Border Zone Of Infarcted Area Research Articles

Sodium hydrosulfide prevents myocardial dysfunction through modulation of extracellular matrix accumulation and vascular density.

The aim was to examine the role of exogenous hydrogen sulfide (H2S) on cardiac remodeling in post-myocardial infarction (MI) rats. MI was induced in rats by ligation of coronary artery. After treatment with sodium hydrosulfide (NaHS, an exogenous H2S donor, 56 μM/kg·day) for 42 days, the effects of NaHS on left ventricular morphometric features, echocardiographic parameters, heme oxygenase-1 (HO-1), matrix metalloproteinases-9 (MMP-9), type I and type III collagen, vascular endothelial growth factor (VEGF), CD34, and α-smooth muscle actin (α-SMA) in the border zone of infarct area were analyzed to elucidate the protective mechanisms of exogenous H2S on cardiac function and fibrosis. Forty-two days post MI, NaHS-treatment resulted in a decrease in myocardial fibrotic area in association with decreased levels of type I, type III collagen and MMP-9 and improved cardiac function. Meanwhile, NaHS administration significantly increased cystathionine γ-lyase (CSE), HO-1, α-SMA, and VEGF expression. This effect was accompanied by an increase in vascular density in the border zone of infarcted myocardium. Our results provided the strong evidences that exogenous H2S prevented cardiac remodeling, at least in part, through inhibition of extracellular matrix accumulation and increase in vascular density.

Effects of electrical stimulation on motor function and the expressions of microtubule-associated protein-2 and survivin after cerebral infarction in rats

Objective To investigate the effects of unilateral and bilateral electrical stimulation of the upper and lower limbs on motor function following cerebral infarction and the expressions of microtubule-associated protein-2 (MAP-2) and survivin in the infarction border zone of rats. Methods Adult male Sprague-Dawley (SD) rats were randomly divided into sham operation, control, impaired limb and bilateral limbs electrical stimulation groups (each group included 32 rats). Acute cerebral infarction was mimicked using a middle cerebral artery occlusion tech-nique. After cerebral infarction for 24 h, the rats were treated daily with or without electrical stimulation. A beam walking test (BWT) was used to measure limbs motor function and immunohistochemistry and HE staining were used to detect the expressions of MAP-2 and survivin in the border zone of infarcted area after electrical stimulation treat-ment for 3, 7, 14 and 21 d. Results Comparet with the control group treatment with electric stimulation led to BWT scores increasing significantly, and bilateral stimulation was more potent in ameliorating motor function thanstimulating the impaired limb only. The expression of MAP-2 was significantly higher in eleetrieal stimulation groups than in control group from the 7th of treatment, and it was higher in bilateral stimulation group than that in unilateral stimulation group from tbe 14th day of treatment. There was no significant difference in MAP-2 expression between bi-lateral stimulation group and sham operation group at the 21st day of treatment. In electrical stimulation groups, at every time point the expressions of survivin were obviously higher than that in sham operation group, and it was higher than that in control group and peaked at the 7tb and 14th day of treatment and in bilateral stimulation group it was no-tably higher than that in unilateral stimulation group. At the 21st d of treatment the level of survivin expression drop-per; however, there was no significant difference between unilateral and bilateral electrical stimulation groups. Con-clusions Treatment with electrical stimulation, particularly in bilateral limbs stimulation, could induce MAP-2 and survivin expressions in the infarction border zone of rats. It also could promote the recovery of motor function in para-lyzed limbs after cerebral infarction of rats. The improvement might involve the up-regulation of MAP-2 and survivin expressions. Key words: Motor function; Cerebral infarction; Electrical stimulation; Microtubule-assoeiated protein-2; Survivin

Cell body distribution after bone marrow mesenchymal stem cells intramyocardial injection into a rat myocardial infarction model

Objective To study the systemic distribution of bone marrow derived mesenchymal stem cells (MSCs) 24 h and 2 weeks after cell injection into the border zone of myocardial infarction area. Methods MSCs from male SD rats were labeled with Bromodeoxyuridine (BrdU). Three weeks after in-duction of myocardial infarction,female SD rats were randomized into 2 groups. Labeled cells (3 × 10~6 ,50 μl) were injected into the border zone of infarcted area in the one group (n = 12) ,and PBS of equal vol-ume was injected into the border zone of infarcted area in the other group ( n = 8 ). The systemic distribu-tion of MSCs was evaluated through real-time PCR and immunohistochemistry at time points of 24 h and 2 weeks after injection, respectively. Results Cells injected into border zone of infarcted area were distribu-ted to extra-cardiac organs such as spleen,lung and liver. Twenty-four h after injection,cells mainly con-centrated in the heart (467 467 ± 191 387) ,while obvious cell loss was noted in all organs including the heart ( 112 388 ±43 751 ) 2 weeks after injection. Of immunostaining were consistent with those of real-time PCR. Conclusion After injected into the border zone of infarcted area, MSCs mainly gathered in the heart with distributions into spleen, lung, and liver. However, substantial number of cells lost with pro-longed time span. Key words: Myocardial infarction; Cell transplantation; Cell distribution

