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  • 1
    Online Resource
    Online Resource
    SAGE Publications ; 1996
    In:  Asian Cardiovascular and Thoracic Annals Vol. 4, No. 2 ( 1996-06), p. 126-129
    In: Asian Cardiovascular and Thoracic Annals, SAGE Publications, Vol. 4, No. 2 ( 1996-06), p. 126-129
    Type of Medium: Online Resource
    ISSN: 0218-4923 , 1816-5370
    Language: English
    Publisher: SAGE Publications
    Publication Date: 1996
    detail.hit.zdb_id: 2044527-1
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  • 2
    In: Circulation, Ovid Technologies (Wolters Kluwer Health), Vol. 130, No. suppl_2 ( 2014-11-25)
    Abstract: Introduction: After myocardial infarction (MI), cardiomyocyte death results in a non-contractile fibrotic scar and altered electrical properties, including delayed impulse propagation across the scar region which may contribute to ventricular dysfunction. Hydrogels such as chitosan have been used clinically to stabilize the LV free wall and prevent dilation. We chemically modified chitosan with the charge-carrying conductive polymer polypyrrole (PPy), yielding a biomaterial with more than 100X the conductivity of chitosan alone. Chitosan-PPy is capable of carrying electrical impulses and may enhance synchronous contraction. Methods: Biomaterials were synthesized under sterile conditions and were thoroughly characterized in vitro . Myocardial infarction was created by coronary artery ligation in Sprague-Dawley rats (n = 36), and 1 week later chitosan, chitosan-PPy or saline were injected into the border zone regions. Animals were followed for 8 or 16 weeks (n = 6/treatment/time-point) and cardiac conduction and function were assessed with ECG, echocardiography, impedance catheter analysis and finally Langendorff-perfused epicardial optical mapping. Results: Eight weeks post-injection, QRS duration was increased in saline and chitosan treated hearts, but was maintained in chitosan-PPy hearts until 16 weeks ( p 〈 0.01), suggesting less maladaptive ventricular remodeling associated with slowing of depolarizing conduction in the chitosan-PPy group. Echocardiography revealed that fractional shortening was enhanced in chitosan-PPy treated hearts at both 8 and 16 weeks ( p 〈 0.01). At 16 weeks, chitosan-PPy hearts had increased stroke work capacity, and better maintained (lower) end systolic volume ( p 〈 0.05). Optical mapping demonstrated that chitosan-PPy-treated hearts had faster transverse conduction velocities measured along the border zone epicardial surface ( p 〈 0.01). Conclusions: We synthesized and characterized a novel conductive polymer hydrogel that may be used therapeutically to enhance favorable cardiac recovery at the LV border zone following an MI. Chitosan-PPy enhanced heart function by augmenting synchronized contraction.
    Type of Medium: Online Resource
    ISSN: 0009-7322 , 1524-4539
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2014
    detail.hit.zdb_id: 1466401-X
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  • 3
    Online Resource
    Online Resource
    Ovid Technologies (Wolters Kluwer Health) ; 2007
    In:  Circulation Vol. 116, No. suppl_16 ( 2007-10-16)
    In: Circulation, Ovid Technologies (Wolters Kluwer Health), Vol. 116, No. suppl_16 ( 2007-10-16)
    Abstract: Background: The inability of skeletal myoblasts to transdifferentiate into cardiomyocytes supports the hypothesis that their beneficial effects on cardiac function after a myocardial infarction (MI) are mediated by paracrine effects. In order to explore the role of the timing of cell therapy on the resultant angiogenesis and matrix remodeling, we compared the effects of myoblast transplantation early or late after MI. Methods: MI was generated in Lewis rats by coronary artery ligation. Skeletal myoblasts (5X10 6 ) or control media were injected into the scar and border zone either 5 days (early; n=33) or 30 days (late; n=29) after ligation. Function was assessed by echocardiography before transplantation (Tx), and 14 and 30 days thereafter. Invasive hemodynamics were measured with a Millar catheter at 30 days after Tx, following which explanted hearts were processed to assess LV volumes (computerized planimetry), fibrillar collagen (confocal microscopy), and myoblast engraftment, angiogenesis and extra-cellular matrix characteristics (immunohistochemistry). Results: Load-independent indices of left ventricular (LV) function (Emax, preload recruitable stroke work) were significantly increased in myoblast recipients compared with controls regardless of whether cells were implanted early (p=0.003, p=0.03, respectively) or late (p=0.003, p=0.0007, respectively) after MI. Changes in fractional shortening (by echocardiography) followed a similar pattern. These changes were associated with a significant reduction in LV volume (p=0.04, p=0.01 for early and late Tx groups vs. controls, respectively), and an increase in angiogenesis (p=0.02) whether the myoblasts were injected early or late after MI. The length and width of collagen fibers both in the scar and remote myocardium were also significantly increased (p 〈 0.001) regardless of the timing of myoblast injection. Conclusions: The data suggest that myoblast transplantation improved cardiac function whether cells were injected early or late after MI. In each case, functional recovery was associated with enhanced angiogenesis, favourable effects on extracellular matrix remodeling, and improved LV geometry, supporting the paracrine hypothesis for myoblast transplantation.
