RESUMEN
Reoperative vascular ring surgery is uncommon. Standard redo ipsilateral thoracotomy may present technical challenges and risks. We describe a patient with right aortic arch, aberrant left subclavian artery, and a Kommerell diverticulum in whom previous vascular ring division via left thoracotomy did not relieve dysphagia. Three years after the unsuccessful operation, left subclavian-carotid transposition via supraclavicular incision followed by resection of the Kommerell diverticulum via right thoracotomy with extracorporeal circulation relieved symptoms. Contralateral thoracotomy with extracorporeal circulation provides a safe, alternative approach to redo ipsilateral thoracotomy for resection of a symptomatic Kommerell diverticulum. We review the literature on the incidence, surgical indications, and operative approaches to manage symptoms from a Kommerell diverticulum.
Asunto(s)
Anomalías Cardiovasculares , Divertículo , Cardiopatías Congénitas , Anillo Vascular , Humanos , Anillo Vascular/cirugía , Aorta Torácica/cirugía , Toracotomía , Arteria Subclavia/cirugía , Anomalías Cardiovasculares/cirugía , Cardiopatías Congénitas/cirugía , Circulación Extracorporea , Divertículo/diagnósticoRESUMEN
Direct hepatic veins-to-hemiazygos connection offers the balanced distribution of hepatic venous blood to both lungs, not requiring anticoagulation. We report a 13-year follow-up after this type of off-pump Fontan completion. Patient's hepatic veins-to-hemiazygos confluence increased with growth to allow for unobstructed flow. This unique technique can be recommended in heterotaxy patients, if atrial hepatic venous drainage and hemiazygos vein are in close proximity.
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Procedimiento de Fontan , Síndrome de Heterotaxia , Venas Pulmonares , Vena Ácigos/diagnóstico por imagen , Vena Ácigos/cirugía , Venas Hepáticas/cirugía , Humanos , Venas Pulmonares/cirugíaRESUMEN
BACKGROUND: For neonates with critical left ventricular outflow tract obstruction (LVOTO), hybrid procedures are an alternative to the Norwood stage 1 procedure. Despite perceived advantages, however, outcomes are not well defined. Therefore, we compared outcomes after stage 1 hybrid and Norwood procedures. METHODS: In a critical LVOTO inception cohort (2005-2014; 20 institutions), a total of 564 neonates underwent stage 1 palliation with the Norwood operation with a modified Blalock-Taussig shunt (NW-BT; n = 232; 41%), Norwood operation with a right ventricle-to-pulmonary artery conduit (NW-RVPA; n = 222; 39%), or a hybrid procedure (n = 110; 20%). Post-stage 1 outcomes were analyzed via competing-risks and parametric hazard analyses and compared among all 564 patients and between patients who underwent propensity-matched hybrid and those who underwent NW-BT/NW-RVPA. RESULTS: By 6 years after the stage 1 operation, 50% ± 3%, 7% ± 2%, and 4% ± 1% of patients transitioned to Fontan, transplantation, and biventricular repair, respectively, whereas 7% ± 2% were alive without transition and 32% ± 2% died. Risk factors for death without transition included procedure type, smaller ascending aorta, aortic valve atresia, and lower birth weight. Risk-adjusted 4-year survival was better after NW-RVPA than after NW-BT or hybrid (76% vs 60% vs 61%; P < .001). Furthermore, for neonates with lower birth weight (<â¼2 kg), an interaction between birth weight and hybrid resulted in a trend toward better survival after hybrid compared with NW-BT or NW-RVPA. For propensity-matched neonates between hybrid and NW-BT (88 pairs), 4-year survival was similar (62% vs 57%; P = .58). For propensity-matched neonates between hybrid and NW-RVPA (81 pairs), 4-year survival was better after NW-RVPA (59% vs 75%; P = .008). CONCLUSIONS: For neonates with critical LVOTO undergoing single-ventricle palliation, NW-RVPA was associated with the best overall survival. Hybrid strategies are not a lower-risk alternative to Norwood operations overall; however, the impact of lower birth weight on survival may be mitigated after hybrid procedures compared with Norwood operations.
