Cardioprotective effect of 'Marutham' a polyherbal formulation on isoproterenol induced myocardial infarction in Wistar rats

Myocardial infarction is the number one killer disease in many parts of the world. The cardioprotective effect of Marutham, a polyherbal formulation on serum and heart tissue lipids, serum lipoproteins and heart membrane bound enzymes in isoproterenol induced myocardial infarction was studied in Wistar rats. Pretreatment with Marutham at different doses of 30, 60 and 90 mg kg(-1) to isoproterenol treated rats significantly prevented the altered lipid profile and membrane bound enzymes to near normal status. The results of our study showed the cardioprotective potential of Marutham on isoproterenol induced myocardial infarction in rats.     

Overexpression of integrin-linked kinase improves survival and proliferation of cardiac c-Kit+ cells

AIM: To investigate the effects of integrin-linked kinase (ILK) overexpression on survival and proliferation of cardiac c-Kit⁺ cells, and the role of ILK-overexpressing c-Kit⁺ cell transplantation in cardiac function in a rat myocardial infarction (MI) model.METHODS: Cardiac c-Kit⁺ cells were isolated from the hearts of neonatal Sprague-Dawley (SD) rats and cultured to prepare the ILK-c-Kit⁺ cells by infected with recombinant adenoviral vector harboring human wild-type ILK cDNA. The survival and proliferation of cardiac c-Kit⁺ cells were detected by cell counting and CCK-8 assay at 48 h after infection, respectively. The protein levels of cyclin D1 and proliferating cell nuclear antigen (PCNA) in the cardiac c-Kit⁺ cells were examined by Western blot. MI was induced by coronary artery ligation in 40 adult rats. After 15 min, ILK-c-Kit⁺ cells were transplanted into the hearts by myocardial injection at 3 different sites in the infracted zone and border zone. All rats were randomly divided into 4 groups:sham group, MI plus saline injection group (MI group), MI plus null vector-infected cardiac c-Kit⁺ cell injection group (Ad-null-c-Kit⁺ cell group), and MI plus ILK-overexpressing cardiac c-Kit⁺ cells injection group (ILK-c-Kit⁺ cell group), with 10 rats in each group. At 2 weeks after MI, the protein levels of c-Kit in MI hearts were investigated by immunohistochemical assay. At 4 weeks, left ventricular function was examined by hemodynamic measurement.RESULTS: The survival and proliferation of cardiac c-Kit⁺ cells and the protein levels of cyclin D1 and PCNA were enhanced by ILK overexpression compared with Ad-null group. In MI rat model, the number of c-Kit⁺ cells was increased by ILK-c-Kit⁺ cell injection compared with Ad-null-c-Kit⁺ cell group at 2 weeks after MI. Cardiac function was significantly improved in ILK-c-Kit⁺ cell-transplanted rats.CONCLUSION: ILK overexpression improves survival and proliferation of cardiac c-Kit⁺ cells by increasing the protein levels of cyclin D1 and PCNA. ILK-c-Kit⁺ cell transplantation enhances the therapeutic efficiency of cardiac c-Kit⁺ cells in the post-MI hearts of rats.     

Effects of granulocyte colony-stimulating factor on the myocardial infarction in experimental rats

AIM: To investigate the effects of granulocyte colony-stimulating factor (G-CSF) on the myocardial infarction in experimental rats. METHODS: Rats were randomly divided into GT group and saline control group (SC).The rats of GT group were treated with G-CSF (10 μg/kg) once a day subcutaneously for 5 days and those of SC group were received saline.On the third day, both groups were injected with isoprenaline (ISO) interaperitoneally to develop acute ischemic model. The hearts were harvested from 2 weeks to 4 weeks after administration of ISO for histopathological examination. RESULTS: Compared with saline control group, G-CSF treatment group significantly reduced the scar size (P<0.05). We also found the regeneration of myocytes, smooth muscle and endothelial cells. CONCLUSION: G-CSF treatment could be benefical to the regeneration of infarcted myocardium and significantly reduce scar size and it could be used for therapeutic intervention of the acute myocardial infarction.     

