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Sample records for binucleated myocardial cells

  1. Formation of binucleated myocardial cells in the neonatal rat. An index for growth hypertrophy

    International Nuclear Information System (INIS)

    Clubb, F.J. Jr.; Bishop, S.P.

    1984-01-01

    The purposes of this study were to characterize myocardial cell growth in neonatal rats and investigate the mechanism of binucleation in myocardial cells. To test the hypothesis that binucleated myocardial cells result from karyokinesis without cytokinesis, experiments were designed to measure the rate of DNA synthesis and the percentage of binucleated myocardial cells in neonatal rats during growth. Estimates of myocardial cell nuclear divisions were obtained from rats pulsed with tritiated thymidine at 17 days of gestation. Autoradiograms were prepared from isolated myocardial cells of rats killed at various ages postpartum, and the number of developed silver halide grains over myocardial cell nuclei was calculated. This estimated the mitotic activity of nuclei. To determine myocardial cell DNA synthesis postpartum, another set of rats were injected at various time periods with 4 hourly doses of tritiated thymidine, and hearts were fixed by perfusion 1 hour later. Labeling index of myocardial cells was calculated (labeled/total myocardial cells) from autoradiograms. Results indicated that the growth of myocardial cells in period can be divided into three phases: (a) a hyperplastic phase, (b) a transitional phase, and (c) a hypertrophic phase. Binucleation of myocardial cells was not due to fusion of mononucleated cells

  2. Origin and evolution of binucleated cells and binucleated cells with micronuclei in cisplatin-treated CHO cultures.

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    Rodilla, V

    1993-08-01

    It has recently been described that cisplatin is an agent able to induce binucleated cells (BC) in cultured CHO cells. Both the origin and the significance of those cells within a population are unknown although several hypothesis have been suggested such as blocking of cytokinesis or cell fusion. Using interval photography we have found that at least two mechanisms are involved in the production of BC. These cells can arise in a culture as a result of an incomplete process of cell division, i.e. karyokinesis with incomplete cytokinesis or as a result of the mitotic division of a pre-existent BC. The mitotic division of a BC can give rise to different types of daughter cells. These BC sometimes enter mitosis but fail to divide and as a consequence they remain BC. When the process of division is successful (in the vast majority of cases), the results that have been found are either two mononucleated cells or one mononucleated and one binucleated cell. The possible implications and significance of BC and BC with micronuclei in a given population are discussed.

  3. Automated Detection of Binucleated Cell and Micronuclei using CellProfiler 2.0 Software

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    DWI RAMADHANI

    2013-12-01

    Full Text Available Micronucleus assay in human peripheral lymphocytes usually used to assess chromosomal damage. Manual scoring of micronuclei can be time consuming and large numbers of binucleated cells have to be analyzed to obtain statistically relevant data. Automation of the micronuclei analysis using image processing analysis software can provide a faster and more reliable analysis of micronucleus assay. Here the used of CellProfiler an open access cell image analysis software for automatic detection of binucleated cells and micronuclei were reported. We aimed to know whether there was a significant difference in the number of binucleated cells and micronuclei that obtained by manual and CellProfiler counting. Wilcoxon Rank test was used for statistical analysis to test H0 hypothesis that there was no significant difference in the number of binucleated cells and micronuclei that obtained by manual and CellProfiler counting. We analyzed 135 images for both manual and CellProfiler counting. Our results showed that there was no significant difference between manual and CellProfiler counting for binucleated cells (P = 0.851 and for micronuclei (P = 0.917. In conclusion, the binucleated cells and micronuclei counting using CellProfiler were comparable but not better than manual counting.

  4. Human papillomavirus 16 E5 induces bi-nucleated cell formation by cell-cell fusion

    International Nuclear Information System (INIS)

    Hu Lulin; Plafker, Kendra; Vorozhko, Valeriya; Zuna, Rosemary E.; Hanigan, Marie H.; Gorbsky, Gary J.; Plafker, Scott M.; Angeletti, Peter C.; Ceresa, Brian P.

    2009-01-01

    Human papillomaviruses (HPV) 16 is a DNA virus encoding three oncogenes - E5, E6, and E7. The E6 and E7 proteins have well-established roles as inhibitors of tumor suppression, but the contribution of E5 to malignant transformation is controversial. Using spontaneously immortalized human keratinocytes (HaCaT cells), we demonstrate that expression of HPV16 E5 is necessary and sufficient for the formation of bi-nucleated cells, a common characteristic of precancerous cervical lesions. Expression of E5 from non-carcinogenic HPV6b does not produce bi-nucleate cells. Video microscopy and biochemical analyses reveal that bi-nucleates arise through cell-cell fusion. Although most E5-induced bi-nucleates fail to propagate, co-expression of HPV16 E6/E7 enhances the proliferation of these cells. Expression of HPV16 E6/E7 also increases bi-nucleated cell colony formation. These findings identify a new role for HPV16 E5 and support a model in which complementary roles of the HPV16 oncogenes lead to the induction of carcinogenesis

  5. Binucleate cell formation correlates to loss of colony-forming ability in X-irradiated cultured mammalian cells

    International Nuclear Information System (INIS)

    Sasaki, H.; Yoshinaga, H.; Kura, S.

    1986-01-01

    The relationship between binucleate cell formation and the loss of colony-forming ability was examined in several cultured mammalian cell lines irradiated with X rays. The maximum fraction of binucleate cells after X irradiation increased dose-dependently within the range in which reproductive cell death might predominate over interphase cell death. When the logarithm of percentage survival was plotted against the percentage binucleate cells, a similar correlation was found for all cell lines tested, with the exception of mouse leukemia L5178Y cells, the most radiosensitive cells used. These observations suggest that the fraction of binucleate cells in the cell population can serve as a measure of cellular radiation damage

  6. Effect of oxygen on formation of micronuclei and binucleated cells and cell survival in γ-irradiated 3T3 cells

    International Nuclear Information System (INIS)

    Zhang Peng; Zheng Xiulong

    1991-01-01

    Formation of micronuclei and binucleate cells and their relationships with cell survival were studied in the aerobically- and anaerobically-irradiated 3T3 cells. The results showed taht frequency of micronuclei, percentage of micronucleus cells and percentage of binucleate cells increased linearly with the radiation dose in certain range. Oxygen enhancement ratios (OER) of micronucleus frequency, percentage of micronucleus cells, percentage of binucleate cells and cell survival were 2.02, 1.96, 1.87 and 1.83 respectively. The percentage of micronucleus cells or the percentage of micronucleus cells plus binucleate cells correlated negatively well with cell survival. The mechanism of oxygen effect in the radiation response of 3T3 cells and the significance of formation of micronuclei and binucleate cells were discussed

  7. Isoform-specific functions of Mud/NuMA mediate binucleation of Drosophila male accessory gland cells.

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    Taniguchi, Kiichiro; Kokuryo, Akihiko; Imano, Takao; Minami, Ryunosuke; Nakagoshi, Hideki; Adachi-Yamada, Takashi

    2014-12-20

    In standard cell division, the cells undergo karyokinesis and then cytokinesis. Some cells, however, such as cardiomyocytes and hepatocytes, can produce binucleate cells by going through mitosis without cytokinesis. This cytokinesis skipping is thought to be due to the inhibition of cytokinesis machinery such as the central spindle or the contractile ring, but the mechanisms regulating it are unclear. We investigated them by characterizing the binucleation event during development of the Drosophila male accessory gland, in which all cells are binucleate. The accessory gland cells arrested the cell cycle at 50 hours after puparium formation (APF) and in the middle of the pupal stage stopped proliferating for 5 hours. They then restarted the cell cycle and at 55 hours APF entered the M-phase synchronously. At this stage, accessory gland cells binucleated by mitosis without cytokinesis. Binucleating cells displayed the standard karyokinesis progression but also showed unusual features such as a non-round shape, spindle orientation along the apico-basal axis, and poor assembly of the central spindle. Mud, a Drosophila homolog of NuMA, regulated the processes responsible for these three features, the classical isoform Mud(PBD) and the two newly characterized isoforms Mud(L) and Mud(S) regulated them differently: Mud(L) repressed cell rounding, Mud(PBD) and Mud(S) oriented the spindle along the apico-basal axis, and Mud(S) and Mud(L) repressed central spindle assembly. Importantly, overexpression of Mud(S) induced binucleation even in standard proliferating cells such as those in imaginal discs. We characterized the binucleation in the Drosophila male accessory gland and examined mechanisms that regulated unusual morphologies of binucleating cells. We demonstrated that Mud, a microtubule binding protein regulating spindle orientation, was involved in this binucleation. We suggest that atypical functions exerted by three structurally different isoforms of Mud regulate

  8. Centrosome Clustering in the Development of Bovine Binucleate Trophoblast Giant Cells.

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    Klisch, Karl; Schraner, Elisabeth M; Boos, Alois

    2017-01-01

    Binucleate trophoblast giant cells (BNC) are the characteristic feature of the ruminant placenta. During their development, BNC pass through 2 acytokinetic mitoses and become binucleate with 2 tetraploid nuclei. In this study, we investigate the number and location of centrosomes in bovine BNC. Centrosomes typically consist of 2 centrioles surrounded by electron-dense pericentriolar material. Duplication of centrosomes is tightly linked to the cell cycle, which ensures that the number of centrosomes remains constant in proliferating diploid cells. Alterations of the cell cycle, which affect the number of chromosome sets, also affect the number of centrosomes. In this study, we use placentomal tissue from pregnant cows (gestational days 80-230) for immunohistochemical staining of γ-tubulin (n = 3) and transmission electron microscopy (n = 3). We show that mature BNC have 4 centrosomes with 8 centrioles, clustered in the angle between the 2 cell nuclei. During the second acytokinetic mitosis, the centrosomes must be clustered to form the poles of a bipolar spindle. In rare cases, centrosome clustering fails and tripolar mitosis leads to the formation of trinucleate "BNC". Generally, centrosome clustering occurs in polyploid tumor cells, which have an increased number of centrioles, but it is absent in proliferating diploid cells. Thus, inhibition of centrosome clustering in tumor cells is a novel promising strategy for cancer treatment. BNC are a cell population in which centrosome clustering occurs as part of the normal life history. Thus, they might be a good model for the study of the molecular mechanisms of centrosome clustering. © 2016 S. Karger AG, Basel.

  9. Dose dependency of the frequency of micronucleated binucleated clone cells and of division related median clone sizes difference. Pt. 2

    International Nuclear Information System (INIS)

    Hagemann, G,; Kreczik, A.; Treichel, M.

    1996-01-01

    Following irradiation of the progenitor cells the clone growth of CHO cells decreases as a result of cell losses. Lethally acting expressions of micronuclei are produced by heritable lethal mutations. The dependency of the frequency of micronucleated binucleated clone cells and of the median clone sizes difference on the radiation dose was measured and compared to non-irradiated controls. Using the cytokinesis-block-micronucleus-method binucleated cells with micronuclei were counted as ratio of all binucleated cells within a clone size distribution. This ratio (shortened: micronucleus yield) was determined for all clone size distributions, which had been exposed to different irradiation doses and incubation times. The micronucleus yields were compared to the corresponding median clone sizes differences. The micronucleus yield is linearly dependent on the dose and is independent of the incubation time. The same holds true for the division related median clone sizes difference, which as a result is also linearly dependent on the micronucleus yield. Due to the inevitably errors of the cell count of micronucleated binucleated cells, an automatic measurement of the median clone sizes differences is the preferred method for evaluation of cellular radiation sensitivity for heritable lethal mutations. This value should always be determined in addition, if clone survival fractions are used as predictive test because it allows for an estimation of the remission probability of surviving cells. (orig.) [de

  10. Significance of the proportion of binucleate cells in the micronucleus assay; A methodological study

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    Imamura, Masahiro; Edgren, M.R. (Karolinska Inst., Stockholm (Sweden). Dept. of Radiation Physics)

    1994-03-01

    Using treatment with cytochalasin-B (Cyt-B) for the induction of a cytokinetic block, the significance of the proportion of binucleate cells (BNC) in the micronucleus (MN) assay was investigated in a methodological study. A Chinese hamster cell line V79 was used in which MN were induced by radiation. In complementary tests the radiation effect in inducing MN was enhanced by depletion of the cellular glutathione content with buthionine sulfoximine (BSO). The data indicated that the concentration of Cyt-B is the major factor which determines the proportion of BNC. This proportion was shown to be independent of radiation dose and of BSO. Furthermore, the MN frequency was not related to the percentage of BNC. Therefore, a high proportion of BNC may be practical for the MN assay, but may not make the technique more accurate. (author).

  11. Significance of the proportion of binucleate cells in the micronucleus assay

    International Nuclear Information System (INIS)

    Imamura, Masahiro; Edgren, M.R.

    1994-01-01

    Using treatment with cytochalasin-B (Cyt-B) for the induction of a cytokinetic block, the significance of the proportion of binucleate cells (BNC) in the micronucleus (MN) assay was investigated in a methodological study. A Chinese hamster cell line V79 was used in which MN were induced by radiation. In complementary tests the radiation effect in inducing MN was enhanced by depletion of the cellular glutathione content with buthionine sulfoximine (BSO). The data indicated that the concentration of Cyt-B is the major factor which determines the proportion of BNC. This proportion was shown to be independent of radiation dose and of BSO. Furthermore, the MN frequency was not related to the percentage of BNC. Therefore, a high proportion of BNC may be practical for the MN assay, but may not make the technique more accurate. (author)

  12. Immunolocalization of progesterone receptors in binucleate trophoblast cells of the buffalo placenta (Bubalus bubalis

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    Carlos Eduardo Ambrósio

    2007-06-01

    Full Text Available The binucleate trophoblast cells (CTBs of the water buffalo placenta (Bubalus bubalis were studied with emphasis on the presence of progesterone receptor. Placentomal tissues from 27 buffalos (2-10 months of pregnancy were processed and embedded in paraplast (Paraplast Embedding Media – Paraplast Plus to locate the progesterone receptors using the immunohistochemistry technique. The immunohistochemical reaction for progesterone receptor through monoclonal antibody PgR Ab2 showed staining of CTBs, caruncular epithelial and estromal cells and blood vessel estromal pericitos present in the placentome throughout the entire gestational period analyzed. These results indicate the production of progesterone with autocrine and paracrine action in the placentome growth, differentiation and functional regulation.

  13. Induction of micronuclei and binucleated cells by treatment with radiation and cisplatin in CHO cells

    International Nuclear Information System (INIS)

    Rodilla, V.; Seymour, C.B.; Mothersill, C.; Pertusa, J.; Pellicer, J.A.

    1991-01-01

    The frequencies of CHO cells with micronuclei in the cisplatin-treated cultures showed an increase reaching a maximum 48 hours after treatment. Within the next 48 hours a slight decrease in the frequencies was observed. In γ-irradiated cultures (1.2 Gy/min at 80 cm source-skin distance) the maximum in micronuclei-induction was reached at 24 hours post-irradiation, decreasing thereafter. Cultures receiving both treatments showed a similar curve, with a peak at 24 hours, decreasing thereafter. (UK)

  14. Hydrocortisone Increases the Vinblastine-Induced Chromosomal Damages in L929 Cells Investigated by the Micronucleus Assay on Cytokinesis-Blocked Binucleated Cells

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    Tahere Ebrahimipour

    2017-03-01

    Full Text Available Background: Stress may cause damages to DNA or/and change the ability of the cells to overcome these damages. It may also cause irregularities in the cell cycle and induce abnormal cell divisions through glucocorticoid-dependent functions. The abnormal cell divisions, in turn, lead to chromosomal mal-segregation and aneuploidy. In this study, the effects of the stress hormone, hydrocortisone (HYD, were investigated on the induced chromosomal abnormalities by vinblastine (VIN during cell cycle in L929 cells. Methods: This work was performed in winter 2013 at Department of Biology, University of Ferdowsi, Mashhad, Iran. Cultured cells were divided into different groups including control, VIN-treated, HYD treated and VIN+HYD co-treated cells. The induced chromosomal damages were investigated by micronucleus assay in cytokinesis-blocked binucleated cells. Results: Although HYD by itself did not increase the micronuclei (Mn frequency, co-treatment of cells with VIN and HYD led to significant increase (P<0.05 in the frequency of Mn in comparison to control and VIN treated groups. Conclusion: Cells treated with stress hormone are more sensitive to damages induced by VIN. Therefore, stress may not directly result in genetic instability, it can increase the harmful effects associated with other genotoxic agents.

  15. Increased levels of lead in the blood and frequencies of lymphocytic micronucleated binucleated cells among workers from an electronic-waste recycling site.

    Science.gov (United States)

    Wang, Qian; He, An M; Gao, Bo; Chen, Lan; Yu, Qiang Z; Guo, Huan; Shi, Bin J; Jiang, Pu; Zhang, Zeng Y; Li, Ping L; Sheng, Ying G; Fu, Mo J; Wu, Chun T; Chen, Min X; Yuan, Jing

    2011-01-01

    In recent years, adverse health effects of chemicals from electronic waste (e-waste) have been reported. However, little is known about the genotoxic effects of chemicals in e-waste. In the present study, air concentrations of the toxic metals at e-waste and control sites were analyzed using inductively-coupled plasma mass spectrometry. Levels of toxic metals (lead, copper and cadmium) in blood and urine were detected using atomic absorption spectrophotometry in 48 exposed individuals and 56 age- and sex-matched controls. The frequencies of lymphocytic micronucleated binucleated cells (MNBNCs) were determined using a cytokinesis-block micronucleus assay. Results indicated that blood lead levels were significantly higher in the exposed group (median: 11.449 μg/dL, 1st/3rd quartiles: 9.351-14.410 μg/dL) than in the control group (median: 9.104 μg/dL, 1st/3rd quartiles: 7.275-11.389 μg/dL). The exposed group had higher MNBNCs frequencies (median: 4.0 per thousand, 1st/3rd quartiles: 2.0-7.0 per thousand) compared with the controls (median: 1.0 per thousand, 1st/3rd quartiles: 0.0-2.0 per thousand). Additionally, MNBNCs frequencies and blood lead levels were positively correlated (r = 0.254, phistory of working with e-waste was a predictor for increased blood lead levels and MNBNCs frequencies in the subjects. The results suggest that both the living and occupational environments at the e-waste site may be risk factors for increased MNBNCs frequencies among those who are exposed.

  16. TGFbeta Induces Binucleation/Polyploidization in Hepatocytes through a Src-Dependent Cytokinesis Failure.

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    Marco De Santis Puzzonia

    Full Text Available In all mammals, the adult liver shows binucleated as well as mononucleated polyploid hepatocytes. The hepatic polyploidization starts after birth with an extensive hepatocyte binucleation and generates hepatocytes of several ploidy classes. While the functional significance of hepatocyte polyploidy is becoming clearer, how it is triggered and maintained needs to be clarified. Aim of this study was to identify a major inducer of hepatocyte binucleation/polyploidization and the cellular and molecular mechanisms involved. We found that, among several cytokines analyzed, known to be involved in early liver development and/or mass control, TGFbeta1 was capable to induce, together with the expected morphological changes, binucleation in hepatocytes in culture. Most importantly, the pharmacological inhibition of TGFbeta signaling in healthy mice during weaning, when the physiological binucleation occurs, induced a significant decrease of hepatocyte binucleation rate, without affecting cell proliferation and hepatic index. The TGFbeta-induced hepatocyte binucleation resulted from a cytokinesis failure, as assessed by video microscopy, and is associated with a delocalization of the cytokinesis regulator RhoA-GTPase from the mid-body of dividing cells. The use of specific chemical inhibitors demonstrated that the observed events are Src-dependent. Finally, the restoration of a fully epithelial phenotype by TGFbeta withdrawal gave rise to a cell progeny capable to maintain the polyploid state. In conclusion, we identified TGFbeta as a major inducer of hepatocyte binucleation both in vitro and in vivo, thus ascribing a novel role to this pleiotropic cytokine. The production of binucleated/tetraploid hepatocytes is due to a cytokinesis failure controlled by the molecular axis TGFbeta/Src/RhoA.

  17. TGFbeta Induces Binucleation/Polyploidization in Hepatocytes through a Src-Dependent Cytokinesis Failure.

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    De Santis Puzzonia, Marco; Cozzolino, Angela Maria; Grassi, Germana; Bisceglia, Francesca; Strippoli, Raffaele; Guarguaglini, Giulia; Citarella, Franca; Sacchetti, Benedetto; Tripodi, Marco; Marchetti, Alessandra; Amicone, Laura

    2016-01-01

    In all mammals, the adult liver shows binucleated as well as mononucleated polyploid hepatocytes. The hepatic polyploidization starts after birth with an extensive hepatocyte binucleation and generates hepatocytes of several ploidy classes. While the functional significance of hepatocyte polyploidy is becoming clearer, how it is triggered and maintained needs to be clarified. Aim of this study was to identify a major inducer of hepatocyte binucleation/polyploidization and the cellular and molecular mechanisms involved. We found that, among several cytokines analyzed, known to be involved in early liver development and/or mass control, TGFbeta1 was capable to induce, together with the expected morphological changes, binucleation in hepatocytes in culture. Most importantly, the pharmacological inhibition of TGFbeta signaling in healthy mice during weaning, when the physiological binucleation occurs, induced a significant decrease of hepatocyte binucleation rate, without affecting cell proliferation and hepatic index. The TGFbeta-induced hepatocyte binucleation resulted from a cytokinesis failure, as assessed by video microscopy, and is associated with a delocalization of the cytokinesis regulator RhoA-GTPase from the mid-body of dividing cells. The use of specific chemical inhibitors demonstrated that the observed events are Src-dependent. Finally, the restoration of a fully epithelial phenotype by TGFbeta withdrawal gave rise to a cell progeny capable to maintain the polyploid state. In conclusion, we identified TGFbeta as a major inducer of hepatocyte binucleation both in vitro and in vivo, thus ascribing a novel role to this pleiotropic cytokine. The production of binucleated/tetraploid hepatocytes is due to a cytokinesis failure controlled by the molecular axis TGFbeta/Src/RhoA.

  18. Significance of Compression in Binucleation while Differentiating Reactive Cellular Changes Between Human Papillomavirus and Candida Infections

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    Okodo, Mitsuaki; Okayama, Kaori; Fukui, Tadasi; Shiina, Natsuko; Caniz, Timothy; Yabusaki, Hiromi; Fujii, Masahiko

    2017-09-27

    Purpose: Binucleation is a reactive cellular change (RCC) in Pap smears due to Candida infection. However, the origin of these binucleated cells as RCCs remains unclear. The purpose of this study was to examine binucleation in patients negative for intraepithelial lesion or malignancy (NILM) and infected with Candida and those infected with high-risk human papillomavirus (hr-HPV) and to clarify the origin of the binucleated cells. Methods: A total of 115 endocervical swab specimens with a combined diagnosis of NILM, Candida infection, and RCCs were used for this study. Pap smears were used to identify binucleated cells and then separate them into two groups, compression-positive and compression-negative. In addition, hr-HPV was detected using polymerase chain reaction (PCR) with a specific primer on the DNA extracted from the remaining residual cytology specimens. To make the hr-HPV-infected binucleated cells visible, an in situ PCR assay was performed on the Pap smear. Result: Of the 115 specimens, 69.6% contained binucleated cells, 26 (32.5%) showed only the compressed form, 35 (43.8%) showed only the non-compressed form, and 19 showed both the compressed and non-compressed forms of binucleated cells. Also, 34 specimens (29.6%) were positive for hr-HPV. The sensitivity and specificity of compression-positive binucleated cells were 91.2% and 82.7% (p compression-negative group (p = 0.156). Also, 34 cases with hr-HPV contained 99 compression-positive and 24 compression-negative cells. The hr-HPV-positive cells accounted for 68 (68.7%) of the 99 compression-positive and 2 (8.3%) of the 24 compression-negative binucleated cells as determined by an in situ PCR assay for hr-HPV. The relationship between compression and hr-HPV was statistically significant (p Compression-positive binucleated cells may be present as a result of hr-HPV infection and not RCC, which is caused due to inflammation in NILM cases infected with Candida. Creative Commons Attribution License

  19. Myocardial regeneration potential of adipose tissue-derived stem cells

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    Bai, Xiaowen, E-mail: baixw01@yahoo.com [Department of Molecular Pathology, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe, Houston, TX 77030 (United States); Alt, Eckhard, E-mail: ealt@mdanderson.org [Department of Molecular Pathology, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe, Houston, TX 77030 (United States)

    2010-10-22

    Research highlights: {yields} Various tissue resident stem cells are receiving tremendous attention from basic scientists and clinicians and hold great promise for myocardial regeneration. {yields} For practical reasons, human adipose tissue-derived stem cells are attractive stem cells for future clinical application in repairing damaged myocardium. {yields} This review summarizes the characteristics of cultured and freshly isolated stem cells obtained from adipose tissue, their myocardial regeneration potential and the, underlying mechanisms, and safety issues. -- Abstract: Various tissue resident stem cells are receiving attention from basic scientists and clinicians as they hold promise for myocardial regeneration. For practical reasons, adipose tissue-derived stem cells (ASCs) are attractive cells for clinical application in repairing damaged myocardium based on the following advantages: abundant adipose tissue in most patients and easy accessibility with minimally invasive lipoaspiration procedure. Several recent studies have demonstrated that both cultured and freshly isolated ASCs could improve cardiac function in animal model of myocardial infarction. The mechanisms underlying the beneficial effect of ASCs on myocardial regeneration are not fully understood. Growing evidence indicates that transplantation of ASCs improve cardiac function via the differentiation into cardiomyocytes and vascular cells, and through paracrine pathways. Paracrine factors secreted by injected ASCs enhance angiogenesis, reduce cell apoptosis rates, and promote neuron sprouts in damaged myocardium. In addition, Injection of ASCs increases electrical stability of the injured heart. Furthermore, there are no reported cases of arrhythmia or tumorigenesis in any studies regarding myocardial regeneration with ASCs. This review summarizes the characteristics of both cultured and freshly isolated stem cells obtained from adipose tissue, their myocardial regeneration potential, and the

  20. Myocardial regeneration potential of adipose tissue-derived stem cells

    International Nuclear Information System (INIS)

    Bai, Xiaowen; Alt, Eckhard

    2010-01-01

    Research highlights: → Various tissue resident stem cells are receiving tremendous attention from basic scientists and clinicians and hold great promise for myocardial regeneration. → For practical reasons, human adipose tissue-derived stem cells are attractive stem cells for future clinical application in repairing damaged myocardium. → This review summarizes the characteristics of cultured and freshly isolated stem cells obtained from adipose tissue, their myocardial regeneration potential and the, underlying mechanisms, and safety issues. -- Abstract: Various tissue resident stem cells are receiving attention from basic scientists and clinicians as they hold promise for myocardial regeneration. For practical reasons, adipose tissue-derived stem cells (ASCs) are attractive cells for clinical application in repairing damaged myocardium based on the following advantages: abundant adipose tissue in most patients and easy accessibility with minimally invasive lipoaspiration procedure. Several recent studies have demonstrated that both cultured and freshly isolated ASCs could improve cardiac function in animal model of myocardial infarction. The mechanisms underlying the beneficial effect of ASCs on myocardial regeneration are not fully understood. Growing evidence indicates that transplantation of ASCs improve cardiac function via the differentiation into cardiomyocytes and vascular cells, and through paracrine pathways. Paracrine factors secreted by injected ASCs enhance angiogenesis, reduce cell apoptosis rates, and promote neuron sprouts in damaged myocardium. In addition, Injection of ASCs increases electrical stability of the injured heart. Furthermore, there are no reported cases of arrhythmia or tumorigenesis in any studies regarding myocardial regeneration with ASCs. This review summarizes the characteristics of both cultured and freshly isolated stem cells obtained from adipose tissue, their myocardial regeneration potential, and the underlying

  1. Apparent amitosis in the binucleate dinoflagellate Peridinium balticum.

    Science.gov (United States)

    Tippit, D H; Pickett-Heaps, J D

    1976-07-01

    Mitosis and cytokinesis in the free-living binucleate dinoflagellate Peridinium balticum are described, P. balticum contains 2 nuclei; one is a typical dinoflagellate nucleus and the other resembles the interphase nuclei of some eucaryotic cells and is here named the supernumerary nucleus (formerly called the eucaryotic nucleus). The dinoflagellate nucleus divides in the characteristic manner already described for certain other dinoflagellates. The supernumerary nucleus does not undergo normal mitosis; its chromatin does not condense, a spindle is not differentiated for its division, nor are any microtubules present inside the nucleus during any stage of its division. Instead the supernumerary nucleus divides by simple cleavage, which is concurrent with cytoplasmic cleavage. The nucleus cleaves first on its side facing the wall, but later it cleaves circumferentially as the cytoplasmic cleavage furrow draws closer. Invariably at late cytokinesis, a portion of the dividing nucleus passes through the only remaining uncleaved area of the cell. The final separation of the supernumerary nucleus is probably accomplished by the ingrowing furrow pinching the nucleus in two. There is no apparent precise segregation of genetic material during division, nor are there any structural changes inside the dividing nucleus which distinguish it from the interphase nucleus. Certain aspects of amitosis, and previously postulated theories concerning the endosymbiont origin of the second nucleus, are discussed.

  2. Myocardial SPECT in children with sickle cell disease

    International Nuclear Information System (INIS)

    Maunoury, C.; Hallaj, I.; Barritault, L.; Acar, P.; Montalembert, M. de

    2002-01-01

    Aim: While cerebral and bones strokes are well documented in children with sickle cell disease (SCD), impairment of myocardial perfusion is an unknown complication. Conventional techniques such as exercise testing and echocardiography have a low sensitivity and specificity to detect myocardial ischemia in patients with SCD. The aim of this prospective study was to assess myocardial perfusion with 201 Tl SPECT in children with SCD. Materials and Methods: Twenty-two patients, aged 12 ± 4 years, were included. Myocardial perfusion was assessed by 201 Tl SPECT after stress and 3 hours later after reinjection on a single head gammacamera equipped with a LEAP collimator (64x64 matrix size format, 30 projections over 180 0 , 30 seconds per step). Left ventricular ejection fraction (LVEF) was assessed by equilibrium radionuclide angiography at rest on the same day. Results: Myocardial perfusion was impaired in 13/22 patients: 8 had reversible defects and 5 had fixed defects. The left ventricular cavity was dilated in 13/22 patients. The mean LVEF was 63 ± 9%. There was no relationship between myocardial perfusion and left ventricular dilation or function. Conclusion: Myocardial perfusion is frequently impaired in children with SCD. Treatment with hydroxyurea should be considered in SCD patients with perfusion defects

  3. Impairment of myocardial perfusion in children with sickle cell disease

    International Nuclear Information System (INIS)

    Maunoury, C.; Acar, P.; Montalembert, M. de

    2003-01-01

    While brain, bone and spleen strokes are well documented in children with sickle cell disease (SCD), impairment of myocardial perfusion is an unknown complication. Non invasive techniques such as exercise testing and echocardiography have a low sensitivity to detect myocardial ischemia in patients with SCD. We have prospectively assessed myocardial perfusion with Tl-201 SPECT in 23 patients with SCD (10 female, 13 male, mean age 12 ± 5 years). Myocardial SPECT was performed after stress and 3 hours later after reinjection on a single head gamma camera equipped with a LEAP collimator (64 x 64 matrix size format, 30 projections over 180 deg C, 30 seconds per step). Left ventricular ejection fraction (LVEF) was assessed by equilibrium radionuclide angiography at rest on the same day. Myocardial perfusion was impaired in 14/23 patients: 9 reversible defects and 5 fixed defects. The left ventricular cavity was dilated in 14/23 patients. The mean LVEF was 63 ± 9%. There was no relationship between myocardial perfusion and left ventricular dilation or function. The frequent impairment of myocardial perfusion in children with SCD could lead to suggest a treatment with hydroxyurea, an improvement of perfusion can be noted with hydroxyurea. (author)

  4. Mesenchymal Stem Cells : Promising for Myocardial Regeneration?

    NARCIS (Netherlands)

    Przybyt, Ewa; Harmsen, Martin C.

    The pandemic of cardiovascular disease is continuously expanding as the result of changing life styles and diets throughout the Old and New World. Immediate intervention therapy saves the lives of many patients after acute myocardial infarction (MI). However, for many this comes at the price of

  5. Stem Cell Therapy for Myocardial Infarction: Are We Missing Time?

    NARCIS (Netherlands)

    ter Horst, Kasper W.

    2010-01-01

    The success of stem cell therapy in myocardial infarction (MI) is modest, and for stem cell therapy to be clinically effective fine-tuning in regard to timing, dosing, and the route of administration is required. Experimental studies suggest the existence of a temporal window of opportunity bound by

  6. Association of myocardial cell necrosis with experimental cardiac hypertrophy

    Energy Technology Data Exchange (ETDEWEB)

    Revis, N W; Cameron, A J.V.

    1979-01-01

    Cardiac hypertrophy was induced in rabbits by injecting thyroxime or isoprenaline, or by surgically constricting the abdominal aorta. An increase in heart weight was associated with a change in the ratios of bound to free forms of five lysosomal enzymes, a change in serum creatine phosphokinase and lactate dehydrogenase, and a change in the morphology of the myocardial cells. Isoprenaline treatment for 5 days induced a maximal change in heart weight, in the ratio of lysosomal enzymes, and in the serum enzymes. Thyroxine treatment was required for 15 days before maximal changes in heart weight, ratio, and serum enzymes were observed. In contrast, coarctation of the aorta caused a progressive change in heart weight, in the ratio of lysosomal enzymes, and in serum enzymes. These results suggest that necrosis of the myocardial cells does indeed accompany cardiac hypertrophy. It was further observed that autophagosomes, degenerating mitochondria in the myocardial cells during the induction of cardiac hypertrophy, and myofibril lysis were found, all of which confirms the suggestion of myocardial cell necrosis in the experimentally enlarged heart.

  7. The myocardial perfusion imaging of bone marrow mesenchymal stem cell transplantation treated acute myocardial infarction in pig

    International Nuclear Information System (INIS)

    He Miao; Hou Xiancun; Li Yaomei; Zhou Peng; Qi Chunmei; Wu Weihuan; Li Li

    2006-01-01

    Objective: To evaluate the clinical value of bone marrow mesenchymal stem cell transplantation on acute myocardial infarction in pig with myocardial perfusion imaging. Methods: Acute myocardial infarction models were established by 21 minitype Chinese pigs and were divided into two groups. After 10 days, experimental group (n=11) was transplanted with bone marrow mesenchymal stem cell at the infarct areas, and the control group (n=10) with incubation solution. Before and eight weeks after transplantation, both groups were examined by 99 Tc m -methoxyisobutylisonitrile (MIBI) myocardial perfusion imaging and with semi-quantitative analysis. Besides, echocardiogram and immunohistochemistry were also performed. Results: There was significant difference of total myocardial perfusion abnormal segments (46 vs 26), infarct areas [(34±12)% vs (21±10)%] and myocardial ischemia score [(20.0±4.3) vs (12.1±3.6)] between two groups (P<0.05). Also, there were accordant results with echocardiogram and immunohistochemistry findings. Conclusions: Bone marrow mesenchymal stem cell transplantation may improve blood perfusion and viability of the ischemic areas: Myocardial perfusion imaging can accurately observe the survival of bone marrow mesenchymal stem cell transplanted at the infarct areas. (authors)

  8. Effect of nicorandil on the myocardial tissue perfusion and myocardial cell injury in patients with diabetes after PCI

    Directory of Open Access Journals (Sweden)

    Xue-Li Ren1

    2017-04-01

    Full Text Available Objective: To study the effect of nicorandil on the myocardial tissue perfusion and myocardial cell damage in patients with diabetes after percutaneous coronary intervention (PCI. Methods: 68 patients with coronary heart disease and type 2 diabetes mellitus who received PCI in our hospital between May 2011 and September 2015 were collected and then divided into observation group and control group (n=34 according to the single-blind randomized control method. Control group of patients received PCI alone, and the observation group of patients received nicorandil therapy after PCI. After treatment, real-time myocardial ultrasound contrast was used to evaluate the myocardial perfusion of two groups of patients; blood biochemical analyzer was used to detect the contents of peripheral blood myocardial enzyme spectrum indexes; the ELISA method was used to detect the contents of serum oxidative stress indicators; RIA method was used to detect the contents of serum apoptosis molecules. Results: After treatment, the myocardial tissue perfusion parameters plateau peak intensity (A, slope rate of curve (β and myocardial blood flow (A×β levels of observation group were significantly higher than those of control group (P<0.05; peripheral blood myocardial enzyme spectrum indexes creatine kinase (CK, lactate dehydrogenase (LDH, troponin I (cTnI and glutamic oxalacetic transaminase (GOT contents of observation group were significantly lower than those of control group (P<0.05; serum vitamin E (VitE and vitamin C (VitC contents of observation group were significantly higher than those of control group while malondialdehyde (MDA, advanced oxidation protein products (AOPPs, soluble apoptosis-associated factor (sFas and soluble apoptosis-associated factor ligand (sFasL contents were lower than those of control group (P<0.05. Conclusion: Adjuvant nicorandil therapy can improve the myocardial perfusion and reduce the myocardial cell injury in patients with coronary

  9. Cells involved in extracellular matrix remodeling after acute myocardial infarction

    Energy Technology Data Exchange (ETDEWEB)

    Garcia, Larissa Ferraz [Faculdade de Medicina do ABC, Santo André, SP (Brazil); Mataveli, Fábio D’Aguiar [Universidade Federal de São Paulo, São Paulo, SP (Brazil); Mader, Ana Maria Amaral Antônio; Theodoro, Thérèse Rachell [Faculdade de Medicina do ABC, Santo André, SP (Brazil); Justo, Giselle Zenker; Pinhal, Maria Aparecida da Silva [Universidade Federal de São Paulo, São Paulo, SP (Brazil)

    2015-07-01

    Evaluate the effects of VEGF{sub 165} gene transfer in the process of remodeling of the extracellular matrix after an acute myocardial infarct. Wistar rats were submitted to myocardial infarction, after the ligation of the left descending artery, and the left ventricle ejection fraction was used to classify the infarcts into large and small. The animals were divided into groups of ten, according to the size of infarcted area (large or small), and received or not VEGF{sub 165} treatment. Evaluation of different markers was performed using immunohistochemistry and digital quantification. The primary antibodies used in the analysis were anti-fibronectin, anti-vimentin, anti-CD44, anti-E-cadherin, anti-CD24, anti-alpha-1-actin, and anti-PCNA. The results were expressed as mean and standard error, and analyzed by ANOVA, considering statistically significant if p≤0.05. There was a significant increase in the expression of undifferentiated cell markers, such as fibronectin (protein present in the extracellular matrix) and CD44 (glycoprotein present in the endothelial cells). However, there was decreased expression of vimentin and PCNA, indicating a possible decrease in the process of cell proliferation after treatment with VEGF{sub 165}. Markers of differentiated cells, E-cadherin (adhesion protein between myocardial cells), CD24 (protein present in the blood vessels), and alpha-1-actin (specific myocyte marker), showed higher expression in the groups submitted to gene therapy, compared to non-treated group. The value obtained by the relation between alpha-1-actin and vimentin was approximately three times higher in the groups treated with VEGF{sub 165}, suggesting greater tissue differentiation. The results demonstrated the important role of myocytes in the process of tissue remodeling, confirming that VEGF{sub 165} seems to provide a protective effect in the treatment of acute myocardial infarct.

  10. Cells involved in extracellular matrix remodeling after acute myocardial infarction

    International Nuclear Information System (INIS)

    Garcia, Larissa Ferraz; Mataveli, Fábio D’Aguiar; Mader, Ana Maria Amaral Antônio; Theodoro, Thérèse Rachell; Justo, Giselle Zenker; Pinhal, Maria Aparecida da Silva

    2015-01-01

    Evaluate the effects of VEGF_1_6_5 gene transfer in the process of remodeling of the extracellular matrix after an acute myocardial infarct. Wistar rats were submitted to myocardial infarction, after the ligation of the left descending artery, and the left ventricle ejection fraction was used to classify the infarcts into large and small. The animals were divided into groups of ten, according to the size of infarcted area (large or small), and received or not VEGF_1_6_5 treatment. Evaluation of different markers was performed using immunohistochemistry and digital quantification. The primary antibodies used in the analysis were anti-fibronectin, anti-vimentin, anti-CD44, anti-E-cadherin, anti-CD24, anti-alpha-1-actin, and anti-PCNA. The results were expressed as mean and standard error, and analyzed by ANOVA, considering statistically significant if p≤0.05. There was a significant increase in the expression of undifferentiated cell markers, such as fibronectin (protein present in the extracellular matrix) and CD44 (glycoprotein present in the endothelial cells). However, there was decreased expression of vimentin and PCNA, indicating a possible decrease in the process of cell proliferation after treatment with VEGF_1_6_5. Markers of differentiated cells, E-cadherin (adhesion protein between myocardial cells), CD24 (protein present in the blood vessels), and alpha-1-actin (specific myocyte marker), showed higher expression in the groups submitted to gene therapy, compared to non-treated group. The value obtained by the relation between alpha-1-actin and vimentin was approximately three times higher in the groups treated with VEGF_1_6_5, suggesting greater tissue differentiation. The results demonstrated the important role of myocytes in the process of tissue remodeling, confirming that VEGF_1_6_5 seems to provide a protective effect in the treatment of acute myocardial infarct

  11. Stem cell therapy for myocardial infarction

    NARCIS (Netherlands)

    A.D. Moelker (Amber)

    2007-01-01

    textabstractCoronary heart disease and heart failure continue to be significant burdens to healthcare systems in the Western world and are predicted to become so in emerging economies. Despite mixed results in both experimental and clinical studies, stem cell therapy is a promising option for

  12. Stem cell mobilization by granulocyte colony-stimulating factor for myocardial recovery after acute myocardial infarction: a meta-analysis

    DEFF Research Database (Denmark)

    Zohlnhofer, D.; Dibra, A.; Koppara, T.

    2008-01-01

    OBJECTIVES: The objective of this meta-analysis was to evaluate the effect of stem cell mobilization by granulocyte colony-stimulating factor (G-CSF) on myocardial regeneration on the basis of a synthesis of the data generated by randomized, controlled clinical trials of G-CSF after acute...

  13. Stem Cells for Cardiac Regeneration by Cell Therapy and Myocardial Tissue Engineering

    Science.gov (United States)

    Wu, Jun; Zeng, Faquan; Weisel, Richard D.; Li, Ren-Ke

    Congestive heart failure, which often occurs progressively following a myocardial infarction, is characterized by impaired myocardial perfusion, ventricular dilatation, and cardiac dysfunction. Novel treatments are required to reverse these effects - especially in older patients whose endogenous regenerative responses to currently available therapies are limited by age. This review explores the current state of research for two related approaches to cardiac regeneration: cell therapy and tissue engineering. First, to evaluate cell therapy, we review the effectiveness of various cell types for their ability to limit ventricular dilatation and promote functional recovery following implantation into a damaged heart. Next, to assess tissue engineering, we discuss the characteristics of several biomaterials for their potential to physically support the infarcted myocardium and promote implanted cell survival following cardiac injury. Finally, looking ahead, we present recent findings suggesting that hybrid constructs combining a biomaterial with stem and supporting cells may be the most effective approaches to cardiac regeneration.

  14. Stem cell regenerative potential combined with nanotechnology and tissue engineering for myocardial regeneration.

    Science.gov (United States)

    Calin, Manuela; Stan, Daniela; Simion, Viorel

    2013-07-01

    The stem cell-based therapy for post-infarction myocardial regeneration has been introduced more than a decade ago, but the functional improvement obtained is limited due to the poor retention and short survival rate of transplanted cells into the damaged myocardium. More recently, the emerging nanotechnology concepts for advanced diagnostics and therapy provide promising opportunities of using stem cells for myocardial regeneration. In this paper will be provided an overview of the use of nanotechnology approaches in stem cell research for: 1) cell labeling to track the distribution of stem cells after transplantation, 2) nanoparticle-mediated gene delivery to stem cells to promote their homing, engraftment, survival and differentiation in the ischemic myocardium and 3) obtaining of bio-inspired materials to provide suitable myocardial scaffolds for delivery of stem cells or stem cell-derived factors.

  15. Nuclear localization signal targeting to macronucleus and micronucleus in binucleated ciliate Tetrahymena thermophila.

    Science.gov (United States)

    Iwamoto, Masaaki; Mori, Chie; Osakada, Hiroko; Koujin, Takako; Hiraoka, Yasushi; Haraguchi, Tokuko

    2018-06-08

    Ciliated protozoa possess two morphologically and functionally distinct nuclei: a macronucleus (MAC) and a micronucleus (MIC). The MAC is transcriptionally active and functions in all cellular events. The MIC is transcriptionally inactive during cell growth, but functions in meiotic events to produce progeny nuclei. Thus, these two nuclei must be distinguished by the nuclear proteins required for their distinct functions during cellular events such as cell proliferation and meiosis. To understand the mechanism of the nuclear transport specific to either MAC or MIC, we identified specific nuclear localization signals (NLSs) in two MAC- and MIC-specific nuclear proteins, macronuclear histone H1 and micronuclear linker histone-like protein (Mlh1), respectively. By expressing GFP-fused fragments of these proteins in Tetrahymena thermophila cells, two distinct regions in macronuclear histone H1 protein were assigned as independent MAC-specific NLSs and two distinct regions in Mlh1 protein were assigned as independent MIC-specific NLSs. These NLSs contain several essential lysine residues responsible for the MAC- and MIC-specific nuclear transport, but neither contains any consensus sequence with known monopartite or bipartite NLSs in other model organisms. Our findings contribute to understanding how specific nuclear targeting is achieved to perform distinct nuclear functions in binucleated ciliates. © 2018 The Authors. Genes to Cells published by Molecular Biology Society of Japan and John Wiley & Sons Australia, Ltd.

  16. Nuclear and plastid DNAs from the binucleate dinoflagellates Glenodinium (Peridinium) foliaceum and Peridinium balticum.

    Science.gov (United States)

    Kite, G C; Rothschild, L J; Dodge, J D

    1988-01-01

    The binucleate dinoflagellates Glenodinium (Peridinium) foliaceum Stein and Peridinium balticum (Levander) Lemmermann were found to contain two major buoyant density classes of DNA. The heavier peak (1.730 g/cm3) was derived from the "dinokaryotic" nucleus and the lighter peak (1.706 g/cm3) from the "endosymbiont" nucleus and this allowed for the fractionation of G. foliaceum DNA in CsCl/EtBr density gradients. An initial CsCl/Hoechst Dye gradient removed a minor A-T rich satellite species which was identified as plastid DNA with a size of about 100-106 kb. Analysis of the nuclear DNA by agarose gel electrophoresis and renaturation studies showed that the endosymbiont nucleus lacked amplified gene-sized DNA molecules, however, this nucleus did have a comparatively high level of DNA. The total amount of DNA per cell and the relative contributions of the two nuclei appeared to vary between two strains of G. foliaceum (75 pg/cell in CCAP strain and 58 pg in UTEX strain). The only strain of P. balticum examined contained 73 pg cell. These results are discussed in relation to the status and possible functioning of the endosymbiont nucleus and the idea that these dinoflagellates provide model systems with which to study the evolution of plastids.

  17. Comparison of human adipose-derived stem cells and bone marrow-derived stem cells in a myocardial infarction model

    DEFF Research Database (Denmark)

    Rasmussen, Jeppe; Frøbert, Ole; Holst-Hansen, Claus

    2014-01-01

    Background: Treatment of myocardial infarction with bone marrow-derived mesenchymal stem cells and recently also adipose-derived stem cells has shown promising results. In contrast to clinical trials and their use of autologous bone marrow-derived cells from the ischemic patient, the animal...... myocardial infarction models are often using young donors and young, often immune-compromised, recipient animals. Our objective was to compare bone marrow-derived mesenchymal stem cells with adipose-derived stem cells from an elderly ischemic patient in the treatment of myocardial infarction, using a fully...... grown non-immunecompromised rat model. Methods: Mesenchymal stem cells were isolated from adipose tissue and bone marrow and compared with respect to surface markers and proliferative capability. To compare the regenerative potential of the two stem cell populations, male Sprague-Dawley rats were...

  18. Titanium dioxide nanoparticle-induced cytotoxicity and the underlying mechanism in mouse myocardial cells

    Science.gov (United States)

    Zhou, Yingjun; Hong, Fashui; Wang, Ling

    2017-11-01

    Exposure to fine particulate matter (PM) is known to cause cardiovascular disease. While extensive research has focused on the risk of atmospheric PM to public health, particularly heart disease, limited studies to date have attempted to clarify the molecular mechanisms underlying myocardial cell damage caused by exposure to titanium dioxide nanoparticles (TiO2 NPs). Data from the current investigation showed that TiO2 NPs are deposited in myocardial mitochondria via the blood circulation accompanied by obvious ultrastructural changes and impairment of mitochondrial structure and function in mouse myocardial cells, including reduction in mitochondrial membrane potential and ATP production, aggravation of oxidative stress along with increased levels of reactive oxygen species, malondialdehyde and protein carbonyl, and decreased glutathione content and enzymatic activities, including superoxide dismutase and glutathione peroxidase. Furthermore, TiO2 NPs induced a significant decrease in the activities of complex I, complex II, complex III, complex IV, succinate dehydrogenase, NADH oxidase, Ca2+-ATPase, Na+/K+-ATPase, and Ca2+/Mg2+-ATPase, and upregulation of cytokine expression (including cytochrome c, caspase-3, and p-JNK) in mitochondria-mediated apoptosis while downregulating Bcl-2 expression in mouse myocardial cells. Our results collectively indicate that chronic exposure to TiO2 NPs induces damage in mitochondrial structure and function as well as mitochondria-mediated apoptosis in mouse myocardial cells, which may be closely associated with heart disease in animals and humans.

  19. Bioengineering of injectable encapsulated aggregates of pluripotent stem cells for therapy of myocardial infarction

    Science.gov (United States)

    Zhao, Shuting; Xu, Zhaobin; Wang, Hai; Reese, Benjamin E.; Gushchina, Liubov V.; Jiang, Meng; Agarwal, Pranay; Xu, Jiangsheng; Zhang, Mingjun; Shen, Rulong; Liu, Zhenguo; Weisleder, Noah; He, Xiaoming

    2016-10-01

    It is difficult to achieve minimally invasive injectable cell delivery while maintaining high cell retention and animal survival for in vivo stem cell therapy of myocardial infarction. Here we show that pluripotent stem cell aggregates pre-differentiated into the early cardiac lineage and encapsulated in a biocompatible and biodegradable micromatrix, are suitable for injectable delivery. This method significantly improves the survival of the injected cells by more than six-fold compared with the conventional practice of injecting single cells, and effectively prevents teratoma formation. Moreover, this method significantly enhances cardiac function and survival of animals after myocardial infarction, as a result of a localized immunosuppression effect of the micromatrix and the in situ cardiac regeneration by the injected cells.

  20. Myocardial regeneration by transplantation of modified endothelial progenitor cells expressing SDF-1 in a rat model

    DEFF Research Database (Denmark)

    Schuh, A.; Kroh, A.; Konschalla, S.

    2012-01-01

    Cell based therapy has been shown to attenuate myocardial dysfunction after myocardial infarction (MI) in different acute and chronic animal models. It has been further shown that stromal-cell derived factor-1a (SDF-1a) facilitates proliferation and migration of endogenous progenitor cells...... into injured tissue. The aim of the present study was to investigate the role of exogenously applied and endogenously mobilized cells in a regenerative strategy for MI therapy. Lentivirally SDF-1a-infected endothelial progenitor cells (EPCs) were injected after 90 min. of ligation and reperfusion of the left...... compared to medium control. Intracoronary application of cells did not lead to significant differences compared to medium injected control hearts. Histology showed a significantly elevated rate of apoptotic cells and augmented proliferation after transplantation of EPCs and EPCs + SDF-1 alpha in infarcted...

  1. rDNA-based characterization of a new binucleate Rhizoctonia spp. causing root rot on kale in Brazil

    NARCIS (Netherlands)

    Kuramae, E.E.; Buzeto, A.L.; Nakatani, A.K.; Souza, N.L.

    2007-01-01

    In this paper we present the first report of the occurrence of a binucleate Rhizoctonia spp. causing hypocotyl and root rot in kale in Brazil. Rhizoctonia spp. were isolated from kale (Brassica oleracea var. acephala) with symptoms of hypocotyl and root rot. The isolates, characterized as binucleate

  2. Experimental myocardial stem cell therapy for ST-elevation myocardial infarction

    DEFF Research Database (Denmark)

    Kastrup, Jens; Mygind, Naja D.; Qayyum, Abbas A.

    2016-01-01

    ), chronic IHD and heart failure. The patients suffer from chest pain (angina), dyspnea and a reduced quality of life. Common for all these conditions is loss of functional cardiomyocytes and endothelial cells. Stem cell therapy to regenerate injured myocardium is a new treatment option which has gained much...... interest in the last 10-15 years especially after STEMI. Many preclinical and clinical studies have shown encouraging results but also very diverse clinical outcomes after stem cell treatment. This diversity in results may be explained by different factors, such as cell isolation technique, infarct...... location, timing and route of delivery, cell dosage, cell type etc. The present review will try to elaborate and clarify the present status for stem cell therapy in STEMI....

  3. Experimental myocardial stem cell therapy for ST-elevation myocardial infarction

    DEFF Research Database (Denmark)

    Kastrup, Jens; Mygind, Naja D; Qayyum, Abbas A

    2016-01-01

    ), chronic IHD and heart failure. The patients suffer from chest pain (angina), dyspnea and a reduced quality of life. Common for all these conditions is loss of functional cardiomyocytes and endothelial cells. Stem cell therapy to regenerate injured myocardium is a new treatment option which has gained much...... location, timing and route of delivery, cell dosage, cell type etc. The present review will try to elaborate and clarify the present status for stem cell therapy in STEMI....... interest in the last 10-15 years especially after STEMI. Many preclinical and clinical studies have shown encouraging results but also very diverse clinical outcomes after stem cell treatment. This diversity in results may be explained by different factors, such as cell isolation technique, infarct...

  4. Hemorrhagic shock impairs myocardial cell volume regulation and membrane integrity in dogs

    International Nuclear Information System (INIS)

    Horton, J.W.

    1987-01-01

    An in vitro myocardial slice technique was used to quantitate alterations in cell volume regulation and membrane integrity after 2 h or hemorrhagic shock. After in vitro incubation in Krebs-Ringer-phosphate medium containing trace [ 14 C]inulin, values (ml H 2 O/g dry wt) for control nonshocked myocardial slices were 4.03 /plus minus/ 0.11 (SE) for total water, 2.16 /plus minus/ 0.07 for inulin impermeable space, and 1.76 /plus minus/ 0.15 for inulin diffusible space. Shocked myocardial slices showed impaired response to cold incubation. After 2 h of in vivo shock, total tissue water, inulin diffusible space, and inulin impermeable space increased significantly for subendocardium, whereas changes in subepicardium parameters were minimal. Shock-induced cellular swelling was accompanied by an increased total tissue sodium, but no change in tissue potassium. Calcium entry blockade in vivo significantly reduced subendocardial total tissue water as compared with shock-untreated dogs. In addition, calcium entry blockade reduced shock-induced increases in inulin diffusible space. In vitro myocardial slice studies confirm alterations in subendocardial membrane integrity after 2 h of in vivo hemorrhagic shock. Shock-induced abnormalities in myocardial cell volume regulation are reduced by calcium entry blockade in vivo

  5. Differential Mechanisms of Myocardial Conduction Slowing by Adipose Tissue-Derived Stromal Cells Derived From Different Species

    NARCIS (Netherlands)

    ten Sande, Judith N.; Smit, Nicoline W.; Parvizi, Mojtaba; van Amersfoorth, Shirley C. M.; Plantinga, Josee A.; van Dessel, Pascal F. H. M.; de Bakker, Jacques M. T.; Harmsen, Marco C.; Coronel, Ruben

    : Stem cell therapy is a promising therapeutic option to treat patients after myocardial infarction. However, the intramyocardial administration of large amounts of stem cells might generate a proarrhythmic substrate. Proarrhythmic effects can be explained by electrotonic and/or paracrine

  6. Cell therapy in myocardial infarction: emphasis on the role of MRI

    International Nuclear Information System (INIS)

    Ye, Yuxiang; Bogaert, Jan

    2008-01-01

    Despite tremendous progress in myocardial infarct (MI) treatment, mortality rates remain substantial. Permanent loss of cardiomyocytes after ischemic injury, results in irreversible loss of myocardial contractility, reduction in ventricular performance, and may initiate the development of dilated heart failure. The discovery that pluripotent progenitor cells bear the capacity to differentiate to mature cardiac cells raised the hope of cell-based regenerative medicine. Engraftment of stem cells in the damaged myocardium, repair and functional improvement appeared suddenly a nearby reality. Promising results in animal models, and preliminary studies reporting the feasibility and safety of adult stem cell therapy in MI patients led to the first double-blinded randomized, placebo-controlled trials. The initial great enthusiasm for this paradigm shift in MI treatment has been tempered by the mainly negative or modestly positive study findings. Before new, larger clinical trials can be initiated, a number of critical questions and issues need to be considered starting with a scrutinized analysis of currently available data to extending our knowledge of the mechanism of scarless myocardial regeneration. Cardiac cell therapy necessitates a multidisciplinary approach, whereby imaging, in particular MRI, and the input of the imaging specialist is crucial to the success of cardiac cell regenerative medicine. MRI is an appealing technique for cell trafficking depicting engraftment, differentiation and survival. Endomyocardial cell administration can be achieved safely with MR fluoroscopy and MRI is without any doubt the most accurate and reproducible technique to measure study end-points. (orig.)

  7. Implantation of stem cells in the treatment of acute myocardial infarction

    International Nuclear Information System (INIS)

    Obregon Santos, Angel; Wilford de Leon, Mario; Aroche Aportela, Ronald; Isla Garcia, Rosa; Conde Cerdeira, Hector; Vila Garcia, Elena

    2007-01-01

    A lot of investigations demonstrate the possibility of regeneration of the cardiomiocity from stem cells. A longitudinal, prospective, observational study was conducted in patients with acute myocardial infarction in CIMEQ'S hospital since January 2004 up to January 2007 with the purpose to evaluate the security and efficacy of the intracoronary transfer of autologous bone-marrow-cells during acute myocardial infarction. Patients within seven days of the onset of symptoms of a first ST-segment elevation myocardial infarction, and between 18 and 70 years old. The patients are evaluated previous to apply the procedure and 6 months for clinic, electrocardiography, echocardiography, ergometry and coronariography. The drug eluting stent is placed on the culprit lesion and the bone marrow is stimulated with granulocyte colony-stimulating factor (G-CSF). The mononuclear's cells which are obtained have been implanted using the intracoronary way. The implantation by means of the intracoronary way of stem cells, after of stimulation of bone marrow during acute myocardial infarction demonstrated to be an effective and safety procedure

  8. Exosomes Derived from Human Umbilical Cord Mesenchymal Stem Cells Relieve Acute Myocardial Ischemic Injury

    Directory of Open Access Journals (Sweden)

    Yuanyuan Zhao

    2015-01-01

    Full Text Available This study is aimed at investigating whether human umbilical cord mesenchymal stem cell- (hucMSC- derived exosomes (hucMSC-exosomes have a protective effect on acute myocardial infarction (AMI. Exosomes were characterized under transmission electron microscopy and the particles of exosomes were further examined through nanoparticle tracking analysis. Exosomes (400 μg protein were intravenously administrated immediately following ligation of the left anterior descending (LAD coronary artery in rats. Cardiac function was evaluated by echocardiography and apoptotic cells were counted using TUNEL staining. The cardiac fibrosis was assessed using Masson’s trichrome staining. The Ki67 positive cells in ischemic myocardium were determined using immunohistochemistry. The effect of hucMSC-exosomes on blood vessel formation was evaluated through tube formation and migration of human umbilical vein endothelial cells (EA.hy926 cells. The results indicated that ligation of the LAD coronary artery reduced cardiac function and induced cardiomyocyte apoptosis. Administration of hucMSC-exosomes significantly improved cardiac systolic function and reduced cardiac fibrosis. Moreover, hucMSC-exosomes protected myocardial cells from apoptosis and promoted the tube formation and migration of EA.hy926 cells. It is concluded that hucMSC-exosomes improved cardiac systolic function by protecting myocardial cells from apoptosis and promoting angiogenesis. These effects of hucMSC-exosomes might be associated with regulating the expression of Bcl-2 family.

  9. The apoptotic effect and the plausible mechanism of microwave radiation on rat myocardial cells.

    Science.gov (United States)

    Zhu, Wenhe; Cui, Yan; Feng, Xianmin; Li, Yan; Zhang, Wei; Xu, Junjie; Wang, Huiyan; Lv, Shijie

    2016-08-01

    Microwaves may exert adverse biological effects on the cardiovascular system at the integrated system and cellular levels. However, the mechanism underlying such effects remains poorly understood. Here, we report a previously uncharacterized mechanism through which microwaves damage myocardial cells. Rats were treated with 2450 MHz microwave radiation at 50, 100, 150, or 200 mW/cm(2) for 6 min. Microwave treatment significantly enhanced the levels of various enzymes in serum. In addition, it increased the malondialdehyde content while decreasing the levels of antioxidative stress enzymes, activities of enzyme complexes I-IV, and ATP in myocardial tissues. Notably, irradiated myocardial cells exhibited structural damage and underwent apoptosis. Furthermore, Western blot analysis revealed significant changes in expression levels of proteins involved in oxidative stress regulation and apoptotic signaling pathways, indicating that microwave irradiation could induce myocardial cell apoptosis by interfering with oxidative stress and cardiac energy metabolism. Our findings provide useful insights into the mechanism of microwave-induced damage to the cardiovascular system.

  10. Uptake and release of 99mTc-CPI in cultured myocardial cells

    International Nuclear Information System (INIS)

    Li Shengting; Xiao Yanling; Yu Qifu; Zhang Hongyuan; Tang Jingrong

    1991-01-01

    The uptake and release of 99m Tc-CPI were studied in cultured monolayer neonatal rat myocardial cells incubated under normal condition (37 deg C, pH 7.4). The plateau level of uptake (4291.6 cpm/mg cell protein) was reached at 41.4 min when incubated with 37 kBq 99m Tc-CPI. The 99m Tc-CPI release was composed of at least two components. The fast component had a half-time (t 1/2 ) of 3.3 min and the slow one 198.0 min. It was suggested by the authors that the uptake of 99m Tc-CPI by cultured myocardial cells might be related to passive diffusion

  11. Effect of low-level laser-treated mesenchymal stem cells on myocardial infarction.

    Science.gov (United States)

    El Gammal, Zaynab H; Zaher, Amr M; El-Badri, Nagwa

    2017-09-01

    Cardiovascular disease is the leading cause of death worldwide. Although cardiac transplantation is considered the most effective therapy for end-stage cardiac diseases, it is limited by the availability of matching donors and the complications of the immune suppressive regimen used to prevent graft rejection. Application of stem cell therapy in experimental animal models was shown to reverse cardiac remodeling, attenuate cardiac fibrosis, improve heart functions, and stimulate angiogenesis. The efficacy of stem cell therapy can be amplified by low-level laser radiation. It is well established that the bio-stimulatory effect of low-level laser is influenced by the following parameters: wavelength, power density, duration, energy density, delivery time, and the type of irradiated target. In this review, we evaluate the available experimental data on treatment of myocardial infarction using low-level laser. Eligible papers were characterized as in vivo experimental studies that evaluated the use of low-level laser therapy on stem cells in order to attenuate myocardial infarction. The following descriptors were used separately and in combination: laser therapy, low-level laser, low-power laser, stem cell, and myocardial infarction. The assessed low-level laser parameters were wavelength (635-804 nm), power density (6-50 mW/cm 2 ), duration (20-150 s), energy density (0.96-1 J/cm 2 ), delivery time (20 min-3 weeks after myocardial infarction), and the type of irradiated target (bone marrow or in vitro-cultured bone marrow mesenchymal stem cells). The analysis focused on the cardioprotective effect of this form of therapy, the attenuation of scar tissue, and the enhancement of angiogenesis as primary targets. Other effects such as cell survival, cell differentiation, and homing are also included. Among the evaluated protocols using different parameters, the best outcome for treating myocardial infarction was achieved by treating the bone marrow by one dose of low

  12. Plant-based foods containing cell wall polysaccharides rich in specific active monosaccharides protect against myocardial injury in rat myocardial infarction models.

    Science.gov (United States)

    Lim, Sun Ha; Kim, Yaesil; Yun, Ki Na; Kim, Jin Young; Jang, Jung-Hee; Han, Mee-Jung; Lee, Jongwon

    2016-12-08

    Many cohort studies have shown that consumption of diets containing a higher composition of foods derived from plants reduces mortality from coronary heart disease (CHD). Here, we examined the active components of a plant-based diet and the underlying mechanisms that reduce the risk of CHD using three rat models and a quantitative proteomics approach. In a short-term myocardial infarction (MI) model, intake of wheat extract (WE), the representative cardioprotectant identified by screening approximately 4,000 samples, reduced myocardial injury by inhibiting apoptosis, enhancing ATP production, and maintaining protein homeostasis. In long-term post-MI models, this myocardial protection resulted in ameliorating adverse left-ventricular remodelling, which is a predictor of heart failure. Among the wheat components, arabinose and xylose were identified as active components responsible for the observed efficacy of WE, which was administered via ingestion and tail-vein injections. Finally, the food components of plant-based diets that contained cell wall polysaccharides rich in arabinose, xylose, and possibly fucose were found to confer protection against myocardial injury. These results show for the first time that specific monosaccharides found in the cell wall polysaccharides in plant-based diets can act as active ingredients that reduce CHD by inhibiting postocclusion steps, including MI and heart failure.

  13. Unexpected severe calcification after transplantation of bone marrow cells in acute myocardial infarction.

    Science.gov (United States)

    Yoon, Young-Sup; Park, Jong-Seon; Tkebuchava, Tengiz; Luedeman, Corinne; Losordo, Douglas W

    2004-06-29

    There has been a rapid increase in the number of clinical trials using unselected bone marrow (BM) cells or the mononuclear fraction of BM cells for treating ischemic heart diseases. Thus far, no significant deleterious effects or complications have been reported in any studies using BM-derived cells for treatment of various cardiac diseases. Seven-week-old female Fisher-344 rats underwent surgery to induce acute myocardial infarction and were randomized into 3 groups of 16 rats, each receiving intramyocardial injection of either 7x10(5) DiI-labeled total BM cells (TBMCs), the same number of DiI-labeled, clonally expanded BM multipotent stem cells, or the same volume of phosphate-buffered saline in the peri-infarct area. Echocardiography 2 weeks after cell transplantation indicated intramyocardial calcification in 4 of 14 surviving rats (28.5%) in the TBMC group. Histological examination with hematoxylin and eosin staining and von Kossa staining confirmed the presence of extensive intramyocardial calcification. Alkaline phosphatase staining revealed strong positivity surrounding the calcified area suggestive of ongoing osteogenic activity. Fluorescent microscopic examination revealed that acellular calcific areas were surrounded by DiI-labeled TBMCs, suggesting the direct involvement of transplanted TBMCs in myocardial calcification. In contrast, in hearts receiving equal volumes of saline or BM multipotent stem cells delivered in the same manner, there was no evidence of calcification. These results demonstrate that direct transplantation of unselected BM cells into the acutely infarcted myocardium may induce significant intramyocardial calcification.

  14. Kinetics of 13N-ammonia uptake in myocardial single cells indicating potential limitations in its applicability as a marker of myocardial blood flow

    International Nuclear Information System (INIS)

    Rauch, B.; Helus, F.; Grunze, M.; Braunwell, E.; Mall, G.; Hasselbach, W.; Kuebler, W.

    1985-01-01

    To study kinetics and principles of cellular uptake of 13 N-ammonia, a marker of coronary perfusion in myocardial scintigraphy, heart muscle cells of adult rats were isolated by perfusion with collagenase and hyaluronidase. Net uptake of 13 N, measured by flow dialysis, reached equilibrium within 20 sec in the presence of sodium bicarbonate and carbon dioxide (pH 7.4, 37 degrees C). Total extraction, 80 sec after the reaction start, was 786 +/- 159 mumol/ml cell volume. Cells destroyed by calcium overload were unable to extract 13 N-ammonia. Omission of bicarbonate and carbon dioxide reduced total extraction to 36% of control. 13 N-Ammonia uptake could also be reduced by 50 muM 4,4' diisothiocyanostilbene 2,2' disulfonic acid, by 100 micrograms/ml 1-methionine sulfoximine, and by preincubation with 5 muM free oleic acid. These results indicate that in addition to metabolic trapping by glutamine synthetase, the extraction of 13 N-ammonia by myocardial cells is influenced by cell membrane integrity, intracellular-extracellular pH gradient, and possibly an anion exchange system for bicarbonate. For this reason, the uptake of 13 N-ammonia may not always provide a valid measurement of myocardial perfusion

  15. Histone occurrence in chromatin from Peridinium balticum, a binucleate dinoflagellate.

    Science.gov (United States)

    Rizzo, P J; Cox, E R

    1977-12-23

    Peridinium balticum is one of two dinoflagellates known to have dissimilar nuclei together in the same cell. One nucleus (dinokaryotic) has permanently condensed chromosomes, while the other (eukaryotic) does not have morphologically distinct chromosomes. Acid extracts of chromatin prepared from a mixture of dinokaryotic and eukaryotic nuclei and purified eukaryotic nuclei give four bands that co-migrate with four of the five histones from calf thymus when analyzed in urea-containing polyacrylamide gels.

  16. The effects of compound danshen dripping pills and human umbilical cord blood mononuclear cell transplant after acute myocardial infarction.

    Science.gov (United States)

    Jun, Yi; Chunju, Yuan; Qi, Ai; Liuxia, Deng; Guolong, Yu

    2014-04-01

    The low frequency of survival of stem cells implanted in the myocardium after acute myocardial infarction may be caused by inflammation and oxidative stress in the myocardial microenvironment. We evaluated the effects of a traditional Chinese medicine, Compound Danshen Dripping Pills, on the cardiac microenvironment and cardiac function when used alone or in combination with human umbilical cord blood mononuclear cell transplant after acute myocardial infarction. After surgically induced acute myocardial infarction, rabbits were treated with Compound Danshen Dripping Pills alone or in combination with human umbilical cord blood mononuclear cell transplant. Evaluation included histology, measurement of left ventricular ejection fraction and fractional shortening, leukocyte count, count of green fluorescent protein positive cells, superoxide dismutase activity, and malondialdehyde content. Combination treatment with Compound Danshen Dripping Pills and human umbilical cord blood mononuclear cell transplant significantly increased the survival of implanted cells, inhibited cardiac cell apoptosis, decreased oxidative stress, decreased the inflammatory response, and improved cardiac function. Rabbits treated with either Compound Danshen Dripping Pills or human umbilical cord blood mononuclear cells alone had improvement in these effects compared with untreated control rabbits. Combination therapy with Compound Danshen Dripping Pills and human umbilical cord blood mononuclear cells may improve cardiac function and morphology after acute myocardial infarction.

  17. Calcium exchange, structure, and function in cultured adult myocardial cells

    International Nuclear Information System (INIS)

    Langer, G.A.; Frank, J.S.; Rich, T.L.; Orner, F.B.

    1987-01-01

    Cells digested from adult rat heart and cultured for 14 days demonstrate all the structural elements, in mature form, associated with the process of excitation-contraction (EC) coupling. The transverse tubular (TT) system is well developed with an extensive junctional sarcoplasmic reticulum (JSR). In nonphosphate-containing buffer contraction of the cells is lost as rapidly as zero extracellular Ca concentration ([Ca] 0 ) solution is applied and a negative contraction staircase is produced on increase of stimulation frequency. Structurally and functionally the cells have the characteristics of adult cells in situ. 45 Ca exchange and total 45 Ca measurement in N-2-hydroxyethylpiperazine N'-2-ethanesulfonic acid (HEPES)-buffered perfusate define three components of cellular Ca: 1) a rapidly exchangeable component accounting for 36% of total Ca, 2) a slowly exchangeable component (t/sub 1/2/ 53 min) accounting for 7% total Ca, and 3) the remaining 57% cellular Ca is inexchangeable (demonstrates no significant exchange within 60 min). The slowly exchangeable component can be increased 10-fold within 60 min by addition of phosphate to the perfusate. The Ca distribution and exchange characteristics are little different from those of 3-day cultures of neonatal rat heart previously studied. The results suggest that the cells are representative of adult cells in situ and that both sarcolemmal-bound and sarcoplasmic reticular Ca contribute to the component of Ca that is rapidly exchangeable

  18. Stem cell mobilization induced by subcutaneous granulocyte-colony stimulating factor to improve cardiac regeneration after acute ST-elevation myocardial infarction: result of the double-blind, randomized, placebo-controlled stem cells in myocardial infarction (STEMMI) trial

    DEFF Research Database (Denmark)

    Ripa, RS; Jorgensen, E; Wang, Y

    2006-01-01

    BACKGROUND: Phase 1 clinical trials of granulocyte-colony stimulating factor (G-CSF) treatment after myocardial infarction have indicated that G-CSF treatment is safe and may improve left ventricular function. This randomized, double-blind, placebo-controlled trial aimed to assess the efficacy of......: Bone marrow stem cell mobilization with subcutaneous G-CSF is safe but did not lead to further improvement in ventricular function after acute myocardial infarction compared with the recovery observed in the placebo group...

  19. Magnetic Nanoparticles for Targeting and Imaging of Stem Cells in Myocardial Infarction

    Directory of Open Access Journals (Sweden)

    Michelle R. Santoso

    2016-01-01

    Full Text Available Stem cell therapy has broad applications in regenerative medicine and increasingly within cardiovascular disease. Stem cells have emerged as a leading therapeutic option for many diseases and have broad applications in regenerative medicine. Injuries to the heart are often permanent due to the limited proliferation and self-healing capability of cardiomyocytes; as such, stem cell therapy has become increasingly important in the treatment of cardiovascular diseases. Despite extensive efforts to optimize cardiac stem cell therapy, challenges remain in the delivery and monitoring of cells injected into the myocardium. Other fields have successively used nanoscience and nanotechnology for a multitude of biomedical applications, including drug delivery, targeted imaging, hyperthermia, and tissue repair. In particular, superparamagnetic iron oxide nanoparticles (SPIONs have been widely employed for molecular and cellular imaging. In this mini-review, we focus on the application of superparamagnetic iron oxide nanoparticles in targeting and monitoring of stem cells for the treatment of myocardial infarctions.

  20. The Citrus Flavanone Naringenin Protects Myocardial Cells against Age-Associated Damage

    Directory of Open Access Journals (Sweden)

    Eleonora Da Pozzo

    2017-01-01

    Full Text Available In recent years, the health-promoting effects of the citrus flavanone naringenin have been examined. The results have provided evidence for the modulation of some key mechanisms involved in cellular damage by this compound. In particular, naringenin has been revealed to have protective properties such as an antioxidant effect in cardiometabolic disorders. Very recently, beneficial effects of naringenin have been demonstrated in old rats. Because aging has been demonstrated to be directly related to the occurrence of cardiac disorders, in the present study, the ability of naringenin to prevent cardiac cell senescence was investigated. For this purpose, a cellular model of senescent myocardial cells was set up and evaluated using colorimetric, fluorimetric, and immunometric techniques. Relevant cellular senescence markers, such as X-gal staining, cell cycle regulator levels, and the percentage of cell cycle-arrested cells, were found to be reduced in the presence of naringenin. In addition, cardiac markers of aging-induced damage, including radical oxidative species levels, mitochondrial metabolic activity, mitochondrial calcium buffer capacity, and estrogenic signaling functions, were also modulated by the compound. These results suggested that naringenin has antiaging effects on myocardial cells.

  1. Adenylate cyclase regulation in intact cultured myocardial cells

    International Nuclear Information System (INIS)

    Marsh, J.D.; Roberts, D.J.

    1987-01-01

    To examine the coupling of cardiac cell-surface β-adrenergic receptors to adenylate cyclase activation and contractile response, the authors studied this receptor-effector response system in monolayers of spontaneously contracting chick embryo ventricular cells under physiological conditions. The hydrophilic ligand 3 H-CGP12177 identified uniformly high-agonist affinity β-adrenergic receptors. Isoproterenol-stimulated cyclic AMP (cAMP) accumulation with 50% effective concentration at (EC 50 ) = 12.1 nM and augmented contractile response with EC 50 = 6 nM under identical conditions. One micromolar isoproterenol induced receptor loss from the cell surface with t/sub 1/2/ = 13.2 min; under identical conditions cAMP content declined with t/sub 1/2/ = 13.5 min and contractile response with t/sub 1/2/ = 20.7 min. After agonist removal cAMP response recovered with t/sub 1/2/ = 15.7 min and receptors with t/sub 1/2/ = 24.7 min. Sixty minutes after agonist removal there was recovery of 52% of maximal cAMP responsiveness and 82% of the initial number of receptors; receptor occupancy was associated with 78% of initial contractile response. Agonist affinity for cell-surface receptors was changed only modestly by agonist exposure. They conclude that for this system there is relatively close coupling between high-affinity receptors, adenylate cyclase stimulation, and contractile response

  2. Assessment of Myocardial Contractile Function Using Global and Segmental Circumferential Strain following Intracoronary Stem Cell Infusion after Myocardial Infarction: MRI Feature Tracking Feasibility Study

    International Nuclear Information System (INIS)

    Bhatti, Sabha; Al-Khalidi, Hussein; Hor, Kan; Hakeem, Abdul; Taylor, Michael; Quyyumi, Arshed A.; Oshinski, John; Pecora, Andrew L.; Kereiakes, Dean; Chung, Eugene; Pedrizzetti, Gianni; Miszalski-Jamka, Tomasz; Mazur, Wojciech

    2012-01-01

    Background. Magnetic resonance imaging (MRI) strain analysis is a sensitive method to assess myocardial function. Our objective was to define the feasibility of MRI circumferential strain (ε cc ) analysis in assessing subtle changes in myocardial function following stem cell therapy. Methods and Results. Patients in the Amorcyte Phase I trial were randomly assigned to treatment with either autologous bone-marrow-derived stem cells infused into the infarct-related artery 5 to 11 days following primary PCI or control. MRI studies were obtained at baseline, 3, and 6 months. ε cc was measured in the short axis views at the base, mid and apical slices of the left ventricle (LV) for each patient (13 treatments and 10 controls). Mid-anterior LV ε cc improved between baseline −18.5 ± 8.6 and 3 months −22.6 ± 7.0, P = 0.03. There were no significant changes in ε cc at 3 months and 6 months compared to baseline for other segments. There was excellent intraobserver and interobserver agreement for basal and mid circumferential strain. Conclusion. MRI segmental strain analysis is feasible in assessment of regional myocardial function following cell therapy with excellent intra- and inter-observer variability's. Using this method, a modest interval change in segmental ε cc was detected in treatment group

  3. Enhancement of myocardial regeneration through genetic engineering of cardiac progenitor cells expressing Pim-1 kinase.