Asunto(s)
Procedimiento de Blalock-Taussing , Cardiopatías Congénitas/cirugía , Procedimientos de Norwood , Obstrucción del Flujo Ventricular Externo/cirugía , Factores de Edad , Peso al Nacer , Procedimiento de Blalock-Taussing/efectos adversos , Procedimiento de Blalock-Taussing/mortalidad , Canadá , Femenino , Procedimiento de Fontan , Cardiopatías Congénitas/diagnóstico por imagen , Cardiopatías Congénitas/mortalidad , Cardiopatías Congénitas/fisiopatología , Trasplante de Corazón , Humanos , Recién Nacido , Masculino , Procedimientos de Norwood/efectos adversos , Procedimientos de Norwood/mortalidad , Cuidados Paliativos , Estudios Prospectivos , Recuperación de la Función , Factores de Riesgo , Factores de Tiempo , Resultado del Tratamiento , Estados Unidos , Obstrucción del Flujo Ventricular Externo/diagnóstico por imagen , Obstrucción del Flujo Ventricular Externo/mortalidad , Obstrucción del Flujo Ventricular Externo/fisiopatologíaRESUMEN
INTRODUCTION: Cardiac migration of ventriculoperitoneal (VP) shunts has been reported, with most easily removed or shortened via a cervical incision. We present a review of the literature, highlighting our unique case with significant scarring requiring open, on-pump, cardiac surgery for removal of migrated distal tubing. CASE PRESENTATION: A 7-year-old boy underwent VP shunt insertion for hydrocephalus secondary to intracranial astrocytoma. He presented at age 17 with evidence of right heart strain, associated with the distal shunt catheter proximally migrated into his heart and pulmonary arteries. Due to his delayed presentation, the catheter was knotted and partially immobilized by scar formation, finally requiring open-heart surgery to remove the catheter. CONCLUSIONS: A multi-disciplinary evaluation with endovascular, neurosurgery, and cardiothoracic surgery may be the safest approach, especially in those patients with knotting on preoperative imaging.
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Procedimientos Quirúrgicos Cardíacos/métodos , Migración de Cuerpo Extraño/etiología , Migración de Cuerpo Extraño/cirugía , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/cirugía , Derivación Ventriculoperitoneal/efectos adversos , Astrocitoma/complicaciones , Neoplasias Encefálicas/complicaciones , Niño , Migración de Cuerpo Extraño/diagnóstico por imagen , Corazón , Humanos , Hidrocefalia/etiología , Hidrocefalia/cirugía , Imagen por Resonancia Magnética , Masculino , Procedimientos Neuroquirúrgicos , Complicaciones Posoperatorias/diagnóstico por imagen , Tomógrafos Computarizados por Rayos XRESUMEN
OBJECTIVE: Early survival advantages after Norwood with right-ventricle-(RV)-to-pulmonary-artery conduit (NW-RVPA) over Norwood-operation with a Blalock-Taussig shunt (NW-BT) are offset by concerns regarding delayed RV dysfunction. We compared trends in survival, RV dysfunction, and tricuspid valve regurgitation (TR) between NW-RVPA and NW-BT for propensity-matched neonates with critical left ventricular outflow tract obstruction (LVOTO). METHODS: In an inception cohort (2005-2014; 21 institutions), 454 neonates with critical LVOTO underwent Norwood stage 1. Propensity-score matching paired 169 NW-RVPA patients with 169 NW-BT patients. End-states were compared between NW-RVPA and NW-BT using competing-risks, multiphase, parametric, hazard analysis. Post-Norwood echocardiogram reports (n = 2993) were used to grade RV dysfunction and TR. Time-related prevalence of ≥moderate RV dysfunction and TR were characterized using nonlinear mixed-model regression, and compared between groups via multiphase, parametric models. RESULTS: Overall 6-year survival was better after NW-RVPA (70%) versus NW-BT (55%; P < .001). Additionally, transplant-free survival during this time was better after NW-RVPA (64%) versus NW-BT (53%; P = .004). Overall prevalence of ≥moderate RV dysfunction reached 11% within 3 months post-Norwood. During this time, RV dysfunction after NW-BT was 16% versus 6% after NW-RVPA (P = .02), and coincided temporally with an increased early hazard for death. For survivors, late RV dysfunction was <5% and was not different between groups (P = .36). Overall prevalence of ≥moderate TR reached 13% at 2 years post-Norwood and was increased after NW-BT (16%) versus NW-RVPA (11%; P = .003). Late TR was similar between groups. CONCLUSIONS: Among propensity-score-matched neonates with critical LVOTO, NW-RVPA offers superior 6-year survival with no greater prevalence of RV dysfunction or TR than conventional NW-BT operations.
