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2.
NPJ Regen Med ; 6(1): 38, 2021 Jul 22.
Artículo en Inglés | MEDLINE | ID: mdl-34294733

RESUMEN

In the field of congenital heart surgery, tissue-engineered vascular grafts (TEVGs) are a promising alternative to traditionally used synthetic grafts. Our group has pioneered the use of TEVGs as a conduit between the inferior vena cava and the pulmonary arteries in the Fontan operation. The natural history of graft remodeling and its effect on hemodynamic performance has not been well characterized. In this study, we provide a detailed analysis of the first U.S. clinical trial evaluating TEVGs in the treatment of congenital heart disease. We show two distinct phases of graft remodeling: an early phase distinguished by rapid changes in graft geometry and a second phase of sustained growth and decreased graft stiffness. Using clinically informed and patient-specific computational fluid dynamics (CFD) simulations, we demonstrate how changes to TEVG geometry, thickness, and stiffness affect patient hemodynamics. We show that metrics of patient hemodynamics remain within normal ranges despite clinically observed levels of graft narrowing. These insights strengthen the continued clinical evaluation of this technology while supporting recent indications that reversible graft narrowing can be well tolerated, thus suggesting caution before intervening clinically.

3.
World J Pediatr Congenit Heart Surg ; 10(4): 505-507, 2019 07.
Artículo en Inglés | MEDLINE | ID: mdl-29614908

RESUMEN

Aortic root dilatation is a well-known complication in patients with congenital aortic valve malformation, tetralogy of Fallot, or a double outlet right ventricle. We report two rare patients who underwent composite graft replacement of the aortic root with a mechanical valve, the so-called Bentall-type operation, after Fontan completion. The pathological examination on the resected aortic wall revealed mucoid degeneration in tunica media and elastic fiber fragmentation. Our report emphasizes the need for close observation of these patients over a long-term period.


Asunto(s)
Aorta Torácica/cirugía , Implantación de Prótesis Vascular/métodos , Procedimiento de Fontan/métodos , Cardiopatías Congénitas/cirugía , Adolescente , Aorta Torácica/diagnóstico por imagen , Niño , Cardiopatías Congénitas/diagnóstico , Humanos , Masculino , Reoperación
4.
Tissue Eng Part A ; 20(1-2): 346-55, 2014 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-23957852

RESUMEN

We previously developed and validated a murine model for investigating neotissue formation in tissue-engineered vascular grafts (TEVGs). Herein, we present the first longitudinal assessment of both the microstructural composition and the mechanical properties of a TEVG through the process of neovessel formation (total scaffold degradation). We show that when (poly)glycolic acid-based biodegradable scaffolds were used as inferior vena cava interposition grafts in mice, the evolving neovessel developed biaxial properties that approached those of the native vein within 24 weeks of implantation. Further, we found that these changes in biaxial properties related temporally to extracellular matrix production and remodeling, including deposition of collagen (types I and III), elastic fibers (elastin and fibrillin-1), and glycosaminoglycans in addition to changes in matrix metalloproteinase (MMP)-2 and -9 activity. Improving our understanding of the mechanobiological principles underlying vascular neotissue formation in TEVGs holds great promise for improving the design of TEVGs and enabling us to continue the translation of this technology from the bench to the clinic.


Asunto(s)
Circulación Sanguínea/fisiología , Prótesis Vascular , Modelos Animales , Presión , Ingeniería de Tejidos/métodos , Andamios del Tejido/química , Vena Cava Inferior/fisiología , Animales , Fenómenos Biomecánicos , Matriz Extracelular/metabolismo , Fibrilina-1 , Fibrilinas , Implantes Experimentales , Metaloproteinasa 2 de la Matriz/metabolismo , Metaloproteinasa 9 de la Matriz/metabolismo , Ratones , Ratones SCID , Proteínas de Microfilamentos/metabolismo
5.
FASEB J ; 25(12): 4150-61, 2011 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-21846838

RESUMEN

A major limitation of tissue engineering research is the lack of noninvasive monitoring techniques for observations of dynamic changes in single tissue-engineered constructs. We use cellular magnetic resonance imaging (MRI) to track the fate of cells seeded onto functional tissue-engineered vascular grafts (TEVGs) through serial imaging. After in vitro optimization, murine macrophages were labeled with ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles and seeded onto scaffolds that were surgically implanted as inferior vena cava interposition grafts in SCID/bg mice. Serial MRI showed the transverse relaxation times (T(2)) were significantly lower immediately following implantation of USPIO-labeled scaffolds (T(2) = 44 ± 6.8 vs. 71 ± 10.2 ms) but increased rapidly at 2 h to values identical to control implants seeded with unlabeled macrophages (T(2) = 63 ± 12 vs. 63 ± 14 ms). This strongly indicates the rapid loss of seeded cells from the scaffolds, a finding verified using Prussian blue staining for iron containing macrophages on explanted TEVGs. Our results support a novel paradigm where seeded cells are rapidly lost from implanted scaffolds instead of developing into cells of the neovessel, as traditionally thought. Our findings confirm and validate this paradigm shift while demonstrating the first successful application of noninvasive MRI for serial study of cellular-level processes in tissue engineering.


