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      Comparación de la eficacia y seguridad de la terapia combinada de cardiomioplastia celular con el factor estimulante de colonias de granulocitos en pacientes con cardiopatía isquémica en dos vías de implatación Translated title: Comparison of efficacy and safety of combined therapy of cellular cardiomyoplasty and granulocyte colony stimulating factor in patients with ischemic cardiomyopathy in two routes of implantation

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          Abstract

          Este estudio tiene como objetivo evaluar la eficacia y seguridad de la terapia combinada de cardiomioplastia celular con el factor estimulante de colonias de granulocitos en pacientes con cardiopatía isquémica, y explorar posibles diferencias entre la vía de implantación. METODOLOGÍA: se hizo un estudio de «antes y después» para datos longitudinales en el que se compararon variables ecocardiográficas y número de MET alcanzados en la prueba de esfuerzo antes, dos, seis y doce meses después del procedimiento; así mismo, se evaluaron la mortalidad y los efectos adversos de la terapia. Se exploraron diferencias en los resultados de acuerdo con la vía de implantación intracoronaria vs. epicárdica. RESULTADOS: se incluyeron dieciocho pacientes, 62,3% hombres, cuya edad promedio fue 49,4 ± 11,7 años y la fracción de eyección promedio fue 31% ± 0,04. La implantación se realizó por vía intracoronaria en doce pacientes y por vía epicárdica en seis. La mediana de fracción de eyección antes de la implantación de las células fue de 30% con un rango intercuartil de 28%-35% y la media de los MET fue de 6 con un rango intercuartil de 5-7; ambas variables, al igual que los volúmenes ventriculares de fin de diástole y sístole se incrementaron de forma significativa después del procedimiento, con tendencia a un mayor incremento de la fracción de eyección en el grupo de pacientes cuya vía de implantación fue la epicárdica en comparación con la vía intracoronaria; sin embargo, el número de pacientes en cada subgrupo impidió hacer análisis definitivos. Un paciente tuvo infección de la herida quirúrgica y tres murieron dos meses después de la implantación (uno de shock séptico y dos de shock cardiogénico). CONCLUSIÓN: en nuestro medio es factible realizar terapia combinada con cardiomioplastia celular y factor estimulante de colonias de granulocito; este es un procedimiento seguro con el que se obtiene una mejoría sostenida de la fracción de eyección y los MET más allá de los beneficios que se logran con la revascularización y la terapia farmacológica óptima.

          Translated abstract

          The objective of this study is to assess efficacy and safety of combined therapy of cellular cardiomyoplasty and granulocyte colony stimulating factor in patients with ischemic cardiomyopathy and explore possible differences between the implantation routes. METHODOLOGY: we performed a before and after study for longitudinal data comparing echocardiographic variables and number of Met achieved in the stress test before and at two, six and twelve months after the procedure. Likewise, mortality and adverse therapy effects were evaluated. Differences in the results were analyzed according to the intracoronary vs. epicardiac route of implantation. RESULTS: eighteen patients were included; 62,3% men, with mean age 49.4 ± 11,7 years. Mean ejection fraction was 31% ± 0,04. In twelve patients implantation was performed by intracoronary route and in six by epicardiac route. Mean ejection fraction before cell implantation was 30% with an interquartil range (IQR) of 28-35%, and MET average was 6 with an interquartil rage of 5-7. Both variables as well as end-systolic and end-diastolic volumes increased significantly after the procedure, with a tendency to greater increase in ejection fraction in the group of patients whose route was epicardial implantation compared with intracoronary route; however, the number of patients in each subgroup prevented to make a definitive analysis. One patient had surgical wound infection and three died two months after implantation (one of septic shock and two of cardiogenic shock). CONCLUSION: in our environment the performance of combination therapy with cellular cardiomyoplasty and granulocyte colony stimulating factor is feasible. This is a safe procedure that achieved a sustained improvement in ejection fraction and MET beyond benefits achieved with revascularization and optimal pharmacological therapy.

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          Most cited references38

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          Multilineage potential of adult human mesenchymal stem cells

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            Intracoronary injection of mononuclear bone marrow cells in acute myocardial infarction.