    Science.gov (United States)

    Fischer, Kimberlee M; Cottage, Christopher T; Wu, Weitao; Din, Shabana; Gude, Natalie A; Avitabile, Daniele; Quijada, Pearl; Collins, Brett L; Fransioli, Jenna; Sussman, Mark A

    2009-11-24

    Despite numerous studies demonstrating the efficacy of cellular adoptive transfer for therapeutic myocardial regeneration, problems remain for donated cells with regard to survival, persistence, engraftment, and long-term benefits. This study redresses these concerns by enhancing the regenerative potential of adoptively transferred cardiac progenitor cells (CPCs) via genetic engineering to overexpress Pim-1, a cardioprotective kinase that enhances cell survival and proliferation. Intramyocardial injections of CPCs overexpressing Pim-1 were given to infarcted female mice. Animals were monitored over 4, 12, and 32 weeks to assess cardiac function and engraftment of Pim-1 CPCs with echocardiography, in vivo hemodynamics, and confocal imagery. CPCs overexpressing Pim-1 showed increased proliferation and expression of markers consistent with cardiogenic lineage commitment after dexamethasone exposure in vitro. Animals that received CPCs overexpressing Pim-1 also produced greater levels of cellular engraftment, persistence, and functional improvement relative to control CPCs up to 32 weeks after delivery. Salutary effects include reduction of infarct size, greater number of c-kit(+) cells, and increased vasculature in the damaged region. Myocardial repair is significantly enhanced by genetic engineering of CPCs with Pim-1 kinase. Ex vivo gene delivery to enhance cellular survival, proliferation, and regeneration may overcome current limitations of stem cell-based therapeutic approaches.

  4. Transplantation of mesenchymal stem cells overexpressing IL10 attenuates cardiac impairments in rats with myocardial infarction.

    Science.gov (United States)

    Meng, Xin; Li, Jianping; Yu, Ming; Yang, Jian; Zheng, Minjuan; Zhang, Jinzhou; Sun, Chao; Liang, Hongliang; Liu, Liwen

    2018-01-01

    Mesenchymal stem cell (MSC) has been well known to exert therapeutic potential for patients with myocardial infarction (MI). In addition, interleukin-10 (IL10) could attenuate MI through suppressing inflammation. Thus, the combination of MSC implantation with IL10 delivery may extend health benefits to ameliorate cardiac injury after MI. Here we established overexpression of IL10 in bone marrow-derived MSC through adenoviral transduction. Cell viability, apoptosis, and IL10 secretion under ischemic challenge in vitro were examined. In addition, MSC was transplanted into the injured hearts in a rat model of MI. Four weeks after the MI induction, MI, cardiac functions, apoptotic cells, and inflammation cytokines were assessed. In response to in vitro oxygen-glucose deprivation (OGD), IL10 overexpression in MSC (Ad.IL10-MSC) enhanced cell viability, decreased apoptosis, and increased IL10 secretion. Consistently, the implantation of Ad.IL10-MSCs into MI animals resulted in more reductions in myocardial infarct size, cardiac impairment, and cell apoptosis, compared to the individual treatments of either MSC or IL10 administration. Moreover, the attenuation of both systemic and local inflammations was most prominent for Ad.IL10-MSC treatment. IL10 overexpression and MSC may exert a synergistic anti-inflammatory effect to alleviate cardiac injury after MI. © 2017 Wiley Periodicals, Inc.

  5. The fine structure of sheep myocardial cells; sarcolemmal invaginations and the transverse tubular system.

    Science.gov (United States)

    SIMPSON, F O; OERTELIS, S J

    1962-01-01

    An electron microscope study of sheep myocardial cells has demonstrated the presence of a transverse tubular system, apparently forming a network across the cell at each Z band level. The walls of these tubules resemble the sarcolemma in consisting of two dense layers-plasma membrane and basement menbrane; continuity of the tubule walls with the sarcolemma can be seen when longitudinal sections of a cell are obtained between two subsarcolemmal myofibrils and at the same time perpendicular to the cell surface. The demonstration of communication between the lumen of the transverse tubular system and the extracellular space appears to be more definite in this study than in any work hitherto published. It provides anatomical evidence of a possible direct pathway for transmission of the activating impulse from the sarcolemma to the myofibril Z bands.

  6. Myocardial Bridge

    Science.gov (United States)

    ... Center > Myocardial Bridge Menu Topics Topics FAQs Myocardial Bridge En español Your heart is made of muscle, ... surface of the heart. What is a myocardial bridge? A myocardial bridge is a band of heart ...

  7. Effect of exogenous apelin-13 on cardiac stem cell mobilization in rats with myocardial infarction

    Directory of Open Access Journals (Sweden)

    Nan ZHENG

    2013-11-01

    0.39±0.08 vs 0.70±0.08, P<0.05; mRNA level: C-kit 2.89±1.89 vs 18.77±14.19, Flk1 2.14±0.95 vs 4.59±0.92, Sca1 4.32±2.44 vs 29.39±11.90, P<0.05, and there was no obvious expression of C-kit, Flk1 or Sca1 protein in sham-operated group. Conclusion Exogenous apelin-13 protein has protective effect on rats against myocardial infarction, which is closely related to stimulating the proliferation of endogenous cardiac stem cells. DOI: 10.11855/j.issn.0577-7402.2013.10.004

  8. Recovery and functional activity of mononuclear bone marrow and peripheral blood cells after different cell isolation protocols used in clinical trials for cell therapy after acute myocardial infarction

    NARCIS (Netherlands)

    van Beem, Rachel T.; Hirsch, Alexander; Lommerse, Ingrid M.; Zwaginga, Jaap Jan; Noort, Willy A.; Biemond, Bart J.; Piek, Jan J.; van der Schoot, C. Ellen; Voermans, Carlijn

    2008-01-01

    AIMS: Clinical trials showed contradictory results in functional recovery after intracoronary infusion of autologous mononuclear (bone marrow) cells in patients with acute myocardial infarction. A recent study suggests that this might be related to the isolation protocol used. In The Netherlands, a

  9. The Role of Bioactive Lipids in Stem Cell Mobilization and Homing: Novel Therapeutics for Myocardial Ischemia

    Directory of Open Access Journals (Sweden)

    Yuri M. Klyachkin

    2014-01-01

    Full Text Available Despite significant advances in medical therapy and interventional strategies, the prognosis of millions of patients with acute myocardial infarction (AMI and ischemic heart disease (IHD remains poor. Currently, short of heart transplantation with all of its inherit limitations, there are no available treatment strategies that replace the infarcted myocardium. It is now well established that cardiomyocytes undergo continuous renewal, with contribution from bone marrow (BM-derived stem/progenitor cells (SPCs. This phenomenon is upregulated during AMI by initiating multiple innate reparatory mechanisms through which BMSPCs are mobilized towards the ischemic myocardium and contribute to myocardial regeneration. While a role for the SDF-1/CXCR4 axis in retention of BMSPCs in bone marrow is undisputed, its exclusive role in their mobilization and homing to a highly proteolytic microenvironment, such as the ischemic/infarcted myocardium, is currently being challenged. Recent evidence suggests a pivotal role for bioactive lipids in the mobilization of BMSPCs at the early stages following AMI and their homing towards ischemic myocardium. This review highlights the recent advances in our understanding of the mechanisms of stem cell mobilization, provides newer evidence implicating bioactive lipids in BMSPC mobilization and differentiation, and discusses their potential as therapeutic agents in the treatment of IHD.

  10. Differential loss of natural killer cell activity in patients with acute myocardial infarction and stable angina pectoris.

    Science.gov (United States)

    Yan, Wenwen; Zhou, Lin; Wen, Siwan; Duan, Qianglin; Huang, Feifei; Tang, Yu; Liu, Xiaohong; Chai, Yongyan; Wang, Lemin

    2015-01-01

    To evaluate the activity of natural killer cells through their inhibitory and activating receptors and quantity in peripheral blood mononuclear cells extracted from patients with acute myocardial infarction, stable angina pectoris and the controls. 100 patients with myocardial infarction, 100 with stable angina, and 20 healthy volunteers were recruited into the study. 20 randomly chosen people per group were examined for the whole human genome microarray analysis to detect the gene expressions of all 40 inhibitory and activating natural killer cell receptors. Flow cytometry analysis was applied to all 200 patients to measure the quantity of natural killer cells. In myocardial infarction group, the mRNA expressions of six inhibitory receptors KIR2DL2, KIR3DL3, CD94, NKG2A, KLRB1, KLRG1, and eight activating receptors KIR2DS3, KIR2DS5, NKp30, NTB-A, CRACC, CD2, CD7 and CD96 were significantly down-regulated (Pangina patients and the controls. There was no statistical difference in receptor expressions between angina patients and control group. The quantity of natural killer cells was significantly decreased in both infarction and angina patients compared with normal range (Pangina patients showed a quantitative loss and dysfunction of natural killer cells in myocardial infarction patients.

  11. CD4+ Foxp3+ T-cells contribute to myocardial ischemia-reperfusion injury.

    Science.gov (United States)

    Mathes, Denise; Weirather, Johannes; Nordbeck, Peter; Arias-Loza, Anahi-Paula; Burkard, Matthias; Pachel, Christina; Kerkau, Thomas; Beyersdorf, Niklas; Frantz, Stefan; Hofmann, Ulrich

    2016-12-01

    The present study analyzed the effect of CD4 + Forkhead box protein 3 negative (Foxp3 - ) T-cells and Foxp3 + CD4 + T-cells on infarct size in a mouse myocardial ischemia-reperfusion model. We examined the infarct size as a fraction of the area-at-risk as primary study endpoint in mice after 30minutes of coronary ligation followed by 24hours of reperfusion. CD4 + T-cell deficient MHC-II KO mice showed smaller histologically determined infarct size (34.5±4.7% in MHCII KO versus 59.4±4.9% in wildtype (WT)) and better preserved ejection fraction determined by magnetic resonance tomography (56.9±2.8% in MHC II KO versus 39.0±4.2% in WT). MHC-II KO mice also displayed better microvascular perfusion than WT mice after 24hours of reperfusion. Also CD4 + T-cell sufficient OT-II mice, which express an in this context irrelevant T-cell receptor, revealed smaller infarct sizes compared to WT mice. However, MHC-II blocking anti-I-A/I-E antibody treatment was not able to reduce infarct size indicating that autoantigen recognition is not required for the activation of CD4 + T-cells during reperfusion. Flow-cytometric analysis also did not detect CD4 + T-cell activation in heart draining lymph nodes in response to 24hours of ischemia-reperfusion. Adoptive transfer of CD4 + T-cells in CD4 KO mice increased the infarct size only when including the Foxp3 + CD25 + subset. Depletion of CD4 + Foxp3 + T-cells in DEREG mice enabling specific conditional ablation of this subset by treatment with diphtheria toxin attenuated infarct size as compared to diphtheria toxin treated WT mice. CD4 + Foxp3 + T-cells enhance myocardial ischemia-reperfusion injury. CD4 + T-cells exert injurious effects without the need for prior activation by MHC-II restricted autoantigen recognition. Copyright © 2016 Elsevier Ltd. All rights reserved.

  12. [Effects of moxibustion with seed-sized moxa cone on apoptosis of myocardial cells after sport fatigue in mice].

    Science.gov (United States)

    Xu, Huiqian; Hu, Yin; Gu, Yihuang; Zhang, Hongru

    2015-03-01

    To observe the effects of moxibustion on factors related with apoptosis of myocardial cells after sports fatigue in mice as well as the relationship among histone acetyltransferases p300 (p300), CREB binding protein (CBP) and cell apoptosis to discuss the role of p300 and CBP in moxibustion against apoptosis of myocardial cells. Sixty clean-grade male Kunming mice were randomly divided into a control group, a sport group and a moxibustion group, 20 cases in each one. Mice in all group received identical feeding environment. Mice in the control group did not received sport nor moxibustion; mice in the sport group and moxibustion group received non-weight swimming training which lasted from 30 min per day to 90 min per day gradually for 21 days; 1 h after swimming training, mice in the moxibustion group received moxibustion with seed-sized moxa cone at "Zusanli" (ST 36) and "Guanyuan" (CV 4), 5 cones at each acupoint, once a day for 21 days. 24 h after the final swimming training, cardiac muscle tissue was collected to test factor associated suicide (Fas), B cell lymphoma/lewkmia-2 (Bcl-2) by immunohistochemical method and expression of p300 and CBP. Compared with the control group, the apoptosis rate of myocardial cells in the sport group was significantly increased (Pprotein was significantly increased (Psport group, the apoptosis rate of myocardial cells in the moxibustion group was significantly reduced (Pprotein was significantly reduced (Psports fatigue in mice to inhibit the starting of apoptotic process, therefore reducing the apoptosis of myocardial cells after heavy exercise and protecting heart function.

  13. G-CSF therapy with mobilization of bone marrow stem cells for myocardial recovery after acute myocardial infarction - a relevant treatment?

    DEFF Research Database (Denmark)

    Ripa, R.S.; Kastrup, J.

    2008-01-01

    -CSF treatment. Current controversies in interpretation of the results include 1) importance of direct cardiac effect of G-CSF vs indirect through bone marrow stem and progenitor cell mobilization, 2) importance of timing of G-CSF therapy, 3) importance of G-CSF dose, and 4) importance of cell types mobilized...... from the bone-marrow. Cell-based therapies to improve cardiac function remain promising and further experimental and clinical studies are warranted to determine the future role of G-CSF Udgivelsesdato: 2008/6......This review of adjunctive therapy with subcutaneous granulocyte-colony stimulating factor (G-CSF) to patients with acute myocardial infarction (AMI) focus on the cardioprotective effects and potential mechanisms of G-CSF and discuss the therapeutic potential of G-CSF. All clinical trials published...

  14. Strategy to prime the host and cells to augment therapeutic efficacy of progenitor cells for patients with myocardial infarction

    Directory of Open Access Journals (Sweden)

    Jeehoon Kang

    2016-11-01

    Full Text Available Cell therapy in myocardial infarction (MI is an innovative strategy that is regarded as a rescue therapy to repair the damaged myocardium and to promote neovascularization for the ischemic border zone. Among several stem cell sources for this purpose, autologous progenitors from bone marrow or peripheral blood would be the most feasible and safest cell-source. Despite the theoretical benefit of cell therapy, this method is not widely adopted in the actual clinical practice due to its low therapeutic efficacy. Various methods have been used to augment the efficacy of cell therapy in MI, such as using different source of progenitors, genetic manipulation of cells, or priming of the cells or hosts (patients with agents. Among these methods, the strategy to augment the therapeutic efficacy of the autologous peripheral blood mononuclear cells by priming agents may be the most feasible and the safest method that can be applied directly to the clinic. In this review, we will discuss the current status and future directions of priming peripheral blood mononuclear cells or patients, as for cell therapy of MI.

  15. Bone Marrow Mononuclear Cell Transplantation Restores Inflammatory Balance of Cytokines after ST Segment Elevation Myocardial Infarction.

    Directory of Open Access Journals (Sweden)

    Kirsi Alestalo

    Full Text Available Acute myocardial infarction (AMI launches an inflammatory response and a repair process to compensate cardiac function. During this process, the balance between proinflammatory and anti-inflammatory cytokines is important for optimal cardiac repair. Stem cell transplantation after AMI improves tissue repair and increases the ventricular ejection fraction. Here, we studied in detail the acute effect of bone marrow mononuclear cell (BMMNC transplantation on proinflammatory and anti-inflammatory cytokines in patients with ST segment elevation myocardial infarction (STEMI.Patients with STEMI treated with thrombolysis followed by percutaneous coronary intervention (PCI were randomly assigned to receive either BMMNC or saline as an intracoronary injection. Cardiac function was evaluated by left ventricle angiogram during the PCI and again after 6 months. The concentrations of 27 cytokines were measured from plasma samples up to 4 days after the PCI and the intracoronary injection.Twenty-six patients (control group, n = 12; BMMNC group, n = 14 from the previously reported FINCELL study (n = 80 were included to this study. At day 2, the change in the proinflammatory cytokines correlated with the change in the anti-inflammatory cytokines in both groups (Kendall's tau, control 0.6; BMMNC 0.7. At day 4, the correlation had completely disappeared in the control group but was preserved in the BMMNC group (Kendall's tau, control 0.3; BMMNC 0.7.BMMNC transplantation is associated with preserved balance between pro- and anti-inflammatory cytokines after STEMI in PCI-treated patients. This may partly explain the favorable effect of stem cell transplantation after AMI.

  16. Basic study on a lower-energy defibrillation method using computer simulation and cultured myocardial cell models.

    Science.gov (United States)

    Yaguchi, A; Nagase, K; Ishikawa, M; Iwasaka, T; Odagaki, M; Hosaka, H

    2006-01-01

    Computer simulation and myocardial cell models were used to evaluate a low-energy defibrillation technique. A generated spiral wave, considered to be a mechanism of fibrillation, and fibrillation were investigated using two myocardial sheet models: a two-dimensional computer simulation model and a two-dimensional experimental model. A new defibrillation technique that has few side effects, which are induced by the current passing into the patient's body, on cardiac muscle is desired. The purpose of the present study is to conduct a basic investigation into an efficient defibrillation method. In order to evaluate the defibrillation method, the propagation of excitation in the myocardial sheet is measured during the normal state and during fibrillation, respectively. The advantages of the low-energy defibrillation technique are then discussed based on the stimulation timing.

  17. Autologous bone marrow concentrate enriched in progenitor cells — An adjuvant in the treatment of acute myocardial infarction

    Directory of Open Access Journals (Sweden)

    Vinay Sanghi

    2016-06-01

    Full Text Available Despite advances in revascularization techniques, acute myocardial infarction (AMI still carries significant morbidity and mortality. Over the past decade, the use of regenerative medicine methodologies, and specifically bone marrow derived progenitor cell therapy has been tested in more than 35 Phase I and Phase II clinical studies demonstrating overall safety and measurable clinical benefit, 12–61 months post-treatment as evaluated by improvement in the Left Ventricular Ejection Fraction (LVEF and changes in infarct size post AMI. Recent meta-analysis on the subject highlighted several important parameters that include timing of the cell therapy post AMI, the cell dose, and the baseline LVEF on enrollment. We further postulate that the mythologies and timing for cell handling and delivery including the specific devices are essential for clinical efficacy. Addressing this we have developed a rapid 60 to 90 minute process and integrated system which is carried out in the heart catheter lab, using a combination product (U.S. Food and Drug broadly defined as the combination of co-labeled optimized “cell friendly” devices, effective cell/biological formulation and dose for harvesting, processing, verifying, and delivering an autologous dose of bone marrow progenitor/stem cells via the intracoronary artery proximal to the infarct myocardial region. The methodology has been demonstrated to be safe and feasible for autologous in vivo use and presented by our groups' earlier studies1–3 and most recently used in a Phase Ib critical limb ischemia trial of 17 subjects (NCT01472289 (manuscript under preparation. This is the first case study prior to beginning the AMIRST trial [Acute Myocardial Infarction Rapid Stem cell Therapy], specific to our proprietary combination product kit for acute myocardial infarction, and was completed under the Independent Ethics Committee and Institutional Committee for Stem Cell Research and Therapy approval (TIEC

  18. Mast cells regulate myofilament calcium sensitization and heart function after myocardial infarction.

    Science.gov (United States)

    Ngkelo, Anta; Richart, Adèle; Kirk, Jonathan A; Bonnin, Philippe; Vilar, Jose; Lemitre, Mathilde; Marck, Pauline; Branchereau, Maxime; Le Gall, Sylvain; Renault, Nisa; Guerin, Coralie; Ranek, Mark J; Kervadec, Anaïs; Danelli, Luca; Gautier, Gregory; Blank, Ulrich; Launay, Pierre; Camerer, Eric; Bruneval, Patrick; Menasche, Philippe; Heymes, Christophe; Luche, Elodie; Casteilla, Louis; Cousin, Béatrice; Rodewald, Hans-Reimer; Kass, David A; Silvestre, Jean-Sébastien

    2016-06-27

    Acute myocardial infarction (MI) is a severe ischemic disease responsible for heart failure and sudden death. Inflammatory cells orchestrate postischemic cardiac remodeling after MI. Studies using mice with defective mast/stem cell growth factor receptor c-Kit have suggested key roles for mast cells (MCs) in postischemic cardiac remodeling. Because c-Kit mutations affect multiple cell types of both immune and nonimmune origin, we addressed the impact of MCs on cardiac function after MI, using the c-Kit-independent MC-deficient (Cpa3(Cre/+)) mice. In response to MI, MC progenitors originated primarily from white adipose tissue, infiltrated the heart, and differentiated into mature MCs. MC deficiency led to reduced postischemic cardiac function and depressed cardiomyocyte contractility caused by myofilament Ca(2+) desensitization. This effect correlated with increased protein kinase A (PKA) activity and hyperphosphorylation of its targets, troponin I and myosin-binding protein C. MC-specific tryptase was identified to regulate PKA activity in cardiomyocytes via protease-activated receptor 2 proteolysis. This work reveals a novel function for cardiac MCs modulating cardiomyocyte contractility via alteration of PKA-regulated force-Ca(2+) interactions in response to MI. Identification of this MC-cardiomyocyte cross-talk provides new insights on the cellular and molecular mechanisms regulating the cardiac contractile machinery and a novel platform for therapeutically addressable regulators. ©2016 Ngkelo et al.

  19. Hybrid approach of ventricular assist device and autologous bone marrow stem cells implantation in end-stage ischemic heart failure enhances myocardial reperfusion

    Directory of Open Access Journals (Sweden)

    Khayat Andre

    2011-01-01

    Full Text Available Abstract We challenge the hypothesis of enhanced myocardial reperfusion after implanting a left ventricular assist device together with bone marrow mononuclear stem cells in patients with end-stage ischemic cardiomyopathy. Irreversible myocardial loss observed in ischemic cardiomyopathy leads to progressive cardiac remodelling and dysfunction through a complex neurohormonal cascade. New generation assist devices promote myocardial recovery only in patients with dilated or peripartum cardiomyopathy. In the setting of diffuse myocardial ischemia not amenable to revascularization, native myocardial recovery has not been observed after implantation of an assist device as destination therapy. The hybrid approach of implanting autologous bone marrow stem cells during assist device implantation may eventually improve native cardiac function, which may be associated with a better prognosis eventually ameliorating the need for subsequent heart transplantation. The aforementioned hypothesis has to be tested with well-designed prospective multicentre studies.

  20. Local myocardial insulin-like growth factor 1 (IGF-1) delivery with biotinylated peptide nanofibers improves cell therapy for myocardial infarction

    Science.gov (United States)

    Davis, Michael E.; Hsieh, Patrick C. H.; Takahashi, Tomosaburo; Song, Qing; Zhang, Shuguang; Kamm, Roger D.; Grodzinsky, Alan J.; Anversa, Piero; Lee, Richard T.

    2006-05-01

    Strategies for cardiac repair include injection of cells, but these approaches have been hampered by poor cell engraftment, survival, and differentiation. To address these shortcomings for the purpose of improving cardiac function after injury, we designed self-assembling peptide nanofibers for prolonged delivery of insulin-like growth factor 1 (IGF-1), a cardiomyocyte growth and differentiation factor, to the myocardium, using a "biotin sandwich" approach. Biotinylated IGF-1 was complexed with tetravalent streptavidin and then bound to biotinylated self-assembling peptides. This biotin sandwich strategy allowed binding of IGF-1 but did not prevent self-assembly of the peptides into nanofibers within the myocardium. IGF-1 that was bound to peptide nanofibers activated Akt, decreased activation of caspase-3, and increased expression of cardiac troponin I in cardiomyocytes. After injection into rat myocardium, biotinylated nanofibers provided sustained IGF-1 delivery for 28 days, and targeted delivery of IGF-1 in vivo increased activation of Akt in the myocardium. When combined with transplanted cardiomyocytes, IGF-1 delivery by biotinylated nanofibers decreased caspase-3 cleavage by 28% and increased the myocyte cross-sectional area by 25% compared with cells embedded within nanofibers alone or with untethered IGF-1. Finally, cell therapy with IGF-1 delivery by biotinylated nanofibers improved systolic function after experimental myocardial infarction, demonstrating how engineering the local cellular microenvironment can improve cell therapy. engineering | maturation | scaffold

  1. Differential cytotoxicity and internalization of graphene family nanomaterials in myocardial cells

    Energy Technology Data Exchange (ETDEWEB)

    Contreras-Torres, Flavio F., E-mail: contreras.flavio@itesm.mx [Laboratorio de Nanotecnología Ambiental, Centro del Agua para América Latina y el Caribe, Tecnológico de Monterrey, Monterrey, 64849 (Mexico); Rodríguez-Galván, Andrés [Department of Chemistry, Universityof Oxford, South Parks Road, Oxford OX1 3QZ (United Kingdom); Guerrero-Beltrán, Carlos E. [Cátedra de Cardiología y Medicina Vascular, Escuela Nacional de Medicina, Tecnológico de Monterrey, Monterrey, 64849 (Mexico); Martínez-Lorán, Erick [Department of NanoEngineering, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093 (United States); Vázquez-Garza, Eduardo [Cátedra de Cardiología y Medicina Vascular, Escuela Nacional de Medicina, Tecnológico de Monterrey, Monterrey, 64849 (Mexico); Ornelas-Soto, Nancy [Laboratorio de Nanotecnología Ambiental, Centro del Agua para América Latina y el Caribe, Tecnológico de Monterrey, Monterrey, 64849 (Mexico); and others

    2017-04-01

    Given the well-known physical properties of graphene oxide (GO), numerous applications for this novel nanomaterial have been recently envisioned to improve the performance of biomedical devices. However, the toxicological assessment of GO, which strongly depends on the used material and the studied cell line, is a fundamental task that needs to be performed prior to its use in biomedical applications. Therefore, the toxicological characterization of GO is still ongoing. This study contributes to this, aiming to synthesize and characterize GO particles and thus investigate their toxic effects in myocardial cells. Herein, GO particles were produced from graphite using the Tour method and subsequent mild reduction was carried out to obtain low-reduced GO (LRGO) particles. A qualitative analysis of the viability, cellular uptake, and internalization of particles was carried out using GO (~ 54% content of oxygen) and LRGO (~ 37% content of oxygen) and graphite. GO and LRGO reduce the viability of cardiac cells at IC{sub 50} of 652.1 ± 1.2 and 129.4 ± 1.2 μg/mL, respectively. This shows that LRGO particles produce a five-fold increase in cytotoxicity when compared to GO. The cell uptake pattern of GO and LRGO particles demonstrated that cardiac cells retain a similar complexity to control cells. Morphological alterations examined with electron microscopy showed that internalization by GO and LRGO-treated cells (100 μg/mL) occurred affecting the cell structure. These results suggest that the viability of H9c2 cells can be associated with the surface chemistry of GO and LRGO, as defined by the amount of oxygen functionalities, the number of graphitic domains, and the size of particles. High angle annular dark-field scanning transmission electron microscopy, dynamic light-scattering, Fourier-transform infrared, Raman, and X-ray photoelectron spectroscopies were used to characterize the as-prepared materials. - Highlights: • H9c2 cells were treated with a family of

  2. Alcohol consumption negates estrogen-mediated myocardial repair in ovariectomized mice by inhibiting endothelial progenitor cell mobilization and function.

    Science.gov (United States)

    Mackie, Alexander R; Krishnamurthy, Prasanna; Verma, Suresh K; Thorne, Tina; Ramirez, Veronica; Qin, Gangjian; Abramova, Tatiana; Hamada, Hiromichi; Losordo, Douglas W; Kishore, Raj

    2013-06-21

    We have shown previously that estrogen (estradiol, E2) supplementation enhances voluntary alcohol consumption in ovariectomized female rodents and that increased alcohol consumption impairs ischemic hind limb vascular repair. However, the effect of E2-induced alcohol consumption on post-infarct myocardial repair and on the phenotypic/functional properties of endothelial progenitor cells (EPCs) is not known. Additionally, the molecular signaling of alcohol-estrogen interactions remains to be elucidated. This study examined the effect of E2-induced increases in ethanol consumption on post-infarct myocardial function/repair. Ovariectomized female mice, implanted with 17β-E2 or placebo pellets were given access to alcohol for 6 weeks and subjected to acute myocardial infarction. Left ventricular functions were consistently depressed in mice consuming ethanol compared with those receiving only E2. Alcohol-consuming mice also displayed significantly increased infarct size and reduced capillary density. Ethanol consumption also reduced E2-induced mobilization and homing of EPCs to injured myocardium compared with the E2-alone group. In vitro, exposure of EPCs to ethanol suppressed E2-induced proliferation, survival, and migration and markedly altered E2-induced estrogen receptor-dependent cell survival signaling and gene expression. Furthermore, ethanol-mediated suppression of EPC biology was endothelial nitric oxide synthase-dependent because endothelial nitric oxide synthase-null mice displayed an exaggerated response to post-acute myocardial infarction left ventricular functions. These data suggest that E2 modulation of alcohol consumption, and the ensuing EPC dysfunction, may negatively compete with the beneficial effects of estrogen on post-infarct myocardial repair.

  3. miR-133a Enhances the Protective Capacity of Cardiac Progenitors Cells after Myocardial Infarction

    Directory of Open Access Journals (Sweden)

    Alberto Izarra

    2014-12-01

    Full Text Available miR-133a and miR-1 are known as muscle-specific microRNAs that are involved in cardiac development and pathophysiology. We have shown that both miR-1 and miR-133a are early and progressively upregulated during in vitro cardiac differentiation of adult cardiac progenitor cells (CPCs, but only miR-133a expression was enhanced under in vitro oxidative stress. miR-1 was demonstrated to favor differentiation of CPCs, whereas miR-133a overexpression protected CPCs against cell death, targeting, among others, the proapoptotic genes Bim and Bmf. miR-133a-CPCs clearly improved cardiac function in a rat myocardial infarction model by reducing fibrosis and hypertrophy and increasing vascularization and cardiomyocyte proliferation. The beneficial effects of miR-133a-CPCs seem to correlate with the upregulated expression of several relevant paracrine factors and the plausible cooperative secretion of miR-133a via exosomal transport. Finally, an in vitro heart muscle model confirmed the antiapoptotic effects of miR-133a-CPCs, favoring the structuration and contractile functionality of the artificial tissue.

  4. Physiologic ischaemic training induces endothelial progenitor cell mobilization and myocardial angiogenesis via endothelial nitric oxide synthase related pathway in rabbits.

    Science.gov (United States)

    Xiao, Mingyue; Lu, Xiao; Li, Jianan; Li, Ling; Li, Yongxue

    2014-04-01

    Ischaemia-induced angiogenesis promises to improve neovascularization by delivery of angiogenic factors or endothelial progenitor cells (EPCs) to cardiac ischaemic areas. In order to avoid the risk of excessive myocardial ischaemia, therefore, we hypothesized that physiological ischaemic training (PIT) of normal skeletal muscle might contribute to myocardial angiogenesis via nitric oxide mediated mobilization of EPCs from the bone marrow in the established rabbit model of controllable myocardial ischaemia. The rabbits were grouped by sham-operation, myocardial ischaemia without PIT, PIT and PIT with pretreatment with the endothelial nitric oxide synthase (eNOS) inhibitor L-nitroarginine methyl ester (L-NAME). Controlled myocardial ischaemia was modelled by a water balloon constrictor implanted on the left ventricular branch in a rabbit. The PIT procedure included three cycles of 3 min of cuff inflation followed by 5 min of deflation on hind limbs of the rabbits for 4 weeks. At the endpoints, circulating EPCs (CD34/Flk-1) were measured by fluorescence-activated cell sorter; capillary density, by immunohistochemistry; blood flow, by a microsphere technique; endothelial nitric oxide synthase (eNOS) mRNA and protein, by real-time reverse transcriptase (RT)-PCR and Western blotting. The mRNA levels of eNOS were significantly higher in the PIT and L-NAME groups than in the sham-operation group (P < 0.05). Phospho-eNOS protein expression was higher in the PIT group than in the sham-operation and myocardial ischaemia without PIT groups (P < 0.05), and the effect was inhibited by L-NAME pretreatment (P < 0.05). Compared with sham-operation and myocardial ischaemia without PIT groups, the PIT group had the highest EPC count (P < 0.001), and the increase of capillary density (P < 0.01) and collateral blood flow (P < 0.05) in the ischaemic myocardium was consistent with the finding of EPC count. These effects were also inhibited by pretreatment with

  5. Cortical Bone Stem Cell Therapy Preserves Cardiac Structure and Function After Myocardial Infarction.

    Science.gov (United States)

    Sharp, Thomas E; Schena, Giana J; Hobby, Alexander R; Starosta, Timothy; Berretta, Remus M; Wallner, Markus; Borghetti, Giulia; Gross, Polina; Yu, Daohai; Johnson, Jaslyn; Feldsott, Eric; Trappanese, Danielle M; Toib, Amir; Rabinowitz, Joseph E; George, Jon C; Kubo, Hajime; Mohsin, Sadia; Houser, Steven R

    2017-11-10

    Cortical bone stem cells (CBSCs) have been shown to reduce ventricular remodeling and improve cardiac function in a murine myocardial infarction (MI) model. These effects were superior to other stem cell types that have been used in recent early-stage clinical trials. However, CBSC efficacy has not been tested in a preclinical large animal model using approaches that could be applied to patients. To determine whether post-MI transendocardial injection of allogeneic CBSCs reduces pathological structural and functional remodeling and prevents the development of heart failure in a swine MI model. Female Göttingen swine underwent left anterior descending coronary artery occlusion, followed by reperfusion (ischemia-reperfusion MI). Animals received, in a randomized, blinded manner, 1:1 ratio, CBSCs (n=9; 2×10 7 cells total) or placebo (vehicle; n=9) through NOGA-guided transendocardial injections. 5-ethynyl-2'deoxyuridine (EdU)-a thymidine analog-containing minipumps were inserted at the time of MI induction. At 72 hours (n=8), initial injury and cell retention were assessed. At 3 months post-MI, cardiac structure and function were evaluated by serial echocardiography and terminal invasive hemodynamics. CBSCs were present in the MI border zone and proliferating at 72 hours post-MI but had no effect on initial cardiac injury or structure. At 3 months, CBSC-treated hearts had significantly reduced scar size, smaller myocytes, and increased myocyte nuclear density. Noninvasive echocardiographic measurements showed that left ventricular volumes and ejection fraction were significantly more preserved in CBSC-treated hearts, and invasive hemodynamic measurements documented improved cardiac structure and functional reserve. The number of EdU + cardiac myocytes was increased in CBSC- versus vehicle- treated animals. CBSC administration into the MI border zone reduces pathological cardiac structural and functional remodeling and improves left ventricular functional reserve

  6. Allogeneic amniotic membrane-derived mesenchymal stromal cell transplantation in a porcine model of chronic myocardial ischemia

    Directory of Open Access Journals (Sweden)

    Kimura M

    2012-01-01

    Full Text Available Introduction. Amniotic membrane contains a multipotential stem cell population and is expected to possess the machinery to regulate immunological reactions. We investigated the safety and efficacy of allogeneic amniotic membrane-derived mesenchymal stromal cell (AMSC transplantation in a porcine model of chronic myocardial ischemia as a preclinical trial. Methods. Porcine AMSCs were isolated from amniotic membranes obtained by cesarean section just before delivery and were cultured to increase their numbers before transplantation. Chronic myocardial ischemia was induced by implantation of an ameroid constrictor around the left circumflex coronary artery. Four weeks after ischemia induction, nine swine were assigned to undergo either allogeneic AMSC transplantation or normal saline injection. Functional analysis was performed by echocardiography, and histological examinations were carried out by immunohistochemistry 4 weeks after AMSC transplantation. Results. Echocardiography demonstrated that left ventricular ejection fraction was significantly improved and left ventricular dilatation was well attenuated 4 weeks after AMSC transplantation. Histological assessment showed a significant reduction in percentage of fibrosis in the AMSC transplantation group. Injected allogeneic green fluorescent protein (GFP-expressing AMSCs were identified in the immunocompetent host heart without the use of any immunosuppressants 4 weeks after transplantation. Immunohistochemistry revealed that GFP colocalized with cardiac troponin T and cardiac troponin I. Conclusions. We have demonstrated that allogeneic AMSC transplantation produced histological and functional improvement in the impaired myocardium in a porcine model of chronic myocardial ischemia. The transplanted allogeneic AMSCs survived without the use of any immunosuppressants and gained cardiac phenotype through either their transdifferentiation or cell fusion.

  7. Mode selection in electrical activities of myocardial cell exposed to electromagnetic radiation

    International Nuclear Information System (INIS)

    Ma, Jun; Wang, Ya; Wang, Chunni; Xu, Ying; Ren, Guodong

    2017-01-01

    Highlights: • Neuronal model under electromagnetic induction and radiation is set up; • The transition of electrical activities under electromagnetic radiation is discussed; • Dynamical response of encoding of neuron is discussed for possible mechanism of heart disease. - Abstract: Based on the Fitzhugh–Nagumo neuron model, the effect of electromagnetic induction is considered and external electromagnetic radiation is imposed to detect the mode transition of electrical activities in a myocardial cell. Appropriate dynamical and functional responses can be observed in the sampled series for membrane potentials by setting different feedback modulation on the membrane potential in presence of electromagnetic radiation. The electromagnetic radiation is described by a periodical forcing on the magnetic flux, and it is found that the response frequency can keep pace with the frequency of external forcing. However, mismatch of frequency occurs by further increasing the frequency of external forcing, it could account for the information encoding of neuron. The dynamical response could be associated with the magnetization and polarization of the media, thus the outputs of membrane potential can become quiescent and/or bursting as well.

  8. Enhanced mesenchymal cell engraftment by IGF-1 improves left ventricular function in rats undergoing myocardial infarction.

    Science.gov (United States)

    Enoki, Chiharu; Otani, Hajime; Sato, Daisuke; Okada, Takayuki; Hattori, Reiji; Imamura, Hiroji

    2010-01-07

    We hypothesized that enhanced mesenchymal cell (MC) engraftment with insulin-like growth factor-1 (IGF-1) improves left ventricular (LV) function and survival. IGF-1 (10 microg/ml) increased adhesion and inhibited apoptosis under hypoxia in vitro through activation of phosphatidylinositol 3-kinase (PI3K) in bone marrow-derived MCs obtained from transgenic rats expressing green fluorescence protein. Myocardial infarction (MI) in rats was produced by ligature of the left coronary artery. One month after MI, rat hearts were injected with MCs in the presence or absence of 10 microg/ml IGF-1 with or without PI3K inhibitor, 5 microM LY294002. IGF-1 significantly increased engraftment of MCs between 6 h and 3 days after transplantation associated with the increase in stromal cell-derived factor-1alpha in the infracted LV. The transplanted MCs had disappeared 1 month after transplantation in all groups. MC transplantation with IGF-1 significantly increased neovascularization and inhibited cardiomyocyte apoptosis 3 days and 1 month after MC transplantation. This was associated with improved LV function 1 month after MC transplantation and eventually survival. LY294002 abrogated all of the beneficial effects of MC transplantation with IGF-1. IGF-1 alone had no effect on neovascularization and did not improve LV function and/or survival. These results suggest that IGF-1 improves engraftment of MCs at the time of transplantation via activation of PI3K and this improved engraftment of MCs may be attributed to an increased neovascularization and inhibition of cardiomyocyte death, leading to improvement of LV function and prolongation of survival despite the eventual loss of the transplanted MCs.

  9. Adipose-derived mesenchymal stromal cells for chronic myocardial ischemia (MyStromalCell Trial)

    DEFF Research Database (Denmark)

    Qayyum, Abbas Ali; Haack-Sørensen, Mandana; Mathiasen, Anders Bruun

    2012-01-01

    Adipose tissue represents an abundant, accessible source of multipotent adipose-derived stromal cells (ADSCs). Animal studies have suggested that ADSCs have the potential to differentiate in vivo into endothelial cells and cardiomyocytes. This makes ADSCs a promising new cell source...... for regenerative therapy to replace injured tissue by creating new blood vessels and cardiomyocytes in patients with chronic ischemic heart disease. The aim of this special report is to review the present preclinical data leading to clinical stem cell therapy using ADSCs in patients with ischemic heart disease....... In addition, we give an introduction to the first-in-man clinical trial, MyStromalCell Trial, which is a prospective, randomized, double-blind, placebo-controlled study using culture-expanded ADSCs obtained from adipose-derived cells from abdominal adipose tissue and stimulated with VEGF-A(165) the week...

  10. Effect of bionic electrical stimulation on the differentiation of embryonic stem cells into cardiomyocytes in the presence myocardial cells in vitro

    Directory of Open Access Journals (Sweden)

    Li-na ZHENG

    2011-08-01

    Full Text Available Objective To investigate the effects of electrical stimulation on the differentiation of embryonic stem cells(ESCs into cardiomyocytes in the presence of myocardial cells in vitro.Methods ESCs and neonate rat cardiomyocytes were isolated and cultured.These cells of primary culture were divided into 5 groups according to whether or not electric stimulation was given and the presence of cardiomyocytes: control group,stimulation group,cardiomyocytes group,stimulation+ cardiomyocyte conditioned medium group,and stimulation+cardiomyocytes group.Expression of troponin T(cTnT in the differentiated cells from ESCs was examined by immunofluoresence on the 5th,7th and 14th day.Results In the group co-cultured with myocardial cell and electrical stimulation,the differentiating ratio of cardiomyocytes derived from ESCs and expressing cTnT was 40.00%±2.39%,and it was higher than that in control group(2.00%±1.60%,stimulation group(3.00%±2.00%,cardiomyocytes group(28.70%±4.06%,stimulation+cardiomyocyte conditioned medium group(17.10%±2.23%,P < 0.05.Conclusion Bionic electric stimulation promotes the differentiation of ESCs into cardiomyocyte in a microenvironment consisting of myocardial cells.

  11. Stimulated mast cells promote maturation of myocardial microvascular endothelial cell neovessels by modulating the angiopoietin-Tie-2 signaling pathway

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Z.H. [Division of Cardiology, Shanghai Sixth People' s Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China, Division of Cardiology, Shanghai Sixth People’s Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai (China); Yancheng People' s First Hospital, Division of Cardiology, Yancheng, Jiangsu, China, Division of Cardiology, Yancheng People’s First Hospital, Yancheng, Jiangsu (China); Zhu, W.; Tao, J.P.; Zhang, Q.Y.; Wei, M. [Division of Cardiology, Shanghai Sixth People' s Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China, Division of Cardiology, Shanghai Sixth People’s Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai (China)

    2013-10-22

    Angiopoietin (Ang)-1 and Ang-2 interact in angiogenesis to activate the Tie-2 receptor, which may be involved in new vessel maturation and regression. Mast cells (MCs) are also involved in formation of new blood vessels and angiogenesis. The present study was designed to test whether MCs can mediate angiogenesis in myocardial microvascular endothelial cells (MMVECs). Using a rat MMVEC and MC co-culture system, we observed that Ang-1 protein levels were very low even though its mRNA levels were increased by MCs. Interestingly, MCs were able to enhance migration, proliferation, and capillary-like tube formation, which were associated with suppressed Ang-2 protein expression, but not Tie-2 expression levels. These MCs induced effects that could be reversed by either tryptase inhibitor [N-tosyl-L-lysine chloromethyl ketone (TLCK)] or chymase inhibitor (N-tosyl-L-phenylalanyl chloromethyl ketone), with TLCK showing greater effects. In conclusion, our data indicated that MCs can interrupt neovessel maturation via suppression of the Ang-2/Tie-2 signaling pathway.

  12. Permanently Hypoxic Cell Culture Yields Rat Bone Marrow Mesenchymal Cells with Higher Therapeutic Potential in the Treatment of Chronic Myocardial Infarction

    Directory of Open Access Journals (Sweden)

    Yihua Liu

    2017-11-01

    Full Text Available Background: The mismatch between traditional in vitro cell culture conditions and targeted chronic hypoxic myocardial tissue could potentially hamper the therapeutic effects of implanted bone marrow mesenchymal stem cells (BMSCs. This study sought to address (i the extent of change to BMSC biological characteristics in different in vitro culture conditions and (ii the effectiveness of permanent hypoxic culture for cell therapy in treating chronic myocardial infarction (MI in rats. Methods: rat BMSCs were harvested and cultured in normoxic (21% O2, n=27 or hypoxic conditions (5% O2, n=27 until Passage 4 (P4. Cell growth tests, flow cytometry, and Bio-Plex assays were conducted to explore variations in the cell proliferation, phenotype, and cytokine expression, respectively. In the in vivo set-up, P3-BMSCs cultured in normoxia (n=6 or hypoxia (n=6 were intramyocardially injected into rat hearts that had previously experienced 1-month-old MI. The impact of cell therapy on cardiac segmental viability and hemodynamic performance was assessed 1 month later by 2-Deoxy-2[18F]fluoro-D-glucose (18F-FDG positron emission tomography (PET imaging and pressure-volume catheter, respectively. Additional histomorphological examinations were conducted to evaluate inflammation, fibrosis, and neovascularization. Results: Hypoxic preconditioning significantly enhanced rat BMSC clonogenic potential and proliferation without altering the multipotency. Different profiles of inflammatory, fibrotic, and angiogenic cytokine secretion were also documented, with a marked correlation observed between in vitro and in vivo proangiogenic cytokine expression and tissue neovessels. Hypoxic-preconditioned cells presented a beneficial effect on the myocardial viability of infarct segments and intrinsic contractility. Conclusion: Hypoxic-preconditioned BMSCs were able to benefit myocardial perfusion and contractility, probably by modulating the inflammation and promoting

  13. Permanently Hypoxic Cell Culture Yields Rat Bone Marrow Mesenchymal Cells with Higher Therapeutic Potential in the Treatment of Chronic Myocardial Infarction.

    Science.gov (United States)

    Liu, Yihua; Yang, Xiaoxi; Maureira, Pablo; Falanga, Aude; Marie, Vanessa; Gauchotte, Guillaume; Poussier, Sylvain; Groubatch, Frederique; Marie, Pierre-Yves; Tran, Nguyen

    2017-01-01

    The mismatch between traditional in vitro cell culture conditions and targeted chronic hypoxic myocardial tissue could potentially hamper the therapeutic effects of implanted bone marrow mesenchymal stem cells (BMSCs). This study sought to address (i) the extent of change to BMSC biological characteristics in different in vitro culture conditions and (ii) the effectiveness of permanent hypoxic culture for cell therapy in treating chronic myocardial infarction (MI) in rats. rat BMSCs were harvested and cultured in normoxic (21% O2, n=27) or hypoxic conditions (5% O2, n=27) until Passage 4 (P4). Cell growth tests, flow cytometry, and Bio-Plex assays were conducted to explore variations in the cell proliferation, phenotype, and cytokine expression, respectively. In the in vivo set-up, P3-BMSCs cultured in normoxia (n=6) or hypoxia (n=6) were intramyocardially injected into rat hearts that had previously experienced 1-month-old MI. The impact of cell therapy on cardiac segmental viability and hemodynamic performance was assessed 1 month later by 2-Deoxy-2[18F]fluoro-D-glucose (18F-FDG) positron emission tomography (PET) imaging and pressure-volume catheter, respectively. Additional histomorphological examinations were conducted to evaluate inflammation, fibrosis, and neovascularization. Hypoxic preconditioning significantly enhanced rat BMSC clonogenic potential and proliferation without altering the multipotency. Different profiles of inflammatory, fibrotic, and angiogenic cytokine secretion were also documented, with a marked correlation observed between in vitro and in vivo proangiogenic cytokine expression and tissue neovessels. Hypoxic-preconditioned cells presented a beneficial effect on the myocardial viability of infarct segments and intrinsic contractility. Hypoxic-preconditioned BMSCs were able to benefit myocardial perfusion and contractility, probably by modulating the inflammation and promoting angiogenesis. © 2017 The Author(s). Published by S. Karger AG

  14. Gold nanoparticles induced cloudy swelling to hydropic degeneration, cytoplasmic hyaline vacuolation, polymorphism, binucleation, karyopyknosis, karyolysis, karyorrhexis and necrosis in the liver

    Directory of Open Access Journals (Sweden)

    Jarrar Bashir M

    2011-09-01

    Full Text Available Abstract Background Nanoparticles (NPs can potentially cause adverse effects on organ, tissue, cellular, subcellular and protein levels due to their unusual physicochemical properties. Advances in nanotechnology have identified promising candidates for many biological and biomedical applications. The aim of the present study was to investigate the particle-size, dose and exposure duration effects of gold nanoparticles (GNPs on the hepatic tissue in an attempt to cover and understand the toxicity and their potential therapeutic and diagnostic use. Methods A total of 70 healthy male Wistar-Kyoto rats were exposed to GNPs received 50 or 100 ul of GNPs infusion of size (10, 20 and 50 nm for 3 or 7 days to investigate particle-size, dose and exposure duration effects of GNPs on the hepatic tissue. Results In comparison with respective control rats, exposure to GNPs doses has produced alterations in the hepatocytes, portal triads and the sinusoids. The alterations in the hepatocytes were mainly vacuolar to hydropic degeneration, cytopasmic hyaline vacuolation, polymorphism, binucleation, karyopyknosis, karyolysis, karyorrhexis and necrosis. Conclusions The hepatocytes swelling might be exhibited as a result of disturbances of membranes function that lead to massive influx of water and Na+ due to GNPs effects accompanied by leakage of lysosomal hydrolytic enzymes that lead to cytoplasmic degeneration and macromolecular crowding. Hydropic degeneration is a result of ion and fluid homestasis that lead to an increase of intracellular water. The vacuolated swelling of the cytoplasm of the hepatocytes of the GNPs treated rats might indicate acute and subacute liver injury induced by the GNPs. Binucleation represents a consequence of cell injury and is a sort of chromosomes hyperplasia which is usually seen in regenerating cells. The induced histological alterations might be an indication of injured hepatocytes due to GNPs toxicity that became unable to deal

  15. Cell therapy attenuates cardiac dysfunction post myocardial infarction: effect of timing, routes of injection and a fibrin scaffold.

    Directory of Open Access Journals (Sweden)

    Juliana S Nakamuta

    Full Text Available BACKGROUND: Cell therapy approaches for biologic cardiac repair hold great promises, although basic fundamental issues remain poorly understood. In the present study we examined the effects of timing and routes of administration of bone marrow cells (BMC post-myocardial infarction (MI and the efficacy of an injectable biopolymer scaffold to improve cardiac cell retention and function. METHODOLOGY/PRINCIPAL FINDINGS: (99mTc-labeled BMC (6 x 10(6 cells were injected by 4 different routes in adult rats: intravenous (IV, left ventricular cavity (LV, left ventricular cavity with temporal aorta occlusion (LV(+ to mimic coronary injection, and intramyocardial (IM. The injections were performed 1, 2, 3, or 7 days post-MI and cell retention was estimated by gamma-emission counting of the organs excised 24 hs after cell injection. IM injection improved cell retention and attenuated cardiac dysfunction, whereas IV, LV or LV* routes were somewhat inefficient (<1%. Cardiac BMC retention was not influenced by timing except for the IM injection that showed greater cell retention at 7 (16% vs. 1, 2 or 3 (average of 7% days post-MI. Cardiac cell retention was further improved by an injectable fibrin scaffold at day 3 post-MI (17 vs. 7%, even though morphometric and function parameters evaluated 4 weeks later displayed similar improvements. CONCLUSIONS/SIGNIFICANCE: These results show that cells injected post-MI display comparable tissue distribution profile regardless of the route of injection and that there is no time effect for cardiac cell accumulation for injections performed 1 to 3 days post-MI. As expected the IM injection is the most efficient for cardiac cell retention, it can be further improved by co-injection with a fibrin scaffold and it significantly attenuates cardiac dysfunction evaluated 4 weeks post myocardial infarction. These pharmacokinetic data obtained under similar experimental conditions are essential for further development of these

  16. Impairment of myocardial perfusion in children with sickle cell disease; Alteration de la perfusion myocardique chez l'enfant drepanocytaire

    Energy Technology Data Exchange (ETDEWEB)

    Maunoury, C. [Hopital Necker-Enfants-Malades, Service de Medecine Nucleaire, 75 - Paris (France); Acar, P. [Centre Hospitalier Universitaire, Hopital des Enfants, Service de Cardiologie Pediatrique, 31 - Toulouse (France); Montalembert, M. de [Hopital Necker-Enfants-Malades, Service de Pediatrie Generale, 75 - Paris (France)

    2003-10-01

    While brain, bone and spleen strokes are well documented in children with sickle cell disease (SCD), impairment of myocardial perfusion is an unknown complication. Non invasive techniques such as exercise testing and echocardiography have a low sensitivity to detect myocardial ischemia in patients with SCD. We have prospectively assessed myocardial perfusion with Tl-201 SPECT in 23 patients with SCD (10 female, 13 male, mean age 12 {+-} 5 years). Myocardial SPECT was performed after stress and 3 hours later after reinjection on a single head gamma camera equipped with a LEAP collimator (64 x 64 matrix size format, 30 projections over 180 deg C, 30 seconds per step). Left ventricular ejection fraction (LVEF) was assessed by equilibrium radionuclide angiography at rest on the same day. Myocardial perfusion was impaired in 14/23 patients: 9 reversible defects and 5 fixed defects. The left ventricular cavity was dilated in 14/23 patients. The mean LVEF was 63 {+-} 9%. There was no relationship between myocardial perfusion and left ventricular dilation or function. The frequent impairment of myocardial perfusion in children with SCD could lead to suggest a treatment with hydroxyurea, an improvement of perfusion can be noted with hydroxyurea. (author)

  17. [Quantitative changes in the ultrastructure of myocardial cells in Japanese quail during hypergravity, hypodynamia and space flight].

    Science.gov (United States)

    Bózner, A; Boda, K; Dostál, J; Matĕjková, Z; Devecka, V

    1993-03-01

    The experimental work aimed at the quantitative ultrastructure of the myocardial cells of the Japanese quail Coturnix coturnix japonica during hypergravitation, hypodynamism and space flight in a Soviet satellite. For the determination of quantitative changes of the myocardial ultrastructure a morphometrical method was used with parameters like the number of mitochondria, average mitochondrial size, relative mitochondrial volume, deficiency of cristae and relative volume of myofibrils. The quails were observed in 3 groups. The absolute control consisted of quails living in normal Earth conditions, in the laboratory group the quails were exposed to conditions of hypergravitation and hypodynamism in a specially constructed centrifuge, and in the flying group the quails were exposed to space flight in a Soviet orbital station MIR. In the group of absolute controls no pathological changes of the myocardial ultrastructure were found. In the flying group there were no significant changes, with the exception of decreased relative volume of myofibrils, which however agrees with the findings on symptoms corresponding to human and animal heart weakness during space flights. In the laboratory group, pathological changes were observed in each of the fractions. The most significant pathological findings were found in the group controls in the center and in hypergravitation combined with hypodynamism. It can be concluded that the laboratories can simulate conditions induced by the start and flight of space ships. (Fig. 2, Ref, 8.)

  18. Bone marrow mononuclear cell implantation in myocardial laser channels in the ischemic heart disease surgery. Long-term results

    Science.gov (United States)

    Chernyavskiy, Alexander; Fomichev, Alexey; Minin, Stanislav; Nikitin, Nikita

    2017-10-01

    Background: The problem of incomplete myocardial revascularization for diffuse and distal lesions of the myocardium is still relevant. We assessed the clinical and instrumental long-term results of autologous bone marrow cell (BMC) implantation in laser channels in ischemic heart disease with diffuse and distal coronary disease. 35 coronary heart disease (CHD) patients with diffuse and distal coronary disease during coronary artery bypass grafting (CABG) underwent BMC implantation in laser channels. The control group consisted of 29 patients. All patients in this group underwent only CABG. Clinical and instrumental assessment of the method's effect was carried out at two weeks, six months, and six years after surgery. Indirect revascularization showed more significant decreasing of the functional class (FC) New York Heart Association (NYHA), myocardial perfusion and contractility improvement. Autologous BMC implantation in laser channels is an effective method of CHD surgical treatment if it is impossible to perform direct myocardial revascularization. The indirect revascularization effect is formed in the first six months after surgery and remains at the same level for six years.

  19. Enhanced cell survival and paracrine effects of mesenchymal stem cells overexpressing hepatocyte growth factor promote cardioprotection in myocardial infarction

    International Nuclear Information System (INIS)

    Zhao, Liyan; Liu, Xiaolin; Zhang, Yuelin; Liang, Xiaoting; Ding, Yue; Xu, Yan; Fang, Zhen; Zhang, Fengxiang

    2016-01-01

    Poor cell survival post transplantation compromises the therapeutic benefits of mesenchymal stem cells (MSCs) in myocardial infarction (MI). Hepatocyte growth factor (HGF) is an important cytokine for angiogenesis, anti-inflammation and anti-apoptosis. This study aimed to evaluate the cardioprotective effects of MSCs overexpressing HGF in a mouse model of MI. The apoptosis of umbilical cord-derived MSCs (UC-MSCs) and HGF-UC-MSCs under normoxic and hypoxic conditions was detected. The conditioned medium (CdM) of UC-MSCs and HGF-UC-MSCs under a hypoxic condition was harvested and its protective effect on neonatal cardiomyocytes (NCMs) exposed to a hypoxic challenge was examined. UC-MSCs and HGF-UC-MSCs were transplanted into the peri-infarct region in mice following MI and heart function assessed 4 weeks post transplantation. The apoptosis of HGF-UC-MSCs under hypoxic conditions was markedly decreased compared with that of UC-MSCs. NCMs treated with HGF-UC-MSC hypoxic CdM (HGF-UC-MSCs-hy-CdM) exhibited less cell apoptosis in response to hypoxic challenge than those treated with UC-MSC hypoxic CdM (UC-MSCs-hy-CdM). HGF-UC-MSCs-hy-CdM released the inhibited p-Akt and lowered the enhanced ratio of Bax/Bcl-2 induced by hypoxia in the NCMs. HGF-UC-MSCs-hy-CdM expressed higher levels of HGF, EGF, bFGF and VEGF than UC-MSCs-hy-CdM. Transplantation of HGF-UC-MSCs or UC-MSCs greatly improved heart function in the mouse model of MI. Compared with UC-MSCs, transplantation of HGF-UC-MSCs was associated with less cardiomyocyte apoptosis, enhanced angiogenesis and increased proliferation of cardiomyocytes. This study may provide a novel therapeutic strategy for MSC-based therapy in cardiovascular disease.

  20. Enhanced cell survival and paracrine effects of mesenchymal stem cells overexpressing hepatocyte growth factor promote cardioprotection in myocardial infarction

    Energy Technology Data Exchange (ETDEWEB)

    Zhao, Liyan; Liu, Xiaolin [Section of Pacing and Electrophysiology, Division of Cardiology, the First Affiliated Hospital of Nanjing Medical University, Nanjing (China); Zhang, Yuelin [Cardiology Division, Department of Medicine, Li Ka Shing Faculty of Medicine, the University of Hong Kong, Hong Kong (China); Liang, Xiaoting; Ding, Yue [Pudong District Clinical Translational Medical Research Center, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai (China); Xu, Yan; Fang, Zhen [Section of Pacing and Electrophysiology, Division of Cardiology, the First Affiliated Hospital of Nanjing Medical University, Nanjing (China); Zhang, Fengxiang, E-mail: njzfx6@njmu.edu.cn [Section of Pacing and Electrophysiology, Division of Cardiology, the First Affiliated Hospital of Nanjing Medical University, Nanjing (China)

    2016-05-15

    Poor cell survival post transplantation compromises the therapeutic benefits of mesenchymal stem cells (MSCs) in myocardial infarction (MI). Hepatocyte growth factor (HGF) is an important cytokine for angiogenesis, anti-inflammation and anti-apoptosis. This study aimed to evaluate the cardioprotective effects of MSCs overexpressing HGF in a mouse model of MI. The apoptosis of umbilical cord-derived MSCs (UC-MSCs) and HGF-UC-MSCs under normoxic and hypoxic conditions was detected. The conditioned medium (CdM) of UC-MSCs and HGF-UC-MSCs under a hypoxic condition was harvested and its protective effect on neonatal cardiomyocytes (NCMs) exposed to a hypoxic challenge was examined. UC-MSCs and HGF-UC-MSCs were transplanted into the peri-infarct region in mice following MI and heart function assessed 4 weeks post transplantation. The apoptosis of HGF-UC-MSCs under hypoxic conditions was markedly decreased compared with that of UC-MSCs. NCMs treated with HGF-UC-MSC hypoxic CdM (HGF-UC-MSCs-hy-CdM) exhibited less cell apoptosis in response to hypoxic challenge than those treated with UC-MSC hypoxic CdM (UC-MSCs-hy-CdM). HGF-UC-MSCs-hy-CdM released the inhibited p-Akt and lowered the enhanced ratio of Bax/Bcl-2 induced by hypoxia in the NCMs. HGF-UC-MSCs-hy-CdM expressed higher levels of HGF, EGF, bFGF and VEGF than UC-MSCs-hy-CdM. Transplantation of HGF-UC-MSCs or UC-MSCs greatly improved heart function in the mouse model of MI. Compared with UC-MSCs, transplantation of HGF-UC-MSCs was associated with less cardiomyocyte apoptosis, enhanced angiogenesis and increased proliferation of cardiomyocytes. This study may provide a novel therapeutic strategy for MSC-based therapy in cardiovascular disease.

  1. Overexpression of Cx43 in cells of the myocardial scar: Correction of post-infarct arrhythmias through heterotypic cell-cell coupling.

    Science.gov (United States)

    Roell, Wilhelm; Klein, Alexandra M; Breitbach, Martin; Becker, Torsten S; Parikh, Ashish; Lee, Jane; Zimmermann, Katrin; Reining, Shaun; Gabris, Beth; Ottersbach, Annika; Doran, Robert; Engelbrecht, Britta; Schiffer, Miriam; Kimura, Kenichi; Freitag, Patricia; Carls, Esther; Geisen, Caroline; Duerr, Georg D; Sasse, Philipp; Welz, Armin; Pfeifer, Alexander; Salama, Guy; Kotlikoff, Michael; Fleischmann, Bernd K

    2018-05-08

    Ventricular tachycardia (VT) is the most common and potentially lethal complication following myocardial infarction (MI). Biological correction of the conduction inhomogeneity that underlies re-entry could be a major advance in infarction therapy. As minimal increases in conduction of infarcted tissue markedly influence VT susceptibility, we reasoned that enhanced propagation of the electrical signal between non-excitable cells within a resolving infarct might comprise a simple means to decrease post-infarction arrhythmia risk. We therefore tested lentivirus-mediated delivery of the gap-junction protein Connexin 43 (Cx43) into acute myocardial lesions. Cx43 was expressed in (myo)fibroblasts and CD45 + cells within the scar and provided prominent and long lasting arrhythmia protection in vivo. Optical mapping of Cx43 injected hearts revealed enhanced conduction velocity within the scar, indicating Cx43-mediated electrical coupling between myocytes and (myo)fibroblasts. Thus, Cx43 gene therapy, by direct in vivo transduction of non-cardiomyocytes, comprises a simple and clinically applicable biological therapy that markedly reduces post-infarction VT.

  2. Multipotent human stromal cells improve cardiac function after myocardial infarction in mice without long-term engraftment

    International Nuclear Information System (INIS)

    Iso, Yoshitaka; Spees, Jeffrey L.; Serrano, Claudia; Bakondi, Benjamin; Pochampally, Radhika; Song, Yao-Hua; Sobel, Burton E.; Delafontaine, Patrick; Prockop, Darwin J.

    2007-01-01

    The aim of this study was to determine whether intravenously administered multipotent stromal cells from human bone marrow (hMSCs) can improve cardiac function after myocardial infarction (MI) without long-term engraftment and therefore whether transitory paracrine effects or secreted factors are responsible for the benefit conferred. hMSCs were injected systemically into immunodeficient mice with acute MI. Cardiac function and fibrosis after MI in the hMSC-treated group were significantly improved compared with controls. However, despite the cardiac improvement, there was no evident hMSC engraftment in the heart 3 weeks after MI. Microarray assays and ELISAs demonstrated that multiple protective factors were expressed and secreted from the hMSCs in culture. Factors secreted by hMSCs prevented cell death of cultured cardiomyocytes and endothelial cells under conditions that mimicked tissue ischemia. The favorable effects of hMSCs appear to reflect the impact of secreted factors rather than engraftment, differentiation, or cell fusion

  3. Design and synthesis of binucleating macrocyclic clefts derived from Schiff-base calixpyrroles.

    Science.gov (United States)

    Givaja, Gonzalo; Volpe, Manuel; Leeland, James W; Edwards, Michael A; Young, Thomas K; Darby, S Barnie; Reid, Stuart D; Blake, Alexander J; Wilson, Claire; Wolowska, Joanna; McInnes, Eric J L; Schröder, Martin; Love, Jason B

    2007-01-01

    The syntheses, characterisation and complexation reactions of a series of binucleating Schiff-base calixpyrrole macrocycles are described. The acid-templated [2+2] condensations between meso-disubstituted diformyldipyrromethanes and o-phenylenediamines generate the Schiff-base pyrrolic macrocycles H(4)L(1) to H(4)L(6) upon basic workup. The single-crystal X-ray structures of both H(4)L(3).2 EtOH and H(4)L(6).H2O confirm that [2+2] cyclisation has occurred, with either EtOH or H2O hydrogen-bonded within the macrocyclic cleft. A series of complexation reactions generate the dipalladium [Pd2(L)] (L=L(1) to L(5)), dinickel [Ni2(L(1))] and dicopper [Cu2(L)] (L=L(1) to L(3)) complexes. All of these complexes have been structurally characterised in the solid state and are found to adopt wedged structures that are enforced by the rigidity of the aryl backbone to give a cleft reminiscent of the structures of Pacman porphyrins. The binuclear nickel complexes [Ni2(mu-OMe)2Cl2(HOMe)2(H(4)L(1))] and [Ni2(mu-OH)2Cl2(HOMe)(H(4)L(5))] have also been prepared, although in these cases the solid-state structures show that the macrocyclic ligand remains protonated at the pyrrolic nitrogen atoms, and the Ni(II) cations are therefore co-ordinated by the imine nitrogen atoms only to give an open conformation for the complex. The dicopper complex [Cu2(L(3))] was crystallised in the presence of pyridine to form the adduct [Cu2(py)(L(3))], in which, in the solid state, the pyridine ligand is bound within the binuclear molecular cleft. Reaction between H(4)L(1) and [Mn(thf){N(SiMe(3))2}2] results in clean formation of the dimanganese complex [Mn2(L(1))], which, upon crystallisation, formed the mixed-valent complex [Mn2(mu-OH)(L(1))] in which the hydroxo ligand bridges the metal centres within the molecular cleft.

  4. Assessment of human MAPCs for stem cell transplantation and cardiac regeneration after myocardial infarction in SCID mice.

    Science.gov (United States)

    Dimomeletis, Ilias; Deindl, Elisabeth; Zaruba, Marc; Groebner, Michael; Zahler, Stefan; Laslo, Saskia M; David, Robert; Kostin, Sawa; Deutsch, Markus A; Assmann, Gerd; Mueller-Hoecker, Josef; Feuring-Buske, Michaela; Franz, Wolfgang M

    2010-11-01

    Clinical studies suggest that transplantation of total bone marrow (BM) after myocardial infarction (MI) is feasible and potentially effective. However, focusing on a defined BM-derived stem cell type may enable a more specific and optimized treatment. Multilineage differentiation potential makes BM-derived multipotent adult progenitor cells (MAPCs) a promising stem cell pool for regenerative purposes. We analyzed the cardioregenerative potential of human MAPCs in a murine model of myocardial infarction. Human MAPCs were selected by negative depletion of CD45(+)/glycophorin(+) BM cells and plated on fibronectin-coated dishes. In vitro, stem cells were analyzed by reverse transcription polymerase chain reaction. In vivo, we transplanted human MAPCs (5 × 10(5)) by intramyocardial injection after MI in severe combined immunodeficient (SCID) beige mice. Six and 30 days after the surgical procedure, pressure-volume relationships were investigated in vivo. Heart tissues were analyzed immunohistochemically. Reverse transcription polymerase chain reaction experiments on early human MAPC passages evidenced an expression of Oct-4, a stem cell marker indicating pluripotency. In later passages, cardiac markers (Nkx2.5, GATA4, MLC-2v, MLC-2a, ANP, cTnT, cTnI,) and smooth muscle cell markers (SMA, SM22α) were expressed. Transplantation of human MAPCs into the ischemic border zone after MI resulted in an improved cardiac function at day 6 (ejection fraction, 26% vs 20%) and day 30 (ejection fraction, 30% vs 23%). Confirmation of human MAPC marker vimentin in immunohistochemistry demonstrated that human MAPC integrated in the peri-infarct region. The proliferation marker Ki67 was absent in immunohistochemistry and teratoma formation was not found, indicating no tumorous potential of transplanted human MAPCs in the tumor-sensitive SCID model. Transplantation of human MAPCs after MI ameliorates myocardial function, which may be explained by trophic effects of human MAPCs. Lack of

  5. Effects of different components of serum after radiation, burn and combined radiation-burn injury on inward rectifier potassium channel of myocardial cells

    International Nuclear Information System (INIS)

    Ye Benlan; Cheng Tianmin; Xiao Jiasi

    1997-01-01

    Objective: To study the effects of different components of serum in rats inflicted with radiation, burn and combined radiation-burn injury on inward rectifier potassium channel of cultured myocardial cells. Method: Using patch clamp method to study the action of single ion channel. Results: The low molecular and lipid components of serum after different injuries models could all activate the inward rectifier potassium channel in cultured myocardial cells. The components of serum after combined radiation-burn injury showed the most significant effect, and the way of this effect was different from that from single injury. Conclusion: The serum components post injury altered the electric characteristic of myocardial cells, which may play a role in the combined effect of depressed cardiac function after combined radiation-burn injury

  6. Assessment of the metabolic effects of the ionophore grisorixin on myocardial cells in culture with 14-C-labelled substrates

    International Nuclear Information System (INIS)

    Maublant, J.C.; Gachon, P.; Ross, M.R.; Davidson, W.D.; Mena, I.

    1984-01-01

    Cultures of myocardial cells were utilized to verify the hypothesis that the ionophore grisorixin could facilitate the anaerobic and impair the aerobic metabolism in the myocardium. This was suggested by previous experiments in which the authors found an increase in the cardiac work without increase in the oxygen consumption, while the myocardial uptake of 123-Iodo-hexadecenoic acid was decreased. Tissue cultures were prepared by trypsinization of the myocardium of two to four-day old newborn mice. The cultures were incubated with 14-C-glucose (n=10), 14-C-octanoate (n=14) or 14-C-acetate (n=12). Except for the controls (n=19), they also received 1 μg/ml of an alcoholic solution of grisorixin or 200 μl of 60% alcohol. The cultures were then placed in a circuit with a closed circulation of air which passed through a vibrating reed electrometer for detection of the beta radiations of the 14-CO/sub 2/ liberated by the 14-C labelled substrates. The activity was permanently recorded for measurements of the rate of consumption of these substrates. Compared to the control values, the metabolic rate with grisorixin was significantly decreased for octanoate (77 +- 22 vs 169 +- 62 rho mole/min/mg prot, rho<0.01) and acetate (2.7 +- 1.0 vs 6.0 +- 1.3 rho mole/min/mg prot, rho<0.01). The results for glucose were 1.05 +- 0.24 vs 0.88 +- 0.24 n mole/min/mg prot, (rho<0.10). Alcohol alone produced no significant effect except on the octanoate consumption. These results provide direct evidence that grisorixin favors the anaerobic pathway in the metabolism of the myocardial cells

  7. Myocardial Bridging

    Directory of Open Access Journals (Sweden)

    Shi-Min Yuan

    2016-02-01

    Full Text Available Abstract Myocardial bridging is rare. Myocardial bridges are most commonly localized in the middle segment of the left anterior descending coronary artery. The anatomic features of the bridges vary significantly. Alterations of the endothelial morphology and the vasoactive agents impact on the progression of atherosclerosis of myocardial bridging. Patients may present with chest pain, myocardial infarction, arrhythmia and even sudden death. Patients who respond poorly to the medical treatment with β-blockers warrant a surgical intervention. Myotomy is a preferred surgical procedure for the symptomatic patients. Coronary stent deployment has been in limited use due to the unsatisfactory long-term results.

  8. CD8+ T-Cells Count in Acute Myocardial Infarction in HIV Disease in a Predominantly Male Cohort

    Directory of Open Access Journals (Sweden)

    Oluwatosin A. Badejo

    2015-01-01

    Full Text Available Human Immunodeficiency Virus- (HIV- infected persons have a higher risk for acute myocardial infarction (AMI than HIV-uninfected persons. Earlier studies suggest that HIV viral load, CD4+ T-cell count, and antiretroviral therapy are associated with cardiovascular disease (CVD risk. Whether CD8+ T-cell count is associated with CVD risk is not clear. We investigated the association between CD8+ T-cell count and incident AMI in a cohort of 73,398 people (of which 97.3% were men enrolled in the U.S. Veterans Aging Cohort Study-Virtual Cohort (VACS-VC. Compared to uninfected people, HIV-infected people with high baseline CD8+ T-cell counts (>1065 cells/mm3 had increased AMI risk (adjusted HR=1.82, P<0.001, 95% CI: 1.46 to 2.28. There was evidence that the effect of CD8+ T-cell tertiles on AMI risk differed by CD4+ T-cell level: compared to uninfected people, HIV-infected people with CD4+ T-cell counts ≥200 cells/mm3 had increased AMI risk with high CD8+ T-cell count, while those with CD4+ T-cell counts <200 cells/mm3 had increased AMI risk with low CD8+ T-cell count. CD8+ T-cell counts may add additional AMI risk stratification information beyond that provided by CD4+ T-cell counts alone.

  9. Clinical utility of labeled cells for detection of allograft rejection and myocardial infarction

    International Nuclear Information System (INIS)

    Fawwaz, R.A.

    1984-01-01

    The choice of a specific radiolabeled blood component for use in detection of allograft rejection depends on several factors including the immunosuppressive agents used, the type of organ allografted, and particularly the length of time the allograft resides in the host and the duration of rejection. To date, only the use of 111In-labeled platelets in renal allograft recipients immunosuppressed with azathioprine and corticosteroids has shown clinical promise in the detection of early allograft rejection. Radiolabeled blood components are unlikely to play a significant role in detection of myocardial infarction. The use of these agents for monitoring therapeutic interventions or as indicators of prognosis in patients with myocardial infarction continues to be investigated

  10. Imaging long-term fate of intramyocardially implanted mesenchymal stem cells in a porcine myocardial infarction model.

    Directory of Open Access Journals (Sweden)

    Emerson C Perin

    Full Text Available The long-term fate of stem cells after intramyocardial delivery is unknown. We used noninvasive, repetitive PET/CT imaging with [(18F]FEAU to monitor the long-term (up to 5 months spatial-temporal dynamics of MSCs retrovirally transduced with the sr39HSV1-tk gene (sr39HSV1-tk-MSC and implanted intramyocardially in pigs with induced acute myocardial infarction. Repetitive [(18F]FEAU PET/CT revealed a biphasic pattern of sr39HSV1-tk-MSC dynamics; cell proliferation peaked at 33-35 days after injection, in periinfarct regions and the major cardiac lymphatic vessels and lymph nodes. The sr39HSV1-tk-MSC-associated [(18F]FEAU signals gradually decreased thereafter. Cardiac lymphography studies using PG-Gd-NIRF813 contrast for MRI and near-infrared fluorescence imaging showed rapid clearance of the contrast from the site of intramyocardial injection through the subepicardial lymphatic network into the lymphatic vessels and periaortic lymph nodes. Immunohistochemical analysis of cardiac tissue obtained at 35 and 150 days demonstrated several types of sr39HSV1-tk expressing cells, including fibro-myoblasts, lymphovascular cells, and microvascular and arterial endothelium. In summary, this study demonstrated the feasibility and sensitivity of [(18F]FEAU PET/CT imaging for long-term, in-vivo monitoring (up to 5 months of the fate of intramyocardially injected sr39HSV1-tk-MSC cells. Intramyocardially transplanted MSCs appear to integrate into the lymphatic endothelium and may help improve myocardial lymphatic system function after MI.

  11. Comparison of parathyroid hormone and G-CSF treatment after myocardial infarction on perfusion and stem cell homing.

    Science.gov (United States)

    Huber, Bruno C; Fischer, Rebekka; Brunner, Stefan; Groebner, Michael; Rischpler, Christoph; Segeth, Alexander; Zaruba, Marc M; Wollenweber, Tim; Hacker, Marcus; Franz, Wolfgang-Michael

    2010-05-01

    Mobilization of stem cells by granulocyte colony-stimulating factor (G-CSF) was shown to have protective effects after myocardial infarction (MI); however, clinical trials failed to be effective. In search for alternative cytokines, parathyroid hormone (PTH) was recently shown to promote cardiac repair by enhanced neovascularization and cell survival. To compare the impact of the two cytokines G-CSF and PTH on myocardial perfusion, mice were noninvasively and repetitively investigated by pinhole single-photon emission computed tomography (SPECT) after MI. Mobilization and homing of bone marrow-derived stem cells (BMCs) was analyzed by fluorescence-activated cell sorter (FACS) analysis. Mice (C57BL/6J) were infarcted by left anterior descending artery ligation. PTH (80 mug/kg) and G-CSF (100 mug/kg) were injected for 5 days. Perfusion defects were determined by (99m)Tc-sestamibi SPECT at days 6 and 30 after MI. The number of BMCs characterized by Lin(-)/Sca-1(+)/c-kit(+) cells in peripheral blood and heart was analyzed by FACS. Both G-CSF and PTH treatment resulted in an augmented mobilization of BMCs in the peripheral blood. Contrary to G-CSF and controls, PTH and the combination showed significant migration of BMCs in ischemic myocardium associated with a significant reduction of perfusion defects from day 6 to day 30. A combination of both cytokines had no additional effects on migration and perfusion. In our preclinical model, SPECT analyses revealed the functional potential of PTH reducing size of infarction together with an enhanced homing of BMCs to the myocardium in contrast to G-CSF. A combination of both cytokines did not improve the functional outcome, suggesting clinical applications of PTH in ischemic heart diseases.

  12. The interactive association between heat shock factor 1 and heat shock proteins in primary myocardial cells subjected to heat stress.

    Science.gov (United States)

    Tang, Shu; Chen, Hongbo; Cheng, Yanfen; Nasir, Mohammad Abdel; Kemper, Nicole; Bao, Endong

    2016-01-01

    Heat shock factor 1 (HSF1) is a heat shock transcription factor that rapidly induces heat shock gene transcription following thermal stress. In this study, we subjected primary neonatal rat myocardial cells to heat stress in vitro to create a model system for investigating the trends in expression and association between various heat shock proteins (HSPs) and HSF1 under adverse environmental conditions. After the cells were subjected to heat stress at 42˚C for different periods of time, HSP and HSF1 mRNA and protein levels were detected by qPCR and western blot analysis in the heat-stressed cells. The HSF1 expression levels significantly increased in the cells following 120 min of exposure to heat stess compared to the levels observed at the beginning of heat stress exposure. HSP90 followed a similar trend in expression to HSF1, whereas HSP70 followed an opposite trend. However, no significant changes were observed in the crystallin, alpha B (CRYAB, also known as HSP beta-5) expression levels during the 480‑min period of exposure to heat stress. The interaction between the HSPs and HSF1 was analyzed by STRING 9.1, and it was found that HSF1 interacted with HSP90 and HSP70, and that it did not play a role in regulating CRYAB expression. Based on our findings, HSP70 may suppress HSF1 in rat myocardial cells under conditions of heat stress. Furthermore, our data demonstrate that HSF1 is not the key factor for all HSPs, and this was particularly the case for CRYAB.