    Type of Medium: Online Resource
    ISSN: 0009-7322 , 1524-4539
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2007
    detail.hit.zdb_id: 1466401-X
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  • 4
    Online Resource
    Online Resource
    Ovid Technologies (Wolters Kluwer Health) ; 2008
    In:  Circulation Vol. 118, No. suppl_18 ( 2008-10-28)
    In: Circulation, Ovid Technologies (Wolters Kluwer Health), Vol. 118, No. suppl_18 ( 2008-10-28)
    Abstract: Rationale: Targeted: Ultrasound targeted microbubble destruction (UTMD) delivers genes directly to the injured myocardium. Tailored: UTMD could permit recurrent treatment until recovery is complete. Hypothesis: Repeated UTMD is a novel strategy to induce tissue regeneration and improve ventricular function after a myocardial infarction. Methods: Microbubbles were mixed with plasmids containing stem cell factor (SCF) and stromal cell-derived factor (SDF)-1α genes. Seven days after coronary artery ligation, adult rats underwent UTMD either 1, 3 or 6 times at 2-day intervals in 4 randomly assigned groups: Control group: 6 UTMD treatments with empty plasmid (n=4); Repeat 1 (n=6), Repeat 3 (n=7), Repeat 6 (n=6) groups: 1, 3 or 6 treatments, respectively, of UTMD with SCF and SDF-1α plasmid DNA. Cardiac function (echocardiography) and myocardial perfusion (myocardial contrast echocardiography) were assessed on days 0, 10 and 24 after the first treatment. Biochemical assessments were performed on day 24. Results: Cardiac function was highest in the Repeat 6 group (p 〈 0.05 vs. Repeat 1). Myocardial SCF levels were higher after multiple rather than single UTMD treatments (p 〈 0.05 for Repeat 3 and Repeat 6 vs. Repeat 1), with the highest levels in the Repeat 6 group (p 〈 0.05 vs. Repeat 3). Myocardial SDF-1α levels and c-kit-positive cell counts also increased with the maximum number of treatments (p 〈 0.05 for Repeat 6 vs. Repeat 1). Myocardial CXCR4-positive cells were more numerous in the remote regions of both multiple UTMD groups (p 〈 0.05 for Repeat 3 and Repeat 6 vs. Repeat 1). Both myocardial perfusion in the infarct region and vascular density (Factor VIII or alpha-smooth muscle actin staining) in the border zone increased with repeated treatments (p 〈 0.05 for Repeat 3 and Repeat 6 vs. Repeat 1), with an additional increase in the Repeat 6 group (p 〈 0.01 vs. Repeat 3). Conclusions: Targeted ultrasound delivery of SCF and SDF-1α genes to the myocardium induced angiogenesis, recruited progenitor cells and improved cardiac function. Multiple UTMD treatments further enhanced regeneration. Tailoring the treatment by providing the number of interventions required to restore function provides a new approach to cardiac regeneration following a myocardial infarction.