Asunto(s)
Prótesis Vascular , Macrófagos/citología , Ingeniería de Tejidos , Animales , Línea Celular , Supervivencia Celular , Macrófagos/metabolismo , Imagen por Resonancia Magnética , Nanopartículas de Magnetita , Ratones , Ratones SCID , Andamios del Tejido , Vena Cava Inferior/citología , Vena Cava Inferior/cirugía
6.
Tissue Eng Part C Methods ; 17(10): 993-8, 2011 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-21609305

RESUMEN

INTRODUCTION: We created the first tissue-engineered vascular graft (TEVG) to be successfully used in humans. The TEVG is made by seeding autologous bone marrow-derived mononuclear cells (BM-MNCs) onto a biodegradable tubular scaffold fabricated from polyglycolic-acid mesh coated with a 50:50 copolymer of poly-L-lactide and-ɛ-caprolactone. In the initial clinical study, the BM-MNCs were isolated using a Ficoll density centrifugation method. Use of this cell isolation technique is problematic in that it is performed using an open system and therefore is susceptible to contamination. As a first step toward creating a closed system for assembling a TEVG, we evaluated the use of a filter-based method for isolating BM-MNCs and compared it to density centrifugation in Ficoll. METHODS: BM-MNCs were isolated from human BM using density centrifugation in Ficoll or a filter-based method. BM-MNCs were seeded onto biodegradable tubular scaffold and incubated for 24 h before implantation. The TEVG were implanted as inferior vena cava interposition grafts in SCID/bg mice (n=24) using microsurgical technique. Grafts were followed with ultrasonography and computed tomography-angiography. Ten weeks after implantation the TEVG were explanted and examined using histology and immunohistochemistry. RESULTS: Both methods isolated similar number of cells (Ficoll: 8.5±6.6×10(6)/mL, Filter: 6.6±3.5×10(6)/mL; p=0.686) with similar viability as assayed using fluorescence-activated cell sorting (FACS) (Ficoll: 97.0%±1.5%, Filter: 95.9%±3.0%; p=0.339). FACS analysis demonstrated that the fraction of lymphocytes and monocytes to total cells was lower in the filter group (CD4 in Ficoll: 8.9%±1.1%, CD4 in Filter: 3.5%±0.8%; p=0.002, CD8 in Ficoll: 9.4%±2.1%, CD8 in Filter: 3.9%±1.4%; p=0.021, Monocyte in Ficoll: 6.9%±1.0%, Monocyte in Filter: 2.7%±1.0%; p=0.008), consistent with granulocyte contamination (Ficoll: 46.6±2.7×10(6)/mL, Filter: 58.1±5.2×10(6)/mL; p<0.001). The ratio of stem cells to BM-MNCs was comparable between groups. There were no statistically significant differences with regard to TEVG patency and morphology between groups. Both methods of cell isolation produced neovessels with similar histology. CONCLUSION: Filter-based BM-MNC isolation is comparable to BM-MNC isolation using density centrifugation in Ficoll for TEVG assembly. The filter-based cell isolation technique has the added advantage of the potential to create a closed disposable system.


Asunto(s)
Prótesis Vascular , Células de la Médula Ósea/citología , Separación Celular/métodos , Centrifugación por Gradiente de Densidad/métodos , Filtración/instrumentación , Leucocitos Mononucleares/citología , Ingeniería de Tejidos/métodos , Animales , Vasos Sanguíneos/diagnóstico por imagen , Vasos Sanguíneos/patología , Citometría de Flujo , Humanos , Ratones , Ratones SCID , Factores de Tiempo , Tomografía Computarizada por Rayos X , Ultrasonografía
7.
FASEB J ; 25(8): 2731-9, 2011 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-21566209