  13. Consideration of myocardial FDG uptake in differentiation of mediastinal lymph node of non-small cell lung cancer

    International Nuclear Information System (INIS)

    Eo, Jae Seon; Lee, Won Woo; Chung, Jin Haeng; So, Young; Lee, Dong Soo; Chung, June Key; Lee, Myung Chul; Kim, Sang Eun

    2004-01-01

    The whole body FDG PET suffers from poor diagnostic competency in differentiation of mediastinal lymph node (LN) in non-small cell lung cancer. In addition to LN FDG uptake. We considered myocardial FDG uptake in mediastinal lymph node staging. Thirty-nine non-small cell lung cancer patients (male: female = 32: 7, age = 63±11 years) who underwent preoperative whole body FDG PET were enrolled. There were 18 squamous cell cancer, 13 adenocarcinoma, and 8 others. Maximum standard uptake values (maxSUVs) of myocardium and LNs using lean body weight were measured and compared with pathological results. Among 187 LNs which were confirmed postoperatively, 31 were malignant, and 156 benign. Of 31 malignant LNs, only 11 were visible on FDG PET (sensitivity : 35.5% = 11/31) but majority of 20 nonvisible metastatic LNs had relevant cause of false negative (11 peribroncheal, 3 mucine producing adenocarcinoma, or 6 low amount of tumor cells). Of 156 benign LNs, 137 were nonvisible (specificity : 87.8% 137/156) and 19 visible. Under subgroup analysis of 30 visible LNs on whole body FDG PET (11 malignant, and 19 benign), maxSUV of myocardium (p = 0.020) as well as maxSUV of LN (p = 0.002) were significant predictor of malignant LN in multivariate analysis. Using the ROC curve, a cut-off value of LN maxSUV > 2.4 provided sensitivity of 81.8% and specificity of 63.2% (AUC 0.775, 95% confidence interval = 0.586 to 0.906). Meanwhile, the composite criterion of LN maxSUV plus square root of myocardial maxSUV > 4.65 provided slightly improved diagnostic competencies (sensitivity 90.9%, specificity 84.2%, AUC 0.876, 95% confidence interval 0.704 to 0.966) (p = 0.08). Taking into consideration myocardial FDG uptake may improve the diagnostic competency of whole body FDG PET in differentiation of mediastinal LNs of non-small cell lung cancer

  14. Effect of everolimus initiation and early calcineurin inhibitor withdrawal on myocardial FOXP3+ regulatory T cells in heart transplantation

    DEFF Research Database (Denmark)

    Mirza, Kiran; Gustafsson, Finn; Gullestad, Lars

    2016-01-01

    BACKGROUND: Through immunosuppression CD4+FoxP3+ regulatory T-cells (Tregs) play an indispensable role in allograft rejection. Post-HTx treatment with everolimus is associated with slower progression of cardiac allograft vasculopathy (CAV) - chronic rejection - than CNI based therapy. We hypothes......BACKGROUND: Through immunosuppression CD4+FoxP3+ regulatory T-cells (Tregs) play an indispensable role in allograft rejection. Post-HTx treatment with everolimus is associated with slower progression of cardiac allograft vasculopathy (CAV) - chronic rejection - than CNI based therapy. We...... hypothesized treatment with everolimus reduced the risk of CAV by modulating myocardial FoxP3 levels. METHODS: 15 patients from the Schedule trial comparing everolimus, MMF, steroid and early CNI (Everolimus, n=8) withdrawal to conventional CNI based immunosuppression (Controls, n=7) after de novo HTx were...

  15. The C60-Fullerene Porphyrin Adducts for Prevention of the Doxorubicin-Induced Acute Cardiotoxicity in Rat Myocardial Cells

    Directory of Open Access Journals (Sweden)

    Seyed Vahid Shetab Boushehri

    2010-10-01

    Full Text Available This is a fullerene-based low toxic nanocationite designed for targeted delivery of the paramagnetic stable isotope of magnesium to the doxorubicin (DXR-induced damaged heart muscle providing a prominent effect close to about 80% recovery of the tissue hypoxia symptoms in less than 24 hrs after a single injection (0.03 - 0.1 LD50. Magnesium magnetic isotope effect selectively stimulates the ATP formation in the oxygen-depleted cells due to a creatine kinase (CK and mitochondrial respiratory chain-focusing "attack" of 25Mg2+ released by nanoparticles. These "smart nanoparticles" with membranotropic properties release the overactivating cations only in response to the intracellular acidosis. The resulting positive changes in the energy metabolism of heart cell may help to prevent local myocardial hypoxic (ischemic disorders and, hence, to protect the heart muscle from a serious damage in a vast variety of the hypoxia-induced clinical situations including DXR side effects.

  16. Lipid lowering and HDL raising gene transfer increase endothelial progenitor cells, enhance myocardial vascularity, and improve diastolic function.

    Directory of Open Access Journals (Sweden)

    Stephanie C Gordts

    Full Text Available BACKGROUND: Hypercholesterolemia and low high density lipoprotein (HDL cholesterol contribute to coronary heart disease but little is known about their direct effects on myocardial function. Low HDL and raised non-HDL cholesterol levels carried increased risk for heart failure development in the Framingham study, independent of any association with myocardial infarction. The objective of this study was to test the hypothesis that increased endothelial progenitor cell (EPC number and function after lipid lowering or HDL raising gene transfer in C57BL/6 low density lipoprotein receptor deficient (LDLr(-/- mice may be associated with an enhanced relative vascularity in the myocardium and an improved cardiac function. METHODOLOGY/PRINCIPAL FINDINGS: Lipid lowering and HDL raising gene transfer were performed using the E1E3E4-deleted LDLr expressing adenoviral vector AdLDLr and the human apolipoprotein A-I expressing vector AdA-I, respectively. AdLDLr transfer in C57BL/6 LDLr(-/- mice resulted in a 2.0-fold (p<0.05 increase of the circulating number of EPCs and in an improvement of EPC function as assessed by ex vivo EPC migration and EPC adhesion. Capillary density and relative vascularity in the myocardium were 28% (p<0.01 and 22% (p<0.05 higher, respectively, in AdLDLr mice compared to control mice. The peak rate of isovolumetric relaxation was increased by 12% (p<0.05 and the time constant of isovolumetric relaxation was decreased by 14% (p<0.05 after AdLDLr transfer. Similarly, HDL raising gene transfer increased EPC number and function and raised both capillary density and relative vascularity in the myocardium by 24% (p<0.05. The peak rate of isovolumetric relaxation was increased by 16% (p<0.05 in AdA-I mice compared to control mice. CONCLUSIONS/SIGNIFICANCE: Both lipid lowering and HDL raising gene transfer have beneficial effects on EPC biology, relative myocardial vascularity, and diastolic function. These findings raise concerns over the

  17. Human adipose stem cell and ASC-derived cardiac progenitor cellular therapy improves outcomes in a murine model of myocardial infarction

    Directory of Open Access Journals (Sweden)

    Davy PMC

    2015-10-01

    Full Text Available Philip MC Davy,1 Kevin D Lye,2,3 Juanita Mathews,1 Jesse B Owens,1 Alice Y Chow,1 Livingston Wong,2 Stefan Moisyadi,1 Richard C Allsopp1 1Institute for Biogenesis Research, 2John A. Burns School of Medicine, University of Hawaii at Mānoa, 3Tissue Genesis, Inc., Honolulu, HI, USA Background: Adipose tissue is an abundant and potent source of adult stem cells for transplant therapy. In this study, we present our findings on the potential application of adipose-derived stem cells (ASCs as well as induced cardiac-like progenitors (iCPs derived from ASCs for the treatment of myocardial infarction. Methods and results: Human bone marrow (BM-derived stem cells, ASCs, and iCPs generated from ASCs using three defined cardiac lineage transcription factors were assessed in an immune-compromised mouse myocardial infarction model. Analysis of iCP prior to transplant confirmed changes in gene and protein expression consistent with a cardiac phenotype. Endpoint analysis was performed 1 month posttransplant. Significantly increased endpoint fractional shortening, as well as reduction in the infarct area at risk, was observed in recipients of iCPs as compared to the other recipient cohorts. Both recipients of iCPs and ASCs presented higher myocardial capillary densities than either recipients of BM-derived stem cells or the control cohort. Furthermore, mice receiving iCPs had a significantly higher cardiac retention of transplanted cells than all other groups. Conclusion: Overall, iCPs generated from ASCs outperform BM-derived stem cells and ASCs in facilitating recovery from induced myocardial infarction in mice. Keywords: adipose stem cells, myocardial infarction, cellular reprogramming, cellular therapy, piggyBac, induced cardiac-like progenitors

  18. Design and implementation of the TRACIA: intracoronary autologous transplant of bone marrow-derived stem cells for acute ST elevation myocardial infarction

    OpenAIRE

    Peña-Duque, Marco A.; Martínez-Ríos, Marco A.; Calderón G, Eva; Mejía, Ana M.; Gómez, Enrique; Martínez-Sánchez, Carlos; Figueroa, Javier; Gaspar, Jorge; González, Héctor; Bialoztosky, David; Meave, Aloha; Uribe-González, Jhonathan; Alexánderson, Erick; Ochoa, Victor; Masso, Felipe

    2011-01-01

    Objective: To describe the design of a protocol of intracoronary autologous transplant of bone marrow-derived stem cells for acute ST-elevation myocardial infarction (STEMI) and to report the safety of the procedure in the first patients included. Methods: The TRACIA study was implemented following predetermined inclusion and exclusion criteria. The protocol includes procedures such as randomization, bone marrow retrieval, stem cells processing, intracoronary infusion of stem cells in the inf...

  19. Glutamine reduces myocardial cell apoptosis in a rat model of sepsis by promoting expression of heat shock protein 90.

    Science.gov (United States)

    Li, Wanxia; Tao, Shaoyu; Wu, Qinghua; Wu, Tao; Tao, Ran; Fan, Jun

    2017-12-01

    Myocardial cell injury and cardiac myocyte apoptosis are associated with sepsis. Glutamine (Gln) has been reported to repair myocardial cell injury. The aim of this study was to explore the role of Gln on cardiac myocytes in a cecal ligation and puncture (CLP) model of sepsis in Wistar rats. Following induction of sepsis in a CLP rat model, viral encoding heat shock protein 90 (Hsp90) gene and Hsp90dsDNA were designed to express and knockdown Hsp90, respectively. Rat cardiac tissues were examined histologically, and apoptosis was detected by terminal deoxynucleotidyl transferase dUTP nick end labeling staining. The expression of B-cell lymphoma-2 (Bcl-2), Bcl-2-associated X protein, Hsp90, p53 upregulated modulator of apoptosis, and p53 was measured by western blotting and real-time polymerase chain reaction. Caspase-3, caspase-8, and caspase-9 were detected by enzyme-linked immunosorbent assay. Rat cardiac myocyte damage induced by CLP was reduced by Gln treatment and Hsp90 overexpression, and these changes were reversed by Hsp90 knockdown. Bcl-2 expression, Bcl-2-associated X protein, p53, p53 upregulated modulator of apoptosis, caspase-8, caspase-9, and caspase-3 activities were significantly upregulated in the CLP model, which were reduced by Gln treatment and Hsp90 overexpression. Gln reduced apoptosis of cardiac myocytes in a rat model of sepsis, by promoting Hsp90 expression. Further studies are needed to determine the possible therapeutic action of Gln in sepsis in human tissue. Copyright © 2017 Elsevier Inc. All rights reserved.

  20. Intracoronary infusion of autologous mononuclear bone marrow cells in patients with acute myocardial infarction treated with primary PCI : Pilot study of the multicenter HEBE trial

    NARCIS (Netherlands)

    Hirsch, Alexander; Nijveldt, Robin; van der Vleuten, Pieter A.; Tio, Rene A.; van der Giessen, Willem J.; Marques, Koen M. J.; Doevendans, Pieter A.; Waltenberger, Johannes; ten Berg, Jurrien M.; Aengevaeren, Wim R. M.; Biemond, Bart J.; Tijssen, Jan G. P.; van Rossum, Albert C.; Piek, Jan J.; Zijlstra, Felix

    2008-01-01

    Objective: This study was a pilot trial to determine safety and feasibility of intracoronary infusion of mononuclear bone marrow cells (MBMC) in patients with acute myocardial infarction (MI). Background: Studies reporting the effect of MBMC therapy on improvement of left ventricular (LV) function

  1. Induction of a monocyte/macrophage phenotype switch by mesenchymal stem cells might contribute to improved infarct healing postacute myocardial infarction

    NARCIS (Netherlands)

    ter Horst, E. N.; Naaijkens, B. A.; Krijnen, P. A.; van der Laan, A. M.; Piek, J. J.; Niessen, H. W.

    2013-01-01

    Inadequate healing following acute myocardial infarction (AMI) can lead to the development of heart failure. The ischemic myocardium triggers an inflammatory response that clears cell debris and initiates the onset of scar tissue formation. The duration and intensity of this inflammatory response

  2. Plant-based foods containing cell wall polysaccharides rich in specific active monosaccharides protect against myocardial injury in rat myocardial infarction models

    OpenAIRE

    Sun Ha Lim; Yaesil Kim; Ki Na Yun; Jin Young Kim; Jung-Hee Jang; Mee-Jung Han; Jongwon Lee

    2016-01-01

    Many cohort studies have shown that consumption of diets containing a higher composition of foods derived from plants reduces mortality from coronary heart disease (CHD). Here, we examined the active components of a plant-based diet and the underlying mechanisms that reduce the risk of CHD using three rat models and a quantitative proteomics approach. In a short-term myocardial infarction (MI) model, intake of wheat extract (WE), the representative cardioprotectant identified by screening app...

  3. Impact of conditioning hyperglycemic on myocardial infarction rats: Cardiac cell survival factors

    Science.gov (United States)

    Malfitano, Christiane; de Souza Junior, Alcione Lescano; Irigoyen, Maria Cláudia

    2014-01-01

    While clinical data have suggested that the diabetic heart is more susceptible to ischemic heart disease (IHD), animal data have so far pointed to a lower probability of IHD. Thus, the aim of this present review is to look at these conflicting results and discuss the protective mechanisms that conditioned hyperglycemia may confer to the heart against ischemic injury. Several mechanisms have been proposed to explain the cardioprotective action of high glucose exposure, namely, up-regulation of anti-apoptotic factor Bcl-2, inactivation of pro-apoptotic factor bad, and activation of pro-survival factors such as protein kinase B (Akt), vascular endothelial growth factor (VEGF), hypoxia inducible factor-1α and protein kinase C-ε. Indeed, cytosolic increase in Ca2+ concentration, the mitochondrial permeability transition pore, plays a key role in the genesis of ischemic injury. Previous studies have shown that the diabetic heart decreased Na+/Ca2+ and Na+/H+ exchanger activity and as such it accumulates less Ca2+ in cardiomyocyte, thus preventing cardiac injury and the associated heart dysfunctions. In addition, the expression of VEGF in diabetic animals leads to increased capillary density before myocardial infarction. Despite poor prognostic in the long-term, all these results suggest that diabetes mellitus and consequently hyperglycemia may indeed play a cardioprotective role against myocardial infarction in the short term. PMID:24976917

  4. Can the outcomes of mesenchymal stem cell-based therapy for myocardial infarction be improved? Providing weapons and armour to cells.

    Science.gov (United States)

    Karpov, Andrey A; Udalova, Daria V; Pliss, Michael G; Galagudza, Michael M

    2017-04-01

    Use of mesenchymal stem cell (MSC) transplantation after myocardial infarction (MI) has been found to have infarct-limiting effects in numerous experimental and clinical studies. However, recent meta-analyses of randomized clinical trials on MSC-based MI therapy have highlighted the need for improving its efficacy. There are two principal approaches for increasing therapeutic effect of MSCs: (i) preventing massive MSC death in ischaemic tissue and (ii) increasing production of cardioreparative growth factors and cytokines with transplanted MSCs. In this review, we aim to integrate our current understanding of genetic approaches that are used for modification of MSCs to enable their improved survival, engraftment, integration, proliferation and differentiation in the ischaemic heart. Genetic modification of MSCs resulting in increased secretion of paracrine factors has also been discussed. In addition, data on MSC preconditioning with physical, chemical and pharmacological factors prior to transplantation are summarized. MSC seeding on three-dimensional polymeric scaffolds facilitates formation of both intercellular connections and contacts between cells and the extracellular matrix, thereby enhancing cell viability and function. Use of genetic and non-genetic approaches to modify MSC function holds great promise for regenerative therapy of myocardial ischaemic injury. © 2016 John Wiley & Sons Ltd.

  5. Omentum-derived stromal cells improve myocardial regeneration in pig post-infarcted heart through a potent paracrine mechanism

    Energy Technology Data Exchange (ETDEWEB)

    De Siena, Rocco; Balducci, Luigi; Blasi, Antonella; Montanaro, Manuela Gessica; Saldarelli, Marilisa [Medestea Research and Production Laboratories, Consorzio Carso, 70010 Valenzano, Bari (Italy); Saponaro, Vittorio [Department of Veterinary Medicine, University of Bari, 70010 Valenzano, Bari (Italy); Martino, Carmela [Medestea Research and Production Laboratories, Consorzio Carso, 70010 Valenzano, Bari (Italy); Logrieco, Gaetano [Department of Surgery, Hospital ' F. Miulli' 70021 AcquaViva delle Fonti, Bari (Italy); Soleti, Antonio; Fiobellot, Simona [Medestea Research and Production Laboratories, Consorzio Carso, 70010 Valenzano, Bari (Italy); Madeddu, Paolo [Experimental Cardiovascular Medicine, Bristol Heart Institute, Bristol BS2 8WH (United Kingdom); Rossi, Giacomo [Department of Pathology, University of Camerino, 63100 Ascoli Piceno (Italy); Ribatti, Domenico [Department of Human Anatomy, University of Bari, 70125 Bari (Italy); Crovace, Antonio [Department of Veterinary Medicine, University of Bari, 70010 Valenzano, Bari (Italy); Cristini, Silvia; Invernici, Gloria; Parati, Eugenio Agostino [Cellular Neurobiology Laboratory, Department of Cerebrovascular Diseases, Fondazione IRCCS Neurological Institute ' Carlo Besta' , 20133 Milan (Italy); Alessandri, Giulio, E-mail: cisiamo2@yahoo.com [Cellular Neurobiology Laboratory, Department of Cerebrovascular Diseases, Fondazione IRCCS Neurological Institute ' Carlo Besta' , 20133 Milan (Italy)

    2010-07-01

    Cell-based therapy could be a valid option to treat myocardial infarct (MI). Adipose-derived stromal cells (ADStCs) have demonstrated tissue regenerative potential including cardiomyogenesis. Omentum is an extremely rich source of visceral fat and its accumulation seems to correlate with cardiovascular diseases. We investigated the capacity of human fat Omentum-derived StCs (FOStCs) to affect heart function upon acute infarct in pigs induced by permanent ligation of the anterior interventricular artery (IVA). We demonstrated for the first time that the local injection of 50 x 10{sup 6} of FOStCs ameliorates the functional parameters of post-infarct heart. Most importantly, histology of FOStCs treated hearts demonstrated a substantial improvement of cardiomyogenesis. In culture, FOStCs produced an impressive number and amount of angiogenic factors and cytokines. Moreover, the conditioned medium of FOStCs (FOStCs-CM) stimulates in vitro cardiac endothelial cells (ECs) proliferation and vascular morphogenesis and inhibits monocytes, EC activation and cardiomyocyte apoptosis. Since FOStCs in vivo did not trans-differentiate into cardiomyocyte-like cells, we conclude that FOStCs efficacy was presumably mediated by a potent paracrine mechanism involving molecules that concomitantly improved angiogenesis, reduced inflammation and prevented cardiomyocytes death. Our results highlight for the first time the important role that human FOStCs may have in cardiac regeneration.

  6. Myocardial infarction

    International Nuclear Information System (INIS)

    Ando, Jyoji; Yasuda, Hisakazu; Miyamoto, Atsushi; Kobayashi, Tsuyoshi

    1980-01-01

    sup(99m)Tc-pyrophosphate (PYP) scintigraphy and 201 Tl myocardial scintigraphy were utilized for the diagnoses of the presence, the region, and the extent of myocardial infarction. Exercise 201 Tl myocardial scintigrams and exercise radionuclide ventriculography were utilized for diagnosis of coronary artery lesions in angina pectoris. Radionuclide ventriculography was used to investigate effects of coronary artery lesions on cardiac function and hemodynamics. In order to select adequate treatments for myocardial infarction and estimate the prognosis, it was necessary to detect the presence, the region, and the extent of acute myocardial infarction and to investigate effects of partial infarction on hemodynamics by using radionuclide imaging. Exercise myocardial scintigraphy could be carried out noninvasively and repeatedly for diagnosis of coronal artery disease. Therefore, this method could be applied widely. It was possible to use this method as a screening test of coronary artery diseases for the diagnoses of asymptomatic patients who showed ST changes in ECG, the patients with cardiac neurosis and the patency after a reconstructive surgery of coronary artery. (Tsunoda, M.)

  7. G-CSF treatment after myocardial infarction: impact on bone marrow-derived vs cardiac progenitor cells.

    Science.gov (United States)

    Brunner, Stefan; Huber, Bruno C; Fischer, Rebekka; Groebner, Michael; Hacker, Marcus; David, Robert; Zaruba, Marc-Michael; Vallaster, Marcus; Rischpler, Christoph; Wilke, Andrea; Gerbitz, Armin; Franz, Wolfgang-Michael

    2008-06-01

    Besides its classical function in the field of autologous and allogenic stem cell transplantation, granulocyte colony-stimulating factor (G-CSF) was shown to have protective effects after myocardial infarction (MI) by mobilization of bone marrow-derived progenitor cells (BMCs) and in addition by activation of multiple signaling pathways. In the present study, we focused on the impact of G-CSF on migration of BMCs and the impact on resident cardiac cells after MI. Mice (C57BL/6J) were sublethally irradiated, and BM from green fluorescent protein (GFP)-transgenic mice was transplanted. Coronary artery ligation was performed 10 weeks later. G-CSF (100 microg/kg) was daily injected for 6 days. Subpopulations of enhanced GFP(+) cells in peripheral blood, bone marrow, and heart were characterized by flow cytometry. Growth factor expression in the heart was analyzed by quantitative real-time polymerase chain reaction. Perfusion was investigated in vivo by gated single photon emission computed tomography (SPECT). G-CSF-treated animals revealed a reduced migration of c-kit(+) and CXCR-4(+) BMCs associated with decreased expression levels of the corresponding growth factors, namely stem cell factor and stromal-derived factor-1 alpha in ischemic myocardium. In contrast, the number of resident cardiac Sca-1(+) cells was significantly increased. However, SPECT-perfusion showed no differences in infarct size between G-CSF-treated and control animals 6 days after MI. Our study shows that G-CSF treatment after MI reduces migration capacity of BMCs into ischemic tissue, but increases the number of resident cardiac cells. To optimize homing capacity a combination of G-CSF with other agents may optimize cytokine therapy after MI.

  8. hHO-1 combined with GATA-4 transduction promotes myocardial transdifferentiation and anti- apoptosis of rat mesenchymal stem cells

    Directory of Open Access Journals (Sweden)

    Ning-bo DENG

    2017-06-01

    Full Text Available Objectives To explore if the rat bone marrow mesenchymal stem cells (BMSCs modified by human heme oxygenase 1 (hHO-1 gene combined with GATA-4 gene may promote the ability of anti-apoptosis and myocardial transdifferentiation in vitro in hypoxia ischemic environment. Methods The rat BMSCs were isolated and cultured by whole bone marrow adherence and identified in vitro, and then were transfected with recombinant adenovirus; Western blotting was used to determinate the optimal time of gene expression; the genetically modified BMSCs were taken to hypoxia serum-free conditions simulating ischemia hypoxia microenvironment in vivo; CCK-8 kit and trypan blue staining were performed to detect the 12, 24, 48 and 72h survival rates in hypoxia ischemia respectively; flow cytometry was used to detect the apoptosis of BMSCs in hypoxia ischemia for 24h. The cardiomyocyte-specific cardiac troponin I (cTnI was detected by Western blotting and cellular immunofluorescence. Results The 12, 24, 48 and 72h survival rates were higher in hHO-1+GATA-4 group cultured in ischemia and hypoxia condition than in hHO-1 group (P<0.05 and GATA-4 group (P<0.05. After 24h cultivation in ischemia hypoxia condition, the apoptotic rates were lower in hHO-1+GATA-4 group than in hHO-1 group (P<0.05 and GATA-4 group (P<0.05. No significant difference existed in cTnI expressions between GATA-4 group and hHO-1+GATA-4 group. Conclusion Compared with transfection of hHO-1 or GATA-4 single gene, hHO-1 combined with GATA-4 transduction can significantly increase the survival rate of BMSCs in hypoxia ischemic condition, but myocardial transdifferentiation does not increase significantly. DOI: 10.11855/j.issn.0577-7402.2017.04.08

  9. Improvement of myocardial perfusion reserve detected by cardiovascular magnetic resonance after direct endomyocardial implantation of autologous bone marrow cells in patients with severe coronary artery disease

    Directory of Open Access Journals (Sweden)

    Lau Chu-Pak

    2010-01-01

    Full Text Available Abstract Background Recent studies suggested that bone marrow (BM cell implantation in patients with severe chronic coronary artery disease (CAD resulted in modest improvement in symptoms and cardiac function. This study sought to investigate the functional changes that occur within the chronic human ischaemic myocardium after direct endomyocardial BM cells implantation by cardiovascular magnetic resonance (CMR. Methods and Results We compared the interval changes of left ventricular ejection fraction (LVEF, myocardial perfusion reserve and the extent of myocardial scar by using late gadolinium enhancement CMR in 12 patients with severe CAD. CMR was performed at baseline and at 6 months after catheter-based direct endomyocardial autologous BM cell (n = 12 injection to viable ischaemic myocardium as guided by electromechanical mapping. In patients randomized to receive BM cell injection, there was significant decrease in percentage area of peri-infarct regions (-23.6%, P = 0.04 and increase in global LVEF (+9.0%, P = 0.02, the percentage of regional wall thickening (+13.1%, P= 0.04 and MPR (+0.25%, P = 0.03 over the target area at 6-months compared with baseline. Conclusions Direct endomyocardial implantation of autologous BM cells significantly improved global LVEF, regional wall thickening and myocardial perfusion reserve, and reduced percentage area of peri-infarct regions in patients with severe CAD.

  10. Retention and Functional Effect of Adipose-Derived Stromal Cells Administered in Alginate Hydrogel in a Rat Model of Acute Myocardial Infarction

    Directory of Open Access Journals (Sweden)

    Bjarke Follin

    2018-01-01

    Full Text Available Background. Cell therapy for heart disease has been proven safe and efficacious, despite poor cell retention in the injected area. Improving cell retention is hypothesized to increase the treatment effect. In the present study, human adipose-derived stromal cells (ASCs were delivered in an in situ forming alginate hydrogel following acute myocardial infarction (AMI in rats. Methods. ASCs were transduced with luciferase and tested for ASC phenotype. AMI was inducted in nude rats, with subsequent injection of saline (controls, 1 × 106 ASCs in saline or 1 × 106 ASCs in 1% (w/v alginate hydrogel. ASCs were tracked by bioluminescence and functional measurements were assessed by magnetic resonance imaging (MRI and 82rubidium positron emission tomography (PET. Results. ASCs in both saline and alginate hydrogel significantly increased the ejection fraction (7.2% and 7.8% at 14 days and 7.2% and 8.0% at 28 days, resp.. After 28 days, there was a tendency for decreased infarct area and increased perfusion, compared to controls. No significant differences were observed between ASCs in saline or alginate hydrogel, in terms of retention and functional salvage. Conclusion. ASCs improved the myocardial function after AMI, but administration in the alginate hydrogel did not further improve retention of the cells or myocardial function.

  11. Comparison of the Cytotoxic Potential of Cigarette Smoke and Electronic Cigarette Vapour Extract on Cultured Myocardial Cells

    Directory of Open Access Journals (Sweden)

    Dimitris Tsiapras

    2013-10-01

    Full Text Available Background: Electronic cigarettes (ECs have been marketed as an alternative-to-smoking habit. Besides chemical studies of the content of EC liquids or vapour, little research has been conducted on their in vitro effects. Smoking is an important risk factor for cardiovascular disease and cigarette smoke (CS has well-established cytotoxic effects on myocardial cells. The purpose of this study was to evaluate the cytotoxic potential of the vapour of 20 EC liquid samples and a “base” liquid sample (50% glycerol and 50% propylene glycol, with no nicotine or flavourings on cultured myocardial cells. Included were 4 samples produced by using cured tobacco leaves in order to extract the tobacco flavour. Methods: Cytotoxicity was tested according to the ISO 10993-5 standard. By activating an EC device at 3.7 volts (6.2 watts—all samples, including the “base” liquid and at 4.5 volts (9.2 watts—four randomly selected samples, 200 mg of liquid evaporated and was extracted in 20 mL of culture medium. Cigarette smoke (CS extract from three tobacco cigarettes was produced according to ISO 3308 method (2 s puffs of 35 mL volume, one puff every 60 s. The extracts, undiluted (100% and in four dilutions (50%, 25%, 12.5%, and 6.25%, were applied to myocardial cells (H9c2; percent-viability was measured after 24 h incubation. According to ISO 10993-5, viability of 6.25% (viability: 76.9 ± 2.0% at 6.25%, 38.2 ± 0.5% at 12.5%, 3.1 ± 0.2% at 25%, 5.2 ± 0.8% at 50%, and 3.9 ± 0.2% at 100% extract concentration. Three EC extracts (produced by tobacco leaves were cytotoxic at 100% and 50% extract concentrations (viability range: 2.2%–39.1% and 7.4%–66.9% respectively and one (“Cinnamon-Cookies” flavour was cytotoxic at 100% concentration only (viability: 64.8 ± 2.5%. Inhibitory concentration 50 was >3 times lower in CS extract compared to the worst-performing EC vapour extract. For EC extracts produced by high-voltage and energy, viability was

  12. Myocardial scintigraphy

    International Nuclear Information System (INIS)

    Bunko, Hisashi; Hisada, Kinichi

    1982-01-01

    Among the various methods of image diagnosis of the cardiovascular disorder, nuclear cardiology provides noninvasive means for evaluation of myocardial perfusion as well as morphological and functional informations. In this article, clinical application and image diagnosis of myocardial scintigraphy including Tl-201 myocardial perfusion scintigraphy, single photon emission computed tomography with Tl-201, acute myocardial infarction scintigraphy with Tc-99m-pyrophosphate and Ga-67 imaging of the heart, were discussed. Multiplanar imaging of the heart with Tl-201 after stress and at redistribution was the accepted method for detection and evaluation of the ischemic heart disease. Although it achieved high sensitivity and specificity for ischemic heart disease, detection of the small ischemia and quantation of the regional Tl-201 accumulation were difficult with conventional multiplanar imaging. Application of emission computed tomography improved detectability and quantitativity of the ischemia. However, 7-pinhole tomography did not increase the diagnostic accuracy significantly. It had limited clinical applicability due to poor quantitativity in spite of improved image contrast and its tomographic nature. Advantage and limitation of these tomographic imaging and multiplanar imaging were discussed. Problems and prognostic significance of pyrophosphate imaging of the acute myocardial infarction were also discussed. Visualization of the heart with Ga-67 was helpful for identification of the tumor or inflammation of the heart as well as evaluation of the effect of the therapy. (author)

  13. Adult Bone Marrow Mesenchymal Stem Cells Primed for fhe Repair of Damaged Cardiac Tissue After Myocardial Infarction

    Science.gov (United States)

    Marks, Edward D.

    The burden of cardiovascular disease around the world is growing, despite improvements in hospital care and time to treatment. As more people survive an initial myocardial infarction (MI), the decompensated heart tissue is strained, leading to heart failure (HF) and an increased risk for a second MI. While extensive progress has been made in treating the symptoms after MI, including HF and angina, little success has come from repairing the damaged heart tissue to alleviate the progression to these end- stage symptoms. One promising area of regenerative research has been the use of adult stem cells, particularly from the bone marrow (BMSCs). These cells can differentiate towards the cardiac cell lineage in vitro while producing trophic factors that can repair damaged tissue. When placed in the heart after MI though, BMSCs have mixed results, producing profound changes in some patients but zero or even negative effects in others. In this report, we used BMSCs as a stem cell base for a regenerative medicine system for the repair of damaged cardiac tissue. These cells are seeded on a polycaprolactone nanoscaffolding support system, which provides a growth substrate for in vitro work, as well as a housing system for protected in vivo delivery. When the nanoscaffold is pre-coated with a novel combination of a cardiac protein, thymosin beta4 (Tbeta4), and a small molecule effector of the WNT protein pathway, IWP-2, BMSCs differentiated towards the cardiac lineage in as little as 24hours. When injected into rat hearts that have been given an ischemic MI, the nanoscaffolding system slowly dissolves, leaving the cells in place of the damaged cardiac tissue. After two weeks of monitoring, BMSCs are present within the damaged hearts, as evidenced by immunofluorescence and nanoparticle tracking. Injections of the nanoscaffolding/cell system led to robust healing of the rat hearts that had been given small- and medium- damage heart attacks, outperforming PBS sham and cell

  14. Acute myocardial infarction

    International Nuclear Information System (INIS)

    RISCHPLER, Christoph

    2016-01-01

    Inflammatory processes after myocardial infarction have gained major interest in recent cardiovascular research. It is believed that not only the degree of cell recruitment to the heart plays a pivotal role in the quality of wound healing after myocardial infarction, but also the balance between different types or even subtypes of cells. It is also this balance which is thought to control key processes in tissue repair, such as apoptosis and neoangiogenesis. In this paper, we aim to review imaging strategies (with a special focus on nuclear molecular imaging strategies) that target cells and processes involved in postischemic inflammation and that have a high potential to be translated into clinic or that are already being used and evaluated in humans.

  15. Human Umbilical Cord-Derived Mesenchymal Stromal Cells Improve Left Ventricular Function, Perfusion, and Remodeling in a Porcine Model of Chronic Myocardial Ischemia

    Science.gov (United States)

    Liu, Chuan-Bin; Huang, He; Sun, Ping; Ma, Shi-Ze; Liu, An-Heng; Xue, Jian; Fu, Jin-Hui; Liang, Yu-Qian; Liu, Bing; Wu, Dong-Ying

    2016-01-01

    Stem cell therapy has emerged as a new strategy for treatment of ischemic heart disease. Although umbilical cord-derived mesenchymal stromal cells (UC-MSCs) have been used preferentially in the acute ischemia model, data for the chronic ischemia model are lacking. In this study, we investigated the effect of UC-MSCs originated from Wharton’s jelly in the treatment of chronic myocardial ischemia in a porcine model induced by ameroid constrictor. Four weeks after ameroid constrictor placement, the surviving animals were divided randomly into two groups to undergo saline injection (n = 6) or UC-MSC transplantation (n = 6) through the left main coronary artery. Two additional intravenous administrations of UC-MSCs were performed in the following 2 weeks to enhance therapeutic effect. Cardiac function and perfusion were examined just before and at 4 weeks after intracoronary transplantation. The results showed that pigs with UC-MSC transplantation exhibited significantly greater left ventricular ejection fraction compared with control animals (61.3% ± 1.3% vs. 50.3% ± 2.0%, p UC-MSC treatment improves left ventricular function, perfusion, and remodeling in a porcine model with chronic myocardial ischemia. Significance Ischemic heart disease is the leading cause of death worldwide. Many patients with chronic myocardial ischemia are not suitable for surgery and have no effective drug treatment; they are called “no-option” patients. This study finds that umbilical cord-derived mesenchymal stromal cells transplanted by intracoronary delivery combined with two intravenous administrations was safe and could significantly improve left ventricular function, perfusion, and remodeling in a large-animal model of chronic myocardial ischemia, which provides a new choice for the no-option patients. In addition, this study used clinical-grade mesenchymal stem cells with delivery and assessment methods commonly used clinically to facilitate further clinical transformation. PMID

  16. Progenitor/stem cell transplantation for repair of myocardial infarction: Hype or hope?

    OpenAIRE

    Feng, Yuliang; Wang, Yuhua; Cao, Nan; Yang, Huangtian; Wang, Yigang

    2012-01-01

    Despite significant therapeutic advances, heart failure remains the predominant cause of mortality worldwide. Currently, progenitor/stem cell biology holds great promise for a new era of cell-based therapy for salvaging the failing heart. However, the translational arm of progenitor/stem cell science is in a relatively primitive state. For the time being, the clinical trials have been both encouraging and disappointing. How to improve the engraftment, long-term survival and appropriate differ...

  17. Fractalkine levels are elevated early after PCI-treated ST-elevation myocardial infarction; no influence of autologous bone marrow derived stem cell injection.

    Science.gov (United States)

    Njerve, Ida Unhammer; Solheim, Svein; Lunde, Ketil; Hoffmann, Pavel; Arnesen, Harald; Seljeflot, Ingebjørg

    2014-09-01

    Fractalkine (CX3CL1) is a chemokine associated with atherosclerosis and inflammation. There is limited knowledge of fractalkine levels during acute myocardial infarction (AMI) and stem cell treatment. We aimed to investigate the time profile of circulating fractalkine and gene expression of its receptor CX3CR1 during AMI, and the influence of intracoronary autologous bone marrow stem cell (mBMC) transplantation (given 6 days after AMI) on fractalkine levels. We examined fractalkine levels at different time points by enzyme-linked immunosorbent assay (ELISA) in 20 patients with AMI, and 10 patients with stable angina pectoris (AP) undergoing percutaneous coronary intervention (PCI), and in 100 patients included in the randomized Autologous Stem-Cell Transplantation in Acute Myocardial Infarction (ASTAMI) trial. Patients with AMI had significantly elevated levels 3- and 12 h after PCI compared to patients with stable AP. After 12 h levels were similar in the two groups. An inverse pattern was observed in gene expression levels. No correlation between fractalkine levels and myocardial injury or infarct size was seen. We could not demonstrate any influence of autologous mBMC transplantation on fractalkine levels. Fractalkine levels are elevated the first 12 h after PCI in patients with AMI, however, not correlated to infarct size. The inverse pattern in gene expression of fractalkine receptor (CX3CR1) might be a compensatory mechanism. No effect of autologous mBMC transplantation given 6 days after AMI on fractalkine levels was observed. Copyright © 2014 Elsevier Ltd. All rights reserved.

  18. Discrepant Results of Experimental Human Mesenchymal Stromal Cell Therapy after Myocardial Infarction: Are Animal Models Robust Enough?

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    Melina C den Haan

    Full Text Available Human mesenchymal stromal cells (MSCs have been reported to preserve cardiac function in myocardial infarction (MI models. Previously, we found a beneficial effect of intramyocardial injection of unstimulated human MSCs (uMSCs on cardiac function after permanent coronary artery ligation. In the present study we aimed to extend this research by investigating the effect of intramyocardial injection of human MSCs pre-stimulated with the pro-inflammatory cytokine interferon-gamma (iMSCs, since pro-inflammatory priming has shown additional salutary effects in multiple experimental disease models.MI was induced in NOD/Scid mice by permanent ligation of the left anterior descending coronary artery. Animals received intramyocardial injection of uMSCs, iMSCs or PBS. Sham-operated animals were used to determine baseline characteristics. Cardiac performance was assessed after 2 and 14 days using 7-Tesla magnetic resonance imaging and pressure-volume loop measurements. Histology and q-PCR were used to confirm MSC engraftment in the heart.Both uMSC and iMSC therapy had no significant beneficial effect on cardiac function or remodelling in contrast to our previous studies.Animal models for cardiac MSC therapy appear less robust than initially envisioned.

  19. Exercise training-induced different improvement profile of endothelial progenitor cells function in mice with or without myocardial infarction.

    Science.gov (United States)

    Guo, Yuan; Peng, Ran; Liu, Qiong; Xu, Danyan

    2016-10-15

    Neovascularization in response to ischemia after myocardial infarction (MI) has been widely considered as being initiated by endothelial progenitor cells (EPCs). Well-documented evidences in recent years have proved exercise training (ET) improving EPC function. However, whether ET-induced improvement of EPC function under or without ischemic state is different has not been reported. Mice performed ET following an exercise prescription 1week after MI or non-MI surgery respectively. Bone marrow-derived EPCs were isolated at 0day, 3days, 1week, 2weeks, 4weeks, and 8weeks of ET. After 7days cultivation, EPC functions including proliferation, adhesion, migration, and in vitro angiogenesis were measured. AKT/glycogen synthase kinase 3β (GSK3β) signaling pathway was tested by western blotting. EPC function in mice underwent non-MI surgery was attenuated overtime, while ET ameliorated this tendency. EPC function was peaked at 4weeks ET in non-MI surgery mice and maintained with an extended exercise time. Besides, simple ischemia was sufficient to enhanced EPC function, with a maximum at 2weeks of MI surgery. In MI mice, ET further improved EPC function and achieved peak at 2weeks exercise. Furthermore, AKT/GSK3β signaling pathway activation was consistent with EPC function change after ischemia, which was further promoted by 4weeks exercise. ET significantly increased EPC function in mice both with and without MI, but the time points of peak function were different. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  20. Apelin enhances cardiac neovascularization after myocardial infarction by recruiting aplnr+ circulating cells

    NARCIS (Netherlands)

    Tempel, D.; de Boer, M.; van Deel, E.D.; Haasdijk, R.A.; Duncker, D.J.G.M.; Cheng, C.; Schulte-Merker, S.; Duckers, H.J.

    2012-01-01

    RATIONALE: Neovascularization stimulated by local or recruited stem cells after ischemia is a key process that salvages damaged tissue and shows similarities with embryonic vascularization. Apelin receptor (Aplnr) and its endogenous ligand apelin play an important role in cardiovascular development.

  1. Apelin Enhances Cardiac Neovascularization After Myocardial Infarction By Recruiting Aplnr+ Circulating Cells

    NARCIS (Netherlands)

    Tempel, D.; Boer, de M.; Deel, van E.D.; Haasdijk, A.; Duncker, D.J.; Cheng, C.; Schulte-Merker, S.; Duckers, H.J.

    2012-01-01

    Rationale: Neovascularization stimulated by local or recruited stem cells after ischemia is a key process that salvages damaged tissue and shows similarities with embryonic vascularization. Apelin receptor (Aplnr) and its endogenous ligand apelin play an important role in cardiovascular development.

  2. The Influence of Autologous Bone Marrow Stem Cell Transplantation on Matrix Metalloproteinases in Patients Treated for Acute ST-Elevation Myocardial Infarction

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    Eline Bredal Furenes

    2014-01-01

    Full Text Available Background. Matrix metalloproteinase-9 (MMP-9, regulated by tissue inhibitor of metalloproteinase-9 (TIMP-1 and the extracellular matrix metalloproteinase inducer (EMMPRIN, contributes to plaque instability. Autologous stem cells from bone marrow (mBMC treatment are suggested to reduce myocardial damage; however, limited data exists on the influence of mBMC on MMPs. Aim. We investigated the influence of mBMC on circulating levels of MMP-9, TIMP-1, and EMMPRIN at different time points in patients included in the randomized Autologous Stem-Cell Transplantation in Acute Myocardial Infarction (ASTAMI trial (n=100. Gene expression analyses were additionally performed. Results. After 2-3 weeks we observed a more pronounced increase in MMP-9 levels in the mBMC group, compared to controls (P=0.030, whereas EMMPRIN levels were reduced from baseline to 2-3 weeks and 3 months in both groups (P<0.0001. Gene expression of both MMP-9 and EMMPRIN was reduced from baseline to 3 months. MMP-9 and EMMPRIN were significantly correlated to myocardial injury (CK: P=0.005 and P<0.001, resp. and infarct size (SPECT: P=0.018 and P=0.008, resp.. Conclusion. The results indicate that the regulation of metalloproteinases is important during AMI, however, limited influenced by mBMC.

  3. Cell tracking and therapy evaluation of bone marrow monocytes and stromal cells using SPECT and CMR in a canine model of myocardial infarction

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    Merrifield Peter

    2009-04-01

    Full Text Available Abstract Background The clinical application of stem cell therapy for myocardial infarction will require the development of methods to monitor treatment and pre-clinical assessment in a large animal model, to determine its effectiveness and the optimum cell population, route of delivery, timing, and flow milieu. Objectives To establish a model for a in vivo tracking to monitor cell engraftment after autologous transplantation and b concurrent measurement of infarct evolution and remodeling. Methods We evaluated 22 dogs (8 sham controls, 7 treated with autologous bone marrow monocytes, and 7 with stromal cells using both imaging of 111Indium-tropolone labeled cells and late gadolinium enhancement CMR for up to12 weeks after a 3 hour coronary occlusion. Hearts were also examined using immunohistochemistry for capillary density and presence of PKH26 labeled cells. Results In vivo Indium imaging demonstrated an effective biological clearance half-life from the injection site of ~5 days. CMR demonstrated a pattern of progressive infarct shrinkage over 12 weeks, ranging from 67–88% of baseline values with monocytes producing a significant treatment effect. Relative infarct shrinkage was similar through to 6 weeks in all groups, following which the treatment effect was manifest. There was a trend towards an increase in capillary density with cell treatment. Conclusion This multi-modality approach will allow determination of the success and persistence of engraftment, and a correlation of this with infarct size shrinkage, regional function, and left ventricular remodeling. There were overall no major treatment effects with this particular model of transplantation immediately post-infarct.

  4. Sca-1+ cardiosphere-derived cells are enriched for Isl1-expressing cardiac precursors and improve cardiac function after myocardial injury.

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    Jianqin Ye

    Full Text Available BACKGROUND: Endogenous cardiac progenitor cells are a promising option for cell-therapy for myocardial infarction (MI. However, obtaining adequate numbers of cardiac progenitors after MI remains a challenge. Cardiospheres (CSs have been proposed to have cardiac regenerative properties; however, their cellular composition and how they may be influenced by the tissue milieu remains unclear. METHODOLOGY/PRINCIPAL FINDING: Using "middle aged" mice as CSs donors, we found that acute MI induced a dramatic increase in the number of CSs in a mouse model of MI, and this increase was attenuated back to baseline over time. We also observed that CSs from post-MI hearts engrafted in ischemic myocardium induced angiogenesis and restored cardiac function. To determine the role of Sca-1(+CD45(- cells within CSs, we cloned these from single cell isolates. Expression of Islet-1 (Isl1 in Sca-1(+CD45(- cells from CSs was 3-fold higher than in whole CSs. Cloned Sca-1(+CD45(- cells had the ability to differentiate into cardiomyocytes, endothelial cells and smooth muscle cells in vitro. We also observed that cloned cells engrafted in ischemic myocardium induced angiogenesis, differentiated into endothelial and smooth muscle cells and improved cardiac function in post-MI hearts. CONCLUSIONS/SIGNIFICANCE: These studies demonstrate that cloned Sca-1(+CD45(- cells derived from CSs from infarcted "middle aged" hearts are enriched for second heart field (i.e., Isl-1(+ precursors that give rise to both myocardial and vascular tissues, and may be an appropriate source of progenitor cells for autologous cell-therapy post-MI.

  5. Effects of sildenafil and/or muscle derived stem cells on myocardial infarction

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    Wang Judy SC

    2012-08-01

    Full Text Available Abstract Background Previous studies have shown that long-term oral daily PDE 5 inhibitors (PDE5i counteract fibrosis, cell loss, and the resulting dysfunction in tissues of various rat organs and that implantation of skeletal muscle-derived stem cells (MDSC exerts some of these effects. PDE5i and stem cells in combination were found to be more effective in non-MI cardiac repair than each treatment separately. We have now investigated whether sildenafil at lower doses and MDSC, alone or in combination are effective to attenuate LV remodeling after MI in rats. Methods MI was induced in rats by ligature of the left anterior descending coronary artery. Treatment groups were: “Series A”: 1 untreated; 2 oral sildenafil 3 mg/kg/day from day 1; and “Series B”: intracardiac injection at day 7 of: 3 saline; 4 rat MDSC (106 cells; 5 as #4, with sildenafil as in #2. Before surgery, and at 1 and 4 weeks, the left ventricle ejection fraction (LVEF was measured. LV sections were stained for collagen, myofibroblasts, apoptosis, cardiomyocytes, and iNOS, followed by quantitative image analysis. Western blots estimated angiogenesis and myofibroblast accumulation, as well as potential sildenafil tachyphylaxis by PDE 5 expression. Zymography estimated MMPs 2 and 9 in serum. Results As compared to untreated MI rats, sildenafil improved LVEF, reduced collagen, myofibroblasts, and circulating MMPs, and increased cardiac troponin T. MDSC replicated most of these effects and stimulated cardiac angiogenesis. Concurrent MDSC/sildenafil counteracted cardiomyocyte and endothelial cells loss, but did not improve LVEF or angiogenesis, and upregulated PDE 5. Conclusions Long-term oral sildenafil, or MDSC given separately, reduce the MI fibrotic scar and improve left ventricular function in this rat model. The failure of the treatment combination may be due to inducing overexpression of PDE5.

  6. Cardiac Bmi1(+) cells contribute to myocardial renewal in the murine adult heart.

    Science.gov (United States)

    Valiente-Alandi, Iñigo; Albo-Castellanos, Carmen; Herrero, Diego; Arza, Elvira; Garcia-Gomez, Maria; Segovia, José C; Capecchi, Mario; Bernad, Antonio

    2015-10-26

    The mammalian adult heart maintains a continuous, low cardiomyocyte turnover rate throughout life. Although many cardiac stem cell populations have been studied, the natural source for homeostatic repair has not yet been defined. The Polycomb protein BMI1 is the most representative marker of mouse adult stem cell systems. We have evaluated the relevance and role of cardiac Bmi1 (+) cells in cardiac physiological homeostasis. Bmi1 (CreER/+);Rosa26 (YFP/+) (Bmi1-YFP) mice were used for lineage tracing strategy. After tamoxifen (TM) induction, yellow fluorescent protein (YFP) is expressed under the control of Rosa26 regulatory sequences in Bmi1 (+) cells. These cells and their progeny were tracked by FACS, immunofluorescence and RT-qPCR techniques from 5 days to 1 year. FACS analysis of non-cardiomyocyte compartment from TM-induced Bmi1-YFP mice showed a Bmi1 (+)-expressing cardiac progenitor cell (Bmi1-CPC: B-CPC) population, SCA-1 antigen-positive (95.9 ± 0.4 %) that expresses some stemness-associated genes. B-CPC were also able to differentiate in vitro to the three main cardiac lineages. Pulse-chase analysis showed that B-CPC remained quite stable for extended periods (up to 1 year), which suggests that this Bmi1 (+) population contains cardiac progenitors with substantial self-maintenance potential. Specific immunostaining of Bmi1-YFP hearts serial sections 5 days post-TM induction indicated broad distribution of B-CPC, which were detected in variably sized clusters, although no YFP(+) cardiomyocytes (CM) were detected at this time. Between 2 to 12 months after TM induction, YFP(+) CM were clearly identified (3 ± 0.6 % to 6.7 ± 1.3 %) by immunohistochemistry of serial sections and by flow cytometry of total freshly isolated CM. B-CPC also contributed to endothelial and smooth muscle (SM) lineages in vivo. High Bmi1 expression identifies a non-cardiomyocyte resident cardiac population (B-CPC) that contributes to the main lineages of the heart in

  7. Effect of hypoxia on thallium kinetics in cultured chick myocardial cells

    International Nuclear Information System (INIS)

    Friedman, B.J.; Beihn, R.; Friedman, J.P.

    1987-01-01

    To assess the effect of hypoxia on cellular thallium-201 ( 201 Tl) uptake and washout independent of coronary flow, we studied thallium kinetics during normoxia and hypoxia in cultured chick ventricular cells. Monolayers of contracting ventricular cells grown on coverslips were placed in a chamber and perfused to asymptote with media containing 201 Tl. Perfusates were equilibrated with 5% CO 2 -95% air or 5% CO 2 -95% nitrogen for normoxia and hypoxia, respectively. Washout thallium kinetics were then observed during perfusion with unlabeled media. Twenty paired experiments were performed, randomly alternating the sequence of normoxia and hypoxia. Pharmacokinetics for thallium were determined by computer using standard formulae. Thallium uptake and washout were best described by assuming that intracellular thallium was contained within a single compartment. Cellular thallium uptake, as well as transfer rate constants for thallium uptake and for thallium washout during normoxia and hypoxia, were compared using paired t-tests. During normoxia and hypoxia, respectively, thallium uptake was 22 +/- 7% and 19 +/- 7% of asymptote (p less than 0.01); the compartmental rate constant for uptake by the cell was 0.16 +/- 0.07 min-1 and 0.15 +/- 0.06 min-1 (N.S.); and the transfer rate constant for washout from the cell was 0.26 +/- 0.06 min-1 and 0.23 +/- 0.05 min-1 (p less than 0.01). We conclude that there was a small (14%) decrease in thallium uptake during hypoxia. The rate of thallium uptake and washout was slightly less during hypoxia, although only the rate of washout was significantly less. These data show that cellular accumulation of thallium and the rate of washout of thallium were minimally decreased by hypoxia independent of blood flow

  8. In vitro three-dimensional coculturing poly3-hydroxybutyrate-co-3-hydroxyhexanoate with mouse-induced pluripotent stem cells for myocardial patch application.

    Science.gov (United States)

    Shijun, Xu; Junsheng, Mu; Jianqun, Zhang; Ping, Bo

    2016-03-01

    Identifying a suitable polymeric biomaterial for myocardial patch repair following myocardial infarction, cerebral infarction, and cartilage injury is essential. This study aimed to investigate the effect of the novel polymer material, poly3-hydroxybutyrate-co-3-hydroxyhexanoate, on the adhesion, proliferation, and differentiation of mouse-induced pluripotent stem cells in vitro. Mouse-induced pluripotent stem cells were isolated, expanded, and cultured on either two-dimensional or three-dimensional poly3-hydroxybutyrate-co-3-hydroxyhexanoate films (membranes were perforated to imitate three-dimensional space). Following attachment onto the films, mouse-induced pluripotent stem cell morphology was visualized using scanning electron microscopy. Cell vitality was detected using the Cell Counting Kit-8 assay and cell proliferation was observed using fluorescent 4',6-diamidino-2-phenylindole (DAPI) staining. Mouse-induced pluripotent stem cells were induced into cardiomyocytes by differentiation medium containing vitamin C. A control group in the absence of an inducer was included. Mouse-induced pluripotent stem cell survival and differentiation were observed using immunofluorescence and flow cytometry, respectively. Mouse-induced pluripotent stem cells growth, proliferation, and differentiation were observed on both two-dimensional and three-dimensional poly3-hydroxybutyrate-co-3-hydroxyhexanoate films. Vitamin C markedly improved the efficiency of mouse-induced pluripotent stem cells differentiation into cardiomyocytes on poly3-hydroxybutyrate-co-3-hydroxyhexanoate films. Three-dimensional culture was better at promoting mouse-induced pluripotent stem cell proliferation and differentiation compared with two-dimensional culture. © The Author(s) 2016.

  9. Suicide gene reveals the myocardial neovascularization role of mesenchymal stem cells overexpressing CXCR4 (MSC(CXCR4.

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    Jialiang Liang

    Full Text Available BACKGROUND: Our previous studies indicated that MSC(CXCR4 improved cardiac function after myocardial infarction (MI. This study was aimed to investigate the specific role of MSC(CXCR4 in neovascularization of infarcted myocardium using a suicide gene approach. METHODS: MSCs were transduced with either lentivirus-null vector/GFP (MSC(Null as control or vector encoding for overexpressing CXCR4/GFP. The MSC derived-endothelial cell (EC differentiation was assessed by a tube formation assay, Dil-ac-LDL uptake, EC marker expression, and VE-cadherin promoter activity assay. Gene expression was analyzed by quantitative RT-PCR or Western blot. The suicide gene approach was under the control of VE-cadherin promoter. In vivo studies: Cell patches containing MSC(Null or MSC(CXCR4 were transduced with suicide gene and implanted into the myocardium of MI rat. Rats received either ganciclovir (GCV or vehicle after cell implantation. After one month, the cardiac functional changes and neovascularization were assessed by echocardiography, histological analysis, and micro-CT imaging. RESULTS: The expression of VEGF-A and HIF-1α was significantly higher in MSC(CXCR4 as compared to MSC(Null under hypoxia. Additionally, MSC(CXCR4 enhanced new vessel formation and EC differentiation, as well as STAT3 phosphorylation under hypoxia. STAT3 participated in the transcription of VE-cadherin in MSC(CXCR4 under hypoxia, which was inhibited by WP1066 (a STAT3 inhibitor. In addition, GCV specifically induced death of ECs with suicide gene activation. In vivo studies: MSC(CXCR4 implantation promoted cardiac functional restoration, reduced infarct size, improved cardiac remodeling, and enhanced neovascularization in ischemic heart tissue. New vessels derived from MSC(CXCR4 were observed at the injured heart margins and communicated with native coronary arteries. However, the derived vessel networks were reduced by GCV, reversing improvement of cardiac function. CONCLUSION: The

  10. Dietary broccoli sprouts protect against myocardial oxidative damage and cell death during ischemia-reperfusion.

    Science.gov (United States)

    Akhlaghi, Masoumeh; Bandy, Brian

    2010-09-01

    Cruciferous vegetables are known for antioxidant and anti-carcinogenic effects. In the current study we asked whether dietary broccoli sprouts can protect the heart from ischemia-reperfusion. Rats were fed either control diet (sham and control groups) or a diet mixed with 2% dried broccoli sprouts for 10 days. After 10 days the isolated hearts were subjected to ischemia for 20 min and reperfusion for 2 h, and evaluated for cell death, oxidative damage, and Nrf2-regulated phase 2 enzyme activities. Broccoli sprouts feeding inhibited markers of necrosis (lactate dehydrogenase release) and apoptosis (caspase-3 activity) by 78-86%, and decreased indices of oxidative stress (thiobarbituric acid reactive substances and aconitase inactivation) by 82-116%. While broccoli sprouts increased total glutathione and activities of the phase 2 enzymes glutamate cysteine ligase and quinone reductase in liver, they did not affect these in ischemic-reperfused heart. While the mechanism is not clear, the results show that a relatively short dietary treatment with broccoli sprouts can strongly protect the heart against oxidative stress and cell death caused by ischemia-reperfusion.

  11. Clinical Characteristics and Outcomes of Patients with Myocardial Infarction, Myocardial Injury, and Nonelevated Troponins

    DEFF Research Database (Denmark)

    Sarkisian, Laura; Saaby, Lotte; Poulsen, Tina S

    2016-01-01

    BACKGROUND: Cardiac troponins have emerged as the preferred biomarkers for detecting myocardial necrosis and diagnosing myocardial infarction. However, current cardiac troponin assays do not discriminate between ischemic and nonischemic causes of myocardial cell death. Thus, when an increased...... troponin value is encountered in the absence of obvious myocardial ischemia, a careful search for other clinical conditions is crucial. METHODS: In 2010 to 2011, we prospectively studied hospitalized patients who had cardiac troponin I measured on clinical indication. An acute myocardial infarction...... was diagnosed in cases of a cardiac troponin I increase or decrease pattern with at least 1 value >30 ng/L (99th percentile) together with myocardial ischemia. Myocardial injury was defined as cardiac troponin I values >30 ng/L, but without signs or symptoms indicating overt cardiac ischemia. Patients with peak...

  12. De-novo Collateral Formation Following Acute Myocardial Infarction: Dependence on CCR2+ Bone Marrow Cells

    Science.gov (United States)

    Zhang, Hua; Faber, James E

    2015-01-01

    Wide variation exists in the extent (number and diameter) of native pre-existing collaterals in tissues of different strains of mice, with supportive indirect evidence recently appearing for humans. This variation is a major determinant of the wide variation in severity of tissue injury in occlusive vascular disease. Whether such genetic-dependent variation also exists in the heart is unknown because no model exists for study of mouse coronary collaterals. Also owing to methodological limitations, it is not known if ischemia can induce new coronary collaterals to form (“neo-collaterals”) versus remodeling of pre-existing ones. The present study sought to develop a model to study coronary collaterals in mice, determine whether neo-collateral formation occurs, and investigate the responsible mechanisms. Four strains with known rank-ordered differences in collateral extent in brain and skeletal muscle were studied: C57BLKS>C57BL/6>A/J>BALB/c. Unexpectedly, these and 5 additional strains lacked native coronary collaterals. However after ligation, neo-collaterals formed rapidly within 1-to-2 days, reaching their maximum extent in ≤ 7 days. Rank-order for neo-collateral formation differed from the above: C57BL/6>BALB/c>C57BLKS>A/J. Collateral network conductance, infarct volume−1, and contractile function followed this same rank-order. Neo-collateral formation and collateral conductance were reduced and infarct volume increased in MCP1−/− and CCR2−/− mice. Bone-marrow transplant rescued collateral formation in CCR2−/− mice. Involvement of fractalkine→CX3CR1 signaling and endothelial cell proliferation were also identified. This study introduces a model for investigating the coronary collateral circulation in mice, demonstrates that neocollaterals form rapidly after coronary occlusion, and finds that MCP→CCR2-mediated recruitment of myeloid cells is required for this process. PMID:26254180

  13. Clinical outcome after stem cell mobilization with granulocyte-colony-stimulating factor after acute ST-elevation myocardial infarction:

    DEFF Research Database (Denmark)

    Ripa, Rasmus S; Jørgensen, Erik; Kastrup, Jens

    2013-01-01

    Background. Granulocyte-colony-stimulating factor (G-CSF) has been investigated in trials aiming to promote recovery of myocardial function after myocardial infarction. Long-term safety-data have never been reported. A few studies indicated an increased risk of in-stent re-stenosis. We aimed to i.......8; 0.3). Conclusions. We found no indication of increased risk of adverse events up to 5 years after G-CSF treatment. These results support the continued investigation of G-CSF for cardiac therapy....

  14. [Effects of Chinese herbal compound for supplementing qi and activating blood circulation on actin, Cx43 expressions and gap junctional intercellular communication functions of myocardial cells in patients with Coxsackie virus B 3 viral myocarditis].

    Science.gov (United States)

    Zhang, Ming-xue; He, Wei; Gu, Ping

    2010-08-01

    To observe the effect of Chinese herbal compound for supplementing qi and activating blood circulation (CHC) on the gap junctional intercellular communication (GJIC) function of myocardial cells in patients with Coxsackie virus B 3 (CVB3) viral myocarditis. Expressions of actin and connexin43 (Cx43) in myocardial cells of patients arranged in three groups (the normal control group, the viral infected group and the CHC treated group) were detected by immunohistochemical method; the fluorescence photobleaching recovery rate of cells was detected by laser scanning confocal microscope. As compared with the viral infected group, the expressions of actin and Cx43 were increased and the GJIC function was improved in the CHC treated group. CHC could antagonize viral injury on skeleton protein, and repair the structure of gap junction channel to improve the GJIC function of myocardial cells after being attacked by CVB3.

  15. E2/ER β Enhances Calcineurin Protein Degradation and PI3K/Akt/MDM2 Signal Transduction to Inhibit ISO-Induced Myocardial Cell Apoptosis

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    Kuan-Ho Lin

    2017-04-01

    Full Text Available Secretion of multifunctional estrogen and its receptor has been widely considered as the reason for markedly higher frequency of heart disease in men than in women. 17β-Estradiol (E2, for instance, has been reported to prevent development of cardiac apoptosis via activation of estrogen receptors (ERs. In addition, protein phosphatase such as protein phosphatase 1 (PP1 and calcineurin (PP2B are also involved in cardiac hypertrophy and cell apoptosis signaling. However, the mechanism by which E2/ERβ suppresses apoptosis is not fully understood, and the role of protein phosphatase in E2/ERβ action also needs further investigation. In this study, we observed that E2/ERβ inhibited isoproterenol (ISO-induced myocardial cell apoptosis, cytochrome c release and downstream apoptotic markers. Moreover, we found that E2/ERβ blocks ISO-induced apoptosis in H9c2 cells through the enhancement of calcineurin protein degradation through PI3K/Akt/MDM2 signaling pathway. Our results suggest that supplementation with estrogen and/or overexpression of estrogen receptor β gene may prove to be effective means to treat stress-induced myocardial damage.

  16. Cardiac-Restricted IGF-1Ea Overexpression Reduces the Early Accumulation of Inflammatory Myeloid Cells and Mediates Expression of Extracellular Matrix Remodelling Genes after Myocardial Infarction

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    Enrique Gallego-Colon

    2015-01-01

    Full Text Available Strategies to limit damage and improve repair after myocardial infarct remain a major therapeutic goal in cardiology. Our previous studies have shown that constitutive expression of a locally acting insulin-like growth factor-1 Ea (IGF-1Ea propeptide promotes functional restoration after cardiac injury associated with decreased scar formation. In the current study, we investigated the underlying molecular and cellular mechanisms behind the enhanced functional recovery. We observed improved cardiac function in mice overexpressing cardiac-specific IGF-1Ea as early as day 7 after myocardial infarction. Analysis of gene transcription revealed that supplemental IGF-1Ea regulated expression of key metalloproteinases (MMP-2 and MMP-9, their inhibitors (TIMP-1 and TIMP-2, and collagen types (Col 1α1 and Col 1α3 in the first week after injury. Infiltration of inflammatory cells, which direct the remodelling process, was also altered; in particular there was a notable reduction in inflammatory Ly6C+ monocytes at day 3 and an increase in anti-inflammatory CD206+ macrophages at day 7. Taken together, these results indicate that the IGF-1Ea transgene shifts the balance of innate immune cell populations early after infarction, favouring a reduction in inflammatory myeloid cells. This correlates with reduced extracellular matrix remodelling and changes in collagen composition that may confer enhanced scar elasticity and improved cardiac function.

  17. Meta-analysis of cell-based CaRdiac stUdiEs (ACCRUE) in patients with acute myocardial infarction based on individual patient data

    DEFF Research Database (Denmark)

    Gyöngyösi, Mariann; Wojakowski, Wojciech; Lemarchand, Patricia

    2015-01-01

    RATIONALE: The meta-Analysis of Cell-based CaRdiac study is the first prospectively declared collaborative multinational database, including individual data of patients with ischemic heart disease treated with cell therapy. OBJECTIVE: We analyzed the safety and efficacy of intracoronary cell...... therapy after acute myocardial infarction (AMI), including individual patient data from 12 randomized trials (ASTAMI, Aalst, BOOST, BONAMI, CADUCEUS, FINCELL, REGENT, REPAIR-AMI, SCAMI, SWISS-AMI, TIME, LATE-TIME; n=1252). METHODS AND RESULTS: The primary end point was freedom from combined major adverse.......1), end-diastolic volume, or systolic volume were observed compared with controls. These results were not influenced by anterior AMI location, reduced baseline ejection fraction, or the use of MRI for assessing left ventricular parameters. CONCLUSIONS: This meta-analysis of individual patient data from...

  18. Intra-myocardial injection of both growth factors and heart derived Sca-1+/CD31- cells attenuates post-MI LV remodeling more than does cell transplantation alone: neither intervention enhances functionally significant cardiomyocyte regeneration.

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    Xiaohong Wang

    Full Text Available Insulin-like growth factor 1 (IGF-1 and hepatocyte growth factor (HGF are two potent cell survival and regenerative factors in response to myocardial injury (MI. We hypothesized that simultaneous delivery of IGF+HGF combined with Sca-1+/CD31- cells would improve the outcome of transplantation therapy in response to the altered hostile microenvironment post MI. One million adenovirus nuclear LacZ-labeled Sca-1+/CD31- cells were injected into the peri-infarction area after left anterior descending coronary artery (LAD ligation in mice. Recombinant mouse IGF-1+HGF was added to the cell suspension prior to the injection. The left ventricular (LV function was assessed by echocardiography 4 weeks after the transplantation. The cell engraftment, differentiation and cardiomyocyte regeneration were evaluated by histological analysis. Sca-1+/CD31- cells formed viable grafts and improved LV ejection fraction (EF (Control, 54.5+/-2.4; MI, 17.6+/-3.1; Cell, 28.2+/-4.2, n = 9, P<0.01. IGF+HGF significantly enhanced the benefits of cell transplantation as evidenced by increased EF (38.8+/-2.2; n = 9, P<0.01 and attenuated adverse structural remodeling. Furthermore, IGF+HGF supplementation increased the cell engraftment rate, promoted the transplanted cell survival, enhanced angiogenesis, and minimally stimulated endogenous cardiomyocyte regeneration in vivo. The in vitro experiments showed that IGF+HGF treatment stimulated Sca-1+/CD31- cell proliferation and inhibited serum free medium induced apoptosis. Supperarray profiling of Sca-1+/CD31- cells revealed that Sca-1+/CD31- cells highly expressed various trophic factor mRNAs and IGF+HGF treatment altered the mRNAs expression patterns of these cells. These data indicate that IGF-1+HGF could serve as an adjuvant to cell transplantation for myocardial repair by stimulating donor cell and endogenous cardiac stem cell survival, regeneration and promoting angiogenesis.

  19. Design of a trial evaluating myocardial cell protection with cariporide, an inhibitor of the transmembrane sodium-hydrogen exchanger: the Guard During Ischemia Against Necrosis (GUARDIAN trial

    Directory of Open Access Journals (Sweden)

    Schroeder John S

    2000-08-01

    Full Text Available Synopsis Background Direct myocardial cell protection in patients with unstable angina or evolving myocardial infarction (MI could prevent cell necrosis or reduce its extent, and minimize the risk of MI and death associated with percutaneous coronary interventions (PCIs and coronary artery bypass surgery. The myocardial NHE plays a critical role in mediating the progression of ischemia to necrosis by promoting intracellular accumulation of sodium and calcium in exchange for hydrogen. Blockage of the system in various experimental models of ischemia and reperfusion had a strong antinecrotic effect. The present paper describes a trial that was intended to investigate the potential clinical benefit of cariporide, a potent and selective inhibitor of the NHE, in a large spectrum of at-risk patients. Trial design The GUARDIAN trial was a multicenter, double-blind, randomized, four-arm trial that compared three cariporide dosages with placebo in patients with unstable angina and non-ST-segment elevation myocardial infarction (UA/NSTEMI and in patients undergoing a high-risk PCI or coronary artery bypass surgery. A total of 11 590 patients with one of the three possible entry diagnoses were enroled in 23 countries. The trial was designed as a combined phase 2/phase 3 study. The primary objective was to evaluate the efficacy of cariporide in reducing all-cause mortality and/or MI across the various entry populations 36 days after randomization. Three different doses of cariporide were compared with placebo. Secondary end-points were death or non-fatal MI at 10 days and 6 months, and cardiac events related to left ventricular dysfunction. The extent of MI was also assessed by peak elevation in creatinine kinase (CK-MB and a ratio of peak elevation to normal values. The sample size was driven by a total event rate of 1200 patients experiencing a primary end-point, powered to detect a 25% risk reduction in any of the three treatment groups compared with

  20. Acute myocardial infarction is associated with endothelial glycocalyx and cell damage and a parallel increase in circulating catecholamines

    DEFF Research Database (Denmark)

    Ostrowski, Sisse R; Pedersen, Sune H; Jensen, Jan S

    2013-01-01

    INTRODUCTION: Excessive sympathoadrenal activation in critical illness contributes directly to organ damage, and high concentrations of catecholamines damage the vascular endothelium. This study investigated associations between potential drivers of sympathoadrenal activation, circulating...... catecholamines and biomarkers of endothelial damage and outcome in ST segment elevation myocardial infarction (STEMI)-patients, hypothesizing that the catecholamine surge would reflect shock degree and correlate with biomarkers of endothelial damage. METHODS: This was a prospective study of 678 consecutive STEMI...

  1. Secoisolariciresinol diglucoside prevents the oxidative stress-induced apoptosis of myocardial cells through activation of the JAK2/STAT3 signaling pathway.

    Science.gov (United States)

    Huang, Guiqiong; Huang, Xiaofang; Liu, Min; Hua, Yue; Deng, Bo; Jin, Wen; Yan, Wen; Tan, Zhangbin; Wu, Yifen; Liu, Bin; Zhou, Yingchun

    2018-06-01

    Myocardial cell apoptosis mediated by oxidative stress has previously been identified as a key process in ischemic heart disease. Secoisolariciresinol diglucoside (SDG), a polyphenolic plant lignan primarily found in flaxseed, has been demonstrated to effectively protect myocardial cells from apoptosis. In the present study, the role of the Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) was investigated in mediating the protective effect of SDG. Findings of the present study revealed that treatment with H2O2 reduced cell viability and induced apoptosis in H9C2 rat cardiomyocytes. However, SDG was able to reduce the effect of H2O2 in a dose‑dependent manner. H2O2 reduced the expression level of phosphorylated STAT3 and inhibited the levels of B‑cell lymphoma‑extra‑large and induced myeloid leukemia cell differentiation protein, which are the STAT3 target genes. Conversely, SDG rescued phosphorylation of STAT3 and increased the levels of STAT3 target genes. Treatment with SDG alone led to a dose‑dependent increased phosphorylation of JAK2 and STAT3, without activating Src. Furthermore, the anti‑apoptotic effects of SDG were partially abolished by a JAK2/STAT3 inhibitor. In addition, molecular docking revealed that SDG may bind to the protein kinase domain of JAK2, at a binding energy of ‑8.258 kcal/mol. Molecular dynamics simulations revealed that JAK2‑SDG binding was stable. In conclusion, activation of the JAK2/STAT3 signaling pathway contributed to the anti‑apoptotic activity of SDG, which may be a potential JAK2 activator.

  2. Intra-myocardial injection of both growth factors and heart derived Sca-1+/CD31- cells attenuates post-MI LV remodeling more than does cell transplantation alone: neither intervention enhances functionally significant cardiomyocyte regeneration.

    Science.gov (United States)

    Wang, Xiaohong; Li, Qinglu; Hu, Qingsong; Suntharalingam, Piradeep; From, Arthur H L; Zhang, Jianyi

    2014-01-01

    Insulin-like growth factor 1 (IGF-1) and hepatocyte growth factor (HGF) are two potent cell survival and regenerative factors in response to myocardial injury (MI). We hypothesized that simultaneous delivery of IGF+HGF combined with Sca-1+/CD31- cells would improve the outcome of transplantation therapy in response to the altered hostile microenvironment post MI. One million adenovirus nuclear LacZ-labeled Sca-1+/CD31- cells were injected into the peri-infarction area after left anterior descending coronary artery (LAD) ligation in mice. Recombinant mouse IGF-1+HGF was added to the cell suspension prior to the injection. The left ventricular (LV) function was assessed by echocardiography 4 weeks after the transplantation. The cell engraftment, differentiation and cardiomyocyte regeneration were evaluated by histological analysis. Sca-1+/CD31- cells formed viable grafts and improved LV ejection fraction (EF) (Control, 54.5+/-2.4; MI, 17.6+/-3.1; Cell, 28.2+/-4.2, n = 9, Pcell transplantation as evidenced by increased EF (38.8+/-2.2; n = 9, Pcell engraftment rate, promoted the transplanted cell survival, enhanced angiogenesis, and minimally stimulated endogenous cardiomyocyte regeneration in vivo. The in vitro experiments showed that IGF+HGF treatment stimulated Sca-1+/CD31- cell proliferation and inhibited serum free medium induced apoptosis. Supperarray profiling of Sca-1+/CD31- cells revealed that Sca-1+/CD31- cells highly expressed various trophic factor mRNAs and IGF+HGF treatment altered the mRNAs expression patterns of these cells. These data indicate that IGF-1+HGF could serve as an adjuvant to cell transplantation for myocardial repair by stimulating donor cell and endogenous cardiac stem cell survival, regeneration and promoting angiogenesis.

  3. Stem cell mobilization induced by subcutaneous granulocyte-colony stimulating factor to improve cardiac regeneration after acute ST-elevation myocardial infarction: result of the double-blind, randomized, placebo-controlled stem cells in myocardial infarction (STEMMI) trial

    DEFF Research Database (Denmark)

    Ripa, Rasmus Sejersten; Jørgensen, Erik; Wang, Yongzhong

    2006-01-01

    BACKGROUND: Phase 1 clinical trials of granulocyte-colony stimulating factor (G-CSF) treatment after myocardial infarction have indicated that G-CSF treatment is safe and may improve left ventricular function. This randomized, double-blind, placebo-controlled trial aimed to assess the efficacy...... hours after symptom onset. Patients were randomized to double-blind treatment with G-CSF (10 microg/kg of body weight) or placebo for 6 days. The primary end point was change in systolic wall thickening from baseline to 6 months determined by cardiac magnetic resonance imaging (MRI). An independent core...

  4. Myocardial perfusion in silent myocardial ischemia

    International Nuclear Information System (INIS)

    Narita, Michihiro; Kurihara, Tadashi; Murano, Kenichi; Usami, Masahisa

    1989-01-01

    To investigate myocardial perfusion in silent myocardial ischemia, we performed exercise stress myocardial tomography with thallium-201 (Tl) in 85 patients with coronary artery disease (CAD). Exercise stress myocardial tomography was obtained both immediately after exercise and three hours later. Patients were classified into two groups according to the presence (Symptomatic Group, n=36) or absence (Silent Group, n=49) of chest pain during exercise stress. Clinical features (age, gender and history of myocardial infarction) and arteriographically determined severity of CAD were the same in both groups. The extent of myocardial ischemia (% Ischemia) estimated by exercise stress myocardial tomography was the same in each group (30±10 % in Silent Group, 28±12 % in Symptomatic Group, NS). The severity of exercise-induced myocardial ischemia was expressed as a minimal value of myocardial Tl washout rate (minimal WOR) of each patient. Although exercise heart rate was identical in both groups, minimal WOR in Silent Group was significantly higher than that of Symptomatic Group (4±10% vs -16±14%, p<0.001). The study in patients who exhibited both silent and symptomatic ischemia showed the same results. These findings suggest that the severity of ischemia is a fundamental factor in determining the presence or absence of pain during exercise induced ischemia. (author)

  5. Classification of myocardial infarction

    DEFF Research Database (Denmark)

    Saaby, Lotte; Poulsen, Tina Svenstrup; Hosbond, Susanne Elisabeth

    2013-01-01

    The classification of myocardial infarction into 5 types was introduced in 2007 as an important component of the universal definition. In contrast to the plaque rupture-related type 1 myocardial infarction, type 2 myocardial infarction is considered to be caused by an imbalance between demand...

  6. Preparation of high bioactivity multilayered bone-marrow mesenchymal stem cell sheets for myocardial infarction using a 3D-dynamic system.

