RESUMEN
BACKGROUND: Implantation of a left ventricular assist device (LVAD) is an acceptable therapy for patients with advanced heart failure. LVADs may be used as a bridge to recovery, a bridge to transplantation or as destination therapy. Although the morbidity rate of individuals on device support remains high, experience suggests that patients who are discharged home have satisfactory outcomes during support and following heart transplantation. METHODS: A retrospective review of 24 patients implanted with an LVAD between October 2001 and December 2006 was performed. Nineteen patients received a device as a bridge to transplantation and five received a device as destination therapy. Postoperative follow-up was performed routinely in the heart function/LVAD clinic at the Toronto General Hospital (Toronto, Ontario) and all adverse events were recorded. RESULTS: The majority of patients were men, with a mean age of 44 years and a diagnosis of dilated cardiomyopathy (62%). Seventeen patients (71%) were discharged home on support; one died, 14 were transplanted, one was explanted and one patient remains on support in the community. Post-transplant survival was 93% in patients discharged home compared with 40% transplanted during their hospital stay. Outpatients spent 56% of their overall support time at home, with only 12 readmissions totalling 120 patient days. CONCLUSIONS: LVAD patients can be safely managed in the community. Patients who are discharged home experience better outcomes in both pre- and post-transplant survival. Successful outpatient management provides a strong foundation for the establishment of destination therapy within mechanical circulatory support programs in Canada.
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Cardiomiopatía Dilatada/cirugía , Relaciones Comunidad-Institución , Continuidad de la Atención al Paciente , Insuficiencia Cardíaca/cirugía , Corazón Auxiliar , Adulto , Anciano , Cardiomiopatía Dilatada/diagnóstico , Cardiomiopatía Dilatada/mortalidad , Estudios de Cohortes , Femenino , Estudios de Seguimiento , Insuficiencia Cardíaca/diagnóstico , Insuficiencia Cardíaca/mortalidad , Trasplante de Corazón/estadística & datos numéricos , Mortalidad Hospitalaria/tendencias , Hospitales Generales , Humanos , Masculino , Persona de Mediana Edad , Ontario , Alta del Paciente , Estudios Retrospectivos , Medición de Riesgo , Índice de Severidad de la Enfermedad , Análisis de Supervivencia , Población UrbanaRESUMEN
Muscle precursor cell (myoblasts) transplantation is considered as a potential approach to restore dystrophin expression in Duchenne muscular dystrophy (DMD) patients. The study purpose was to verify the implication of hypoxia in the myoblast death observed after their transplantation and also to evaluate the potential beneficial effects of vascular endothelial growth factor (VEGF) overexpression on myoblast engraftment in a murine model. Pimonidazole hydrochloride (hypoxyprobe-1) was used to mark selectively myoblasts to evaluate their hypoxia in vivo. In vitro, hypoxia was induced by culturing human myoblasts in hypoxic environment. In vitro effects of VEGF(165) on survival of human cells was assessed by Hoescht-PI labeling. Tibialis anterior (TA) female mouse muscles were electroporated with a plasmid containing the VEGF(165) or with an empty vector. Circulating VEGF concentration was assessed by ELISA. After 2 weeks of electroporation, severe combined immunodeficient (SCID) mice were transplanted with 800 000 human male myoblasts labeled with radioactive thymidine. Mouse muscles were harvested 2 and 4 days later and myoblast survival and proliferation were evaluated by scintigraphy and Y chromosome quantitative PCR. The long-term graft success was evaluated using gamma-radiograph imaging and by counting the dystrophin positive muscle fibers. Hypoxyprobe labeling has shown that most of the transplanted myoblasts were hypoxic. The transplantation of radioactive male myoblasts in female mice electroporated with the VEGF(165) plasmid demonstrated that VEGF reduced their death by 10% but did not improve their proliferation. VEGF(165) enhanced human myoblast survival in vitro under hypoxic conditions. Electroporation of TA muscles of SCID mouse with the vector coding for VEGF(165) promoted angiogenesis and improved by 1.5-fold the success of myoblast transplantation in comparison with the control mice that were electroporated with the empty vector. These results indicate that hypoxia is partially responsible for the death of the transplanted myoblasts. VEGF can be used to improve myoblast survival and the graft success.
