Astragaloside IV protects heart from ischemia and reperfusion injury via energy regulation mechanisms.

OBJECTIVE: This study was designed to investigate the protective potential of AS-IV against ischemia and I/R-induced myocardial damage, with focusing on possible involvement of energy metabolism modulation in its action and the time phase in which it takes effect. METHODS: SD rats were subjected to 30 minutes LADCA occlusion, followed by reperfusion. MBF, myocardial infarct size, and cardiac function were evaluated. Myocardial structure and myocardial apoptosis were assessed by double immunofluorescence staining of F-actin and TUNEL. Content of ATP, ADP, and AMP in myocardium, cTnI level, expression of ATP5D, P-MLC2, and apoptosis-related molecules were determined. RESULTS: Pretreatment with AS-IV suppressed MBF decrease, myocardial cell apoptosis, and myocardial infarction induced by I/R. Moreover, ischemia and I/R both caused cardiac malfunction, decrease in the ratio of ATP/ADP and ATP/AMP, accompanying with reduction of ATP 5D protein and mRNA, and increase in P-MLC2 and serum cTnI, all of which were significantly alleviated by pretreatment with AS-IV, even early in ischemia phase for the insults that were implicated in energy metabolism. CONCLUSIONS: AS-IV prevents I/R-induced cardiac malfunction, maintains the integrity of myocardial structure through regulating energy metabolism. The beneficial effect of AS-IV on energy metabolism initiates during the phase of ischemia.

Shengxian decoction protects against chronic heart failure in a rat model via energy regulation mechanisms.

BACKGROUND: Chronic heart failure (CHF) is actually a disease caused by an imbalanced energy metabolism between myocardial energy demand and supply, ultimately resulting in abnormal myocardial cell structure and function. Energy metabolism imbalance plays an important role in the pathological process of chronic heart failure (CHF). Improving myocardial energy metabolism is a new strategy for the treatment of CHF. Shengxian decoction (SXT), a well-known traditional Chinese medicine (TCM) formula, has good therapeutic effects on the cardiovascular system. However, the effects of SXT on the energy metabolism of CHF is unclear. In this study, we probed the regulating effects of SXT on energy metabolism in CHF rats using various research methods. METHODS: High-performance liquid chromatography (HPLC) analysis was used to perform quality control of SXT preparations. Then, SD rats were randomly assigned into 6 groups: sham, model, positive control (trimetazidine) and high-, middle-, and low-dose SXT groups. Specific reagent kits were used to detect the expression levels of ALT and AST in rats' serum. Echocardiography was used to evaluate cardiac function. H&E, Masson and TUNEL staining were performed to examine myocardial structure and myocardial apoptosis. Colorimetry was used to determine myocardial ATP levels in experimental rats. Transmission electron microscopy was used to observe the ultrastructure of myocardial mitochondria. ELISA was used to estimate CK, cTnI, and NT-proBNP levels, and LA、FFA、MDA、SOD levels. Finally, Western blotting was used to examine the protein expression of CPT-1, GLUT4, AMPK, p-AMPK, PGC-1α, NRF1, mtTFA and ATP5D in the myocardium. RESULTS: HPLC showed that our SXT preparation method was feasible. The results of ALT and AST tests indicate that SXT has no side effect on the liver function of rats. Treatment with SXT improved cardiac function and ventricular remodelling and inhibited cardiomyocyte apoptosis and oxidative stress levels induced by CHF. Moreover, CHF caused decrease ATP synthesis, which was accompanied by a reduction in ATP 5D protein levels, damage to mitochondrial structure, abnormal glucose and lipid metabolism, and changes in the expression of PGC-1α related signal pathway proteins, all of which were significantly alleviated by treatment with SXT. CONCLUSION: SXT reverses CHF-induced cardiac dysfunction and maintains the integrity of myocardial structure by regulating energy metabolism. The beneficial effect of SXT on energy metabolism may be related to regulating the expression of the PGC-1α signalling pathway.

Blood pressure trajectories in early adulthood and myocardial structure and function in later life.