RESUMEN

We developed a tissue-engineered vascular graft composed of biodegradable scaffold seeded with autologous bone marrow-derived mononuclear cells (BMMCs) that is currently in clinical trial and developed analogous mouse models to study mechanisms of neovessel formation. We previously reported that seeded human BMMCs were rapidly lost after implantation into immunodeficient mice as host macrophages invaded the graft. As a consequence, the resulting neovessel was entirely of host cell origin. Here, we investigate the source of neotissue cells in syngeneic BMMC-seeded grafts, implanted into immunocompetent mouse recipients. We again find that seeded BMMCs are lost, declining to 0.02% at 14 d, concomitant with host macrophage invasion. In addition, we demonstrate using sex-mismatched chimeric hosts that bone marrow is not a significant source of endothelial or smooth muscle cells that comprise the neovessel. Furthermore, using composite grafts formed from seeded scaffold anastomosed to sex-mismatched natural vessel segments, we demonstrate that the adjacent vessel wall is the principal source of these endothelial and smooth muscle cells, forming 93% of proximal neotissue. These findings have important implications regarding fundamental mechanisms underlying neotissue formation; in this setting, the tissue-engineered construct functions by mobilizing the body's innate healing capabilities to "regenerate" neotissue from preexisting committed tissue cells.


Asunto(s)
Prótesis Vascular , Vasos Sanguíneos/fisiología , Regeneración Tisular Dirigida/métodos , Animales , Trasplante de Médula Ósea , Supervivencia Celular , Femenino , Humanos , Leucocitos Mononucleares/trasplante , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Transgénicos , Andamios del Tejido , Trasplante Isogénico
8.
Asian Cardiovasc Thorac Ann ; 18(1): 22-6, 2010 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-20124292

RESUMEN

Heparin is the routine anticoagulant for cardiopulmonary bypass, but complications due to heparin are often reported. This study assessed argatroban as an alternative to heparin. Normothermic cardiopulmonary bypass with hemodilution was performed for 2 h in 15 dogs (mean weight, 9.8 kg) randomly assigned to 3 groups of 5 each. The controls were given heparin 200 IU x kg(-1) before cardiopulmonary bypass; group A had argatroban infused continuously at a rate of 20 microg x kg(-1) x min(-1); group H/A had half doses of both heparin (100 IU x kg(-1)) and argatroban (10 microg x kg(-1) x min(-1)). Blood samples were collected at 5 time points during the experiment. Activated clotting time, hemoglobin level, platelet counts, and serum concentrations of fibrinogen, antithrombin III, and thrombin-antithrombin III complex were measured. The platelet count was reduced significantly, and the production of thrombin-antithrombin III complex was inhibited in group H/A. Activated clotting time remained <300 sec at all time points in group A, but it was maintained at approximately 400 sec in group H/A. Fibrinogen and antithrombin III levels were reduced to half in all groups after initiation of cardiopulmonary bypass. The simultaneous use of heparin and argatroban infusion might be useful for cardiopulmonary bypass with hemodilution.


Asunto(s)
Anticoagulantes/administración & dosificación , Puente Cardiopulmonar/métodos , Heparina/administración & dosificación , Cuidados Intraoperatorios/métodos , Ácidos Pipecólicos/administración & dosificación , Animales , Anticoagulantes/sangre , Antitrombina III/efectos de los fármacos , Arginina/análogos & derivados , Coagulación Sanguínea/efectos de los fármacos , Plaquetas/efectos de los fármacos , Perros , Esquema de Medicación , Quimioterapia Combinada/métodos , Fibrinógeno/efectos de los fármacos , Hemoglobinas/efectos de los fármacos , Heparina/sangre , Infusiones Intravenosas , Ácidos Pipecólicos/sangre , Sulfonamidas , Trombina/efectos de los fármacos
9.
Stem Cells Dev ; 19(1): 105-16, 2010 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-19580375

RESUMEN

Previous studies have revealed c-kit-positive (c-kit(+)) cardiac stem cells (CSCs) in the adult mammalian heart and these cells could be a suitable cell source for heart regeneration therapy. However, these cells have not been fully evaluated in terms of characterization and effect of long-term culture, which is necessary for their safe and optimal usage. Therefore, we isolated c-kit(+) CSCs from adult rat hearts to characterize these cells and investigate stability over long-term culture. We performed isolations of c-kit(+) CSCs 11 times and passaged them 40 times in a bulk culture system; we termed these cultures, bulk culture CSCs (CSC-BC). c-kit(+) CSCs expressed stemness genes and exhibited stem cell properties of single cell-derived clone formation, cardiosphere generation, and potential to differentiate into the three main cardiac lineages: cardiomyocyte, smooth muscle, and endothelial cells in vitro. Over long-term culture, some CSC-BC up-regulated GATA-4 expression, which resulted in enhanced cardiomyocyte differentiation, suggesting that the GATA-4 high c-kit(+) CSCs have potent cardiac regenerative potential. We also observed the spontaneous differentiation into cells other than cardiac lineages, such as adipocyte and skeletal myocyte. This effect of long-term culture on the c-kit(+) CSCs has not been previously reported. Interestingly, when c-kit(+) CSCs were co-cultured with adult rat cardiomyocytes, we found increased cardiomyocyte survival, and the growth factors, insulin-like growth factor 1 (IGF-1) and vascular endothelial growth factor (VEGF), appeared to be responsible factors. The present study suggests that c-kit(+) CSCs have great therapeutic potential yet should be further investigated and optimized as a cell source for regenerative therapies prior to transplantation.