Asunto(s)
Terapia Genética/métodos , Distrofia Muscular de Duchenne/terapia , Mioblastos/trasplante , Factor A de Crecimiento Endotelial Vascular/uso terapéutico , Animales , Muerte Celular , Electroporación , Femenino , Cámaras gamma , Humanos , Hipoxia , Inmunohistoquímica , Ratones , Ratones SCID , Mioblastos/metabolismo , Mioblastos/patología , Retroviridae/genética , Trasplante Heterólogo , Resultado del Tratamiento , Factor A de Crecimiento Endotelial Vascular/genéticaRESUMEN
BACKGROUND AND OBJECTIVES: Excessive blood loss (EBL) is a common complication of cardiac surgery that is associated with adverse events. The objective of this before/after study was to determine whether the implementation of a protocol for management of cardiac surgical patients with EBL was associated with improved clinical outcomes. MATERIALS AND METHODS: In November 2002, a protocol for prompt identification and aggressive management of cardiac surgical patients with EBL was implemented at our institution. The independent relationship between protocol implementation and adverse outcomes was measured by comparing the outcomes of patients who received > or = 4 RBC (red blood cell) units within 1 day of surgery and were operated on before protocol implementation (2000-02) with those operated on after protocol implementation (2003-05), using multivariable logistic regression analysis to control for the effects of confounders. The primary outcome was a composite of adverse events that included death, renal failure, stroke, and sepsis. Bootstrapping was used to confirm the validity of the results. RESULTS: Of the 11,314 patients who underwent surgery during the study period, 1875 (16.6%) received > or = 4 RBC units within 1 day of surgery, with 958 and 917 in the pre- and postprotocol periods, respectively. The composite adverse outcome occurred in 164 (17.1%) patients in the preprotocol period and 115 (12.5%) patients in the postprotocol period (P = 0.005). Protocol implementation was independently associated with reduced odds of the composite adverse outcome (odds ratio 0.67; 95% confidence interval 0.50, 0.91; P = 0.01). This estimate was stable in bootstrap sampling. CONCLUSION: Implementation of a protocol to manage EBL in cardiac surgery was independently associated with improved outcomes.
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Transfusión de Componentes Sanguíneos/normas , Pérdida de Sangre Quirúrgica , Puente Cardiopulmonar , Protocolos Clínicos , Anciano , Pérdida de Sangre Quirúrgica/mortalidad , Pérdida de Sangre Quirúrgica/prevención & control , Canadá , Puente Cardiopulmonar/efectos adversos , Puente Cardiopulmonar/mortalidad , Distribución de Chi-Cuadrado , Transfusión de Eritrocitos/normas , Femenino , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Estadísticas no Paramétricas , Resultado del TratamientoRESUMEN
Cardiac surgery with cardiopulmonary bypass (CPB) induces an acute phase reaction that has been implicated in the pathogenesis of several postoperative complications. Recent data indicate that a complex sequence of events leads to the final activation of leukocytes and endothelial cells (EC), which is responsible for cell dysfunction in different organs. Activation of the contact system, endotoxemia, ischemia and reperfusion injury and surgical trauma are all potential triggers of inflammation following CPB. Different pro- and anti-inflammatory mediators (cytokines, adhesion molecules) are involved and their release is mediated by intracellular transcription factors (nuclear factor-kappa B, NF-kappa B). In this review, we examine recent advances in the understanding of the pathophysiology of the CPB-induced acute phase reaction and evaluate the different pharmacological, technical and surgical strategies used to reduce its effects. Emphasis is given to the central role of transcription factor NF-kappa B in the complex mechanism of the inflammatory reaction and to the effects of compounds such as heparin and glycosaminoglycans, phosphodiesterase inhibitors and protease inhibitors whose role as anti-inflammatory agent has only recently been recognized.
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Reacción de Fase Aguda/tratamiento farmacológico , Reacción de Fase Aguda/fisiopatología , Puente Cardiopulmonar/efectos adversos , Citocinas/metabolismo , Complicaciones Posoperatorias/tratamiento farmacológico , Puente Cardiopulmonar/métodos , Quimioterapia Combinada , Femenino , Humanos , Mediadores de Inflamación/metabolismo , Mediadores de Inflamación/fisiología , Masculino , Complicaciones Posoperatorias/fisiopatología , Pronóstico , Medición de Riesgo , Factores de RiesgoRESUMEN
PURPOSE: Myocardial angiogenesis may improve regional perfusion and perhaps function after cardiac injury. We evaluated the effect of endothelial cell transplantation into a myocardial scar on angiogenesis and ventricular function, as an alternative to angiogenic gene or protein therapy. METHODS AND RESULTS: A transmural myocardial scar was created in the left ventricular free wall of rat hearts by cryoinjury. Allogeneic aortic endothelial cells were injected into the scar 2 weeks after cryoinjury. A cluster of transplanted cells was identified at the site of injection 1 day and 1 week after transplantation, but not after 2 weeks. The size of this cluster of transplanted cells decreased as vascular density in the transplanted scar tissue increased with time. Six weeks after transplantation, vascular density was significantly greater in transplanted hearts than in control hearts. Regional blood flow, by microsphere analysis, was greater in the transplanted rats. Systolic and diastolic ventricular function was similar between groups. In a second series of experiments, syngeneic aortic endothelial cells labeled with bromodeoxyuridine were transplanted 2 weeks after cryoinjury. Vascular density in the transplanted scar was greater than in controls. Labeled transplanted endothelial cells were identified forming part of the newly developed blood vessels. No difference in vascular density was found between allogeneic and syngeneic cell transplantation. Vascular endothelial growth factor was not expressed at greater levels in the transplanted cells or the myocardial scar. CONCLUSION: Transplanted endothelial cells stimulated angiogenesis, were incorporated into the new vessels, and increased regional perfusion in myocardial scar tissue, but did not improve global function in this cryoinjury rat model.