AIMS: This study sought to investigate the association between blood pressure (BP) trajectories from early to middle adulthood and echocardiographic indices of structure and function in middle age. METHODS AND RESULTS: This prospective cohort study included 4717 black and white adults aged 18-30 years at baseline (1985-86) who were followed over 30 years in the Coronary Artery Risk Development in Young Adults (CARDIA) study. Trajectories of systolic BP (SBP), diastolic BP (DBP), and pulse pressure (PP) from the Year 0 examination to Year 30 examination were identified using latent mixture modelling. Echocardiographic indices of myocardial structure, systolic function, and diastolic function were assessed at the Year 30 examination. Five distinct SBP trajectory groups were identified: low-stable [1110 participants (23.5%)], moderate-stable [2188 (46.4%)], high-stable [850 (18.0%)], moderate-increasing [416 (8.8%)], and high-increasing [153 (3.2%)]. After adjustment for clinical variables, a significant decreasing trend was observed from the high-increasing and moderate-increasing groups through to the low-stable group for left ventricular (LV) mass index [mean (SE): high-increasing, 112.3 (3.4); moderate-increasing, 99.3 (2.6); high-stable, 88.9 (2.5); moderate-stable, 86.1 (2.3); low-stable, 82.1 (2.4), P trend < 0.01], as well as LV end-diastolic dimension, left atrial volume index, and E/e', while an increasing trend was apparent for LV longitudinal strain, E/A ratio, and average e' velocities. Results were generally consistent for trajectories of DBP and PP. CONCLUSIONS: Higher BP trajectories from early to middle adulthood were associated with worse indices of myocardial modelling and LV systolic and diastolic function at middle age.

Shenqi Lixin Decoction improves cardiac function in rats with adriamycin-induced heart failure through modulation of PGC-1α and mitochondrial apoptosis pathway.

BACKGROUND: Heart failure (HF) is a complex clinical syndrome and a serious manifestation or late stage of various heart diseases. This study aimed to explore the protective effects and underlying mechanisms of Shenqi Lixin Decoction (SQLXD) in HF. METHODS: A HF rat model was induced by intraperitoneal injection of adriamycin (3 mg/kg in the first 3 weeks, 2 mg/kg in the next 3 weeks, once a week, subcutaneous injection, 6 weeks cumulative dose is 15 mg/kg). After 4 weeks of intragastric administration of SQLXD (9.975, 19.95, 39.90 g/kg, once a day, gavage), the indexes of cardiac function were measured by cardiac color Doppler ultrasound, the cardiac muscle structure and pathological changes were observed by transmission electron microscope, hematoxylin-eosin (HE) staining and Masson. The plasma N-terminal B-type natriuretic peptide (NT-proBNP) level and myocardial tissue adenosine triphosphate (ATP) content were detected by ELISA. FITC detected the cardiomyocyte apoptosis rate (CMAR) labeled Annexin V/PI. Expression of B cell lymphoma factor 2 (Bcl-2), Bcl-2 associated X (Bax), cysteine protease-3 (Caspase-3), and peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) mRNA in myocardial tissue were detected by real-time PCR (RT-PCR). The expression of Bcl-2, Bax, Caspase-3 and P53 protein in myocardial tissue were detected by Western blot. RESULTS: Compared to the normal group, left ventricular end systolic diameter (LVSD), left ventricular end diastolic diameter (LVDD), CMAR and the expression of P53 protein, mRNA and protein of Bax and Caspase-3 were significantly increased in model group, while left ventricular ejection fraction (LVEF), left ventricular fractional shortening (LVFS), stroke volume (SV) and the expression of Bcl-2 protein, mRNA of PGC-1α and Bcl-2 were significantly reduced. Compared to the model group, LVSD, LVDD, CMAR and the expressions of P53 protein, mRNA and protein of Bax and Caspase-3 in the medium and high dose SQLXD groups and the control group were significantly decreased, while LVEF, LVFS, SV and the expression of Bcl-2 protein, mRNA of PGC-1α and Bcl-2 were obviously increased. Pathological findings by transmission electron microscope, Masson, and HE staining all revealed protective effects of SQLXD on heart. CONCLUSIONS: SQLXD can effectively protect HF rats' hearts. The potential mechanism may be related to the modulation of the expression of PGC-1α and the mitochondrial apoptosis pathway.