Asunto(s)
Células Madre Adultas/citología , Células Madre Adultas/fisiología , Miocardio/citología , Proteínas Proto-Oncogénicas c-kit/metabolismo , Adipocitos/fisiología , Células Madre Adultas/metabolismo , Factores de Edad , Animales , Técnicas de Cultivo de Célula , Diferenciación Celular , Proliferación Celular , Separación Celular , Células Cultivadas , Fibras Musculares Esqueléticas/fisiología , Miocardio/metabolismo , Miocitos Cardíacos/citología , Miocitos Cardíacos/fisiología , Ratas , Ratas Endogámicas Lew , Ratas Transgénicas , Ratas Wistar , Factores de Tiempo
10.
Heart Vessels ; 23(6): 436-9, 2008 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-19037593

RESUMEN

Left ventricular outflow tract obstruction in children is classified according to the site of the obstruction into a supra-aortic type, valvular type, and subaortic type (subaortic stenosis). Subaortic stenosis, in turn, is classified into two major subtypes, i.e., a discrete type, which accounts for most cases and a tunnel type, and one minor subtype, the accessory mitral tissue type, which is rare. Systolic anterior motion (SAM) is a phenomenon that is commonly observed in hypertrophic cardiomyopathy. We report a rare case of subaortic stenosis associated with SAM, which was caused by cleft anterior mitral leaflet and an accessory papillary muscle. Surgical treatment was successful, and there were no complications.


Asunto(s)
Cardiomiopatía Hipertrófica/complicaciones , Estenosis Subaórtica Fija/etiología , Contracción Miocárdica/fisiología , Músculos Papilares/anomalías , Adolescente , Procedimientos Quirúrgicos Cardíacos/métodos , Cardiomiopatía Hipertrófica/fisiopatología , Diagnóstico Diferencial , Estenosis Subaórtica Fija/diagnóstico , Estenosis Subaórtica Fija/fisiopatología , Ecocardiografía Transesofágica , Estudios de Seguimiento , Ventrículos Cardíacos/diagnóstico por imagen , Humanos , Masculino , Radiografía Torácica , Sístole
11.
Circulation ; 118(17): 1737-47, 2008 Oct 21.
Artículo en Inglés | MEDLINE | ID: mdl-18838562

RESUMEN

BACKGROUND: Rupture of the chordae tendineae cordis (CTC) is a well-known cause of mitral regurgitation. Despite its importance, the mechanisms by which the CTC is protected and the cause of its rupture remain unknown. CTC is an avascular tissue. We investigated the molecular mechanisms underlying the avascularity of CTC and the correlation between avascularity and CTC rupture. METHODS AND RESULTS: We found that tenomodulin, which is a recently isolated antiangiogenic factor, was expressed abundantly in the elastin-rich subendothelial outer layer of normal rodent, porcine, canine, and human CTC. Conditioned medium from cultured CTC interstitial cells strongly inhibited tube formation and mobilization of endothelial cells; these effects were partially inhibited by small-interfering RNA against tenomodulin. The immunohistochemical analysis was performed on 12 normal and 16 ruptured CTC obtained from the autopsy or surgical specimen. Interestingly, tenomodulin was locally absent in the ruptured areas of CTC, where abnormal vessel formation, strong expression of vascular endothelial growth factor-A and matrix metalloproteinases, and infiltration of inflammatory cells were observed, but not in the normal or nonruptured area. In anesthetized open-chest dogs, the tenomodulin layer of tricuspid CTC was surgically filed, and immunohistological analysis was performed after several months. This intervention gradually caused angiogenesis and expression of vascular endothelial growth factor-A and matrix metalloproteinases in the core collagen layer in a time-dependent manner. CONCLUSIONS: These findings provide evidence that tenomodulin is expressed universally in normal CTC in a concentric pattern and that local absence of tenomodulin, angiogenesis, and matrix metalloproteinase activation are associated with CTC rupture.