    Type of Medium: Online Resource
    ISSN: 0009-7322 , 1524-4539
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2008
    detail.hit.zdb_id: 1466401-X
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  • 5
    In: Circulation, Ovid Technologies (Wolters Kluwer Health), Vol. 116, No. suppl_16 ( 2007-10-16)
    Abstract: Background: Inhibition of toll-like receptors (TLRs) may be a new treatment to prevent congestive heart failure during post-myocardial infarction (MI) surgical interventions. TLR2 knockout (KO) mice provide an opportunity to predict the effects of inhibitors and to establish the mechanisms responsible for their beneficial effects. This study was performed to establish the pathways responsible for myocardial protection in the absence of TLRs after MI. Methods and Results: In vivo study: MI was induced in TLR2 KO and wild-type (WT) C56B/6J mice by anterior coronary artery ligation. Cardiac function was preserved in the KO mice compared to the WT mice (echocardiography demonstrated higher fractional shortening and fractional area change, p 〈 0.05) at 3, 7 and 28 days after the MI. To evaluate the mechanisms responsible for the functional improvements, cardiac cytokine production was measured. TNF-α, IL-1β and IL-6 were significantly decreased in the infarct region of KO compared to WT mice at 3 days post-MI. On day 7, IL-6 production was significantly decreased in the infarct region and TNF-α was decreased in the non-infarcted region of KO compared to WT mice. Phosphorylation of p38 MAPK was prevented, and the number of TUNEL positive nuclei was reduced in the infarct region of KO compared to WT mice. Phosphorylation of Akt was upregulated in the non-infarcted region of KO mice at 3 days after MI. There were no differences in the phosphorylation of ERK or JNK at the same time point. In vitro study: Myocardial fibroblasts were isolated from KO and WT mice, cultured, and then exposed to hydrogen peroxide. Compared to cells from WT mice, cells from KO mice exhibited greater protection (less cell death) and reduced p38 phosphorylation as early as 5 and 15 minutes after hydrogen peroxide stimulation. Conclusions: TLR2 KO mice allow the assessment of the potential benefits of TLR inhibitors. Reducing TLR2 after an infarction will decrease cytokine production and cell death in a p38 MAPK-dependent manner, which in turn will contribute to the preservation of cardiac function. Early inhibition of TLR2 function may represent a new target to prevent heart failure after MI.
    Type of Medium: Online Resource
    ISSN: 0009-7322 , 1524-4539
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2007
    detail.hit.zdb_id: 1466401-X
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  • 6
    Online Resource
    Online Resource
    Ovid Technologies (Wolters Kluwer Health) ; 2008
    In:  Circulation Vol. 118, No. suppl_18 ( 2008-10-28)
    In: Circulation, Ovid Technologies (Wolters Kluwer Health), Vol. 118, No. suppl_18 ( 2008-10-28)
    Abstract: Rationale: Allogeneic bone marrow mesenchymal stem cells (MSC) are currently undergoing clinical trials to test their potential to repair the heart after a myocardial infarction (MI). MSCs can improve function, but neither the host immune responses nor the fate of these cells has been extensively investigated. This study compared the outcomes of allogeneic and syngeneic MSC transplantation after an MI. Methods: Female Lewis rat underwent coronary ligation. Three weeks later, allogeneic or syngeneic MSCs (3×10 6 /rat) from male rats (Wister or Lewis, respectively) were implanted into the infracted region. We evaluated implanted cell survival (real-time PCR to quantify Y-chromosomes), cytokines (RT-PCR) and infiltrating cells (immunostaining) in the heart, and allogeneic antibodies in the blood. Cardiac function was assessed by echocardiography and pressure-volume catheters. Immune antigen expression (RT-PCR, immunostaining and flow cytometry) was characterized in the MSCs before and after myogenic differentiation. Results: At 1 week post implantation, cell survival was similar in the allogeneic and syngeneic groups. Gene expression of 11 cytokines and T-cell infiltration into the cell-implanted region were also similar, but more B-cells were observed in the allogeneic group (p 〈 0.05 vs. syngeneic group). Allo-antibodies (IgG1) against Wistar MSCs were detected in the peripheral blood of animals that received allogeneic cells. At 5 weeks after delivery, implanted MSCs were detected only in the syngeneic group. Cardiac function was equally restored in both cell groups (ejection fraction: allogeneic=30.4±1.8%; syngeneic=29.5±2.8%; p 〈 0.05 vs. media controls; control=24.8±3.2%); these data were supported by the pressure-volume analysis. Myogenic differentiation (expression of Nkx2.5, MyoD, MHCβ), CD86 expression and MHC class II molecules were observed in the MSCs after prolonged culture, which could explain why the cells were rejected. Conclusions: Allogeneic BMSC transplantation produced a robust cardiac functional improvement, but following myogenic differentiation the cells were no longer immunoprivileged. Rejection of the allogeneic cells could limit their long term benefit on cardiac remodeling after an MI.