Binge Alcohol Exposure in Adolescence Impairs Normal Heart Growth.

Background Approximately 1 in 6 adolescents report regular binge alcohol consumption, and we hypothesize it affects heart growth during this period. Methods and Results Adolescent, genetically diverse, male Wistar rats were gavaged with water or ethanol once per day for 6 days. In vivo structure and function were assessed before and after exposure. Binge alcohol exposure in adolescence significantly impaired normal cardiac growth but did not affect whole-body growth during adolescence, therefore this pathology was specific to the heart. Binge rats also exhibited signs of accelerated pathological growth (concentric cellular hypertrophy and thickening of the myocardial wall), suggesting a global reorientation from physiologic to pathologic growth. Binge rats compensated for their smaller filling volumes by increasing systolic function and sympathetic stimulation. Consequently, binge alcohol exposure increased PKA (protein kinase A) phosphorylation of troponin I, inducing myofilament calcium desensitization. Binge alcohol also impaired in vivo relaxation and increased titin-based cellular stiffness due to titin phosphorylation by PKCα (protein kinase C α). Mechanistically, alcohol inhibited extracellular signal-related kinase activity, a nodal signaling kinase activating physiology hypertrophy. Thus, binge alcohol exposure depressed genes involved in growth. These cardiac structural alterations from binge alcohol exposure persisted through adolescence even after cessation of ethanol exposure. Conclusions Alcohol negatively impacts function in the adult heart, but the adolescent heart is substantially more sensitive to its effects. This difference is likely because adolescent binge alcohol impedes the normal rapid physiological growth and reorients it towards pathological hypertrophy. Many adolescents regularly binge alcohol, and here we report a novel pathological consequence as well as mechanisms involved.

Cardiac Sarcoidosis: A Picture May Be Worth a Thousand Words, But Do We Need More?

See Article Okasha et al.

Myocardial Involvement in Patients With Histologically Diagnosed Cardiac Sarcoidosis: A Systematic Review and Meta-Analysis of Gross Pathological Images From Autopsy or Cardiac Transplantation Cases.

Background In patients with suspected cardiac sarcoidosis, late gadolinium enhancement on cardiovascular magnetic resonance imaging and/or 18F-fluorodeoxyglucose uptake on positron emission tomography are often used to reach a clinical diagnosis of cardiac sarcoidosis. On the basis of data from the imaging literature of clinical cardiac sarcoidosis, no specific features of myocardial involvement are regarded as pathognomonic for cardiac sarcoidosis. Thus, a diagnosis of cardiac sarcoidosis is challenging to make. There has been no systematic analysis of histologically diagnosed cardiac sarcoidosis for patterns of myocardial involvement. We hypothesized that certain patterns of myocardial involvement are more frequent in histologically diagnosed cardiac sarcoidosis. Methods and Results We performed a systematic review and meta-analysis of gross pathological images from the published literature of patients with histologically diagnosed cardiac sarcoidosis who underwent autopsy or cardiac transplantation. Thirty-three eligible articles provided images of 49 unique hearts. Analysis of these hearts revealed certain features of myocardial involvement in >90% of cases: left ventricular (LV) subepicardial, LV multifocal, septal, and right ventricular free wall involvement. In contrast, other patterns were seen in 0% to 6% of cases: absence of gross LV myocardial involvement, isolated LV midmyocardial involvement, isolated LV subendocardial involvement, isolated LV transmural involvement, absence of septal involvement, or isolated involvement of only one LV level. Conclusions In this systematic review and meta-analysis of histologically diagnosed cardiac sarcoidosis, we identified certain features of myocardial involvement that occurred frequently and others that occurred rarely or never. These patterns could aid the interpretation of cardiovascular magnetic resonance imaging and positron emission tomography imaging and improve the diagnosis and the prognostication of patients with suspected cardiac sarcoidosis.