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Endotelio Vascular/trasplante , Revascularización Miocárdica/métodos , Animales , Trasplante de Células , Ciclosporina/uso terapéutico , Factores de Crecimiento Endotelial/metabolismo , Endotelio Vascular/citología , Lesiones Cardíacas/terapia , Inmunosupresores/uso terapéutico , Linfocinas/metabolismo , Masculino , Miocardio/patología , Neovascularización Fisiológica , Isoformas de Proteínas , Ratas , Ratas Sprague-Dawley , Factor A de Crecimiento Endotelial Vascular , Factores de Crecimiento Endotelial VascularRESUMEN
UNLABELLED: BACKGROUND The combination of myocardial cell transplantation and angiogenic gene transfer may improve postinfarction left ventricular (LV) perfusion. We evaluated the angiogenic effect of heart cells transfected with vascular endothelial growth factor (VEGF) and transplanted into a myocardial scar. METHODS AND RESULTS: Donor rat heart cells were transfected with plasmids encoding VEGF(165) and green fluorescence protein. Syngeneic adult rats underwent LV cryoinjury to create a transmural scar. Three weeks later, 4x10(6) transfected heart cells (n=14), untransfected heart cells (n=13), or culture medium (n=16) were transplanted into the center of the scar. After 5 weeks, LV function, quantitative histology, and regional blood flow were evaluated. Plates of heart cells transfected with VEGF(165) produced 6.1 times more intracellular VEGF than nontransfected cells. Capillary density (mean+/-SEM) per high-power field in the center of the myocardial scar was 1.1+/-0.02 in control rats, 3.9+/-0.11 in untransfected rats, and 6.3+/-0.11 in transfected rats (P=0.0002). Capillary density in the border zone around the scar was 1.9+/-0.03 in control rats, 6.4+/-0.10 in untransfected rats, and 8.7+/-0.16 in transfected rats (P=0.004). Regional blood flow within the scar was 8.8+/-0.8% of normalized flow in control hearts, 10.4+/-0.7% in hearts transplanted with untransfected cells, but 17.6+/-1.2% in hearts transplanted with transfected cells (P=0.03 versus control, P=0.07 versus nontransfected). There was no difference in LV function attributable to transplantation with transfected cells at the time point studied. CONCLUSIONS: Transplantation of heart cells transfected with VEGF induced greater angiogenesis than transplantation of unmodified cells. Combined gene transfer and cell transplantation strategies may improve postinfarction LV perfusion and function.
Asunto(s)
Trasplante de Células , Factores de Crecimiento Endotelial/genética , Transferencia de Gen Horizontal , Linfocinas/genética , Revascularización Miocárdica/métodos , Miocardio/citología , Neovascularización Fisiológica/genética , Animales , Velocidad del Flujo Sanguíneo/efectos de los fármacos , Velocidad del Flujo Sanguíneo/genética , Recuento de Células , Células Cultivadas , Circulación Coronaria/efectos de los fármacos , Circulación Coronaria/genética , Factores de Crecimiento Endotelial/biosíntesis , Factores de Crecimiento Endotelial/farmacología , Expresión Génica , Genes Reporteros/genética , Proteínas Fluorescentes Verdes , Proteínas Luminiscentes/genética , Linfocinas/biosíntesis , Linfocinas/farmacología , Masculino , Miocardio/patología , Neovascularización Fisiológica/efectos de los fármacos , Ratas , Ratas Endogámicas Lew , Transfección , Factor A de Crecimiento Endotelial Vascular , Factores de Crecimiento Endotelial Vascular , Función Ventricular IzquierdaRESUMEN
OBJECTIVE: To evaluate the results of the maze procedure combined with mitral valve (MV) surgery in patients with chronic atrial fibrillation (AF). METHODS: From 1994--1999, 47 patients with chronic AF underwent the maze procedure combined with MV surgery (maze group). They were compared to 47 patients matched for age, sex, left ventricular function and type of MV surgery (non-maze group). The maze group had less severe symptoms but larger left atrium, and AF of longer duration than the non-maze group. One surgeon performed all operations in both groups of patients. RESULTS: There were two early deaths in the maze group (4.5%) and one (2.2%) in the non-maze group. The duration of cardiopulmonary bypass (P=0.0001) and aortic crossclamping (P=0.0001) were greater in the maze group. Mean follow-up was 26+/-3 months in the maze group and 32+/-4 months in the non-maze group, and was 100% complete. Three-year survival was 96+/-3% for the maze group compared to 85+/-7% for the non-maze group (P=0.16). At the latest follow-up, 75% of the maze patients were in sinus rhythm compared to 36% of the non-maze patients (P=0.0004); 38% of the maze group were on coumadin postoperatively, compared to 69% in the non-maze group (P=0.003); and patients in the maze group were on fewer antiarrhythmic medications (P=0.0002). Three-year freedom from thromboembolic complications was 100% for the maze group compared to 83+/-7% for the non-maze group (P=0.03). CONCLUSIONS: In this retrospective study the maze procedure did not seem to increase operative mortality of MV surgery, was effective in eliminating atrial fibrillation, and reduced the risk of thromboembolic complications and the need for long-term anticoagulation after mitral valve repair or replacement with a bioprosthesis.