    Type of Medium: Online Resource
    ISSN: 0009-7322 , 1524-4539
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2008
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  • 7
    In: Circulation, Ovid Technologies (Wolters Kluwer Health), Vol. 132, No. suppl_3 ( 2015-11-10)
    Abstract: Introduction: We previously reported that bone marrow (BM) reconstitution with young BM cells into aged recipients restored progenitors in both the BM and the myocardium and improved functional recovery post-injury. Here, our goal was to identify the specific cell type responsible for the improved cardiac regeneration and to restore that capacity in aged individuals after myocardial infarction (MI). Methods and Results: We reconstituted old mice with BM cells from young or old GFP+ mice to generate young chimeras and old chimeras. The number of BM-derived Sca-1+ progenitors homing to the heart was significantly greater in young chimeras compared to old ones (7.14±0.32/field for young vs 2.48±0.78/field for old, P 〈 0.01, 5 high-powered fields/section, 3 sections/heart, 3 animals/group). We then separated Sca-1+ from Sca-1- young donor BM cells using magnetic cell sorting and transplanted them into lethally-irradiated old recipients to generate Sca-1+ and Sca-1- chimeras. Quantification by flow cytometry of heart tissue revealed: 1) the Sca-1+ chimeras had more BM-derived cells that co-expressed PDGFRβ (1.65±0.13% for Sca-1+ vs 0.52±0.09% for Sca-1-, P 〈 0.05, n=4/group) and 2) the number of GFP+ PDGFRβ+ cells was greater in the Sca-1+ chimeric hearts than the Sca-1- chimeric hearts after MI (3.77±0.55% for Sca-1+ vs 0.85±0.106% for Sca-1-, P 〈 0.05, n=3/group). The BM-derived cells that homed to the heart in the Sca-1+ chimeras actively proliferated, stimulated proliferation of the host’s aged progenitors and improved ventricular function after MI. BM chimerism with Sca-1+ cells in aged mice restored the regenerative capability of cardiac resident progenitors and improved functional healing of the aged heart. Conclusions: BM Sca-1+ cells that homed to the heart in aged recipients proliferated and stimulated the propagation of host aged progenitor cells post-MI. This improved regeneration involved activation of the PDGFRβ/Akt/p27Kip1 signaling pathway. The number of BM-derived Sca-1+ progenitor cells in the aged myocardium was the major determinant for successful cardiac functional recovery. Restoration of the Sca-1 subset of stem cells by BM reconstitution improved cardiac repair and prevented heart failure.
    Type of Medium: Online Resource
    ISSN: 0009-7322 , 1524-4539
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2015
    detail.hit.zdb_id: 1466401-X
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  • 8
    Online Resource
    Online Resource
    Elsevier BV ; 2001
    In:  The Annals of Thoracic Surgery Vol. 71, No. 6 ( 2001-06), p. 1925-1930
    In: The Annals of Thoracic Surgery, Elsevier BV, Vol. 71, No. 6 ( 2001-06), p. 1925-1930
    Type of Medium: Online Resource
    ISSN: 0003-4975
    RVK:
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2001
    detail.hit.zdb_id: 1499869-5
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  • 9
    In: The Annals of Thoracic Surgery, Elsevier BV, Vol. 76, No. 6 ( 2003-12), p. 2062-2070
    Type of Medium: Online Resource
    ISSN: 0003-4975
    RVK:
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2003
    detail.hit.zdb_id: 1499869-5
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  • 10
    Online Resource
    Online Resource
    Elsevier BV ; 2002
    In:  The Annals of Thoracic Surgery Vol. 74, No. 6 ( 2002-12), p. 2160-
    In: The Annals of Thoracic Surgery, Elsevier BV, Vol. 74, No. 6 ( 2002-12), p. 2160-
    Type of Medium: Online Resource
    ISSN: 0003-4975
    RVK:
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2002
    detail.hit.zdb_id: 1499869-5
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