Asunto(s)
Procedimiento de Blalock-Taussing , Ventrículos Cardíacos/cirugía , Procedimientos de Norwood , Arteria Pulmonar/cirugía , Función Ventricular/fisiología , Procedimiento de Blalock-Taussing/mortalidad , Niño , Preescolar , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Procedimientos de Norwood/mortalidad , Insuficiencia de la Válvula Tricúspide/etiología , Obstrucción del Flujo Ventricular Externo/cirugíaRESUMEN
OBJECTIVES: To determine the association between surgical management of pulmonary blood flow (PBF) at initial and staged procedures with survival to Fontan/Kreutzer operation (Fontan) in patients with tricuspid atresia. METHODS: Infants aged <3 months with tricuspid atresia type I (n = 303) were enrolled from 34 institutions (1999-2013). Among those who underwent surgical intervention (n = 302), initial procedures were: systemic to pulmonary artery shunt (SPS; n = 189; 62%); pulmonary artery banding (PAB; n = 50; 17%); and superior cavopulmonary connection (SCPC; n = 63; 21%). Multiphase parametric-hazard models were used to analyze competing outcomes. RESULTS: Risk-adjusted 6-year survival was lower after SPS (85%; P = .04) versus PAB (93%) or SCPC (93%). Survival after SPS when the main pulmonary artery (MPA) was closed (n = 21) or banded (n = 4) was 60%, versus 93% without MPA intervention (P = .02). After SPS, survival before SCPC was lower with an open ductus arteriosus (n = 7; 76% vs 97%; P = .02). Similarly, after SPS, risk-adjusted survival was similar to that for patients who had an initial PAB or SCPC when MPA intervention was avoided and the ductus arteriosus either closed spontaneously before SPS, or was closed during SPS. For all patients reaching SCPC (n = 277), survival to Fontan was not significantly influenced by whether PBF persisted through the MPA. CONCLUSIONS: Tricuspid atresia patients with SPS represent a high-risk subgroup. Avoiding an open ductus arteriosus and concomitant MPA intervention during SPS may help mitigate the risk associated with SPS. The presence of antegrade PBF through the MPA, at initial and staged operations, did not significantly influence survival to Fontan operation.
Asunto(s)
Procedimiento de Fontan , Arteria Pulmonar/cirugía , Circulación Pulmonar , Atresia Tricúspide/cirugía , Válvula Tricúspide/cirugía , Canadá , Procedimiento de Fontan/efectos adversos , Procedimiento de Fontan/mortalidad , Humanos , Lactante , Estimación de Kaplan-Meier , Complicaciones Posoperatorias/etiología , Estudios Prospectivos , Arteria Pulmonar/fisiopatología , Factores de Riesgo , Factores de Tiempo , Resultado del Tratamiento , Atresia Tricúspide/clasificación , Atresia Tricúspide/diagnóstico , Atresia Tricúspide/mortalidad , Atresia Tricúspide/fisiopatología , Válvula Tricúspide/anomalías , Válvula Tricúspide/fisiopatología , Estados UnidosRESUMEN
A 5-month-old infant presented with a rare, congenital heart disease: aortopulmonary window with an anomalous origin of the right coronary artery from the aortopulmonary window. Using echocardiography and computed tomography, the exact diagnosis could only be ascertained retrospectively; however, cardiac catheterization and angiography confirmed the diagnosis, which led to elective open-heart surgery. The infant made a full recovery.