    Science.gov (United States)

    Wang, Yingwei; Zhang, Jianhua; Qin, Zixi; Fan, Zepei; Lu, Cheng; Chen, Baoxin; Zhao, Jupeng; Li, Xiaojuan; Xiao, Fei; Lin, Xi; Wu, Zheng

    2018-05-01

    Cell sheet techniques offer a promising future for myocardial infarction (MI) therapy; however, insufficient nutrition supply remains the major limitation in maintaining stem cell bioactivity in vitro. In order to enhance cell sheet mechanical strength and bioactivity, a decellularized porcine pericardium (DPP) scaffold was prepared by the phospholipase A2 method, and aspartic acid was used as a spacer arm to improve the vascular endothelial growth factor crosslink efficiency on the DPP scaffold. Based on this scaffold, multilayered bone marrow mesenchymal stem cell sheets were rapidly constructed, using RAD16-I peptide hydrogel as a temporary 3D scaffold, and cell sheets were cultured in either the 3D-dynamic system (DCcs) or the traditional static condition (SCcs). The multilayered structure, stem cell bioactivity, and ultrastructure of DCcs and SCcs were assessed. The DCcs exhibited lower apoptosis, lower differentiation, and an improved paracrine effect after a 48 h culture in vitro compared to the SCcs. Four groups were set to evaluate the cell sheet effect in rat MI model: sham group, MI control group, DCcs group, and SCcs group. The DCcs group improved cardiac function and decreased the infarcted area compared to the MI control group, while no significant improvements were observed in the SCcs group. Improved cell survival, angiogenesis, and Sca-1 + cell and c-kit + cell amounts were observed in the DCcs group. In conclusion, the DCcs maintained higher stem cell bioactivity by using the 3D-dynamic system to provide sufficient nutrition, and transplanting DCcs significantly improved the cardiac function and angiogenesis. This study provides an efficient method to prepare vascular endothelial growth factor covalent decellularized pericardium scaffold with aspartic acid, and a multilayered bone marrow mesenchymal stem cell (BMSC) sheet is constructed on it using a 3D-dynamic system. The dynamic nutrition supply showed a significant benefit on BMSC bioactivity

  7. The effect of intracoronary infusion of bone marrow-derived mononuclear cells on all-cause mortality in acute myocardial infarction

    DEFF Research Database (Denmark)

    Mathur, Anthony; Arnold, Roman; Assmus, Birgit

    2017-01-01

    Over the past 13 years bone marrow-derived mononuclear cells (BM-MNCs) have been widely investigated for clinical efficacy in patients following acute myocardial infarction (AMI). These early phase II trials have used various surrogate markers to judge efficacy and, although promising, the results...... have been inconsistent. The phase III BAMI trial has therefore been designed to demonstrate that intracoronary infusion of BM-MNCs is safe and will significantly reduce the time to first occurrence of all-cause death in patients with reduced left ventricular ejection fraction after successful...... of optimal standard of care. The control group will receive optimal standard of care. The primary endpoint is time from randomization to all-cause death. The BAMI trial is pivotal and the largest trial to date of BM-MNCs in patients with impaired left ventricular function following AMI. The aim of the trial...

  8. Longitudinal monitoring adipose-derived stem cell survival by PET imaging hexadecyl-4-{sup 124}I-iodobenzoate in rat myocardial infarction model

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Min Hwan [Molecular Imaging Research Center, Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of); School of Life Sciences and Biotechnology, Korea University, Seoul (Korea, Republic of); Woo, Sang-Keun; Lee, Kyo Chul; An, Gwang Il [Molecular Imaging Research Center, Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of); Pandya, Darpan [Department of Molecular Medicine, BK21 Plus KNU Biomedical Convergence Program, Kyungpook National University, Daegu (Korea, Republic of); Park, Noh Won; Nahm, Sang-Soep; Eom, Ki Dong [College of Veterinary Medicine, Konkuk University, Seoul (Korea, Republic of); Kim, Kwang Il; Lee, Tae Sup [Molecular Imaging Research Center, Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of); Kim, Chan Wha [School of Life Sciences and Biotechnology, Korea University, Seoul (Korea, Republic of); Kang, Joo Hyun [Molecular Imaging Research Center, Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of); Yoo, Jeongsoo, E-mail: yooj@knu.ac.kr [Department of Molecular Medicine, BK21 Plus KNU Biomedical Convergence Program, Kyungpook National University, Daegu (Korea, Republic of); Lee, Yong Jin, E-mail: yjlee@kirams.re.kr [Molecular Imaging Research Center, Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of)

    2015-01-02

    Highlights: • We developed a safe, simple and appropriate stem cell labeling method with {sup 124}I-HIB. • ADSC survival can be monitored with PET in MI model via direct labeling. • Tracking of ADSC labeled with {sup 124}I-HIB was possible for 3 days in MI model using PET. • ADSC viability and differentiation were not affected by {sup 124}I-HIB labeling. • Survival of ADSC in living bodies can be longitudinally tracked with PET imaging. - Abstract: This study aims to monitor how the change of cell survival of transplanted adipose-derived stem cells (ADSCs) responds to myocardial infarction (MI) via the hexadecyl-4-{sup 124}I-iodobenzoate ({sup 124}I-HIB) mediated direct labeling method in vivo. Stem cells have shown the potential to improve cardiac function after MI. However, monitoring of the fate of transplanted stem cells at target sites is still unclear. Rat ADSCs were labeled with {sup 124}I-HIB, and radiolabeled ADSCs were transplanted into the myocardium of normal and MI model. In the group of {sup 124}I-HIB-labeled ADSC transplantation, in vivo imaging was performed using small-animal positron emission tomography (PET)/computed tomography (CT) for 9 days. Twenty-one days post-transplantation, histopathological analysis and apoptosis assay were performed. ADSC viability and differentiation were not affected by {sup 124}I-HIB labeling. In vivo tracking of the {sup 124}I-HIB-labeled ADSCs was possible for 9 and 3 days in normal and MI model, respectively. Apoptosis of transplanted cells increased in the MI model compared than that in normal model. We developed a direct labeling agent, {sup 124}I-HIB, and first tried to longitudinally monitor transplanted stem cell to MI. This approach may provide new insights on the roles of stem cell monitoring in living bodies for stem cell therapy from pre-clinical studies to clinical trials.

  9. Myocardial imaging. Coxsackie myocarditis

    Energy Technology Data Exchange (ETDEWEB)

    Wells, R.G.; Ruskin, J.A.; Sty, J.R.

    1986-09-01

    A 3-week-old male neonate with heart failure associated with Coxsackie virus infection was imaged with Tc-99m PYP and TI-201. The abnormal imaging pattern suggested myocardial infarction. Autopsy findings indicated that the cause was myocardial necrosis secondary to an acute inflammatory process. Causes of abnormal myocardial uptake of Tc-99m PYP in pediatrics include infarction, myocarditis, cardiomyopathy, bacterial endocarditis, and trauma. Myocardial imaging cannot provide a specific cause diagnosis. Causes of myocardial infarction in pediatrics are listed in Table 1.

  10. Myocardial imaging. Coxsackie myocarditis

    International Nuclear Information System (INIS)

    Wells, R.G.; Ruskin, J.A.; Sty, J.R.

    1986-01-01

    A 3-week-old male neonate with heart failure associated with Coxsackie virus infection was imaged with Tc-99m PYP and TI-201. The abnormal imaging pattern suggested myocardial infarction. Autopsy findings indicated that the cause was myocardial necrosis secondary to an acute inflammatory process. Causes of abnormal myocardial uptake of Tc-99m PYP in pediatrics include infarction, myocarditis, cardiomyopathy, bacterial endocarditis, and trauma. Myocardial imaging cannot provide a specific cause diagnosis. Causes of myocardial infarction in pediatrics are listed in Table 1

  11. Acute myocardial infarction: 'telomerasing' for cardioprotection

    OpenAIRE

    Sanchís-Gomar, Fabián; Lucía Mulas, Alejandro

    2015-01-01

    Reactivating the telomerase gene through gene therapy after acute myocardial infarction (AMI) has been recently reported to improve survival in mice. Given that regular physical exercise also activates this gene, therapeutic and lifestyle interventions targeting telomerase need to be explored as possible additions to the current armamentarium for myocardial regeneration. 9.292 JCR (2015) Q1, 17/289 Biochemistry & mollecular biology, 17/187 Cell biology, 8/124 Medicine, research & experimen...

  12. Results from functional and cellular studies using an ovine model to assess response to mesenchymal stem cell therapy after induction of myocardial infarction

    International Nuclear Information System (INIS)

    Bailey, Elizabeth A.; Bailey, Dale L; Roach, Paul J.; Bautovich, George; Hunyor, Stephen

    2009-01-01

    Full text: Background: Assessing functional and cellular consequences following myocardial infarction (MI) using large animals has advantages of similarity in size, shape and coronary supply to human heart. Aim: To confirm presence of MI and detect recovery of perfusion and function following implantation of ovine bone-marrow derived mesenchymal stem cells (MSC) using intra-myocardial (1 M ) and intra-coronary (I C ) methods. Methods: Eighteen ewes (wt: 45-50 k g, LV-EDV: 80-90 m L) included, with 10 completing protocol (3=control, 4= IM , 3= IC ). MlBI MPI SPECT/CT performed at baseline, 5-7 days post induction of Ml and 6 weeks post cellular therapy with male MSCs. At completion, sheep sacrificed and heart slices reviewed microscopically to confirm Ml, assess neovascularisation and correlate with MPI findings. MPI studies reconstructed using OSEM CT-based AC and analysed using QPS/QGS software. Calculation of Recovery Difference (RD%), Recovery Ratio (RR) and relative change to baseline determined for each study and per segment per study. Results: M I confirmed in 10 of 12 studies (I showed no perfusion abnormality, another pre-existing defect), confirmed anatomically by identification of fibrous scar tissue with lymphoid aggregates, histiocytes and calcium deposits. Reduction in perfusion was 14% to 48%. No improvement in perfusion seen in control (RR=0.8, RD=-16.9) and IC (RR=0.9, RD=-7.1) studies. Significant reperfusion seen on 1 M studies, with RR=1.5, RD=1.1 and perfusion recovery 8%, around periphery of infarct zone. Conclusions: Presence of acute Ml identified on MlBl MPI SPECT/CT correlates with anatomical findings. Improvement in perfusion and function at infarct zone seen using 1 M method of MSC implantation, correlating with significant neovascularisation identified microscopically.

  13. Apoptosis in response to heat stress is positively associated with heat-shock protein 90 expression in chicken myocardial cells in vitro.

    Science.gov (United States)

    Zhang, Xiao-Hui; Wu, Hong; Tang, Shu; Li, Qiao-Ning; Xu, Jiao; Zhang, Miao; Su, Ya-Nan; Yin, Bin; Zhao, Qi-Ling; Kemper, Nicole; Hartung, Joerg; Bao, En-Dong

    2017-06-30

    To determine heat-shock protein (Hsp)90 expression is connected with cellular apoptotic response to heat stress and its mechanism, chicken ( Gallus gallus ) primary myocardial cells were treated with the Hsp90 promoter, aspirin, and its inhibitor, geldanamycin (GA), before heat stress. Cellular viability, heat-stressed apoptosis and reactive oxygen species level under different treatments were measured, and the expression of key proteins of the signaling pathway related to Hsp90 and their colocalization with Hsp90 were detected. The results showed that aspirin treatment increased the expression of protein kinase B (Akt), the signal transducer and activator of transcription (STAT)-3 and p-IKKα/β and the colocalization of Akt and STAT-3 with Hsp90 during heat stress, which was accompanied by improved viability and low apoptosis. GA significantly inhibited Akt expression and p-IKKα/β level, but not STAT-3 quantity, while the colocalization of Akt and STAT-3 with Hsp90 was weakened, followed by lower cell viability and higher apoptosis. Aspirin after GA treatment partially improved the stress response and apoptosis rate of tested cells caused by the recovery of Akt expression and colocalization, rather than the level of STAT-3 (including its co-localization with Hsp90) and p-IKKα/β. Therefore, Hsp90 expression has a positive effect on cellular capacity to resist heat-stressed injury and apoptosis. Moreover, inhibition of Hsp90 before stress partially attenuated its positive effects.

  14. Predictors of ventricular remodelling in patients with reperfused acute myocardial infarction and left ventricular dysfunction candidates for bone marrow cell therapy: insights from the BONAMI trial

    International Nuclear Information System (INIS)

    Manrique, Alain; Lemarchand, Patricia; Delasalle, Beatrice; Lamirault, Guillaume; Trochu, Jean-Noel; Le Tourneau, Thierry; Lairez, Olivier; Roncalli, Jerome; Sportouch-Duckan, Catherine; Piot, Christophe; Le Corvoisier, Philippe; Neuder, Yannick; Richardson, Marjorie; Lebon, Alain; Teiger, Emmanuel; Hossein-Foucher, Claude

    2016-01-01

    Few data are available regarding the relation of left ventricular (LV) mechanical dyssynchrony to remodelling after acute myocardial infarction (MI) and stem cell therapy. We evaluated the 1-year time course of both LV mechanical dyssynchrony and remodelling in patients enrolled in the BONAMI trial, a randomized, multicenter controlled trial assessing cell therapy in patients with reperfused MI. Patients with acute MI and ejection fraction (EF) ≤ 45 % were randomized to cell therapy or to control and underwent thallium single-photon emission computed tomography (SPECT), radionuclide angiography, and echocardiography at baseline, 3 months, and 1 year. Eighty-three patients with a comprehensive 1-year follow-up were included. LV dyssynchrony was assessed by the standard deviation (SD) of the LV phase histogram using radionuclide angiography. Remodelling was defined as a 20 % increase in LV end-systolic volume index (LVESVI) at 1 year. At baseline, LVEF, wall motion score index, and perfusion defect size were significantly impaired in the 43 patients (52 %) with LV remodelling (all p < 0.001), without significant increase in LV mechanical dyssynchrony. During follow-up, there was a progressive increase in LV SD (p = 0.01). Baseline independent predictors of LV remodelling were perfusion SPECT defect size (p = 0.001), LVEF (p = 0.01) and a history of hypertension (p = 0.043). Bone marrow cell therapy did not affect the time-course of LV remodelling and dyssynchrony. LV remodelling 1 year after reperfused MI is associated with progressive LV dyssynchrony and is related to baseline infarct size and ejection fraction, without impact of cell therapy on this process. (orig.)

  15. Predictors of ventricular remodelling in patients with reperfused acute myocardial infarction and left ventricular dysfunction candidates for bone marrow cell therapy: insights from the BONAMI trial

    Energy Technology Data Exchange (ETDEWEB)

    Manrique, Alain [Nuclear Medicine, CHU de Caen, Caen (France); Universite de Caen Normandie, EA 4650, Caen (France); CHU de Caen et GIP Cyceron, Caen cedex 6 (France); Lemarchand, Patricia; Delasalle, Beatrice; Lamirault, Guillaume; Trochu, Jean-Noel; Le Tourneau, Thierry [L' Institut du thorax, INSERM, UMR1087, Nantes (France); CNRS, UMR 6291, Nantes (France); Universite de Nantes, Nantes (France); CHU de Nantes, Nantes (France); Lairez, Olivier; Roncalli, Jerome [Institut CARDIOMET-Toulouse, Cardiac Imaging Center, CIC Biotherapies, CHU de Toulouse, Toulouse (France); Sportouch-Duckan, Catherine; Piot, Christophe [Universite Montpellier, Institut de Genomique Fonctionnelle, INSERM U661, CNRS UMR 5203, Montpellier (France); Clinique du Millenaire, Montpellier (France); Le Corvoisier, Philippe [Hopital Henri Mondor, INSERM, Centre d' Investigation Clinique 1430 et U955 equipe 3, Creteil (France); Neuder, Yannick [CHU de Grenoble, Pole Thorax et Vaisseaux, Grenoble (France); Richardson, Marjorie [CHRU Lille, Service d' Explorations Fonctionnelles Cardiovasculaires, Hopital Cardiologique, Lille (France); Lebon, Alain [CHU de Caen, Service de Cardiologie, Caen (France); Teiger, Emmanuel [Hopital Henri Mondor, AP-HP, Unite de Cardiologie Interventionnelle et Federation de Cardiologie, Creteil (France); Hossein-Foucher, Claude [Hopital Salengro CHRU de Lille, Service de Medecine Nucleaire, Lille (France); Universite de Lille 2, UFR de Medecine, Lille (France)

    2016-04-15

    Few data are available regarding the relation of left ventricular (LV) mechanical dyssynchrony to remodelling after acute myocardial infarction (MI) and stem cell therapy. We evaluated the 1-year time course of both LV mechanical dyssynchrony and remodelling in patients enrolled in the BONAMI trial, a randomized, multicenter controlled trial assessing cell therapy in patients with reperfused MI. Patients with acute MI and ejection fraction (EF) ≤ 45 % were randomized to cell therapy or to control and underwent thallium single-photon emission computed tomography (SPECT), radionuclide angiography, and echocardiography at baseline, 3 months, and 1 year. Eighty-three patients with a comprehensive 1-year follow-up were included. LV dyssynchrony was assessed by the standard deviation (SD) of the LV phase histogram using radionuclide angiography. Remodelling was defined as a 20 % increase in LV end-systolic volume index (LVESVI) at 1 year. At baseline, LVEF, wall motion score index, and perfusion defect size were significantly impaired in the 43 patients (52 %) with LV remodelling (all p < 0.001), without significant increase in LV mechanical dyssynchrony. During follow-up, there was a progressive increase in LV SD (p = 0.01). Baseline independent predictors of LV remodelling were perfusion SPECT defect size (p = 0.001), LVEF (p = 0.01) and a history of hypertension (p = 0.043). Bone marrow cell therapy did not affect the time-course of LV remodelling and dyssynchrony. LV remodelling 1 year after reperfused MI is associated with progressive LV dyssynchrony and is related to baseline infarct size and ejection fraction, without impact of cell therapy on this process. (orig.)

  16. Mesenchymal Stem Cells Induce Expression of CD73 in Human Monocytes In Vitro and in a Swine Model of Myocardial Infarction In Vivo

    Directory of Open Access Journals (Sweden)

    Marta Monguió-Tortajada

    2017-11-01

    Full Text Available The ectoenzymes CD39 and CD73 regulate the purinergic signaling through the hydrolysis of adenosine triphosphate (ATP/ADP to AMP and to adenosine (Ado, respectively. This shifts the pro-inflammatory milieu induced by extracellular ATP to the anti-inflammatory regulation by Ado. Mesenchymal stem cells (MSCs have potent immunomodulatory capabilities, including monocyte modulation toward an anti-inflammatory phenotype aiding tissue repair. In vitro, we observed that human cardiac adipose tissue-derived MSCs (cATMSCs and umbilical cord MSCs similarly polarize monocytes toward a regulatory M2 phenotype, which maintained the expression of CD39 and induced expression of CD73 in a cell contact dependent fashion, correlating with increased functional activity. In addition, the local treatment with porcine cATMSCs using an engineered bioactive graft promoted the in vivo CD73 expression on host monocytes in a swine model of myocardial infarction. Our results suggest the upregulation of ectonucleotidases on MSC-conditioned monocytes as an effective mechanism to amplify the long-lasting immunomodulatory and healing effects of MSCs delivery.

  17. Novel strategies for enhancing myocardial infarction

    NARCIS (Netherlands)

    Liu, J.

    2011-01-01

    Ischemic heart disease is a leading cause of morbidity and mortality worldwide. Massive cell loss initiated a series of cascade events upon ischemic injury. Enourmous effort has been put to investigate strategies for enhancing myocardial healing. Cell therapy emerges as a promising strategy for

  18. Ultrasound-Targeted Microbubble Destruction Improves the Migration and Homing of Mesenchymal Stem Cells after Myocardial Infarction by Upregulating SDF-1/CXCR4: A Pilot Study

    Directory of Open Access Journals (Sweden)

    Lu Li

    2015-01-01

    Full Text Available Mesenchymal stem cell (MSC therapy shows considerable promise for the treatment of myocardial infarction (MI. However, the inefficient migration and homing of MSCs after systemic infusion have limited their therapeutic applications. Ultrasound-targeted microbubble destruction (UTMD has proven to be promising to improve the homing of MSCs to the ischemic myocardium, but the concrete mechanism remains unclear. We hypothesize that UTMD promotes MSC homing by upregulating SDF-1/CXCR4, and this study was aimed at exploring this potential mechanism. We analyzed SDF-1/CXCR4 expression after UTMD treatment in vitro and in vivo and counted the number of homing MSCs in MI areas. The in vitro results demonstrated that UTMD not only led to elevated secretion of SDF-1 but also resulted in an increased proportion of MSCs that expressed surface CXCR4. The in vivo findings show an increase in the number of homing MSCs and higher expression of SDF-1/CXCR4 in the UTMD combined with MSCs infusion group compared to other groups. In conclusion, UTMD can increase SDF-1 expression in the ischemic myocardium and upregulate the expression of surface CXCR4 on MSCs, which provides a molecular mechanism for the homing of MSCs assisted by UTMD via SDF-1/CXCR4 axis.

  19. Meta-Analysis of Cell-based CaRdiac stUdiEs (ACCRUE) in patients with acute myocardial infarction based on individual patient data.

    Science.gov (United States)

    Gyöngyösi, Mariann; Wojakowski, Wojciech; Lemarchand, Patricia; Lunde, Ketil; Tendera, Michal; Bartunek, Jozef; Marban, Eduardo; Assmus, Birgit; Henry, Timothy D; Traverse, Jay H; Moyé, Lemuel A; Sürder, Daniel; Corti, Roberto; Huikuri, Heikki; Miettinen, Johanna; Wöhrle, Jochen; Obradovic, Slobodan; Roncalli, Jérome; Malliaras, Konstantinos; Pokushalov, Evgeny; Romanov, Alexander; Kastrup, Jens; Bergmann, Martin W; Atsma, Douwe E; Diederichsen, Axel; Edes, Istvan; Benedek, Imre; Benedek, Theodora; Pejkov, Hristo; Nyolczas, Noemi; Pavo, Noemi; Bergler-Klein, Jutta; Pavo, Imre J; Sylven, Christer; Berti, Sergio; Navarese, Eliano P; Maurer, Gerald

    2015-04-10

    The meta-Analysis of Cell-based CaRdiac study is the first prospectively declared collaborative multinational database, including individual data of patients with ischemic heart disease treated with cell therapy. We analyzed the safety and efficacy of intracoronary cell therapy after acute myocardial infarction (AMI), including individual patient data from 12 randomized trials (ASTAMI, Aalst, BOOST, BONAMI, CADUCEUS, FINCELL, REGENT, REPAIR-AMI, SCAMI, SWISS-AMI, TIME, LATE-TIME; n=1252). The primary end point was freedom from combined major adverse cardiac and cerebrovascular events (including all-cause death, AMI recurrance, stroke, and target vessel revascularization). The secondary end point was freedom from hard clinical end points (death, AMI recurrence, or stroke), assessed with random-effects meta-analyses and Cox regressions for interactions. Secondary efficacy end points included changes in end-diastolic volume, end-systolic volume, and ejection fraction, analyzed with random-effects meta-analyses and ANCOVA. We reported weighted mean differences between cell therapy and control groups. No effect of cell therapy on major adverse cardiac and cerebrovascular events (14.0% versus 16.3%; hazard ratio, 0.86; 95% confidence interval, 0.63-1.18) or death (1.4% versus 2.1%) or death/AMI recurrence/stroke (2.9% versus 4.7%) was identified in comparison with controls. No changes in ejection fraction (mean difference: 0.96%; 95% confidence interval, -0.2 to 2.1), end-diastolic volume, or systolic volume were observed compared with controls. These results were not influenced by anterior AMI location, reduced baseline ejection fraction, or the use of MRI for assessing left ventricular parameters. This meta-analysis of individual patient data from randomized trials in patients with recent AMI revealed that intracoronary cell therapy provided no benefit, in terms of clinical events or changes in left ventricular function. URL: http://www.clinicaltrials.gov. Unique

  20. Intracoronary artery transplantation of cardiomyoblast-like cells from human adipose tissue-derived multi-lineage progenitor cells improve left ventricular dysfunction and survival in a swine model of chronic myocardial infarction

    Energy Technology Data Exchange (ETDEWEB)

    Okura, Hanayuki [The Center for Medical Engineering and Informatics, Osaka University, 2-2 Yamada-oka, Suita, Osaka 565-0879 (Japan); Department of Somatic Stem Cell Therapy and Health Policy, Institute of Biomedical Research and Innovation, Foundation for Biomedical Research and Innovation, 2-2 Minatojima-minamimachi, Chuo-ku, Kobe, Hyogo 650-0047 (Japan); Saga, Ayami; Soeda, Mayumi [Department of Somatic Stem Cell Therapy and Health Policy, Institute of Biomedical Research and Innovation, Foundation for Biomedical Research and Innovation, 2-2 Minatojima-minamimachi, Chuo-ku, Kobe, Hyogo 650-0047 (Japan); Miyagawa, Shigeru; Sawa, Yoshiki [Department of Surgery, Osaka University Graduate School of Medicine, 2-2 Yamada-oka, Suita, Osaka 565-0879 (Japan); Daimon, Takashi [Division of Biostatistics, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo 663-8501 (Japan); Ichinose, Akihiro [Department of Plastic Surgery, Kobe University Hospital, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe, Hyogo (Japan); Matsuyama, Akifumi, E-mail: akifumi-matsuyama@umin.ac.jp [The Center for Medical Engineering and Informatics, Osaka University, 2-2 Yamada-oka, Suita, Osaka 565-0879 (Japan); Department of Plastic Surgery, Kobe University Hospital, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe, Hyogo (Japan); RIKEN Program for Drug Discovery and Medical Technology Platforms, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama, Kanagawa 230-0045 (Japan)

    2012-09-07

    Highlights: Black-Right-Pointing-Pointer We administered human CLCs in a swine model of MI via intracoronary artery. Black-Right-Pointing-Pointer Histological studies demonstrated engraftment of hCLCs into the scarred myocardium. Black-Right-Pointing-Pointer Echocardiography showed rescue of cardiac function in the hCLCs transplanted swine. Black-Right-Pointing-Pointer Transplantation of hCLCs is an effective therapeutics for cardiac regeneration. -- Abstract: Transplantation of human cardiomyoblast-like cells (hCLCs) from human adipose tissue-derived multi-lineage progenitor cells improved left ventricular function and survival of rats with myocardial infarction. Here we examined the effect of intracoronary artery transplantation of human CLCs in a swine model of chronic heart failure. Twenty-four pigs underwent balloon-occlusion of the first diagonal branch followed by reperfusion, with a second balloon-occlusion of the left ascending coronary artery 1 week later followed by reperfusion. Four weeks after the second occlusion/reperfusion, 17 of the 18 surviving animals with severe chronic MI (ejection fraction <35% by echocardiography) were immunosuppressed then randomly assigned to receive either intracoronary artery transplantation of hCLCs hADMPCs or placebo lactic Ringer's solution with heparin. Intracoronary artery transplantation was followed by the distribution of DiI-stained hCLCs into the scarred myocardial milieu. Echocardiography at post-transplant days 4 and 8 weeks showed rescue and maintenance of cardiac function in the hCLCs transplanted group, but not in the control animals, indicating myocardial functional recovery by hCLCs intracoronary transplantation. At 8 week post-transplantation, 7 of 8 hCLCs transplanted animals were still alive compared with only 1 of the 5 control (p = 0.0147). Histological studies at week 12 post-transplantation demonstrated engraftment of the pre DiI-stained hCLCs into the scarred myocardium and their expression of

  1. Plasma Concentration of Biomarkers Reflecting Endothelial Cell- and Glycocalyx Damage are Increased in Patients with Suspected St-Elevation Myocardial Infarction Complicated by Cardiogenic Shock

    DEFF Research Database (Denmark)

    Frydland, Martin; Ostrowski, Sisse Rye; Møller, Jacob Eifer

    2018-01-01

    BACKGROUND: Mortality in ST-elevation myocardial infarction (STEMI)-patients developing cardiogenic shock (CS) during hospitalization is high. Catecholamines, ischemia, and inflammation (parameters present in CS) affect the endothelium. We hypothesized that plasma level of biomarkers reflecting e...

  2. 99Tcm-MIBI and 18F-FDG DISA imaging in the evaluation of CABG combined with autologous bone marrow mononuclear cell transplantation in patients with myocardial infarction

    International Nuclear Information System (INIS)

    Zhang Fuqiang; Chen Xianying; Zhang Guoxu; Wang Zhiguo; Ma Dongchu; Wang Huishan

    2009-01-01

    Objective: Autologous bone marrow mononuclear cell transplantation is a treatment modality under investigation for severe coronary heart disease. Its beneficial effects on ventricular function, myocardial perfusion and metabolism remain to be evaluated. The present study proposed a 18 F-fluorodeoxyglucose (FDG) and 99 Tc m -methoxyisobutylisinitrile (MIBI) dual-isotope simultaneous acquisition (DISA) imaging technique to assess the effects of coronary artery bypass grafting (CABG) combined with autologous bone marrow mononuclear cell transplantation in patients with old myocardial infarction (OMI). Methods: Twenty patients with OMI, whose diagnosis was confirmed with angiography. were divided into a convention. al CABG group (group A, n=11) and CABG+ autologous bone marrow mononuclear cell transplantation group (group B, n=9). All subjects underwent gated cardiac DISA tomography at one week preoperatively and four months postoperatively. The segmental myocardial uptake of the tracers was scored as 3, 2, 1 and 0. Paired-samples t test was used to compare data of the two groups. Results In group A, there were 52 perfusion/metabolism mismatched segments, 99 Tc m -MIBI and 18 F-FDG uptake scores of these segments in-creased from preoperatively 1.48 ± 0.75( 99 Tc m -MIBI)and 1.90 ± 0.75( 18 F-FDG) to postoperatively 1.75 ± 0.68 and 2.13 ± 0.74 (t=3.25 and 2.37, both P 0.05). However, in group B, there was significant increase of the myocardial uptake scores both in mismatched segments and matched segments. In the 45 mismatched segments of this group,preoperative and postoperative 99 Tc m -MIBI/ 18 F-FDG uptake scores were 1.24 ± 0.68/1.71 ± 0.76 and 1.53 ± 0.66/2.00 ± 0.64, respectively (t=2.93 and 2.56. both P 99 Tc m -MIBI/ 18 F-FDG uptake scores were 0.94 ± 0.75/1.50 ± 0.74 and 1.22 ± 0.76/1.78 ± 0.64. respectively (t=2.71 and 3.37. both P 0.05). Conclusions: CABG combined with autologous bone marrow mononuclear cell transplantation may improve myocardial

  3. Histochemical and immunohistochemical analyses of the myocardial scar fallowing acute myocardial infarction

    Directory of Open Access Journals (Sweden)

    Tatić Vujadin

    2012-01-01

    Full Text Available Background/Aim. The heart has traditionally been considered as a static organ without capacity of regeneration after trauma. Currently, the more and more often asked question is whether the heart has any intrinsic capacities to regenerate myocytes after myocardial infarction. The aim of this study was to present the existence of the preserved muscle fibers in the myocardial scar following myocardial infarction as well as the presence of numerous cells of various size and form that differently reacted to the used immunohistochemical antibodies. Methods. Histological, histochemical and immunohistochemical analyses of myocardial sections taken from 177 patients who had died of acute myocardial infarction and had the myocardial scar following myocardial infarction, were carried out. More sections taken both from the site of acute infarction and scar were examined by the following methods: hematoxylin-eosin (HE, periodic acid schiff (PAS, PAS-diastasis, Masson trichrom, Malory, van Gieson, vimentin, desmin, myosin, myoglobin, alpha actin, smoth muscle actin (SMA, p53, leukocyte common antigen (LCA, proliferating cell nuclear antigen (PCNA, Ki-67, actin HHF35, CD34, CD31, CD45, CD45Ro, CD8, CD20. Results. In all sections taken from the scar region, larger or smaller islets of the preserved muscle fibers with the signs of hypertrophy were found. In the scar, a large number of cells of various size and form: spindle, oval, elongated with abundant cytoplasm, small with one nucleus and cells with scanty cytoplasm, were found. The present cells differently reacted to histochemical and immunohistochemical methods. Large oval cells showed negative reaction to lymphocytic and leukocytic markers, and positive to alpha actin, actin HHF35, Ki-67, myosin, myoglobin and desmin. Elongated cells were also positive to those markers. Small mononuclear cells showed positive reaction to lymphocytic markers. Endothelial and smooth muscle cells in the blood vessel walls

  4. Current Understanding of the Pathophysiology of Myocardial Fibrosis and Its Quantitative Assessment in Heart Failure

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    Tong Liu

    2017-04-01

    Full Text Available Myocardial fibrosis is an important part of cardiac remodeling that leads to heart failure and death. Myocardial fibrosis results from increased myofibroblast activity and excessive extracellular matrix deposition. Various cells and molecules are involved in this process, providing targets for potential drug therapies. Currently, the main detection methods of myocardial fibrosis rely on serum markers, cardiac magnetic resonance imaging, and endomyocardial biopsy. This review summarizes our current knowledge regarding the pathophysiology, quantitative assessment, and novel therapeutic strategies of myocardial fibrosis.

  5. Direct implantation versus platelet-rich fibrin-embedded adipose-derived mesenchymal stem cells in treating rat acute myocardial infarction.

    Science.gov (United States)

    Sun, Cheuk-Kwan; Zhen, Yen-Yi; Leu, Steve; Tsai, Tzu-Hsien; Chang, Li-Teh; Sheu, Jiunn-Jye; Chen, Yung-Lung; Chua, Sarah; Chai, Han-Tan; Lu, Hung-I; Chang, Hsueh-Wen; Lee, Fan-Yen; Yip, Hon-Kan

    2014-05-15

    This study tested whether adipose-derived mesenchymal stem cells (ADMSC) embedded in platelet-rich fibrin (PRF) scaffold is superior to direct ADMSC implantation in improving left ventricular (LV) performance and reducing LV remodeling in a rat acute myocardial infarction (AMI) model of left anterior descending coronary artery (LAD) ligation. Twenty-eight male adult Sprague Dawley rats equally divided into group 1 [sham control], group 2 (AMI only), group 3 (AMI+direct ADMSC implantation), and group 4 (AMI+PRF-embedded autologous ADMSC) were sacrificed on day 42 after AMI. LV systolic and diastolic dimensions and volumes, and infarct/fibrotic areas were highest in group 2, lowest in group 1 and significantly higher in group 3 than in group 4, whereas LV performance and LV fractional shortening exhibited a reversed pattern (p<0.005). Protein expressions of inflammation (oxidative stress, IL-1β, MMP-9), apoptosis (mitochondrial Bax, cleaved PARP), fibrosis (Smad3, TGF-β), and pressure-overload biomarkers (BNP, MHC-β) displayed a pattern similar to that of LV dimensions, whereas anti-inflammatory (IL-10), anti-apoptotic (Bcl-2), and anti-fibrotic (Smad1/5, BMP-2) indices showed a pattern similar to that of LV performance among the four groups (all p<0.05). Angiogenesis biomarkers at protein (CXCR4, SDF-1α, VEGF), cellular (CD31+, CXCR4+, SDF-1α+), and immunohistochemical (small vessels) levels, and cardiac stem cell markers (C-kit+, Sca-1+) in infarct myocardium were highest in group 4, lowest in group 1, and significantly higher in group 3 than in group 2 (all p<0.005). PRF-embedded ADMSC is superior to direct ADMSC implantation in preserving LV function and attenuating LV remodeling. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  6. Periodontitis and myocardial hypertrophy.

    Science.gov (United States)

    Suzuki, Jun-Ichi; Sato, Hiroki; Kaneko, Makoto; Yoshida, Asuka; Aoyama, Norio; Akimoto, Shouta; Wakayama, Kouji; Kumagai, Hidetoshi; Ikeda, Yuichi; Akazawa, Hiroshi; Izumi, Yuichi; Isobe, Mitsuaki; Komuro, Issei

    2017-04-01

    There is a deep relationship between cardiovascular disease and periodontitis. It has been reported that myocardial hypertrophy may be affected by periodontitis in clinical settings. Although these clinical observations had some study limitations, they strongly suggest a direct association between severity of periodontitis and left ventricular hypertrophy. However, the detailed mechanisms between myocardial hypertrophy and periodontitis have not yet been elucidated. Recently, we demonstrated that periodontal bacteria infection is closely related to myocardial hypertrophy. In murine transverse aortic constriction models, a periodontal pathogen, Aggregatibacter actinomycetemcomitans markedly enhanced cardiac hypertrophy with matrix metalloproteinase-2 activation, while another pathogen Porphyromonas gingivalis (P.g.) did not accelerate these pathological changes. In the isoproterenol-induced myocardial hypertrophy model, P.g. induced myocardial hypertrophy through Toll-like receptor-2 signaling. From our results and other reports, regulation of chronic inflammation induced by periodontitis may have a key role in the treatment of myocardial hypertrophy. In this article, we review the pathophysiological mechanism between myocardial hypertrophy and periodontitis.

  7. Terapias celulares do miocárdio com células da medula óssea: critérios de qualidade e perspectivas Myocardial cell therapy with bone marrow cells: criteria for quality and future perspectives

    Directory of Open Access Journals (Sweden)

    Maria Isabel D. Rossi

    2009-05-01

    Full Text Available A terapia celular pode ser uma nova opção terapêutica para pacientes cardíacos, modificando o processo de remodelamento cardíaco e prevenindo a falência cardíaca pós-infarto. Estudos clínicos até o presente usaram células mononucleadas de medula óssea, isoladas por centrifugação em gradiente de densidade a partir de aspirados de medula óssea da crista ilíaca. Embora esta nova estratégia revolucionária pareça ser segura e melhorar a função cardíaca, resultados negativos surgiram desafiando o futuro de terapias baseadas em células para o reparo cardíaco. Aqui discutimos alguns resultados laboratoriais que podem explicar, pelo menos parcialmente, as diferenças obtidas em protocolos similares. Uma análise da correlação entre a composição celular da fração mononuclear do aspirado da medula óssea e o êxito clínico da terapia indicou que os linfócitos não favorecem o reparo do miocárdio. Uma seleção negativa eliminando as linhagens do sistema imunitário pode ser proposta para melhorar a terapia celular do miocárdio.Cell therapy may provide a novel therapeutic option for cardiac patients, modifying myocardium remodeling processes and preventing post-infarction heart failure. Currently clinical studies predominantly use bone marrow mononuclear cells isolated by density gradient centrifugation of iliac crest bone marrow aspirates. Although this revolutionary new strategy seems to be safe and to improve myocardial function, negative data have emerged challenging the future of cell-based therapy for heart repair. Here we discuss some laboratory data that might explain, at least in part, variations in outcomes using similar protocols. Analysis of the correlation between the cell composition of the mononuclear fraction of bone marrow aspirates and the clinical outcome of the therapy has indicated that cells of the lymphocyte lineage are not beneficial in myocardial regeneration. A proposal of selection to eliminate

  8. Effects of timing on intracoronary autologous bone marrow-derived cell transplantation in acute myocardial infarction: a meta-analysis of randomized controlled trials.

    Science.gov (United States)

    Xu, Jia-Ying; Liu, Dai; Zhong, Yang; Huang, Rong-Chong

    2017-10-16

    Several cell-based therapies for adjunctive treatment of acute myocardial infarction have been investigated in multiple clinical trials, but the timing of transplantation remains controversial. We conducted a meta-analysis of randomized controlled trials to investigate the effects of timing on bone marrow-derived cell (BMC) therapy in acute myocardial infarction (AMI). A systematic literature search of PubMed, MEDLINE, and Cochrane Evidence-Based Medicine databases from January 2000 to June 2017 was performed on randomized controlled trials with at least a 3-month follow-up for patients with AMI undergoing emergency percutaneous coronary intervention (PCI) and receiving intracoronary BMC transfer thereafter. The defined end points were left ventricular (LV) ejection fraction, LV end-diastolic and end-systolic index. The data were analyzed to evaluate the effects of timing on BMC therapy. Thirty-four RCTs comprising a total of 2,307 patients were included; the results show that, compared to the control group, AMI patients who received BMC transplantation showed significantly improved cardiac function. BMC transplantation 3-7 days after PCI (+3.32%; 95% CI, 1.91 to 4.74; P BMC transplantation 3-7 days after PCI reduced LV end-diastolic indexes (-4.48; 95% CI, -7.98 to -0.98; P = 0.01) and LV end-systolic indexes (-6.73; 95% CI, -11.27 to -2.19; P = 0.004). However, in the groups who received BMC transplantation either within 24 hours or later than 7 days there was no significant effect on treatment outcome. In subgroup analysis, the group with LVEF ≤ 50% underwent a significant decrease in LV end-diastolic index after BMC transplantation (WMD = -3.29, 95% CI, -4.49 to -2.09; P BMC transplantation in the group with LVEF ≤ 50% (WMD = -5.25, 95% CI, -9.30 to -1.20; P = 0.01), as well as in patients who received a dose of 10^7-10^8 cells (WMD = -12.99, 95% CI, -19.07 to -6.91; P BMC transfer at 3 to 7 days post-AMI was

  9. Myocardial thallium-201 kinetics in normal and ischemic myocardium

    International Nuclear Information System (INIS)

    Grunwald, A.M.; Watson, D.D.; Holzgrefe, H.H. Jr.; Irving, J.F.; Beller, G.A.

    1981-01-01

    The net myocardial accumulation of thallium-201 after injection depends upon the net balance between continuing myocardial extraction from low levels of recirculating thallium in the blood compartment and the net rate of efflux of thallium from the myocardium into the extracardiac blood pool. These experiments were designed to measure separately the myocardial extraction and intrinsic myocardial efflux of thallium-201 at normal and at reduced rates of myocardial blood flow. The average myocardial extraction fraction at normal blood flow in 10 anesthetized dogs was 82 +/- 6% (+/- SD) at normal coronary arterial perfusion pressures and increased insignificantly, to 85 +/- 7%, at coronary perfusion pressures of 10--35 mm Hg. At normal coronary arterial perfusion pressures in 12 additional dogs, the intrinsic thallium washout in the absence of systemic recirculation had a half-time (T 1/2) of 54 +/- 7 minutes. The intrinsic cellular washout rate began to increase as distal perfusion pressures fell below 60 mm Hg and increased markedly to a T 1/2 of 300 minutes at perfusion pressures of 25--30 mm Hg. A second, more rapid component of intrinsic thallium washout (T 1/2 2.5 minutes) representing approximately 7% of the total initially extracted myocardial thallium was observed. The faster washout component is presumed to be due to washout of interstitial thallium unextracted by myocardial cells, whereas the slower component is presumed due to intracellular washout. The net clearance time of thallium measured after i.v. injection is much longer than the intrinsic myocardial cellular washout rate because of continuous replacement of myocardial thallium from systemic recirculation. Myocardial redistribution of thallium-201 in states of chronically reduced perfusion cannot be the result of increased myocardial extraction efficiency, but rather, is the result of the slower intrinsic cellular washout rate at reduced perfusion levels

  10. Hemostatic Status of Pre and Post Intracoronary Injection of Peripheral Blood Stem Cells in Patients with Recent Myocardial Infarction

    Directory of Open Access Journals (Sweden)

    Cosphiadi Irawan

    2014-01-01

    Full Text Available Aim: to investigate hemostatic parameter changes, such as platelet aggregation, blood and plasma viscosity, prothrombin time, APTT, CRP and fibrinogen, before and after administration of stem cell therapy. Methods: a total of 24 patients were enrolled. Peripheral blood stem cells (PBSCs were harvested and injected into the infarct-related artery after 5 consecutive days of G-CSF administration. Recombinant human erythropoietin was administered at the time of intracoronary PBSCs injection. Results: we were able to evaluate 11 from 24 of patients regarding hemostatic status pre–post stem cell injection. There were no significant difference between baseline vs 3 months in spontaneous aggregation (p=0.350, PT (p=0.793, aPTT (p=0.255 and TT (p=0.254. There were also no significant difference between baseline vs 3 months in plasma viscosity (p=0.442 and blood viscosity (p=0.843. Nevertheless the patient who had their blood and plasma viscosity above or below normal laboratory range return to normal level after the treatment. Both PT and APTT also show normalization value. Both Fibrinogen and CRP level show significant decrease between baseline and 3 months after treatment (p=0.009 and (p=0.04 respectively. Conclusion: combined G-CSF and EPO based-intracoronary infusion of PBSCs may open new perspective in the treatment of hypercoagulable state post AMI.

  11. X-ray microanalysis of chromatin-bound period 4 metals in Glenodinium foliaceum: A binucleate dinoflagellate

    International Nuclear Information System (INIS)

    Sigee, D.C.; Kearns, L.P.

    1981-01-01

    Each vegetative cell of the dinoflagellate Glenodinium foliaceum possesses two distinct types of nucleus, both of which have high levels of chromatinbound Period 4 (Periodic Table) metal elements. The typical dinoflagellate (dinocaryotic) nucleus has chromatin which differs from the atypical (supernumerary) nucleus in its high degree of condensation and in the related high levels of P, Ca, and Transition metals Fe, Ni, Cu, and Zn. The complete absence of detectable Fe and Ni in the supernumerary chromatin represents a major difference which may relate to differences in phyllogenetic origin of the two nuclei. The two types of chromatin show close similarities a the molecular level, including the possession of 40 atoms of Period 4 elements per 100 atoms of P-of which approximately half are Ca atoms, and half Transition metals. In both cases, the levels of Ca and Zn show a high correlation with the level of P, suggesting a direct association of these particular metal atoms with nucleic acid phosphate groups. The close similarity in metal binding at the molecular level suggests that the association of Period 4 elements with the two types of chromatin is unrelated to any differences in chromatin proteins-such as the presence or absence of histones. (author)

  12. Assessment of re-distribution and efficacy of stem cell transplantation in different heart status after acute myocardial infarction by MRI: an experimental study

    International Nuclear Information System (INIS)

    Lu Minjie; Zhao Shihua; Song Peng

    2011-01-01

    Objective: To evaluate the efficacy of MRI for assessment of re-distribution of bone marrow mesenchymal stem cells injected intramyocardially in main organs (heart, liver, spleen and kidney) under different heart status (beating or arresting) in a porcine model. Methods: Bone marrow-derived mesenchymal stem cells were obtained from the male swine and labeled with iron oxide during culture. Acute myocardial infarction was created in female swine, one week later, the survivors were randomly divided into 4 groups. Cardiopulmonary bypass was set up to arrest the heart, and then labeled cells (1 × 10 8 ) were intramyocardially injected into the border of the infracted myocardium in group 1 (n=6). The same volume of cells was grafted into the beating heart in group 2 (n=6). In group 3 and 4, saline was injected into either the arresting or beating myocardium. Three days later, re-distribution of stem cells and cardiac function were assessed by T 2 * WI and cine MRI, respectively. All animals were sacrificed for histology and real-time quantitative polymerase chain reaction (RT-PCR) of sex-determining region on Y-chromosome (SRY) investigation. The ANOVA and t test was used for statistics. Results: The left ventricular end- diastolic volume (LVEDV) before transplantation for group 1-4 were: (56.8±5.3), (54.8±6.8), (57.4±4.3) and (56.8±2.8) ml, and after transplantation for group 1-4 were: (65.2±5.2), (63.2± 3.7), (60.2±4.7) and (62.2±4.4) ml. The left ventricular end-systolic volume (LVESV) before transplantation for group 1-4 were : (33.5±7.6), (32.3±5.3), (33.5±3.6) and (32.7±4.6) ml, and after transplantation for group 1-4 were: (37.3±5.6), (36.3±6.9), (34.3±5.4) and (36.3± 8.1) ml. The left ventricular EF values (LVEF) before transplantation for group 1-4 were: (42.3± 7.2)%, (41.7±6.8)%, (41.8±8.6)% and (42.7±7.7)%, and after transplantation for group 1- 4 were: (44.5±8.7)%, (43.1±7.4)%, (42.8±5.6)% and (43.3±8.4)%. The myocardial infarction

  13. Shexiang Baoxin pills promotes angiogenesis in myocardial infarction rats via up-regulation of 20-HETE-mediated endothelial progenitor cells mobilization.

    Science.gov (United States)

    Huang, Feifei; Liu, Yang; Yang, Xia; Che, Di; Qiu, Kaifeng; Hammock, Bruce D; Wang, Jingfeng; Wang, Mong-Heng; Chen, Jie; Huang, Hui

    2017-08-01

    Therapeutic angiogenesis is a pivotal strategy for ischemic heart disease. The aim of the present study was to determine the effect and molecular mechanism of Shexiang Baoxin pills, a widely-used traditional Chinese medicine for ischemic heart disease, on angiogenesis in a rat model of myocardial infarction (MI). We used the occlusion of left anterior descending coronary artery of Sprague-Dawley rats as a model of MI. The MI rats were treated with distilled water, Shexiang Baoxin pills, or Shexiang Baoxin pills + HET0016 (a selective blocker of the biosynthesis of 20-hydroxyeicosatetraenoic acid (20-HETE) at 10 mg/kg/day), respectively. Sham-operated rats were used as controls. Treatment with Shexiang Baoxin pills increases the level of serum 20-HETE in MI rats, which can be suppressed by HET0016 treatment. Shexiang Baoxin pills shows cardio-protective effects on MI rats, including improving cardiac function, decreasing infarction area, and promoting angiogenesis in peri-infarct area. The protective effects of Shexiang Baoxin pills are partly inhibited by HET0016. Furthermore, Shexiang Baoxin pills enhances the number of circulating endothelial progenitor cells (EPCs) and the expression of the vascular endothelial growth factor (VEGF), based on immunohistochemical analysis, in peri-infarct area of MI rats, which is partly suppressed by HET0016. Shexiang Baoxin pills may partially participate in angiogenesis in MI rats. The protective mechanism of Shexiang Baoxin pills may be mediated via up-regulation of 20-HETE, which promotes EPCs mobilization and VEGF expression. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. LncRNA TUG1 serves an important role in hypoxia-induced myocardial cell injury by regulating the miR‑145‑5p‑Binp3 axis.

    Science.gov (United States)

    Wu, Zhongwei; Zhao, Shengji; Li, Chunfu; Liu, Chaoquan

    2018-02-01

    The aim of the present study was to investigate the function of long non‑coding RNA TUG1 in hypoxia‑induced myocardial cell injury and to explore the potential molecular mechanisms. The cardiomyocyte cell line H9c2 was cultured under hypoxic and normoxic conditions. TUG1 expression under hypoxic conditions was then detected. The effects of TUG1 overexpression on viability, apoptosis, migration and invasion were assayed. In addition, the microRNA (miR)‑145‑5p expression was detected. Following H9c2 cell transfection with miR‑145‑5p mimics, the H9c2 cell viability, apoptosis, migration and invasion were also detected. Additionally, the target gene of miR‑145‑5p was assayed by Luciferase reporter assay. The protein expressions of Wnt‑3a, Wnt5a, and β‑catenin in H9c2 cells under hypoxic conditions were also determined. The results revealed that hypoxia induced injury in H9c2 cells, including inhibiting cell viability, migration and invasion, and promoting cell apoptosis. Overexpression of TUG1 aggravated hypoxia‑induced injury in H9c2 cells. In addition, miR‑145‑5p was negatively regulated by TUG1, and TUG1 overexpression aggravated hypoxia‑induced injury via the downregulation of miR‑145‑5p. Furthermore, B‑cell lymphoma 2 interacting protein 3 (Bnip3) was a target of miR‑145‑5p, and overexpression of Bnip3 aggravated hypoxia‑induced cell injury by activating Wnt/β‑catenin signaling pathways in H9c2 cells. In conclusion, overexpression of TUG1 aggravated hypoxia‑induced injury in cardiomyocytes by regulating the miR‑145‑5p‑Binp3 axis. Activation of the Wnt/β‑catenin signaling pathway may be a key mechanism to mediate the role of TUG1 in regulating hypoxia‑induced myocardial injury. TUG1 may be an effective diagnostic marker and therapeutic target for myocardial ischemia.

  15. LncRNA TUG1 serves an important role in hypoxia-induced myocardial cell injury by regulating the miR-145-5p-Binp3 axis

    Science.gov (United States)

    Wu, Zhongwei; Zhao, Shengji; Li, Chunfu; Liu, Chaoquan

    2018-01-01

    The aim of the present study was to investigate the function of long non-coding RNA TUG1 in hypoxia-induced myocardial cell injury and to explore the potential molecular mechanisms. The cardiomyocyte cell line H9c2 was cultured under hypoxic and normoxic conditions. TUG1 expression under hypoxic conditions was then detected. The effects of TUG1 overexpression on viability, apoptosis, migration and invasion were assayed. In addition, the microRNA (miR)-145-5p expression was detected. Following H9c2 cell transfection with miR-145-5p mimics, the H9c2 cell viability, apoptosis, migration and invasion were also detected. Additionally, the target gene of miR-145-5p was assayed by Luciferase reporter assay. The protein expressions of Wnt-3a, Wnt5a, and β-catenin in H9c2 cells under hypoxic conditions were also determined. The results revealed that hypoxia induced injury in H9c2 cells, including inhibiting cell viability, migration and invasion, and promoting cell apoptosis. Overexpression of TUG1 aggravated hypoxia-induced injury in H9c2 cells. In addition, miR-145-5p was negatively regulated by TUG1, and TUG1 overexpression aggravated hypoxia-induced injury via the downregulation of miR-145-5p. Furthermore, B-cell lymphoma 2 interacting protein 3 (Bnip3) was a target of miR-145-5p, and overexpression of Bnip3 aggravated hypoxia-induced cell injury by activating Wnt/β-catenin signaling pathways in H9c2 cells. In conclusion, overexpression of TUG1 aggravated hypoxia-induced injury in cardiomyocytes by regulating the miR-145-5p-Binp3 axis. Activation of the Wnt/β-catenin signaling pathway may be a key mechanism to mediate the role of TUG1 in regulating hypoxia-induced myocardial injury. TUG1 may be an effective diagnostic marker and therapeutic target for myocardial ischemia. PMID:29207102

  16. Alcohol and the risk of myocardial infarction.

    Science.gov (United States)

    Flesch, M; Rosenkranz, S; Erdmann, E; Böhm, M

    2001-04-01

    Epidemiological studies have repeatedly demonstrated a beneficial effect of moderate alcohol consumption on the incidence of coronary heart disease, myocardial infarction and overall mortality. The latter increases with excessive alcohol consumption. Although most epidemiological studies demonstrate a beneficial effect of alcohol consumption independent from the specific kind of alcoholic beverage, there is increasing evidence that wine and in particular red wine might contain pharmacological substances, which prevent atherosclerosis and myocardial infarction independent from the wine ethanol. Pathophysiological mechanisms mediating these beneficial effects include effects of wine phenols and tannins on LDL-cholesterol oxidation status, thrombocyte aggregation, endothelial function and smooth muscle cell proliferation. Identification and characterization of the pharmacologically active substances might provide the stage for the development of new substances to be used in the prevention of coronary artery disease and myocardial infarction.

  17. De-novo collateral formation following acute myocardial infarction: Dependence on CCR2⁺ bone marrow cells.

    Science.gov (United States)

    Zhang, Hua; Faber, James E

    2015-10-01

    Wide variation exists in the extent (number and diameter) of native pre-existing collaterals in tissues of different strains of mice, with supportive indirect evidence recently appearing for humans. This variation is a major determinant of the wide variation in severity of tissue injury in occlusive vascular disease. Whether such genetic-dependent variation also exists in the heart is unknown because no model exists for study of mouse coronary collaterals. Also owing to methodological limitations, it is not known if ischemia can induce new coronary collaterals to form ("neo-collaterals") versus remodeling of pre-existing ones. The present study sought to develop a model to study coronary collaterals in mice, determine whether neo-collateral formation occurs, and investigate the responsible mechanisms. Four strains with known rank-ordered differences in collateral extent in brain and skeletal muscle were studied: C57BLKS>C57BL/6>A/J>BALB/c. Unexpectedly, these and 5 additional strains lacked native coronary collaterals. However after ligation, neo-collaterals formed rapidly within 1-to-2 days, reaching their maximum extent in ≤7 days. Rank-order for neo-collateral formation differed from the above: C57BL/6>BALB/c>C57BLKS>A/J. Collateral network conductance, infarct volume(-1), and contractile function followed this same rank-order. Neo-collateral formation and collateral conductance were reduced and infarct volume increased in MCP1(-/-) and CCR2(-/-) mice. Bone-marrow transplant rescued collateral formation in CCR2(-/-) mice. Involvement of fractalkine➔CX3CR1 signaling and endothelial cell proliferation were also identified. This study introduces a model for investigating the coronary collateral circulation in mice, demonstrates that neo-collaterals form rapidly after coronary occlusion, and finds that MCP➔CCR2-mediated recruitment of myeloid cells is required for this process. Copyright © 2015 Elsevier Ltd. All rights reserved.

  18. Growth factor-induced mobilization of cardiac progenitor cells reduces the risk of arrhythmias, in a rat model of chronic myocardial infarction.

    Directory of Open Access Journals (Sweden)

    Leonardo Bocchi

    Full Text Available Heart repair by stem cell treatment may involve life-threatening arrhythmias. Cardiac progenitor cells (CPCs appear best suited for reconstituting lost myocardium without posing arrhythmic risks, being commissioned towards cardiac phenotype. In this study we tested the hypothesis that mobilization of CPCs through locally delivered Hepatocyte Growth Factor and Insulin-Like Growth Factor-1 to heal chronic myocardial infarction (MI, lowers the proneness to arrhythmias. We used 133 adult male Wistar rats either with one-month old MI and treated with growth factors (GFs, n = 60 or vehicle (V, n = 55, or sham operated (n = 18. In selected groups of animals, prior to and two weeks after GF/V delivery, we evaluated stress-induced ventricular arrhythmias by telemetry-ECG, cardiac mechanics by echocardiography, and ventricular excitability, conduction velocity and refractoriness by epicardial multiple-lead recording. Invasive hemodynamic measurements were performed before sacrifice and eventually the hearts were subjected to anatomical, morphometric, immunohistochemical, and molecular biology analyses. When compared with untreated MI, GFs decreased stress-induced arrhythmias and concurrently prolonged the effective refractory period (ERP without affecting neither the duration of ventricular repolarization, as suggested by measurements of QTc interval and mRNA levels for K-channel α-subunits Kv4.2 and Kv4.3, nor the dispersion of refractoriness. Further, markers of cardiomyocyte reactive hypertrophy, including mRNA levels for K-channel α-subunit Kv1.4 and β-subunit KChIP2, interstitial fibrosis and negative structural remodeling were significantly reduced in peri-infarcted/remote ventricular myocardium. Finally, analyses of BrdU incorporation and distribution of connexin43 and N-cadherin indicated that cytokines generated new vessels and electromechanically-connected myocytes and abolished the correlation of infarct size with deterioration

  19. Absence of accelerated atherosclerotic disease progression after intracoronary infusion of bone marrow derived mononuclear cells in patients with acute myocardial infarction--angiographic and intravascular ultrasound--results from the TErapia Celular Aplicada al Miocardio Pilot study.

    Science.gov (United States)

    Arnold, Roman; Villa, Adolfo; Gutiérrez, Hipólito; Sánchez, Pedro L; Gimeno, Federico; Fernández, Maria E; Gutiérrez, Oliver; Mota, Pedro; Sánchez, Ana; García-Frade, Javier; Fernández-Avilés, Francisco; San Román, Jose A

    2010-06-01

    We tried to evaluate a putative negative effect on coronary atherosclerosis in patients receiving intracoronary infusion of unfractionated bone marrow mononuclear cells (BMMC) following an acute ST-elevation myocardial infarction. Peripheral blood mononuclear cells or enriched CD133(+) BMMC have been associated with accelerated atherosclerosis of the distal segment of the infarct related artery (IRA). Thirty-seven patients with ST-elevation myocardial infarction from the TECAM pilot study underwent intracoronary infusion of autologous BMMC 9 +/- 3.1 days after onset of symptoms. We compared angiographic changes from baseline to 9 months of follow-up in the distal non-stented segment of the IRA, as well as in the contralateral coronary artery, with a matched control group. A subgroup of 15 treated patients underwent additional IVUS within the distal segment of the IRA. No difference between stem cell and control group were found regarding changes in minimum lumen diameter (0.006 +/- 0.42 vs 0.06 +/- 0.41 mm, P = ns) and the percentage of stenosis (-2.68 +/- 12.33% vs -1.78 +/- 8.75%, P = ns) at follow-up. Likewise, no differences were seen regarding changes in the contralateral artery (minimum lumen diameter -0.004 +/- 0.54 mm vs -0.06 +/- 0.35 mm, P = ns). In the intravascular ultrasound substudy, no changes were demonstrated comparing baseline versus follow-up in maximum area stenosis and plaque volume. In this pilot study, analysis of a subgroup of patients found that intracoronary injection of unfractionated BMMC in patients with acute ST-elevation myocardial infarction was not associated with accelerated atherosclerosis progression at mid term. Prospective, randomised studies in large cohorts with long-term angiographic and intravascular ultrasound follow-up are necessary to determine the safety of this therapy. Copyright 2010 Mosby, Inc. All rights reserved.

  20. Melatonin protects against myocardial hypertrophy induced by lipopolysaccharide.

    Science.gov (United States)

    Lu, Qi; Yi, Xin; Cheng, Xiang; Sun, Xiaohui; Yang, Xiangjun

    2015-04-01

    Melatonin is thought to have the ability of antiatherogenic, antioxidant, and vasodilatory. It is not only a promising protective in acute myocardial infarction but is also a useful tool in the treatment of pathological remodeling. However, its role in myocardial hypertrophy remains unclear. In this study, we investigated the protective effects of melatonin on myocardial hypertrophy induced by lipopolysaccharide (LPS) and to identify their precise mechanisms. The cultured myocardial cell was divided into six groups: control group, LPS group, LPS + ethanol (4%), LPS + melatonin (1.5 mg/ml) group, LPS + melatonin (3 mg/ml) group, and LPS + melatonin (6 mg/ml) group. The morphologic change of myocardial cell was observed by inverted phase contrast microscope. The protein level of myocardial cell was measured by Coomassie brilliant blue protein kit. The secretion level of tumor necrosis factor-α (TNF-α) was evaluated by enzyme-linked immunosorbent assay (ELISA). Ca(2+) transient in Fura-2/AM-loaded cells was measured by Till image system. The expression of Ca(2+)/calmodulin-dependent kinase II (CaMKII) and calcineurin (CaN) was measured by Western blot analysis. Our data demonstrated that LPS induced myocardial hypertrophy, promoted the secretion levels of TNF-α, and increased Ca(2+) transient level and the expression of CaMKII and CaN. Administration of melatonin 30 min prior to LPS stimulation dose-dependently attenuated myocardial hypertrophy. In conclusion, the results revealed that melatonin had the potential to protect against myocardial hypertrophy induced by LPS in vitro through downregulation of the TNF-α expression and retains the intracellular Ca(2+) homeostasis.

  1. A randomized double-blind control study of early intra-coronary autologous bone marrow cell infusion in acute myocardial infarction

    DEFF Research Database (Denmark)

    Choudry, Fizzah; Hamshere, Stephen; Saunders, Natalie

    2016-01-01

    increased compared with baseline in both groups, the between-group difference favouring BMC was small (2.2%; 95% confidence interval, CI: -0.5 to 5.0; P = 0.10). However, there was a significantly greater myocardial salvage index in the BMC-treated group compared with placebo (0.1%; 95% CI: 0.0-0.20; P = 0...

  2. Myocardial scintigraphy with thallium-201

    Energy Technology Data Exchange (ETDEWEB)

    Lichte, H [Zentralkrankenhaus Gauting (Germany, F.R.). Nuklearmedizinische Abt.

    1977-04-01

    Myocardial scintigraphy with /sup 201/thallium is a non-invasive method for detection of myocardial infarction and coronary heart disease. Redistribution-analysis as a sequential-scintigraphy of an exercise-scan permits to distinguish between myocardial scars and coronary vessel disease.

  3. In vitro incorporation of tritiated thymidine by the Sternberg-Reed cells in Hodgkin disease

    Energy Technology Data Exchange (ETDEWEB)

    Marinello, M; Tkachenko, G; Gavilondo, J; Baeza, B [National Institute of Oncology and Radiology, Havana (Cuba)

    1975-01-01

    A new DNA synthesis by the Sternberg-Reed cells in Hodgkin disease was studied using tritiated thymidine and autoradiography. The results show that after incubation pulses of 30 and 60 minutes, cells with lobulated nucleus, binucleated and trinucleated cells identifiable to the diagnostic Sternberg-Reed cells could undergo a new DNA synthesis. This points to a more dynamic interpretation of this type of cell.

  4. Myocardial myoglobin release after acute myocardial infarction

    Energy Technology Data Exchange (ETDEWEB)

    Robinson, P S; Saltissi, S; Coltart, D J; Croft, D N [Saint Thomas' Hospital, London (UK)

    1980-03-01

    The magnitude and time course of myoglobin release from the myocardium following infarction was assessed by radioimmunoassay. The assay showed acceptable precision over a working range from 50 to 750 ng cm/sup -3/, provided careful control of the assay temperature was maintained. The use of this radioimmunoassay as an early diagnostic test for infarction and as a potential measure of the extent of necrosis is considered and comparison made with the release of CK-MB, the myocardial specific isoenzyme of creatine kinase. Of the twenty patients studied with myocardial infarction, all had elevated levels of serum myoglobin including those admitted within 3 hours of the onset of pain. In contrast, CK-MB was not detected in the serum within 5 hours of the onset of pain. Peak serum levels of myoglobin (mean 852 +- 365 ng cm/sup -3/) and CK-MB (mean 71 +- 25 mIU cm/sup -3/) were detected at 8-16 hours and 20-24 hours respectively after the onset of pain. A comparison of peak serum levels of myoglobin and CK-MB showed a good correlation (r = 0.84).

  5. Reversible myocardial ischaemia or irreversible myocardial fibrosis

    International Nuclear Information System (INIS)

    Mathey, D.; Hanrath, P.; Kupper, W.; Bleifeld, W.; Montz, R.; Knop, J.; Stritzke, P.; Kroeger, E.; Bleese, N.

    1978-01-01

    The results of biphasis 201 thallium ( 201 Tl) scanning were compared with those of coronary arteriography, left ventricular angiography and stress ECG in 56 patients with coronary artery disease and six with no evidence of heart disease. There were 104 201 Tl defects, 50 of them reversible. The defects were always located in the area supplied by a critically stenotic coronary artery. Correlation of regional wall motion with 201 Tl activity demonstrated that in all forms of abnormal wall motion there was either ischaemia or fibrosis. The resting LV angiogram thus does not make it possible to distinguish between myocardial ischaemia and fibrosis. Taking the LV angiogram as a standard, the rate of false-positive 201 Tl scintigrams was 5%, that of false-negative ones 23%. The biphasic 201 Tl scintigram was more sensitive than the stress ECG in detecting myocardial ischaemia. It furthermore made it possible to localize the ischaemic (or fibrotic) region within the LV and to estimate its size. (orig.) [de

  6. Cardioprotection against experimental myocardial ischemic injury using cornin

    Directory of Open Access Journals (Sweden)

    Y. Xu

    2016-01-01

    Full Text Available Phosphorylated-cyclic adenosine monophosphate response element-binding protein (Phospho-CREB has an important role in the pathogenesis of myocardial ischemia. We isolated the iridoid glycoside cornin from the fruit of Verbena officinalis L, investigated its effects against myocardial ischemia and reperfusion (I/R injury in vivo, and elucidated its potential mechanism in vitro. Effects of cornin on cell viability, as well as expression of phospho-CREB and phospho-Akt in hypoxic H9c2 cells in vitro, and myocardial I/R injury in vivo, were investigated. Cornin attenuated hypoxia-induced cytotoxicity significantly in H9c2 cells in a concentration-dependent manner. Treatment of H9c2 cells with cornin (10 µM blocked the reduction of expression of phospho-CREB and phospho-Akt in a hypoxic condition. Treatment of rats with cornin (30 mg/kg, iv protected them from myocardial I/R injury as indicated by a decrease in infarct volume, improvement in hemodynamics, and reduction of severity of myocardial damage. Cornin treatment also attenuated the reduction of expression of phospho-CREB and phospho-Akt in ischemic myocardial tissue. These data suggest that cornin exerts protective effects due to an increase in expression of phospho-CREB and phospho-Akt.

  7. Evaluation of myocardial abnormalities in patients with collagen diseases by thallium-201 myocardial scintigram

    Energy Technology Data Exchange (ETDEWEB)

    Yamano, Shigeru (Nara Medical Univ., Kashihara (Japan))

    1992-08-01

    This study was performed to evaluate myocardial lesions in patients with collagen diseases by rest and exercise thallium-201 myocardial scintigraphies. A total of 76 patients without ischemic ECG changes, consisting of 27 cases of systemic lupus erythematosus (SLE), 17 cases of polymyositis or dermatomyositis (PM[center dot]DM), 11 cases of progressive systemic sclerosis (PSS), and 21 cases of Sjoegren's syndrome (SjS), were enrolled in this study. Reversible exercise-induced defects suggesting myocardial ischemia were noted in 12 cases of SLE, 5 cases of PM[center dot]DM, 3 cases of PSS, and 3 cases of SjS. Of the 23 patients who had exercise-induced defects, 9 patients showed normal coronary angiograms by cardiac catheterization. Fixed hypoperfusion areas were observed in 5 cases of SLE, 6 cases of PM[center dot]DM, 4 cases of PSS and 3 cases of SjS. Rest thallium-201 myocardial scintigraphy disclosed hypoperfusion areas, which were not induced by exercise, in 1 case of SLE, 4 cases of PM[center dot]DM, 1 case of PSS and 5 cases of SjS. Endomyocardial biopsy was performed on 20 patients. Myocardial lesions in PM[center dot]DM and PSS were more severe and wide spread than in SLE. Ejection fraction and fractional shortening evaluated by echocardiography had no significant differences between each disease group and the healthy control group. These findings suggest that patients with collagen diseases show the presence of abnormalities of coronary circulation at the level of the intramyocardial vasculature in the stage before impairment of cardiac function, myocardial fibrosis and functional abnormalities of the cell membrane level that were not dependent on myocardial ischemia. (author).

  8. Evidence of heritable lethal mutations in progeny of X-irradiated CHO cells by micronucleus count in clon-cells

    International Nuclear Information System (INIS)

    Hagemann, G.; Kreczik, A.; Treichel, M.

    1996-01-01

    Low doses of ionizing radiation reduce the growth rates of clones following irradiation of the progenitor cells. Such reductions of clone growth have been proven by means of measurements of clone size distributions. The medians of such distributions can be used to quantify the radiation damage. Prolongations of generation times and cell death as result of heritable lethal mutations have been discussed as causes for the reduction of clone growth. The cell number of a clone of hypotetraploid CHO-cells was compared to the frequency of micronucleated binucleated cells in the same clone using the cytokinesis-block-micronucleus method. The dose dependent reduction of clone sizes is measured by the difference of the medians (after log transformation) of the clone size distributions. At cytochalasin-B concentrations of 1 μg/ml and after an incubation time of 16 h a yield of binucleated cells of about 50% was obtained. Median clone size differences as a measure of clonal radiation damage increased linearly with incubation times of 76, 100, 124, and 240 h following irradiation with 3, 5, 7, and 12 Gy. The frequency of binucleated clone cells with micronuclei strongly increased with decreasing clone size by a factor up to 20 following irradiation with 3, 5, and 7 Gy. The frequency of micronucleated binucleated clone cells was found to be independent of incubation time after irradiation. Radiation induced clone size reductions result from cell losses caused by intraclonal expression of micronuclei which have its origin in heritable lethal mutations. Measurements of clone size distributions can be done automatically. They can serve as predictive test for determination of median cell loss rates of surviving cell clones. (orig./MG) [de

  9. Impact of intracoronary injection of mononuclear bone marrow cells in acute myocardial infarction on left ventricular perfusion and function: a 6-month follow-up gated 99mTc-MIBI single-photon emission computed tomography study

    International Nuclear Information System (INIS)

    Lipiec, Piotr; Krzeminska-Pakula, Maria; Plewka, Michal; Kasprzak, Jaroslaw D.; Kusmierek, Jacek; Plachcinska, Anna; Szuminski, Remigiusz; Robak, Tadeusz; Korycka, Anna

    2009-01-01

    We investigated the impact of intracoronary injection of autologous mononuclear bone marrow cells (BMC) in patients with acute ST elevation myocardial infarction (STEMI) on left ventricular volumes, global and regional systolic function and myocardial perfusion. The study included 39 patients with first anterior STEMI treated successfully with primary percutaneous coronary intervention. They were randomly assigned to the treatment group or the control group in a 2:1 ratio. The patients underwent baseline gated single-photon emission computed tomography (G-SPECT) 3-10 days after STEMI with quantitative and qualitative analysis of left ventricular perfusion and systolic function. On the following day, patients from the BMC treatment group were subjected to bone marrow aspiration, mononuclear BMC isolation and intracoronary injection. No placebo procedure was performed in the control group. G-SPECT was repeated 6 months after STEMI. Baseline and follow-up G-SPECT studies were available for 36 patients. At 6 months in the BMC group we observed a significantly enhanced improvement in the mean extent of the perfusion defect, the left ventricular perfusion score index, the infarct area perfusion score and the infarct area wall motion score index compared to the control group (p=0.01-0.04). However, the changes in left ventricular volume, ejection fraction and the left ventricular wall motion score index as well as the relative changes in the infarct area wall motion score index did not differ significantly between the groups. Intracoronary injection of autologous mononuclear BMC in patients with STEMI improves myocardial perfusion at 6 months. The benefit in infarct area systolic function is less pronounced and there is no apparent improvement of global left ventricular systolic function. (orig.)

  10. Myocardial perfusion SPECT imaging in patients with myocardial bridging

    International Nuclear Information System (INIS)

    Fang Wei; Qiu Hong; Yang Weixian; Wang Feng; He Zuoxiang

    2008-01-01

    Objective: Stress myocardial perfusion SPECT imaging was used to assess myocardial ischemia in patients with myocardial bridging. Methods: Ninety-six patients with myocardial bridging of the left anterior descending artery documented by coronary angiography were included in this study. All under- went exercise or pharmacological stress myocardial perfusion SPECT assessing myocardial ischemia. None had prior myocardial infarction. One year follow-up by telephone interview was performed in all patients. Results The mean stenotic severity of systolic phase on angiography was (65 ± 19)%. In the SPECT study, 20 of 96 (20.8%) patients showed abnormal perfusion. This percentage was significantly higher than that of stress electrocardiogram (ECG). The higher positive rate of SPECT perfusion images was showed in the group of patients with severe systolic narrowing (≥75%) than that with mild-to-moderate systolic narrowing (50% vs 6.3%, P<0.001). The prevalence of abnormal image was significantly higher in ELDERLY PEOPLE; patients with STT change on rest ECG than in those with normal rest ECG (54.2% vs 9.7%, P<0.001). During follow-up, one patient with abnormal SPECT perfusion image sustained angina and accepted percutaneous coronary intervention, and no cardiac event occurred in patients with normal images. Conclusions: Stress myocardial perfusion SPECT imaging can be used effectively for assessing myocardial ischemia and has potential prognostic value for patients with myocardial bridging. (authors)

  11. Evaluation of myocardial abnormalities in collagen diseases by thallium-201 myocardial scintigraphy

    Energy Technology Data Exchange (ETDEWEB)

    Yamano, Shigeru; Kagoshima, Tadashi; Sugihara, Kiyotaka (Nara Medical Univ., Kashihara (Japan)) (and others)

    1993-12-01

    This study was performed to evaluate myocardial abnormalities in patients with collagen diseases by exercise and rest thallium-201 myocardial scintigrams. A total of 65 patients without ischemic ECG changes, consisting of 18 with systemic lupus erythematosus (SLE), 18 with polymyositis (PM), 8 with progressive systemic sclerosis (PSS), and 21 with Sjoegren's syndrome (SjS), was enrolled in this study. Reversible exercise-induced defects scintigraphically suggesting myocardial ischemia were noted in 8 cases of SLE, 4 cases of PM, 4 cases of PSS, and 3 cases of SjS. Nineteen patients had exercise-induced defects and underwent cardiac catheterization, 8 of whom had normal coronary angiograms. Fixed hypoperfusion areas were observed in one case of SLE, 6 cases of PM and 3 cases of SjS. Rest thallium-201 myocardial scintigram disclosed hypoperfusion areas which were not induced by exercise in 2 cases of SLE, 3 cases of PM, one case of PSS and 5 cases of SjS. Echocardiogram showed no significant differences in ejection fraction and % fractional shortening between the disease groups and healthy control group. These findings suggest that patients with collagen diseases have abnormalities of coronary circulation at the level of the intramural vasculature before cardiac function impairment, myocardial fibrosis and functional abnormalities at the cell membrane. (author).

  12. Surgical myocardial revascularization without extracorporeal circulation

    Directory of Open Access Journals (Sweden)

    Salomón Soriano Ordinola Rojas

    2003-05-01

    Full Text Available OBJECTIVE: To assess the immediate postoperative period of patients undergoing myocardial revascularization without extracorporeal circulation with different types of grafts. METHODS: One hundred and twelve patients, 89 (79.5% of whom were males, were revascularized without extracorporeal circulation. Their ages ranged from 39 to 85 years. The criteria for indicating myocardial revascularization without extracorporeal circulation were as follows: revascularized coronary artery caliber > 1.5 mm, lack of intramyocardial trajectory on coronary angiography, noncalcified coronary arteries, and tolerance of the heart to the different rotation maneuvers. RESULTS: Myocardial revascularization without extracorporeal circulation was performed in 112 patients. Three were converted to extracorporeal circulation, which required a longer hospital stay but did not impact mortality. During the procedure, the following events were observed: atrial fibrillation in 10 patients, ventricular fibrillation in 4, total transient atrioventricular block in 2, ventricular extrasystoles in 58, use of a device to retrieve red blood cells in 53, blood transfusion in 8, and arterial hypotension in 89 patients. Coronary angiography was performed in 20 patients on the seventh postoperative day when the grafts were patent. CONCLUSION: Myocardial revascularization without extracorporeal circulation is a reproducible technique that is an alternative for treating ischemic heart disease.

  13. Thallium-201 myocardial imaging

    International Nuclear Information System (INIS)

    Wackers, F.J.Th.

    1980-01-01

    Three views are routinely obtained for 201 Tl scintigraphy: 0 0 anterior, 45 0 left-anterior-oblique, both views with the patient supine and a left-lateral view, with the patient lying on his right side. Following intravenous injection of 201 Tl, the scintiscans of a normal subject only demonstrate the left ventricle. In patients with normal myocardial perfusion, the left ventricle appears horseshoe or ovoid in shape. The central area of decreased activity represents the left ventricular cavity and is normal. The accumulation of 201 Tl in the normal left ventricle is usually homogeneous. However, some areas with apparent diminished uptake may occur in the normal subject. These variations of the normal image are discussed. The right ventricle, because of its smaller myocardial mass and relatively less 201 Tl accumulation per gram of tissue, is usually on a resting study not, or only faintly, visualized. However, following exercise, the right ventricle is clearly visualized. (Auth.)

  14. Myocardial ischemia in hypertrophic cardiomyopathy

    International Nuclear Information System (INIS)

    Lima Filho, Moyses de Oliveira; Figueiredo, Geraldo L.; Simoes, Marcus V.; Pyntia, Antonio O.; Marin Neto, Jose Antonio

    2000-01-01

    Myocardial ischemia in hypertrophic cardiomyopathy is multifactorial and explains the occurrence of angina, in about 50% of patients. The pathophysiology of myocardial ischemia may be explained by the increase of the ventricular mass and relative paucity of the coronary microcirculation; the elevated ventricular filling pressures and myocardial stiffness causing a compression of the coronary microvessels; the impaired coronary vasodilator flow reserve caused by anatomic and functional abnormalities; and the systolic compression of epicardial vessel (myocardial bridges). Myocardial ischemia must be investigated by perfusion scintigraphic methods since its presence influences the prognosis and has relevant clinical implications for management of patients. Patients with hypertrophic cardiomyopathy and documented myocardial ischemia usually need to undergo invasive coronary angiography to exclude the presence of concomitant atherosclerotic coronary disease. (author)

  15. Acute myocardial infarcts

    International Nuclear Information System (INIS)

    Just, H.