Asunto(s)
Cuerdas Tendinosas/lesiones , Cuerdas Tendinosas/fisiología , Enfermedades de las Válvulas Cardíacas/metabolismo , Metaloproteinasas de la Matriz/metabolismo , Proteínas de la Membrana/deficiencia , Neovascularización Patológica/metabolismo , Anciano , Anciano de 80 o más Años , Animales , Células Cultivadas , Cuerdas Tendinosas/enzimología , Perros , Elastina/metabolismo , Endotelio Vascular/enzimología , Endotelio Vascular/metabolismo , Activación Enzimática/fisiología , Femenino , Enfermedades de las Válvulas Cardíacas/genética , Enfermedades de las Válvulas Cardíacas/fisiopatología , Humanos , Masculino , Proteínas de la Membrana/genética , Proteínas de la Membrana/fisiología , Ratones , Ratones Endogámicos ICR , Persona de Mediana Edad , Neovascularización Patológica/genética , Neovascularización Patológica/fisiopatología , Conejos , Rotura/genética , Rotura/metabolismo , Porcinos
12.
Asian Cardiovasc Thorac Ann ; 16(4): 309-12, 2008 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-18670025

RESUMEN

Dense adhesions in the retrosternal space make reoperations difficult in the field of cardiovascular surgery. Several substitutes for pericardium have been employed to prevent dense adhesions forming, but they have been unsatisfactory because of peel formation, calcification, and infection. To overcome these drawbacks, a novel biodegradable pericardial substitute was developed from gelatin obtained from specific-pathogen-free porcine skin and a bioabsorbable polyester mesh, which persists while the adhesion reaction occurs in the retrosternal space. A clinical pilot study of this gelatin sheet was carried out in patients scheduled to receive multistage cardiac surgery. From February 2003 to July 2004, the material was used in 5 patients aged 0.4 to 3.0 years. There were no complications related to the gelatin sheet. The effectiveness of the material was evaluated when the sternum was reopened 1.4 +/- 0.5 years later. It took 24.5 +/- 6.0 min for the resternotomy, and all surgeons who participated in the surgery rated the effectiveness of the gelatin sheet as "good". This anti-adhesive sheet prevented dense adhesions, suggesting that this material may be useful as a pericardial substitute for multistage pediatric cardiac surgery.


Asunto(s)
Materiales Biocompatibles , Procedimientos Quirúrgicos Cardíacos/instrumentación , Gelatina , Cardiopatías Congénitas/cirugía , Pericardio , Adherencias Tisulares/prevención & control , Procedimientos Quirúrgicos Cardíacos/efectos adversos , Preescolar , Femenino , Estudios de Seguimiento , Humanos , Lactante , Masculino , Proyectos Piloto , Complicaciones Posoperatorias/prevención & control , Diseño de Prótesis , Estudios Retrospectivos , Adherencias Tisulares/etiología , Resultado del Tratamiento
13.
J Thorac Cardiovasc Surg ; 135(4): 850-6, 2008 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-18374766

RESUMEN

OBJECTIVE: This study was to evaluate the efficacy of the hyaluronic acid (HA) bioabsorbable membrane combined use with both expanded-polytetrafluoroethylene (ePTFE) and autologous pericardium for preventing postoperative pericardial adhesions. METHODS: The HA bioresorbable surgical membrane (Seprafilm, Genzyme, Cambridge, Mass) was used with either ePTFE or autologous pericardium in an experimental pericardial adhesion model. Twenty-four beagle dogs were classified as follows; Group A (n = 6): ePTFE only, Group B (n = 6): Seprafilm + ePTFE, Group C (n = 6): autologous pericardium only, Group D (n = 6): Seprafilm + autologous pericardium. Pericardial adhesions were evaluated at necropsy at 4, 8, and 12 weeks. The tenacity of adhesion was graded by macroscopic examination, and the adhesion tissue thickness was analyzed microscopically with an image processing program. The regeneration of mesothelial cells on neo-tissue fibrils were immunohistochemically studied. RESULTS: In groups B and D, the adhesions were significant lower compared with those of control groups in the tenacity (Group A vs B: 2.5 +/- 0.55 vs 1.5 +/- 0.55, P < 0.05; Group C vs D: 3.2 +/- 0.75 vs 0.33 +/- 0.52, P < 0.01) and the tissue thickness (Group A vs B: 30.4 +/- 12.9 vs 10.3 +/- 4.42, P < 0.01; Group C vs D: 22.6 +/- 11.5 vs 4.96 +/- 4.87, P < 0.01). Immunohistochemically, a single layer of mesothelial cells were regenerated on the surface of neo-tissue fibrils in HA treated groups. CONCLUSION: The combined use of Seprafilm with either ePTFE or autologous pericardium effectively reduced the formation of pericardial adhesion.