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Fibrilación Atrial/cirugía , Procedimientos Quirúrgicos Cardíacos , Prótesis Valvulares Cardíacas , Insuficiencia de la Válvula Mitral/cirugía , Válvula Mitral/cirugía , Anciano , Estudios de Casos y Controles , Enfermedad Crónica , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Resultado del TratamientoAsunto(s)
Trasplante de Células , Músculo Esquelético/citología , Infarto del Miocardio/terapia , Anciano , Animales , Humanos , MasculinoRESUMEN
OBJECTIVE: The synthetic materials currently available for the repair of cardiac defects are nonviable, do not grow as the child develops, and do not contract synchronously with the heart. We developed a beating patch by seeding fetal cardiomyocytes in a biodegradable scaffold in vitro. The seeded patches survived in the right ventricular outflow tract of adult rats. METHODS: Cultured fetal or adult rat heart cells (1 x 10(6) cells) were seeded into a gelatin sponge (15 x 15 x 1 mm), and the cell number was expanded in culture for 1 or 3 weeks, respectively. The free wall of the right ventricular outflow tract in syngeneic adult rats was resected and repaired with either unseeded patches or patches seeded with either fetal or adult cardiomyocytes (n = 10 for each group). The patches were examined histologically over a 12-week period. RESULTS: A significant inflammatory reaction was noted in the patch at 4 weeks as the scaffold dissolved. At 12 weeks, the gelatin scaffold had completely dissolved. Both types of the seeded cells were detected in the patch with 5-bromo-2'-deoxyuridine staining, and they maintained their continuity. Unseeded patches had an ingrowth of fibrous tissue. The patches became thinner between the fourth and the twelfth weeks in unseeded (P =.003), fetal (P =.0001), and adult (P =.07) cardiomyocyte groups as the scaffold dissolved. The control patch, but not the cell-seeded patches, was thinner than the normal right ventricular outflow tract. The endocardial surface area of each patch was covered with endothelial cells identified by factor VIII staining. CONCLUSIONS: A gelatin patch was used to replace the right ventricular outflow tract in syngeneic rats. The seeded cells survived in the right ventricular outflow tract after the scaffold dissolved 12 weeks after implantation. In addition, the unseeded patches encouraged the ingrowth of fibrous tissue as the scaffold dissolved and the patches remained completely endothelialized.
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Implantes Absorbibles , Trasplante de Células , Ventrículos Cardíacos , Miocardio/citología , Animales , Materiales Biocompatibles , Ingeniería Biomédica , Células Cultivadas , Esponja de Gelatina Absorbible , Ventrículos Cardíacos/citología , Masculino , Ratas , Ratas Endogámicas Lew , Trasplante IsogénicoRESUMEN
OBJECTIVE: To determine the effects of patent or diseased aorta-coronary bypass grafts and retrograde cardioplegia on mortality during reoperative coronary bypass surgery. METHODS: We conducted a retrospective review of prospectively gathered data, supplemented by systematic chart review, of all patients (n = 744) undergoing reoperative coronary bypass surgery at our institution between 1990 and 1997. Independent predictors of survival were determined by stepwise logistic regression analysis. RESULTS: At least one patent or stenosed graft to the left anterior descending artery was present in 50% of patients, to the circumflex territory in 27% of patients, and to the right coronary artery territory in 33% of patients. The previous left anterior descending graft was a saphenous vein in 82% and a left internal thoracic artery in 18% of patients. In-hospital mortality occurred in 42 (5.6%) patients. Patent or diseased grafts of any coronary artery territory did not significantly increase the risk of mortality. Retrograde cardioplegia use increased in more recent years, was more frequent in patients with stenosed grafts, and was associated with improved survival. Independent predictors of mortality were as follows (with odds ratios and 95% confidence intervals in parentheses): failure to use retrograde cardioplegia (odds ratio 2.81; 1.28-6.20), New York Heart Association class (odds ratio 2.69; 1.25-5.81), peripheral vascular disease (odds ratio 2.60; 1.25-5.41), and left ventricular grade (2.07; 1.31-3.27). CONCLUSIONS: In this series, patent or stenosed grafts were not associated with an increased risk of mortality during reoperative coronary bypass surgery, possibly because of increased use of retrograde cardioplegia in this patient group. We strongly recommend the routine use of retrograde cardioplegia during redo coronary bypass surgery.