    1988-01-01

    Acute myocardial infarction is a major complication of stenosing coronary artery disease and constitutes the most frequent single cause of death. It is caused by thrombotic occlusion of one of the major epicardial coronary arterial branches in most cases. Sudden death due to ventricular fibrillation is responsible for the majority of early fatalities. In 60% of all fatal infarcts, death occurs within 1 h of the onset of pain. The final extension of myocardial necrosis is reached within 2-4 h. An integrated programme has therefore been developed for the supervision and treatment of patients suffering acute coronary attack; it has been shown that it can markedly lower infarct mortality. It includes mobile prehospital care, intensive care treatment in the hospital, and rehabilitative procedures for application during reconvalescence. Early antiarrhythmic treatment and myocardial reperfusion via fibrinolysis are the main therapeutic procedures in the earliest stage. In hospital an operating room and an operating team must be available round the clock for the performance of coronary angiography followed by percutaneous transluminal coronary angioplasty or bypass surgery, which can be safely carried out in the acute stage provided the indications are strictly observed. Mortality and morbidity can be significantly lowered and both life expectancy and quality of life can be remarkably improved. (orig.) [de

  16. Heart dysfunction and fibrosis in rat treated with myocardial ...

    African Journals Online (AJOL)

    use

    2011-11-16

    Nov 16, 2011 ... choosing a suitable animal model provides good test material for MI and helps in clinical ... good material for regenerative medicine and cell therapy research in MI and .... model animal can be used to study drug treatment to improve the condition of myocardial ischemia, stem cell therapy research, and ...

  17. DNA double-strand breaks and Aurora B mislocalization induced by exposure of early mitotic cells to H2O2 appear to increase chromatin bridges and resultant cytokinesis failure.

    Science.gov (United States)

    Cho, Min-Guk; Ahn, Ju-Hyun; Choi, Hee-Song; Lee, Jae-Ho

    2017-07-01

    Aneuploidy, an abnormal number of chromosomes that is a hallmark of cancer cells, can arise from tetraploid/binucleated cells through a failure of cytokinesis. Reactive oxygen species (ROS) have been implicated in various diseases, including cancer. However, the nature and role of ROS in cytokinesis progression and related mechanisms has not been clearly elucidated. Here, using time-lapse analysis of asynchronously growing cells and immunocytochemical analyses of synchronized cells, we found that hydrogen peroxide (H 2 O 2 ) treatment at early mitosis (primarily prometaphase) significantly induced cytokinesis failure. Cytokinesis failure and the resultant formation of binucleated cells containing nucleoplasmic bridges (NPBs) seemed to be caused by increases in DNA double-strand breaks (DSBs) and subsequent unresolved chromatin bridges. We further found that H 2 O 2 induced mislocalization of Aurora B during mitosis. All of these effects were attenuated by pretreatment with N-acetyl-L-cysteine (NAC) or overexpression of Catalase. Surprisingly, the PARP inhibitor PJ34 also reduced H 2 O 2 -induced Aurora B mislocalization and binucleated cell formation. Results of parallel experiments with etoposide, a topoisomerase IIα inhibitor that triggers DNA DSBs, suggested that both DNA DSBs and Aurora B mislocalization contribute to chromatin bridge formation. Aurora B mislocalization also appeared to weaken the "abscission checkpoint". Finally, we showed that KRAS-induced binucleated cell formation appeared to be also H 2 O 2 -dependent. In conclusion, we propose that a ROS, mainly H 2 O 2 increases binucleation through unresolved chromatin bridges caused by DNA damage and mislocalization of Aurora B, the latter of which appears to augment the effect of DNA damage on chromatin bridge formation. Copyright © 2017 Elsevier Inc. All rights reserved.

  18. SURGERY OF SYMPTOMATIC MYOCARDIAL BRIDGING

    Directory of Open Access Journals (Sweden)

    N. Maghamipour N. Safaei

    2007-06-01

    Full Text Available Myocardial bridging with systolic compression of the left anterior descending coronary artery (LAD may be associated with myocardial ischemia. In symptomatic myocardial bridging unresponsive to medical treatment, surgical unroofing of the left LAD can be performed. Little information is available about the long-term prognosis of patients with this coronary anomaly after the surgical unroofing, so we decided to evaluate the result of this operation. A total of 26 patients underwent surgical unroofing of myocardial bridging. Patients had a myocardial bridge of at least 3 cm in length in the middle of LAD and with more than 70% compression during systole. Unroofing was performed with cardiopulmonary bypass in 16 and with off pump technique in 10 patients. In 6 patients repeat angiographies for control of myotomy were done. In one of them a nonsignificant 20% narrowing was seen. Postoperative scintigraphic and angiographic studies demonstrated restoration of coronary flow and myocardial perfusion without residual myocardial bridges under beta-stimulation in 24 patients. Two patients had residual narrowing. With off pump technique, 1 patient had perforation of the right ventricle and 1 patient underwent reoperation because of incomplete unroofing during the first operation. None of the patients with cardiopulmonary bypass technique had residual chest pain or other complications. Surgical unroofing of myocardial bridging with the aid of cardiopulmonary bypass is a safe and easy procedure with low operative risk and with excellent functional results.

  19. Value of serum tenascin-C in patients with acute myocardial infarction

    African Journals Online (AJOL)

    Background: Myocardial infarction (MI) is defined as myocardial cell necrosis due to significant and sustained ischemia. TN-C is an extracellular matrix glycoprotein that is expressed in several important steps during the very early stage of cardiogenesis. TN-C is not normally expressed in the adult heart, but transiently ...

  20. The Myocardial Unfolded Protein Response during Ischemic Cardiovascular Disease

    Directory of Open Access Journals (Sweden)

    Edward B. Thorp

    2012-01-01

    Full Text Available Heart failure is a progressive and disabling disease. The incidence of heart failure is also on the rise, particularly in the elderly of industrialized societies. This is in part due to an increased ageing population, whom initially benefits from improved, and life-extending cardiovascular therapy, yet ultimately succumb to myocardial failure. A major cause of heart failure is ischemia secondary to the sequence of events that is dyslipidemia, atherosclerosis, and myocardial infarction. In the case of heart failure postmyocardial infarction, ischemia can lead to myocardial cell death by both necrosis and apoptosis. The extent of myocyte death postinfarction is associated with adverse cardiac remodeling that can contribute to progressive heart chamber dilation, ventricular wall thinning, and the onset of loss of cardiac function. In cardiomyocytes, recent studies indicate that myocardial ischemic injury activates the unfolded protein stress response (UPR and this is associated with increased apoptosis. This paper focuses on the intersection of ischemia, the UPR, and cell death in cardiomyocytes. Targeting of the myocardial UPR may prove to be a viable target for the prevention of myocyte cell loss and the progression of heart failure due to ischemic injury.

  1. Stem-cells transplantation for myocardial regeneration Trasplante autólogo de médula ósea: propuesta basada en la evidencia, para un consenso en enfermedad cardiovascular

    Directory of Open Access Journals (Sweden)

    Francisco Cuellar Ambrosi

    2005-04-01

    Full Text Available Heart failure is a heterogeneous clinical syndrome that develops after an "index event" which damages cardiac tissue with loss of cardimyocytes and/or alteration of myocardial ability to generate an efficient ventricular contraction. The initial injury can appear suddenly as in the acute coronary syndrome or gradually as happens in chronic coronary arteries disease, and primary or secondary cardiomyopathies. Regardless of the etiologic factor, a series of hemodynamic alterations and neurohormonal responses with complex molecular changes is produced, leading to progression of ventricular dysfunction and to greater loss of contractile cells due to necrosis or apoptosis. Therapeutic strategies developed so far to interrupt this vicious circle of myocardial dysfunction and ventricular remodeling, do change the conditions of myocardial work, improving the situation of patients and their survival probability. However, this therapeutic approach does not produce myocardial regeneration, and consequently, the disease may progress to terminal heart failure and death. Experimental and clinical studies have revealed that implantation of bone marrow stem cells may produce angiogenesis and improve cardiac function in patients with acute or chronic ischaemic heart disease. It has been found that this therapy produces significant improvement of several parameters such as: symptoms, exercise capacity, functional state, size of the myocardial perfusion defect and ejection fraction; besides, there is a decrease in the end-systolic left ventricle volume. The procedure is not associated with complications. In conclusion, bone marrow stem cells transplantation is an effective and safe form of therapy to promote neovascularization and improve myocardial perfusion and contractility in patients with acute or chronic ischaemic heart disease who are not appropriate candidates for standard revascularization therapies. La falla cardíaca es un síndrome clínico heterog

  2. [Myocardial ultrastructural changes in rats following different levels of acute +Gz exposure].

    Science.gov (United States)

    Zheng, Jun; Liu, Cheng-gang; Ren, Li; Xiao, Xiao-guang; Xu, Shu-xuan; Wang, Ping; Ji, Gui-ying

    2004-06-01

    To observe the effects of different levels of acute +Gz exposure on myocardial ultrastructure of rats and provide experimental basis for further development of anti-G measures. Twenty male Wistar rats were randomly divided into 4 groups (n=5): normal control group, +20 Gz group, +10 Gz group and +5 Gz group. Profile of the centrifuge +Gz exposure was trapezoidal, in which +20 Gz lasted for 30 s, +10 Gz for 1.5 min. +5 Gz exposure was repeated for 3 times with 30 min interval and each for 1.5 min. Myocardial tissue of left ventricle was sampled for transmission electron microscopy 5 h after exposure. +20 Gz and +10 Gz exposure caused obvious edema of myocardial and endothelial cells, myofibril disorder and injuries of mitochondria and nucleus. Breaks of myocardial fiber, formation of contraction bands and rupture of mitochondria were also observed in +20 Gz group. In +5 Gz group, there was still slight edema of myocardial and endothelial cells, while organic changes of myocardial ultrastructure were not observed. High +Gz exposure can cause myocardial ultrastructural injury in rats. Slight reversible injured response can also be observed in myocardial cell after repeated moderate level of +Gz exposure. This indicates that attention should be paid to the study of the effect of high +Gz on heart in pilots.

  3. Depression following myocardial infarction

    DEFF Research Database (Denmark)

    Larsen, Karen Kjær

    2013-01-01

    whether the mental burden of MI is so heavy that it increases the risk of suicide. Although post-MI depression is common and burdensome, the condition remains under-recognised and under-treated. The development of new strategies to improve the quality of care for people with post-MI depression requires...... between post-MI depression and new cardiovascular events or death, taking potential mediators into account (Paper III); 4. To examine the association between MI and suicide (Paper IV). Two different study designs were employed: a population-based cohort study using data obtained from registers......Myocardial infarction (MI) is a severe life event that is accompanied by an increased risk of depression. Mounting evidence suggests that post-MI depression is associated with adverse outcomes, but the underlying mechanisms of this association remain unclear, and no previous studies have examined...

  4. [Effect of compound danshen dripping pill combined with intravenous transplantation of human umbilical cord blood mononuclear cells on local inflammatory response in the myocardium of rabbits with acute myocardial infarction].

    Science.gov (United States)

    Deng, Liu-xia; Yu, Guo-long; Al, Qi; Yuan, Chun-ju

    2013-11-01

    To investigate effect of Compound Danshen Dripping Pill (CDDP) on the inflammatory response of the myocardium of acute myocardial infarction (AMI) rabbits, to observe the therapeutic effect of CDDP combined intravenous transplantation of human umbilical cord blood mononuclear cells (HUCBMCs) on inflammatory response, pro-inflammatory cytokine tumor necrosis factor alpha (TNF-alpha) , and heart function in the myocardium of AMI rabbits, and to explore the possible protective mechanisms of the combined therapy. The AMI model was successfully established by ligation of the left anterior coronary artery (LAD) in 40 healthy rabbits.Then they were randomly divided into four groups, i.e., the control group, the CDDP group, the transplantation group, and the combined group, 10 in each group. Rabbits in the control group received intravenous injection of 0.5 mL normal saline via ear vein within 24 h after AMI and then intragastric infusion of normal saline at 5 mL per day. Rabbits in the CDDP group received intravenous injection of 0.5 mL normal saline via ear vein within 24 h after AMI and then intragastric infusion of solution obtained by solving 270 mg CDDP in 5 mL normal saline per day. Rabbits in the transplantation group received intravenous injection of 0.5 mL normal saline labeled with green fluorescent protein (GFP) containing 3 x 10(7) of HUCBMCs via ear vein within 24 h after AMI and then intragastric infusion of normal saline at 5 mL per day. Rabbits in the combined group received intravenous injection of 0.5 mL normal saline labeled with GFP containing 3 x 10(7) of HUCBMCs via ear vein within 24 h after AMI and then intragastric infusion of solution obtained by solving 270 mg CDDP in 5 mL normal saline per day. At week 1 and 4 after treatment, cardiac function indices such as left ventricular fractional shorting (LVFS) and left ventricular ejection fraction (LVEF) were performed by echocardiography; the number of transplanted cells in the myocardium was found

  5. Evaluation of myocardial damage and cardiac residual capacity by Tl-201 myocardial scintigraphy in valvular heart diseases

    International Nuclear Information System (INIS)

    Indo, Shunju

    1992-01-01

    This study was performed to clarify whether the extent-score (Ex-Score) calculated by Tl-201 myocardial scintigraphy is a reliable indicator of the severity of myocardial damage and cardiac residual capacity in valvular heart diseases. The subjects consisted of 38 patients (10 with aortic regurgitation (AR), 4 with aortic stenosis (AS), 13 with mitral regurgitation (MR) and 11 with mitral stenosis (MS)). Ex-Scores were significantly correlated with the severity of myocardial damage found in biopsied specimens obtained intraoperatively (correlation efficiency to Ex-Score with cell diameter in AR, % fibrosis in AR, cell diameter in AS, electron microscopic score in MR and % fibrosis in MS was 0.873, 0.734, 0.970, 0.913 and 0.659, respectively). Ex-Scores were also correlated with cardiac residual capacity determined by radioisotope angiography (correlation efficiency to Ex-Score with %Δ ejection fraction in AR, %Δ end-systolic volume in MR, %Δ end-diastolic volume in MS was -0.764, 0.790 and -0.763, respectively). These results suggest that the severity of myocardial damage and cardiac residual capacity can be estimated by Tl-201 myocardial scintigraphy (Ex-Score) in valvular heart diseases. (author)

  6. Scan analysis in myocardial infarction

    Energy Technology Data Exchange (ETDEWEB)

    Ell, P J [Landesunfallkrankenhaus, Feldkirch (Austria). Inst. fuer Strahlenmedizin

    1976-08-01

    Myocardial scans with sup(99m)Tc-labelled phosphates are reported to be useful in the diagnosis of acute myocardial infarction. A retrospective survey of 205 patients referred for sup(99m)Tc-phophate bone scanning and with no evidence of recent heart disease revealed an occurrence of 10% of false positive images, that is to say, uptake of phosphate in non-infarcted mayocardium. These striking findings stress the need for critical assessment of the usefulness of this diagnostic technique.

  7. Cell phone radiation effects on cytogenetic abnormalities of oral mucosal cells.

    Science.gov (United States)

    Daroit, Natália Batista; Visioli, Fernanda; Magnusson, Alessandra Selinger; Vieira, Geila Radunz; Rados, Pantelis Varvaki

    2015-01-01

    The aim of this study was to evaluate the effects of exposure to cell phone electromagnetic radiation on the frequency of micronuclei, broken eggs cells, binucleated cells, and karyorrhexis in epithelial cells of the oral mucosa. The sample was composed of 60 cell phone users, who were non-smokers and non-drinkers, and had no clinically visible oral lesions. Cells were obtained from anatomical sites with the highest incidence of oral cancer: lower lip, border of the tongue, and floor of the mouth. The Feulgen reaction was used for quantification of nuclear anomalies in 1,000 cells/slide. A slightly increase in the number of micronucleated cells in the lower lip and in binucleated cells on the floor of the mouth was observed in individuals who used their phones > 60 minutes/week. The analysis also revealed an increased number of broken eggs in the tongue of individuals owning a cell phone for over eight years. Results suggest that exposure to electromagnetic waves emitted by cell phones can increase nuclear abnormalities in individuals who use a cell phone for more than 60 minutes per week and for over eight years. Based on the present findings, we suggest that exposure to electromagnetic radiation emitted by cell phones may interfere with the development of metanuclear anomalies. Therefore, it is demonstrated that, despite a significant increase in these anomalies, the radiation emitted by cell phones among frequent users is within acceptable physiological limits.

  8. Cell phone radiation effects on cytogenetic abnormalities of oral mucosal cells

    Directory of Open Access Journals (Sweden)

    Natália Batista DAROIT

    2015-01-01

    Full Text Available The aim of this study was to evaluate the effects of exposure to cell phone electromagnetic radiation on the frequency of micronuclei, broken eggs cells, binucleated cells, and karyorrhexis in epithelial cells of the oral mucosa. The sample was composed of 60 cell phone users, who were non-smokers and non-drinkers, and had no clinically visible oral lesions. Cells were obtained from anatomical sites with the highest incidence of oral cancer: lower lip, border of the tongue, and floor of the mouth. The Feulgen reaction was used for quantification of nuclear anomalies in 1,000 cells/slide. A slightly increase in the number of micronucleated cells in the lower lip and in binucleated cells on the floor of the mouth was observed in individuals who used their phones > 60 minutes/week. The analysis also revealed an increased number of broken eggs in the tongue of individuals owning a cell phone for over eight years. Results suggest that exposure to electromagnetic waves emitted by cell phones can increase nuclear abnormalities in individuals who use a cell phone for more than 60 minutes per week and for over eight years. Based on the present findings, we suggest that exposure to electromagnetic radiation emitted by cell phones may interfere with the development of metanuclear anomalies. Therefore, it is demonstrated that, despite a significant increase in these anomalies, the radiation emitted by cell phones among frequent users is within acceptable physiological limits.

  9. Healing human myocardial infarction associated with increased chymase immunoreactivity

    NARCIS (Netherlands)

    Daemen, M. J.; Urata, H.

    1997-01-01

    We studied the immunoreactivity of the chymase protein in normal human myocardium and in human myocardial infarctions at various postinfarction times using immuno-histochemistry. In noninfarcted hearts chymase was mainly present in cardiomyocytes and endothelial cells. At 6 h after infarction the

  10. Molecular and functional MRI of cardiac remodeling after myocardial infarction

    NARCIS (Netherlands)

    Paulis, L.E.M.

    2012-01-01

    Myocardial infarction is the leading cause of death world-wide. It is characterized by cardiomyocyte cell death resulting from local oxygen deprivation caused by obstructions in the coronary microcirculation. The heart has very limited potential to regenerate new myocardium, and instead the dead

  11. Myocardial scintigraphy: methods and indications

    International Nuclear Information System (INIS)

    Knapp, W.H.

    1993-01-01

    Myocardial scintigraphy comprises perfusion imaging using TI-201 or - more recently - Tc-99m-labeled compounds with high affinity to myocytes. Imaging with these agents has become an important procedure in the detection of coronary artery disease, particularly in patients with non-diagnostic stress-ECG, in the functional evaluation of coronary stenoses after angiographical documentation in order to meet the adequate therapy decision, in therapy monitoring and follow-up, in the post infarction assessment of myocardial viability and differentiation between severe ischemia and scar and, occasionally, in acute ischemia. The use of positron emitters does not offer significant advantages for mere perfusion imaging, but is indispensable for the scintigraphic investigation of certain aspects of myocardial metabolism, particularly for the differentiation of viable ischemic wall segments from irreversibly damaged tissue. Imaging of myocardial necrosis has been improved by the introduction of labeled antimyosin antibody fragments and offers a considerable clinical potential in the diagnosis of myocarditis and cardiac transplant rejection. Neurohumoral aspects are increasingly involved in our understanding of myocardial failure. Scintigraphy of innervation/neurotransmission contributes to the investigation of pathophysiological alterations in myocardial insufficiency and in heart transplants. (orig.) [de

  12. Myocardial Autophagy after Severe Burn in Rats

    Science.gov (United States)

    Zhang, Qiong; Shi, Xiao-hua; Huang, Yue-sheng

    2012-01-01

    Background Autophagy plays a major role in myocardial ischemia and hypoxia injury. The present study investigated the effects of autophagy on cardiac dysfunction in rats after severe burn. Methods Protein expression of the autophagy markers LC3 and Beclin 1 were determined at 0, 1, 3, 6, and 12 h post-burn in Sprague Dawley rats subjected to 30% total body surface area 3rd degree burns. Autophagic, apoptotic, and oncotic cell death were evaluated in the myocardium at each time point by immunofluorescence. Changes of cardiac function were measured in a Langendorff model of isolated heart at 6 h post-burn, and the autophagic response was measured following activation by Rapamycin and inhibition by 3-methyladenine (3-MA). The angiotensin converting enzyme inhibitor enalaprilat, the angiotensin receptor I blocker losartan, and the reactive oxygen species inhibitor diphenylene iodonium (DPI) were also applied to the ex vivo heart model to examine the roles of these factors in post-burn cardiac function. Results Autophagic cell death was first observed in the myocardium at 3 h post-burn, occurring in 0.008 ± 0.001% of total cardiomyocytes, and continued to increase to a level of 0.022 ± 0.005% by 12 h post-burn. No autophagic cell death was observed in control hearts. Compared with apoptosis, autophagic cell death occurred earlier and in larger quantities. Rapamycin enhanced autophagy and decreased cardiac function in isolated hearts 6 h post-burn, while 3-MA exerted the opposite response. Enalaprilat, losartan, and DPI all inhibited autophagy and enhanced heart function. Conclusion Myocardial autophagy is enhanced in severe burns and autophagic cell death occurred early at 3 h post-burn, which may contribute to post-burn cardiac dysfunction. Angiotensin II and reactive oxygen species may play important roles in this process by regulating cell signaling transduction. PMID:22768082

  13. Acute Myocardial Infarction Patients

    Directory of Open Access Journals (Sweden)

    Bruce Ovbiagele

    2011-01-01

    Full Text Available Background. Diabetes mellitus (DM confers high vascular risk and is a growing national epidemic. We assessed clinical characteristics and prevalence of diagnosed DM among patients hospitalized with acute myocardial infarction (AMI in the US over the last decade. Methods. Data were obtained from all states within the US that contributed to the Nationwide Inpatient Sample. All patients admitted to hospitals between 1997 and 2006 with a primary discharge diagnosis of AMI were included. Time trends in the proportion of these patients with DM diagnosis were computed. Results. The portion of patients with comorbid diabetes among AMI hospitalizations increased substantially from 18% in 1997 to 30% in 2006 (<.0001. Absolute numbers of AMI hospitalizations in the US decreased 8% (from 729, 412 to 672, 243, while absolute numbers of AMI hospitalizations with coexisting DM rose 51% ((131, 189 to 198, 044, both (<.0001. Women with AMI were significantly more likely to have DM than similarly aged men, but these differences diminished with increasing age. Conclusion. Although overall hospitalizations for AMI in the US diminished over the last decade, prevalence of diabetes rose substantially. This may have important consequences for the future societal vascular disease burden.

  14. The effect of periodontal therapy on neopterin and vascular cell adhesion molecule-1 levels in chronic periodontitis patients with and without acute myocardial infarction: a case-control study.

    Science.gov (United States)

    Turgut Çankaya, Zeynep; Bodur, Ayşen; Taçoy, Gülten; Ergüder, Imge; Aktuna, Derya; Çengel, Atiye

    2018-04-05

    The presence of neopterin in gingival crevicular fluid (GCF) is a marker for local and acute immune activation, and the presence of vascular cell adhesion molecule (VCAM-1) in GCF is accepted as a marker for chronic vascular inflammation. This study aimed to evaluate effects of periodontal treatment on GCF levels of neopterin and VCAM-1 in patients with chronic periodontitis (CP) with acute myocardial infarction (AMI) compared with systemically healthy CP patients. Sixty subjects (20 CP patients with AMI, 20 healthy CP patients, and 20 healthy controls) were included. GCF samples were analyzed at baseline and after 3 and 6 months, and the probing pocket depth (PD), clinical attachment level (CAL), bleeding on probing, gingival (GI) and plaque (PI) indices were recorded. We determined neopterin and VCAM-1 levels (concentration and total amount) using enzyme-linked immunosorbent assay (ELISA). No significant differences were seen between the AMI+CP and CP groups for PI, GI, GCF levels of neopterin and VCAM-1 at baseline. The number of teeth with 5 mm≤CALperiodontal inflammation and the presence of neopterin and VCAM-1 in GCF prior to and following periodontal treatment, and between the GCF volume and clinical parameters. Data suggest that the total amount and concentration of neopterin and VCAM-1 in GCF seemed to be closely associated with periodontal disease severity in CP patients with AMI. Moreover, the results of our study demonstrate that the past periodontal status is potentially correlated between groups, with similar periodontal disease severity.

  15. Intramyocardial injection of autologous bone marrow-derived ex vivo expanded mesenchymal stem cells in acute myocardial infarction patients is feasible and safe up to 5 years of follow-up.

    Science.gov (United States)

    Rodrigo, Sander F; van Ramshorst, Jan; Hoogslag, Georgette E; Boden, Helèn; Velders, Matthijs A; Cannegieter, Suzanne C; Roelofs, Helene; Al Younis, Imad; Dibbets-Schneider, Petra; Fibbe, Willem E; Zwaginga, Jaap Jan; Bax, Jeroen J; Schalij, Martin J; Beeres, Saskia L; Atsma, Douwe E

    2013-10-01

    In experimental studies, mesenchymal stem cell (MSC) transplantation in acute myocardial infarction (AMI) models has been associated with enhanced neovascularization and myogenesis. Clinical data however, are scarce. Therefore, the present study evaluates the safety and feasibility of intramyocardial MSC injection in nine patients, shortly after AMI during short-term and 5-year follow-up. Periprocedural safety analysis demonstrated one transient ischemic attack. No other adverse events related to MSC treatment were observed during 5-year follow-up. Clinical events were compared to a nonrandomized control group comprising 45 matched controls. A 5-year event-free survival after MSC-treatment was comparable to controls (89 vs. 91 %, P = 0.87). Echocardiographic imaging for evaluation of left ventricular function demonstrated improvements up to 5 years after MSC treatment. These findings were not significantly different when compared to controls. The present safety and feasibility study suggest that intramyocardial injection of MSC in patients shortly after AMI is feasible and safe up to 5-year follow-up.

  16. Studying Dynamic Features in Myocardial Infarction Progression by Integrating miRNA-Transcription Factor Co-Regulatory Networks and Time-Series RNA Expression Data from Peripheral Blood Mononuclear Cells.

    Directory of Open Access Journals (Sweden)

    Hongbo Shi

    Full Text Available Myocardial infarction (MI is a serious heart disease and a leading cause of mortality and morbidity worldwide. Although some molecules (genes, miRNAs and transcription factors (TFs associated with MI have been studied in a specific pathological context, their dynamic characteristics in gene expressions, biological functions and regulatory interactions in MI progression have not been fully elucidated to date. In the current study, we analyzed time-series RNA expression data from peripheral blood mononuclear cells. We observed that significantly differentially expressed genes were sharply up- or down-regulated in the acute phase of MI, and then changed slowly until the chronic phase. Biological functions involved at each stage of MI were identified. Additionally, dynamic miRNA-TF co-regulatory networks were constructed based on the significantly differentially expressed genes and miRNA-TF co-regulatory motifs, and the dynamic interplay of miRNAs, TFs and target genes were investigated. Finally, a new panel of candidate diagnostic biomarkers (STAT3 and ICAM1 was identified to have discriminatory capability for patients with or without MI, especially the patients with or without recurrent events. The results of the present study not only shed new light on the understanding underlying regulatory mechanisms involved in MI progression, but also contribute to the discovery of true diagnostic biomarkers for MI.

  17. Early spontaneous intermittent myocardial reperfusion during acute myocardial infarction is associated with augmented thrombogenic activity and less myocardial damage

    NARCIS (Netherlands)

    Haider, A.W.; Andreotti, F.; Hackett, D.R.; Tousoulis, D.; Kluft, C.; Maseri, A.; Davies, G.J.

    1995-01-01

    Objectives. This study investigated the influence of early spontaneous intermittent reperfusion on the extent of myocardial damage and its relation to endogenous hemostatic activity, Background. In the early phase of acute myocardial infarction coronary occlusion is often intermittent, even before

  18. Thallium-201 myocardial imaging in acute-myocardial infarction

    International Nuclear Information System (INIS)

    Wackers, F.J.Th.; Lie, K.I.; Sokole, E.B.; Wellens, H.J.J.; Samson, G.; Schoot, J.B. van der

    1980-01-01

    Thallium-201 scintigraphy has proven to be an early and highly sensitive technique to detect myocardial perfusion abnormalities in patients with acute myocardial infarction. During the early phase of acute myocardial infarction, patients may be hemodynamically and electrically unstable. Therefore, scintigraphy is performed preferably at the bed side in the Coronary Care Unit using a mobile gamma camera. Additionally, in order to shorten imaging time in these often critically ill patients, the authors recommend injecting no less than 2 mCi of 201 Tl. Using this dosage, the imaging time per view will be approximately five minutes. Routinely, three views are taken: the first view is a supine 45 0 left-anterior-oblique view, followed by a supine anterior view and finally a left-lateral view, the latter with the patient turned on the right side. (Auth.)

  19. Myocardial perfusion imaging for detection of silent myocardial ischemia

    International Nuclear Information System (INIS)

    Beller, G.A.

    1988-01-01

    Despite the widespread use of the exercise stress test in diagnosing asymptomatic myocardial ischemia, exercise radionuclide imaging remains useful for detecting silent ischemia in numerous patient populations, including those who are totally asymptomatic, those who have chronic stable angina, those who have recovered from an episode of unstable angina or an uncomplicated myocardial infarction, and those who have undergone angioplasty or received thrombolytic therapy. Studies show that thallium scintigraphy is more sensitive than exercise electrocardiography in detecting ischemia, i.e., in part, because perfusion defects occur more frequently than ST depression and before angina in the ischemic cascade. Thallium-201 scintigraphy can be performed to differentiate a true- from a false-positive exercise electrocardiographic test in patients with exercise-induced ST depression and no angina. The development of technetium-labeled isonitriles may improve the accuracy of myocardial perfusion imaging. 11 references

  20. Myocardial perfusion alterations observed months after radiotherapy are related to the cellular damage

    Energy Technology Data Exchange (ETDEWEB)

    Dogan, I.; Sonmez, B. [Karadeniz Technical Univ., Trabzon (Turkey). Dept. of Nuclear Medicine; Sezen, O.; Zengin, A.Y.; Bahat, Z. [Karadeniz Technical Univ., Trabzon (Turkey). Dept. of Radiation Oncology; Yenilmez, E.; Yulug, E. [Karadeniz Technical Univ., Trabzon (Turkey). Dept. of Histology and Embryology; Abidin, I. [Karadeniz Technical Univ., Trabzon (Turkey). Dept. of Biophysics

    2010-07-01

    Myocardial perfusion scintigraphy (MPS) is one of the widely used tools to follow developing radiation-induced heart disease (RIHD). But the clinical significance of MPS defects has not been fully understood. We have investigated the biodistribution alterations related to perfusion defects following radiotherapy (RT) and showed coexisting morphological changes. Animals, methods: A total of 18 Wistar rats were divided into three groups (1 control and 2 irradiated groups). A single cardiac 20 Gy radiation dose was used to induce long term cardiac defects. Biodistribution studies with technetium ({sup 99m}Tc) sestamibi and histological evaluations were performed 4 and 6 months after irradiation. The percent radioactivity (%ID/g) was calculated for each heart. For determination of the myocardial damage, positive apoptotic cardiomyocytes, myocardial cell degeneration, myocardial fibrosis, vascular damage and ultrastructural structures were evaluated. Results: Six months after treatment, a significant drop of myocardial uptake was observed (p < 0.05). Irradiation-induced apoptosis rose within the first 4 months after radiation treatment and were stayed elevated until the end of the observation period (p < 0.05). Also, the irradiation has induced myocardial degeneration, perivascular and interstitial fibrosis in the heart at the end of six and four months (p < 0.01). The severity and extent of myocardial injury has became more evident at the end of six month (p < 0.05). At ultrastructural level, prominent changes have been observed in the capillary endothelial and myocardial cells. Conclusion: Our findings suggest that the reduced rest myocardial perfusion, occuring months after the radiation, indicates a serious myocard tissue damage which is characterized by myocardial degeneration and fibrosis. (orig.)

  1. Myocardial perfusion alterations observed months after radiotherapy are related to the cellular damage

    International Nuclear Information System (INIS)

    Dogan, I.; Sonmez, B.; Sezen, O.; Zengin, A.Y.; Bahat, Z.; Yenilmez, E.; Yulug, E.; Abidin, I.

    2010-01-01

    Myocardial perfusion scintigraphy (MPS) is one of the widely used tools to follow developing radiation-induced heart disease (RIHD). But the clinical significance of MPS defects has not been fully understood. We have investigated the biodistribution alterations related to perfusion defects following radiotherapy (RT) and showed coexisting morphological changes. Animals, methods: A total of 18 Wistar rats were divided into three groups (1 control and 2 irradiated groups). A single cardiac 20 Gy radiation dose was used to induce long term cardiac defects. Biodistribution studies with technetium ( 99m Tc) sestamibi and histological evaluations were performed 4 and 6 months after irradiation. The percent radioactivity (%ID/g) was calculated for each heart. For determination of the myocardial damage, positive apoptotic cardiomyocytes, myocardial cell degeneration, myocardial fibrosis, vascular damage and ultrastructural structures were evaluated. Results: Six months after treatment, a significant drop of myocardial uptake was observed (p < 0.05). Irradiation-induced apoptosis rose within the first 4 months after radiation treatment and were stayed elevated until the end of the observation period (p < 0.05). Also, the irradiation has induced myocardial degeneration, perivascular and interstitial fibrosis in the heart at the end of six and four months (p < 0.01). The severity and extent of myocardial injury has became more evident at the end of six month (p < 0.05). At ultrastructural level, prominent changes have been observed in the capillary endothelial and myocardial cells. Conclusion: Our findings suggest that the reduced rest myocardial perfusion, occuring months after the radiation, indicates a serious myocard tissue damage which is characterized by myocardial degeneration and fibrosis. (orig.)

  2. Influence of drugs on myocardial iodine-123 metaiodobenzylguanidine uptake in rabbit myocardium

    Energy Technology Data Exchange (ETDEWEB)

    Mayer, S.; Karanikas, G.; Rodrigues, M.; Sinzinger, H. [Dept. of Nuclear Medicine, University of Vienna (Austria)

    2000-03-01

    About 15 years ago, iodine-123 metaiodobenzylguanidine (MIBG) myocardial imaging was introduced for the evaluation of myocardial sympathetic nerve function. Two uptake mechanisms for MIBG have so far been identified: uptake type I, a saturable, energy-dependent mechanism, and uptake type II, a non-saturable, energy-independent mechanism. We incubated isolated rabbit myocardial tissue samples with{sup 123}I-MIBG in order to assess the uptake characteristics and the influence of varying incubation conditions. Furthermore, we examined the effects of several drugs and uptake inhibitors on the myocardial uptake of MIBG. The in vitro myocardial uptake of MIBG reached a steady plateau at 23.87%{+-}3.63% after 1 h, i.e. a concentration gradient of 10, in a thermo-independent manner within a concentration range from 1.5 to 1500 {mu}M. This indicates an unsaturable uptake process in the tested concentrations. Pre-incubation with the following drugs caused a significant inhibitory effect on myocardial MIBG uptake: haloperidol, levomepromazine, metoprolol, labetalol and clomipramine. According to our findings, the uptake mechanism seems to be an unspecific process, but the concentration gradient of 10 makes passive diffusion unlikely. Further studies with uptake-II-blocking substances as well as with isolated myocardial cells will be needed to clarify the nature of the myocardial MIBG uptake mechanism. (orig.)

  3. Assessment of myocardial perfusion and metabolism for assessment of myocardial viability

    International Nuclear Information System (INIS)

    Beller, G.

    1996-01-01

    Identifying preserved myocardial viability in the presence of severe regional left ventricular dysfunction is becoming increasingly more important for clinical decision-making to better select those patients with coronary artery disease who will benefit most from revascularization. 201 Tl remains the most commonly employed radionuclide for detecting both ischemia and viability. A severe persistent defect with 201 Tl uptake compared to peak to improved perfusion and corresponding improved function after revascularisation. Detection of defect reversibility on 201 Tl imaging is enhanced by 'reinjection' of a second 201 Tl dose after acquisition of redistribution images. Initial and 4-hour rest/redistribution imaging has proven most usefull for detection of viability in the resting state in patients with ischemic cardiomyopathy. The greater the extent of preoperative viability, the greater is the improvement in regional and global function after revascularisation. 99 Tc sestamibi has also been demonstrated to be extracted by myocardial cells in proportion to regional blood flow in the presence of viable myocities. Although this agrnt does not redistribute after intravenous injection, its >50% uptake of the tracer implies viablility and predicts improved regional function after revascularisation. Finally positron emission tomography with 18 F fluorodeoxoglucose (FDG) is perhaps the most sensitive noninvasive imaging technique for detection of viability in stunned or hibernating myocardium. A mismatch pattern between regional flow and FDG uptake as approximately an 80-85% positive preicted value for predicting improved function in asynergic myocardial regions after revascualarisation

  4. Myocardial scintigraphy with thallium-201

    International Nuclear Information System (INIS)

    Schwaiger, M.; Silber, S.; Klein, U.; Rudolph, W.

    1980-01-01

    Thallium-201 myocardial scintigraphy is an important non-invasive method for assessment of coronary artery disease. Other applications of the method such as delineation of the right ventricular free wall in right ventricular overload, or the detection of hypertrophic cardiomyopathies or myocardial infiltrations are of subordinate importance. In heart disease such as congestive cardiomyopathy and mitral valve prolapse thallium-201 uptake defects have been described, the clinical implications of these findings, however, cannot be adequately interpreted at this time. Myocardial uptake of thallium-201 is an active process, dependent on and proportional to perfusion. Differentiation between myocardial ischemia and myocardial scar is based on the presence or absence of thallium-201 'redistribution'. That is, in the presence of acute reversible ischemia there is increased thallium-201 uptake in the post-ischemic phase in previously hypoperfused myocardium and, subsequently, equilibrium of the initially registered activity differences. 'Redistribution' has also been described in the resting scintigram of patients with severe coronary artery disease and chronic hypoperfusion. (orig.) [de

  5. Mortality rate in type 2 myocardial infarction

    DEFF Research Database (Denmark)

    Saaby, Lotte; Poulsen, Tina Svenstrup; Diederichsen, Axel Cosmus Pyndt

    2014-01-01

    myocardial infarction, hypercholesterolemia, high p-creatinine, and diabetes mellitus. The multivariable-adjusted hazard ratio for type 2 myocardial infarction was 2.0 (95% confidence interval, 1.3-3.0). With shock as the only exception, mortality was independent of the triggering conditions leading to type....../119) in those with type 2 myocardial infarction and 26% (92/360) in those with type 1 myocardial infarction (P high age, prior myocardial infarction, type 2...... 2 myocardial infarction. CONCLUSIONS: Mortality in patients with type 2 myocardial infarction is high, reaching approximately 50% after 2 years. Further descriptive and survival studies are needed to improve the scientific evidence on which treatment of type 2 myocardial infarction is based....

  6. Sgarbossa criteria and acute myocardial infarction.

    Science.gov (United States)

    Alang, Neha; Bathina, Jaya; Kranis, Mark; Angelis, Dimitrios

    2010-01-01

    Diagnosis of acute ST-elevation myocardial infarction in the presence of left bundle branch block is difficult. present a case of acute myocardial infarction with LBBB diagnosed and treated using the Sgarbossa criteria.

  7. The endothelial glycocalyx protects against myocardial edema

    NARCIS (Netherlands)

    van den Berg, Bernard M.; Vink, Hans; Spaan, Jos A. E.

    2003-01-01

    Myocardial tissue edema attributable to increased microvascular fluid loss contributes to cardiac dysfunction after myocardial ischemia, cardiopulmonary bypass, hypertension, and sepsis. Recent studies suggest that carbohydrate structures on the luminal surface of microvascular endothelium are

  8. Myocardial infarction after near drowning.

    Science.gov (United States)

    Chen, Li-Bang; Lai, Yen-Chun; Chen, Chang-Chih; Chang, Wen-Han; Su, Yu-Jang

    2008-06-01

    During summer, near drowning is a common accident in Taiwan. It may lead to multiple organ damages in cases where severe hypothermia and hypoxemia occur. We present a case of myocardial infarction after near drowning. The patient was sent to our ED by the emergency medical services called by the witness. On arrival to our ED, hypothermia and hypoxemia overcame him. Endotracheal intubation and warm intravenous fluid were applied at once owing to drowsy consciousness, respiratory distress, and hypothermia. Electrocardiogram showed diffuse ST-segment elevation over the precordial leads V2-V6. The initial level of cardiac enzymes was within normal limit but elevated in troponin I on the second day after hospitalization. We presumed that the possibility of myocardial infarction resulted from near drowning-related hypoxemia. To our knowledge, this is the first case describing myocardial injury with electrocardiogram changes after near drowning.

  9. Dynamic CT myocardial perfusion imaging

    International Nuclear Information System (INIS)

    Caruso, Damiano; Eid, Marwen; Schoepf, U. Joseph; Jin, Kwang Nam; Varga-Szemes, Akos; Tesche, Christian; Mangold, Stefanie

    2016-01-01

    Highlights: • CT myocardial perfusion provides functional assessment of the myocardium. • CCTA is limited in determining the hemodynamic significance of coronary stenosis. • CT-MPI can accurately detect hemodynamically significant coronary artery stenosis. - Abstract: Non-invasive cardiac imaging has rapidly evolved during the last decade due to advancements in CT based technologies. Coronary CT angiography has been shown to reliably assess coronary anatomy and detect high risk coronary artery disease. However, this technique is limited to anatomical assessment, thus non-invasive techniques for functional assessment of the heart are necessary. CT myocardial perfusion is a new CT based technique that provides functional assessment of the myocardium and allows for a comprehensive assessment of coronary artery disease with a single modality when combined with CTA. This review aims to discuss dynamic CT myocardial perfusion as a new technique in the assessment of CAD.

  10. Dynamic CT myocardial perfusion imaging

    Energy Technology Data Exchange (ETDEWEB)

    Caruso, Damiano [Division of Cardiovascular Imaging, Department of Radiology and Radiological Science, Medical University of South Carolina, Charleston, SC (United States); Department of Radiological Sciences, Oncological and Pathological Sciences, University of Rome “Sapienza”, Latina (Italy); Eid, Marwen [Division of Cardiovascular Imaging, Department of Radiology and Radiological Science, Medical University of South Carolina, Charleston, SC (United States); Schoepf, U. Joseph, E-mail: schoepf@musc.edu [Division of Cardiovascular Imaging, Department of Radiology and Radiological Science, Medical University of South Carolina, Charleston, SC (United States); Division of Cardiology, Department of Medicine, Medical University of South Carolina, Charleston, SC (United States); Jin, Kwang Nam [Division of Cardiovascular Imaging, Department of Radiology and Radiological Science, Medical University of South Carolina, Charleston, SC (United States); Department of Radiology, Seoul Metropolitan Government-Seoul National University Boramae Medical Center, Seoul (Korea, Republic of); Varga-Szemes, Akos [Division of Cardiovascular Imaging, Department of Radiology and Radiological Science, Medical University of South Carolina, Charleston, SC (United States); Tesche, Christian [Division of Cardiovascular Imaging, Department of Radiology and Radiological Science, Medical University of South Carolina, Charleston, SC (United States); Department of Cardiology and Intensive Care Medicine, Heart Center Munich-Bogenhausen, Munich (Germany); Mangold, Stefanie [Division of Cardiovascular Imaging, Department of Radiology and Radiological Science, Medical University of South Carolina, Charleston, SC (United States); Department of Diagnostic and Interventional Radiology, University Hospital of Tuebingen, Tuebingen (Germany); and others

    2016-10-15

    Highlights: • CT myocardial perfusion provides functional assessment of the myocardium. • CCTA is limited in determining the hemodynamic significance of coronary stenosis. • CT-MPI can accurately detect hemodynamically significant coronary artery stenosis. - Abstract: Non-invasive cardiac imaging has rapidly evolved during the last decade due to advancements in CT based technologies. Coronary CT angiography has been shown to reliably assess coronary anatomy and detect high risk coronary artery disease. However, this technique is limited to anatomical assessment, thus non-invasive techniques for functional assessment of the heart are necessary. CT myocardial perfusion is a new CT based technique that provides functional assessment of the myocardium and allows for a comprehensive assessment of coronary artery disease with a single modality when combined with CTA. This review aims to discuss dynamic CT myocardial perfusion as a new technique in the assessment of CAD.

  11. Morphological aspects of myocardial bridges.

    Science.gov (United States)

    Lujinović, Almira; Kulenović, Amela; Kapur, Eldan; Gojak, Refet

    2013-11-01

    Although some myocardial bridges can be asymptomatic, their presence often causes coronary disease either through direct compression of the "tunnel" segment or through stimulation and accelerated development of atherosclerosis in the segment proximally to the myocardial bridge. The studied material contained 30 human hearts received from the Department of Anatomy. The hearts were preserved 3 to 5 days in 10% formalin solution. Thereafter, the fatty tissue was removed and arterial blood vessels prepared by careful dissection with special reference to the presence of the myocardial bridges. Length and thickness of the bridges were measured by the precise electronic caliper. The angle between the myocardial bridge fibre axis and other axis of the crossed blood vessel was measured by a goniometer. The presence of the bridges was confirmed in 53.33% of the researched material, most frequently (43.33%) above the anterior interventricular branch. The mean length of the bridges was 14.64 ± 9.03 mm and the mean thickness was 1.23 ± 1.32 mm. Myocardial bridge fibres pass over the descending blood vessel at the angle of 10-90 degrees. The results obtained on a limited sample suggest that the muscular index of myocardial bridge is the highest for bridges located on RIA, but that the difference is not significant in relation to bridges located on other branches. The results obtained suggest that bridges located on other branches, not only those on RIA, could have a great contractive power and, consequently, a great compressive force, which would be exerted on the wall of a crossed blood vessel.

  12. Different Causes of Death in Patients with Myocardial Infarction Type 1, Type 2, and Myocardial Injury.

    Science.gov (United States)

    Lambrecht, Sascha; Sarkisian, Laura; Saaby, Lotte; Poulsen, Tina S; Gerke, Oke; Hosbond, Susanne; Diederichsen, Axel C P; Thygesen, Kristian; Mickley, Hans

    2018-05-01

    Data outlining the mortality and the causes of death in patients with type 1 myocardial infarction, type 2 myocardial infarction, and those with myocardial injury are limited. During a 1-year period from January 2010 to January 2011, all hospitalized patients who had cardiac troponin I measured on clinical indication were prospectively studied. Patients with at least one cardiac troponin I value >30 ng/L underwent case ascertainment and individual evaluation by an experienced adjudication committee. Patients were classified as having type 1 myocardial infarction, type 2 myocardial infarction, or myocardial injury according to the criteria of the universal definition of myocardial infarction. Follow-up was ensured until December 31, 2014. Data on mortality and causes of death were obtained from the Danish Civil Registration System and the Danish Register of Causes of Death. Overall, 3762 consecutive patients were followed for a mean of 3.2 years (interquartile range 1.3-3.6 years). All-cause mortality differed significantly among categories: Type 1 myocardial infarction 31.7%, type 2 myocardial infarction 62.2%, myocardial injury 58.7%, and 22.2% in patients with nonelevated troponin values (log-rank test; P causes, vs 42.6% in patients with type 2 myocardial infarction (P = .015) and 41.2% in those with myocardial injury (P causes of death did not differ substantially between patients with type 2 myocardial infarction and those with myocardial injury. Patients with type 2 myocardial infarction and myocardial injury exhibit a significantly higher long-term mortality compared with patients with type 1 myocardial infarction . However, most patients with type 1 myocardial infarction die from cardiovascular causes in contrast to patients with type 2 myocardial infarction and myocardial injury, in whom noncardiovascular causes of death predominate. Copyright © 2018 Elsevier Inc. All rights reserved.

  13. The Effects of Diabetes Induction on the Rat Heart: Differences in Oxidative Stress, Inflammatory Cells, and Fibrosis between Subendocardial and Interstitial Myocardial Areas

    Directory of Open Access Journals (Sweden)

    Maria C. Guido

    2017-01-01

    Full Text Available Diabetic cardiomyopathy (DCM is characterized by cardiac remodeling and impaired diastolic function that may lead to heart failure. The aim of this study was to evaluate oxidative stress, inflammatory cells, and fibrosis in both subendocardial (SEN and interstitial (INT areas of the myocardium. Male Wistar rats were allocated to 2 groups of 9 animals, a control (CT group and streptozotocin-induced diabetes (DM. After 8 weeks, echocardiography morphometry, protein expression, and confocal microscopy in SEN and INT areas of the left ventricle (LV were performed. The echocardiographic analysis showed that diabetes induction leads to cardiac dilation, hypertrophy, and LV diastolic dysfunction. As compared to CT, the induction of diabetes increased inflammatory cells and fibrosis in both SEN and INT areas of DM myocardium and increased ROS generation only in SEN. Comparing the SEN and INT areas in the DM group, inflammatory cells and fibrosis in SEN were greater than in INT. In conclusion, diabetic myocardium SEN area, wherein oxidative stress was more pronounced, is more susceptible to cardiac dysfunction than INT area. This finding can be important for the understanding of the heart remodeling process occurring in DCM and perhaps to engender targeted therapies to attenuate or revert DCM-related diastolic dysfunction.

  14. Imaging techniques for myocardial inflammation

    International Nuclear Information System (INIS)

    O'Connell, J.B.; Henkin, R.E.; Robinson, J.A.

    1986-01-01

    Dilated cardiomyopathy (DC) represents a heterogeneous group of disorders which results in morbidity and mortality in young individuals. Recent evidence suggests that a subset of these patients have histologic evidence of myocarditis which is potentially treatable with immunosuppression. The identification of myocardial inflammation may therefore lead to development of therapeutic regimens designed to treat the cause rather than the effect of the myocardial disease. Ultimately, this may result in improvement in the abysmal prognosis of DC. The currently accepted technique for identification of active myocardial inflammation is endomyocardial biopsy. This technique is not perfect, however, since pathologic standards for the diagnosis of myocarditis have not been established. Furthermore, focal inflammation may give rise to sampling error. The inflammation-avid radioisotope gallium-67 citrate has been used as an adjunct to biopsy improving the yield of myocarditis from 7 percent to 36 percent. Serial imaging correlates well to biopsy results. Future studies are designed to study the applicability of lymphocyte labelling techniques to myocardial inflammatory disease

  15. Dosimetry in myocardial perfusion imaging

    Energy Technology Data Exchange (ETDEWEB)

    Toledo, Janine M.; Trindade, Bruno; Ribeiro, Tarcisio P.C. [Universidade Federal de Minas Gerais (DEN/UFMG), Belo Horizonte (Brazil). Dept. de Engenharia Nuclear. Programa de Pos-Graduacao em Ciencias e Tecnicas Nucleares

    2011-07-01

    This paper conducts a dosimetric investigation on the myocardial perfusion image protocol, together with a literature reviewing, motivated by the significant statistic increasing on mortality, morbidity and disability associated with cardiovascular disease, surpassing infectious diseases. Nuclear Cardiology plays a role n the diagnostic functional evaluation of the heart and in the prognostic of patients with suspected or known cardiac ischemia. In the context of unstable myocardial ischemic syndrome, myocardial perfusion scintigraphy is a non-invasive procedure performed by administering a radiopharmaceutical targeted to the heart. As tool for this study are that the images obtained by thoracic angiotomography and abdominal aorta as a anatomic and functional information for model reproduction in SISCODES - System of Codes for Absorbed Dose Calculations based on Stochastic Methods. Data were manipulated in order to create a voxel computational model of the heart to be running in MCNP - Monte Carlo Neutron Particle Code. . It was assumed a homogeneous distribution of Tl-201 in cardiac muscle. Simulations of the transport of particles through the voxel and the interaction with the heart tissue were performed. As a result, the isodose curves in the heart model are displayed as well as the dose versus volume histogram of the heart muscle. We conclude that the present computational tools can generate doses distributed in myocardial perfusion. (author)

  16. Dosimetry in myocardial perfusion imaging

    International Nuclear Information System (INIS)

    Toledo, Janine M.; Trindade, Bruno; Ribeiro, Tarcisio P.C.

    2011-01-01

    This paper conducts a dosimetric investigation on the myocardial perfusion image protocol, together with a literature reviewing, motivated by the significant statistic increasing on mortality, morbidity and disability associated with cardiovascular disease, surpassing infectious diseases. Nuclear Cardiology plays a role n the diagnostic functional evaluation of the heart and in the prognostic of patients with suspected or known cardiac ischemia. In the context of unstable myocardial ischemic syndrome, myocardial perfusion scintigraphy is a non-invasive procedure performed by administering a radiopharmaceutical targeted to the heart. As tool for this study are that the images obtained by thoracic angiotomography and abdominal aorta as a anatomic and functional information for model reproduction in SISCODES - System of Codes for Absorbed Dose Calculations based on Stochastic Methods. Data were manipulated in order to create a voxel computational model of the heart to be running in MCNP - Monte Carlo Neutron Particle Code. . It was assumed a homogeneous distribution of Tl-201 in cardiac muscle. Simulations of the transport of particles through the voxel and the interaction with the heart tissue were performed. As a result, the isodose curves in the heart model are displayed as well as the dose versus volume histogram of the heart muscle. We conclude that the present computational tools can generate doses distributed in myocardial perfusion. (author)

  17. Myocardial contusion following nonfatal blunt chest trauma

    International Nuclear Information System (INIS)

    Kumar, S.A.; Puri, V.K.; Mittal, V.K.; Cortez, J.

    1983-01-01

    Currently available diagnostic techniques for myocardial contusion following blunt chest trauma were evaluated. We investigated 30 patients prospectively over a period of 1 year for the presence of myocardial contusion. Among the 30 patients, eight were found to have myocardial contusion on the basis of abnormal electrocardiograms, elevated creatine phosphokinase MB fraction (CPK-MB), and positive myocardial scan. Myocardial scan was positive in seven of eight patients (87.5%). CPK-MB fraction was elevated in four of eight patients (50%). Definitive electrocardiographic changes were seen in only two of eight patients (25%). It appears that myocardial scan using technetium pyrophosphate and CPK-MB fraction determinations are the most reliable aids in diagnosis of myocardial contusion following blunt chest trauma

  18. Myocardial imaging with cesium-130

    International Nuclear Information System (INIS)

    Harper, P.V.; Resnekov, L.; Stark, V.; Odeh, N.

    1984-01-01

    Recently comparative studies using nitrogen-13 ammonia and cesium-130 have shown strikingly different myocardial localization patterns in the same subjects with ischemic heart disease. Initial localization of ammonia, an avidly extracted agent, reflects the perfusion pattern in viable myocardial tissue. The myocardial localization of cesium ion, taking place more slowly over 15 to 20 minutes, is apparently much less flow dependent, causing uptake defects shown with ammonia to be largely filled in. Cesium thus appears to provide information on the extent of the viable myocardial mass, apart from perfusion. Cesium-130 (t1/2 30 m) decays by positron emission and electron capture. The whole body radiation absorbed dose, assuming uniform distribution, is 24 mrad/mCi. While abundant production of Cs-130 results from proton bombardment of natural xenon [Xe-130(rho,n)Cs-130] at 15 MeV, small amounts of Cs-129, -131, and -132 are also produced, and enriched Xe-130 is not available. Alternatively almost completely uncontaminated Cs-130 is available by alpha bombardment of natural I-127. Anhydrous sodium iodide is dissolved in acetone and a thin layer (≅20 mg per centimeter squared) is evaporated onto the gold plated tip of the internal target backing which is oscillated vertically to spread out the area upon which the beam is incident. The target surface is inclined 2.5 degrees to the beam giving a power density of about 400 watts per centimeter squared at 100μA which is adequately handled by water cooling. A 30-minute bombardment yields 4 to 5 mCi of Cs-130 which is dissolved directly from the target. This approach appears to offer a new and helpful method for evaluating ischemic heart disease by permitting evaluation of viable myocardial mass

  19. Myocardial protection in heart surgery.

    Science.gov (United States)

    Mentzer, Robert M

    2011-01-01

    One of the unmet clinical needs in heart surgery is the prevention of myocardial stunning and necrosis that occurs as a result of ischemia-reperfusion. Myocardial stunning, a frequent consequence after heart surgery, is characterized by a requirement for postoperative inotropic support despite a technically satisfactory heart operation. In high-risk patients with marginal cardiac reserve, stunning is a major cause of prolonged critical care and may be associated with as much as a 5-fold increase in mortality. In contrast, the frequency of myocardial necrosis (myocardial infarction [MI]) after cardiac surgery is less appreciated and its consequences are much more subtle. The consequences may not be apparent for months to years. While we now have a much better understanding of the molecular mechanisms underlying myocardial stunning and MI, we still have no effective way to prevent these complications, nor a consistently effective means to engage the well-studied endogenous mechanisms of cardioprotection. The failure to develop clinically effective interventions is multifactorial and can be attributed to reliance on findings obtained from subcellular and cellular studies, to drawing conclusions from preclinical large animal studies that have been conducted in a disease-free state, and to accepting less than robust surrogate markers of injury in phase II clinical trials. These factors also explain the disappointing failure to identify effective adjuvant therapy in the setting of percutaneous coronary revascularization for acute MI (AMI) and reperfusion injury. These issues have contributed to the disappointing outcomes of large and costly phase III trials, resulting in a lack of enthusiasm on the part of the pharmaceutical industry to engage in further drug development for this indication. The purpose of this review is to (1) define the scope of the clinical problem; (2) summarize the outcomes of selected phases II and III clinical trials; and (3) identify the gap that

  20. Myocardial ischemia in Kawasaki disease

    International Nuclear Information System (INIS)

    Fukuda, Tsuyoshi

    1993-01-01

    The detection of myocardial ischemia is essential for evaluation of patients with Kawasaki disease, especially who have had coronary artery lesions. To evaluate the clinical efficacy of Tl-201 single photon emission computed tomography (SPECT) after dipyridamole infusion (maximum dose 0.70 mg/kg) for detecting myocardial ischemia, 44 patients with Kawasaki disease aged 7.7±4.8 years at the study and 10 age matched controls were observed. In the Kawasaki disease group, significant coronary artery stenosis was observed in 14, coronary aneurysm without stenosis in 18, the regression of the coronary aneurysms in 2 and without coronary lesions in 10 patients. In 24 of 44 patients, treadmill exercise stress test was also performed at the same period. Myocardial ischemic changes were observed in 11 patients, all combined with significant coronary artery stenosis. The sensitivity of SPECT for detection of overall coronary stenosis was 79%, coronary that of treadmill exercise test was only 33% (p<0.001). Furthermore, among the patients having significant coronary stenosis, the severity score was significantly elevated in patients who had electrocardiographic abnormal Q wave compared to those without abnormal Q wave (51.0±38.8 versus 20.0±12.1, p<0.05). These data suggest that the pharmacological stress scintigraphy using dipyridamole injection provides not only the accurate detection but quantitative evaluation of myocardial ischemia in these patients. This noninvasive technique may become one of the most useful index for detection and follow-up of myocardial ischemia in Kawasaki disease. (author)

  1. Myocardial ischemia and angina pectoris

    International Nuclear Information System (INIS)

    Selwyn, A.P.; Fox, K.M.; Jonathan, A.; Lavender, P.; Watson, I.

    1981-01-01

    Ambulatory monitoring of ST segment changes was performed in 60 patients presenting with angina, positive ECG stress tests and coronary artery disease, 85% of ischemic ECG events were asymptomatic, 37% occurred with no increase in heart rate and 15% of episodes either lasted 20 minutes or more or fluctuated in severity. A controlled pilot study in ten patients showed depression. Radionuclide studies in 50 patients with angina and coronary artery disease have shown that stress (i.e., atrial pacing) produced different patterns of disturbed regional myocardial perfusion related to the patient's exercise capacity and eventually leading to a decrease in regional myocardial perfusion during the ischemic episode. ST segment depression appeared only after the decrease in regional myocardial perfusion. These findings combined with past research suggest that patients with angina and coronary artery disease can suffer frequent asymptomatic disturbances of the regional myocardial perfusion. The frequency of these episodes and the time course for the recovery of the metabolic consequences mean that segments of ventricular myocardium may be constantly abnormal. The relative importance of changes in coronary tone and malfunction of platelets in the diseased coronary tree needs to be examined in clinical research. Pilot studies of antiplatelet agents have shown a significant beneficial effect on episodes of ischemia occurring at night and those occurring without any increase in heart rate. The techniques and observations in these patients with coronary artery disease all suggest that acute transient regional myocardial ischemia is caused by a variety of mechnisms. Further research using objective methods is required to discover the causes of ischemia and to rationalize treatment. (orig./MG) [de

  2. Radioiodinated tracers for myocardial imaging

    International Nuclear Information System (INIS)

    Kulkarni, P.V.; Corbett, J.R.

    1990-01-01

    Recent advances in the efficient production of high purity radioiodine (123I) and new efficient radiolabeling techniques have allowed the development of new classes of cardiovascular radiopharmaceuticals. These include 123I-labeled fatty acids to assess myocardial metabolism, 123I-metaiodobenzylguanidine (MIBG) for myocardial neuronal activity, labeled monoclonal antibodies for myocardial necrosis, and labeled lipoproteins for receptor concentration. 123I-labeled fatty acids and MIBG are under clinical investigation with encouraging results. 123I- and 111In-labeled fragments of monoclonal antibodies to myosin have been used for imaging myocardial necrosis in humans. The development of radiotracers for imaging of cholinergic and adrenergic receptors is still in the experimental stage. Recent advances in imaging instrumentation and radiopharmaceuticals have resulted in cardiac imaging applications beyond blood pool ventriculography, perfusion, and infarct-avid imaging. Developments of radioiodine (123I)-labeled agents promise to play an important role in the assessment of myocardial metabolism, neuronal activity, and receptor concentration. The chemistry of iodine is well defined compared with that of 99mTc; therefore, iodine isotopes are well suited for labeling biologically important molecules. Among the iodine isotopes, 123I has nearly ideal nuclear properties for nuclear medical applications with a 13.3-hour half-life (T1/2) and 159 keV gamma emission (83%). Despite the nearly ideal chemical and nuclear properties of 123I, the widespread application of 123I-based radiopharmaceuticals in clinical practice has been limited by high production costs (123I is produced in a cyclotron), relatively limited availability, and the presence of undesirable radionuclidic impurities (124I, T1/2 = 4.2 days; 125I, T1/2 = 60 days; 126I, T1/2 = 13.1 days). 77 references

  3. Complete regression of myocardial involvement associated with lymphoma following chemotherapy.

    Science.gov (United States)

    Vinicki, Juan Pablo; Cianciulli, Tomás F; Farace, Gustavo A; Saccheri, María C; Lax, Jorge A; Kazelian, Lucía R; Wachs, Adolfo

    2013-09-26

    Cardiac involvement as an initial presentation of malignant lymphoma is a rare occurrence. We describe the case of a 26 year old man who had initially been diagnosed with myocardial infiltration on an echocardiogram, presenting with a testicular mass and unilateral peripheral facial paralysis. On admission, electrocardiograms (ECG) revealed negative T-waves in all leads and ST-segment elevation in the inferior leads. On two-dimensional echocardiography, there was infiltration of the pericardium with mild effusion, infiltrative thickening of the aortic walls, both atria and the interatrial septum and a mildly depressed systolic function of both ventricles. An axillary biopsy was performed and reported as a T-cell lymphoblastic lymphoma (T-LBL). Following the diagnosis and staging, chemotherapy was started. Twenty-two days after finishing the first cycle of chemotherapy, the ECG showed regression of T-wave changes in all leads and normalization of the ST-segment elevation in the inferior leads. A follow-up Two-dimensional echocardiography confirmed regression of the myocardial infiltration. This case report illustrates a lymphoma presenting with testicular mass, unilateral peripheral facial paralysis and myocardial involvement, and demonstrates that regression of infiltration can be achieved by intensive chemotherapy treatment. To our knowledge, there are no reported cases of T-LBL presenting as a testicular mass and unilateral peripheral facial paralysis, with complete regression of myocardial involvement.

  4. Study progress of cardiac MRI technology in assessment of myocardial viability after myocardial infarction

    International Nuclear Information System (INIS)

    Wang Jing; Zhang Hao

    2013-01-01

    Acute myocardial infarction (AMI) is one of the most common diseases that cause disability and death around the world. Correctly and effectively assessing the myocardial viability after myocardial infarction can reduce the disabled rate and mortality rate. At present, many methods could be used to assess myocardial viability. The cardiac magnetic resonance imaging (CMR) technology has a lot of advantages compared to other methods. In this paper, we reviewed the research progress of CMR in assessment of myocardial viability after myocardial infarction, and compared CMR with other technologies. (authors)

  5. Evaluation of left ventricular function in patient with old myocardial infarction by 201-thallium myocardial scintigraphy

    Energy Technology Data Exchange (ETDEWEB)

    Takahashi, Kanji; Shimohara, Yasuaki; Ito, Misao; Okada, Keisei [Kure Kyosai Hospital, Hiroshima (Japan); Kodama, Kazunori

    1984-08-01

    Correlation between the ratio of myocardial defect calculated by 201-thallium myocardial scintigraphy and the left ventricular ejection fraction (LVEF) obtained by gated blood pool scintigraphy and the maximum level of creatine phosphokinase (CPK) was studied in 70 patients with old myocardial infarction. There was a significant correlation between the defect ratio and the LVEF or CPK level in patients with anterior or septal myocardial infarction. In all patients with inferior myocardial infarction in whom no defect was seen, the LVEF was more than 40%. However, no distinct correlation between the defect ratio and the LVEF or CPK level was obtained in cases of inferior myocardial infarction.

  6. Podoplanin and the posterior heart field: epicardial-myocardial interaction

    OpenAIRE

    Mahtab, Edris Ahmad Faiz

    2008-01-01

    This thesis introduces the posterior heart field contributing to the venous pole of the heart by epithelial-mesenchymal-transformation of the coelomic epithelium. Based on studying of podoplanin and Sp3 (novel genes in cardiogenesis) wildtype and knockout mouse embryos between stages 9.5-18.5, we postulate that the posterior heart field contributes through mesenchymal and myocardial cell populations. The mesenchymal population is involved in the formation of the proepicardial organ, epicardiu...

  7. The effects of escitalopram on myocardial apoptosis and the expression of Bax and Bcl-2 during myocardial ischemia/reperfusion in a model of rats with depression.

    Science.gov (United States)

    Wang, Yiming; Zhang, Hongming; Chai, Fangxian; Liu, Xingde; Berk, Michael

    2014-12-04

    Major depressive disorder (MDD) is an independent risk factor for coronary heart disease (CHD), and influences the occurrence and prognosis of cardiovascular events. Although there is evidence that antidepressants may be cardioprotective after acute myocardial infarction (AMI) comorbid with MDD, the operative pathophysiological mechanisms remain unclear. Our aim was therefore to explore the molecular mechanisms of escitalopram on myocardial apoptosis and the expression of Bax and Bcl-2 in a rat model of depression during myocardial ischemia/reperfusion (I/R). Rats were divided randomly into 3 groups (n = 8): D group (depression), DI/R group (depression with myocardial I/R) and escitalopram + DI/R group. The rats in all three groups underwent the same chronic mild stress and separation for 21 days, at the same time, in the escitalopram + DI/R group, rats were administered escitalopram by gavage (10 mg/kg/day). Ligation of the rat's left anterior descending branch was done in the myocardial I/R model. Following which behavioral tests were done. The size of the myocardial infarction was detected using 1.5% TTC dye. The Tunel method was used to detect apoptotic myocardial cells, and both the Rt-PCR method and immunohistochemical techniques were used to detect the expression of Bcl-2 and Bax. Compared with the D and DI/R groups, rats in Escitalopram + DI/R group showed significantly increased movements and sucrose consumption (P escitalopram + DI/R group was significantly decreased (P escitalopram + DI/R groups (P escitalopram + DI/R group were significantly decreased (P escitalopram + DI/R group (P escitalopram. This suggests that clinically escitalopram may have a direct cardioprotective after acute myocardial infarction.

  8. Myocardial perfusion modeling using MRI

    DEFF Research Database (Denmark)

    Larsson, H B; Fritz-Hansen, T; Rostrup, Egill

    1996-01-01

    In the present study, it is shown that it is possible to quantify myocardial perfusion using magnetic resonance imaging in combination with gadolinium diethylenetriaminopentaacetic acid (Gd-DTPA). Previously, a simple model and method for measuring myocardial perfusion using an inversion recovery...... turbo-FLASH (fast low-angle shot) sequence and Gd-DTPA has been presented. Here, an extension of the model is presented taking into account fast and slow water exchange between the compartments, enabling the calculation of the unidirectional influx constant (Ki) for Gd-DTPA, the distribution volume...... of Gd-DTPA (lambda), the vascular blood volume (Vb), and the time delay through the coronary arteries (delta T). The model was evaluated by computer simulation and used on experimental results from seven healthy subjects. The results in the healthy volunteers for a region of interest placed...

  9. Expression of a transgene encoding mutant p193/CUL7 preserves cardiac function and limits infarct expansion after myocardial infarction

    NARCIS (Netherlands)

    Hassink, R. J.; Nakajima, H.; Nakajima, H. O.; Doevendans, P. A.; Field, L. J.

    2009-01-01

    Background: Transgenic mice expressing the dominant interfering p193 protein in cardiomyocytes (MHC-1152stop mice) exhibit an induction of cell cycle activity and altered remodelling after experimental myocardial infarction (MI). Objective: To determine whether the altered remodelling results in

  10. Functional tests for myocardial ischemia

    International Nuclear Information System (INIS)

    Levinson, J.R.; Guiney, T.E.; Boucher, C.A.

    1991-01-01

    Functional tests for myocardial ischemia are numerous. Most depend upon a combination of either exercise or pharmacologic intervention with analysis of the electrocardiogram, of regional perfusion with radionuclide imaging, or of regional wall motion with radionuclide imaging or echocardiography. While each test has unique features, especially at the research level, they are generally quite similar in clinical practice, so the clinician is advised to concentrate on one or two in which local expertise is high.22 references

  11. Protection of MICU1 against myocardial hypertrophy induced by angiotensin Ⅱ

    Directory of Open Access Journals (Sweden)

    Yi YANG

    2017-12-01

    Full Text Available Objective To investigate the role of mitochondrial calcium uptake 1 (MICU1 in myocardial hypertrophy of mice and underlying mechanism. Methods The model of myocardial hypertrophy was established via incubation of mouse cardiac myocytes (MCM with 300nmol/L angiotensin Ⅱ (Ang Ⅱ for 48 hours in vitro. After that, MICU1 specific small interfering RNA (siRNA was delivered to knockdown MICU1 levels in MCM. On the other hand, adenovirus-mediated over-expression of MICU1 was transfected into MCM. Accordingly, the expressions of ANP and BNP in myocardial cells were measured by qRT- PCR. Mitochondrial membrane potential and ATP contents were detected by JC-1 assay kit and ATP assay kit, respectively. Then, Western blotting and qRT-PCR were used to detect the levels of MICU1 in myocardial cells. The mitochondrial Ca2+ contents were measured via atomic absorption flame spectroscopy. The size of myocardial cells was determined by α-actinin staining. Results Mitochondrial membrane potential and ATP contents in hypertrophic cardiomyocytes induced by AngⅡ were both decreased. Meanwhile, myocardial hypertrophy significantly increased mitochondrial Ca2+ contents but decreased MICU1 levels. With the method of genetic intervention, we found that MICU1 deficiency exacerbated mitochondrial Ca2+ overload, increased cell surface and elevated the expression of BNP. Conversely, the overexpression of MICU1 obviously decreased mitochondrial Ca2+ overload, cell surface of MCM and expressions of ANP and BNP. Conclusion MICU1 alleviates AngⅡ-induced myocardial hypertrophy via inhibiting mitochondrial Ca2+ overload. DOI: 10.11855/j.issn.0577-7402.2017.12.05

  12. Quantitative Assessment of Myocardial Infarction by In-111 Antimyosin Antibody

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Myung Chul; Lee, Kyung Han; Choi, Yoon Ho; Chung, June Key; Park, Young Bae; Koh, Chang Soon [Seoul National University College of Medicine, Seoul (Korea, Republic of); Moon, Dae Hyuk [Asan Medical Center, Ulsan University College of Medicine, Seoul (Korea, Republic of)

    1991-03-15

    Infarct size is a major determinant of prognosis after acute myocardial infarction. Up to date, however, clinically available tests to estimate this size have not been sufficiently accurate. Twelve lead electrocardiogram and wall motion abnormality measurement are not quantitative, and creatine phosphokinase (CPK) measurement is inaccurate in the presence of reperfusion or right ventricular infarction. Methods have been developed to localize and size acute myocardial infarcts with agents that are selectively sequestered in areas of myocardial damage, but previously used agents have lacked sufficient specificity. Antibodies that bind specifically only to damaged myocardial cells may resolve this problem and provide an accurate method for noninvasively measuring infarct size. We determined the accuracy with which infarcted myocardial mass can be measured using single photon emission computed tomography (SPECT) and radiolabeled antimyosin antibodies. Seven patients with acute myocardial infarction and one stable angina patient were injected with 2 mCi of Indium-111 labeled antimyosin antibodies. Planar image and SPECT was performed 24 hours later. None of the patients had history of prior infarcts, and none had undergone reperfusion techniques prior to the study, which was done within 4 days of the attack. Planar image showed all infarct patients to have positive uptakes in the cardiac region. The location of this uptake correlated to the infarct site as indicated by electrocardiography in most of the cases. The angina patient, however, showed no such abnormal uptake. Infarct size was determined from transverse slices of the SPECT image using a 45% threshold value obtained from a phantom study. Measured infarct size ranged from 40 to 192 gr. There was significant correlation between the infarct size measured by SPECT and that estimated from serial measurements of CPK (r=0.73, p<0,05). These date suggest that acute myocardial infarct size can be accurately measured

  13. Cardiac MRI for myocardial ischemia.

    LENUS (Irish Health Repository)

    Daly, Caroline

    2013-01-01

    Proper assessment of the physiologic impact of coronary artery stenosis on the LV myocardium can affect patient prognosis and treatment decisions. Cardiac magnetic resonance imaging (CMR) assesses myocardial perfusion by imaging the myocardium during a first-pass transit of an intravenous gadolinium bolus, with spatial and temporal resolution substantially higher than nuclear myocardial perfusion imaging. Coupled with late gadolinium enhancement (LGE) imaging for infarction during the same imaging session, CMR with vasodilating stress perfusion imaging can qualitatively and quantitatively assess the myocardial extent of hypoperfusion from coronary stenosis independent of infarcted myocardium. This approach has been validated experimentally, and multiple clinical trials have established its diagnostic robustness when compared to stress single-photon emission computed tomography. In specialized centers, dobutamine stress CMR has been shown to have incremental diagnostic value above stress echocardiography due to its high imaging quality and ability to image the heart with no restriction of imaging window. This paper reviews the technical aspects, diagnostic utility, prognostic values, challenges to clinical adaptation, and future developments of stress CMR imaging.

  14. O papel de Rhizoctonia spp. binucleadas na indução de resistência a mela da soja = The role of binucleate Rhizoctonia spp. inducing resistance to the soybean foliar blight

    Directory of Open Access Journals (Sweden)

    Marco Antonio Basseto

    2008-04-01

    Full Text Available O papel de Rhizoctonia spp. binucleadas (RBN, no biocontrole de doenças causadas por R. solani Kühn em várias culturas, tem sido relatado na literatura. No entanto, não há informação, no Brasil, sobre o potencial de RBN como agentes de biocontrole contradoenças causadas por Rhizoctonia na soja. A hipótese testada foi de que isolados de RBN podem induzir resistência na soja contra a mela, causada por R. solani do grupo de anastomose (AG 1 IA. Desta forma, o objetivo deste trabalho foi avaliar isolados de RBN, obtidos de amendoim, feijão e soja quanto à capacidade de induzir resistência na soja contra a mela, em condições de casa de vegetação. Esta pesquisa evidencia a ação de RBN na indução de resistência em plantas de soja contra a mela. Entretanto, a manifestação e a efetividade do fenômeno de indução de resistência são dependentes da época de cultivo da soja.The role of non-pathogenic binucleate Rhizoctonia spp. (BNR onthe biocontrol of diseases caused by R. solani on many crops has been reported in the literature. However, in Brazil, there is no information about the potential of BNR as biocontrol agents against Rhizoctonia diseases on soybean. On this research we tested thehypothesis that BNR can induce resistance on soybean against the foliar blight caused by R. solani anastomosis group (AG 1 IA. Thus, the objective of this research was to evaluate BNR isolates isolated from peanuts, snapbeans and soybean according to their ability forinducing resistance on soybean against the foliar blight disease, under greenhouse conditions. This research evidenced the role of BNR inducing resistance on soybeans against the foliar blight. However, both the occurrence and effectiveness of the phenomenon of induced resistance are dependent on the soybean cultivation season.

  15. Xylan polysaccharides fabricated into nanofibrous substrate for myocardial infarction

    International Nuclear Information System (INIS)

    Venugopal, J.; Rajeswari, R.; Shayanti, M.; Sridhar, R.; Sundarrajan, S.; Balamurugan, R.; Ramakrishna, S.

    2013-01-01

    Myocardial infarction, a main cause of heart failure, leads to loss of cardiac tissue impairment of left ventricular function. Repair of diseased myocardium with in vitro engineered cardiac muscle patch/injectable biopolymers with cells may become a viable option for myocardial infarction. We attempted to solve these problems by in vitro study by selecting a plant based polysaccharides beech wood Xylan for the normal functioning of infarcted myocardium. The present study fabricated Xylan based nanofibrous scaffolds cross-linked with glutaraldehyde (Glu) vapors for 24 h, 48 h and 1% Glu blended fibers for the culture of neonatal rat cardiac cells for myocardial infarction. These nanofibers were characterized by SEM, FT-IR, tensile testing and cell culture studies for the normal expression of cardiac proteins. The observed results showed that the Xylan/polyvinyl alcohol (PVA) 24 h Glu vapor cross-linked nanofibers (427 nm) having mechanical strength of 2.43 MPa and Young modulus of 3.74 MPa are suitable for the culture of cardiac cells. Cardiac cells proliferation increased only by 11% in Xylan/PVA 24 h Glu cross-linked nanofibers compared to control tissue culture plate (TCP). The normal cardiac cell morphology was observed in 24 h cross-linked Xylan/PVA nanofibers but 48 h cross-linked fibers cell morphology was changed to flattened and elongated on the fibrous surfaces. Confocal analysis for cardiac expression proteins actinin, connexin 43 was observed normally in 24 h Glu cross-linked nanofibers compared to all other nanofibrous scaffolds. The fabricated Xylan/PVA nanofibrous scaffold may have good potential for the normal functioning of infarcted myocardium. - Highlights: ► Fabrication of polysaccharides Xylan/PVA nanofibers for cardiac tissue engineering ► Nanofibers characterized by SEM, FT-IR, tensile testing and cell culture studies ► Isolation of cardiac cells and cultured on Xylan/PVA nanofibrous scaffolds ► Cultured cells on 24 h Glu cross

  16. Xylan polysaccharides fabricated into nanofibrous substrate for myocardial infarction

    Energy Technology Data Exchange (ETDEWEB)

    Venugopal, J., E-mail: nnijrv@nus.edu.sg; Rajeswari, R.; Shayanti, M.; Sridhar, R.; Sundarrajan, S.; Balamurugan, R.; Ramakrishna, S.