Asunto(s)
Materiales Biocompatibles/administración & dosificación , Ácido Hialurónico/administración & dosificación , Membranas Artificiales , Pericardio/trasplante , Politetrafluoroetileno/administración & dosificación , Adherencias Tisulares/prevención & control , Animales , Procedimientos Quirúrgicos Cardíacos , Modelos Animales de Enfermedad , Perros , Adherencias Tisulares/etiología , Trasplante Autólogo
14.
Arterioscler Thromb Vasc Biol ; 28(4): 637-43, 2008 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-18202326

RESUMEN

OBJECTIVE: Peripheral arterial disease (PAD) can have severe consequences on patient mortality and morbidity. In contrast to approaches using growth factor administration or isolated cell transplantation, we attempted to develop an alternative method for ischemic therapy using the transplantation of tissue engineered cell sheets with angiogenic potential. METHODS AND RESULTS: Human smooth muscle cell (SMC) and fibroblast cell (FbC) sheets were harvested from temperature-responsive culture dishes and transplanted into ischemic hind limbs of athymic rats. ELISA showed significantly increased in vitro secretion of angiogenic factors by SMCs in comparison to FbCs. Twenty-one days after transplantation, laser doppler analysis demonstrated significantly increased blood perfusion in the SMC group. Perfusion with Indian ink and immunohistochemistry also revealed significantly greater numbers of functional capillaries in the SMC group. Finally, cell tracing experiments revealed that some SMCs from the transplanted cell sheets migrated into the ischemic tissues, contributing to newly formed vessels. CONCLUSIONS: SMC sheet transplantation allows for controlled and localized delivery of cells that possess angiogenic potential directly to ischemic tissues. Through the secretion of angiogenic factors, as well as cell migration and integration with newly formed vessels, SMC sheet transplantation provides an effective method for the revascularization of ischemic tissues.


Asunto(s)
Músculo Liso Vascular/trasplante , Neovascularización Fisiológica , Enfermedades Vasculares Periféricas/terapia , Proteínas Angiogénicas/metabolismo , Animales , Velocidad del Flujo Sanguíneo , Fibroblastos/trasplante , Miembro Posterior/irrigación sanguínea , Humanos , Isquemia/diagnóstico por imagen , Isquemia/terapia , Flujometría por Láser-Doppler , Masculino , Músculo Liso Vascular/citología , Miocitos del Músculo Liso/trasplante , Enfermedades Vasculares Periféricas/diagnóstico por imagen , Ratas , Ratas Desnudas , Técnicas de Cultivo de Tejidos , Ingeniería de Tejidos/métodos , Trasplante Heterólogo , Ultrasonografía
15.
Eur J Cardiothorac Surg ; 32(2): 202-8, 2007 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-17512210

RESUMEN

OBJECTIVE: Our treatment strategy for pulmonary atresia with ventricular septal defect (VSD) and major aortopulmonary collateral arteries is a staged repair that comprises the first complete unifocalization (UF) with 'unification' of intrapulmonary arteries and then the definitive repair. The purpose of this study is to evaluate the outcome of our staged repair strategy with complete UF and to determine the results of our current management strategy. METHODS: From 1982 to 2004, 113 consecutive patients were treated with staged repair at our institute. We evaluated the risk of definitive repair failure or death in the 3 years after definitive repair using logistic regression. Furthermore, we compared the early group (patients who underwent UF before December 1995) and the late group (patients who underwent UF after January 1996). RESULTS: The mean follow-up interval was 8.8 years (0.8 months to 23.3 years), and Kaplan-Meier-estimated overall survival rates after first UF were 80.9, 73.8, and 69.9% at 5, 10, and 15 years, respectively. Survival in patients with an absent central pulmonary artery (PA) was significantly lower than in those with a central PA (p<0.05), and the factor that was significantly associated with definitive repair failure or death in the 3 years after definitive repair was central PA morphology (p<0.05). Higher mean PA pressure after UF was detected in patients with hypoplastic central PA, compared with those without hypoplastic PA (30.9 mmHg vs 23.3 mmHg, p<0.05). In the late group, age (in years) at first UF (3.9 vs 8.4, p<0.01), second UF (4.3 vs 9.2, p<0.01), and definitive repair (5.8 vs 9.1, p<0.01) was significantly younger than in early group, and the survival rate after first UF in the late group was 96.2 and 91.3% at 3 and 7 years, respectively. Systolic right ventricular pressure and the pressure ratio between the right and the left ventricles after definitive repair in the late group were significantly lower than in the early group (53.6 mmHg vs 75.0 mmHg, p<0.01; 61.7% vs 75.9%, p<0.05). CONCLUSIONS: Hypoplastic central PA was a significant risk factor in this disease. The overall survival was improved by our current management strategy. Improved RV pressure after definitive repair appears to affect the long-term outcome.