The experimental study of homogenous bone marrow mesenchymal stem cells transplantation in treating acute myocardial infarction

Objective To investigate the allngeneic bone marrow mesenchymal stem cells (mesenchymal stem cells, MSCs) transplantation on cardiac rehabilitation and cardiac function after acute myocardial infarction (AMI). Method Acute myocardial infarction models were made by ligating the left anterior descending coronary artery of rats. A total of 90 rats were randomly divided into the cell transplantation group and control group, 45 rars in each group. Rats in the cell transplantation group were subdivided into 3 groups according to the administration time of the allogeneic bone marrow mesenchymal stem cells (2 weeks, 4 weeks and 12 weeks), and the control group was subdivided the same as in the cell transplantation group. The success criteria included the anterior my-ocardial wall darked and the Sr-segment elevation. The rat femur bone marrow cells were separated using centrifu-gal method, mononuclear cells were isolated by lymphocyte fluid, and the third generation of mesenchymal stem cells were obtained by washing, culture, passage and marked by 4, 6 diacetyl-2-phenyl Indole (DAPI). The ani-mals' chest was opened again a week later, the stem cell suspension was injected into the border zone of infarct area, and the control group was injected with medium. Pre-operative,2 weeks, 4 weeks and 12 weeks after trans-plantation, cardiac function was tested by ultrasonic, myocardial biopsy was observed by HE conventional staining, cardiac stem cells division were observed by immunofluorescence. All data was analyzed by software SPSS 10.0, Independent-Samples T test and Chi-Square test was used, and P≤0.05 was considered as statistically signif-icant. Results The markered hone marrow mesenchymal stem cells were left in the myocardial cells and differen-tiated to eardiomyocyte-like cells. After 12 weeks, the left ventricular internal diameter of rats in cell transplanta-tion group was about (0.58±0.09) mm(P<0.05). Thickness of myocardial infarction zone was (0.25±0.01) mm (P<0.05),ejection fraction was (67.52±0.61) (P<0.05) and left ventricular fractional shortening was (39.86±3.00) (P<0.05). In the transplantation group, the DAPI marked nucleus presented as blue, and the cytoplasm of myocardial cell presented as green. HE staining showed that, in the cell transplantation group, there was less scar tissue and a large proportion of nuclear, similar to the fetal or newhom myocardium cells. Conclu-sions The homogeneus mesenchymal stem cell could repair myocardial infarction and improve cardiac function af-ter infarction. Key words: Homogenous mesenchymal stem cell; Cell transplantation; Acute myocardia infarction; My-ocardia repaire; Cardiac function

Up-regulation of myocardial DNA base excision repair activities in experimental heart failure

Base excision repair (BER) is the major pathway to counteract the genotoxic effect of endogenous DNA damaging agents. The present study investigated the enzymatic activities and gene transcription of DNA glycosylases initiating BER in an experimental heart failure (HF) model. Rats were subjected to myocardial infarction or sham-operated. Twenty-eight days after surgical intervention cell-free protein extracts, total RNA and genomic DNA were isolated to analyze DNA glycosylase and AP-endonuclease activities, transcript levels of DNA glycosylases and accumulation of oxidative DNA damage. The capacity to remove major oxidation products (e.g., formamidopyrimidine and 5-hydroxycytosine) was significantly increased in the border zone of infarcted area, while the capacity to remove the highly mutagenic 8-oxoguanine residue was enhanced both in non-infarcted and infarcted areas of left ventricle (LV). DNA glycosylase activities towards 3-methyladenine and uracil were up-regulated in infarcted and non-infarcted areas of LV, indicating that generation of alkylated and deaminated base lesions on DNA increase during HF. Finally, we found no difference in accumulation of oxidative DNA damage in myocardial tissue between rats with post-myocardial infarction and sham-operated rats. This up-regulation of activities, initiating the BER pathway, could play an important role during HF by counteracting the effect of genotoxic stress, structural damage of tissue and myocardial remodeling.