugar,glycosylated hemoglobin,total cholesterol and glycerol triglyceride were significantly reduced( P<0. 01,P<0. 05). Cardiac weight index,left ventricle weight index,LVEDP and the protein expressions of TLR4,MyD88 and NF-κB p65 were significantly reduced( P<0. 01,P<0. 05). LVSP,+dp/dtmaxand-dp/dtmaxincreased significantly( P<0. 01,P< 0. 05). Moreover,the pathological damage of myocardial tissue in rats improved significantly. Meanwhile,the protein expressions of TLR4,MyD88 and NF-κB p65 in cardiomyocytes induced by high sugar were significantly inhibited( P<0. 01).It showed that DJC were effective in preventing and treating myocardial injury induced by diabetes and its mechanism may be related to the over-expression of TLR4/MyD88/NF-κB signaling pathway induced by high sugar.
Animals ; Blood Glucose ; Capsules ; Diabetes Mellitus, Experimental/complications* ; Diabetic Cardiomyopathies/drug therapy* ; Drugs, Chinese Herbal/therapeutic use* ; Myeloid Differentiation Factor 88/metabolism* ; NF-kappa B/metabolism* ; Rats ; Rats, Sprague-Dawley ; Signal Transduction ; Toll-Like Receptor 4/metabolism*

OBJECTIVE: To investigate the epidemiology and independent risk factors of septic cardiomyopathy. METHODS: A prospective study was conducted. Patients with sepsis in intensive care unit (ICU) of Subei People's Hospital of Jiangsu Province, Yangzhou University, Fuxing Hospital, Capital Medical University and Beijing Electric Power Hospital from May 2016 to August 2019 were enrolled. All patients received standardized treatments according to the Surviving Sepsis Campaign (SSC) guidelines. Blood were collected within 24 hours of admission to ICU, and plasma histone H4, cardiac troponin I (cTnI) and N-terminal pro-brain natriuretic peptide (NT-proBNP) were detected by enzyme linked immunosorbent assay (ELISA). Transthoracic echocardiography was performed to record the ultrasonic parameters within 24 hours after admission. Sequential organ failure assessment (SOFA) score, usage of vasopressor drugs, and the prognosis of ICU were recorded. Patients were divided into two groups according to whether cardiomyopathy occurred or not, and the differences of each index between the two groups were compared. The correlation between plasma histone H4 and SOFA score, cTnI, NT-proBNP were investigated. Multivariate binary Logistic regression was used to determine the risk factors for septic cardiomyopathy. The predictive value of histone H4 in septic cardiomyopathy was shown by the receiver operating characteristic (ROC) curve. RESULTS: 121 patients were included in this study, and there were 60 patients (49.6%) with septic cardiomyopathy. Thirty-six patients died, with an ICU mortality of 29.8%. (1) Correlation analysis showed that plasma histone H4 in patients with septic cardiomyopathy was positively correlated with cTnI, SOFA score and NT-proBNP (r value was 0.512, 0.403 and 0.274, respectively, all P < 0.01). (2) Compared with the non-cardiomyopathy group, the plasma histone H4, cTnI, usage of vasopressor drugs, SOFA score and ICU mortality in the cardiomyopathy group were significantly increased [histone H4 (mg/L): 0.26 (0.23, 0.30) vs. 0.22 (0.17, 0.27), cTnI (μg/L): 0.21 (0.17, 0.30) vs. 0.18 (0.14, 0.22), usage of vasopressor drugs: 83.3% (50/60) vs. 65.6% (40/61), SOFA score: 11 (9, 12) vs. 9 (8, 10), ICU mortality: 40.0% (24/60) vs. 19.7% (12/61), all P < 0.05]. Multivariate binary Logistic regression analysis showed that high histone H4 level [odds ratio (OR) = 6.502, 95% confidence interval (95%CI) was 1.203-78.231, P = 0.044] and usage of vasopressor drugs (OR = 2.622, 95%CI was 1.034-6.849, P = 0.042) were independent risk factors for septic cardiomyopathy. (4) ROC curve analysis showed the cut-off of histones H4 for predicting septic cardiomyopathy was 0.24 mg/L, the area under the curve was 0.684 (P < 0.01), with the sensitivity of 65.2%, and specificity of 68.9%. CONCLUSIONS Septic cardiomyopathy had a high incidence. Higher plasma histone H4 and the usage of vasopressor drugs were independent risk factors for septic cardiomyopathy.
Cardiomyopathies ; Histones/blood* ; Humans ; Intensive Care Units ; Organ Dysfunction Scores ; Prognosis ; Prospective Studies ; ROC Curve ; Retrospective Studies ; Risk Factors ; Sepsis