    2013-04-01

    Myocardial infarction, a main cause of heart failure, leads to loss of cardiac tissue impairment of left ventricular function. Repair of diseased myocardium with in vitro engineered cardiac muscle patch/injectable biopolymers with cells may become a viable option for myocardial infarction. We attempted to solve these problems by in vitro study by selecting a plant based polysaccharides beech wood Xylan for the normal functioning of infarcted myocardium. The present study fabricated Xylan based nanofibrous scaffolds cross-linked with glutaraldehyde (Glu) vapors for 24 h, 48 h and 1% Glu blended fibers for the culture of neonatal rat cardiac cells for myocardial infarction. These nanofibers were characterized by SEM, FT-IR, tensile testing and cell culture studies for the normal expression of cardiac proteins. The observed results showed that the Xylan/polyvinyl alcohol (PVA) 24 h Glu vapor cross-linked nanofibers (427 nm) having mechanical strength of 2.43 MPa and Young modulus of 3.74 MPa are suitable for the culture of cardiac cells. Cardiac cells proliferation increased only by 11% in Xylan/PVA 24 h Glu cross-linked nanofibers compared to control tissue culture plate (TCP). The normal cardiac cell morphology was observed in 24 h cross-linked Xylan/PVA nanofibers but 48 h cross-linked fibers cell morphology was changed to flattened and elongated on the fibrous surfaces. Confocal analysis for cardiac expression proteins actinin, connexin 43 was observed normally in 24 h Glu cross-linked nanofibers compared to all other nanofibrous scaffolds. The fabricated Xylan/PVA nanofibrous scaffold may have good potential for the normal functioning of infarcted myocardium. - Highlights: ► Fabrication of polysaccharides Xylan/PVA nanofibers for cardiac tissue engineering ► Nanofibers characterized by SEM, FT-IR, tensile testing and cell culture studies ► Isolation of cardiac cells and cultured on Xylan/PVA nanofibrous scaffolds ► Cultured cells on 24 h Glu cross

  17. Clinical studies on diabetic myocardial disease using exercise testing with myocardial scintigraphy and endomyocardial biopsy

    International Nuclear Information System (INIS)

    Genda, A.; Mizuno, S.; Nunoda, S.

    1986-01-01

    Nine diabetics without significant coronary stenosis participated in an exercise testing protocol with thallium-201 myocardial scintigraphy. Endomyocardial biopsy of right ventricle was also obtained. There were 4 patients with abnormal perfusion (positive group) and 5 patients with normal perfusion (negative group). All cases of the positive group were familial diabetics and there was only one case of dietary treatment, whereas in the negative group, there were only 2 cases of familial diabetics and 3 cases receiving dietary treatment. No statistical differences between the positive and negative groups were observed for the data of exercise performance and hemodynamic parameters in cardiac catheterization at rest. However, the mean ejection fraction in the positive group (62 +/- 13%) was significantly lower than in the negative group (77 +/- 4%). In both groups, the mean diameter of myocardial cells and the mean percent fibrosis of biopsy specimens showed significant increases compared with the control group. The mean percent fibrosis in the positive group (24.1 +/- 8.5%) compared with that in the negative group (16.5 +/- 5.9%) showed a tendency to increase. It is suggested that the abnormal perfusion of thallium-201 in the positive group indicates subclinically a pathological change of microcirculation caused by diabetes mellitus

  18. Screening for silent myocardial ischemia caseof diabetics : interest of myocardial perfusion scintigraphy

    International Nuclear Information System (INIS)

    Bahri, Haifa

    2007-01-01

    Silent myocardial ischemia is a major cause of morbidity and mortality in diabetic patients. Its diagnosis by noninvasive means such as myocardial SPECT would improve the management of these patients. The purpose of this study is to assess the frequency of silent myocardial ischemia in asymptomatic diabetics and their evolution. As a result, the myocardial SPECT is a reliable tool for screening for silent myocardial ischemia in diabetic patients. Its prognostic value allows to stratify the cardiac risk and guide therapeutic management. Its integration into a screening strategy in Tunisia seems limited by its low availability and cost. The latter could be reduced by better patient selection.

  19. Single-cell analysis of ploidy and centrosomes underscores the peculiarity of normal hepatocytes.

    Directory of Open Access Journals (Sweden)

    Francesca Faggioli

    Full Text Available Polyploidization is the most well recognized feature of the liver. Yet, a quantitative and behavioral analysis of centrosomes and DNA content in normal hepatocytes has been limited by the technical challenges of methods available. By using a novel approach employing FISH for chromosomes 18, X and Y we provide, for the first time, a detailed analysis of DNA copies during physiological development in the liver at single cell level. We demonstrate that aneuploidy and unbalanced DNA content in binucleated hepatocytes are common features in normal adult liver. Despite the common belief that hepatocytes contain 1, 2 or no more than 4 centrosomes, our double staining for centrosome associated proteins reveals extranumerary centrosomes in a high percentage of cells as early as 15 days of age. We show that in murine liver the period between 15 days and 1.5 months marks the transition from a prevalence of mononucleated cells to up to 75% of binucleated cells. Our data demonstrate that this timing correlates with a switch in centrosomes number. At 15 days the expected 1 or 2 centrosomes converge with several hepatocytes that contain 3 centrosomes; at 1.5 months the percentage of cells with 3 centrosomes decreases concomitantly with the increase of cells with more than 4 centrosomes. Our analysis shows that the extranumerary centrosomes emerge in concomitance with the process of binucleation and polyploidization and maintain α-tubulin nucleation activity. Finally, by integrating interphase FISH and immunofluorescent approaches, we detected an imbalance between centrosome number and DNA content in liver cells that deviates from the equilibrium expected in normal cells. We speculate that these unique features are relevant to the peculiar biological function of liver cells which are continuously challenged by stress, a condition that could predispose to genomic instability.

  20. Myocardial contusion in patients with blunt chest trauma as evaluated by thallium 201 myocardial scintigraphy

    International Nuclear Information System (INIS)

    Bodin, L.; Rouby, J.J.; Viars, P.

    1988-01-01

    Fifty five patients suffering from blunt chest trauma were studied to assess the diagnosis of myocardial contusion using thallium 201 myocardial scintigraphy. Thirty-eight patients had consistent scintigraphic defects and were considered to have a myocardial contusion. All patients with scintigraphic defects had paroxysmal arrhythmias and/or ECG abnormalities. Of 38 patients, 32 had localized ST-T segment abnormalities; 29, ST-T segment abnormalities suggesting involvement of the same cardiac area as scintigraphic defects; 21, echocardiographic abnormalities. Sixteen patients had segmental hypokinesia involving the same cardiac area as the scintigraphic defects. Fifteen patients had clinical signs suggestive of myocardial contusion and scintigraphic defects. Almost 70 percent of patients with blunt chest trauma had scintigraphic defects related to areas of myocardial contusion. When thallium 201 myocardial scintigraphy directly showed myocardial lesion, two-dimensional echocardiography and standard ECG detected related functional consequences of cardiac trauma

  1. Nifedipine for angina and acute myocardial ischemia

    NARCIS (Netherlands)

    P.G. Hugenholtz (Paul); J.W. de Jong (Jan Willem); P.D. Verdouw (Pieter); P.W.J.C. Serruys (Patrick)

    1983-01-01

    textabstractThis paper reviews the mechanisms believed to be responsible for myocardial ischaemia and the mode of action of calcium antagonist drugs. The clinical management of patients with myocardial ischaemia is discussed in the context of current knowledge about patho-physiology and drug action.

  2. The end of the unique myocardial band

    DEFF Research Database (Denmark)

    MacIver, David H; Partridge, John B; Agger, Peter

    2018-01-01

    Two of the leading concepts of mural ventricular architecture are the unique myocardial band and the myocardial mesh model. We have described, in an accompanying article published in this journal, how the anatomical, histological and high-resolution computed tomographic studies strongly favour th...

  3. When is 201Tl myocardial scintigraphy indicated?

    International Nuclear Information System (INIS)

    Klepzig, H. Jr.; Kaltenbach, M.

    1987-01-01

    Myocardial scintigraphy with thallium-201 has met with good acceptance in cardiology and has proven its value. The method implies only low risk and yields diagnostic results that allow verification or disqualification of suspected myocardial ischemia in those cases where there is only reduced accuracy of the exercise electrocardiogram. (TRV) [de

  4. Do episodes of anger trigger myocardial infarction?

    DEFF Research Database (Denmark)

    Möller, J; Hallqvist, J; Diderichsen, Finn

    1999-01-01

    Our objectives were to study anger as a trigger of acute myocardial infarction (MI) and to explore potential effect modification by usual behavioral patterns related to hostility.......Our objectives were to study anger as a trigger of acute myocardial infarction (MI) and to explore potential effect modification by usual behavioral patterns related to hostility....

  5. Monitoring of myocardial edema following acute myocardial infarction

    International Nuclear Information System (INIS)

    Tahir, E.; Sinn, M.; Avanesov, M.; Wien, J.; Saering, D.; Stehning, C.; Radunski, U. K.; Muellerleile, K.; Adam, G.; Lund, G. K.

    2015-01-01

    Full text: Currently, myocardial edema monitoring after acute myocardial infarction (AMI) is based on visualization of the region with increased signal-intensity on T2-weighted images. Native T1 and T2 mapping are promising novel MRI techniques to quantitatively assess myocardial edema. The purpose of the study was to quantitatively evaluate resorption of myocardial edema following AMI by native T1 and T2 -mapping cardiac magnetic resonance imaging (CMR). CMR (1.5 Tesla Philips Achieva) was performed in 30 patients four times after reperfused AMI at baseline (BL) at 9±6 days after infarction and at 7±1 weeks (follow-up 1, FU1), 3.6±0.5 months (FU2) and 6.5±0.7 months (FU3), respectively. Edema sensitive black-blood T2-weighted (T2w) STIR CMR was performed on end-diastolic LV short-axes. A free-breathing, navigatorgated multi-echo sequence was used for short-axis T2 mapping. T1 mapping was performed using the modified look-locker inversion recovery (MOLLI) sequence. T2 maps were calculated from nine and T1 maps from eight echoes using a dedicated plug-in written for OsiriX software. Two experienced observers independently evaluated T2w-CMR as well as T1 and T2 mapping using the HeAT-Software applying a threshold method. Size of edema and prolongation of the native T1- or T2-time was measured using a cutoff >2SD of remote normal myocardium. Edema size continuously decreased from BL with 32.8 %LV to 24.6 %LV at FU1, to 19.1 %LV at FU2 and to 16.4 %LV at FU3 using T2w-CMR. An almost identical decrease of edema size was observed using native T1 and T2 - mapping. T2 times only decreased between BL from 79±5 ms to 73±2 ms at FU1 (P<0.05), but no further change was observed at later time points with 70±5 ms at FU2 and 70±6 ms at FU3. At all time points the T2 times of remote normal myocardium were about 50±2 ms and significantly lower compared to the edema zone. Also native T1 time within the edema was with 1253 ±103 ms significantly increased compared to remote

  6. Quantitative evaluation of myocardial perfusion and heart function using a non-invasive double isotope technique

    Energy Technology Data Exchange (ETDEWEB)

    Knapp, W H; Doll, J; Georgi, P [Deutsches Krebsforschungszentrum, Heidelberg (Germany, F.R.). Inst. fuer Nuklearmedizin; Tillmanns, H [Heidelberg Univ. (Germany, F.R.). Innere Medizin 3

    1976-11-01

    This paper describes a non-invasive double nuclide technique for the simultaneous measurement of minimal cardiac transit times (MTT) and regional 'myocardial appearance times' (MAT) using gamma camera and computer. MAT is defined as the time lag between the appearance of an indicator with myocardial affinity in the aortic root and its extraction in the myocardial cells. The extraction can be identified as an increase of the ratio between the count rates of the two nuclides e.g. /sup 201/Tl-chloride and sup(113m)In DTPA. The clinical evaluation of this method allows the following conclusions: 1) MAT, determined over several circumscript myocardial regions permits the qualitative diagnosis of a coronary artery disease with high confidence. 2) Indices of nutritive myocardial blood flow (INF), derived by MAT using several representative areas of myocardium, show a definite correlation to the degree of coronary artery disease. In addition to the localization of infarction and the determination of infarct size, the technique described promises a quantitative evaluation of the regional myocardial perfusion. Simultaneously measured MTT help to assess segmental cardiac performance.

  7. The usefulness of the nuclear cardiology in the cellular implant in patients with severe myocardial damage

    International Nuclear Information System (INIS)

    Omelas A, M.; Arguero S, R.; Garrido G, M.H.; Rodriguez C, A.; Careaga, G.; Castano G, R.; Nambo, M.J.; Pascual P, J.; Ortega R, A.; Gaxiola A, A.; Magana S, J.A.; Estrada A, H.; Equipo de Tecnicos en Medicina Nuclear

    2005-01-01

    The recent therapeutic advances as the cellular implant as well as those different protocols of image acquisition in the field of the Nuclear Cardiology its have allowed that the patient with severe myocardial damage and without some possibility of revascularization is benefited with these advances. Doubtless the Tl-201 par excellence has an important paper for standardize the more appropriate therapeutic behavior for the heart attack patient; reason by this investigation protocol was developed. The objective of the study was to identify the heart attack regions without viable tissue with SPECT in patient with important myocardial damage without some possibility of traditional revascularization; for the 'Stem cell' cellular implantation therapy. The methodology it was carried out by a study of myocardial perfusion in 10 patients with important myocardial damage previous cellular implants, with PICANUC/ SPECT methodology and using a software (Emory Tool Box) for the image processing validated by the University of Emory Atlanta GA; and using as tracer the Tl - 201 to identify the heart attack regions without presence of viable tissue with an analysis model of 17 segments standardized for the left ventricle; qualifying this way the myocardial perfusion in: 0 (normal), 1 (light), 2 (moderate), 3 (severe), 4 (absent) and x (bad technique). The conclusions were that the SPECT study with PICANUC methodology with Tl-201 is safe and effective for the precise localization for the cellular implantation via direct intra myocardial. (Author)

  8. Reduction of myocardial ischemia-reperfusion injury by mechanical tissue resuscitation using sub-atmospheric pressure.

    Science.gov (United States)

    Argenta, Louis C; Morykwas, Michael J; Mays, Jennifer J; Thompson, Edreca A; Hammon, John W; Jordan, James E

    2010-03-01

    Reperfusion-induced injury after myocardial infarction is associated with a well-defined sequence of early and late cardiomyocyte death. Most present attempts to ameliorate this sequence focus on a single facet of the complex process in an attempt to salvage cardiomyocytes. We examined, as proof of concept, the effects of mechanical tissue resuscitation (MTR) with controlled negative pressure on myocardial injury following acute myocardial infarction. Anesthetized swine were subjected to 75 minutes of left coronary artery occlusion and three hours of reperfusion. Animals were assigned to one of three groups: (A) untreated control; treatment of involved myocardium for 180 minutes of MTR with (B) -50 mmHg, or (C) -125 mmHg. All three groups were subjected to equivalent ischemic stress. Treatment of the ischemic area with MTR for 180 minutes significantly (p control: 9.3 +/- 1.8% (-50 mmHg) and 11.9 +/- 1.2% (-125 mmHg) versus 26.4 +/- 2.1% (control). Total area of cell death was reduced by 65% with -50 mmHg treatment and 55% in the -125 mmHg group. Treatment of ischemic myocardium with MTR, for a controlled period of time during reperfusion, successfully reduced the extent of myocardial death after acute myocardial infarction. These data provide evidence that MTR using subatmospheric pressure may be a simple, efficacious, nonpharmacological, mechanical strategy for decreasing cardiomyocyte death following myocardial infarction, which can be delivered in the operating room.

  9. Ventricular and myocardial scintiscanning: Methodical fundamentals

    International Nuclear Information System (INIS)

    Standke, R.; Hoer, G.; Maul, F.D.

    1984-01-01

    Nuclear cardiology is concerned with non invasive procedures to quantitate global and regional left ventricular function (Radionuclide ventriculography), also the imaging of vitally perfused myocardium (Myocardial scintigraphy) is achieved. A gammacamera and a minicomputer are necessary. Radionuclide ventriculography enables the analysis of global and regional time dependent left ventricular volume curves and hence the evaluation of contraction and contractility of the heart muscle. The basis is a sequence of scans covering an average heartcycle. This sequence may be produced either by first pass or equilibrium technique. Myocardial scintigraphy at rest images vital myocardium, scans immediately after exercise represent the interference of myocardial perfusion and muscle mass. The regional difference (Redistribution) between normalized exercise- and rest scans provide quantitative parameters to detect impairment of exercise-induced myocardial perfusion anomalies. The procedures of sectorial analysis of left ventricular function and myocardial perfusion are presented. (orig.) [de

  10. Effect of limb ischemic preconditioning on myocardial apoptosis-related proteins in ischemia-reperfusion injury

    Science.gov (United States)

    GAO, JIANZHI; ZHAO, LINJING; WANG, YONGLING; TENG, QINGLEI; LIANG, LIDONG; ZHANG, JINYING

    2013-01-01

    The aim of this study was to investigate the effect of limb ischemic preconditioning (LIPC) on myocardial apoptosis in myocardial ischemia-reperfusion injury (MIRI), as well as the regulation of caspase-3 and the B cell lymphoma 2 (Bcl-2) gene in LIPC. A total of 50 rats were divided randomly into 5 groups (n=10). Four rats in each group were drawn out for detection of apoptosis. The sham, MIRI and LIPC groups underwent surgery without additional treatment. In the LY294002 group, LY294002 preconditioning was administered 15 min before reperfusion. In the LY294002+LIPC group, following LIPC, LY294002 was administered 15 min before reperfusion. The relative expression of myocardial Bcl-2 and caspase-3 mRNA and the apoptotic index for each group were determined by reverse transcription-polymerase chain reaction (RT-PCR) and terminal deoxynucleotidyl transferase deoxyuridine triphosphate (dUTP) nick end labeling (TUNEL), respectively. The ultrastructure of the cardiac muscle tissues was observed by election microscopy. Compared with the sham group, the expression of caspase-3 mRNA in the MIRI group significantly increased (P<0.05) and the expression of Bcl-2 mRNA clearly decreased. Compared with the MIRI group, LIPC reduced the expression of caspase-3 and increased the expression of Bcl-2 mRNA (P<0.05). There were no significant differences between the LY294002+LIPC group and the MIRI group. Compared with the sham group, the apoptotic index of myocardial cells in the MIRI group significantly increased (P<0.05). Compared with the MIRI group, LIPC significantly decreased the apoptotic index of myocardial cells (P<0.05) and LY294002 increased the apoptotic index of myocardial cells. Compared with the LIPC group, LY294002+LIPC significantly increased the apoptotic index of myocardial cells (P<0.05). There were no significant differences between the LY294002+LIPC and MIRI groups. In conclusion, LIPC increased the expression of Bcl-2 and decreased caspase-3 mRNA and

  11. Erythrocyte-rich thrombus aspirated from patients with ST-elevation myocardial infarction: association with oxidative stress and its impact on myocardial reperfusion

    NARCIS (Netherlands)

    Yunoki, Kei; Naruko, Takahiko; Sugioka, Kenichi; Inaba, Mayumi; Iwasa, Yoko; Komatsu, Ryushi; Itoh, Akira; Haze, Kazuo; Inoue, Takeshi; Yoshiyama, Minoru; Becker, Anton E.; Ueda, Makiko

    2012-01-01

    Recent studies have demonstrated that erythrocytes are a potential component in atheromatous lesions and thrombus formation in patients with ST-elevation myocardial infarction (STEMI). The purpose of this study was to determine the associations of red blood cell (RBC) component of coronary thrombi

  12. Adult mouse epicardium modulates myocardial injury by secreting paracrine factors

    Science.gov (United States)

    Zhou, Bin; Honor, Leah B.; He, Huamei; Ma, Qing; Oh, Jin-Hee; Butterfield, Catherine; Lin, Ruei-Zeng; Melero-Martin, Juan M.; Dolmatova, Elena; Duffy, Heather S.; von Gise, Alexander; Zhou, Pingzhu; Hu, Yong Wu; Wang, Gang; Zhang, Bing; Wang, Lianchun; Hall, Jennifer L.; Moses, Marsha A.; McGowan, Francis X.; Pu, William T.

    2011-01-01

    The epicardium makes essential cellular and paracrine contributions to the growth of the fetal myocardium and the formation of the coronary vasculature. However, whether the epicardium has similar roles postnatally in the normal and injured heart remains enigmatic. Here, we have investigated this question using genetic fate-mapping approaches in mice. In uninjured postnatal heart, epicardial cells were quiescent. Myocardial infarction increased epicardial cell proliferation and stimulated formation of epicardium-derived cells (EPDCs), which remained in a thickened layer on the surface of the heart. EPDCs did not adopt cardiomyocyte or coronary EC fates, but rather differentiated into mesenchymal cells expressing fibroblast and smooth muscle cell markers. In vitro and in vivo assays demonstrated that EPDCs secreted paracrine factors that strongly promoted angiogenesis. In a myocardial infarction model, EPDC-conditioned medium reduced infarct size and improved heart function. Our findings indicate that epicardium modulates the cardiac injury response by conditioning the subepicardial environment, potentially offering a new therapeutic strategy for cardiac protection. PMID:21505261

  13. Cardiac-Specific SOCS3 Deletion Prevents In Vivo Myocardial Ischemia Reperfusion Injury through Sustained Activation of Cardioprotective Signaling Molecules.

    Directory of Open Access Journals (Sweden)

    Takanobu Nagata

    Full Text Available Myocardial ischemia reperfusion injury (IRI adversely affects cardiac performance and the prognosis of patients with acute myocardial infarction. Although myocardial signal transducer and activator of transcription (STAT 3 is potently cardioprotective during IRI, the inhibitory mechanism responsible for its activation is largely unknown. The present study aimed to investigate the role of the myocardial suppressor of cytokine signaling (SOCS-3, an intrinsic negative feedback regulator of the Janus kinase (JAK-STAT signaling pathway, in the development of myocardial IRI. Myocardial IRI was induced in mice by ligating the left anterior descending coronary artery for 1 h, followed by different reperfusion times. One hour after reperfusion, the rapid expression of JAK-STAT-activating cytokines was observed. We precisely evaluated the phosphorylation of cardioprotective signaling molecules and the expression of SOCS3 during IRI and then induced myocardial IRI in wild-type and cardiac-specific SOCS3 knockout mice (SOCS3-CKO. The activation of STAT3, AKT, and ERK1/2 rapidly peaked and promptly decreased during IRI. This decrease correlated with the induction of SOCS3 expression up to 24 h after IRI in wild-type mice. The infarct size 24 h after reperfusion was significantly reduced in SOCS3-CKO compared with wild-type mice. In SOCS3-CKO mice, STAT3, AKT, and ERK1/2 phosphorylation was sustained, myocardial apoptosis was prevented, and the expression of anti-apoptotic Bcl-2 family member myeloid cell leukemia-1 (Mcl-1 was augmented. Cardiac-specific SOCS3 deletion led to the sustained activation of cardioprotective signaling molecules including and prevented myocardial apoptosis and injury during IRI. Our findings suggest that SOCS3 may represent a key factor that exacerbates the development of myocardial IRI.

  14. Direct Evidence that Myocardial Insulin Resistance following Myocardial Ischemia Contributes to Post-Ischemic Heart Failure

    Science.gov (United States)

    Fu, Feng; Zhao, Kun; Li, Jia; Xu, Jie; Zhang, Yuan; Liu, Chengfeng; Yang, Weidong; Gao, Chao; Li, Jun; Zhang, Haifeng; Li, Yan; Cui, Qin; Wang, Haichang; Tao, Ling; Wang, Jing; Quon, Michael J; Gao, Feng

    2015-01-01

    A close link between heart failure (HF) and systemic insulin resistance has been well documented, whereas myocardial insulin resistance and its association with HF are inadequately investigated. This study aims to determine the role of myocardial insulin resistance in ischemic HF and its underlying mechanisms. Male Sprague-Dawley rats subjected to myocardial infarction (MI) developed progressive left ventricular dilation with dysfunction and HF at 4 wk post-MI. Of note, myocardial insulin sensitivity was decreased as early as 1 wk after MI, which was accompanied by increased production of myocardial TNF-α. Overexpression of TNF-α in heart mimicked impaired insulin signaling and cardiac dysfunction leading to HF observed after MI. Treatment of rats with a specific TNF-α inhibitor improved myocardial insulin signaling post-MI. Insulin treatment given immediately following MI suppressed myocardial TNF-α production and improved cardiac insulin sensitivity and opposed cardiac dysfunction/remodeling. Moreover, tamoxifen-induced cardiomyocyte-specific insulin receptor knockout mice exhibited aggravated post-ischemic ventricular remodeling and dysfunction compared with controls. In conclusion, MI induces myocardial insulin resistance (without systemic insulin resistance) mediated partly by ischemia-induced myocardial TNF-α overproduction and promotes the development of HF. Our findings underscore the direct and essential role of myocardial insulin signaling in protection against post-ischemic HF. PMID:26659007

  15. Three-dimension structure of ventricular myocardial fibers after myocardial infarction

    Directory of Open Access Journals (Sweden)

    Li Libin

    2010-11-01

    Full Text Available Abstract Background To explore the pathological changes of three-dimension structure of ventricular myocardial fibers after anterior myocardial infarction in dog heart. Methods Fourteen acute anterior myocardial infarction models were made from healthy dogs (mean weight 17.6 ± 2.5 kg. Six out of 14 dogs with old myocardial infarction were sacrificed, and their hearts were harvested after they survived the acute anterior myocardial infarction for 3 months. Each heart was dissected into ventricular myocardial band (VMB, morphological characters in infarction region were observed, and infarct size percents in descending segment and ascending segment were calculated. Results Six dog hearts were successfully dissected into VMB. Uncorresponding damages in myocardial fibers of descending segment and ascending segment were found in apical circle in anterior wall infarction. Infarct size percent in the ascending segment was significantly larger than that in the descending segment (23.36 ± 3.15 (SD vs 30.69 ± 2.40%, P = 0.0033; the long axis of infarction area was perpendicular to the orientation of myocardial fibers in ascending segment; however, the long axis of the infarction area was parallel with the orientation of myocardial fibers in descending segment. Conclusions We found that damages were different in both morphology and size in ascending segment and descending segment in heart with myocardial infarction. This may provide an important insight for us to understand the mechanism of heart failure following coronary artery diseases.

  16. Diagnostic value of exercise induced 18F-FDG myocardial metabolism scintigraphy in myocardial ischemia

    International Nuclear Information System (INIS)

    Shen Rui; He Zuoxiang; Shi Rongfang; Liu Xiujie; Tian Yueqin; Guo Feng; Wei Hongxing; Wu Yongjian; Qin Xuewen; Gao Runlin

    2006-01-01

    Objective: To evaluate the feasibility and diagnostic accuracy of exercise induced myocardial imaging with 18 F-fluorodeoxyglucose (FDG) in myocardial ischemia. Methods: Twenty-six patients with known or suspected coronary artery, disease (CAD) and with no prior myocardial infarction underwent simultaneous myocardial perfusion and metabolism imaging following intravenous injection of 99 Tc m -methoxy-isobutylisonitrile ( 99 Tc m -sestamibi) and 18 F-FDG at peak exercise. Subsequently rest perfusion imaging and coronary angiography (CAG) were performed in all patients. Exercise 18 F-FDG myocardial imaging was compared with 99 Tc m -sestamibi imaging and CAG. Results: In 22 patients with ≥50% narrowing over l coronary artery, 18 had perfusion abnormalities (sensitivity 82%), whereas 20 had abnormal myocardial 18 F-FDG uptake (sensitivity 91%, P>0.05). Patients with reversible (12 cases) or partial reversible (3 cases) perfusion abnormalities had increased myocardial 18 F-FDG uptake in abnormal perfusion segments. Compared with CAG, perfusion defect was seen in myocardial segments corresponding to 25 vascular territories of 51 vessels with ≥50% narrowing in 22 patients in 99 Tc m -sestamibi imaging (sensitivity 49%), whereas increased 18 F-FDG uptake was seen in 34 vascular territories (sensitivity 67%, P=0.008). Conclusions: Exercise induced myocardial ischemia can be imaged directly with 18 F-FDG. Combined exercise 18 F-FDG and 99 Tc m -sestamibi imaging provides a better assessment of exercise-induced myocardial ischemia as compared with exercise-rest perfusion imaging. (authors)

  17. Myocardial perfusion imaging with dual energy CT

    Energy Technology Data Exchange (ETDEWEB)

    Jin, Kwang Nam [Division of Cardiovascular Imaging, Department of Radiology and Radiological Science, Medical University of South Carolina, Charleston, SC (United States); Department of Radiology, SMG-SNU Boramae Medical Center, Seoul (Korea, Republic of); De Cecco, Carlo N. [Division of Cardiovascular Imaging, Department of Radiology and Radiological Science, Medical University of South Carolina, Charleston, SC (United States); Caruso, Damiano [Division of Cardiovascular Imaging, Department of Radiology and Radiological Science, Medical University of South Carolina, Charleston, SC (United States); Department of Radiological Sciences, Oncology and Pathology, University of Rome “Sapienza”, Rome (Italy); Tesche, Christian [Division of Cardiovascular Imaging, Department of Radiology and Radiological Science, Medical University of South Carolina, Charleston, SC (United States); Department of Cardiology and Intensive Care Medicine, Heart Center Munich-Bogenhausen, Munich (Germany); Spandorfer, Adam; Varga-Szemes, Akos [Division of Cardiovascular Imaging, Department of Radiology and Radiological Science, Medical University of South Carolina, Charleston, SC (United States); Schoepf, U. Joseph, E-mail: schoepf@musc.edu [Division of Cardiovascular Imaging, Department of Radiology and Radiological Science, Medical University of South Carolina, Charleston, SC (United States); Division of Cardiology, Department of Medicine, Medical University of South Carolina, Charleston, SC (United States)

    2016-10-15

    Highlights: • Stress dual-energy sCTMPI offers the possibility to directly detect the presence of myocardial perfusion defects. • Stress dual-energy sCTMPI allows differentiating between reversible and fixed myocardial perfusion defects. • The combination of coronary CT angiography and dual-energy sCTMPI can improve the ability of CT to detect hemodynamically relevant coronary artery disease. - Abstract: Dual-energy CT (DECT) enables simultaneous use of two different tube voltages, thus different x-ray absorption characteristics are acquired in the same anatomic location with two different X-ray spectra. The various DECT techniques allow material decomposition and mapping of the iodine distribution within the myocardium. Static dual-energy myocardial perfusion imaging (sCTMPI) using pharmacological stress agents demonstrate myocardial ischemia by single snapshot images of myocardial iodine distribution. sCTMPI gives incremental values to coronary artery stenosis detected on coronary CT angiography (CCTA) by showing consequent reversible or fixed myocardial perfusion defects. The comprehensive acquisition of CCTA and sCTMPI offers extensive morphological and functional evaluation of coronary artery disease. Recent studies have revealed that dual-energy sCTMPI shows promising diagnostic accuracy for the detection of hemodynamically significant coronary artery disease compared to single-photon emission computed tomography, invasive coronary angiography, and cardiac MRI. The aim of this review is to present currently available DECT techniques for static myocardial perfusion imaging and recent clinical applications and ongoing investigations.

  18. Nitrogen-13-labeled ammonia for myocardial imaging

    Energy Technology Data Exchange (ETDEWEB)

    Walsh, W.F.; Fill, H.R.; Harper, P.V.

    1977-01-01

    Cyclotron-produced nitrogen-13 (half-life 10 min), as labeled ammonia (/sup 13/NH/sub 4//sup +/), has been evaluated as a myocardial perfusion imaging agent. The regional myocardial uptake of /sup 13/NH/sub 4//sup +/ has been shown to be proportional to regional tissue perfusion in animal studies. Intravenously administered /sup 13/NH/sub 4//sup +/ is rapidly cleared from the circulation, being extracted by the liver (15 percent), lungs, myocardium (2 percent--4 percent), brain, kidney, and bladder. Myocardial ammonia is metabolized mainly to glutamine via the glutamine synthetase pathway. Pulmonary uptake is substantial, but usually transient, except in smokers where clearance may be delayed. The positron annihilation irradiation (511 keV) of /sup 13/N may be imaged with a scintillation camera, using either a specially designed tungsten collimator or a pinhole collimator. After early technical problems with collimation and the production method of /sup 13/NH/sub 4//sup +/ were overcome, reproducible high quality myocardial images were consistently obtained. The normal myocardial image was established to be of a homogeneous ''doughnut'' configuration. Imaging studies performed in patients with varying manifestations of ischemic and valvular heart disease showed a high incidence of localized perfusion defects, especially in patients with acute myocardial infarction. Sequential studies at short intervals in patients with acute infarction showed correlation between alterations in regional perfusion and the clinical course of the patient. It is concluded that myocardial imaging with /sup 13/NH/sub 4//sup +/ and a scintillation camera provides a valid and noninvasive means of assessing regional myocardial perfusion. This method is especially suitable for sequential studies of acute cardiac patients at short intervals. Coincidence imaging of the 511 keV annihilation irradiation provides a tomographic and potentially quantitative assessment of the

  19. Specific expression patterns and cell distribution of ancient and modern PAG in bovine placenta during pregnancy.

    Science.gov (United States)

    Touzard, Eve; Reinaud, Pierrette; Dubois, Olivier; Guyader-Joly, Catherine; Humblot, Patrice; Ponsart, Claire; Charpigny, Gilles

    2013-10-01

    Pregnancy-associated glycoproteins (PAGs) constitute a multigenic family of aspartic proteinases expressed in the trophoblast of the ruminant placenta. In Bos taurus, this family comprises 21 members segregated into ancient and modern phylogenetic groups. Ancient PAGs have been reported to be synthesized throughout the trophoblastic cell layer whereas modern PAGs are produced by binucleate cells of cotyledons. The aim of this study was to investigate modern and ancient PAGs during gestation in cotyledonary and intercotyledonary tissues. To obtain convincing and innovative results despite the high sequence identity shared between PAGs, we designed specific tools such as amplification primers and antibodies. Using real-time RT-PCR, we described the transcript expression of 16 bovine PAGs. Overall, PAGs are characterized by an increase in their expression during gestation. However, we demonstrated a segregation of modern PAGs in cotyledons and of ancient PAGs in the intercotyledonary chorion, except for the ancient PAG2 expressed in cotyledons. By raising specific antibodies against the modern PAG1 and ancient PAG11 and PAG2, we established the expression kinetics of the proteins using western blotting. Immunohistochemistry showed that PAGs were produced by specific cellular populations: PAG1 by binucleate cells in the whole trophoblastic layer, PAG11 was localized in binucleate cells of the intercotyledonary trophoblast and the chorionic plate of the cotyledon, while PAG2 was produced in mononucleate cells of the internal villi of the cotyledon. These results revealed a highly specific regulation of PAG expression and cell localization as a function of their phylogenetic status, suggesting distinct biological functions within placental tissues.

  20. Tumor Necrosis Factor-α Produced in Cardiomyocytes Mediates a Predominant Myocardial Inflammatory Response to Stretch in Early Volume Overload

    OpenAIRE

    Chen, Yuanwen; Pat, Betty; Zheng, Junying; Cain, Laura; Powell, Pamela; Shi, Ke; Sabri, Abdelkarim; Husain, Ahsan; Dell’Italia, Louis J

    2010-01-01

    Acute stretch caused by volume overload (VO) of aorto-caval fistula (ACF) induces a variety of myocardial responses including mast cell accumulation, matrix metalloproteinase (MMP) activation and collagen degradation, all of which are critical in dictating long term left ventricle (LV) outcome to VO. Meanwhile, these responses can be part of myocardial inflammation dictated by tumor necrosis factor-α (TNF-α) which is elevated after acute ACF. However, it is unknown whether TNF-α mediates a ma...

  1. Inhibition of Matrix Metalloproteinase Activity Prevents Increases in Myocardial Tumor Necrosis Factor-α

    Science.gov (United States)

    Murray, David B.; Levick, Scott P; Brower, Gregory L.; Janicki, Joseph S.

    2010-01-01

    Aim TNF-α is known to cause adverse myocardial remodeling. While we have previously shown a role for cardiac mast cells in mediating myocardial TNF-α, matrix metalloproteinases (MMP) activation of TNF-α may also be contributory. We sought to determine the relative roles of MMPs and cardiac mast cells in the activation of TNF-α in the hearts of rats subjected to chronic volume overload. Methods Interventions with the broad spectrum MMP inhibitor, GM6001, or the mast cell stabilizer, nedocromil, were performed in the rat aortocaval fistula (ACF) model of volume overload. Results Myocardial TNF-α levels were significantly increased in the ACF. This increase was prevented by MMP inhibition with GM6001 (p ≤ 0.001 vs. ACF). Conversely, myocardial TNF-α levels were increased in the ACF + nedocromil treated fistula groups (p ≤ 0.001 vs. sham). The degradation of interstitial collagen volume fraction seen in the untreated ACF group was prevented in both the GM6001 and nedocromil treated hearts. Significant increases in LV myocardial ET-1 levels also occurred in the ACF group at 3 days post-fistula. Whereas administration of GM6001 significantly attenuated this increase, mast cell stabilization with nedocromil markedly exacerbated the increase, producing ET-1 levels 6.5 fold and 2 fold greater than that in the sham-operated control and ACF group, respectively. Conclusion The efficacy of the MMP inhibitor, GM6001, to prevent increased levels of myocardial TNF-α is indicative of MMP-mediated cleavage of latent extracellular membrane bound TNF-α protein as the primary source of bioactive TNF-α in the myocardium of the volume-overload heart. PMID:20403361

  2. Myocardial infarction, androgen and the skin.

    Science.gov (United States)

    Halim, M M; Meyrick, G; Jeans, W D; Murphy, D; Burton, J L

    1978-01-01

    Various indices of masculinity were compared in 48 men who had recovered from myocardial infarction and in their age-matched controls. We found little evidence to support the idea that myocardial infarction is related to increased androgenic stimulation. The patients with myocardial infarction had no increase in plasma testosterone, muscle thickness, sebum excretion rate, maximal sweat secretion rate, male pattern alopecia or density of terminal body hair, but as a group they had a slight increase in skin and bone thickness compared with the controls.

  3. Safety and effectiveness of the Genous™ endothelial progenitor cell-capture stent in the first year following ST-elevation acute myocardial infarction: A single center experience and review of the literature

    Energy Technology Data Exchange (ETDEWEB)

    Pereira-da-Silva, Tiago, E-mail: tiagopsilva@sapo.pt; Bernardes, Luís; Cacela, Duarte; Fiarresga, António; Sousa, Lídia; Patrício, Lino; Ferreira, Rui Cruz

    2013-11-15

    Purpose: The Genous™ stent (GS) is designed to accelerate endothelization, which is potentially useful in the pro-thrombotic environment of ST-elevation acute myocardial infarction (STEMI). We aimed to evaluate the safety and effectiveness of the GS in the first year following primary percutaneous coronary intervention (PCI) and to compare our results with the few previously published studies. Methods and Materials: All patients admitted to a single center due to STEMI that underwent primary PCI using exclusively GS, between May 2006 and January 2012, were enrolled. The primary study endpoints were major adverse cardiac events (MACEs), defined as the composite of cardiac death, acute myocardial infarction and target vessel revascularization, at one and 12 months. Results: In the cohort of 109 patients (73.4% male, 59 ± 12 years), 24.8% were diabetic. PCI was performed in 116 lesions with angiographic success in 99.1%, using 148 GS with median diameter of 3.00 mm (2.50–4.00) and median length of 15 mm (9–33). Cumulative MACEs were 2.8% at one month and 6.4% at 12 months. Three stent thromboses (2.8%), all subacute, and one stent restenosis (0.9%) occurred. These accounted for the four target vessel revascularizations (3.7%). At 12 months, 33.9% of patients were not on dual antiplatelet therapy. Conclusions: GS was safe and effective in the first year following primary PCI in STEMI, with an apparently safer profile comparing with the previously published data. Summary: We report the safety and effectiveness of the Genous™ stent (GS) in the first year following primary percutaneous coronary intervention in ST-elevation acute myocardial infarction. A comprehensive review of the few studies that have been published on this subject was included and some suggest a less safe profile of the GS. Our results and the critical review included may add information and reinforce the safety and effectiveness of the GS in ST-elevation in acute myocardial infarction.

  4. Safety and effectiveness of the Genous™ endothelial progenitor cell-capture stent in the first year following ST-elevation acute myocardial infarction: A single center experience and review of the literature

    International Nuclear Information System (INIS)

    Pereira-da-Silva, Tiago; Bernardes, Luís; Cacela, Duarte; Fiarresga, António; Sousa, Lídia; Patrício, Lino; Ferreira, Rui Cruz

    2013-01-01

    Purpose: The Genous™ stent (GS) is designed to accelerate endothelization, which is potentially useful in the pro-thrombotic environment of ST-elevation acute myocardial infarction (STEMI). We aimed to evaluate the safety and effectiveness of the GS in the first year following primary percutaneous coronary intervention (PCI) and to compare our results with the few previously published studies. Methods and Materials: All patients admitted to a single center due to STEMI that underwent primary PCI using exclusively GS, between May 2006 and January 2012, were enrolled. The primary study endpoints were major adverse cardiac events (MACEs), defined as the composite of cardiac death, acute myocardial infarction and target vessel revascularization, at one and 12 months. Results: In the cohort of 109 patients (73.4% male, 59 ± 12 years), 24.8% were diabetic. PCI was performed in 116 lesions with angiographic success in 99.1%, using 148 GS with median diameter of 3.00 mm (2.50–4.00) and median length of 15 mm (9–33). Cumulative MACEs were 2.8% at one month and 6.4% at 12 months. Three stent thromboses (2.8%), all subacute, and one stent restenosis (0.9%) occurred. These accounted for the four target vessel revascularizations (3.7%). At 12 months, 33.9% of patients were not on dual antiplatelet therapy. Conclusions: GS was safe and effective in the first year following primary PCI in STEMI, with an apparently safer profile comparing with the previously published data. Summary: We report the safety and effectiveness of the Genous™ stent (GS) in the first year following primary percutaneous coronary intervention in ST-elevation acute myocardial infarction. A comprehensive review of the few studies that have been published on this subject was included and some suggest a less safe profile of the GS. Our results and the critical review included may add information and reinforce the safety and effectiveness of the GS in ST-elevation in acute myocardial infarction

  5. The effect of levosimendan on myocardial ischemia–reperfusion injury in streptozotocin-induced diabetic rats

    Directory of Open Access Journals (Sweden)

    Hasan Ali Kiraz

    2015-12-01

    Full Text Available Objective: Ischemia/reperfusion (I/R injury is an important cause of myocardial damage by means of oxidative, inflammatory, and apoptotic mechanisms. The aim of the present study was to examine the potential cardio protective effects of levosimendan in a diabetic rat model of myocardial I/R injury. Methods: A total of 18 streptozotocin-induced diabetic Wistar Albino rats (55 mg/kg were randomly divided into three equal groups as follows: the diabetic I/R group (DIR in which myocardial I/R was induced following left thoracotomy, by ligating the left anterior descending coronary artery for 60 min, followed by 2 h of reperfusion; the diabetic I/R levosimendan group (DIRL, which underwent I/R by the same method while taking levosimendan intraperitoneal 12 µg kg−1; and the diabetic control group (DC which underwent sham operations without tightening of the coronary sutures. As a control group (C, six healthy age-matched Wistar Albino rats underwent sham operations similar to the DC group. Two hours after the operation, the rats were sacrificed and the myocardial tissue samples were examined by light microscopy for evidence of myonecrosis and inflammatory cell infiltration. Results: Myonecrosis findings were significantly different among groups (p=0.008. Myonecrosis was more pronounced in the DIR group compared with the C, DC, and DIRL groups (p=0.001, p=0.007 and p=0.037, respectively. Similarly, the degree of inflammatory cell infiltration showed significant difference among groups (p<0.0001. Compared with C, DC, and DIRL groups, the inflammatory cell infiltration was significantly higher among the DIR group (p<0.0001, p<0.0001, and p=0.020, respectively. Also, myocardial tissue edema was significantly different among groups (p=0.006. The light microscopic myocardial tissue edema levels were significantly higher in the DIR group than the C, DC, and DIRL groups (p=0.001, p=0.037, and p=0.014, respectively. Conclusion: Taken together, our data

  6. The effect of levosimendan on myocardial ischemia–reperfusion injury in streptozotocin-induced diabetic rats

    Science.gov (United States)

    Kiraz, Hasan Ali; Poyraz, Fatih; Kip, Gülay; Erdem, Özlem; Alkan, Metin; Arslan, Mustafa; Özer, Abdullah; Şivgin, Volkan; Çomu, Faruk Metin

    2015-01-01

    Objective Ischemia/reperfusion (I/R) injury is an important cause of myocardial damage by means of oxidative, inflammatory, and apoptotic mechanisms. The aim of the present study was to examine the potential cardio protective effects of levosimendan in a diabetic rat model of myocardial I/R injury. Methods A total of 18 streptozotocin-induced diabetic Wistar Albino rats (55 mg/kg) were randomly divided into three equal groups as follows: the diabetic I/R group (DIR) in which myocardial I/R was induced following left thoracotomy, by ligating the left anterior descending coronary artery for 60 min, followed by 2 h of reperfusion; the diabetic I/R levosimendan group (DIRL), which underwent I/R by the same method while taking levosimendan intraperitoneal 12 µg kg−1; and the diabetic control group (DC) which underwent sham operations without tightening of the coronary sutures. As a control group (C), six healthy age-matched Wistar Albino rats underwent sham operations similar to the DC group. Two hours after the operation, the rats were sacrificed and the myocardial tissue samples were examined by light microscopy for evidence of myonecrosis and inflammatory cell infiltration. Results Myonecrosis findings were significantly different among groups (p=0.008). Myonecrosis was more pronounced in the DIR group compared with the C, DC, and DIRL groups (p=0.001, p=0.007 and p=0.037, respectively). Similarly, the degree of inflammatory cell infiltration showed significant difference among groups (p<0.0001). Compared with C, DC, and DIRL groups, the inflammatory cell infiltration was significantly higher among the DIR group (p<0.0001, p<0.0001, and p=0.020, respectively). Also, myocardial tissue edema was significantly different among groups (p=0.006). The light microscopic myocardial tissue edema levels were significantly higher in the DIR group than the C, DC, and DIRL groups (p=0.001, p=0.037, and p=0.014, respectively). Conclusion Taken together, our data indicate that

  7. SPECT Myocardial Blood Flow Quantitation Concludes Equivocal Myocardial Perfusion SPECT Studies to Increase Diagnostic Benefits.

    Science.gov (United States)

    Chen, Lung-Ching; Lin, Chih-Yuan; Chen, Ing-Jou; Ku, Chi-Tai; Chen, Yen-Kung; Hsu, Bailing

    2016-01-01

    Recently, myocardial blood flow quantitation with dynamic SPECT/CT has been reported to enhance the detection of coronary artery disease in human. This advance has created important clinical applications to coronary artery disease diagnosis and management for areas where myocardial perfusion PET tracers are not available. We present 2 clinical cases that undergone a combined test of 1-day rest/dipyridamole-stress dynamic SPECT and ECG-gated myocardial perfusion SPECT scans using an integrated imaging protocol and demonstrate that flow parameters are capable to conclude equivocal myocardial perfusion SPECT studies, therefore increasing diagnostic benefits to add value in making clinical decisions.

  8. Myocardial glucose metabolism assessed by positron emission tomography and the histopathologic findings of microvessels in syndrome X

    International Nuclear Information System (INIS)

    Satake, Osamichi; Kajinami, Kouji; Ishikawa, Yoshimaro; Ueda, Tadashi; Tsugawa, Hiroichi; Kanemitsu, Seiyu; Okubo, Shinji; Takekoshi, Noboru

    2004-01-01

    Syndrome X has been recognized as a disease that is primarily reflected in the cardiac microvasculature. Myocardial metabolism in this condition has been studied, but not in relation to small vessel pathology. In order to examine the relationship between myocardial metabolism and small vessel pathology, 24 consecutive patients with syndrome X (7 men, 17 women; mean age 58 years) were evaluated by the thallium exercise stress test, positron emission tomography using F-18 fluoro-deoxyglucose (FDG), and an endomyocardial biopsy. All patients showed either diffuse or focal increase in the myocardial uptake of FDG, but only 17 patients (71%) showed hypoperfused areas with partial or complete redistribution in the thallium study. Quantification of myocardial FDG uptake revealed that the value in syndrome X patients was 10-fold higher than in controls (p<0.0001). Histopathological examination revealed that in syndrome X there is an extensive increase in smooth muscle cells and thickening of the vascular wall, even in capillary vessels, and the small vessel lumen was markedly narrowed. There was a significant inverse correlation between FDG myocardial uptake and the microvessel luminal area. In syndrome X patients, myocardial FDG uptake is increased extensively, which is strongly associated with narrowed myocardial microvasculature. (author)

  9. Application of 123I-labelled long-chained fatty acids for the study of myocardial metabolism

    International Nuclear Information System (INIS)

    Freundlieb, C.; Hoeck, A.; Vyska, F.; Feinendegen, L.E.; Machulla, H.J.; Stoecklin, G.

    1978-01-01

    Radioiodine-labelled fatty acids are useful tracers for myocardial imaging. The present study extends myocardial scintigraphy with ω-123-I-heptadecanoic acid to measuring myocardial metabolism. 4 normal individuals and 6 patients with cardiac disease received i.v. 1-2 mCi ω-123-I-heptadecanoic acid. Immediately fast serial scintigrams of the myocardium were taken for 30 minutes. Disappearance of the tracer, and appearance of anorganic 123-I, was measured in the peripheral blood. The myocardial images were of high quality later than 5 minutes after injection. By correcting for anorganic 123-I in the peripheral blood and the interstitium, the turnover of tracer in the myocardial cells could be measured. Activity was lost from the myocardium with a half time between 14 and 32 minutes. Within regions of old myocardials infarctions the half time of tracer loss was prolonged. The data clearly indicate the feasibility of using ω-123-I-heptadecanoic acid for measuring myocardial metabolism. (author)

  10. The clinical application value of myocardial perfusion imaging in evaluating coronary artery myocardial bridge patients with symptoms

    International Nuclear Information System (INIS)

    Wang Yuetao; Fu Ning; Ding Xuemei; Lu Cunzhi; Zhu Feng; Wang Guanmin; Huang Yijie; Wang Linguang

    2008-01-01

    Objective: Myocardial bridge is a common inborn coronary artery anomaly, myocardial bridge may be associated with myocardial ischemia. Only a few patients with coronary artery myocardial bridge were evaluated with nuclear medicine techniques. The aim of this study was to investigate the role of nuclear cardiology with myocardial perfusion technique in symptomatic myocardial bridge patients. Methods Nineteen myocardial bridge patients with the symptoms of chest pain and chest distress were analyzed retrospectively. 99 Tc m -methoxyisobutylisonitrile (MIBI) myocardial perfusion images (both exercise and rest) were performed in all. Imaging results were compared with the results of movement electrocardiogram (ECG) and coronary arteriography. The t test or χ 2 test was used to statistically analyze the data with Stata 7.0 software. Results: Of the 19 patients, 18 patients had myocardial bridge locating at the left anterior descending artery, 1 patient at the left anterior descending and left circumflex artery, the mean angiographic systolic occlusion within the myocardial bridge was (65.4 ± 22.1)%. Of these 19 patients, Exercise-rest 99 Tc m -MIBI myocardial perfusion imaging defined positive myocardial ischemia in 10 and negative in 9 patients. Of the 10 patients with 99 Tc m -MIBI myocardial perfusion imaging defined myocardial ischemia, 8 had reversible radioactive defect of partial anterior wall and (or) apex, 1 had reversible defect of post lateral wall and post septal wall, and 1 had reversible defect of inferior wall. The positive predictive value of myocardial perfusion imaging was 52.6% (10/19), which was higher than movement ECG [21.1% (4/19), χ 2 = 4.07, P 99 Tc m -MIBI myocardial periusion imaging defined myocardial ischemia. Six cases with Grade II stenosis, two were 99 Tc m -MIBI myocardial perfusion imaging defined myocardial ischemia. Eight cases with Grade III stenosis, seven were 99 Tc m -MIBI myocardial perfusion imaging defined myocardial

  11. Quantitative aspects of myocardial perfusion imaging

    International Nuclear Information System (INIS)

    Vogel, R.A.

    1980-01-01

    Myocardial perfusion measurements have traditionally been performed in a quantitative fashion using application of the Sapirstein, Fick, Kety-Schmidt, or compartmental analysis principles. Although global myocardial blood flow measurements have not proven clinically useful, regional determinations have substantially advanced our understanding of and ability to detect myocardial ischemia. With the introduction of thallium-201, such studies have become widely available, although these have generally undergone qualitative evaluation. Using computer-digitized data, several methods for the quantification of myocardial perfusion images have been introduced. These include orthogonal and polar coordinate systems and anatomically oriented region of interest segmentation. Statistical ranges of normal and time-activity analyses have been applied to these data, resulting in objective and reproducible means of data evaluation

  12. Myocardial perfusion scintigraphy - possibilities of diagnosing CAD

    International Nuclear Information System (INIS)

    Tsonevska, A.

    1998-01-01

    A reviewing the diagnostic methods used in the intricate process of evaluating CAD patients in a attempt to establish the role played by radionuclide methods in the diagnostic strategy is done. The perfusion cardiotropic radiopharmaceuticals used and the various methods of evaluating myocardial are discussed. Although 210 Tl-chloride is the most widely used myocardial perfusion agent, recently 99m Tc-MIBI is proposed as an alternative because of its advantages. Myocardial perfusion assessment is done by various techniques depending on the specific aim, each of them having its proper advantages and shortcomings. The inference is reached that regardless of the routine practical implementation of myocardial perfusion scintigraphy and comprehensive studies along this line in course, there are problems still not well enough clarified awaiting solution

  13. The Pathogenesis of Human Myocardial Infarction

    Science.gov (United States)

    Rona, George

    1966-01-01

    Coronary arteriography, dissection of the coronary arteries and histopathological examination of the heart were carried out in 150 autopsies to study the effect of coronary narrowing and occlusion, of the presence of collaterals, and of coronary artery predominance on the development of myocardial infarction. The thrombosis rate was related to the severity of coronary sclerosis. The development of collaterals was not enhanced by coronary sclerosis and occlusion, and collaterals did not protect the myocardium against reinfarction. Coronary occlusion was regularly demonstrable in recent myocardial infarct cases. The association of atrial and posterior ventricular infarcts was explained by occlusion of their common arterial branch. The interdependence between coronary sclerosis, thrombosis and myocardial infarction in human autopsy material emphasizes the importance of mural coronary artery disease in the genesis of coronary occlusion and myocardial infarction, and it is at variance with statistical data and experimental results. ImagesFig. 1Fig. 2Fig. 3Fig. 4Fig. 5Fig. 6 PMID:5924947

  14. DEPRESSIVE DISORDERS IN PATIENTS AFTER MYOCARDIAL INFARCTION

    OpenAIRE

    MUXAMADIYEVA NIGINA BAKHODIROVNA

    2016-01-01

    In article the depressions arising at patients after a myocardial infarction (MI) are shined, necessity of overcoming stigma concerning weight of the transferred MI, rational under-standing of illness especially in early period of the post infraction is defined.

  15. Echocardiography diagnosis of myocardial infarction complications

    Directory of Open Access Journals (Sweden)

    N.D. Oryshchyn

    2016-03-01

    Full Text Available Diagnosis and management of myocardial infarction complications are discussed in this article. These complications are associated with high level of mortality and surgery is a main treatment method. High level of suspicion and early diagnosis are essential for appropriate treatment and improvement of prognosis. Echocardiography is a main diagnostic method. Analysis of literature about contemporary management of mechanical complications of myocardial infarction has been performed, case reports are presented.

  16. Improved exercise myocardial perfusion during lidoflazine therapy

    International Nuclear Information System (INIS)

    Shapiro, W.; Narahara, K.A.; Park, J.

    1983-01-01

    Lidoflazine is a synthetic drug with calcium-channel blocking effects. In a study of 6 patients with severe classic angina pectoris, single-blind administration of lidoflazine was associated with improved myocardial perfusion during exercise as determined by thallium-201 stress scintigraphy. These studies demonstrate that lidoflazine therapy is associated with relief of angina, an increased physical work capacity, and improved regional myocardial perfusion during exercise

  17. Measurement of myocardial perfusion using magnetic resonance

    DEFF Research Database (Denmark)

    Fritz-Hansen, T.; Jensen, L.T.; Larsson, H.B.

    2008-01-01

    Cardiac magnetic resonance imaging (MRI) has evolved rapidly. Recent developments have made non-invasive quantitative myocardial perfusion measurements possible. MRI is particularly attractive due to its high spatial resolution and because it does not involve ionising radiation. This paper reviews...... myocardial perfusion imaging with MR contrast agents: methods, validation and experiences from clinical studies. Unresolved issues still restrict the use of these techniques to research although clinical applications are within reach Udgivelsesdato: 2008/12/8...

  18. Milrinone and levosimendan during porcine myocardial ischemia -- no effects on calcium overload and metabolism.

    Science.gov (United States)

    Axelsson, B; Johansson, G; Abrahamsson, P; Gupta, A; Tydén, H; Wouters, P; Haney, M

    2013-07-01

    Although inotropic stimulation is considered harmful in the presence of myocardial ischaemia, both calcium sensitisers and phosphodiesterase inhibitors may offer cardioprotection. We hypothesise that these cardioprotective effects are related to an acute alteration of myocardial metabolism. We studied in vivo effects of milrinone and levosimendan on calcium overload and ischaemic markers using left ventricular microdialysis in pigs with acute myocardial ischaemia. Anaesthetised juvenile pigs, average weight 36 kg, were randomised to one of three intravenous treatment groups: milrinone 50 μg/kg bolus plus infusion 0.5 μg/kg/min (n = 7), levosimendan 24 μg/kg plus infusion 0.2 μg/kg/min (n = 7), or placebo (n = 6) for 60 min prior to and during a 45 min acute regional coronary occlusion. Systemic and myocardial haemodynamics were assessed, and microdialysis was performed with catheters positioned in the left ventricular wall. (45) Ca(2+) was included in the microperfusate in order to assess local calcium uptake into myocardial cells. The microdialysate was analysed for glucose, lactate, pyruvate, glycerol, and for (45) Ca(2+) recovery. During ischaemia, there were no differences in microdialysate-measured parameters between control animals and milrinone- or levosimendan-treated groups. In the pre-ischaemic period, arterial blood pressure decreased in all groups while myocardial oxygen consumption remained stable. These findings reject the hypothesis of an immediate energy-conserving effect of milrinone and levosimendan during acute myocardial ischaemia. On the other hand, the data show that inotropic support with milrinone and levosimendan does not worsen the metabolic parameters that were measured in the ischaemic myocardium. © 2013 The Acta Anaesthesiologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

  19. Diagnosis of early human myocardial ischemic damage with electron probe microanalysis

    International Nuclear Information System (INIS)

    Singh, S.; Abraham, J.L.; Raasch, F.; Wolf, P.; Bloor, C.M.

    1983-01-01

    We determined the Na/K x-ray intensity ratio in frozen sections of myocardial tissues obtained at autopsy from patients who died from various causes, using electron probe analysis. We have been able to distinguish between the ischemically injured and normal cells. The method is simple, fast, and dependable even when the duration of ischemia is only 30 minutes

  20. The past, the present and the future of experimental research on myocardial ischemia and protection

    Czech Academy of Sciences Publication Activity Database

    Ošťádal, Bohuslav

    2009-01-01

    Roč. 61, č. 1 (2009), s. 3-12 ISSN 1734-1140 R&D Projects: GA MŠk(CZ) 1M0510 Institutional research plan: CEZ:AV0Z50110509 Keywords : myocardial ischemia * protection * cell death Subject RIV: FA - Cardiovascular Disease s incl. Cardiotharic Surgery Impact factor: 2.086, year: 2009

  1. Automated quantitative coronary computed tomography correlates of myocardial ischaemia on gated myocardial perfusion SPECT

    International Nuclear Information System (INIS)

    Graaf, Michiel A. de; Boogers, Mark J.; Veltman, Caroline E.; El-Naggar, Heba M.; Bax, Jeroen J.; Delgado, Victoria; Broersen, Alexander; Kitslaar, Pieter H.; Dijkstra, Jouke; Kroft, Lucia J.; Younis, Imad Al; Reiber, Johan H.; Scholte, Arthur J.

    2013-01-01

    Automated software tools have permitted more comprehensive, robust and reproducible quantification of coronary stenosis, plaque burden and plaque location of coronary computed tomography angiography (CTA) data. The association between these quantitative CTA (QCT) parameters and the presence of myocardial ischaemia has not been explored. The aim of the present investigation was to evaluate the association between QCT parameters of coronary artery lesions and the presence of myocardial ischaemia on gated myocardial perfusion single-photon emission CT (SPECT). Included in the study were 40 patients (mean age 58.2 ± 10.9 years, 27 men) with known or suspected coronary artery disease (CAD) who had undergone multidetector row CTA and gated myocardial perfusion SPECT within 6 months. From the CTA datasets, vessel-based and lesion-based visual analyses were performed. Consecutively, lesion-based QCT was performed to assess plaque length, plaque burden, percentage lumen area stenosis and remodelling index. Subsequently, the presence of myocardial ischaemia was assessed using the summed difference score (SDS ≥2) on gated myocardial perfusion SPECT. Myocardial ischaemia was seen in 25 patients (62.5 %) in 37 vascular territories. Quantitatively assessed significant stenosis and quantitatively assessed lesion length were independently associated with myocardial ischaemia (OR 7.72, 95 % CI 2.41-24.7, p 2 = 20.7) and lesion length (χ 2 = 26.0) to the clinical variables and the visual assessment (χ 2 = 5.9) had incremental value in the association with myocardial ischaemia. Coronary lesion length and quantitatively assessed significant stenosis were independently associated with myocardial ischaemia. Both quantitative parameters have incremental value over baseline variables and visually assessed significant stenosis. Potentially, QCT can refine assessment of CAD, which may be of potential use for identification of patients with myocardial ischaemia. (orig.)

  2. Effect of eating on thallium myocardial imaging

    International Nuclear Information System (INIS)

    Wilson, R.A.; Sullivan, P.J.; Okada, R.D.; Boucher, C.A.; Morris, C.; Pohost, G.M.; Strauss, H.W.

    1986-01-01

    To determine if eating between initial and delayed thallium images alters the appearance of the delayed thallium scan, a prospective study was performed; 184 subjects sent for routine thallium imaging were randomized into two groups, those who ate a meal high in carbohydrates between initial and delayed thallium myocardial images (n = 106), and those who fasted (n = 78). The 201 Tl images were interpreted in blinded fashion for global myocardial and pulmonary clearance of 201 Tl myocardial defects. The eating group had a significantly lower incidence of transient myocardial defects compared to the noneating group (7 percent vs 18 percent, respectively; p less than 0.05). The time between initial and delayed images and the incidence of exercise-induced ischemic ST-segment depression or pathologic Q waves on the electrocardiogram were not significantly different between the two groups. These data suggest that eating a high-carbohydrate meal between initial and delayed 201 Tl images causes increased 201 Tl myocardial clearance rates and may alter 201 Tl myocardial redistribution over time

  3. Myocardial infarction in Swedish subway drivers.

    Science.gov (United States)

    Bigert, Carolina; Klerdal, Kristina; Hammar, Niklas; Gustavsson, Per

    2007-08-01

    Particulate matter in urban air is associated with the risk of myocardial infarction in the general population. Very high levels of airborne particles have been detected in the subway system of Stockholm, as well as in several other large cities. This situation has caused concern for negative health effects among subway staff. The aim of this study was to investigate whether there is an increased incidence of myocardial infarction among subway drivers. Data from a population-based case-control study of men aged 40-69 in Stockholm County in 1976-1996 were used. The study included all first events of myocardial infarction in registers of hospital discharges and deaths. The controls were selected randomly from the general population. National censuses were used for information on occupation. Altogether, 22 311 cases and 131 496 controls were included. Among these, 54 cases and 250 controls had worked as subway drivers. The relative risk of myocardial infarction among subway drivers was not increased. It was 0.92 [95% confidence interval (95% CI) 0.68-1.25] when the subway drivers were compared with other manual workers and 1.06 (95% CI 0.78-1.43) when the subway drivers were compared with all other gainfully employed men. Subgroup analyses indicated no influence on the risk of myocardial infarction from the duration of employment, latency time, or time since employment stopped. Subway drivers in Stockholm do not have a higher incidence of myocardial infarction than other employed persons.

  4. Myocardial regeneration in adriamycin cardiomyopathy by nuclear expression of GLP1 using ultrasound targeted microbubble destruction

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Shuyuan [Baylor Research Institute, Baylor University Medical Center, 3812 Elm Street, Dallas, TX (United States); Chen, Jiaxi [The University of Texas Southwestern Medical Center at Dallas, Medical School, 5235 Harry Hine Blvd., Dallas, TX (United States); Huang, Pintong [Department of Ultrasonography, The 2nd Affiliated Hospital of Zhejiang University College of Medicine, Hangzhou, Zhejiang Province (China); Meng, Xing-Li; Clayton, Sandra; Shen, Jin-Song [Baylor Research Institute, Baylor University Medical Center, 3812 Elm Street, Dallas, TX (United States); Grayburn, Paul A., E-mail: paulgr@baylorhealth.edu [Baylor Research Institute, Baylor University Medical Center, 3812 Elm Street, Dallas, TX (United States); Department of Internal Medicine, Division of Cardiology, Baylor Heart and Vascular Institute, Baylor University Medical Center, 621 N. Hall St, Suite H030, Dallas, TX (United States)

    2015-03-20

    Recently GLP-1 was found to have cardioprotective effects independent of those attributable to tight glycemic control. Methods and results: We employed ultrasound targeted microbubble destruction (UTMD) to deliver piggybac transposon plasmids encoding the GLP-1 gene with a nuclear localizing signal to rat hearts with adriamycin cardiomyopathy. After a single UTMD treatment, overexpression of transgenic GLP-1 was found in nuclei of rat heart cells with evidence that transfected cardiac cells had undergone proliferation. UTMD-GLP-1 gene therapy restored LV mass, fractional shortening index, and LV posterior wall diameter to nearly normal. Nuclear overexpression of GLP-1 by inducing phosphorylation of FoxO1-S256 and translocation of FoxO1 from the nucleus to the cytoplasm significantly inactivated FoxO1 and activated the expression of cyclin D1 in nuclei of cardiac muscle cells. Reversal of adriamycin cardiomyopathy appeared to be mediated by dedifferentiation and proliferation of nuclear FoxO1-positive cardiac muscle cells with evidence of embryonic stem cell markers (OCT4, Nanog, SOX2 and c-kit), cardiac early differentiation markers (NKX2.5 and ISL-1) and cellular proliferation markers (BrdU and PHH3) after UTMD with GLP-1 gene therapy. Conclusions: Intranuclear myocardial delivery of the GLP-1gene can reverse established adriamycin cardiomyopathy by stimulating myocardial regeneration. - Highlights: • The activation of nuclear FoxO1 in cardiac muscle cells associated with adriamycin cardiomyopathy. • Myocardial nuclear GLP-1 stimulates myocardial regeneration and reverses adriamycin cardiomyopathy. • The process of myocardial regeneration associated with dedifferentiation and proliferation.

  5. Myocardial regeneration in adriamycin cardiomyopathy by nuclear expression of GLP1 using ultrasound targeted microbubble destruction

    International Nuclear Information System (INIS)

    Chen, Shuyuan; Chen, Jiaxi; Huang, Pintong; Meng, Xing-Li; Clayton, Sandra; Shen, Jin-Song; Grayburn, Paul A.

    2015-01-01

    Recently GLP-1 was found to have cardioprotective effects independent of those attributable to tight glycemic control. Methods and results: We employed ultrasound targeted microbubble destruction (UTMD) to deliver piggybac transposon plasmids encoding the GLP-1 gene with a nuclear localizing signal to rat hearts with adriamycin cardiomyopathy. After a single UTMD treatment, overexpression of transgenic GLP-1 was found in nuclei of rat heart cells with evidence that transfected cardiac cells had undergone proliferation. UTMD-GLP-1 gene therapy restored LV mass, fractional shortening index, and LV posterior wall diameter to nearly normal. Nuclear overexpression of GLP-1 by inducing phosphorylation of FoxO1-S256 and translocation of FoxO1 from the nucleus to the cytoplasm significantly inactivated FoxO1 and activated the expression of cyclin D1 in nuclei of cardiac muscle cells. Reversal of adriamycin cardiomyopathy appeared to be mediated by dedifferentiation and proliferation of nuclear FoxO1-positive cardiac muscle cells with evidence of embryonic stem cell markers (OCT4, Nanog, SOX2 and c-kit), cardiac early differentiation markers (NKX2.5 and ISL-1) and cellular proliferation markers (BrdU and PHH3) after UTMD with GLP-1 gene therapy. Conclusions: Intranuclear myocardial delivery of the GLP-1gene can reverse established adriamycin cardiomyopathy by stimulating myocardial regeneration. - Highlights: • The activation of nuclear FoxO1 in cardiac muscle cells associated with adriamycin cardiomyopathy. • Myocardial nuclear GLP-1 stimulates myocardial regeneration and reverses adriamycin cardiomyopathy. • The process of myocardial regeneration associated with dedifferentiation and proliferation

  6. Quantitative myocardial blood flow with Rubidium-82 PET

    DEFF Research Database (Denmark)

    Hagemann, Christoffer E; Ghotbi, Adam A; Kjær, Andreas

    2015-01-01

    Positron emission tomography (PET) allows assessment of myocardial blood flow in absolute terms (ml/min/g). Quantification of myocardial blood flow (MBF) and myocardial flow reserve (MFR) extend the scope of conventional semi-quantitative myocardial perfusion imaging (MPI): e.g. in 1) identificat......Positron emission tomography (PET) allows assessment of myocardial blood flow in absolute terms (ml/min/g). Quantification of myocardial blood flow (MBF) and myocardial flow reserve (MFR) extend the scope of conventional semi-quantitative myocardial perfusion imaging (MPI): e.g. in 1...... global MFR and major adverse cardiovascular events (MACE), and together with new diagnostic possibilities from measuring the longitudinal myocardial perfusion gradient, cardiac (82)Rb PET faces a promising clinical future. This article reviews current evidence on quantitative (82)Rb PET's ability...

  7. Effect of limb ischemic preconditioning on myocardial apoptosis-related proteins in ischemia-reperfusion injury

    OpenAIRE

    GAO, JIANZHI; ZHAO, LINJING; WANG, YONGLING; TENG, QINGLEI; LIANG, LIDONG; ZHANG, JINYING

    2013-01-01

    The aim of this study was to investigate the effect of limb ischemic preconditioning (LIPC) on myocardial apoptosis in myocardial ischemia-reperfusion injury (MIRI), as well as the regulation of caspase-3 and the B cell lymphoma 2 (Bcl-2) gene in LIPC. A total of 50 rats were divided randomly into 5 groups (n=10). Four rats in each group were drawn out for detection of apoptosis. The sham, MIRI and LIPC groups underwent surgery without additional treatment. In the LY294002 group, LY294002 pre...

  8. Trophoblast cells of ruminant placentas - A mini review

    International Nuclear Information System (INIS)

    Igwebuike, U.M.

    2004-09-01

    Understanding of ruminant placental structure and function is essential for veterinarians and researchers. The ruminant placenta is classified as cotyledonary and synepitheliochorial on the bases of its gross anatomical features and histological characteristics respectively. The richly vascularized embryonic chorioallantois is lined on its outer surface by cells of the trophectodermal epithelium. These cells which assume specialized functions are referred to as trophoblast cells. Two morphologically and functionally distinct cell types have been recognized in the trophectoderm of the placenta of ruminant animals. These are the mononucleate trophoblast cells and the binucleate trophoblast cells. The occurrence, morphological characteristics, and specialized functions of these trophoblast cells, in relation to conceptus nutrition and survival in utero are discussed in this review. (author)

  9. Role of adenosine as adjunctive therapy in acute myocardial infarction.

    Science.gov (United States)

    Forman, Mervyn B; Stone, Gregg W; Jackson, Edwin K

    2006-01-01

    Although early reperfusion and maintained patency is the mainstay therapy for ST elevation myocardial infarction, experimental studies demonstrate that reperfusion per se induces deleterious effects on viable ischemic cells. Thus "myocardial reperfusion injury" may compromise the full potential of reperfusion therapy and may account for unfavorable outcomes in high-risk patients. Although the mechanisms of reperfusion injury are complex and multifactorial, neutrophil-mediated microvascular injury resulting in a progressive decrease in blood flow ("no-reflow" phenomenon) likely plays an important role. Adenosine is an endogenous nucleoside found in large quantities in myocardial and endothelial cells. It activates four well-characterized receptors producing various physiological effects that attenuate many of the proposed mechanisms of reperfusion injury. The cardio-protective effects of adenosine are supported by its role as a mediator of pre- and post-conditioning. In experimental models, administration of adenosine in the peri-reperfusion period results in a marked reduction in infarct size and improvement in ventricular function. The cardioprotective effects in the canine model have a narrow time window with the drug losing its effect following three hours of ischemia. Several small clinical studies have demonstrated that administration of adenosine with reperfusion therapy reduces infarct size and improves ventricular function. In the larger AMISTAD and AMISTAD II trials a 3-h infusion of adenosine as an adjunct to reperfusion resulted in a striking reduction in infarct size (55-65%). Post hoc analysis of AMISTAD II showed that this was associated with significantly improved early and late mortality in patients treated within 3.17 h of symptoms. An intravenous infusion of adenosine for 3 h should be considered as adjunctive therapy in high risk-patients undergoing reperfusion therapy.

  10. Metallic ion content and damage to the DNA in oral mucosa cells patients treated dental implants.

    Science.gov (United States)

    López-Jornet, Pía; Perrez, Francisco Parra; Calvo-Guirado, José Luis; Ros-Llor, Irene; LLor-Ros, Irene; Ramírez-Fernández, Piedad

    2014-07-01

    The aim of this study was to assess the potential genotoxicity of dental implants, evaluating biomarkers of DNA damage (micronuclei and/or nuclear buds), cytokinetic defects (binucleated cells) and the presence of trace metals in gingival cells of patients with implants, comparing these with a control group. A total of 60 healthy adults (30 patients with dental implants and 30 control patients without) were included in the study. Medical and dental histories were made for each including life-style factors. Genotoxicity effects were assessed by micronucleus assays in the gingival epithelial cells of each patient; 1,000 epithelial cells were analyzed, evaluating the frequency of micronucleated cells and other nuclear anomalies. The concentration of metals (Al(27), Ag(107), Co (59), Cr (52), Cu(63), Fe(56), Sn(118), Mn(55), Mo(92), Ni(60), Pb(208), Ti(47)) were assayed by means of coupled plasma-mass spectrophotometry (ICP-MS). The frequency of micronuclei in the patient group with implants was higher than in the control group but without statistically significant differences (P > 0.05). Similar results were found for binucleated cells and nuclear buds (P > 0.05). For metals assayed by ICP-MS, significant differences were found for Ti(47) (P ≤ 0.045). Univariate analysis identified a significant association between the presence of micronuclei and age. Dental implants do not induce DNA damage in gingival cells, the slight effects observed cannot be indicated as biologically relevant.

  11. Myocardial fatty acid utilisation during exercise induced ischemia in patients with coronary artery disease

    International Nuclear Information System (INIS)

    Virtanen, K.S.; Nikkinen, P.; Lindroth, L.; Kuikka, J.T.

    2002-01-01

    Aim: Reversible or irreversible myocardial damage due to ischemia correlates with altered membrane functions of the cells. To compare myocardial free fatty acid (FFA) metabolism and flow during exercise induced ischemia we studied ten patients with coronary artery disease but without previous myocardial infarction. Methods: A series of post-exercise single-photon emission computed tomography (SPECT) measurements was performed after injection of 123 I labelled heptadecanoic acid (HDA). Myocardial perfusion was estimated from the separately performed exercise-redistribution thallium study. Fatty acid metabolic rate, thallium uptake and washout were calculated for anterior, lateral, posterior and septal segments. Results: The more reduced post-exercise FFA metabolic rate (-63±18%, mean ±1 SD) compared to flow (-36±16%) was related to the severity of myocardial ischemia and wall motion abnormalities. Conclusion: In this small group of patients, the reduced post-exercise FFA metabolic rate tentatively suggests a parsimonious workload of the exercising myocardium by reducing oxygen consumption in patients with coronary artery disease. (orig.) [de

  12. Intravenous Administration of Lycopene, a Tomato Extract, Protects against Myocardial Ischemia-Reperfusion Injury.

    Science.gov (United States)

    Tong, Chao; Peng, Chuan; Wang, Lianlian; Zhang, Li; Yang, Xiaotao; Xu, Ping; Li, Jinjin; Delplancke, Thibaut; Zhang, Hua; Qi, Hongbo

    2016-03-03

    Oral uptake of lycopene has been shown to be beneficial for preventing myocardial ischemia-reperfusion (I/R) injury. However, the strong first-pass metabolism of lycopene influences its bioavailability and impedes its clinic application. In this study, we determined an intravenous (IV) administration dose of lycopene protects against myocardial infarction (MI) in a mouse model, and investigated the effects of acute lycopene administration on reactive oxygen species (ROS) production and related signaling pathways during myocardial I/R. In this study, we established both in vitro hypoxia/reoxygenation (H/R) cell model and in vivo regional myocardial I/R mouse model by ligating left anterior artery descending. TTC dual staining was used to assess I/R induced MI in the absence and presence of acute lycopene administration via tail vein injection. Lycopene treatment (1 μM) before reoxygenation significantly reduced cardiomyocyte death induced by H/R. Intravenous administration of lycopene to achieve 1 μM concentration in circulating blood significantly suppressed MI, ROS production, and JNK phosphorylation in the cardiac tissue of mice during in vivo regional I/R. Elevating circulating lycopene to 1 μM via IV injection protects against myocardial I/R injury through inhibition of ROS accumulation and consequent inflammation in mice.

  13. Effects and Mechanisms of Chinese Herbal Medicine in Ameliorating Myocardial Ischemia-Reperfusion Injury

    Directory of Open Access Journals (Sweden)

    Qing Liu

    2013-01-01

    Full Text Available Myocardial ischemia-reperfusion (MIR injury is a major contributor to the morbidity and mortality associated with coronary artery disease, which accounts for approximately 450,000 deaths a year in the United States alone. Chinese herbal medicine, especially combined herbal formulations, has been widely used in traditional Chinese medicine for the treatment of myocardial infarction for hundreds of years. While the efficacy of Chinese herbal medicine is well documented, the underlying molecular mechanisms remain elusive. In this review, we highlight recent studies which are focused on elucidating the cellular and molecular mechanisms using extracted compounds, single herbs, or herbal formulations in experimental settings. These studies represent recent efforts to bridge the gap between the enigma of ancient Chinese herbal medicine and the concepts of modern cell and molecular biology in the treatment of myocardial infarction.