Asunto(s)
Defecto del Tabique Aortopulmonar/complicaciones , Anomalías de los Vasos Coronarios/complicaciones , Enfermedades Raras/complicaciones , Defecto del Tabique Aortopulmonar/diagnóstico , Defecto del Tabique Aortopulmonar/cirugía , Anomalías de los Vasos Coronarios/diagnóstico , Anomalías de los Vasos Coronarios/cirugía , Femenino , Humanos , Lactante , Enfermedades Raras/diagnóstico , Enfermedades Raras/cirugíaRESUMEN
BACKGROUND: Anomalous aortic origin of a coronary artery (AAOCA) encompasses a wide morphologic spectrum, which has impeded consensus regarding indications for the diverse repair strategies. We constructed a profile of current surgical techniques and explore their application to morphologic variants. METHODS: Patients<30 years old (n=113) with isolated AAOCA who underwent operations at 29 Congenital Heart Surgeons Society (CHSS) institutions from 1998 to 2012 were identified from the CHSS AAOCA Registry. Operative findings were related to surgical techniques at index repairs by cross-tabulation. RESULTS: Anomalous origin of the left main or left anterior descending coronary artery was present in 33 (29%) patients and of the right coronary artery in 78 (69%) patients; 2 arteries originated directly above the commissure between the left and right sinuses. There were 101 (89%) interarterial and intramural (IA/IM) arteries, 10 (9%) were interarterial but not intramural (IA/NIM) and 2 (2%) were neither interarterial nor intramural. Intramural arteries were unroofed in 100 (88%) operations, usually with intimal tacking after incision (n=47) or excision (n=25) of the common wall. Coronary reimplantation (n=11), pulmonary artery relocation (n=7; 5 for IA/NIM), simple ostioplasty (without unroofing; n=3), coronary artery bypass grafting (n=2), and ostial window (n=1) were less common. In 37 (33%) operations, a valvar commissure was taken down; 33 were resuspended. CONCLUSION: Current surgical repair of AAOCA is individualized to morphology, particularly the presence of intramural and/or interarterial segments. This report is foundational for future planned CHSS studies that will examine interventional and noninterventional outcomes and ultimately guide management of AAOCA.
Asunto(s)
Aorta Torácica/anomalías , Aorta Torácica/cirugía , Procedimientos Quirúrgicos Cardíacos/métodos , Anomalías de los Vasos Coronarios/cirugía , Cardiopatías Congénitas/cirugía , Niño , Humanos , Sistema de RegistrosRESUMEN
BACKGROUND: Treatment of congenital heart disease may include placement of a right ventricle to pulmonary artery conduit that requires future surgical replacement. We sought to identify surgeon-modifiable factors associated with durability (defined as freedom from surgical replacement or explantation) of the initial conduit in children less than 2 years of age at initial insertion. METHODS: Since 2002, 429 infants were discharged from 24 Congenital Heart Surgeons' Society member institutions after initial conduit insertion. Parametric hazard analysis identified factors associated with conduit durability while adjusting for patient characteristics, the institution where the conduit was inserted, and time-dependent interval procedures performed after conduit insertion but before replacement/explantation. RESULTS: In all, 138 conduit replacements (32%) and 3 explantations (1%) were performed. Conduit durability at a median follow-up of 6.0 years (range, 0.1 to 11.7) was 63%. After adjusting for interval procedures and institution, placement of a conduit with smaller z-score was associated with earlier replacement/explantation (p = 0.002). Moreover, conduit durability was substantially reduced with aortic allografts (p = 0.002) and pulmonary allografts (p = 0.03) compared with bovine jugular venous valved conduits (JVVC). The JVVC were 12 mm to 22 mm in diameter at insertion (compared with 6 mm to 20 mm for allografts); therefore, a parametric propensity-adjusted analysis of patients with aortic or pulmonary allografts versus JVVC with diameter of 12 mm or greater was performed, which verified the superior durability of JVVC. CONCLUSIONS: Pulmonary conduit type and z-score are associated with late conduit durability independent of the effects of institution and subsequent interval procedures. Surgeons can improve long-term conduit durability by judiciously oversizing, and by selecting a JVVC.