Cyclophosphamide-induced cardiotoxicity is an uncommon complication especially in patients who have never undergone mediastinal irradiation or cardiotoxic chemotherapy and do not have underlying cardiac diseases. Here, we describe the case of a 19-year-old female with chronic myeloid leukemia. She was previously treated with oral tyrosine kinase inhibitors and developed cardiomyopathy after receiving infusion of 60 mg/kg intravenous cyclophosphamide for two days with a conditioning regimen for allogenic hematopoietic stem cell transplantation. Severe thickening of the left ventricle and reduced ejection fraction without triggering agents were characteristic for cyclophosphamide-induced cardiomyopathy. Her NT-pro BNP and troponin T concentrations surged to >70,000 pg/mL (0=130 pg/mL) and 2,031 pg/mL (0-14 pg/mL), respectively, during the course of the therapy and multiple organ failure seemed imminent evidenced by unresponsive decline in blood pressure. However, with close monitoring and persistent conservative management which consisted of intravenous hydration, continuous hemodialysis, and mechanical ventilation, her condition recovered.
Blood Pressure ; Cardiomyopathies* ; Cardiotoxicity ; Cyclophosphamide* ; Drug Therapy ; Female ; Heart Diseases ; Heart Failure* ; Heart Ventricles ; Heart* ; Hematopoietic Stem Cell Transplantation ; Humans ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive ; Multiple Organ Failure ; Protein-Tyrosine Kinases ; Renal Dialysis ; Respiration, Artificial ; Troponin T ; Young Adult

OBJECTIVE: To investigate the effect of tea polyphenols on cardiac function in rats with diabetic cardiomyopathy, and the mechanism by which tea polyphenols regulate autophagy in diabetic cardiomyopathy. METHODS: Sixty Sprague-Dawley (SD) rats were randomly divided into six groups: a normal control group (NC), an obesity group (OB), a diabetic cardiomyopathy group (DCM), a tea polyphenol group (TP), an obesity tea polyphenol treatment group (OB-TP), and a diabetic cardiomyopathy tea polyphenol treatment group (DCM-TP). After successful modeling, serum glucose, cholesterol, and triglyceride levels were determined; cardiac structure and function were inspected by ultrasonic cardiography; myocardial pathology was examined by staining with hematoxylin-eosin; transmission electron microscopy was used to observe the morphology and quantity of autophagosomes; and expression levels of autophagy-related proteins LC3-II, SQSTM1/p62, and Beclin-1 were determined by Western blotting. RESULTS: Compared to the NC group, the OB group had normal blood glucose and a high level of blood lipids; both blood glucose and lipids were increased in the DCM group; ultrasonic cardiograms showed that the fraction shortening was reduced in the DCM group. However, these were improved significantly in the DCM-TP group. Hematoxylin-eosin staining showed disordered cardiomyocytes and hypertrophy in the DCM group; however, no differences were found among the remaining groups. Transmission electron microscopy revealed that the numbers of autophagosomes in the DCM and OB-TP groups were obviously increased compared to the NC and OB groups; the number of autophagosomes in the DCM-TP group was reduced. Western blotting showed that the expression of LC3-II/I and Beclin-1 increased obviously, whereas the expression of SQSTM1/p62 was decreased in the DCM and OB-TP groups (P<0.05). CONCLUSIONS Tea polyphenols had an effect on diabetic cardiomyopathy in rat cardiac function and may alter the levels of autophagy to improve glucose and lipid metabolism in diabetes.
Animals ; Autophagy ; drug effects ; Beclin-1 ; analysis ; Blood Glucose ; analysis ; Body Weight ; Diabetic Cardiomyopathies ; drug therapy ; pathology ; physiopathology ; Lipids ; blood ; Male ; Myocardium ; pathology ; Polyphenols ; pharmacology ; Rats ; Rats, Sprague-Dawley ; Tea ; chemistry

OBJECTIVETo investigate the protective effects of Zhenwutang (ZWT) on cardiac function in mice with uremic cardiomyopathy (UCM).