  14. Natural aminoacyl tRNA synthetase fragment enhances cardiac function after myocardial infarction.

    Directory of Open Access Journals (Sweden)

    Margaret E McCormick

    Full Text Available A naturally-occurring fragment of tyrosyl-tRNA synthetase (TyrRS has been shown in higher eukaryotes to 'moonlight' as a pro-angiogenic cytokine in addition to its primary role in protein translation. Pro-angiogenic cytokines have previously been proposed to be promising therapeutic mechanisms for the treatment of myocardial infarction. Here, we show that systemic delivery of the natural fragment of TyRS, mini-TyrRS, improves heart function in mice after myocardial infarction. This improvement is associated with reduced formation of scar tissue, increased angiogenesis of cardiac capillaries, recruitment of c-kitpos cells and proliferation of myocardial fibroblasts. This work demonstrates that mini-TyrRS has beneficial effects on cardiac repair and regeneration and offers support for the notion that elucidation of the ever expanding repertoire of noncanonical functions of aminoacyl tRNA synthetases offers unique opportunities for development of novel therapeutics.

  15. Myocardial Energetics and Heart Failure: a Review of Recent Therapeutic Trials.

    Science.gov (United States)

    Bhatt, Kunal N; Butler, Javed

    2018-06-01

    Several novel therapeutics being tested in patients with heart failure are based on myocardial energetics. This review will provide a summary of the recent trials in this area, including therapeutic options targeting various aspects of cellular and mitochondrial metabolism. Agents that improve the energetic balance in myocardial cells have the potential to improve clinical heart failure status. The most promising therapies currently under investigation in this arena include (1) elamipretide, a cardiolipin stabilizer; (2) repletion of iron deficiency with intravenous ferrous carboxymaltose; (3) coenzyme Q10; and (4) the partial adenosine receptor antagonists capadenoson and neladenosone. Myocardial energetics-based therapeutics are groundbreaking in that they utilize novel mechanisms of action to improve heart failure symptoms, without causing the adverse neurohormonal side effects associated with current guideline-based therapies. The drugs appear likely to be added to the heart failure therapy armamentarium as adjuncts to current regimens in the near future.

  16. Myocardial adrenergic nerve activity in valvular diseases assessed by iodine-123-metaiodobenzylguanidine myocardial scintigraphy

    International Nuclear Information System (INIS)

    Imamura, Yoshihiro; Fukuyama, Takaya

    1997-01-01

    Iodine-123-metaiodobenzylguanidine (MIBG) imaging was used to assess myocardial adrenergic nerve activity in patients with heart failure. MIBG planar images were obtained in 94 patients. The uptake of MIBG, calculated as the heart-to-mediastinum activity ratio in the immediate image (15 min), showed a significant decrease only in patients with severe heart failure due to cardiomyopathy, but was not changed in those with valvular diseases. Storage and release of MIBG, calculated as the percentage myocardial MIBG washout from 15 min to 4 hours after isotope injection, was substantially accelerated in both patients with cardiomyopathy and valvular diseases in proportion to the severity of heart failure. These data suggest that, in severe heart failure associated with cardiomyopathy, norepinephrine uptake is reduced. Also, myocardial adrenergic nerve activity is accelerated in proportion to the severity of heart failure independent of the underlying cause. MIBG images were analyzed in 20 patients with mitral stenosis with the same methods to clarify whether myocardial adrenergic nerve activity is different in patients with heart failure without left ventricular volume or pressure overload. Myocardial uptake of MIBG did not show any significant difference. The percentage myocardial MIBG washout was increased in patients with severe heart failure. The closest correlation was between myocardial washout and cardiac output. In heart failure due to mitral stenosis, myocardial adrenergic nerve activity is intensified. Decrease in cardiac output associated with mitral stenosis acts as a potent stimulus for this intensification. (author)

  17. The diagnosis of silent myocardial ischemia. Motion-Frozen (or morphing) myocardial perfusion imaging.

    Science.gov (United States)

    Chang, Cheng; Ye, Bo; Xie, Wenhui; Zhang, Daoliang; Lei, Bei; Ye, Xiaodan

    2016-01-01

    Silent myocardial ischemia is typically defined as objective evidence of myocardial ischemia in patients without subjective ischemia symptoms. Currently, coronary artery angiography is the gold standard for diagnosis of asymptomatic coronary artery disease (CAD). Computed tomography coronary angiography (CTCA) can visually demonstrate the morphology, trend and extent of coronary stenosis and is commonly used in clinical screening of CAD. Myocardial perfusion imaging can be used not only to identify whether anatomical stenosis causes myocardial dysfunction, but to also assess the risk stratification and prognosis of myocardial disease (MD). Myocardial perfusion imaging using morphing combined with CTCA can simultaneously show the relationship between CAD and myocardial ischemia from an anatomical and functional aspect. This allows earlier diagnosis of asymptomatic CAD myocardial ischemia, accurate identification of the culprit vessels, and could prevent unnecessary interventional therapy. The 1-day dobutamine stress/resting met-hod is also one of the methods used. The combination of CTCA and the morphing technique can provide anatomical and functional information on coronary arteries at the same time, significantly improving the diagnostic sensitivity, specificity, and accuracy of MD.

  18. Value of the Doppler index of myocardial performance in the early phase of acute myocardial infarction

    DEFF Research Database (Denmark)

    Poulsen, S H; Jensen, S E; Tei, C

    2000-01-01

    Prospective assessment of a nongeometric Doppler-derived index of combined systolic and diastolic myocardial performance was performed in 64 patients with acute myocardial infarction (MI) within 1 hour after their arrival to the hospital and in 39 age-matched healthy subjects. The index is defined...

  19. Polyploidization of liver cells.

    Science.gov (United States)

    Celton-Morizur, Séverine; Desdouets, Chantal

    2010-01-01

    Eukaryotic organisms usually contain a diploid complement of chromosomes. However, there are a number of exceptions. Organisms containing an increase in DNA content by whole number multiples of the entire set of chromosomes are defined as polyploid. Cells that contain more than two sets of chromosomes were first observed in plants about a century ago and it is now recognized that polyploidy cells form in many eukaryotes under a wide variety of circumstance. Although it is less common in mammals, some tissues, including the liver, show a high percentage of polyploid cells. Thus, during postnatal growth, the liver parenchyma undergoes dramatic changes characterized by gradual polyploidization during which hepatocytes of several ploidy classes emerge as a result of modified cell-division cycles. This process generates the successive appearance of tetraploid and octoploid cell classes with one or two nuclei (mononucleated or binucleated). Liver cells polyploidy is generally considered to indicate terminal differentiation and senescence and to lead both to the progressive loss of cell pluripotency and a markedly decreased replication capacity. In adults, liver polyploidization is differentially regulated upon loss of liver mass and liver damage. Interestingly, partial hepatectomy induces marked cell proliferation followed by an increase in liver ploidy. In contrast, during hepatocarcinoma (HCC), growth shifts to a nonpolyploidizing pattern and expansion of the diploid hepatocytes population is observed in neoplastic nodules. Here we review the current state of understanding about how polyploidization is regulated during normal and pathological liver growth and detail by which mechanisms hepatocytes become polyploid.

  20. Prognostic impact of physical activity prior to myocardial infarction

    DEFF Research Database (Denmark)

    Ejlersen, Hanne; Andersen, Zorana Jovanovic; von Euler-Chelpin, My Catarina

    2017-01-01

    the course of myocardial infarction by reducing case fatality and the subsequent risk of heart failure and mortality. Methods: A total of 14,223 participants in the Copenhagen City Heart Study were assessed at baseline in 1976-1978; 1,664 later developed myocardial infarction (mean age at myocardial...... estimated by logistic and Cox proportional hazards regression models, adjusted for age at myocardial infarction and other potential confounders. Results: A total of 425 (25.5%) myocardial infarctions were fatal. Higher levels of LTPA prior to myocardial infarction were associated with lower case fatality...

  1. Evaluation of myocardial involvement in Duchenne's progressive muscular dystrophy with thallium-201 myocardial perfusion imaging

    International Nuclear Information System (INIS)

    Kawai, Naoki; Sotobata, Iwao; Okada, Mitsuhiro

    1985-01-01

    Myocardial involvement in progressive muscular dystrophy of the Duchenne type was evaluated in 19 patients using thallium-201 myocardial perfusion imaging. A qualitative analysis was performed from five projection images by three experienced physicians. Distinct perfusion defects were shown in 13 patients, especially in the LV posterolateral or posterior wall (11 patients). There was no significant relationship between the presence of perfusion defects and the skeletal muscle involvements or thoracic deformities assessed by transmission computed tomography. Extensive perfusion defects were shown in 2 patients who died of congestive heart failure 1 to 2 years after the scintigraphic study. Progression of the myocardial scintigraphic abnormalities were considered to be minimal in 7 of 9 patients who underwent two serial scintigraphic studies over 2 to 3 years. It was concluded that thallium myocardial perfusion imaging is a useful clinical technique to assess myocardial involvement in Duchenne's progressive muscular dystrophy. (author)

  2. Localization and quantification of acute myocardial infarction by myocardial perfusion tomographic imaging

    International Nuclear Information System (INIS)

    Lin Xiufang; Min Changgeng; Lin Zhihu; Ke Ruoyi

    1994-01-01

    The authors reported the result of the quantification and localization of 30 clinically confirmed acute myocardial infarction patients in comparison with that of ECG. A left ventricle model was used to correct the area calculated by the method of Bull's eye. The result indicated that the infarction area calculated by the corrected Bull's eye method correlated closely with that determined by the ECG QRS scoring method (r = 0.706, P<0.01). Myocardial infarctions of all 30 patients were detected by both ECG and myocardial perfusion tomographic imaging. The accuracy of localization of myocardial infarction by myocardial perfusion imaging was similar to that of ECG in the anterior wall, anterior septum, anterior lateral and inferior wall, but superior to that of ECG in the apex, posterior lateral, posterior septum, and posterior wall

  3. Influence of contrast agent dose and ultrasound exposure on cardiomyocyte injury induced by myocardial contrast echocardiography in rats.

    Science.gov (United States)

    Miller, Douglas L; Li, Peng; Dou, Chunyan; Gordon, David; Edwards, Chris A; Armstrong, William F

    2005-10-01

    To detect specific cardiomyocyte injury induced by myocardial contrast material-enhanced echocardiography (ie, myocardial contrast echocardiography) in rats and to ascertain the influences of contrast material dose and ultrasound exposure on this injury. All animal procedures were approved by the university committee for the use and care of animals. Myocardial contrast echocardiography with 1:4 electrocardiographic (ECG) triggering was performed at 1.5 MHz in 61 anesthetized rats. Evans blue (EB) dye was injected as the vital stain for cardiomyocyte injury. At the start of myocardial contrast echocardiography, which lasted 10 minutes, perflutren lipid microsphere-based contrast material was infused through the tail vein for 5 minutes. Premature heartbeats were counted from the ECG record. The numbers of EB-stained cells counted on sections of heart specimens obtained 24 hours after myocardial contrast echocardiography and then either fresh frozen or embedded in paraffin were determined by using fluorescence microscopy. Results were compared statistically by using t tests and Mann-Whitney rank sum tests. EB-stained cells were concentrated in the anterior region of the myocardium. In the paraffin-embedded specimens, EB-stained cells were often accompanied by but largely separate from areas of inflammatory cell infiltration. At end-systolic triggering with a 50 microL/kg dose of microsphere contrast material, the EB-stained cell count increased with increasing peak rarefactional pressure amplitude, with significantly increased cell counts at 1.6 MPa (P .1). EB-stained cell counts increased with increasing contrast material dose, from 10 to 50 microL/kg, at 2.0 MPa. Cardiomyocyte injury was induced by the interaction of ultrasound pulses with contrast agent microbubbles during myocardial contrast echocardiography in rats, and the numbers of injured cells increased with increasing contrast agent dose and ultrasound exposure. RSNA, 2005

  4. [Study on mechanisms and myocardial protective effect of Qishen Yiqi dropping pills on rats with myocardial infarction].

    Science.gov (United States)

    Yang, Quan; Cao, Yunshan

    2017-06-01

    To approach the mechanisms and myocardial protective effect of Qishen Yiqi dropping pills on rats with myocardial infarction. Sixty clean healthy male Sprague-Dawley (SD) rats were randomly divided into sham operation group, model group and observation group (each n = 20). The rat model of acute myocardial infarction (AMI) was established by ligation of left anterior descent (LAD) branch of coronary artery. After modeling, the rats in observation group were given 0.135 g/kg of Qishen Yiqi dropping pills, and sham operation group and model group were administered the same amount of normal saline, once a day for consecutive 28 days. At the end of treatment, the levels of serum inflammatory factors of leukotriene B4 (LTB4), prostaglandin E 2 (PGE 2 ), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) were measured by enzyme linked immunosorbent assay (ELISA); the changes of the indexes of hemodynamic [left ventricular systolic pressure (LVSP), left ventricular end-diastolic pressure (LVEDP), the maximal rate of increase/decrease in left ventricular pressure (±dp/dt max)], the ratio of the heart weight/body weight, and the ratio of the left ventricular weight/heart weight (LVW/HW), the myocardial infarction area, myocardial histopathological changes were observed in the three groups; myocardial tissues inflammatory related factors [the mRNA and protein expressions of cytosolic phospholipase A2 (cPLA2), cyclooxygenase-2 (COX-2), 5-lipoxygenase (5-LOX)], and the expression levels of transforming growth factor-β (TGF-β)/Smads signal transduction pathway related protein (TGF-β1, Smad2/3, Collagen I, Collagen III) and cell apoptosis related factors (Bcl-2, Bax) protein were measured. Compared with the sham operation group, levels of serum inflammatory factors, the index of LVEDP, the ratio of the heart weight/body weight, LVW/HW, myocardial infarction area, the mRNA and protein expression levels of inflammatory factors in myocardium, the expression levels of

  5. The relationship between myocardial blood flow and myocardial viability after reperfusion. Myocardial viability assessed by 15O-water-PET

    International Nuclear Information System (INIS)

    Tsukagoshi, Joichi

    1994-01-01

    The purpose of this study was to examine the relationship between myocardial blood flow and myocardial viability in the ischemic canine myocardium after reperfusion. Transient ischemia was induced by 60-, 90-, and 180-minute occlusion of the left anterior descending coronary artery. Myocardial blood flow (MBF) was measured in the areas in which regional contractility was severely impaired (ehocardiographically akinetic or dyskinetic) in the early reperfusion period by 15 O-water positron emission tomography (PET) 12 hours and 4 weeks after reperfusion. An MBF ratio of ischemic to nonischemic regions 12 hours after reperfusion was inversely correlated with the amount of histologically determined tissue necrosis (r=-0.74). The regional contractility recovered 4 weeks later in the areas where an MBF ratio was 0.48 or greater, but did not recover in the areas with a lower MBF ratio. Thus, myocardial viability can be appropriately predicted in the early phase of myocardial perfusion by PET with 15 O-water even in the absence of metabolic imaging. (author)

  6. [Genetic factors in myocardial infarction].

    Science.gov (United States)

    Hara, Masahiko; Sakata, Yasuhiko; Sato, Hiroshi

    2013-02-01

    One of the main mechanisms of acute myocardial infarction (AMI) is plaque rupture or erosion followed by intraluminal thrombus formation and occlusion of the coronary arteries. Thus far, many underlying conditions or environmental factors, such as hypertension, diabetes, dyslipidemia, smoking or obesity, as well as a family history of coronary artery diseases have been identified as risks for the onset of AMI. These risks suggest that AMI occurs due to interactions between underlying conditions and multiple genetic susceptibilities. For this reason, many target gene-disease association studies have been performed with the recent introduction of genome-wide association studies (GWAS) that have further revealed new genetic susceptibilities for AMI. GWAS is a way to examine many common genetic variants in different individuals to see if any variant is associated with a trait in a case-control fashion, and typically focuses on associations between single-nucleotide polymorphisms (SNP) and traits. SNP on chromosome 9p21 is one of the robust susceptibility variants for AMI which has been identified by many GWAS. In this review, we overview the methodology of GWAS, introduce genetic variants identified by GWAS as those with susceptibility for AMI, and describe the foresight of using GWAS to investigate genetic susceptibility to AMI.

  7. Tl myocardial SPECT demonstrates importance of collateral circulation in patients with myocardial infarction

    International Nuclear Information System (INIS)

    Hattori, Fukunori

    1997-01-01

    The influence of collateral circulation on the preservation of myocardial viability and the efficacy of drug therapy and PTCA were evaluated by exercise 201 Tl myocardial SPECT before and after treatment. Thirty-five patients with a history of myocardial infarction resulting from total or subtotal obstruction of the responsible coronary artery were divided into four groups, according to the method of the treatment and the degree of collateral blood flow. Patients in groups A and B received drug therapy and displayed developed and undeveloped collateral circulation, respectively. Groups C and D received PTCA and displayed developed and undeveloped collateral circulation, respectively. Tl myocardial SPECT was performed before treatment to record the extent of redistribution to the occluded region, the degree of myocardial viability and the nature and extent of the ischemic lesion. In group A, myocardial perfusion improved, although redistribution remained in all cases, while in group B, 4 of 7 cases improved after drug therapy. In group C, myocardial perfusion improved in all cases, and redistribution disappeared in 7 of 12 cases. 5 of 6 cases improved in group D after PTCA. After drug therapy, the %Tl uptake in the infarcted region improved significantly in initial and delayed images of patients in group A. The differences in initial and delayed images in group B before and after drug therapy were not significant. In contrast, groups C and D both registered significant improvement in initial and delayed images after PTCA. The washout rate improved significantly in groups A, C and D after their respective treatments. These results suggest that developed collateral circulation helps to preserve myocardial viability in cases of myocardial infarction. Myocardial perfusion improved after drug therapy in cases with developed collateral circulation, and in patients with developed and undeveloped collateral circulation receiving PTCA. (K.H.)

  8. Decidual cell polyploidization necessitates mitochondrial activity.

    Directory of Open Access Journals (Sweden)

    Xinghong Ma

    Full Text Available Cellular polyploidy has been widely reported in nature, yet its developmental mechanism and function remain poorly understood. In the present study, to better define the aspects of decidual cell polyploidy, we isolated pure polyploid and non-polyploid decidual cell populations from the in vivo decidual bed. Three independent RNA pools prepared for each population were then subjected to the Affymetrix gene chip analysis for the whole mouse genome transcripts. Our data revealed up-regulation of 1015 genes and down-regulation of 1207 genes in the polyploid populations, as compared to the non-polyploid group. Comparative RT-PCR and in situ hybridization results indeed confirmed differential expressional regulation of several genes between the two populations. Based on functional enrichment analyses, up-regulated polyploidy genes appeared to implicate several functions, which primarily include cell/nuclear division, ATP binding, metabolic process, and mitochondrial activity, whereas that of down-regulated genes primarily included apoptosis and immune processes. Further analyses of genes that are related to mitochondria and bi-nucleation showed differential and regional expression within the decidual bed, consistent with the pattern of polyploidy. Consistently, studies revealed a marked induction of mitochondrial mass and ATP production in polyploid cells. The inhibition of mitochondrial activity by various pharmacological inhibitors, as well as by gene-specific targeting using siRNA-mediated technology showed a dramatic attenuation of polyploidy and bi-nucleation development during in vitro stromal cell decidualization, suggesting mitochondria play a major role in positive regulation of decidual cell polyploidization. Collectively, analyses of unique polyploidy markers and molecular signaling networks may be useful to further characterize functional aspects of decidual cell polyploidy at the site of implantation.

  9. Assessment of myocardial viability by MR imaging

    International Nuclear Information System (INIS)

    Sandstede, Joern J.W.

    2003-01-01

    Diagnosis of myocardial viability after infarction focuses on the prediction of functional improvement of dysfunctional myocardium after revascularization therapy. Magnetic resonance imaging provides different approaches for the detection of myocardial viability. Measurement of end-diastolic wall thickness is easy to perform and has a high sensitivity, but a low specificity, and can only be used 4 months after myocardial infarction due to infarct healing processes. Low-dose dobutamine stress has a good sensitivity with a high specificity for the prediction of wall motion improvement, but this is only true for patients with a singular dysfunctional area and only slightly depressed cardiac function. Late enhancement allows for direct visualization of necrotic or scarred tissue. By measuring the transmural extent of late enhancement, the probability of mechanical improvement can precisely be given. Imaging of microvascular obstruction by first-pass perfusion or late enhancement gives additional information on viability and patient prognosis. Metabolic imaging techniques, such as 31 P-MR spectroscopy and 23 Na-MR imaging, provide further insights into the mechanisms of myocardial infarction and viability. In conclusion, cardiac MRI offers several clinically usable approaches for the assessment of myocardial viability and will probably become the method of choice in the near future. (orig.)

  10. Stress myocardial scintigraphy in coronary artery disease

    International Nuclear Information System (INIS)

    Hata, Noritake; Koumi, Shin-ichi; Yasutake, Masahiro; Imaizumi, Takahiro; Saito, Tsutomu; Kishida, Hiroshi; Hayakawa, Hirokazu

    1991-01-01

    To evaluate the clinical significance of asymptomatic ischemic heart disease, exercise electrocardiography and stress myocardial scintigraphy were performed. These were correlated with symptoms during exercise tests and histories of myocardial infarction (MI). The study subjects consisted of 70 patients with coronary artery disease, including 34 with MI, and 36 without MI but with angina pectoris. Stress tests were performed using bicycle ergometer under electrocardiographic monitoring throughout the test. Transient myocardial ischemia was confirmed by perfusion defects on thallium myocardial imaging demonstrated immediately after exercise, but not 3 hours after the stress test. Asymptomatic ST depression was observed in 18 of 34 patients with MI (53%) and in 21 of the 36 patients with angina (58%); however, transient myocardial perfusion defects were confimred in 61% of the patients with MI (11 of 18 patients), but in only 33% of those with angina (7 of 21 patients). The difference was statistically significant (p<0.05). It was suggested that there are some differences in the clinical significance of asymptomatic ST depression between the patients with MI and those without MI but with angina pectoris. (author)

  11. Effect of granulocyte colony stimulating EPC on cardiac function and myocardial energy expenditure in patients with heart failure after myocardial infarction.

    Science.gov (United States)

    Zhao, Zilin; Luo, Jianchun; Ma, Lixian; Luo, Xia; Huang, Liangyan

    2015-01-01

    To study the changes of cardiac function and myocardial energy expenditure following treatment with granulocyte colony stimulating factor (G-CSF) in patients with heart failure after myocardial infarction. Thirty-eight patients with heart failure after myocardial infarction were randomized into G-CSF treatment group and control group. All the patients received conventional treatment (medication and interventional therapy), and the patients in treatment group were given additional G-CSF (600 μg/day) for 7 consecutive days. The plasma level of brain-type natriuretic peptide (BNP) and the number of endothelial progenitor cells (EPC) in the peripheral blood were detected before and at 7 days and 4 months after the treatment. The cardiac functions (LVEF, FS, LVIDs, PWTs, EDV, SV, ET) was evaluated by ultrasonic imaging before and at 2 weeks and 4 months after the treatment. The MEE and circumferential end-systolic wall stress (cESS) were calculated by correlation formula. The number of EPC was significantly higher in the treatment group than in the control group after the treatment especially at 7 days (Pexpenditure were improved in all the patients at 2 weeks and 4 months after the treatment, and the improvement was more obvious in the treatment group (Pexpenditure in patients with heart failure after myocardial infarction.

  12. Meta-Analysis of Stress Myocardial Perfusion Imaging

    Science.gov (United States)

    2017-06-06

    Coronary Disease; Echocardiography; Fractional Flow Reserve, Myocardial; Hemodynamics; Humans; Magnetic Resonance Imaging; Myocardial Perfusion Imaging; Perfusion; Predictive Value of Tests; Single Photon Emission Computed Tomography; Positron Emission Tomography; Multidetector Computed Tomography; Echocardiography, Stress; Coronary Angiography

  13. Association of blood transfusion with increased mortality in myocardial infarction

    DEFF Research Database (Denmark)

    Chatterjee, Saurav; Wetterslev, Jørn; Sharma, Abhishek

    2013-01-01

    The benefit of blood transfusion in patients with myocardial infarction is controversial, and a possibility of harm exists.......The benefit of blood transfusion in patients with myocardial infarction is controversial, and a possibility of harm exists....

  14. Aircraft noise, air pollution, and mortality from myocardial infarction.

    NARCIS (Netherlands)

    Huss, A.; Spoerri, A.; Egger, M.; Roosli, M.

    2010-01-01

    OBJECTIVE: Myocardial infarction has been associated with both transportation noise and air pollution. We examined residential exposure to aircraft noise and mortality from myocardial infarction, taking air pollution into account. METHODS: We analyzed the Swiss National Cohort, which includes

  15. Association between intraoperative hypotension and myocardial injury after vascular surgery

    NARCIS (Netherlands)

    van Waes, JAR; Van Klei, Wilton A.; Wijeysundera, Duminda N.; Van Wolfswinkel, Leo; Lindsay, Thomas F.; Beattie, W. Scott

    2016-01-01

    Background: Postoperative myocardial injury occurs frequently after noncardiac surgery and is strongly associated with mortality. Intraoperative hypotension (IOH) is hypothesized to be a possible cause. The aim of this study was to determine the association between IOH and postoperative myocardial

  16. Role of myocardial perfusion imaging in evaluating thrombolytic therapy for acute myocardial infarction

    International Nuclear Information System (INIS)

    Beller, G.A.

    1987-01-01

    Myocardial thallium-201 scintigraphy is being increasingly employed as a method for assessing the efficacy of coronary reperfusion in acute myocardial infarction. New thallium uptake after intracoronary tracer administration after successful recanalization indicates that nutrient blood flow has been successfully restored. One may also presume that some myocardial salvage occurred if thallium administered in this manner is transported intracellularly by myocytes with intact sarcolemmal membranes. However, if one injects thallium by way of the intracoronary route immediately after reperfusion, the initial uptake of thallium in reperfused myocardium may predominantly represent hyperemic flow and regional thallium counts measured may not be proportional to the mass of viable myocytes. When thallium is injected intravenously during the occlusion phase the degree of redistribution after thrombolysis is proportional to the degree of flow restoration and myocardial viability. When thallium is injected for the first time intravenously immediately after reperfusion, an overestimation of myocardial salvage may occur because of excess thallium uptake in the infarct zone consequent to significant hyperemia. Another approach to myocardial thallium scintigraphy in patients undergoing thrombolytic therapy is to administer two separate intravenous injections before and 24 hours or later after treatment. Finally, patients with acute myocardial infarction who receive intravenous thrombolytic therapy are candidates for predischarge exercise thallium-201 scintigraphy for risk stratification and detection of residual ischemia

  17. Myocardial dysfunction in malnourished children

    Directory of Open Access Journals (Sweden)

    Faddan Nagla Hassan

    2010-01-01

    Full Text Available Background : Malnourished children suffer several alterations in body composition that could produce cardiac abnormalities. Aim : The aim of the present study was to detect the frequency of myocardial damage in malnourished children as shown by echocardiography and cardiac troponin T (cTnT level. Methods : Forty-five malnourished infants and young children (mean±SD of age was 11.24 ±7.88 months were matched with 25 apparently healthy controls (mean±SD of age was 10.78±6.29 months. Blood sample was taken for complete blood picture, liver and kidney function tests, serum sodium, potassium, calcium levels and cTnT. All the malnourished children were subjected to echocardiographic evaluation. Results : Malnourished children showed a significantly lower left ventricular (LV mass than the control group. The LV systolic functions were significantly impaired in patients with severe malnutrition. The cTnT level was higher than the upper reference limits in 11 (24.44% of the studied malnourished children and all of them had a severe degree of malnutrition. The cTnT level was significantly higher in patients with anemia, sepsis and electrolyte abnormalities and it correlated negatively with LV ejection fraction (EF. Six of the studied children with high cTnT levels (54.5% died within 21 days of treatment while only one case (2.9% with normal level of cTnT died within the same period. Conclusions: LV mass is reduced in malnourished children. Children with severe malnutrition have a significant decrease in LV systolic functions. Elevated cTnT levels in malnourished children has both diagnostic and prognostic significance for cardiomyocyte damage.

  18. Delayed ventricular septal rupture complicating acute inferior wall myocardial infarction

    OpenAIRE

    Cho, Jae Hyung; Sattiraju, Srinivasan; Mehta, Sanjay; Missov, Emil

    2013-01-01

    Background Ventricular septal rupture is a potentially fatal complication of acute myocardial infarction. Its incidence has declined with modern reperfusion therapy. In the era of percutaneous coronary interventions, it occurs a median of 18?24?hours after myocardial infarction and is most commonly associated with anterior myocardial infarction. We present a case of delayed ventricular septal rupture complicating acute inferior wall myocardial infarction. Case presentation A 53-year-old Cauca...

  19. Assessment of myocardial viability using multidetector computed tomography in patients with reperfused acute myocardial infarction

    International Nuclear Information System (INIS)

    Kim, T.; Choi, B.J.; Kang, D.K.; Sun, J.S.

    2012-01-01

    Aim: To assess the prognostic value of 64-section multidetector computed tomography (MDCT) to predict follow-up myocardial dysfunction and functional recovery after reperfusion therapy in patients with acute myocardial infarction (MI) as defined by echocardiography. Materials and methods: After reperfusion therapy for acute MI, 71 patients underwent two-phase contrast-enhanced MDCT and follow-up echocardiography. MDCT findings were compared with echocardiographic findings using kappa statistics. The areas under the receiver operating characteristic curves (AUCs) and the odds ratios (ORs) of early perfusion defects (EPD), delayed enhancement (DE), and residual perfusion defects (RPD) for predicting follow-up myocardial dysfunction and functional recovery were calculated on a segmental basis. Results: The presence of transmural EPD (EPD TM ) or RPD showed good agreement (k = 0.611 and 0.658, respectively) with follow-up myocardial dysfunction, while subendocardial EPD (EPD sub ) or subendocardial DE (DE sub ) showed fair agreement with follow-up myocardial dysfunction (k = 0.235 and 0.234, respectively). The AUC of RPD (0.796) was superior (p TM (0.761) and DE TM (0.771). The presence of EPD TM , DE TM , and RPD were significant, independent positive predictors of follow-up myocardial dysfunction (OR = 6.4, 1.9, and 9.8, respectively). EPD TM was a significant, independent negative predictor of myocardial functional recovery (OR = 0.13). Conclusion: Abnormal myocardial attenuation on two-phase MDCT after reperfusion therapy may provide promising information regarding myocardial viability in patients with acute MI.

  20. Rationale and radiopharmaceuticals for myocardial imaging

    International Nuclear Information System (INIS)

    Poe, N.D.

    1976-01-01

    Static radionuclide imaging procedures are now available for evaluating regional myocardial perfusion and for detecting acute myocardial infarction. Thallium-201, a radiopharmaceutical which possesses many of the characteristics of potassium analogs, at present is receiving the greatest attention as a regional blood flow indicator. Ischemic lesions appear as areas of decreased tracer uptake. Unfortunately, this agent is expensive, is in limited supply and has a photopeak which is low for optimum imaging. Positive infarct images can be obtained with various technetium-99m chelates. Pyrophosphate appears to be the best of the technetium compounds studied to date although the mechanism of uptake of the chelates has not yet been fully elucidated. Therefore, quantitative measurements of infarct size are not justified. As perfusion imaging and infarct imaging provide useful, complementary data, a dual tracer approach to evaluating patients with suspected coronary artery disease and/or myocardial infarction is probably justifiable

  1. Perfusion scintigraphy in acute myocardial infarction

    International Nuclear Information System (INIS)

    Schricke, U.; Schwaiger, M.; Kastrati, A.; Schoemig, A.

    1999-01-01

    The Tc-99m sestamibi perfusion SPECT scintigraphy in acute myocardial infarction is a feasible method to assess the size of area at risk and the residual blood flow to this area as the most important determinants of final infarct size without any delay in treatment. In combination with a follow-up study final infarct size as well as myocardial salvage can be quantified. Clinical indications for the use of Tc-99m sestamibi scintigraphy are the noninvasive identification of arterial occlusion in patients suspected to acute myocardial infarction without electrocardiographic ST-elevation and the assessment of reperfusion success. In clinical trials Tc-99m sestamibi scintigraphy has proven to be a useful method to assess the impact of varying reperfusion therapies. The present review article discusses the indication, the study protocol, the interpretation of results and the clinical and scientifically importance of this method. (orig.) [de

  2. Acute myocardial infarction in a young patient

    International Nuclear Information System (INIS)

    Hameed, A.; Ata-ur-Rehman Quraishi

    2004-01-01

    Myocardial infarction (MI) is considered to be the disease of the fifth and sixth decade as seen in the West but an earlier age incidence is not infrequently encountered in the South Asian population. However, occurrence of MI in the teen-age still remains a rare happening. We are reporting a case of a teenager, who suffered a myocardial infarction with cardiogenic shock and pulmonary edema on two separate occasions with ECG and biochemical evidence of myocardial infarction. An exercise stress test done in between the two episodes was negative at a workload of 13.5 METs. A coronary angiogram done after the second event revealed normal coronary arteries and a preserved left ventricular systolic and segmental function. Except for low HDL (high density lipoprotein) and mildly raised homocysteine levels, the patient did not have other conventional or novel risk factors for coronary artery disease. (author)

  3. The Myocardial Performance Index During Low Dose Dobutamine Echocardiography in Normals and Patients With a Recent Myocardial Infarction

    DEFF Research Database (Denmark)

    Nørager, Betina; Husic, Mirza; Møller, Jacob E

    2004-01-01

    BACKGROUND: Wall-motion analysis during low-dose dobutamine echocardiography (LDDE) is a semiquantitative measure of left ventricular contractile reserve after myocardial infarction (MI). The Doppler echocardiographic myocardial performance index (MPI) is a quantitative measure of combined left...

  4. Roles of myocardial blood volume and flow in coronary artery disease: an experimental MRI study at rest and during hyperemia

    International Nuclear Information System (INIS)

    McCommis, Kyle S.; Goldstein, Thomas A.; Pilgram, Thomas; Abendschein, Dana R.; Misselwitz, Bernd; Gropler, Robert J.; Zheng, Jie

    2010-01-01

    To validate fast perfusion mapping techniques in a setting of coronary artery stenosis, and to further assess the relationship of absolute myocardial blood volume (MBV) and blood flow (MBF) to global myocardial oxygen demand. A group of 27 mongrel dogs were divided into 10 controls and 17 with acute coronary stenosis. On 1.5-T MRI, first-pass perfusion imaging with a bolus injection of a blood-pool contrast agent was performed to determine myocardial perfusion both at rest and during either dipyridamole-induced vasodilation or dobutamine-induced stress. Regional values of MBF and MBV were quantified by using a fast mapping technique. Color microspheres and 99m Tc-labeled red blood cells were injected to obtain respective gold standards. Microsphere-measured MBF and 99m Tc-measured MBV reference values correlated well with the MR results. Given the same changes in MBF, changes in MBV are twofold greater with dobutamine than with dipyridamole. Under dobutamine stress, MBV shows better association with total myocardial oxygen demand than MBF. Coronary stenosis progressively reduced this association in the presence of increased stenosis severity. MR first-pass perfusion can rapidly estimate regional MBF and MBV. Absolute quantification of MBV may add additional information on stenosis severity and myocardial viability compared with standard qualitative clinical evaluations of myocardial perfusion. (orig.)

  5. Roles of myocardial blood volume and flow in coronary artery disease: an experimental MRI study at rest and during hyperemia

    Science.gov (United States)

    McCommis, Kyle S.; Goldstein, Thomas A.; Abendschein, Dana R.; Misselwitz, Bernd; Pilgram, Thomas; Gropler, Robert J.

    2010-01-01

    Objective To validate fast perfusion mapping techniques in a setting of coronary artery stenosis, and to further assess the relationship of absolute myocardial blood volume (MBV) and blood flow (MBF) to global myocardial oxygen demand. Methods A group of 27 mongrel dogs were divided into 10 controls and 17 with acute coronary stenosis. On 1.5-T MRI, first-pass perfusion imaging with a bolus injection of a blood-pool contrast agent was performed to determine myocardial perfusion both at rest and during either dipyridamole-induced vasodilation or dobutamine-induced stress. Regional values of MBF and MBV were quantified by using a fast mapping technique. Color microspheres and 99mTc-labeled red blood cells were injected to obtain respective gold standards. Results Microsphere-measured MBF and 99mTc-measured MBV reference values correlated well with the MR results. Given the same changes in MBF, changes in MBV are twofold greater with dobutamine than with dipyridamole. Under dobutamine stress, MBV shows better association with total myocardial oxygen demand than MBF. Coronary stenosis progressively reduced this association in the presence of increased stenosis severity. Conclusions MR first-pass perfusion can rapidly estimate regional MBF and MBV. Absolute quantification of MBV may add additional information on stenosis severity and myocardial viability compared with standard qualitative clinical evaluations of myocardial perfusion. PMID:20182731

  6. Cardioprotective Effect of Aloe vera Biomacromolecules Conjugated with Selenium Trace Element on Myocardial Ischemia-Reperfusion Injury in Rats.

    Science.gov (United States)

    Yang, Yang; Yang, Ming; Ai, Fen; Huang, Congxin

    2017-06-01

    The present study was undertaken to evaluate the cardioprotection potential and underlying molecular mechanism afforded by a selenium (Se) polysaccharide (Se-AVP) from Aloe vera in the ischemia-reperfusion (I/R) model of rats in vivo. Myocardial I/R injury was induced by occluding the left anterior descending coronary artery (LAD) for 30 min followed by 2-h continuous reperfusion. Pretreatment with Se-AVP (100, 200, and 400 mg/kg) attenuated myocardial damage, as evidenced by reduction of the infarct sizes, increase in serum and myocardial endogenous antioxidants (superoxide dismutase (SOD), glutathione peroxidase (GSH), and catalase (CAT)), and decrease in the malondialdehyde (MDA) level in the rats suffering I/R injury. This cardioprotective activity afforded by Se-AVP is further supported by the decreased levels of cardiac marker enzymes creatine kinase (CK) and lactate dehydrogenase (LDH), as well as the rise of myocardial Na + -K + -ATPase and Ca 2+ -Mg 2+ -ATPase activities in I/R rats. Additionally, cardiomyocytic apoptosis was measured by terminal-deoxynucleotidyl transferase-mediated nick end labeling (TUNEL) staining and the result showed that the percent of TUNEL-positive cells in myocardium of Se-AVP-treated groups was lower than I/R rats. In conclusion, we clearly demonstrated that Se-AVP had a protective effect against myocardial I/R injury in rats by augmenting endogenous antioxidants and protecting rat hearts from oxidative stress-induced myocardial apoptosis.

  7. Assessment of myocardial viability by exercise stress myocardial tomography with 201Tl

    International Nuclear Information System (INIS)

    Narita, Michihiro; Kurihara, Tadashi; Murano, Kenichi; Usami, Masahisa

    1992-01-01

    Exercise stress (Ex) and redistribution (RD) myocardial tomography with Tl-201 has been widely used for evaluating myocardial viability. But recent studies have demonstrated that reinjection (ReI) study following RD study is necessary for detecting reversible ischemic myocardium. On the other hand, decreased myocardial washout of Tl-201 after Ex is an indicator of myocardial ischemia. So we have studied the usefulness of myocardial Tl-201 washout rate (WOR) for the evaluation of myocardial viability by comparing it with ReI images. Ex and RD myocardial tomographies were obtained immediately after Ex and 3 hours later. After RD study a small amount of Tl-201 was injected and ReI imaging was repeated. We studied 64 myocardial segments (in 58 patients with coronary artery disease) in which Ex-induced perfusion defects persisted in RD images. According to the changes of perfusion defects between Ex, RD and ReI images, they were classified into 3 types: Type I; perfusion defect on the RD image was identical to ReI image (75%). Type I was divided into 2 subgroups whether perfusion defect at Ex was unchanged (Ia, 42%) or improved (Ib, 33%) on the RD image. Type II; perfusion defect at Ex was reduced on the RD image and it improved furthermore at ReI image (17%). Type III; perfusion defect was the same at Ex and RD but it was reduced on the ReI image (8%). WOR less than 30% was defined as abnormal when Ex heart rate exceeded 120 bpm and lung-myocardial Tl-201 uptake ratio was less than 0.45. The differentiation between Type Ia and Type III is of great importance. History of myocardial infarction, effort angina and Ex induced ST depression could not differentiate these 2 groups. WOR abnormality was observed in all of Type III, but WOR was normal in Type Ia. In conclusion, WOR abnormality in Ex-RD myocardial imaging is useful for evaluating myocardial viability. ReI imaging is necessary for the precise evaluation of viable muscle mass and for inadequate Ex. (author)

  8. Asymptomatic myocardial ischemia following cold provocation

    International Nuclear Information System (INIS)

    Shea, M.J.; Deanfield, J.E.; deLandsheere, C.M.; Wilson, R.A.; Kensett, M.; Selwyn, A.P.

    1987-01-01

    Cold is thought to provoke angina in patients with coronary disease either by an increase in myocardial demand or an increase in coronary vascular resistance. We investigated and compared the effects of cold pressor stimulation and symptom-limited supine bicycle exercise on regional myocardial perfusion in 35 patients with stable angina and coronary disease and in 10 normal subjects. Regional myocardial perfusion was assessed with positron emission tomography and rubidium-82. Following cold pressor stimulation 24 of 35 patients demonstrated significant abnormalities of regional myocardial perfusion with reduced cation uptake in affected regions of myocardium: 52 +/- 9 to 43 +/- 9 (p less than 0.001 vs normal subjects). Among these 24 patients only nine developed ST depression and only seven had angina. In contrast, 29 of 35 patients underwent supine exercise, and abnormal regional myocardial perfusion occurred in all 29, with a reduction in cation intake from 48 +/- 10 to 43 +/- 14 (p less than 0.001 vs normal subjects). Angina was present in 27 of 29 and ST depression in 25 of 29. Although the absolute decrease in cation uptake was somewhat greater following cold as opposed to exercise, the peak heart rate after cold was significantly lower than that after exercise (82 +/- 12 vs 108 +/- 16 bpm, p less than 0.05). Peak systolic blood pressures after cold and exercise were similar (159 +/- 24 vs 158 +/- 28). Thus, cold produces much more frequent asymptomatic disturbances of regional myocardial perfusion in patients with stable angina and coronary disease than is suggested by pain or ECG changes

  9. Efeito do exercício associado ao transplante de células-tronco sobre a função ventricular de ratos pós-infarto agudo do miocárdio Effect of exercise associated with stem cell transplantation on ventricular function in rats after acute myocardial infarction

    Directory of Open Access Journals (Sweden)

    Simone Cosmo

    2012-12-01

    Full Text Available OBJETIVO: Avaliar o efeito da associação terapêutica entre o transplante autólogo de células-tronco e o exercício físico aquático, sobre a fração de ejeção do ventrículo esquerdo (FEVE de ratos com disfunção ventricular pós-infarto agudo do miocárdio (IAM. MÉTODOS: Foram induzidos ao IAM, por ligadura da artéria coronária esquerda, 21 ratos Wistar. Os animais foram submetidos à ecocardiografia para avaliação da FEVE (% e dos volumes diastólico e sistólico finais do ventrículo esquerdo (VDF, VSF, ml, randomizados e ao transplante das células-tronco mononucleares. Os animais foram divididos em quatro grupos: grupo sedentário sem células (n=5, sedentário com células (n=5, treinado sem células (n=5 e treinado com células (n=6. O treinamento físico foi iniciado 30 dias após o IAM e realizado em piscina adaptada durante 30 dias. No início e no final do protocolo de treinamento físico, foram realizadas dosagens de lactato. Os animais foram submetidos a nova ecocardiografia após 60 dias do IAM. RESULTADOS: Comparação dos valores de FEVE 30 dias e 60 dias pós-IAM, respectivamente: sedentário sem (35,20 ± 7,64% vs. 22,39 ± 4,56% P=0,026, com células (25,18 ± 7,73% vs. 23,85 ± 9,51% P=0,860 e no treinado sem (21,49 ± 2,70% vs. 20,71 ± 7,14% P=0,792, treinado com células (28,86 ± 6,68 vs. 38,43 ±7,56% P=0,062. Identificou-se a diminuição de fibras colágenas, nas regiões de fibrose miocárdica no grupo treinado com e sem células. CONCLUSÃO: A associação terapêutica entre exercício físico e o transplante autólogo de células-tronco foi benéfica contra as ações do remodelamento ventricular.OBJECTIVE: To analyze the functional and anatomical-pathological effect of transplantation of bone marrow mononuclear cells associated to aquatic physical activity after myocardial infarction in rats. METHODS: Twenty-one rats were induced by myocardial infarction, through left coronary artery ligation. After

  10. [Effect of puerarin in myocardial protection in rats with acute and chronic alcoholism].

    Science.gov (United States)

    Cui, Shu-qin

    2011-12-01

    To investigate the protective effect of puerarin on the myocardium of rats with acute and chronic alcoholism. In acute alcoholism experiment, normal male SD rats were randomly divided into the control group, alcoholism group and puerarin group (n=8), and high- and low-dose puerarin was administered. In chronic alcoholism experiment, increasing puerarin doses were given. Serum and myocardial levels of spartate aminotransferase (AST) and creatine phosphokinase (CPK) were determined using enzymatic methed, and superoxide dismutase (SOD), malondialdehyde (MDA), Ca(2+)-Mg(2+)-ATPase, and Na(+)-K(+)-ATPase in the myocardium were assayed with colorimetric method. HE staining was used to observe the microscopic changes of the myocardium. Compared with alcoholism group, puerarin-treated groups showed significantly lowered myocardial contents of MDA, CPK and AST and serum levels of AST and CPK (P0.05). HE staining of the myocardium showed cell swelling and obscure cell boundaries in alcoholism group, especially in chronic alcoholism group. The myocardial structure in puerarin group remained clear and regular. Puerarin can protect from myocardial injuries induced by acute and chronic alcoholism in rats.

  11. Effect of Curcuma longa and Ocimum sanctum on myocardial apoptosis in experimentally induced myocardial ischemic-reperfusion injury

    Science.gov (United States)

    Mohanty, Ipseeta; Arya, Dharamvir Singh; Gupta, Suresh Kumar

    2006-01-01

    Background In the present investigation, the effect of Curcuma longa (Cl) and Ocimum sanctum (Os) on myocardial apoptosis and cardiac function was studied in an ischemia and reperfusion (I-R) model of myocardial injury. Methods Wistar albino rats were divided into four groups and orally fed saline once daily (sham, control IR) or Cl (100 mg/kg; Cl-IR) or Os (75 mg/kg; Os-IR) respectively for 1 month. On the 31st day, in the rats of the control IR, Cl-IR and Os-IR groups LAD occlusion was undertaken for 45 min, and reperfusion was allowed for 1 h. The hemodynamic parameters{mean arterial pressure (MAP), heart rate (HR), left ventricular end-diastolic pressure (LVEDP), left ventricular peak positive (+) LVdP/dt (rate of pressure development) and negative (-) LVdP/dt (rate of pressure decline)} were monitored at pre-set points throughout the experimental duration and subsequently, the animals were sacrificed for immunohistopathological (Bax, Bcl-2 protein expression & TUNEL positivity) and histopathological studies. Results Chronic treatment with Cl significantly reduced TUNEL positivity (p < 0.05), Bax protein (p < 0.001) and upregulated Bcl-2 (p < 0.001) expression in comparison to control IR group. In addition, Cl demonstrated mitigating effects on several myocardial injury induced hemodynamic {(+)LVdP/dt, (-) LVdP/dt & LVEDP} and histopathological perturbations. Chronic Os treatment resulted in modest modulation of the hemodynamic alterations (MAP, LVEDP) but failed to demonstrate any significant antiapoptotic effects and prevent the histopathological alterations as compared to control IR group. Conclusion In the present study, significant cardioprotection and functional recovery demonstrated by Cl may be attributed to its anti-apoptotic property. In contrast to Os, Cl may attenuate cell death due to apoptosis and prevent the impairment of cardiac performance. PMID:16504000

  12. Symbolic reasoning about myocardial scintigrams in PROLOG

    International Nuclear Information System (INIS)

    Rosenberg, S.; Itti, R.; Benjelloun, L.

    1986-01-01

    PROLOG (PROgramming in LOGic) is the declarative programming language at the heart of the Japanese fifth-generation computer project. It is proposed that PROLOG is a suitable tool for symbolic image processing, once standard preprocessing has been done. In the present application, the problem of prediction of coronary anatomy from myocardial scintigrams is addressed. Uncertainty is dealt with by a combination of fuzzy-set theoretic and probabilistic reasoning. Heuristic classification rules are based on clinical experience and on a set of 247 myocardial scintigrams with their corresponding coronary angiograms. (orig.)

  13. Scintigraphic demonstration of acute myocardial infarcts

    International Nuclear Information System (INIS)

    Holman, B.L.; Lesch, M.

    1976-01-01

    The feasibility of acute infarct scintigraphy for the clinical evaluation of patients with known or suspected acute myocardial infarction is established. Further development of this methodologic approach may result in even better agents for the visualization of infarcts. Radiotracers with high affinity for the infarct, rapid blood clearance, and low concentrations in surrounding organs, such as liver and bone, would be more suitable than available radiopharmaceuticals for acute myocardial infarct scintigraphy. Ultimately, labeling these tracers and ultra-short-lived radionuclides will enable rapid sequential imaging to assess changes in the extent of infarction and to determine the efficacy of therapies aimed at limiting infarct size

  14. Proton chemical shift imaging after myocardial infarction

    International Nuclear Information System (INIS)

    Bouchard, A.; Doyle, M.; Pohost, G.M.

    1989-01-01

    The present study was undertaken to test whether chemical shift imaging could detect spatially the lipids known to accumulate in myocardium after an ischemic insult. Seven dogs underwent a 24-hour coronary artery occlusion. Hearts were removed and imaged ex vivo by the Dixon method (1.5 T), and myocardial samples were obtained for high-resolution H-1 spectroscopy. Lipid images revealed regions of increased signal intensity in the periphery f the myocardial infarction. The zones of high lipid signal corresponded to zones with elevated mobile lipids as detected by H-1 spectroscopy

  15. Myocardial Na,K-ATPase: Clinical aspects

    OpenAIRE

    Kjeldsen, Keld

    2003-01-01

    The specific binding of digitalis glycosides to Na,K-ATPase is used as a tool for Na,K-ATPase quantification with high accuracy and precision. In myocardial biopsies from patients with heart failure, total Na,K-ATPase concentration is decreased by around 40%; a correlation exists between a decrease in heart function and a decrease in Na,K-ATPase concentration. During digitalization, around 30% of remaining pumps are occupied by digoxin. Myocardial Na,K-ATPase is also influenced by other drugs...

  16. Symbolic reasoning about myocardial scintigrams in PROLOG

    Energy Technology Data Exchange (ETDEWEB)

    Rosenberg, S; Itti, R; Benjelloun, L

    1986-06-01

    PROLOG (PROgramming in LOGic) is the declarative programming language at the heart of the Japanese fifth-generation computer project. It is proposed that PROLOG is a suitable tool for symbolic image processing, once standard preprocessing has been done. In the present application, the problem of prediction of coronary anatomy from myocardial scintigrams is addressed. Uncertainty is dealt with by a combination of fuzzy-set theoretic and probabilistic reasoning. Heuristic classification rules are based on clinical experience and on a set of 247 myocardial scintigrams with their corresponding coronary angiograms.

  17. [Establishment of myocardial targeted nanoparticles and preliminary evaluation of its effects on prevention and treatment of myocardial injury].

    Science.gov (United States)

    Liu, Y Y; Wang, C; Luo, P F; Xia, Z F

    2017-11-20

    Objective: To establish 3-{4-[2-hydroxyl-(1-methylethylamino) propoxy] phenyl} propionic acid cetylesters (PAC) modified nanoparticles, and preliminarily explore its cardiomyocyte-targeting function and protection effects on myocardium. Methods: (1) HL-1 myocardial cells were divided into cyanidin-3 (Cy3) marked non-targeted small interference RNA (Cy3-siNC) group and Cy3 marked small interference RNA designed for the nuclear factor kappa B (NF-κB)-p65 gene (Cy3-si435) group according to the random number table, with 3 wells in each group. Cells in Cy3-siNC group were transfected with Cy3-siNC, while cells in Cy3-si435 group were transfected with Cy3-si435. At transfection hour 24, the mRNA expression of NF-κB-p65 of cells was determined by real-time fluorescent quantitative polymerase chain reaction. (2) Multiple emulsificating solvent evaporating method was adopted to prepare PAC modified nanoparticles carried with Cy3-siNC (Cy3-siNC-PAC) and PAC modified nanoparticles carried with Cy3-si435 (Cy3-si435-PAC). The morphology of Cy3-si435-PAC nanoparticles was observed with scanning electron microscope, and the size and potential of Cy3-si435-PAC nanoparticles were detected by nanometer particle size and zeta potential analyzer. The entrapment efficiency and drug loadings of Cy3-si435-PAC nanoparticle were determined with ultraviolet spectrophotometer. The release of Cy3-si435 of Cy3-si435-PAC nanoparticles was determined by dialysis method. (3) Another batch of HL-1 cells were divided into 4 groups according to the random number table, with 9 wells in each group. Cells in negative control group were added with 5 μL phosphate buffer. Cells in 25, 50, and 100 mg/mL Cy3-si435-PAC nanoparticles groups were added with 5 μL 25, 50, and 100 mg/mL Cy3-si435-PAC nanoparticles, respectively. At transfection hour 6, 12, and 24, proliferation activity of cells in 3 wells of each group was detected by methyl thiazolyl tetrazolium method, respectively. (4) Another batch of

  18. The expression of myocardial injury in cold induced myocardial imaging and echocardiography of systematic scleroderma

    International Nuclear Information System (INIS)

    Liang Jiugen; Zhu Xiaojun; Jiang Ningyi; Chen Shaoxiong

    1999-01-01

    The study was performed with cold-induced 99m Tc(MIBI) myocardial imaging (MI) in 23 patients with systematic scleroderma. The left ventricular function and wall motion were also observed by dimensional echocardiography (UCG). 14 patients had myocardial perfusion abnormalities visualized by MI, including 5 cases with fixed defects of 9 segments, 3 cases with reversible defects of 6 segments and 6 cases with both fixed and reversible one of 14 segments. The positive rate in myocardial imaging had no significant differences between patients with and without Raynaud's phenomenon (0.5>P>0.25). Compared with baseline, the ejection fraction, stroke volume, cardiac output were significantly decreased during cold-induced in patients with abnormal myocardial scintigraphy (P<0.05), and had significant difference compared with normal group (P<0.05). 4 cases with cold-induced reversible perfusion defects had anatomically correlated regional ventricular hypokinesia in UCG

  19. Automated quantitative coronary computed tomography correlates of myocardial ischaemia on gated myocardial perfusion SPECT

    Energy Technology Data Exchange (ETDEWEB)

    Graaf, Michiel A. de; Boogers, Mark J.; Veltman, Caroline E. [Leiden University Medical Center, Department of Cardiology, Leiden (Netherlands); The Interuniversity Cardiology Institute of The Netherlands, Utrecht (Netherlands); El-Naggar, Heba M.; Bax, Jeroen J.; Delgado, Victoria [Leiden University Medical Center, Department of Cardiology, Leiden (Netherlands); Broersen, Alexander; Kitslaar, Pieter H.; Dijkstra, Jouke [Leiden University Medical Center, Department of Radiology, Division of Image Processing, Leiden (Netherlands); Kroft, Lucia J. [Leiden University Medical Center, Department of Radiology, Leiden (Netherlands); Younis, Imad Al [Leiden University Medical Center, Department of Nuclear Medicine, Leiden (Netherlands); Reiber, Johan H. [Leiden University Medical Center, Department of Radiology, Division of Image Processing, Leiden (Netherlands); Medis medical imaging systems B.V., Leiden (Netherlands); Scholte, Arthur J. [Leiden University Medical Center, Department of Cardiology, Leiden (Netherlands)

    2013-08-15

    Automated software tools have permitted more comprehensive, robust and reproducible quantification of coronary stenosis, plaque burden and plaque location of coronary computed tomography angiography (CTA) data. The association between these quantitative CTA (QCT) parameters and the presence of myocardial ischaemia has not been explored. The aim of the present investigation was to evaluate the association between QCT parameters of coronary artery lesions and the presence of myocardial ischaemia on gated myocardial perfusion single-photon emission CT (SPECT). Included in the study were 40 patients (mean age 58.2 {+-} 10.9 years, 27 men) with known or suspected coronary artery disease (CAD) who had undergone multidetector row CTA and gated myocardial perfusion SPECT within 6 months. From the CTA datasets, vessel-based and lesion-based visual analyses were performed. Consecutively, lesion-based QCT was performed to assess plaque length, plaque burden, percentage lumen area stenosis and remodelling index. Subsequently, the presence of myocardial ischaemia was assessed using the summed difference score (SDS {>=}2) on gated myocardial perfusion SPECT. Myocardial ischaemia was seen in 25 patients (62.5 %) in 37 vascular territories. Quantitatively assessed significant stenosis and quantitatively assessed lesion length were independently associated with myocardial ischaemia (OR 7.72, 95 % CI 2.41-24.7, p < 0.001, and OR 1.07, 95 % CI 1.00-1.45, p = 0.032, respectively) after correcting for clinical variables and visually assessed significant stenosis. The addition of quantitatively assessed significant stenosis ({chi} {sup 2} = 20.7) and lesion length ({chi} {sup 2} = 26.0) to the clinical variables and the visual assessment ({chi} {sup 2} = 5.9) had incremental value in the association with myocardial ischaemia. Coronary lesion length and quantitatively assessed significant stenosis were independently associated with myocardial ischaemia. Both quantitative parameters have

  20. Exercise induced ST elevation and residual myocardial ischemia in previous myocardial infarction

    International Nuclear Information System (INIS)

    Shimonagata, Tsuyoshi; Nishimura, Tsunehiko; Uehara, Toshiisa; Hayashida, Kohei; Saito, Muneyasu; Sumiyoshi, Tetsuya

    1987-01-01

    The purpose of this study was to evaluate the clinical significance of stress induced ST elevation on infarcted area in 65 patients with previous myocardial infarction (single vessel disease) who had stress thallium scan. Stress induced ST changes on infarcted area were compared with quantitative assessment of myocardial ischemia (thallium ischemic score; TIS) and extent of myocardial infarction (defect score; DS) derived from circumferential profile analysis. In patients with previous myocardial infarction in less than 3 month from the onset (n = 36), left ventricular ejection fraction (LVEF) and extent of abnormal LV wall motion were not significantly different between patients with stress induced ST elevation ( ≥ 2 mm, n = 26) and those with stress induced ST elevation ( < 2 mm, n = 10), while, in patients with previous myocardial infarction in more than 3 month (n = 29), patients with stress induced ST elevation ( ≥ 2 mm, n = 15) showed left ventricular dyskinesis more frequently than those with ST elevation ( < 2 mm, n = 14). In addition, the former showed significantly higher DS and significantly lower TIS than the latter. In patients with previous myocardial infarction in less than 3 month, patients with ST elevation ( ≥ 2 mm, n = 15) with prominent upright T wave (n = 15) had transient thallium defect in infarcted area in 73 % and they had significantly higher LVEF and TIS than those with ST elevation ( < 2 mm, n = 11). These results indicated that ST elevation in infarcted area reflect different significance according to the recovery of injured myocardium and stress induced ST elevation with prominent upright T wave in infarcted area reflect residual myocardial ischemia in less than 3 month from the onset of myocardial infarction. (author)

  1. Usefulness of myocardial parametric imaging to evaluate myocardial viability in experimental and in clinical studies.

    Science.gov (United States)

    Korosoglou, G; Hansen, A; Bekeredjian, R; Filusch, A; Hardt, S; Wolf, D; Schellberg, D; Katus, H A; Kuecherer, H

    2006-03-01

    To evaluate whether myocardial parametric imaging (MPI) is superior to visual assessment for the evaluation of myocardial viability. Myocardial contrast echocardiography (MCE) was assessed in 11 pigs before, during, and after left anterior descending coronary artery occlusion and in 32 patients with ischaemic heart disease by using intravenous SonoVue administration. In experimental studies perfusion defect area assessment by MPI was compared with visually guided perfusion defect planimetry. Histological assessment of necrotic tissue was the standard reference. In clinical studies viability was assessed on a segmental level by (1) visual analysis of myocardial opacification; (2) quantitative estimation of myocardial blood flow in regions of interest; and (3) MPI. Functional recovery between three and six months after revascularisation was the standard reference. In experimental studies, compared with visually guided perfusion defect planimetry, planimetric assessment of infarct size by MPI correlated more significantly with histology (r2 = 0.92 versus r2 = 0.56) and had a lower intraobserver variability (4% v 15%, p < 0.05). In clinical studies, MPI had higher specificity (66% v 43%, p < 0.05) than visual MCE and good accuracy (81%) for viability detection. It was less time consuming (3.4 (1.6) v 9.2 (2.4) minutes per image, p < 0.05) than quantitative blood flow estimation by regions of interest and increased the agreement between observers interpreting myocardial perfusion (kappa = 0.87 v kappa = 0.75, p < 0.05). MPI is useful for the evaluation of myocardial viability both in animals and in patients. It is less time consuming than quantification analysis by regions of interest and less observer dependent than visual analysis. Thus, strategies incorporating this technique may be valuable for the evaluation of myocardial viability in clinical routine.

  2. TOWARD THE QUESTION OF ISCHEMIC MYOCARDIAL DYSFUNCTION

    Directory of Open Access Journals (Sweden)

    V. V. Kalyuzhin

    2014-01-01

    Full Text Available The authors of the review have analyzed papers published on the problem of ischemic myocardial dysfunction. They begin with a definition of the term “ischemia” (derived from two Greek words: ischō, meaning to hold back, and haima, meaning blood - a condition at which the arterial blood flow is insufficient to provide enough oxygen to prevent intracellular respiration from shifting from the aerobic to the anaerobic form. The poor rate of ATP generation from this process causes a decrease in cellular ATP, a concomitant rise in ADP, and ultimately, to depression inotropic (systolic and lusitropic (diastolic function of the affected segments of the myocardium. But with such simplicity of basic concepts, the consequences of ischemia so diverse. Influence of an ischemia on myocardial function so unequally at different patients, which is almost impossible to find two identical cases (as in the case of fingerprints. It depends on the infinite variety of lesions of coronary arteries, reperfusion (time and completeness of restoration of blood flow and reactions of a myocardium which, apparently, has considerable flexibility in its response. Ischemic myocardial dysfunction includes a number of discrete states, such as acute left ventricular failure in angina, acute myocardial infarction, ischemic cardiomyopathy, stunning, hibernation, pre- and postconditioning. There are widely differing underlying pathophysiologic states. The possibility exists that several of these states can coexist.

  3. Adverse events while awaiting myocardial revascularization

    DEFF Research Database (Denmark)

    Head, Stuart J.; da Costa, Bruno R.; Beumer, Berend

    2017-01-01

    OBJECTIVES: The aim of the current study was to estimate adverse event rates while awaiting myocardial revascularization and review criteria for prioritizing patients. METHODS: A PubMed search was performed on 19 January 2015, to identify English-language, original, observational studies reportin...

  4. Symptomatic myocardial bridging or cardiac Whipple's Diseas

    OpenAIRE

    Cabral,Virgínia L. Ribeiro; Knecht,Daniella; Pego,Regina Célia; Silva,Nuno C. Figueiredo

    2003-01-01

    This report concerns a patient with articular and cardiac manifestations of Whipple's disease. The disease was diagnosed only when gastrointestinal symptoms had appeared, because all cardiac symptoms were attributed exclusively to myocardial bridging. After 18 months of treatment with trimethoprim-sulfamethoxazole, the patient is fully asymptomatic with a normal echocardiogram.

  5. Rehabilitation of Patients Following Myocardial Infarction.

    Science.gov (United States)

    Blumenthal, James A.; Emery, Charles F.

    1988-01-01

    Examines three behavioral strategies in cardiac rehabilitation (CR) for formal treatment for physical and psychosocial sequelae of myocardial infarction (MI): exercise therapy, Type A modification, and nonspecific psychological therapies. Concludes CR improves the quality of life among post-MI patients, but does not prolong life or significantly…

  6. The treatment of perioperative myocardial infarctions following ...

    African Journals Online (AJOL)

    Background: Perioperative myocardial infarction (PMI) is a common complication following noncardiac surgery, with a 30-day mortality of 10-20%. Effective therapeutic interventions are of public health importance. Method: This is a systematic review, aimed to determine the evidence for therapies following PMI. Results: A ...

  7. Statins and perioperative myocardial infarction. | Levin | Southern ...

    African Journals Online (AJOL)

    The growing prevalence of atherosclerosis means that perioperative myocardial infarction (PMI) is of significant concern to anesthesiologists. Perioperative revascularization (if indicated medically), beta blockade (in high risk patients) and statin therapy are therapeutic modalities that are currently employed to reduce PMI.

  8. Safety and feasibility of local myocardial hypothermia

    NARCIS (Netherlands)

    Otterspoor, L.C.; van 't Veer, M.; van Nunen, L.X.; Wijnbergen, I.F.; Tonino, W.A.L.; Pijls, N.H.J.

    2016-01-01

    Background In ST-elevation myocardial infarction (STEMI), reduction in time to reperfusion of the occluded coronary artery reduces infarct size. In animal models, an additional reduction of infarct size was observed when hypothermia was induced before reperfusion, despite a longer ischemic time.

  9. Symptomatic myocardial bridging or cardiac Whipple's Diseas

    Directory of Open Access Journals (Sweden)

    Cabral Virgínia L. Ribeiro

    2003-01-01

    Full Text Available This report concerns a patient with articular and cardiac manifestations of Whipple's disease. The disease was diagnosed only when gastrointestinal symptoms had appeared, because all cardiac symptoms were attributed exclusively to myocardial bridging. After 18 months of treatment with trimethoprim-sulfamethoxazole, the patient is fully asymptomatic with a normal echocardiogram.

  10. Does heavy physical exertion trigger myocardial infarction?

    DEFF Research Database (Denmark)

    Hallqvist, J; Möller, J; Ahlbom, A

    2000-01-01

    To study possible triggering of first events of acute myocardial infarction by heavy physical exertion, the authors conducted a case-crossover analysis (1993-1994) within a population-based case-referent study in Stockholm County, Sweden (the Stockholm Heart Epidemiology Program). Interviews were...

  11. Management of myocardial damage in muscular dystrophy

    International Nuclear Information System (INIS)

    Tamura, Takuhisa

    2011-01-01

    Heart failure (HF) is a fatal complication in many muscular dystrophy cases and has become the most common cause of death in Duchenne muscular dystrophy (DMD) since 2001. HF deaths in DMD occur in young patients and increase, along with respiratory failure, in older patients. Managing HF, therefore, is the most important component of DMD treatment. Management of HF is necessary in DMD patients of all ages because myocardial damage progresses regardless of age and disability. Electrocardiography, echocardiography, myocardial single-photon emission computed tomography (SPECT), and natriuretic peptides are used for the diagnosis of myocardial damage and chronic HF. Tissue Doppler echocardiography is in particularly useful for early detection of minute myocardial damage and dysfunction in DMD. The first-line drugs for chronic HF are angiotensin-converting enzyme inhibitors, and the prognosis of DMD patients has been improved using these drugs and beta-blockers. Diuretics are added in the presence of pulmonary congestion. Digoxin is most effective at a blood level of 0.5-0.8 ng/mL because of its pharmacokinetics in DMD. Surgical treatment may be necessary in cases of intractable HF. Cardiac resynchronization therapy (biventricular pacing), a treatment with an artificial pacemaker, is indicated for cases that meet specific criteria, including HF with ventricular dyssynchrony. Applications of partial left ventriculectomy (Batista procedure) and left ventricular assist devices in muscular dystrophy are likely in the near future. (author)

  12. Quantitative assessment of 201TlCl myocardial SPECT

    International Nuclear Information System (INIS)

    Uehara, Toshiisa

    1987-01-01

    Clinical evaluation of the quantitative analysis of Tl-201 myocardial tomography by SPECT (Single Photon Emission Computed Tomography) was performed in comparison with visual evaluation. The method of quantitative analysis has been already reported in our previous paper. In this study, the program of re-standardization in the case of lateral myocardial infarction was added. This program was useful mainly for the evaluation of lesions in the left circumflex coronary artery. Regarding the degree of diagnostic accuracy of myocardial infarction in general, quantitative evaluation of myocardial SPECT images was highest followed by visual evaluation of myocardial SPECT images, and visual evaluation of myocardial planar images. However, in the case of anterior myocardial infarction, visual evaluation of myocardial SPECT images has almost the same detectability as quantitative evaluation of myocardial SPECT images. In the case of infero-posterior myocardial infarction, quantitative evaluation was superior to visual evaluation. As for specificity, quantitative evaluation of SPECT images was slightly inferior to visual evaluation of SPECT images. An infarction map was made by quantitative analysis and this enabled us to determine the infarction site, extent and degree according to easily recognizable patterns. As a result, the responsible coronary artery lesion could be inferred correctly and the calculated infarction score could be correlated with the residual left ventricular function after myocardial infarction. (author)

  13. delta-Opioid-induced pharmacologic myocardial hibernation during cardiopulmonary resuscitation.

    Science.gov (United States)

    Fang, Xiangshao; Tang, Wanchun; Sun, Shijie; Weil, Max Harry

    2006-12-01

    Cardiac arrest and cardiopulmonary resuscitation is an event of global myocardial ischemia and reperfusion, which is associated with severe postresuscitation myocardial dysfunction and fatal outcome. Evidence has demonstrated that mammalian hibernation is triggered by cyclic variation of a delta-opiate-like compound in endogenous serum, during which the myocardial metabolism is dramatically reduced and the myocardium tolerates the stress of ischemia and reperfusion without overt ischemic and reperfusion injury. Previous investigations also proved that the delta-opioid agonist elicited the cardioprotection in a model of regional ischemic intact heart or myocyte. Accordingly, we were prompted to search for an alternative intervention of pharmacologically induced myocardial hibernation that would result in rapid reductions of myocardial metabolism and therefore minimize the myocardial ischemic and reperfusion injury during cardiac arrest and cardiopulmonary resuscitation. Prospective, controlled laboratory study. University-affiliated research laboratory. In the series of studies performed in the established rat and pig model of cardiac arrest and cardiopulmonary resuscitation, the delta-opioid receptor agonist, pentazocine, was administered during ventricular fibrillation. : The myocardial metabolism reflected by the concentration of lactate, or myocardial tissue PCO2 and PO2, is dramatically reduced during cardiac arrest and cardiopulmonary resuscitation. These are associated with less severe postresuscitation myocardial dysfunction and longer duration of postresuscitation survival. delta-Opioid-induced pharmacologic myocardial hibernation is an option to minimize the myocardial ischemia and reperfusion injury during cardiac arrest and cardiopulmonary resuscitation.

  14. Myocardial perfusion imaging in hyperthrophic cardiomyopathy

    International Nuclear Information System (INIS)

    Moorin, B.

    1998-01-01

    Full text: Patients with Hyperthrophic Cardiomyopathy (HCM) frequently suffer from syncope and cardiac arrest which may lead to sudden death. This is most often caused by ventricular arrhythmia's in adults, however in young patients the mechanisms are thought to be different. Ischaemia may play a significant role even in young asymptomatic HCM patients. The mechanisms of ischaemic development in HCM differ from those in the 'normal' myocardium (Due to intramural small vessel abnormalities and abnormal myocellular architecture). In HCM the coronary microcirculation is most often affected and massive hypertrophy means more energy is required to promote contraction thus increasing oxygen demand and compounding the effects of any ischaemic changes. A case of a 12 year old HCM patient is presented who has symptoms of syncope associated with exercise whose mother died suddenly of cardiac arrest developed from HCM. A myocardial perfusion rest/stress study was undertaken to detect any underlying myocardial ischaemia. Myocardial perfusion scintigraphy demonstrates any reduction in the microcirculation in addition to that present in the macrocirculation, unlike angiography which will only detect the latter. In this case the scan clearly showed evidence of ischaemia in the lateral wall and this may be an explanation for her episodes of syncope. We suggest an algorithm or the routine work-up of young patients with HCM which makes aggressive use of myocardial perfusion imaging to detect ischaemic changes. This may identify patients who are at higher risk and will assist with treatment decisions. We feel myocardial perfusion scintigraphy is a sensitive non-invasive accurate method of detecting microcirculatory ischaemia and is thus invaluable in HCM patients

  15. Clinical use of 201Tl myocardial scintigraphy

    International Nuclear Information System (INIS)

    Senda, Kohei; Imaeda, Takeyoshi; Kato, Toshimitsu; Asada, Shuichi; Doi, Hidetaka

    1977-01-01

    Myocardial imaging with 201 Tl and scinticamera was studied experimentally using specially designed phantoms and clinically in 23 patients with myocardial infarction or other heart disease. In the phantom experiment, quality of image, accumulative count rate, and detectability of the defect were compared to obtain the best technique for their detection, using four different collimators, i.e., converging, pin-hole, 4000-hole, and 140 keV high-resolution, at two photopeak levels of 201 Tl of 75 and 167 keV, and combining a radiation absorber. In patient examination, myocardial images taken at different periods after injection, different detecting conditions of the scinticamera, and various detecting projections were compared. Images of the converging collimator at the 75 keV photopeak revealed considerably higher accumulative counts and relatively higher quality than those of other detecting conditions. It was necessary to take as many images as possible in various projections, in order to detect the location and size of the myocardial ischemic lesion because the lesion was demonstrated as a clear defect only in profile. It became evident that images taken between about 25 and 90 min delineated the myocardium more clearly than those taken in other periods. Normal images taken in 8 patients without ischemic heart disease appeared in the shape of a doughnut of horseshoe, demonstrating mainly the left venticular myocardium. The image was faint in the region of the aortic or mitral valve and thin in the region of the apical wall. A faint image of the right ventricular myocardium was sometimes seen. In 3 patients with valvular heart disease, findings suggested changes in the thickness of myocardium and the distribution of coronary blood flow. In 11 of 12 patients with old myocardial infarction, the location and size of the lesion was detected. (Evans, J.)

  16. Inflammatory and apoptotic remodeling in autonomic nervous system following myocardial infarction.

    Directory of Open Access Journals (Sweden)

    Chen Gao

    Full Text Available Chronic myocardial infarction (MI triggers pathological remodeling in the heart and cardiac nervous system. Abnormal function of the autonomic nervous system (ANS, including stellate ganglia (SG and dorsal root ganglia (DRG contribute to increased sympathoexcitation, cardiac dysfunction and arrythmogenesis. ANS modulation is a therapeutic target for arrhythmia associated with cardiac injury. However, the molecular mechanism involved in the pathological remodeling in ANS following cardiac injury remains to be established.In this study, we performed transcriptome analysis by RNA-sequencing in thoracic SG and (T1-T4 DRG obtained from Yorkshire pigs following either acute (3 to 5 hours or chronic (8 weeks myocardial infarction. By differential expression and weighted gene co-expression network analysis (WGCNA, we identified significant transcriptome changes and specific gene modules in the ANS tissues in response to myocardial infarction at either acute or chronic phases. Both differential expressed genes and the member genes of the WGCNA gene module associated with post-infarct condition were significantly enriched for inflammatory signaling and apoptotic cell death. Targeted validation analysis supported a significant induction of inflammatory and apoptotic signal in both SG and DRG following myocardial infarction, along with cellular evidence of apoptosis induction based on TUNEL analysis. Importantly, these molecular changes were observed specifically in the thoracic segments but not in their counterparts obtained from lumbar sections.Myocardial injury leads to time-dependent global changes in gene expression in the innervating ANS. Induction of inflammatory gene expression and loss of neuron cell viability in SG and DRG are potential novel mechanisms contributing to abnormal ANS function which can promote cardiac arrhythmia and pathological remodeling in myocardium.

  17. Synthesis and Characterization of Injectable Hydrogels with Varying Collagen–Chitosan–Thymosin β4 Composition for Myocardial Infarction Therapy

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    Achmad Dzihan Shaghiera

    2018-04-01

    Full Text Available Thirty percent of global mortalities are caused by cardiovascular disease, and 54% of the aforementioned amount is instigated by ischemic heart disease that triggered myocardial infarction. Myocardial infarction is due to blood flow cessation in certain coronary arteries that causes lack of oxygen (ischemia and stimulates myocardial necrosis. One of the methods to treat myocardial infarction consists in injecting cells or active biomolecules and biomaterials into heart infarction locations. This study aimed to investigate the characteristics of a collagen–chitosan-based hydrogel with variations in its chitosan composition. The prepared hydrogels contained thymosin β4 (Tβ4, a 43-amino acid peptide with angiogenic and cardioprotective properties which can act as a bioactive molecule for the treatment of myocardial infarction. A morphological structure analysis showed that the hydrogels lacked interconnecting pores. All samples were not toxic on the basis of a cytotoxicity test. A histopathological anatomy test showed that the collagen–chitosan–thymosin β4 hydrogels could stimulate angiogenesis and epicardial heart cell migration, as demonstrated by the evaluation of the number of blood vessels and the infiltration extent of myofibroblasts.

  18. Mesenchymal stromal cells of osteosarcoma patients do not show evidence of neoplastic changes during long-term culture.

    Science.gov (United States)

    Buddingh, Emilie P; Ruslan, S Eriaty N; Reijnders, Christianne M A; Szuhai, Karoly; Kuijjer, Marieke L; Roelofs, Helene; Hogendoorn, Pancras C W; Maarten Egeler, R; Cleton-Jansen, Anne-Marie; Lankester, Arjan C

    2015-01-01

    In vitro expanded mesenchymal stromal cells (MSCs) are increasingly used as experimental cellular therapy. However, there have been concerns regarding the safety of their use, particularly with regard to possible oncogenic transformation. MSCs are the hypothesized precursor cells of high-grade osteosarcoma, a tumor with often complex karyotypes occurring mainly in adolescents and young adults. To determine if MSCs from osteosarcoma patients could be predisposed to malignant transformation we cultured MSCs of nine osteosarcoma patients and five healthy donors for an average of 649 days (range 601-679 days). Also, we compared MSCs derived from osteosarcoma patients at diagnosis and from healthy donors using genome wide gene expression profiling. Upon increasing passage, increasing frequencies of binucleate cells were detected, but no increase in proliferation suggestive of malignant transformation occurred in MSCs from either patients or donors. Hematopoietic cell specific Lyn substrate 1 (HLCS1) was differentially expressed (fold change 0.25, P value 0.0005) between MSCs of osteosarcoma patients (n = 14) and healthy donors (n = 9). This study shows that although HCLS1 expression was downregulated in MSCs of osteosarcoma patients and binucleate cells were present in both patient and donor derived MSCs, there was no evidence of neoplastic changes to occur during long-term culture.

  19. Nuclear abnormalities in cells from nasal epithelium: a promising assay to evaluate DNA damage related to air pollution in infants

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    Michelle Mergener

    2014-12-01

    Full Text Available OBJECTIVES: This study intends to provide a quick, easy, and inexpensive way to assess nuclear abnormalities such as micronuclei and bud frequencies; binucleated, karyorrhectic, karyolytic, pycnotic, and condensed chromatin cells in nasal scrapings of infants, which are particularly important for conducting genotoxic studies related to the inhaled atmosphere in pediatric populations. METHODS: Nasal swab samples were collected from 40 infants under 12 months of age using a small cytobrush. 2,000 cells from each infant sample were analyzed and classified according to the frequency of nuclear abnormalities. RESULTS: Rates of nuclear abnormalities found agree with values reported in other studies of neonates and children. This study found 0.13% of cells with micronuclei; 1.20% karyorrhexis; 0.03% pyknosis; 10.85% karyolysis; 1.11% condensed chromatin; 0.54 binucleated cells; and 0.02% nuclear bud. Differences were not observed between genders or environmental passive smoking, nor was any age correlation found. CONCLUSION: The assay proposed here is suitable for assessing the frequency of nuclear abnormalities from nasal cells in infants.