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Prótesis Vascular , Cardiopatías Congénitas/cirugía , Arteria Pulmonar/cirugía , Estudios Transversales , Estudios de Seguimiento , Humanos , Lactante , Estudios Prospectivos , Diseño de Prótesis , Falla de PrótesisRESUMEN
Two decades after surgery for transposition of the great arteries, the clinical status, cardiac function, cardiorespiratory performance, and neurohormonal activity of patients who underwent either atrial switch (Mustard) operations or arterial switch operations (ASOs) were compared. Sixty-two patients with simple transposition of the great arteries who underwent either Mustard (n = 34) or ASO (n = 28) procedures were included in this cross-sectional study. Following the same study protocol, clinical workup including echocardiography, stress testing, and blood work was completed for all patients. Mean ages in the 2 groups were comparable, at 20.6 ± 2.1 and 20.6 ± 3.4 years in the ASO and Mustard groups, respectively. All ASO patients were in New York Heart Association class I, whereas 59% of Mustard patients were in class II or III. Peak oxygen uptake was higher in ASO patients (percentage of predicted 80% vs 69%, p <0.01). Compared with healthy subjects, the mean Tei index for systemic ventricle was high in the 2 groups, but this parameter was significantly higher in Mustard than ASO patients (0.60 ± 0.16 vs 0.47 ± 0.14, p <0.01). The median plasma N-terminal pro-brain natriuretic peptide level in ASO patients was within the normal range, but the Mustard group had significantly higher levels (42 ng/ml [range 18 to 323] vs 172 ng/ml [range 26 to 1,018], p <0.0001). In conclusion, this cross-sectional assessment 2 decades after surgery reveals better clinical status in patients who underwent ASO compared with Mustard patients. This holds in terms of cardiac function, cardiorespiratory performance, and neurohormonal activity.
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Procedimientos Quirúrgicos Cardíacos/métodos , Péptido Natriurético Encefálico/sangre , Transposición de los Grandes Vasos/cirugía , Estudios Transversales , Femenino , Estudios de Seguimiento , Alemania/epidemiología , Humanos , Masculino , Pronóstico , Estudios Retrospectivos , Tasa de Supervivencia/tendencias , Factores de Tiempo , Transposición de los Grandes Vasos/sangre , Transposición de los Grandes Vasos/mortalidad , Adulto JovenRESUMEN
BACKGROUND: Box isolation of the posterior left atrium is one surgical or catheter ablative approach for treating atrial fibrillation (AF). In such cases, incomplete transmurality or recovery of pulmonary vein conduction after the application of various ablative techniques is considered the main reason for the recurrence of postprocedural arrhythmia. The use of solely cut-and-sew box isolation does not have these disadvantages and therefore demonstrates maximum efficacy for this therapeutic approach. METHODS: We treated 15 patients with both an indication for open heart surgery and AF (2 paroxysmal, 6 short persistent [<12 months], and 7 long persistent [>12 months] cases) with a solely cut-and-sew box lesion. These patients were then retrospectively followed up over the long term with respect to the end point of freedom of atrial tachyarrhythmias >30 seconds. RESULTS: The median follow-up duration was 42 months (range, 32-84 months). Five (63%) of 8 patients with preoperative paroxysmal or short persistent AF had no arrhythmia recurrence, whereas arrhythmia recurrence was documented in all 7 patients with preoperative long persistent AF. CONCLUSIONS: Despite reliable transmural isolation with cut-and-sew lesions, we observed long-term arrhythmia recurrence in patients who had preoperative paroxysmal or short persistent AF, suggesting that therapy approaches that are more complex than box isolation might be needed for selected patients to achieve long-term stable sinus rhythm, despite the initially paroxysmal or short persistent character of the arrhythmia. A high rate of recurrence in patients with severe structural heart disease and preoperative long persistent AF might indicate that, in general, isolation of the left posterior atrium alone is not an adequate therapeutic approach for these patients.