Asunto(s)
Defecto del Tabique Aortopulmonar/cirugía , Circulación Colateral/fisiología , Defectos del Tabique Interventricular/cirugía , Atresia Pulmonar/cirugía , Anomalías Múltiples/mortalidad , Anomalías Múltiples/fisiopatología , Anomalías Múltiples/cirugía , Adolescente , Adulto , Aorta/anomalías , Aorta/cirugía , Aorta Torácica/anomalías , Aorta Torácica/cirugía , Defecto del Tabique Aortopulmonar/mortalidad , Defecto del Tabique Aortopulmonar/fisiopatología , Presión Sanguínea/fisiología , Procedimientos Quirúrgicos Cardíacos/métodos , Niño , Femenino , Defectos del Tabique Interventricular/mortalidad , Defectos del Tabique Interventricular/fisiopatología , Humanos , Estimación de Kaplan-Meier , Masculino , Arteria Pulmonar/anomalías , Arteria Pulmonar/patología , Atresia Pulmonar/mortalidad , Atresia Pulmonar/fisiopatología , Factores de Riesgo , Arteria Subclavia/anomalías , Arteria Subclavia/cirugía , Resultado del Tratamiento
16.
J Thorac Cardiovasc Surg ; 133(5): 1318-28, 1328.e1-4, 2007 May.
Artículo en Inglés | MEDLINE | ID: mdl-17467450

RESUMEN

OBJECTIVE: This study was undertaken to compare long-term results of various types of surgical repairs for either congenitally corrected transposition of the great arteries or double outlet right ventricle with discordant atrioventricular connections, and to analyze the risk factors that affect early and late mortality and reintervention. METHODS: Between January 1972 and September 2005, a total of 189 patients (median age 8.3 years, range 2 months to 47 years old) with congenitally corrected transposition of the great arteries or double outlet right ventricle with discordant atrioventricular connections underwent definitive repairs. The definitive repairs comprised a conventional repair (atrial septal defect, or ventricular septal defect closure with or without pulmonary stenosis release, or isolated tricuspid valve surgery) in 36 patients (group I), conventional Rastelli in 31 patients (group II), double-switch operation (atrial switch plus arterial switch) in 15 patients (group III), atrial switch plus intraventricular rerouting (with or without extracardiac conduits) in 69 patients (group IV), and a Fontan-type repair in 38 patients (group V). The mean follow-up period was 10.1 years. Hospitalization and late mortality and reoperation were indicated as events. Risk factors for these events were analyzed by logistic regression for hospital death and a Cox proportional hazards model for late events. RESULTS: The Kaplan-Meier survival including hospital and late mortality was 62.4% at 32 years in group I, 78.5% at 27 years in group II, 74.5% at 15 years in group III, 80% at 16 years in group IV, and 79.3% at 22 years in group V. The reoperation-free ratio was 64.2% in group I, 76.6% in group II, 84.4% in group III, 89.6% in group IV, and 91.3% in group V. Risk analyses showed that the risk for hospital death was preoperative in patients with more than moderate tricuspid regurgitation and a cardiopulmonary bypass time of more than 240 minutes. A risk for late mortality was the presence of tricuspid regurgitation. Risks for reoperation were preoperative cardiomegaly, preoperative tricuspid regurgitation of more than grade II, ventricular septal defect enlargement, and body weight less than 10 kg. Risks for pacemaker implantation, as indicated by multivariate analysis, were ventricular septal defect enlargement during operation and age less than 3 years. CONCLUSIONS: There were no statistical differences between long-term survival rates of patients who underwent conventional surgical repair versus those of patients who underwent anatomic surgical repair. Results of conventional repair were satisfactory except in patients with significant tricuspid regurgitation. Results of anatomic repair were also satisfactory even for patients with significant tricuspid regurgitation, and therefore, anatomic repair should be the procedure of choice for those patients.