Gualou Xiebai Decoction, a Traditional Chinese Medicine, Prevents Cardiac Reperfusion Injury of Hyperlipidemia Rat via Energy Modulation.

Background: Gualou Xiebai Decoction (GLXB) is a classic prescription of Chinese medicine used for the treatment of cardiac problems. The present study was designed to explore the effect and mechanism of GLXB on ischemia/reperfusion (I/R) induced disorders in myocardial structure and function, focusing on the regulation of energy metabolism and the RhoA/ROCK pathway. Methods: After hyperlipidemic rat model was established by oral administration of high fat diet, the rats were treated with GLXB for 6 weeks and subjected to 30 min occlusion of the left anterior descending coronary artery (LADCA) followed by 90 min reperfusion to elicit I/R challenge. Myocardial infarct size was assessed by Evans blue-TTC staining. Myocardial blood flow (MBF) and cardiac function were evaluated. Enzyme-linked immunosorbent assay was performed to examine the content of ATP, ADP, AMP, CK, CK-MB, LDH, cTnT, cTnI, and IL-6. Double staining of F-actin and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling was conducted to assess myocardial apoptosis. Expressions of ATP synthase subunit δ (ATP 5D), and RhoA and ROCK were determined by Western blotting. Results: Administration with GLXB at high dose for 6 weeks protected heart against I/R-induced MBF decrease, myocardial infarction and apoptosis, ameliorated I/R-caused impairment of cardiac function and myocardial structure, restored the decrease in the ratio of ADP/ATP and AMP/ATP, and the expression of ATP 5D with inhibiting the expression of RhoA and ROCK. Conclusions: Treatment with GLXB effectively protects myocardial structure and function from I/R challenge, possibly via regulating energy metabolism involving inactivation of RhoA/ROCK signaling pathway.

The Memory of the Heart.

The embryological development of the heart is one of the most fascinating phenomena in nature and so is its final structure and function. The various ontogenetic passages form the evolutive basis of the final configuration of the heart. Each key step can be recognized in the final features, as the heart maintains a kind of "memory" of these passages. We can identify the major lines of development of the heart and trace these lines up to the mature organ. The aim of this review is to identify these key parameters of cardiac structure and function as essential elements of the heart's proper functioning and bases for its treatment. We aim to track key steps of heart development to identify what it "remembers" and maintains in its final form as positively selected. A new vision based on the whole acquired knowledge must guide an in-depth scientific approach in future papers and guidelines on the topic and a complete, farsighted therapeutic conduct able to ensure the physiological correction of cardiac pathologies. The application of this modern, functional vision of the heart could improve the clinical treatment of heart disease, filling the gaps still present.

Swimming exercise reverses aging-related contractile abnormalities of female heart by improving structural alterations.

BACKGROUND: The objective of this study was to examine the effect of swimming exercise on aging-related Ca2+ handling alterations and structural abnormalities of female rat heart. METHODS: For this purpose, 4-month and 24-month old female rats were used and divided into three following groups: sedentary young (SY), sedentary old (SO), and exercised old (Ex-O). Swimming exercise was performed for 8 weeks (60 min/day, 5 days/week). Myocyte shortening, L-type Ca2+ currents and associated Ca2+ transients were measured from ventricular myocytes at 36 ± 1°C. NOX-4 levels, aconitase activity, glutathione measurements and ultrastructural examination by electron microscopy were conducted in heart tissue. RESULTS: Swimming exercise reversed the reduced shortening and slowed kinetics of aged cardiomyocytes. Although the current density was similar for all groups, Ca2+ transients were higher in SO and Ex-O myocytes with respect to the SY group. Caffeine-induced Ca2+ transients and the integrated NCX current were lower in cardiomyocytes of SY rats compared with other groups, suggesting an increased sarcoplasmic reticulum Ca2+ content in an aged heart. Aging led to upregulated cardiac NOX-4 along with declined aconitase activity. Although it did not reverse these oxidative parameters, swimming exercise achieved a significant increase in glutathione levels and improved structural alterations of old rats' hearts. CONCLUSIONS: We conclude that swimming exercise upregulates antioxidant defense capacity and improves structural abnormalities of senescent female rat heart, although it does not change Ca2+ handling alterations further. Thereby, it improves contractile function of aged myocardium by mitigating detrimental effects of oxidative stress.