  20. Molecular Basis of Cardioprotective Effect of Antioxidant Vitamins in Myocardial Infarction

    Science.gov (United States)

    Rodrigo, Ramón; Feliú, Felipe; Hasson, Daniel

    2013-01-01

    Acute myocardial infarction (AMI) is the leading cause of mortality worldwide. Major advances in the treatment of acute coronary syndromes and myocardial infarction, using cardiologic interventions, such as thrombolysis or percutaneous coronary angioplasty (PCA) have improved the clinical outcome of patients. Nevertheless, as a consequence of these procedures, the ischemic zone is reperfused, giving rise to a lethal reperfusion event accompanied by increased production of reactive oxygen species (oxidative stress). These reactive species attack biomolecules such as lipids, DNA, and proteins enhancing the previously established tissue damage, as well as triggering cell death pathways. Studies on animal models of AMI suggest that lethal reperfusion accounts for up to 50% of the final size of a myocardial infarct, a part of the damage likely to be prevented. Although a number of strategies have been aimed at to ameliorate lethal reperfusion injury, up to date the beneficial effects in clinical settings have been disappointing. The use of antioxidant vitamins could be a suitable strategy with this purpose. In this review, we propose a systematic approach to the molecular basis of the cardioprotective effect of antioxidant vitamins in myocardial ischemia-reperfusion injury that could offer a novel therapeutic opportunity against this oxidative tissue damage. PMID:23936799

  1. Molecular Basis of Cardioprotective Effect of Antioxidant Vitamins in Myocardial Infarction

    Directory of Open Access Journals (Sweden)

    Ramón Rodrigo

    2013-01-01

    Full Text Available Acute myocardial infarction (AMI is the leading cause of mortality worldwide. Major advances in the treatment of acute coronary syndromes and myocardial infarction, using cardiologic interventions, such as thrombolysis or percutaneous coronary angioplasty (PCA have improved the clinical outcome of patients. Nevertheless, as a consequence of these procedures, the ischemic zone is reperfused, giving rise to a lethal reperfusion event accompanied by increased production of reactive oxygen species (oxidative stress. These reactive species attack biomolecules such as lipids, DNA, and proteins enhancing the previously established tissue damage, as well as triggering cell death pathways. Studies on animal models of AMI suggest that lethal reperfusion accounts for up to 50% of the final size of a myocardial infarct, a part of the damage likely to be prevented. Although a number of strategies have been aimed at to ameliorate lethal reperfusion injury, up to date the beneficial effects in clinical settings have been disappointing. The use of antioxidant vitamins could be a suitable strategy with this purpose. In this review, we propose a systematic approach to the molecular basis of the cardioprotective effect of antioxidant vitamins in myocardial ischemia-reperfusion injury that could offer a novel therapeutic opportunity against this oxidative tissue damage.

  2. Cardioprotective effect of vitamin D2 on isoproterenol-induced myocardial infarction in diabetic rats.

    Science.gov (United States)

    El Agaty, Sahar M

    2018-03-08

    To assess the effect of vitamin D 2 and to elucidate the underlying mechanisms on acute myocardial injury induced by isoproterenol (ISO) in diabetic rats. Rats were divided into control rats, diabetic rats (DM), diabetic rats received ISO (DM-ISO), and diabetic rats pretreated with vitamin D 2 and received ISO (DM-D 2 -ISO). Vitamin D 2 pretreatment significantly decreased fasting glucose and myocardial malondialdehyde, associated with increased insulin, myocardial glutathione and superoxide dismutase in DM-D 2 -ISO versus DM-ISO. The serum triglycerides, total cholesterol, and LDL were significantly decreased, along with increased HDL and adiponectin. Poly-ADP ribose polymerase, cyclooxygenase-2, tumour necrosis factor alpha, interleukin-6, caspase-3, BAX, and p53 were significantly downregulated in myocardium of DM-D 2 -ISO versus DM-ISO. Histological studies showed diminished inflammatory cells infiltration in myocardium of DM-D 2 -ISO versus DM-ISO. Vitamin D 2 ameliorates hyperglycaemia, dyslipidaemia, redox imbalance, inflammatory and apoptotic processes, protecting the myocardium of diabetic rats against acute myocardial infarction.

  3. Mechanism of the Protective Effect of Yulangsan Flavonoid on Myocardial Ischemia/Reperfusion Injury in Rats

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    Xudong Zhang

    2014-09-01

    Full Text Available Aims: Effect and mechanism of Yulangsan flavonoid (YLSF on rat myocardial ischemia/reperfusion injury (MI/RI has been investigated. Methods: Sprague-Dawley (SD rats were randomly divided into seven groups (sham group, model group and NS group: 2 mL of normal saline/kg body weight was administered; diltiazem group: 5 mg of diltiazem hydrochloride/kg body weight was administered; YLSFL, YLSFM and YLSFH groups: 20, 40 and 80 mg of YLSF/kg body weight was administered and the MI/RI model was established. Myocardial infarct area, levels of myocardial enzymes and nitric oxide synthase (NOS were measured. Caspase-3 and adenine nucleotide translocator-1 (ANT1 mRNA expression were evaluated by reverse transcription polymerase chain reaction (RT-PCR. Pathological structure and cardiocyte ultrastructure were also analysed. Results: Compared with the MI/RI group, pretreatment with YLSF or diltiazem hydrochloride decreased the infarct area, levels of inducible nitric oxide synthase (iNOS, caspase-3 as well as the leakage of myocardial enzyme and increased activities of total nitric oxide synthase (tNOS as well as constitutive nitric oxide synthase (cNOS. Cellular edema and the infiltration of inflammatory cells were alleviated. Conclusions: The experiment showed that YLSF protected the heart against MI/RI, possibly by reducing lipid peroxidation damage, regulating NOS activity and modulating the apoptosis genes expression.

  4. Comparison of blood biochemics between acute myocardial infarction models with blood stasis and simple acute myocardial infarction models in rats

    International Nuclear Information System (INIS)

    Qu Shaochun; Yu Xiaofeng; Wang Jia; Zhou Jinying; Xie Haolin; Sui Dayun

    2010-01-01

    Objective: To construct the acute myocardial infarction models in rats with blood stasis and study the difference on blood biochemics between the acute myocardial infarction models with blood stasis and the simple acute myocardial infarction models. Methods: Wistar rats were randomly divided into control group, acute blood stasis model group, acute myocardial infarction sham operation group, acute myocardial infarction model group and of acute myocardial infarction model with blood stasis group. The acute myocardial infarction models under the status of the acute blood stasis in rats were set up. The serum malondialdehyde (MDA), nitric oxide (NO), free fatty acid (FFA), tumor necrosis factor-α (TNF-α) levels were detected, the activities of serum superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and the levels of prostacycline (PGI2), thromboxane A 2 (TXA 2 ) and endothelin (ET) in plasma were determined. Results: There were not obvious differences in MDA, SOD, GSH-Px and FFA between the acute myocardial infarction models with blood stasis in rats and the simple acute myocardial infarction models (P 2 and NO, and the increase extents of TXA 2 , ET and TNF-α in the acute myocardial infarction models in rats with blood stasis were higher than those in the simple acute myocardial infarction models (P 2 and NO, are significant when the acute myocardial infarction models in rats with blood stasis and the simple acute myocardial infarction models are compared. The results show that it is defective to evaluate pharmacodynamics of traditional Chinese drug with only simple acute myocardial infarction models. (authors)

  5. Tissue Inhibitor of Matrix Metalloproteinase-1 Promotes Myocardial Fibrosis by Mediating CD63-Integrin β1 Interaction.

    Science.gov (United States)

    Takawale, Abhijit; Zhang, Pu; Patel, Vaibhav B; Wang, Xiuhua; Oudit, Gavin; Kassiri, Zamaneh

    2017-06-01

    Myocardial fibrosis is excess accumulation of the extracellular matrix fibrillar collagens. Fibrosis is a key feature of various cardiomyopathies and compromises cardiac systolic and diastolic performance. TIMP1 (tissue inhibitor of metalloproteinase-1) is consistently upregulated in myocardial fibrosis and is used as a marker of fibrosis. However, it remains to be determined whether TIMP1 promotes tissue fibrosis by inhibiting extracellular matrix degradation by matrix metalloproteinases or via an matrix metalloproteinase-independent pathway. We examined the function of TIMP1 in myocardial fibrosis using Timp1 -deficient mice and 2 in vivo models of myocardial fibrosis (angiotensin II infusion and cardiac pressure overload), in vitro analysis of adult cardiac fibroblasts, and fibrotic myocardium from patients with dilated cardiomyopathy (DCM). Timp1 deficiency significantly reduced myocardial fibrosis in both in vivo models of cardiomyopathy. We identified a novel mechanism for TIMP1 action whereby, independent from its matrix metalloproteinase-inhibitory function, it mediates an association between CD63 (cell surface receptor for TIMP1) and integrin β1 on cardiac fibroblasts, initiates activation and nuclear translocation of Smad2/3 and β-catenin, leading to de novo collagen synthesis. This mechanism was consistently observed in vivo, in cultured cardiac fibroblasts, and in human fibrotic myocardium. In addition, after long-term pressure overload, Timp1 deficiency persistently reduced myocardial fibrosis and ameliorated diastolic dysfunction. This study defines a novel matrix metalloproteinase-independent function of TIMP1 in promoting myocardial fibrosis. As such targeting TIMP1 could prove to be a valuable approach in developing antifibrosis therapies. © 2017 American Heart Association, Inc.

  6. Cardiac cell damage in hypertrophic cardiomyopathy evaluated by beta-methyl-branched fatty acid analogue, iodine-123-15-(p-iodophenyl)-3-(R,S)-methylpen-tadecanoic acid (BMIPP) myocardial fatty-acid imaging and late gadolinium-enhanced contrast magnetic resonance imaging. Usefulness of combining the two techniques

    International Nuclear Information System (INIS)

    Kawade, Masafumi; Teraoka, Kunihiko; Hirano, Masaharu; Igarashi, Yuko; Yamada, Masao; Chikamori, Taishiro; Takazawa, Kenji; Yamashina, Akira

    2011-01-01

    Late gadolinium-enhanced (LGE) magnetic resonance imaging (MRI) has been found to be a highly valuable imaging modality for myocardial characterization in cases of hypertrophic cardiomyopathy (HCM). In addition, abnormalities of BMIPP uptake have also been recognized in HCM. In this study, we hypothesized that abnormalities of fatty acid uptake and metabolism may be detected before fibrosis can be recognized on cardiovascular MRI in patients with HCM. Twenty-four patients with HCM were examined by both BMIPP myocardial fatty acid imaging and LGE MRI, and the results of the two imaging methods were compared. BMIPP uptake abnormalities were recognized in 23 of the 24 HCM patients (95.8%) and 126 out of the 408 segments (30.9%) examined, and were most frequently located in the interventricular septum and anterior wall of the left ventricle, the inferior wall and apex of the heart. Areas of LGE were recognized in 18 of the 24 HCM patients (75%) and 50 of the 408 segments (12.2%) examined, and were most frequently located in the interventricular septum of the left ventricle. Double-positive results of both BMIPP uptake abnormalities and LGE were recognized in 18 of the 24 cases (75.0%) and 45 of the 408 segments (11.0%) examined. Double-positive results were noted most frequently in the interventricular septum of the left ventricle and the anterior wall. The areas showing BMIPP uptake abnormalities were more extensive than those showing LGE on MRI. In addition, the positivity rate for BMIPP uptake abnormalities in areas showing LGE on MRI was considerably higher than that of LGE positivity in areas positive for BMIPP uptake abnormalities. These results are not contradictory to our hypothesis. Therefore, differences between the examination methods in terms of the extent and positivity rate in cases of HCM may be related to the stage of progression of the cardiac muscle cell damage in cases of HCM. Thus, the use of both examinations together might be useful in the

  7. Quantitative assessment of myocardial blood flow by measurement of fractional myocardial uptake of 201Tl

    International Nuclear Information System (INIS)

    Yonekura, Yoshiharu; Ishii, Yasushi; Torizuka, Kanji; Kadota, Kazunori; Kambara, Hirofumi

    1980-01-01

    Fractional Myocardial uptake of 201 Tl was measured for the quantitative assessment of myocardial blood flow in coronary artery disease (CAD). 10 normals and 28 CAD, 7 of which have less than 50% stenosis (CAD I) and 21 of which have more than 50% stenosis (CAD II) in the proximal portion of coronary arteries, were studied at rest and with submaximal exercise loading by bicycle ergometer. After intravenous injection of 201 Tl, its rapid transport process was recorded during the initial 5 minutes by a scintillation camera and a minicomputer. Total injected dosage (T) was obtained from the counts of the entire chest region during the initial passage of the tracer through the heart and lung. Myocardial uptake (M) was counted with the same geometry from the subsequent accumulation within the myocardial region with subtraction of the background activities in the upper mediastinal region (B). The fractional myocardial uptake of 201 Tl ((M-B)/T) is assumed to be proportional to the fractional myocardial blood flow to cardiac output (MBF/CO) according to the indicator fractionation principle. The average value of MBF/CO at rest in CAD (4.11 +- 1.12%) was significantly greater than in normals (3.36 +- 0.49%), which may be caused by an increased left ventricular mass in CAD. Change rate of MBF/CO on the exercise loading was significantly less in CAD I (1.36 +- 0.14) and in CAD II (1.11 +- 0.21) than in normals (1.75 +- 0.11). MBF/CO increased proportionally to the increment of the double product of heart rate and systolic blood pressure by exercise loading in normals, whereas it didn't in CAD. The sensitivity of this method was superior to the stress electrocardiogram and the stress myocardial perfusion imaging, not only in CAD II but also in CAD I. This result indicated that this type of global assessment of the myocardial reserve capacity is valuable in addition to the simple stress myocardial perfusion imaging. (author)

  8. Myocardial overexpression of TIMP3 after myocardial infarction exerts beneficial effects by promoting angiogenesis and suppressing early proteolysis.

    Science.gov (United States)

    Takawale, Abhijit; Zhang, Pu; Azad, Abul; Wang, Wang; Wang, Xiuhua; Murray, Allan G; Kassiri, Zamaneh

    2017-08-01

    Myocardial infarction (MI) results in loss of cardiomyocytes, adverse extracellular matrix (ECM) and structural remodeling, and left ventricular (LV) dilation and dysfunction. Tissue inhibitors of metalloproteinase (TIMPs) inhibit matrix metalloproteinases (MMPs), the main regulators of ECM turnover. TIMPs also have MMP-independent functions. TIMP3 levels are reduced in the heart within 24 h of MI in mice. We investigated if overexpression of TIMP3 post-MI limits adverse remodeling and LV dilation and dysfunction. MI was induced by left anterior descending coronary artery ligation in 10- to 12-wk-old male C57BL/6J mice, and adenoviral constructs expressing human (h)TIMP3 (Ad-hTIMP3) or no TIMP (Ad-Null) were injected in the peri-infarct zone (5.4 × 10 7 plaque-forming units/heart, 5 injections/heart). Cardiac function assessed by echocardiography showed improved LV physiology and reduced LV dilation after TIMP3 overexpression compared with the Ad-Null-MI group. Post-MI adverse remodeling was attenuated in the Ad-hTIMP3-MI group, as assessed by greater cardiomyocyte density, less infarct expansion, and ECM disruption. TIMP3 overexpression blunted the early rise in proteolytic activities post-MI. A higher density of coronary arteries and a greater number of proliferating endothelial cells were detected in the infarct and peri-infarct regions in the Ad-hTIMP3-MI group compared with the Ad-Null-MI group. In vitro three-dimensional angiogenesis assay confirmed that recombinant TIMP3 promotes angiogenesis in human endothelial cells, although biphasically and in a dose-dependent manner. Intriguingly, overexpression of Ad-hTIMP3 at 10-fold higher concentration had no beneficial effects, consistent with antiangiogenic effects of TIMP3 at higher doses. In conclusion, optimal overexpression of TIMP3 can be a promising therapeutic approach to limit adverse post-MI remodeling by dually inhibiting early proteolysis and promoting angiogenesis. NEW & NOTEWORTHY Here, we report

  9. Use of resting myocardial scintigraphy during chest pain to exclude diagnosis of acute myocardial infarction

    International Nuclear Information System (INIS)

    Barbirato, Gustavo Borges; Azevedo, Jader Cunha de; Felix, Renata Christian Martins; Correa, Patricia Lavatori; Volschan, Andre; Viegas, Monica; Pimenta, Lucia; Dohmann, Hans Fernando Rocha; Mesquita, Evandro Tinoco; Mesquita, Claudio Tinoco

    2009-01-01

    Background: Images of myocardial perfusion taken during an episode of chest pain have been used for patients in the emergency department. Objective: To evaluate the operating characteristics of 99m Tc-Tetrofosmin scintigraphy during an episode of chest pain to exclude the diagnosis of cute myocardial infarction. Methods: One hundred and eight patients admitted with chest pain, or up to four hours after the end of symptoms and non diagnostic electrocardiogram, underwent resting scintigraphy and measurement of troponin I concentrations. Patients with a history of myocardial infarction (MI) were not excluded (24 patients). Troponin I concentrations were determined at admission and 6 hours later. Nuclear physicians performed a blind analysis of the images, and myocardial infarction was confirmed whenever troponin I level increase was three times that of the control. Results: Resting perfusion image was abnormal in all 6 patients with MI. Only 1 patient had a normal image and increased troponin levels. Fifty-five patients had positive images without MI, and 46 patients had normal images and troponin levels. The prevalence of the disease was 6.5%. The sensitivity and specificity of the resting images during an episode of chest pain to diagnose MI was 85.7% and 45.5%, respectively. The negative predictive value was 97.7%. Conclusion: Patients undergoing chest pain protocol with SPECT showed an excellent negative predictive value to exclude diagnosis of myocardial infarction. These results suggest that resting perfusion image is an important tool at the chest pain unit. (author)

  10. ST segment elevation after myocardial infarction: Viability or ventricular dysfunction? Comparison with myocardial scintigraphy

    International Nuclear Information System (INIS)

    Chalela, William Azem; Soares, J. Jr.; Meneghetti, J.C.; Olivera, C.G.; Moffa, P.J.; Falcao, A.M.; Ramires, J.A.F.

    2004-01-01

    The detection of viable myocardium after myocardial infarction is an important indication for revascularization. We compared exercise-induced ST segment elevation with reversibility at Thallium-201 SPECT scintigraphy and regional wall motion assessment by ventriculography. Thirty two patients with previous myocardial infarction and with left ventricular ejection fraction of < 50% were studied. Patients underwent coronary angiography and Thallium-201 SPECT scintigraphy with re-injection protocol before and after coronary artery bypass graft surgery. Group I comprised 11 patients with ST segment elevation during treadmill stress testing. Group II comprised 21 patients without ST segment elevation. Minimal or moderate hypokinesis was present in 2 patients of Group I and in 4 patients of Group II. Nine patients of Group I and 17 patients of Group II had severe hypokinetic, akinetic or dyskinetic myocardium. Scintigraphy revealed reversibility in the myocardial infarction area in 4 patients from Group I (36.4%) and 11 (52.4%) patients from Group II. Improvement in perfusion after coronary artery bypass grafting was observed in 4 patients from Group I and 8 patients from Group II. Sensitivity, specificity, accuracy, and positive and negative predictive values of ST segment elevation were 33.3, 70.6, 55.2, 44.5 and 60% respectively. It was concluded that exercise-induced ST segment elevation after myocardial infarction is present more frequently in cases of severe regional myocardial dysfunction. (author)

  11. Evaluation of myocardial damage in Duchenne's muscular dystrophy with thallium-201 myocardial SPECT

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    Tamura, Takuhisa; Shibuya, Noritoshi (Kawatana National Hospital, Nagasaki (Japan)); Hashiba, Kunitake; Oku, Yasuhiko; Mori, Hideki; Yano, Katsusuke

    1993-01-01

    Myocardial damage and cardiopulmonary functions in patients with Duchenne's muscular dystrophy (DMD) were assessed using thallium-201 myocardial single-photon emission computed tomography (SPECT) and technetium-99m multigated radionuclide angiography. Twenty-five patients with DMD were divided into 4 groups according to percent of perfusion defect (%PD) calculated by the bull's-eye method and age. PD was detected in 24 (96.0%) of 25 patients with DMD, and it spread from the left ventricular lateral wall to the anterior wall and/or interventricular septum. PD was detected even in a 6-year-old DMD boy. Patients in Group I (%PD[>=]10% and age<15 years old) were shown to have a higher risk of left-sided heart failure without respiratory failure. Patients in Group II (%PD[>=]10 and age[>=]15) showed decreased pulmonary function and worsened arterial blood gas values as compared with Group IV (%PD<10 and age[>=]15). There was no significant difference in cardiac function among the 4 groups. It is postulated that myocardial damage in Group II patients is dependent primarily on a deficiency of dystrophin and on chronic respiratory failure, and that some of them are at risk of cardiopulmonary failure. It is concluded that myocardial SPECT is useful for the early diagnosis of myocardial damage and evaluation of cardiopulmonary function in DMD patients. (author).

  12. Evaluation of myocardial damage in Duchenne's muscular dystrophy with thallium-201 myocardial SPECT

    International Nuclear Information System (INIS)

    Tamura, Takuhisa; Shibuya, Noritoshi; Hashiba, Kunitake; Oku, Yasuhiko; Mori, Hideki; Yano, Katsusuke.

    1993-01-01

    Myocardial damage and cardiopulmonary functions in patients with Duchenne's muscular dystrophy (DMD) were assessed using thallium-201 myocardial single-photon emission computed tomography (SPECT) and technetium-99m multigated radionuclide angiography. Twenty-five patients with DMD were divided into 4 groups according to percent of perfusion defect (%PD) calculated by the bull's-eye method and age. PD was detected in 24 (96.0%) of 25 patients with DMD, and it spread from the left ventricular lateral wall to the anterior wall and/or interventricular septum. PD was detected even in a 6-year-old DMD boy. Patients in Group I (%PD≥10% and age<15 years old) were shown to have a higher risk of left-sided heart failure without respiratory failure. Patients in Group II (%PD≥10 and age≥15) showed decreased pulmonary function and worsened arterial blood gas values as compared with Group IV (%PD<10 and age≥15). There was no significant difference in cardiac function among the 4 groups. It is postulated that myocardial damage in Group II patients is dependent primarily on a deficiency of dystrophin and on chronic respiratory failure, and that some of them are at risk of cardiopulmonary failure. It is concluded that myocardial SPECT is useful for the early diagnosis of myocardial damage and evaluation of cardiopulmonary function in DMD patients. (author)

  13. VO(2peak), myocardial hypertrophy, and myocardial blood flow in endurance-trained men.

    Science.gov (United States)

    Laaksonen, Marko S; Heinonen, Ilkka; Luotolahti, Matti; Knuuti, Juhani; Kalliokoski, Kari K

    2014-08-01

    Endurance training induces cardiovascular and metabolic adaptations, leading to enhanced endurance capacity and exercise performance. Previous human studies have shown contradictory results in functional myocardial vascular adaptations to exercise training, and we hypothesized that this may be related to different degrees of hypertrophy in the trained heart. We studied the interrelationships between peak aerobic power (V˙O2peak), myocardial blood flow (MBF) at rest and during adenosine-induced vasodilation, and parameters of myocardial hypertrophy in endurance-trained (ET, n = 31) and untrained (n = 17) subjects. MBF and myocardial hypertrophy were studied using positron emission tomography and echocardiography, respectively. Both V˙O2peak (P negatively with adenosine-stimulated MBF, but when LV mass was taken into account as a partial correlate, this correlation disappeared. The present results show that increased LV mass in ET subjects explains the reduced hyperemic myocardial perfusion in this subject population and suggests that excessive LV hypertrophy has negative effect on cardiac blood flow capacity.

  14. Detecting Myocardial Ischemia With 99mTechnetium-Tetrofosmin Myocardial Perfusion Imaging in Ischemic Stroke.

    Science.gov (United States)

    Giannopoulos, Sotirios; Markoula, Sofia; Sioka, Chrissa; Zouroudi, Sofia; Spiliotopoulou, Maria; Naka, Katerina K; Michalis, Lampros K; Fotopoulos, Andreas; Kyritsis, Athanassios P

    2017-10-01

    To assess the myocardial status in patients with stroke, employing myocardial perfusion imaging (MPI) with 99m Technetium-tetrofosmin ( 99m Tc-TF)-single-photon emission computed tomography (SPECT). Fifty-two patients with ischemic stroke were subjected to 99m Tc-TF-SPECT MPI within 1 month after stroke occurrence. None of the patients had any history or symptoms of coronary artery disease or other heart disease. Myocardial perfusion imaging was evaluated visually using a 17-segment polar map. Myocardial ischemia (MIS) was defined as present when the summed stress score (SSS) was >4; MIS was defined as mild when SSS was 4 to 8, and moderate/severe with SSS ≥9. Patients with SSS >4 were compared to patients with SSS SSS >9 were compared to patients with SSS SSS, with the oldest age exhibiting the highest SSS ( P = .01). The association of age with SSS remained statistically significant in the multivariate analysis ( P = .04). The study suggested that more than half of patients with stroke without a history of cardiac disease have MIS. Although most of them have mild MIS, we suggest a thorough cardiological evaluation in this group of patients for future prevention of severe myocardial outcome.

  15. G-CSF in acute myocardial infarction - experimental and clinical findings.

    Science.gov (United States)

    Ince, Hüseyin; Petzsch, Michael; Rehders, Tim C; Dunkelmann, Simone; Nienaber, Christoph A

    2006-09-01

    Early data from clinical studies suggest that intracoronary injection of autologous progenitor cells may beneficially affect postinfarction remodeling and perfusion. Beyond intracoronary infusion of autologous bone marrow mononuclear CD34+ cells (MNCCD34+), mobilization of stem cells by G-CSF has recently attracted attention because of various advantages such as the noninvasive nature of MNCCD34+ mobilization by subcutaneous injections. It is the aim of the present work to give an overview about the current experimental and clinical findings of G-CSF treatment in acute myocardial infarction.

  16. Quantitative analysis of thallium-201 myocardial scintigraphy

    International Nuclear Information System (INIS)

    Kanemoto, Nariaki; Hoer, G.; Johost, S.; Maul, F.-D.; Standke, R.

    1981-01-01

    The method of quantitative analysis of thallium-201 myocardial scintigraphy using computer assisted technique was described. Calculated indices are washout factor, vitality index and redistribution factor. Washout factor is the ratio of counts at certain period of time after exercise and immediately after exercise. This value is neccessary for the evaluation of redistribution to the ischemic areas in serial imagings to correct the Tl-201 washout from the myocardium under the assumption that the washout is constant in the whole myocardium. Vitality index is the ratio between the Tl-201 uptake in the region of interest and that of the maximum. Redistribution factor is the ratio of the redistribution in the region of interest in serial imagings after exercise to that of immediately after exercise. Four examples of exercise Tl-201 myocardial scintigrams and the quantitative analyses before and after the percutaneous transluminal coronary angioplasty were presented. (author)

  17. Toll-Like Receptors and Myocardial Inflammation

    Directory of Open Access Journals (Sweden)

    Yan Feng

    2011-01-01

    Full Text Available Toll-like receptors (TLRs are a member of the innate immune system. TLRs detect invading pathogens through the pathogen-associated molecular patterns (PAMPs recognition and play an essential role in the host defense. TLRs can also sense a large number of endogenous molecules with the damage-associated molecular patterns (DAMPs that are produced under various injurious conditions. Animal studies of the last decade have demonstrated that TLR signaling contributes to the pathogenesis of the critical cardiac conditions, where myocardial inflammation plays a prominent role, such as ischemic myocardial injury, myocarditis, and septic cardiomyopathy. This paper reviews the animal data on (1 TLRs, TLR ligands, and the signal transduction system and (2 the important role of TLR signaling in these critical cardiac conditions.

  18. Regional myocardial perfusion of cardioplegic solutions

    International Nuclear Information System (INIS)

    Eugene, J.; Lyons, K.P.; Ott, R.A.; Gelezunas, V.L.; Chang, C.W.; Kowall, M.G.; Haiduc, N.J.

    1987-01-01

    We compared the regional myocardial perfusion of blood cardioplegic solution (BCP) and crystalloid cardioplegic solution (CCP) in 14 mongrel dogs. Cardiopulmonary bypass was established at 28 degrees C, and a hydraulic occluder was placed around the proximal left anterior descending (LAD) coronary artery. In group 1 (N = 7) collateral coronary arteries were ligated; in group 2 (N = 7) collateral coronary arteries were left in situ. After the aorta was clamped, BCP and CCP were alternately perfused at 200 ml/min. The occluder was inflated to produce moderate, severe, and critical LAD stenosis, and regional perfusion was measured by xenon-133 washout with the Silicon Avalanche Radiation Detector. BCP infusion produced a consistently higher aortic pressure, but CCP flow was better than BCP flow under all conditions, particularly without coronary collaterals. Regional myocardial perfusion of CCP is superior to BCP

  19. Heart failure due to severe myocardial calcification

    International Nuclear Information System (INIS)

    Takahashi, Shouichi; Maida, Kiyoshi; Yokoyama, Hitoshi; Tanaka, Shigeo

    1993-01-01

    A 28-year-old female who had had irradiation on the chest wall at the age of 5 as a remedy for keloid granulation after burn, recently developed congestive heart failure. Severe tricuspid regurgitation was demonstrated by echocardiography with a certain calcification in the cardiac shadow on chest radiogram. Calcified right ventricle and ventricular septum were noticed operatively, which disturbed ventricular motion and also caused tricuspid valve deformity. These calcified myocardium apparently corresponded with the irradiation field. After tricuspid valve replacement, she regained physical activity satisfactorily without congestive heart failure. Because she had no other known causes of cardiac calcification such as hypercalcemia, myocarditis, myocardial infarction or renal diseases, irradiation on the chest wall could be responsible for the severe myocardial calcification. (author)

  20. Myocardial production and release of MCP-1 and SDF-1 following myocardial infarction: differences between mice and man

    Directory of Open Access Journals (Sweden)

    Palasubramaniam Dharshan

    2011-09-01

    Full Text Available Abstract Background Stem cell homing to the heart is mediated by the release of chemo-attractant cytokines. Stromal derived factor -1 alpha (SDF-1a and monocyte chemotactic factor 1(MCP-1 are detectable in peripheral blood after myocardial infarction (MI. It remains unknown if they are produced by, and released from, the heart in order to attract stem cells to repair the damaged myocardium. Methods Murine hearts were studied for expression of MCP-1 and SDF-1a at day 3 and day 28 following myocardial infarction to determine whether production is increased following MI. In addition, we studied the coronary artery and coronary sinus (venous blood from patients with normal coronary arteries, stable coronary artery disease (CAD, unstable angina and MI to determine whether these cytokines are released from the heart into the systemic circulation following MI. Results Both MCP-1 and SDF-1a are constitutively produced and released by the heart. MCP-1 mRNA is upregulated following murine experimental MI, but SDF-1a is suppressed. There is less release of SDF-1a into the systemic circulation in patients with all stages of CAD including MI, mimicking the animal model. However MCP-1 release from the human heart following MI is also suppressed, which is the exact opposite of the animal model. Conclusions SDF-1a and MCP-1 release from the human heart are suppressed following MI. In the case of SDF-1a, the animal model appropriately reflects the human situation. However, for MCP-1 the animal model is the exact opposite of the human condition. Human observational studies like this one are paramount in guiding translation from experimental studies to clinical trials.

  1. Sodium 4-Phenylbutyrate Attenuates Myocardial Reperfusion Injury by Reducing the Unfolded Protein Response.

    Science.gov (United States)

    Takatori, Osamu; Usui, Soichiro; Okajima, Masaki; Kaneko, Shuichi; Ootsuji, Hiroshi; Takashima, Shin-Ichiro; Kobayashi, Daisuke; Murai, Hisayoshi; Furusho, Hiroshi; Takamura, Masayuki

    2017-05-01

    The unfolded protein response (UPR) plays a pivotal role in ischemia-reperfusion (I/R) injury in various organs such as heart, brain, and liver. Sodium 4-phenylbutyrate (PBA) reportedly acts as a chemical chaperone that reduces UPR. In the present study, we evaluated the effect of PBA on reducing the UPR and protecting against myocardial I/R injury in mice. Male C57BL/6 mice were subjected to 30-minute myocardial I/R, and were treated with phosphate-buffered saline (as a vehicle) or PBA. At 4 hours after reperfusion, mice treated with PBA had reduced serum cardiac troponin I levels and numbers of apoptotic cells in left ventricles (LVs) in myocardial I/R. Infarct size had also reduced in mice treated with PBA at 48 hours after reperfusion. At 2 hours after reperfusion, UPR markers, including eukaryotic initiation of the factor 2α-subunit, activating transcription factor-6, inositol-requiring enzyme-1, glucose-regulated protein 78, CCAAT/enhancer-binding protein (C/EBP) homologous protein, and caspase-12, were significantly increased in mice treated with vehicle compared to sham-operated mice. Administration of PBA significantly reduced the I/R-induced increases of these markers. Cardiac function and dimensions were assessed at 21 days after I/R. Sodium 4-phenylbutyrate dedicated to the improvement of cardiac parameters deterioration including LV end-diastolic diameter and LV fractional shortening. Consistently, PBA reduced messenger RNA expression levels of cardiac remodeling markers such as collagen type 1α1, brain natriuretic peptide, and α skeletal muscle actin in LV at 21 days after I/R. Unfolded protein response mediates myocardial I/R injury. Administration of PBA reduces the UPR, apoptosis, infarct size, and preserved cardiac function. Hence, PBA may be a therapeutic option to attenuate myocardial I/R injury in clinical practice.

  2. Interpretation of elevated plasma visfatin concentrations in patients with ST-elevation myocardial infarction.

    Science.gov (United States)

    Lu, Li-Fen; Wang, Chao-Ping; Yu, Teng-Hung; Hung, Wei-Chin; Chiu, Cheng-An; Chung, Fu-Mei; Tsai, I-Ting; Yang, Chih-Ying; Cheng, Ya-Ai; Lee, Yau-Jiunn; Yeh, Lee-Ren

    2012-01-01

    Visfatin is a cytokine that is expressed in many tissues, including the heart, and has been proposed to play a role in plaque destabilization leading to acute myocardial injury. The present study evaluates plasma levels of visfatin in acute ST-elevation myocardial infarction (STEMI) patients and examines the temporal changes in visfatin levels from the acute period to the subacute period to determine a correlation with the degree of myocardial ischemia. We evaluated 54 patients with STEMI. Circulating levels of visfatin and brain natriuretic peptide (BNP) were measured by ELISA. In addition, local expression of visfatin and BNP were detected by quantitative real-time polymerase chain reaction and immunohistochemical (IHC) analysis of left ventricular myocytes in a mouse model of myocardial infarction (MI). Plasma levels of visfatin were significantly increased in patients with STEMI on admission, relative to controls (effort angina patients and individuals without coronary artery disease). The visfatin levels reached a peak 24h after percutaneous coronary intervention (PCI) and then decreased toward the control range during the first week after PCI. The basal plasma visfatin levels were found to correlate with peak troponin-I, peak creatine kinase-MB, total white blood cell count, and BNP levels. Trend analyses confirmed that visfatin levels correlated with the number of diseased coronary arteries. Further, in MI mice, mRNA levels of visfatin and BNP were found to be higher than in sham-treated mice. IHC analysis showed that visfatin and BNP immunoreactivity was diffusely observable in left ventricular myocytes of the MI mice. This study indicates that plasma visfatin levels are significantly higher in STEMI patients and that these higher visfatin levels correlate with elevated levels of cardiac enzymes, suggesting that increased plasma visfatin may be closely related to the degree of myocardial damage. Copyright © 2011 Elsevier Ltd. All rights reserved.

  3. Myocardial fatty acid utilisation during exercise induced ischemia in patients with coronary artery disease

    Energy Technology Data Exchange (ETDEWEB)

    Virtanen, K.S. [First Dept. of Medicine, Helsinki Univ. Central Hospital (Finland); Nikkinen, P. [Dept. of Clinical Chemistry, Helsinki Univ. Central Hospital (Finland); Lindroth, L. [Medix Diacor Lab. Services, Ltd., Espoo (Finland); Kuikka, J.T. [Dept. of Clinical Physiology and Nuclear Medicine, Kuopio Univ. Hospital, Univ. of Kuopio and Niuvanniemi Hospital, Kuopio (Finland)

    2002-06-01

    Aim: Reversible or irreversible myocardial damage due to ischemia correlates with altered membrane functions of the cells. To compare myocardial free fatty acid (FFA) metabolism and flow during exercise induced ischemia we studied ten patients with coronary artery disease but without previous myocardial infarction. Methods: A series of post-exercise single-photon emission computed tomography (SPECT) measurements was performed after injection of {sup 123}I labelled heptadecanoic acid (HDA). Myocardial perfusion was estimated from the separately performed exercise-redistribution thallium study. Fatty acid metabolic rate, thallium uptake and washout were calculated for anterior, lateral, posterior and septal segments. Results: The more reduced post-exercise FFA metabolic rate (-63{+-}18%, mean {+-}1 SD) compared to flow (-36{+-}16%) was related to the severity of myocardial ischemia and wall motion abnormalities. Conclusion: In this small group of patients, the reduced post-exercise FFA metabolic rate tentatively suggests a parsimonious workload of the exercising myocardium by reducing oxygen consumption in patients with coronary artery disease. (orig.) [German] Ziel: Bei reversibler und irreversibler Myokardschaedigung infolge Ischaemie sind die Membranfunktionen der Zellen veraendert. Um myokardialen Metabolismus freier Fettsaeuren (FFA) und Durchblutung bei belastungsinduzierter Ischaemie zu vergleichen, untersuchten wir zehn Patienten mit Koronarinsuffizienz, aber ohne vorangegangenen Myokardinfarkt. Methoden: Nach Injektion von {sup 123}I-markierter Heptadekansaeure (HDA) wurde eine Serie von SPECT-Messungen nach Belastung aufgenommen. Die myokardiale Perfusion wurde abgeschaetzt durch die separat durchgefuehrte Thalliumverteilungsstudie nach Belastung. Fettsaeurestoffwechsel, Thallium-Uptake und -Washout wurden fuer die anterioren, posterioren und septalen Segmente berechnet. Ergebnisse: Eine eingeschraenktere FFA-Stoffwechselrate (-63{+-}18%, {+-}1 SD

  4. Moderate elevation of intracellular creatine by targeting the creatine transporter protects mice from acute myocardial infarction

    Science.gov (United States)

    Lygate, Craig A.; Bohl, Steffen; ten Hove, Michiel; Faller, Kiterie M.E.; Ostrowski, Philip J.; Zervou, Sevasti; Medway, Debra J.; Aksentijevic, Dunja; Sebag-Montefiore, Liam; Wallis, Julie; Clarke, Kieran; Watkins, Hugh; Schneider, Jürgen E.; Neubauer, Stefan

    2012-01-01

    Aims Increasing energy storage capacity by elevating creatine and phosphocreatine (PCr) levels to increase ATP availability is an attractive concept for protecting against ischaemia and heart failure. However, testing this hypothesis has not been possible since oral creatine supplementation is ineffectual at elevating myocardial creatine levels. We therefore used mice overexpressing creatine transporter in the heart (CrT-OE) to test for the first time whether elevated creatine is beneficial in clinically relevant disease models of heart failure and ischaemia/reperfusion (I/R) injury. Methods and results CrT-OE mice were selected for left ventricular (LV) creatine 20–100% above wild-type values and subjected to acute and chronic coronary artery ligation. Increasing myocardial creatine up to 100% was not detrimental even in ageing CrT-OE. In chronic heart failure, creatine elevation was neither beneficial nor detrimental, with no effect on survival, LV remodelling or dysfunction. However, CrT-OE hearts were protected against I/R injury in vivo in a dose-dependent manner (average 27% less myocardial necrosis) and exhibited greatly improved functional recovery following ex vivo I/R (59% of baseline vs. 29%). Mechanisms contributing to ischaemic protection in CrT-OE hearts include elevated PCr and glycogen levels and improved energy reserve. Furthermore, creatine loading in HL-1 cells did not alter antioxidant defences, but delayed mitochondrial permeability transition pore opening in response to oxidative stress, suggesting an additional mechanism to prevent reperfusion injury. Conclusion Elevation of myocardial creatine by 20–100% reduced myocardial stunning and I/R injury via pleiotropic mechanisms, suggesting CrT activation as a novel, potentially translatable target for cardiac protection from ischaemia. PMID:22915766

  5. Myocardial perfusion imaging by digital subtraction angiography

    International Nuclear Information System (INIS)

    Kadowaki, Hiroyuki; Ishikawa, Kinji; Ogai, Toshihiro; Katori, Ryo

    1986-01-01

    Several methods of digital subtraction angiography (DSA) were compared to determine which could better visualize regional myocardial perfusion using coronary angiography in seven patients with myocardial infarction, two with angina pectoris and five with normal coronary arteries. Satisfactory DSA was judged to be achieved if the shape of the heart on the mask film was identical to that on the live film and if both films were exactly superimposed. To obtain an identical mask film in the shape of each live film, both films were selected from the following three phases of the cardiac cycle; 1) at the R wave of the electrocardiogram, 2) 100 msec before the R wave, and 3) 200 msec before the R wave. The last two were superior for obtaining mask and live films which were similar in shape, because the cardiac motion in these phases was relatively small. Using these mask and live films, DSA was performed either with the continuous image mode (CI mode) or the time interval difference mode (TID mode). The overall perfusion of contrast medium through the artery to the vein was adequately visualized using the CI mode. Passage of contrast medium through the artery, capillary and vein was visualized at each phase using TID mode. Subtracted images were displayed and photographed, and the density of the contrast medium was adequate to display contour lines as in a relief map. Using this DSA, it was found that regional perfusion of the contrast medium was not always uniform in normal subjects, depending on the typography of the coronary artery. In all patients with anterior myocardial infarction, low perfusion was observed at the infarcted portion compared to the non-infarcted myocardium. In patients with inferior myocardial infarction, this low perfusion area was not observed because right coronary angiography was not subjected to DSA in this study. (J.P.N.)

  6. Acute myocardial infarction after mediastinal radiotherapy

    International Nuclear Information System (INIS)

    Gagliardi, Juan; Tezanos Pinto, Miguel; Avalos, Adolfo; Sarubbi, Augusto; Padilla, Lucio; Espinosa, Daniel

    2004-01-01

    Mediastinal radiotherapy can affect the heart and great vessels to different degrees. It may turn up as coronary heart disease and less frequently as acute myocardial infarction. We report the case of a patient without coronary risk factors and an antecedent of mediastinal radiotherapy for Hodgkin's lymphoma. Considerations about mediastinal radiation as a risk factor for early development of coronary heart diseases are exposed. (author) [es

  7. Sequential topographical portrayal of myocardial blood flow

    Energy Technology Data Exchange (ETDEWEB)

    Richeson, J.F.; Waag, R.C.; Zwierzynski, D.; Schenk, E.A. (Univ. of Rochester School of Medicine and Dentistry, NY (USA))

    1989-08-01

    Methods to portray myocardial blood flow in a two-dimensional continuum are advantageous in that they allow blood flow history to be overlaid on histological or histochemical descriptions of the consequences of ischemia. We describe here autoradiographic methods that allow such portrayals at three separate times during the evolution of ischemic injury. A computer-based image-analysis system was used to derive such flow maps by taking advantage of the physical characteristics of radioactive isotopes.

  8. Myocardial perfusion studies in coronary diseases

    International Nuclear Information System (INIS)

    Mut, Fernando

    1994-01-01

    For detecting in precocious form a coronary disease is necessary to apply a diagnostic techniques. The main considerations to be indicated in the present work are: physiological considerations, myocardial perfusion studies with radiotracers such as Talio 201, 99mTc, MIBI, 99mTc-Teboroxima, 99mTc-Fosfinas, instrumentation for obtain good images,proceedings protocols, studies interpretation, standards, SPECT, anomalies standards, coronary diseases

  9. Gender differences in symptoms of myocardial ischaemia.

    Science.gov (United States)

    Mackay, Martha H; Ratner, Pamela A; Johnson, Joy L; Humphries, Karin H; Buller, Christopher E

    2011-12-01

    Better understanding of symptoms of myocardial ischaemia is needed to improve timeliness of treatment for acute coronary syndromes (ACS). Although researchers have suggested sex differences exist in ischaemic symptoms, methodological issues prevent conclusions. Using percutaneous coronary intervention (PCI) balloon inflation as a model of myocardial ischaemia, we explored sex differences in reported symptoms of ischaemia. Patients having non-emergent PCI, but not haemodynamic instability or left bundle branch block or non-acute coronary occlusion, were prospectively recruited. Pre-procedure, descriptions of pre-existing symptoms were obtained using open-ended questioning. Inflation was maintained for 2 min or until moderate discomfort or clinical instability occurred. During inflation, subjects were exhaustively questioned about their symptoms. Concurrent ECG data were collected. The final sample was 305 [39.7% women; mean age 63.9 (± 10.6)]. No sex differences were found in rates of chest or typical ischaemic discomfort, regardless of ischaemic status. Women were significantly more likely to report throat/jaw discomfort [odds ratio: 2.91; 95% confidence interval: 1.58-5.37] even after statistical adjustment for clinical and demographic variables. This prospective study with ECG-affirmed ischaemia found no statistically significant differences in women's and men's rates of chest and other typical symptoms during ischaemia, although women were more likely to experience throat and jaw discomfort. Currently both popular press and some patient education materials suggest women experience myocardial ischaemia differently from men. Steps to ensure women and health professionals are alert for the classic symptoms of myocardial ischaemia in women, as well as men, may be warranted.

  10. Myocardial ischemia in hypertrophic cardiomyopathy; Isquemia miocardica na cardiomiopatia hipertrofica

    Energy Technology Data Exchange (ETDEWEB)

    Lima Filho, Moyses de Oliveira; Figueiredo, Geraldo L.; Simoes, Marcus V.; Pyntia, Antonio O.; Marin Neto, Jose Antonio [Sao Paulo Univ., Ribeirao Preto, SP (Brazil). Faculdade de Medicina. Div. de Cardiologia

    2000-08-01

    Myocardial ischemia in hypertrophic cardiomyopathy is multifactorial and explains the occurrence of angina, in about 50% of patients. The pathophysiology of myocardial ischemia may be explained by the increase of the ventricular mass and relative paucity of the coronary microcirculation; the elevated ventricular filling pressures and myocardial stiffness causing a compression of the coronary microvessels; the impaired coronary vasodilator flow reserve caused by anatomic and functional abnormalities; and the systolic compression of epicardial vessel (myocardial bridges). Myocardial ischemia must be investigated by perfusion scintigraphic methods since its presence influences the prognosis and has relevant clinical implications for management of patients. Patients with hypertrophic cardiomyopathy and documented myocardial ischemia usually need to undergo invasive coronary angiography to exclude the presence of concomitant atherosclerotic coronary disease. (author)

  11. Comparison of several potential myocardial imaging agents

    International Nuclear Information System (INIS)

    Watson, E.E.; Stabin, M.G.; Goodman, M.M.; Knapp, F.F. Jr.; Srivastava, P.C.

    1985-01-01

    Although myocardial imaging is currently dominated by Tl-201, several alternative agents with improved physiologic or radionuclidic properties have been proposed. Based on human and animal studies in the literature, the metabolism of several of these compounds was studied for the purpose of generating radiation dose estimates. Dose estimates are listed for several I-123 labeled free fatty acids, an I-123 labeled phosphonium compound, Rb-82, Cu-64, F-18 FDG (all compounds which are taken up by the normal myocardium), and for Tc-99m pyrophosphate (PYP) (which localizes in myocardial infarcts). Dose estimates could not be generated for C-11 palmitate, but this compound was included in a comparison of myocardial retention times. For the I-123 labeled compounds, I-124 was included as a contaminant in generating the dose estimates. Radiation doses were lowest for Rb-82 (gonads 0.3 to 0.5 μGy/MBq, heart wall 15 μGy/MBq). Doses for the I-123 labeled fatty acids were similar to one another, with IPPA being the lowest (gonads 20 μGy/MBq, heart wall 15 μGy/MBq). Doses for Tc-99m PYP were also low (gonads 4 to 7 μGy/MBq, heart wall 4 μGy/MBq, skeleton 15 μGy/MBq). The desirability of these compounds is discussed briefly, considering half life, imaging mode and energy, and dosimetry, including a comparison of the effective whole body dose equivalents. 34 refs., 11 tabs

  12. Estimation of myocardial infarct size by vectocardiography

    International Nuclear Information System (INIS)

    Takimiya, Akihiko

    1987-01-01

    Correlations between the vectorcardiogram (VCG) indice and infarct size (% defect) obtained from myocardial emission computed tomography with thallium-201 were studied in 45 patients with old infero-posterior myocardial infarction. The patients were divided into two groups, one consisting of eight patients who showed abnormal superior deviation of the QRS loop in a counterclockwise rotation beyond 30 msec in the frontal plane of VCG (referred to hereafter as CCW group), and another a non-CCW group consisting of 37 patients. The results obtained were as follows. (1) In the non-CCW group, there were significant negative correlations between the elevation and the Y-axial component of each instantaneous vector of the QRS loop at 30 msec, 35 msec, 40 msec, 45 msec, and between the Y-axial component of 50 msec instantaneous vector and the % defect. The correlation for both the elevation and the Y-axial component was closest at 40 msec, and there was most significantly close correlation between the elevation of 40 msec instantaneous vector and the % defect. (2) In the non-CCW group, there was also a significant correlation between the elevation of QRS area vector and the % defect. (3) In the CCW group, the infarct size could be estimated by the elevation of 30 msec instantaneous vector. An association with left anterior fascicular block was also indicated in the CCW group. (4) In infero-posterior myocardial infarction, the infarct size can be estimated using these VCG indices. (author)

  13. Acute myocardial infarcts. A changing clinical picture

    Energy Technology Data Exchange (ETDEWEB)

    Just, H.

    1988-09-01

    Acute myocardial infarction is a major complication of stenosing coronary artery disease and constitutes the most frequent single cause of death. It is caused by thrombotic occlusion of one of the major epicardial coronary arterial branches in most cases. Sudden death due to ventricular fibrillation is responsible for the majority of early fatalities. In 60% of all fatal infarcts, death occurs within 1 h of the onset of pain. The final extension of myocardial necrosis is reached within 2-4 h. An integrated programme has therefore been developed for the supervision and treatment of patients suffering acute coronary attack; it has been shown that it can markedly lower infarct mortality. It includes mobile prehospital care, intensive care treatment in the hospital, and rehabilitative procedures for application during reconvalescence. Early antiarrhythmic treatment and myocardial reperfusion via fibrinolysis are the main therapeutic procedures in the earliest stage. In hospital an operating room and an operating team must be available round the clock for the performance of coronary angiography followed by percutaneous transluminal coronary angioplasty or bypass surgery, which can be safely carried out in the acute stage provided the indications are strictly observed. Mortality and morbidity can be significantly lowered and both life expectancy and quality of life can be remarkably improved.

  14. [Interventional therapy of acute myocardial infarction].

    Science.gov (United States)

    Zahn, R; Zeymer, U

    2008-09-01

    Currently an acute myocardial infarction has to be differentiated into ST-elevation myocardial infarction (STEMI) or non ST-elevation myocardial infarction (NSTEMI). However, there exists another definition of acute coronary syndromes (ACS), which is more important in clinical practice, for all recommendations from the guidelines of the cardiac societies concerning the invasive strategies rely on this one. Here one has to differentiate an ACS with ST-elevation (STE-ACS = STEMI) from an ACS without ST-elevation (NSTE-ACS). The last one is further divided into an NSTE-ACS with or without high risk. In patients with an NSTE-ACS with high risk an early invasive strategy is recommended within 72 h after the diagnosis. In patients with an NSTE-ACS without high risk a more conservative approach can be pursued. In STE-ACS patients primary angioplasty is the reperfusion therapy of choice, if it can be performed in a timely fashion within 2 h after diagnosis at an interventional centre with experienced interventionalists and short "door-to-balloon" times. In Germany this goal is achievable almost everywhere. Therefore it is currently the most important task to establish local networks to reach this goal.

  15. Echocardiographic Diagnostics of Myocardial Infarction in Newborns

    Directory of Open Access Journals (Sweden)

    G. V. Revunenkov

    2015-01-01

    Full Text Available Early and correct diagnostics of myocardial infarction in newborns is impossible without modern instrumental methods, among which echocardiography is the leading one. Hypokinesia, akinesia or dyskinesia of local segments of the heart ventricular wall is determined with echocardiography. We examined a 3-days-old baby with circulatory failure requiring cardiotonic support. On auscultation there was a heart murmur. It was an intracardiac conduction disoder and infarction-like changes on ECG, however, a convincing evidence to interpret the patient’s condition as myocardial infarction has not been received. Therefore, it was decided to conduct echocardiography. According to the results of echocardiography the presence of hyperechogenic diskinetic locus in the apical segment of the right ventricle (post-infarction scar, a local pericardial effusion in the same projection, hyperechogenic movable mass (thrombus in the apical segment of the right ventricle were determined that together with the results of the ECG allowed us to set diagnosis myocardial infarction. Transthoracic echocardiography is one of highly informative methods; the data obtained allowed to correctly interpret the clinical picture of heart failure and to reveal the cause of the patien’st dependance on cardiotonic support.

  16. Tomoscintigraphic assessment of myocardial metabolic heterogenity

    International Nuclear Information System (INIS)

    Roesler, H.; Hess, T.; Weiss, M.; Noelpp, U.; Mueller, G.; Hoeflin, F.; Kinser, J.

    1983-01-01

    I-123-omega-heptadecanoic acid (HDA) was evaluated for myocardial scanning in 59 healthy volunteers and 133 patients, using a 7-pinhole collimator. Early (uptake) and late (retention) images were compared visually. Regional HDA elimination was also followed semiquantitatively based on the calculation of a retention-over-uptake ratio, R(phi), derived from the maximal counts/pixel in 60 midventricular slice sectors. The healthy heart concentrated HDA homogeneously in all segments with no difference between early and late images. The minimal R(phi), taken as representative of that myocardium with the best function, was unchanged after maximal ergometer stress and with dipyramidole-induced hyperperfusion. A circumscribed decreased HDA uptake is the clear-cut criterion for an abnormal finding. HDA tomography of the myocardium had an 86% sensitivity for myocardial infarcts (MIs) up to 4 wk old, and 83% for myocardial scars (MSs). Comparing early and late tomograms, we find a cool-warm sequence more often with acute and subacute MIs. A cool-cool or a cold-cold sequence dominated with MSs. HDA tomoscintigraphy cannot replace TI-201 for the evaluation of regional coronary reserve in coronary heart disease

  17. The thallium-201 myocardial scintigraphy, its possibilities and limitations

    International Nuclear Information System (INIS)

    Adam, W.; Meindl, S.; Schmitz, A.; Utech, C.; Boettcher, D.

    1983-01-01

    The Thallium-201 Myocardial Scintigraphy, its Possibilities and limitations: The Thallium-201 myocardial scintigraphy is a simple non-invasive procedure to detect hypo- and non-perfused myocardial regions. In the he last years it was demonstrated to be a helpful method in the diagnostic strategy for the cardiologist. It can not replace the coronary angiogram, but in many cases it appears to be useful in selecting patients for coronary angiography. (orig.) [de

  18. Noninvasive evaluation of myocardial ischemia in patients with heart problems

    Directory of Open Access Journals (Sweden)

    Mehdi Nikseresht

    2018-03-01

    Conclusion: It seems that the higher risk of myocardial ischemia in men aged 60-77 years, as compared to men aged 45-59 years, might be related to aging process and imbalance in the risk factors. Promoting physical activity can favorably affect the risk of myocardial ischemia in the middle-aged or elderly men. It is concluded that physical activity effectively decreased the risk of myocardial ischemia.

  19. Severe myocardial injury and extracorporeal membrane oxygenation following perinatal asphyxia

    Directory of Open Access Journals (Sweden)

    P. Benson Ham

    2015-05-01

    Full Text Available Perinatal asphyxia is a common cause of morbidity and mortality in the newborn and is associated with myocardial injury in a significant proportion of cases. Biomarkers, echocardiography, and rhythm disturbances are sensitive indicators of myocardial ischemia and may predict mortality. We present a case of severe myocardial dysfunction immediately after delivery managed with extracorporeal membrane oxygenation (ECMO and discuss the role of cardiac biomarkers, echocardiography, electrocardiography, and ECMO in the asphyxiated newborn.

  20. Myocardial uptake of thallium-201 augmented with bicarbonate: concise communication

    International Nuclear Information System (INIS)

    Hetzel, K.R.; Westerman, B.R.; Quinn, J.L. III; Meyers, S.; Barresi, V.

    1977-01-01

    Sodium bicarbonate was used to enhance the myocardial concentration of Tl-201 in rabbits and dogs. Organ distribution studies in rabbits and in vivo imaging in dogs showed a 1.5 to 2-fold increase in myocardial Tl-201 concentration in bicarbonate-treated animals as compared with matched controls. Image improvement was noted, with threefold enhancement of myocardium-to-liver ratios. The results suggest that a similar improvement may be possible for clinical myocardial imaging

  1. MRS algorithm: a new method for searching myocardial region in SPECT myocardial perfusion images.

    Science.gov (United States)

    He, Yuan-Lie; Tian, Lian-Fang; Chen, Ping; Li, Bin; Mao, Zhong-Yuan

    2005-10-01

    First, the necessity of automatically segmenting myocardium from myocardial SPECT image is discussed in Section 1. To eliminate the influence of the background, the optimal threshold segmentation method modified for the MRS algorithm is explained in Section 2. Then, the image erosion structure is applied to identify the myocardium region and the liver region. The contour tracing method is introduced to extract the myocardial contour. To locate the centriod of the myocardium, the myocardial centriod searching method is developed. The protocol of the MRS algorithm is summarized in Section 6. The performance of the MRS algorithm is investigated and the conclusion is drawn in Section 7. Finally, the importance of the MRS algorithm and the improvement of the MRS algorithm are discussed.

  2. Multi-micronucleus cells related with viral diseases, detected in the study of children affected by the Chernobyl accident

    International Nuclear Information System (INIS)

    Garcia L, O.; Lamadrid, A.I.; Manzano, J.

    1996-01-01

    Cells with multiple chromosome aberrations have been observed in human peripheral blood lymphocytes. Different explanation have proposed, included hot particle induction in persons related to the Chernobyl accident. The frequency of chromosome aberration and micronuclei were established in 14 Ukrainian children with different hematological disorders. They arrived in Cuba thanks to the program by means of which medical attention is offered to children from areas affected by the Chernobyl accident. At least 500 metaphases and bi-nucleate cells were analyzed in each case. The detection of 4 cells with 7-11 micronuclei in a 14 year old boy with cat scratch disease was the most significant cytogenetical finding. The viral origin of the cat scratch disease has been reported, this suggested a viral etiology of the cells with multiple micronuclei. No rogue cells were detected. Cells with multiple micronuclei or rogue cells were not found in other patients from this group. (authors). 7 refs., 3 tabs

  3. Transient ischemic dilation ratio (TID) correlates with HbA1c in patients with diabetes type 2 with proven myocardial ischemia according to exercise myocardial SPECT

    International Nuclear Information System (INIS)

    Adamikova, A.; Rybka, J.; Bakala, J.; Bernatek, J.; Svacina, S.

    2006-01-01

    Abnormal values of the transient ischemic dilation ratio (TID) according to an exercise myocardial single photon emission computed tomography (SPECT) are linked to severe coronary artery disease. The authors investigated the relationship between TID and the levels of vascular cell adhesion molecule (VCAM), intercellular adhesion molecule (ICAM), E-selectin, microalbuminuria, intimamedia thickness and HbA 1c of diabetic subjects. We observed 38 subjects with diabetes type 2 (10 women, 28 men), of average age 56.08±8.24 years, with no past history of cardiovascular disease. All subjects were examined using an exercise myocardial SPECT. Transient ischemic dilation, summed stress score (SSS), summed rest score (SRS) and stress total severity score (STSS) were determined to quantify myocardial ischemia. The average IMT value was 1.05±0.31 mm. The TID value was 1.02±0.154, VCAM 795.24±163.25 mg/l, ICAM 516.55±164.07, E-selectin 63.82±38.89, HbA 1c 7.09±1.68%, microalbuminuria 68.01±55.21 mg/l. When ascertaining the relation of TID to the other factors we used Pearson's correlation at the level of significance p 1c (p=0.035); the other factors did not show any significant correlation. Diabetes and its long term unsatisfactory compensation can be one of the factors which affect left ventricular transient ischemic dilation. (author)

  4. Abnormal myocardial capillary density in apical hypertrophic cardiomyopathy can be assessed by myocardial contrast echocardiography

    International Nuclear Information System (INIS)

    Moon, Jeonggeun; Cho, In-Jeong; Shim, Chi-Young; Ha, Jong-Won; Jang, Yangsoo; Chung, Namsik; Rim, Se-Joong

    2010-01-01

    Myocardial ischemia and dysfunction can occur in hypertrophic cardiomyopathy (HCM) because of the high muscle-to-blood ratio, even without significant coronary artery disease. Microbubbles reside only in the intravascular space and myocardial video-intensity during systole results mostly from microbubbles within capillaries. The hypothesis explored in the present study was that an abnormal capillary density in apical HCM (ApHCM) can be demonstrated using myocardial contrast echocardiography (MCE). The 56 patients were investigated (31 males, age 58±9 years; 33 ApHCM, 9 hypertensive left ventricular hypertrophy [LVH], 14 controls). MCE was performed with low-mechanical-index power modulation imaging. Tissue Doppler imaging to assess myocardial contractile function was obtained at the mitral annulus (S'), and 99m Tc-MIBI single photon emission computed tomography (SPECT) was also performed. All ApHCM patients exhibited perfusion defects at the hypertrophied segments in the systolic phase during MCE, whereas SPECT showed normal or rather increased perfusion at those sites. The cyclic variation of video-intensity was exaggerated in ApHCM when compared with the LVH or control group (% of [systolic video-intensity]/[diastolic video-intensity]: 33.0±12.3%, 88.3±19.2% and 79.4±13.9%, respectively [P<0.05]). Concurrently, MCE cyclic variation and perfusion defect size were related to decreased S' (P<0.05 for all). A perfusion defect at the hypertrophied segment, representing abnormal myocardial capillary density, was observed in ApHCM patients during MCE. The extent of MCE cyclic variation and the perfusion defect size both correlate with decreased myocardial contractile property in ApHCM. (author)

  5. Myocardial imaging in acute myocardial infarction using β-methyl-p-(123I)-iodophenylpentadecanoic acid

    International Nuclear Information System (INIS)

    Naruse, Hitoshi; Itano, Midoriko; Kondo, Tomohiro

    1992-01-01

    Myocardial imaging using β-methyl-p-( 123 I)-iodophenylpentadecanoic acid (BMIPP) was performed in 11 patients with acute myocardial infarction. The left ventricular images were divided into 12 segments, and myocardial images with BMIPP were compared with coronary angiography (CAG), thallium-201 myocardial scintigraphy (Tl) and wall motion obtained by two-dimensional echocardiography (WM). When the culprit lesion was at the proximal point of the left anterior descending artery (LAD), all segments showed depressed uptake. In 3 cases with single vessel disease of the LAD, inferior wall of the basis showed reduced uptake of BMIPP despite the location of the culprit lesion. In cases with discordant uptake between the two tracers, BMIPP frequently showed more severely depressed uptake than Tl in the subacute phase, although the uptake of BMIPP correlated with that of Tl (τ=0.82, p<0.001). In such cases, the discordance was related to the improvement in WM from the acute phase to the convalescent phase. BMIPP uptake correlated with WM in the subacute phase (τ=0.50, p<0.001). BMIPP showed more severely depressed uptake while WM showed mild asynergy in most cases in which discordance was found between the BMIPP and WM findings. However, there was no correlation between the change in WM from the acute to subacute phases, or the uptakes of BMIPP and Tl alone. We concluded that the myocardial condition can be evaluated in detail in acute myocardial infarction by comparing the findings of BMIPP with those of Tl and WM. (author)

  6. Myocardial Hemorrhage After Acute Reperfused ST-Segment–Elevation Myocardial Infarction

    Science.gov (United States)

    Carrick, David; Haig, Caroline; Ahmed, Nadeem; McEntegart, Margaret; Petrie, Mark C.; Eteiba, Hany; Hood, Stuart; Watkins, Stuart; Lindsay, M. Mitchell; Davie, Andrew; Mahrous, Ahmed; Mordi, Ify; Rauhalammi, Samuli; Sattar, Naveed; Welsh, Paul; Radjenovic, Aleksandra; Ford, Ian; Oldroyd, Keith G.

    2016-01-01

    Background— The success of coronary reperfusion therapy in ST-segment–elevation myocardial infarction (MI) is commonly limited by failure to restore microvascular perfusion. Methods and Results— We performed a prospective cohort study in patients with reperfused ST-segment–elevation MI who underwent cardiac magnetic resonance 2 days (n=286) and 6 months (n=228) post MI. A serial imaging time-course study was also performed (n=30 participants; 4 cardiac magnetic resonance scans): 4 to 12 hours, 2 days, 10 days, and 7 months post reperfusion. Myocardial hemorrhage was taken to represent a hypointense infarct core with a T2* value of hemorrhage 2 days post MI was associated with clinical characteristics indicative of MI severity and inflammation. Myocardial hemorrhage was a multivariable associate of adverse remodeling (odds ratio [95% confidence interval]: 2.64 [1.07–6.49]; P=0.035). Ten (4%) patients had a cardiovascular cause of death or experienced a heart failure event post discharge, and myocardial hemorrhage, but not microvascular obstruction, was associated with this composite adverse outcome (hazard ratio, 5.89; 95% confidence interval, 1.25–27.74; P=0.025), including after adjustment for baseline left ventricular end-diastolic volume. In the serial imaging time-course study, myocardial hemorrhage occurred in 7 (23%), 13 (43%), 11 (33%), and 4 (13%) patients 4 to 12 hours, 2 days, 10 days, and 7 months post reperfusion. The amount of hemorrhage (median [interquartile range], 7.0 [4.9–7.5]; % left ventricular mass) peaked on day 2 (Phemorrhage and microvascular obstruction follow distinct time courses post ST-segment–elevation MI. Myocardial hemorrhage was more closely associated with adverse outcomes than microvascular obstruction. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT02072850. PMID:26763281

  7. Hypertension impairs myocardial blood perfusion reserve in subjects without regional myocardial ischemia

    International Nuclear Information System (INIS)

    Nakajima, Hiroshi; Onishi, Katsuya; Kurita, Tairo

    2010-01-01

    Quantitative analysis of myocardial perfusion MRI can provide noninvasive assessments of myocardial perfusion reserve (MPR), which is associated with endothelial function. Endothelial function is influenced by various factors, including hypertension, diabetes, dyslipidemia, renal dysfunction and anemia. The purpose of this study was to evaluate which risk factor is the strongest effector of MPR in subjects without regional myocardial ischemia. We studied 110 patients (66 years ±10, male 68%, hypertension 76%, diabetes mellitus (DM) 40% and dyslipidemia 65%) without regional myocardial ischemia. Adenosine triphosphate (ATP) stress and rest first-pass perfusion magnetic resonance (MR) images were acquired with a 1.5-T MR system, and MPR was calculated as the ratio of stress to rest myocardial blood flow (MBF). Average rest MBF in 110 patients was 1.07±0.62 ml min -1 g -1 , whereas stress MBF was 3.15±1.93 ml min -1 g -1 and the MPR was 3.33±1.82. Rest MBF correlated significantly with hematocrit, whereas stress MBF showed a strong correlation with estimated glomerular filtration rate (e-GFR). MPR was associated with hypertension, age, e-GFR, hematocrit and left ventricular mass index (LVMI). In multiple regression analysis, hypertension (P=0.003, β=-0.274) showed the strongest correlation with MPR among other risk factors, such as diabetes (P=ns), dyslipidemia (P=ns), e-GFR (P=ns), LVMI (P=0.007, β=-0.248) and hematocrit (P=ns) after adjusting age and gender. Hypertension is the most important effector of MPR in subjects without myocardial ischemia. (author)

  8. Hypertension impairs myocardial blood perfusion reserve in subjects without regional myocardial ischemia

    Energy Technology Data Exchange (ETDEWEB)

    Nakajima, Hiroshi; Onishi, Katsuya; Kurita, Tairo [Mie Univ., Graduate School of Medicine, Tsu, Mie (Japan)

    2010-11-15

    Quantitative analysis of myocardial perfusion MRI can provide noninvasive assessments of myocardial perfusion reserve (MPR), which is associated with endothelial function. Endothelial function is influenced by various factors, including hypertension, diabetes, dyslipidemia, renal dysfunction and anemia. The purpose of this study was to evaluate which risk factor is the strongest effector of MPR in subjects without regional myocardial ischemia. We studied 110 patients (66 years {+-}10, male 68%, hypertension 76%, diabetes mellitus (DM) 40% and dyslipidemia 65%) without regional myocardial ischemia. Adenosine triphosphate (ATP) stress and rest first-pass perfusion magnetic resonance (MR) images were acquired with a 1.5-T MR system, and MPR was calculated as the ratio of stress to rest myocardial blood flow (MBF). Average rest MBF in 110 patients was 1.07{+-}0.62 ml min{sup -1} g{sup -1}, whereas stress MBF was 3.15{+-}1.93 ml min{sup -1} g{sup -1} and the MPR was 3.33{+-}1.82. Rest MBF correlated significantly with hematocrit, whereas stress MBF showed a strong correlation with estimated glomerular filtration rate (e-GFR). MPR was associated with hypertension, age, e-GFR, hematocrit and left ventricular mass index (LVMI). In multiple regression analysis, hypertension (P=0.003, {beta}=-0.274) showed the strongest correlation with MPR among other risk factors, such as diabetes (P=ns), dyslipidemia (P=ns), e-GFR (P=ns), LVMI (P=0.007, {beta}=-0.248) and hematocrit (P=ns) after adjusting age and gender. Hypertension is the most important effector of MPR in subjects without myocardial ischemia. (author)

  9. Re-OPCAB vs. Re-CABG for myocardial revascularization.

    Science.gov (United States)

    Schütz, A; Mair, H; Wildhirt, S M; Gillrath, G; Lamm, P; Kilger, E; Reichart, B

    2001-06-01

    The present study compared redo coronary artery bypass grafting (Re-OPCAB) techniques with conventional redo coronary artery bypass grafting (Re-CABG) with particular focus on myocardial damage and clinical outcome parameters. Redo OPCAB (Re-OPCAB) was performed on 20 consecutive patients (15 males, mean age 63.2 +/- 9.3 years) using either the anterolateral approach for minimally invasive direct coronary artery bypass (n = 4) or the Octopus technique with regular sternotomy (n = 16). The Re-CABG group consisted of 20 consecutive patients (18 males, mean age 67.1 +/- 6.6 years). Groups did not differ in the number of atherosclerotic risk factors, or left ventricular, renal or liver function. Duration of surgery, number of bypass grafts and amount of transfused red blood cells did not differ significantly between both groups. Requirement of epinephrine (mg/h) within the first 24 h was lower in the Re-OPCAB group (Re-OPCAB: 0.14 +/- 0.22 vs. CABG: 0.88 +/- 0.97; p<0.01). In addition, CKMB levels at 24 h after operation were lower in the Re-OPCAB group (Re-OPCAB: 10.0 +/- 10.1 vs. Re-CABG: 38.7 +/- 28.1 U/l, p<0.001). There were no acute myocardial infarctions or deaths in the perioperative period. In the CABG group, there was a longer time period to extubation (hours) (Re-OPCAB: 9.8 +/- 3.9 vs. Re-CABG: 28.7 +/- 25.5; p<0.001), and the length of ICU stay was significantly prolonged (OPCAB: 1.3 +/- 0.5 versus Re-CABG: 4.4 +/- 8.7; p<0.001). The graft patency rate at follow-up was 95% in the Re-OPCAB group. Re-OPCAB results in decreased cardiac specific enzyme release, reduced requirement of inotropes and comparable clinical outcome in the early postoperative period. It is an appropriate alternative to conventional Re-CABG in selected patients awaiting reoperation for myocardial revascularization. Larger prospective and randomized trials are required to select the appropriate patient who benefits most from one or the other treatment regime.

  10. Technetium-99m-pyrophosphate myocardial imaging in unstable angina

    International Nuclear Information System (INIS)

    Willerson, J.T.; Parkey, R.W.; Lewis, S.E.; Buja, L.M.; Bonte, F.J.

    1980-01-01

    The authors have found that approximately one third of patients with the syndrome of unstable angina pectoris have abnormal 99mTc-pyrophosphate myocardial scintigrams even in the absence of abnormal enzymes and electrocardiographic confirmation of the presence of acute myocardial necrosis. Thus, 99mTc-pyrophosphate myocardial imaging technique appears to represent a sensitive means to detect acute multicellular injury associated with the clinical syndrome of unstable angina pectoris even when cardiac enzymes are normal and the electrocardiogram does not definitively document the presence of acute myocardial necrosis. (Auth.)

  11. Inferior ST-Elevation Myocardial Infarction Associated with Takotsubo Cardiomyopathy

    Directory of Open Access Journals (Sweden)

    Oliver Koeth

    2010-01-01

    Full Text Available Takotsubo cardiomyopathy (TCM is usually characterized by transient left ventricular apical ballooning. Due to the clinical symptoms which include chest pain, electrocardiographic changes, and elevated myocardial markers, Takotsubo cardiomyopathy is frequently mimicking ST-elevation myocardial infarction in the absence of a significant coronary artery disease. Otherwise an acute occlusion of the left anterior descending coronary artery can produce a typical Takotsubo contraction pattern. ST-elevation myocardial infarction (STEMI is frequently associated with emotional stress, but to date no cases of STEMI triggering TCM have been reported. We describe a case of a female patient with inferior ST-elevation myocardial infarction complicated by TCM.

  12. Novel curcumin analogue 14p protects against myocardial ischemia reperfusion injury through Nrf2-activating anti-oxidative activity

    Energy Technology Data Exchange (ETDEWEB)

    Li, Weixin [Department of Cardiology, The 5th Affiliated Hospital of Wenzhou Medical University, Lishui, Zhejiang (China); Chemical Biology Research Center, School of Pharmaceutical Science, Wenzhou Medical University, Wenzhou, Zhejiang (China); Wu, Mingchai [Department of Pharmacy, The Third Affiliated Hospital of Wenzhou Medical University, Wenzou, Zhejiang (China); Tang, Longguang; Pan, Yong; Liu, Zhiguo [Chemical Biology Research Center, School of Pharmaceutical Science, Wenzhou Medical University, Wenzhou, Zhejiang (China); Zeng, Chunlai [Department of Cardiology, The 5th Affiliated Hospital of Wenzhou Medical University, Lishui, Zhejiang (China); Wang, Jingying [Chemical Biology Research Center, School of Pharmaceutical Science, Wenzhou Medical University, Wenzhou, Zhejiang (China); Wei, Tiemin, E-mail: lswtm@sina.com [Department of Cardiology, The 5th Affiliated Hospital of Wenzhou Medical University, Lishui, Zhejiang (China); Liang, Guang, E-mail: wzmcliangguang@163.com [Chemical Biology Research Center, School of Pharmaceutical Science, Wenzhou Medical University, Wenzhou, Zhejiang (China)

    2015-01-15

    Background: Alleviating the oxidant stress associated with myocardial ischemia reperfusion has been demonstrated as a potential therapeutic approach to limit ischemia reperfusion (I/R)-induced cardiac damage. Curcumin, a natural compound with anti-oxidative activity, exerts beneficial effect against cardiac I/R injury, but poor chemical and metabolic stability. Previously, we have designed and synthesized a series of mono-carbonyl analogues of curcumin (MACs) with high stability. This study aims to find new anti-oxidant MACs and to demonstrate their effects and mechanisms against I/R-induced heart injury. Methods: H9c2 cells challenged with H{sub 2}O{sub 2} or TBHP were used for in vitro bio-screening and mechanistic studies. The MDA, H{sub 2}O{sub 2} and SOD levels in H9C2 cells were determined, and the cell viability was assessed by MTT assay. Myocardial I/R mouse models administrated with or without the compound were used for in vivo studies. Results: The in vitro cell-based screening showed that curcumin analogues 8d and 14p exhibited strong anti-oxidative effects. Pre-treatment of H9c2 cells with 14p activated Nrf2 signaling pathway, attenuated H{sub 2}O{sub 2}-increased MDA and SOD level, followed by the inhibition of TBHP-induced cell death and Bax/Bcl-2–caspase-3 pathway activation. Silencing Nrf2 significantly reversed the protective effects of 14p. In in vivo animal model of myocardial I/R, administration of low dose 14p (10 mg/kg) reduced infarct size and myocardial apoptosis to the same extent as the high dose curcumin (100 mg/kg). Conclusion: These data support the novel curcumin analogue 14p as a promising antioxidant to decrease oxidative stress and limit myocardial ischemia reperfusion injury via activating Nrf2. - Highlights: • Mono-carbonyl analogue of curcumin, 14p, exhibited better chemical stability. • Compound 14p inhibited TBHP-induced apoptosis through activating Nrf2 in vitro. • Compound 14p limited myocardial ischemia

  13. Acute myocardial infarction in a young adult with myocardial bridging and normal coronary arteries

    Directory of Open Access Journals (Sweden)

    Moris Chansky

    2004-09-01

    Full Text Available The authors present a case of a young adult with acute myocardialinfarction, attended at the Emergency Department of HospitalIsraelita Albert Einstein. Acute myocardial infarction caused bymyocardial bridge (intramyocardial tunneled coronary artery is arare clinical entity. The finding of this condition in patients withnormal arteries (non-obstructed vessels is uncommon; it isusually associated with extracardiac triggering factors. The casereported presented an acute myocardial infarction caused by amyocardial bridge as demonstrated in the clinical picture, ECGprogression, enzyme pattern (troponin, CKMB, TGO and LD andventriculography.

  14. Quantitative Myocardial Perfusion Imaging Versus Visual Analysis in Diagnosing Myocardial Ischemia: A CE-MARC Substudy.

    Science.gov (United States)

    Biglands, John D; Ibraheem, Montasir; Magee, Derek R; Radjenovic, Aleksandra; Plein, Sven; Greenwood, John P

    2018-05-01

    This study sought to compare the diagnostic accuracy of visual and quantitative analyses of myocardial perfusion cardiovascular magnetic resonance against a reference standard of quantitative coronary angiography. Visual analysis of perfusion cardiovascular magnetic resonance studies for assessing myocardial perfusion has been shown to have high diagnostic accuracy for coronary artery disease. However, only a few small studies have assessed the diagnostic accuracy of quantitative myocardial perfusion. This retrospective study included 128 patients randomly selected from the CE-MARC (Clinical Evaluation of Magnetic Resonance Imaging in Coronary Heart Disease) study population such that the distribution of risk factors and disease status was proportionate to the full population. Visual analysis results of cardiovascular magnetic resonance perfusion images, by consensus of 2 expert readers, were taken from the original study reports. Quantitative myocardial blood flow estimates were obtained using Fermi-constrained deconvolution. The reference standard for myocardial ischemia was a quantitative coronary x-ray angiogram stenosis severity of ≥70% diameter in any coronary artery of >2 mm diameter, or ≥50% in