Asunto(s)
Transposición de los Grandes Vasos/cirugía , Adolescente , Presión Sanguínea , Procedimientos Quirúrgicos Cardíacos , Niño , Ventrículo Derecho con Doble Salida/mortalidad , Ventrículo Derecho con Doble Salida/cirugía , Femenino , Estudios de Seguimiento , Cardiopatías Congénitas/patología , Cardiopatías Congénitas/cirugía , Defectos del Tabique Interventricular/cirugía , Humanos , Masculino , Evaluación de Resultado en la Atención de Salud , Atresia Pulmonar/cirugía , Estenosis de la Válvula Pulmonar/congénito , Estenosis de la Válvula Pulmonar/cirugía , Medición de Riesgo , Volumen Sistólico , Tasa de Supervivencia , Transposición de los Grandes Vasos/mortalidad , Insuficiencia de la Válvula Tricúspide/cirugía
17.
J Thorac Cardiovasc Surg ; 133(1): 29-36, 2007 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-17198777

RESUMEN

OBJECTIVES: The effect of hemodilution on neurologic outcome after cardiopulmonary bypass remains unclear. We studied the influences of hematocrit on cerebral oxygenation and neuropathologic outcome in a piglet model. METHODS: Eleven piglets (9.3 +/- 1.1 kg) were randomized into 2 groups. Five piglets (group H) received a total blood prime resulting in a high hematocrit (33.0% +/- 2.3%), and 6 piglets (group L) received a crystalloid prime resulting in a low hematocrit (14.0% +/- 3.2%). Both groups underwent 90 minutes of moderate hypothermic cardiopulmonary bypass (28 degrees C) with alpha-stat strategy. Cerebral oxygenation was monitored by near-infrared spectroscopy. Group L received a blood transfusion immediately after cardiopulmonary bypass to reach the postoperative target hematocrit of 30%. The brain was fixed in situ 6 hours after weaning from cardiopulmonary bypass, and a histologic score for neurologic injury was assessed. RESULTS: There were no significant differences in arterial blood gas analyses throughout the experiment between the groups. Mean arterial pressure, mixed venous oxygen saturation, and heart rate were significantly higher in group H compared with group L during hypothermia. Oxyhemoglobin and total hemoglobin signals detected by near-infrared spectroscopy were significantly lower in group L (analysis of variance, P < .0001), although the tissue oxygenation index was not different during cardiopulmonary bypass. Group L showed a poorer histologic score compared with group H (P = .0071). CONCLUSIONS: Excessive hemodilution, such as a hematocrit of less than 15%, may be associated with a high incidence of neurologic injury. Further studies are required to determine the safety limits of hematocrit during pediatric cardiopulmonary bypass.


Asunto(s)
Encéfalo/patología , Puente Cardiopulmonar , Hematócrito , Hemodilución/efectos adversos , Anemia/etiología , Animales , Presión Sanguínea , Temperatura Corporal , Encéfalo/metabolismo , Citocromos a/metabolismo , Frecuencia Cardíaca , Hemoglobinas/análisis , Monitoreo Intraoperatorio , Oxígeno/sangre , Consumo de Oxígeno , Oxihemoglobinas/análisis , Espectroscopía Infrarroja Corta , Sus scrofa
19.
Interact Cardiovasc Thorac Surg ; 5(5): 599-601, 2006 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-17670657

RESUMEN

OBJECTIVES: A girl who was diagnosed with cyanotic congenital heart disease in a newborn, showed anoxic spell attacks which we thought were correlated with the congenital heart disease. Although she underwent the palliative operation at 8 months old and her SpO2 was increased, she experienced severe and life-threatening respiratory dysfunction many times after that. After careful examinations, the respiratory complaint was proved to be not only due to cyanotic congenital heart disease but also tracheobronchomalacia. METHOD: She had undergone the external stenting to the trachea and right bronchus at 1 year old. After that, she was examined by cardiac catheterization and the Fontan-type operation was successful using a tissue-engineered graft at 2 years old. RESULTS: Her post-operative course was uneventful and she was discharged. CONCLUSION: It is very important to remember the possible existence of tracheobronchomalacia and prevent a life-threatening attack when congenital cardiac patients experience a prolonged respiratory failure or abnormal respiration.

20.
Interact Cardiovasc Thorac Surg ; 5(6): 792-3, 2006 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-17670716

RESUMEN

We report a case of a 13-year-old boy with congenitally corrected transposition of the great arteries after conventional repair who underwent an implantation of ventricular assist device (VAD) due to right (systemic) ventricular failure after tricuspid valve replacement. The anatomical right ventricle (systemic ventricle) was completely unloaded and the function improved over time under LVAD. He had an explantation of the VAD due to bacteremia 43 days after implantation, and his clinical condition improved significantly.

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