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Puente de Arteria Coronaria/métodos , Enfermedad Coronaria/cirugía , Oclusión de Injerto Vascular/cirugía , Paro Cardíaco Inducido , Arterias Torácicas/trasplante , Puente de Arteria Coronaria/mortalidad , Enfermedad Coronaria/mortalidad , Oclusión de Injerto Vascular/mortalidad , Paro Cardíaco Inducido/mortalidad , Humanos , Pronóstico , Recurrencia , Reoperación , Estudios Retrospectivos , Tasa de SupervivenciaRESUMEN
BACKGROUND: The present study examined the survival and rate of contraction of (1) cardiomyocytes cultured from cryopreserved fetal rat myocardium and (2) cryopreserved cultured cardiomyocytes. In addition, the effects of transplantation of cryopreserved fetal cardiomyocytes were evaluated. METHODS: Segments of fetal rat myocardial tissue (0.2, 2.0, and 6.0 mm(3) mince size) and cultured cardiomyocytes were cryopreserved in liquid nitrogen for 1, 2, and 4 weeks. After cryopreservation, the tissue samples and cultured cardiomyocytes were thawed at 37 degrees C and cultured, and cell proliferation and rate of contraction were determined. Cultured cryopreserved (n = 5) and noncryopreserved (control, n = 5) fetal cardiomyocytes were transplanted into the subcutaneous tissue and into a transmural left ventricular free wall scar of Sprague-Dawley rats (n = 3). The survival and rate of contraction of these transplanted cells were also examined. RESULTS: Cryopreservation of cultured fetal cardiomyocytes resulted in viable and functional cardiomyocytes although the cell number and percentage of beating cells were diminished. Survival of cardiomyocytes isolated from cryopreserved fetal myocardium was a function of tissue size before cryopreservation; the lowest survival was recorded in tissues with the largest mince size (6.0 mm(3)). The subcutaneous transplants contracted spontaneously and regularly with an idioventricular rhythm. In addition, the transplanted cardiomyocytes were elongated and formed a myocardium-like pattern with blood vessels present within the contractile tissue. In the transmural left ventricular scar, both control and experimental fetal cardiomyocyte transplants formed myocardium-like tissue. CONCLUSIONS: The present study uncovers the following key observations: (1) cryopreservation of fetal cardiomyocytes and cardiomyocytes isolated from cryopreserved myocardial tissue results in viable and functional cells, (2) cryopreserved fetal cardiomyocytes can be successfully transplanted into subcutaneous and myocardial scar tissue, and (3) improvements in cryopreservation techniques are required to augment the rates of cardiomyocyte survival observed in the study.
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Trasplante de Células/métodos , Criopreservación , Trasplante de Tejido Fetal , Corazón/embriología , Miocardio/citología , Animales , Células Cultivadas , Procedimientos Quirúrgicos Dermatologicos , Corazón/fisiología , Contracción Miocárdica , Ratas , Ratas Sprague-Dawley , Piel/citologíaRESUMEN
BACKGROUND: Little is known about the effect of heart cell transplantation into the dilated cardiomyopathic myocardium. This study was designed to evaluate the effect of heart cell transplantation into dilated cardiomyopathic hamsters. METHODS AND RESULTS: Ventricular heart cells were isolated from 4-week-old BIO 53. 58 hamsters and cultured for 2 weeks before transplantation. The cells were labeled with bromodeoxyuridine (BrdU) before transplantation for identification. Adult hamsters (17 weeks old) were used as recipients. Heart cells (4 x 10(6) cells) or culture medium was transplanted into the left ventricular free wall (transplantation and control groups, respectively, n=12 each). Sham-operated hamsters (n=12) underwent the surgery but not the transplantation. Cyclosporine A was administered subcutaneously to all hamsters daily after the operation. Four weeks after the transplantation, heart function was evaluated with the use of a Langendorff preparation. Histology showed severe focal myocardial necrosis in all groups. BrdU-stained tissue was found at the cell transplantation sites. The transplanted hearts had greater (P:<0. 001) developed pressures at all balloon volumes and improved dP/dt (transplantation 915+/-253 versus control 453+/-120 and sham 530+/-187 mm Hg/s, P:<0.001, balloon volume of 15 microL). No differences in ventricular function were found between control and sham-operated hamsters. CONCLUSIONS: The transplanted ventricular heart cells formed cardiac-like tissue in cardiomyopathic myocardium and improved its contractile function.