Calpain regulates signal transduction contributing to cardiomyocyte hypertrophy

AIM: To induce rat bone marrow mesenchymal stem cells (BMSC) into cardiomyocytes and investigate the influence of serum coming from acute myocardial infarction (AMI) rat on the procedure. METHODS: The passage 3 BMSC were divided into six groups: groupⅠwas control group; groupⅡwas induced with 5-azacytidine; group Ⅲ was induced with 5-azacytidine and serum from AMI rat; group Ⅳ was induced with 5-azacytidine and serum from normal rat; group V and group Ⅵ were induced with serum from AMI rat or normal rat. The cardiac troponin T, GATA-4 and desmin were detected 30 days after induction. RESULTS: After inducing by 5-azacytidine, 5-azacytidine and two kinds of serum, some cells in the three groups differentiated into cardiac like cells. The expressions of cardiac troponin T, GATA-4 and desmin were positive in cells differentiated from BMSC. The troponin T expression in control group and group inducing by AMI serum alone were negative but GATA-4 and desmin expressed weakly. Some cells induced with 5-azacytidine and serum were slowly beating 2 weeks after induction, but the cells induced with 5-azacytidine alone was not beating.CONCLUSION: Serum from AMI can not induce BMSC to differentiate into cardiomyocytes, but it promotes BMSC differentiate into cardiomyocytes induced by 5-azacytidine and facilitate the differentiated cells to mature.     

Effect of bFGF on promoting angiogenesis in infarct area and improving myocardial fibrosis in mouse myocardial infarction model

AIM: To investigate the protective effect of basic fibroblast growth factor (bFGF) on the heart of mice with myocardial infarction and its mechanism. METHODS: The model of myocardial infarction was established by the ligation of left anterior descending artery of C57/B6 mice (8~12 weeks old) after lateral thoracotomy. The mice were divided into sham operation group, myocardial infarction group and bFGF administration group. bFGF at 0.5 μg was intraperitoneally injected on alternate days after myocardial infarction for 7 d. Cardiac Doppler ultrasonography was used to detect cardiac function after myocardial infarction for 28 d, and left ventricular end-diastolic diameter, left ventricular end-systolic diameter, left ventricular ejection fraction and left ventricular shortening fraction (LVFS) were used to evaluate cardiac function. After myocardial infarction for 28 d, the mice were sacrificed and the hearts were collected for preparing pathological sections. The degrees of myocardial fibrosis and angiogenesis in the myocardial infarction area were observed. Western blot was used to detect the indicators of angiogenesis. RESULTS: The results of Masson staining showed that bFGF administration significantly reduced myocardial fibrosis at 28 d after myocardial infarction. Cardiac ultrasound data showed that cardiac functions in myocardial infarction group were poorer than those in sham group, and bFGF administration significantly improved cardiac functions. Immunofluorescence staining showed that neovascularization in myocardial infarction area of bFGF administration group was more than that in myocardial infarction group. The results of Western blot showed that bFGF activated AKT/HIF-1α/VEGF signaling pathway. CONCLUSION: Intraperitoneal injection of bFGF reduces myocardial fibrosis and improves cardiac function in myocardial infarction mice. bFGF may promote angiogenesis by activating AKT/HIF-1α/VEGF signaling pathway.     

Effect of losartan on matrix metalloproteinases of myocardial extracellular matrix after infarction in the rat

AIM: To study the change of the activity of matrix metalloproteinases(MMPs) in the infarcted intestitium of rat heart and the effect of Losartan on them. METHODS: 80 Adult male Sprague-Dawley rats underwent the left descending coronary artery ligation, then being divided randomly into control, treated groups and sham operation group. After hemodynamic parameters were obtained,animals of 8 groups were killed at 4 timepoints ( day 3, day 7,day 14, day 42 after infarction ).Matrix metalloproteinases(MMPs) activity in infarct zone was measured by zymography,so did collagen concentration in both ventricles by the method of chloramine T. RESULTS: The activity of MMPs in the infarcted zone showed a transient increase, which raiesd by 4.5 folds at day 3 (compared with the sham-operated group killed at day 3), 6.5 folds at day 7, and declined thereafter,being 2 folds at day 14, 1.5 folds at day 42. Losaran treatment was associated with significant attenuation of MMPs activity. The activity of MMP-1 (54 kD band) decreased 33%, so did the MMP-2 (58 kD and 62 kD bands) 50%. Compared with control groups, the hypertrophy of the left ventricle was regressed, the rate of LVW/BW dropped significantly at day 14 and day 42 ( P< 0.01) .The collagen concentration decreased at treated day 42 group( P< 0.01).For the regression of heart dysfuncton in Losartan groups, LVEDP demonstrated a slightly raise at day 3, then decreased at day 7,14,42, all of three groups’ systolic function are higher than that in the control ( P< 0.05). CONCLUSION: The latent MMPs were activated after infarction, which resulted in the demage of the fibrillar network and dalitation of the left ventricle.Losartan not only attenuates the activity of MMPs but also prevents collagen synthesis, decreases the total collagen in the necrosis zone at the late stage after infaction, thus regressing the progress dysfuction of the infarcted heart and protecting the myocardium.     