Heart Failure, Left Ventricular Remodeling, and Circulating Nitric Oxide Metabolites.

BACKGROUND: Stable plasma nitric oxide (NO) metabolites (NOM), composed predominantly of nitrate and nitrite, are attractive biomarkers of NO bioavailability. NOM levels integrate the influence of NO-synthase-derived NO production/metabolism, dietary intake of inorganic nitrate/nitrite, and clearance of NOM. Furthermore, nitrate and nitrite, the most abundant NOM, can be reduced to NO via the nitrate-nitrite-NO pathway. METHODS AND RESULTS: We compared serum NOM among subjects without heart failure (n=126), subjects with heart failure and preserved ejection fraction (HFpEF; n=43), and subjects with heart failure and reduced ejection fraction (HFrEF; n=32). LV mass and extracellular volume fraction were measured with cardiac MRI. Plasma NOM levels were measured after reduction to NO via reaction with vanadium (III)/hydrochloric acid. Subjects with HFpEF demonstrated significantly lower unadjusted levels of NOM (8.0 µmol/L; 95% CI 6.2-10.4 µmol/L; ANOVA P=0.013) than subjects without HF (12.0 µmol/L; 95% CI 10.4-13.9 µmol/L) or those with HFrEF (13.5 µmol/L; 95% CI 9.7-18.9 µmol/L). There were no significant differences in NOM between subjects with HFrEF and subjects without HF. In a multivariable model that adjusted for age, sex, race, diabetes mellitus, body mass index, current smoking, systolic blood pressure, and glomerular filtration rate, HFpEF remained a predictor of lower NOM (ß=-0.43; P=0.013). NOM did not correlate with LV mass, or LV diffuse fibrosis. CONCLUSIONS: HFpEF, but not HFrEF, is associated with reduced plasma NOM, suggesting greater endothelial dysfunction, enhanced clearance, or deficient dietary ingestion of inorganic nitrate. Our findings may underlie the salutary effects of inorganic nitrate supplementation demonstrated in recent clinical trials in HFpEF.

Impact of Ischemic Heart Failure Etiology on Cardiac Recovery During Mechanical Unloading.

BACKGROUND: Small-scale studies focused mainly on nonischemic cardiomyopathy (NICM) have shown that a subset of left ventricular assist device (LVAD) patients can achieve significant improvement of their native heart function, but the impact of ischemic cardiomyopathy (ICM) has not been specifically investigated. Many patients with acute myocardial infarction are discharged from their index hospitalization without heart failure (HF), only to return much later with overt HF syndrome, mainly caused by chronic remodeling of the noninfarcted region of the myocardium. OBJECTIVES: This study sought to prospectively investigate the effect of ICM HF etiology on LVAD-associated improvement of cardiac structure and function using NICM as control. METHODS: Consecutive patients (n = 154) with documented chronic and dilated cardiomyopathy (ICM, n = 61; NICM, n = 93) requiring durable support with continuous-flow LVAD were prospectively evaluated with serial echocardiograms and right heart catheterizations. RESULTS: In patients supported with LVAD for at least 6 months, we found that 5% of subjects with ICM and 21% of subjects with NICM achieved left ventricular ejection fraction ≥40% (p = 0.034). LV end-diastolic and end-systolic volumes and diastolic function were significantly and similarly improved in patients with ICM and NICM. CONCLUSIONS: LVAD-associated unloading for 6 months resulted in a substantial improvement in myocardial structure, and systolic and diastolic function in 1 in 20 ICM and 1 in 5 NICM patients. These specific incidence and timeline findings may provide guidance in clinical practice and research design for sequencing and prioritizing advanced HF and heart transplantation therapeutic options in patients with ICM and NICM.

Myocardial Structural and Functional Response After Long-Term Mechanical Unloading With Continuous Flow Left Ventricular Assist Device: Axial Versus Centrifugal Flow.