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Cardiomiopatía Dilatada/cirugía , Ventrículos Cardíacos/citología , Ventrículos Cardíacos/trasplante , Miocardio/citología , Animales , Presión Sanguínea , Bromodesoxiuridina , Volumen Cardíaco , Cardiomiopatía Dilatada/patología , Células Cultivadas , Cricetinae , Diástole , Modelos Animales de Enfermedad , Supervivencia de Injerto , Inmunohistoquímica , Técnicas In Vitro , Masculino , Miocardio/metabolismo , Miocardio/patología , Cadenas Pesadas de Miosina/metabolismo , Cadenas Ligeras de Miosina/metabolismo , Troponina/metabolismo , Función Ventricular Izquierda/fisiologíaRESUMEN
BACKGROUND: Transplantation of myocytes into scarred myocardium has been shown to inhibit ventricular remodeling and maintain myocardial contractility. However, the effect of cell transplantation on hearts with global rather than regional dysfunction is unknown. Therefore, we evaluated the effect of transplantation of autologous smooth muscle cells on the morphometry and function of dilated cardiomyopathic hearts. METHODS: Smooth muscle cells were isolated from the ductus deferens of 13-week-old BIO 53.58 hamsters with dilated cardiomyopathy, and cultured for 4 weeks before transplantation. Smooth muscle cells (4 x 10(6) cells) or culture medium were injected into 17-week-old animals in the transplantation and control groups (n = 12 each), respectively. Prelabeling of the smooth muscle cells with 5-bromo-2'-deoxyuridine was performed before transplantation in a group of transplanted hamsters. Another group (sham, n = 12) underwent the operation but did not receive an injection either of smooth muscle cells or of culture medium. Four weeks after transplantation, heart function was evaluated in a Langendorff preparation. RESULTS: Musclelike tissue, labeled with 5-bromo-2'-deoxyuridine, was found at the site of transplantation in the cell-transplanted animals. The cell-transplanted hearts were smaller (p < 0.001), and had greater developed pressures and maximum rate of increase of left ventricular pressure (both p < 0.001) than control and sham hearts. Control hamsters injected with culture medium did not differ from sham-operated animals. CONCLUSIONS: Transplantation of autologous smooth muscle cells prevented cardiac dilatation and improved ventricular function in hamsters with dilated cardiomyopathy.
Asunto(s)
Cardiomiopatía Dilatada/cirugía , Músculo Liso/citología , Músculo Liso/trasplante , Animales , Cardiomiopatía Dilatada/fisiopatología , Células Cultivadas , Cricetinae , Miocardio/citología , Trasplante Autólogo , Función Ventricular IzquierdaRESUMEN
OBJECTIVE: We noted an increasing risk profile of patients undergoing reoperative coronary surgery. We evaluated the risk compared with primary procedures, our results over a 16-year span, and the predictors of hospital outcomes after redo surgery. METHODS: We analyzed 20,614 patients undergoing isolated coronary surgery at our institution from 1982 to 1997. Of these, 1230 (6.0%) were undergoing reoperation. Independent predictors of outcomes were identified by multivariable regression. RESULTS: The prevalence of reoperation peaked in 1994 at 8.2%. Patients undergoing reoperation were more likely to be male, to have left ventricular dysfunction and worse symptoms, and to require an urgent operation than patients undergoing a primary operation (P <.0001). Perioperative myocardial infarctions (3.7% vs 7.4%), low-output syndrome (9.0% vs 24.0%), and death (2.4% vs 6.8%) were more common in patients undergoing reoperation (all P <.0001). Over the years, the risk profile of patients undergoing reoperation increased. Age, left ventricular dysfunction, severity of symptoms, extent of coronary artery disease, left main stenosis, and requirement for urgent or emergency operations increased with time (P <.05). However, mortality, myocardial infarction, and low-output syndrome have remained constant. The independent predictors of mortality after reoperative surgery were increased age, greater Canadian Cardiovascular Society symptom class, earlier year of operation, and greater left ventricular dysfunction. After 1990, analysis of an expanded data set also identified peripheral vascular disease and failure to use retrograde cardioplegia as predictors of mortality. CONCLUSIONS: Improving results of reoperative surgery have been offset by an increasing patient risk profile. Meticulous operative technique and retrograde cardioplegia may permit good results in these high-risk patients.