METHODSThirty C57BL/6 mice were randomized into 3 equal groups, including a sham-operated group, subtotal nephrectomy (UCM model) group and subtotal nephrectomy with ZWT treatment group. The mice in the former two groups were treated with distilled water. The changes in cardiac functions, myocardial structure and renal function of the mice were evaluated with echocardiography, HE staining and biochemical assay, respectively. Western blotting was used to detect the expression level of adenosine monophosphate-activated protein kinase (AMPK) and mammalian target of rapamycin (mTOR) in the heart tissues.

RESULTSCompared with the sham-operated group, the mice in the model group showed significantly lowered body weight and increased heart weight, heart index, left ventricular posterior wall thickness in diastole (LVPWd) and in systole (LVPWs), blood urea nitrogen (BUN) and serum creatinine (Scr) (P<0.05); Pathological examination revealed myocardial hypertrophy in the model group with markedly decreased expression levels of p-AMPK and significantly increased p-mTOR expression (P<0.05). ZWT treatment significantly decreased the heart weight, heart index, LVPWd, and LVPWs and expression level of p-mTOR (P<0.05), increased the expression level of p-AMPK (P<0.05), and obviously ameliorated histological injury of the heart in mice with UCM.

CONCLUSIONZWT can protect the cardiac function in mice with subtotal nephrectomy-induced UCM possibly via the AMPK-mTOR signal pathway.

AMP-Activated Protein Kinases ; metabolism ; Animals ; Blood Urea Nitrogen ; Cardiomyopathies ; drug therapy ; Creatinine ; blood ; Drugs, Chinese Herbal ; pharmacology ; Heart ; physiopathology ; Heart Ventricles ; Mice ; Mice, Inbred C57BL ; Myocardium ; pathology ; Nephrectomy ; Signal Transduction ; TOR Serine-Threonine Kinases ; metabolism

OBJECTIVEThe beneficial effects of silymarin have been extensively studied in the context of inflammation and cancer treatment, yet much less is known about its therapeutic effect on diabetes. The present study was aimed to investigate the cytoprotective activity of silymarin against diabetes-induced cardiomyocyte apoptosis.

METHODSRats were randomly divided into: control group, untreated diabetes group and diabetes group treated with silymarin (120 mg/kg•d) for 10 d. Rats were sacrificed, and the cardiac muscle specimens and blood samples were collected. The immunoreactivity of caspase-3 and Bcl-2 in the cardiomyocytes was measured. Total proteins, glucose, insulin, creatinine, AST, ALT, cholesterol, and triglycerides levels were estimated.

RESULTSUnlike the treated diabetes group, cardiomyocyte apoptosis increased in the untreated rats, as evidenced by enhanced caspase-3 and declined Bcl-2 activities. The levels of glucose, creatinine, AST, ALT, cholesterol, and triglycerides declined in the treated rats. The declined levels of insulin were enhanced again after treatment of diabetic rats with silymarin, reflecting a restoration of the pancreatic β-cells activity.

CONCLUSIONThe findings of this study are of great importance, which confirmed for the first time that treatment of diabetic subjects with silymarin may protect cardiomyocytes against apoptosis and promote survival-restoration of the pancreatic β-cells.

Alanine Transaminase ; blood ; Animals ; Aspartate Aminotransferases ; blood ; Blood Glucose ; Cholesterol ; blood ; Creatinine ; blood ; Diabetes Mellitus, Experimental ; complications ; Diabetic Cardiomyopathies ; prevention & control ; Heart ; drug effects ; Immunohistochemistry ; Insulin ; blood ; Male ; Myocardium ; pathology ; Myocytes, Cardiac ; drug effects ; Rats ; Silymarin ; pharmacology ; Triglycerides ; blood