OBJECTIVES: The aim of this study was to assess the impact of continuous-flow left ventricular assist device (LVAD) type-axial flow (AX) versus centrifugal flow (CR)-on myocardial structural and functional response following mechanical unloading. BACKGROUND: The use of continuous-flow LVADs is increasing steadily as a therapeutic option for patients with end-stage heart failure who are not responsive to medical therapy. Whether the type of mechanical unloading influences the myocardial response is yet to be determined. METHODS: A total of 133 consecutive patients with end-stage heart failure implanted with continuous-flow LVADs (AX, n = 107 [HeartMate II Thoratec Corporation, Pleasanton, California]; CR, n = 26 [HeartWare, HeartWare International, Framingham, Massachusetts]) were prospectively studied. Echocardiograms were obtained pre-LVAD implantation and then serially at 1, 2, 3, 4, 6, 9, and 12 months post-implantation. RESULTS: The 2 pump types led to similar degrees of mechanical unloading as assessed by invasive hemodynamic status and frequency of aortic valve opening. Myocardial structural and functional parameters showed significant improvement post-LVAD in both AX and CR groups. Left ventricular ejection fraction increased significantly from a mean of 18% to 28% and 26% post-LVAD in the AX and CR groups, respectively. Left ventricular end-systolic volume index and left ventricular end-diastolic volume index decreased significantly as early as 30 days post-implantation in the 2 groups. The degree of myocardial structural or functional response between patients in the AX or CR groups appeared to be comparable. CONCLUSIONS: Long-term mechanical unloading induced by AX and CR LVADs, while operating within their routine clinical range, seems to exert comparable effects on myocardial structural and functional parameters.

Morphometric traits of the heart in standard and mutational colour variants of American mink ( Neovison vison ) / Características morfométricas del corazón en las variantes de color estándar y mutacional del visón americano ( Neovison vison )

The aim of this study was to estimate the values of morphological traits of myocardium in American minks. The study was conducted on 342 male mink hearts and 416 female mink hearts. Mink coat coloration resulting from mutation or crossbreeding of mutational variants with each other and sex were assumed as a source of variation. Carcass, lung and heart weights, heart height, width, depth and circumference, as well as left and right ventricular wall weights and thickness at two locations were determined. The values of 10 indices characterising the relative size of the heart were estimated. The results showed no normal distribution of the heart traits examined. The greatest average heart weight was characteristic of male mutational colour variant minks (17.40 ± 2.34 g). These hearts were heavier by more than 8 % than those of male standard colour variant minks. The hearts of male mutational colour variant minks were characterised by the greatest left and right ventricle weights (P≤0.01) compared to those of male standard colour variant minks, in which in turn the greatest left and right ventricle wall thickness was larger than that in standard colour variant minks. It was found that a greater difference calculated between mean left ventricle wall thickness and mean right ventricle wall thickness in standard colour variant minks may provide more evidence of its adaptation to a greater effort, referring thus to their evolutionary history than to the occurrence of signs of multistage myocardial hypertrophy.

El objetivo de este estudio fue estimar los valores de los rasgos morfológicos del miocardio en el visón americano. El estudio se realizó en 342 corazones de visón macho y 416 corazones de visón hembra. La coloración de la capa de visón resultante de la mutación o el cruce de variantes mutacionales entre sí, y el sexo se asumieron como una fuente de variación. Se determinaron los pesos de la canal, los pulmones y el corazón, la altura del corazón, el ancho, la profundidad y la circunferencia, así como los pesos y el grosor de las paredes de los ventrículos izquierdo y derecho en dos ubicaciones. Se estimaron los valores de 10 índices que caracterizan el tamaño relativo del corazón. Los resultados no mostraron una distribución normal de los rasgos de los corazones examinados. El mayor peso promedio del corazón fue característico de los visones de variante de color mutacional macho (17,40 ± 2,34 g). Estos corazones eran más pesados en más de un 8 % que los de los visones con variante de color estándar machos. Los corazones de los visones de variante de color mutacional macho se caracterizaron por los mayores pesos de los ventrículos izquierdo y derecho (P≤0,01) en comparación con los de los visones de color estándar machos, en los que a su vez el mayor grosor de las paredes de los ventrículos izquierdo y derecho fue mayor que el de las variantes de colores estándar. Se observó que una mayor diferencia entre los grosores medio de las paredes de los ventrículos izquierdo y derecho en las variantes de color estándar, puede proporcionar más pruebas de su adaptación a un mayor esfuerzo, refiriéndose así a su historial evolutivo, pese a la aparición de signos de hipertrofia miocárdica multietapa.