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Puente de Arteria Coronaria/estadística & datos numéricos , Puente de Arteria Coronaria/mortalidad , Femenino , Mortalidad Hospitalaria , Humanos , Cuidados Intraoperatorios , Masculino , Persona de Mediana Edad , Reoperación/tendencias , Factores de Riesgo , Resultado del TratamientoRESUMEN
BACKGROUND: Improved methods of myocardial preservation are required to reduce the morbidity and mortality of coronary bypass surgery for high-risk subgroups. Metabolic stimulation with insulin, glucose solutions, or both has been proposed as a method to preserve the ischemic myocardium. We performed a prospective, double-blind, randomized trial to evaluate the effects of insulin and glucose as cardioplegic additives when used as part of a tepid continuous blood cardioplegic strategy. METHODS: We randomized 56 male patients undergoing elective isolated coronary bypass surgery to 1 of 4 cardioplegic groups containing either 42 or 84 mmol/L glucose with or without 10 IU/L of insulin. Perioperative assessments of myocardial metabolism and left ventricular function were performed. RESULTS: Insulin-enhanced cardioplegia was associated with beneficial effects on both myocardial metabolic and functional recovery after cardioplegic arrest. Insulin's effect was independent of the ambient glucose concentration. CONCLUSIONS: Cardioplegic formulations containing a 42 mmol/L concentration of glucose and a 10 IU/L concentration of insulin provide significant benefit to patients undergoing isolated coronary bypass surgery. The clinical effect of these formulations will need to be assessed in high-risk subgroups of patients, such as those with unstable angina, recent myocardial infarction, or poor left ventricular function.
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Puente de Arteria Coronaria , Glucosa/administración & dosificación , Paro Cardíaco Inducido , Insulina/administración & dosificación , Complicaciones Posoperatorias/prevención & control , Método Doble Ciego , Procedimientos Quirúrgicos Electivos , Glucosa/metabolismo , Hemodinámica , Humanos , Insulina/metabolismo , Masculino , Persona de Mediana Edad , Miocardio/metabolismo , Estudios ProspectivosRESUMEN
OBJECTIVES: Currently available graft materials for repair of congenital heart defects cause significant morbidity and mortality because of their lack of growth potential. An autologous cell-seeded graft may improve patient outcomes. We report our initial experience with the construction of a biodegradable graft seeded with cultured rat or human cells and identify their 3-dimensional growth characteristics. METHODS: Fetal rat ventricular cardiomyocytes, stomach smooth muscle cells, skin fibroblasts, and adult human atrial and ventricular cardiomyocytes were isolated and cultured in vitro. These cells were injected into or laid onto biodegradable gelatin meshes, and their rate of proliferation and spatial location within the mesh was evaluated by using a cell counter and histologic analysis. RESULTS: Rat cardiomyocytes, smooth muscle cells, and fibroblasts demonstrated steady proliferation over 3 to 4 weeks. The gelatin mesh was slowly degraded, but this process was most rapid after seeding with fibroblasts. Human atrial cardiomyocytes proliferated within the gelatin meshes but at a slower rate than that of fetal rat cardiomyocytes. Human ventricular cardiomyocytes survived within the gelatin mesh matrix but did not increase in number during the 2-week duration of evaluation. Grafts seeded with rat ventricular cells exhibited spontaneous rhythmic contractility. All cell types preferentially migrated to the uppermost surface of each graft and formed a 300- to 500-microm thick layer. CONCLUSIONS: Fetal rat ventricular cardiomyocytes, gastric smooth muscle cells, skin fibroblasts, and adult human atrial cardiomyocytes can grow in a 3-dimensional pattern within a biodegradable gelatin mesh. Similar autologous cell-seeded constructs may eventually be applied to repair congenital heart defects.
Asunto(s)
Ingeniería Biomédica , Bioprótesis , Fibroblastos/citología , Trasplante de Corazón , Ventrículos Cardíacos/citología , Músculo Liso/citología , Adulto , Animales , Biodegradación Ambiental , División Celular , Supervivencia Celular , Células Cultivadas , Corazón Fetal/citología , Corazón Fetal/fisiología , Fibroblastos/fisiología , Humanos , Músculo Liso/fisiología , Contracción Miocárdica , Ratas , Función VentricularRESUMEN
BACKGROUND: We reviewed our experience with the Ross procedure to identify the prevalence and predictors of late pulmonary homograft stenosis. METHODS: Between June 1992 and December 1997, 109 consecutive patients (age 34.5 +/- 8.6 years) underwent the Ross procedure, with reconstruction of the right ventricular outflow tract with a cryopreserved pulmonary homograft (22 to 30 mm diameter). There was one early and one late death. Echocardiographic follow-up was available in 105 of 108 patients (97%), with a follow-up of 39 +/- 20 months. Homograft donor and preservation measurements and patient variables were subjected to multivariable analyses to identify independent predictors of late homograft performance. RESULTS: The major physiopathologic finding was homograft stenosis. Peak systolic gradients across the homograft were 20 mm Hg or more in 30 of 105 patients (28.5%) and 40 mm Hg or more in 4 of 105 patients (3.8%). One patient required two re-replacements of her homograft for severe stenosis. Moderate or severe homograft insufficiency was noted in 10 of 105 patients (9.5%). The independent predictors of late pulmonary homograft stenosis were younger donor age (p = 0.03), shorter duration of cryopreservation (p = 0.01), and smaller homograft size (p = 0.06). Beating heart donor status, short homograft ischemic time, and other factors that have been shown to be associated with increased graft viability were associated with graft stenosis but did not reach statistical significance. However, mean gradients across the homograft were significantly related (p = 0.002) to the number of these risk factors in each patient. CONCLUSIONS: Stenosis of the pulmonary homograft can be a significant problem following the Ross procedure, and was predicted by younger donor age and shorter duration of cryopreservation. These factors may be related to increased cellular viability, which might actually predispose to late homograft stenosis in a subgroup of patients.