Effect of PPARδ activation on expression of MMP-9 and fibronectin in infarcted myocardium

AIM:To investigate the effect of peroxisome proliferator-activated receptor δ (PPARδ) activation with dietary GW610742X on the expression of matrix metalloproteinase-9 (MMP-9) and fibronectin (FN) in infarcted and remodeling myocardium. METHODS: Wistar rats were divided into 4 groups: control group, sham group, myocardial infarction (MI) group and MI+GW610742X (GW) group. The left coronary artery was ligated to establish the MI model. PPARδ activator GW610742X (100 mg·kg^-1·d^-1) was given to the rats in GW group. At the 3rd month of the procedure, the expression of PPARδ, MMP-9 and FN at mRNA and protein levels in the left ventricular free wall(LVFW) of the heart from each group was identified and the distribution of FN was detected by immunofluorescence. RESULTS: After 3 months following the procedure, obvious necrosis and fibrosis in LVFW were observed in MI group. The expression of PPARδ in MI group was higher than that in control, sham and GW groups (P<0.01), and PPARδ expression in GW group was lower than that in control and sham group (P<0.05). In MI and GW groups, the expression of MMP-9 was higher while the expression of FN was lower than those in control and sham group (P<0.05 or P<0.01). In GW group, the expression of MMP-9 was lower (P<0.05) while the expression of FN was higher (P<0.01) than those in MI group. Meanwhile, the expression of MMP-9 and FN in sham group was similar to those in control group (P>0.05). CONCLUSION: MMP-9 is upregulated and FN is downregulated in infarcted myocardium during the remodeling process. Activation of PPARδ inhibits the upregulation of MMP-9 and degradation of FN, thus ameliorating the myocardial remodeling.     

46例一氧化碳中毒合并脑梗塞患者的智能测评

目的探讨一氧化碳中毒合并脑梗塞患者的智能变化．方法对患者仿用智力量表进行检测,严格按操作规程进行,检测期间患者意识清楚,能够合作．数据以（x±s）表示,进行t检验．结果46例病例组比45例对照组测验得分明显减少,尤其是计算力和近记忆力更为明显,有显著性差异（P〈0．01）．结论一氧化碳中毒合并脑梗塞患者在恢复期进行智能测评是判断患者智能恢复程度的一项重要指标．     

MAGNETIC RESONANCE IMAGING OF BRAIN INFARCTION IN SEVEN DOGS

Magnetic resonance imaging was performed in seven dogs with histopathologically-confirmed brain infarcts. The infarcts were non-hemorrhagic in four dogs and hemorrhagic in three dogs. Six dogs had single infarcts involving the cerebrum and one dog had multiple infarcts involving the cerebrum and brain stem. Non-hemorrhagic infarcts were typically wedge-shaped, hypointense on T1-weighted images, hyperintense on T2-weighted images, and did not enhance with gadolinium-DTPA. Hemorrhagic infarcts had mixed intensity on T1- and T2-weighted images, with variable patterns of enhancement.     

Computed tomography diagnosis of eight dogs with brain infarction

Objective Medical records of eight dogs presenting with acute onset of neurological signs and a diagnosis of brain infarction as determined by computed tomography (CT) imaging were reviewed. Design Retrospective single-centre case review Results Ischaemic infarction in the territory of the rostral cerebellar artery was identified in three spaniel-breed dogs. All cerebellar infarcts were non-haemorrhagic. Telencephalic infarcts were identified in five dogs, in the territories of the middle cerebral artery (2/5) and rostral cerebral artery (3/5). One of these dogs had an ischaemic infarction, but all other infarctions appeared haemorrhagic. All dogs were geriatric (≥8 years old), with concurrent medical conditions identified in six dogs. One dog was euthanased after diagnosis because of the severity of its neurological signs and one dog was euthanased as a result of associated renal disease 2 months after diagnosis. Six dogs were alive at least 1 year after diagnosis. Conclusions CT is useful in the diagnosis of cerebrovascular accident in dogs, which can present as a spectrum of images with early changes in attenuation and subtle mass effects detected after infarction. CT is particularly sensitive for detecting haemorrhagic infarction, but under-represent ischaemic and lacunar infarctions when compared with MRI.