Effects of Ganoderma lucidum polysaccharides combined with metformin on myocardial structure and hemodynamics in type 2 diabetic rats / 中国药理学通报

Aim To discuss the effects and mechanism of Ganoderma lucidum polysaccharides and metformin on myocardial structure and hemodynamics in type 2 diabetic rats.Methods High fat diet combined with intraperitoneal injection of low dose streptozotocin 30 mg· kg -1 was applied to establish rat model of type 2 diabetes mellitus .The diabetic rats were randomly into normal control group ,diabetes group , ganoderma lucid-um polysaccharides group (600 mg· kg -1 ) , metformin group ( 600 mg · kg -1 ) , combination group ( ganoder-ma lucidum polysaccharides 300 mg · kg -1 +metform-in 300 mg· kg -1 ) .After 12 weeks′treatment,the lev-els of fasting serum glucose were determined and the hemodynamic parameters (LVSP,LVEDP,dp/dtmax,-dp/dtmax ) were determined.Collagen volume fraction ( CVF ) was detected by Van Gieson . Immunohisto-chemical method and Western blot were used to detect myocardial tissue MMP-2 protein expression .Results The fasting blood glucose was significantly decreased in the combined treatment group .Combined medication could significantly improve hemodynamic parameters in diabetic rats: reduced LVEP and raised LVEDP , dp/dtmax and -dp/dtmax .CVF was significantly decreased in combination group .The expression of MMP-2 in my-ocardial tissue was significantly inhibited .Conclusions The combination of Ganoderma lucidum polysaccha-ride and metformin can significantly improve the hemo-dynamic parameters in type 2 diabetic rats, and have a preventive effect on diabetic cardiomyopathy . The mechanism may be related to the down regulation of the expression of MMP-2.

Protective effects of trimetazidine on myocardial structure inj ury induced by pyran adriamycin and its mechanism / 吉林大学学报(医学版)

Objective To explore the effect of trimetazidine on myocardial structure injury induced by pyran adriamycin and to clarify the protective effect of trimetazidine on. the changes of myocardial structure and its mechanism.Methods 36 Wistar rats were randomly divided into control group,model group and treatment group. The rats in model group and treatment group were injected with pyran doxorubicin 2.5 mg·kg-1 (concentration 2 g·L-1 )by the caudal vein once a week.The rats in control group were injected with equivalent normal saline for 6 weeks.The rats in treatment group were intragastricly infused with trimetazidine 5.4 mg · kg · d-1 one day before making the model.The rats in control group and model group were injected with equivalent normal saline for 8 weeks.At the end of the experiment, the myocardial enzymes in serum of the rats in various groups were measured. The morphology of myocardium tissue was detected by light microscope and electron microscope. Results Compared with model group,the levels of myoglobin,troponin I and alanine transaminase (ALT)of the rats in treatment group were significantly decreased (P<0.05).Under light microscope the myocardium of the rats in model group arranged disorderly, the structure was severely damaged, emyocardial was seen, the myofilament was dissolved;the myocardium of the rats in treatment group arranged in order, the structure was nearly integrated,partial dissolution and fracture were found.Under electron microscope in model group the myocardial muscle bundle dissolved, fractured and disappeared, and the mitochondria was decreased,and the cytoplasmic matrix cavitation was seen;the cardiomyocytes sarcomeres of the rats in treatment group arranged in order,local myofilaments were reduced slightly, the surrounding mitochondria were oval and arranged in parallel between the muscle bundles.Conclusion Trimetazidine has protective effect on the cardiomyocyte injury caused by pyran adriamycin,and its mechanism may be related to decreasing the injury of mitochondria and myocytes.