Asunto(s)
Bioprótesis , Implantación de Prótesis Vascular , Prótesis Vascular , Oclusión de Injerto Vascular/etiología , Cardiopatías Congénitas/cirugía , Implantación de Prótesis de Válvulas Cardíacas , Complicaciones Posoperatorias/etiología , Válvula Pulmonar/cirugía , Adolescente , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Válvula Pulmonar/anomalías , Trasplante Homólogo , Resultado del TratamientoRESUMEN
OBJECTIVES: Mitral valve repair may be technically feasible in patients with suitable anatomy, but the appropriateness of repair for rheumatic disease remains controversial. We evaluated our late outcomes after mitral repair and replacement for rheumatic disease. METHODS: Five hundred seventy-three patients underwent mitral valve surgery for rheumatic disease at our institution from 1978-1995. Follow-up was 98% complete (mean, 68 +/- 46 months). Survival and morbidity were evaluated by Kaplan-Meier analysis and Cox regression, including propensity score analysis. RESULTS: Mean age was 54 +/- 14 years, 55% of patients had congestive heart failure, 22% were undergoing redo mitral valve surgery, and 9% also underwent coronary bypass. Mitral stenosis was present in 53%, regurgitation in 15%, and both in 32%. Valve repair was performed in 25%, bioprosthetic replacement was performed in 28%, and a mechanical valve was placed in 47%. Patients undergoing repair were younger and less likely to be undergoing reoperation or to have atrial fibrillation than those undergoing replacement (P =.001). The operative mortality rate was 4. 2%. Better late cardiac survival was independently predicted by valve repair rather than replacement (P =.04) after adjustment for baseline differences between patients. Freedom from reoperation was greatest (P =.005) but that from thromboembolic complications was worst (P <.0001) after mechanical valve replacement. Twenty-three patients underwent reoperation after initial repair, with no operative deaths. CONCLUSIONS: Mechanical valves minimize reoperation but limit survival and increase thromboembolic complications. Patients undergoing valve repair had improved late cardiac survival independent of their preoperative characteristics. Rheumatic mitral valves should be repaired when technically feasible, accepting a risk of reoperation, to maximize survival and reduce morbidity.
Asunto(s)
Implantación de Prótesis de Válvulas Cardíacas , Válvula Mitral/cirugía , Cardiopatía Reumática/cirugía , Adulto , Análisis de Varianza , Distribución de Chi-Cuadrado , Femenino , Humanos , Masculino , Persona de Mediana Edad , Selección de Paciente , Complicaciones Posoperatorias , Modelos de Riesgos Proporcionales , Estudios Prospectivos , Curva ROC , Reoperación , Tasa de Supervivencia , Trombosis/etiología , Resultado del TratamientoRESUMEN
OBJECTIVE: Fetal cardiomyocyte transplantation improved heart function after cardiac injury. However, cellular allografts were rejected despite cyclosporine (INN: ciclosporin) therapy. We therefore evaluated autologous heart cell transplantation in an adult swine model of a myocardial infarction. METHODS: In 16 adult swine a myocardial infarction was created by occlusion of the distal left anterior descending coronary artery by an intraluminal coil. Four weeks after infarction, technetium 99m-sestamibi single photon emission tomography showed minimal perfusion and viability in the infarcted region. Porcine heart cells were isolated and cultured from the interventricular septum at the time of infarction and grown in vitro for 4 weeks. Through a left thoracotomy, either cells (N = 8) or culture medium (N = 8) was injected into the infarct zone. RESULTS: Four weeks after cell transplantation, technetium 99m-sestamibi single photon emission tomography demonstrated greater wall motion scores in the pigs receiving transplantation than in control animals (P =.01). Pigs receiving transplantation were more likely to have an improvement in perfusion scores (P =.03). Preload recruitable stroke work (P =.009) and end-systolic elastance (P =. 02) were greater in the pigs receiving transplantation than in control animals. Scar areas were not different, but scar thickness was greater (P =.02) in pigs receiving transplantation. Cells labeled with bromodeoxyuridine in vitro could be identified in the infarct zone 4 weeks after transplantation. Swine receiving transplantation gained more weight than control animals (P =.02). CONCLUSION: Autologous porcine heart cell transplantation improved regional perfusion and global ventricular function after a myocardial infarction.