            Previous studies have shown improvement in left ventricular function after intracoronary injection of autologous cells derived from bone marrow (BMC) in the acute phase of myocardial infarction. We designed a randomized, controlled trial to further investigate the effects of this treatment. Patients with acute ST-elevation myocardial infarction of the anterior wall treated with percutaneous coronary intervention were randomly assigned to the group that underwent intracoronary injection of autologous mononuclear BMC or to the control group, in which neither aspiration nor sham injection was performed. Left ventricular function was assessed with the use of electrocardiogram-gated single-photon-emission computed tomography (SPECT) and echocardiography at baseline and magnetic resonance imaging (MRI) 2 to 3 weeks after the infarction. These procedures were repeated 6 months after the infarction. End points were changes in the left ventricular ejection fraction (LVEF), end-diastolic volume, and infarct size. Of the 50 patients assigned to treatment with mononuclear BMC, 47 underwent intracoronary injection of the cells at a median of 6 days after myocardial infarction. There were 50 patients in the control group. The mean (+/-SD) change in LVEF, measured with the use of SPECT, between baseline and 6 months after infarction for all patients was 7.6+/-10.4 percentage points. The effect of BMC treatment on the change in LVEF was an increase of 0.6 percentage point (95% confidence interval [CI], -3.4 to 4.6; P=0.77) on SPECT, an increase of 0.6 percentage point (95% CI, -2.6 to 3.8; P=0.70) on echocardiography, and a decrease of 3.0 percentage points (95% CI, 0.1 to -6.1; P=0.054) on MRI. The two groups did not differ significantly in changes in left ventricular end-diastolic volume or infarct size and had similar rates of adverse events. With the methods used, we found no effects of intracoronary injection of autologous mononuclear BMC on global left ventricular function. 2006 Massachusetts Medical Society
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              The role of stem cells in skeletal and cardiac muscle repair.

              In postnatal muscle, skeletal muscle precursors (myoblasts) can be derived from satellite cells (reserve cells located on the surface of mature myofibers) or from cells lying beyond the myofiber, e.g., interstitial connective tissue or bone marrow. Both of these classes of cells may have stem cell properties. In addition, the heretical idea that post-mitotic myonuclei lying within mature myofibers might be able to re-form myoblasts or stem cells is examined and related to recent observations for similar post-mitotic cardiomyocytes. In adult hearts (which previously were not considered capable of repair), the role of replicating endogenous cardiomyocytes and the recruitment of other (stem) cells into cardiomyocytes for new cardiac muscle formation has recently attracted much attention. The relative contribution of these various sources of precursor cells in postnatal muscles and the factors that may enhance stem cell participation in the formation of new skeletal and cardiac muscle in vivo are the focus of this review. We concluded that, although many endogenous cell types can be converted to skeletal muscle, the contribution of non-myogenic cells to the formation of new postnatal skeletal muscle in vivo appears to be negligible. Whether the recruitment of such cells to the myogenic lineage can be significantly enhanced by specific inducers and the appropriate microenvironment is a current topic of intense interest. However, dermal fibroblasts appear promising as a realistic alternative source of exogenous myoblasts for transplantation purposes. For heart muscle, experiments showing the participation of bone marrow-derived stem cells and endothelial cells in the repair of damaged cardiac muscle are encouraging.
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                Author and article information

                Contributors
                Role: ND
                Role: ND
                Role: ND
                Role: ND
                Role: ND
                Journal
                rcca
                Revista Colombiana de Cardiología
                Rev. Colomb. Cardiol.
                Sociedad Colombiana de Cardiologia. Oficina de Publicaciones (Bogota )
                0120-5633
                April 2011
                : 18
                : 2
                : 111-118
                Affiliations
                [1 ] Universidad de Antioquia Colombia
                Article
                S0120-56332011000200006
                10.1016/S0120-5633(11)70173-5
                ee6b9350-c9bf-49fb-aabd-cd0258b9d584

                http://creativecommons.org/licenses/by/4.0/

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                Product

                SciELO Colombia

                Self URI (journal page): http://www.scielo.org.co/scielo.php?script=sci_serial&pid=0120-5633&lng=en
                Categories
                CARDIAC & CARDIOVASCULAR SYSTEMS

                Cardiovascular Medicine
                stem cells,coronary heart disease,ventricular function,granulocyte colony stimulating factor,células madre,enfermedad coronaria,función ventricular,factor estimulante de colonias de granulocito

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