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Fibrilación Atrial/cirugía , Procedimientos Quirúrgicos Cardíacos/métodos , Ablación por Catéter/métodos , Atrios Cardíacos/cirugía , Anciano , Fibrilación Atrial/patología , Procedimientos Quirúrgicos Cardíacos/instrumentación , Enfermedad Crónica , Femenino , Atrios Cardíacos/patología , Humanos , Masculino , Recurrencia , Estudios Retrospectivos , Factores de TiempoRESUMEN
We present a silicon sheet for temporary wound covering and gradual wound closure after open fasciotomy. Fasciotomy was performed in a total of 70 limbs with compartment syndrome (CS). The main etiology of CS was predominantly vascular. All patients were treated with a silicon sheet to cover the soft tissue defect and gradually reapproximate the skin margins. In 53% of the patients, a delayed final wound closure was achieved after a mean of 11.9 days. This method allows final closure of fasciotomy wounds without scar contractures, marginal necrosis, infection, or significant pain.
Asunto(s)
Síndromes Compartimentales/cirugía , Descompresión Quirúrgica/métodos , Fasciotomía , Apósitos Oclusivos , Siliconas/uso terapéutico , Técnicas de Cierre de Heridas/instrumentación , Cicatrización de Heridas , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Factores de Tiempo , Resultado del Tratamiento , Adulto JovenRESUMEN
Neonatal interventions for critical aortic coarctation may be associated with considerable morbidity and mortality if the patient is extremely premature. We report the successful treatment of critical coarctation in a 25-week, 740-gram infant using initial clipping of the duct until continued prostaglandin E1 infusion delayed end-to-end anastomosis 7 weeks later.
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Coartación Aórtica/terapia , Recien Nacido con Peso al Nacer Extremadamente Bajo , Enfermedad Crítica , Humanos , Recién NacidoRESUMEN
The reliability of implantable blood sensors is often hampered by unspecific adsorption of plasma proteins and blood cells. This not only leads to a loss of sensor signal over time, but can also result in undesired host vs. graft reactions. Within this study we evaluated the hemocompatibility of isocyanate conjugated star shaped polytheylene oxide-polypropylene oxide co-polymers NCO-sP(EO-stat-PO) when applied to gold surfaces as an auspicious coating material for gold sputtered blood contacting sensors. Quartz crystal microbalance (QCM) sensors were coated with ultrathin NCO-sP(EO-stat-PO) films and compared with uncoated gold sensors. Protein resistance was assessed by QCM measurements with fibrinogen solution and platelet poor plasma (PPP), followed by quantification of fibrinogen adsorption. Hemocompatibility was tested by incubation with human platelet rich plasma (PRP). Thrombin antithrombin-III complex (TAT), ß-thromboglobulin (ß-TG) and platelet factor 4 (PF4) were used as coagulation activation markers. Furthermore, scanning electron microscopy (SEM) was used to visualize platelet adhesion to the sensor surfaces. Compared to uncoated gold sensors, NCO-sP(EO-stat-PO) coated sensors revealed significant better resistance against protein adsorption, lower TAT generation and a lower amount of adherent platelets. Moreover, coating with ultrathin NCO-sP(EO-stat-PO) films creates a cell resistant hemocompatible surface on gold that increases the chance of prolonged sensor functionality and can easily be modified with specific receptor molecules.
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Técnicas Biosensibles/instrumentación , Oro/química , Tecnicas de Microbalanza del Cristal de Cuarzo/instrumentación , Adsorción , Técnicas Biosensibles/métodos , Fibrinógeno/química , Humanos , Plasma/química , Tecnicas de Microbalanza del Cristal de Cuarzo/métodosRESUMEN
New drug-eluting stent (DES) methods have recently been demonstrated to improve outcomes of intravascular interventions. A novel technique is the design of gene-silencing stents that elute specific small-interfering RNAs (siRNAs) for better vascular wall regeneration. Although siRNAs used to alter gene expression have surpassed expectations in in vitro experiments, the functional and local delivery of siRNAs is still the major obstacle for the in vivo application of RNA interference. In this preliminary in vitro study we investigated a surface-immobilized siRNA delivery technique that would be readily adaptable for local intravascular applications in vivo. The transfection potency of gelatin coatings consisting of a specific siRNA complexed with polyethylenimine (PEI) was examined in primary human endothelial cells by flow cytometry and quantitative real-time polymerase chain reaction. Several media conditions, such as the presence or absence of serum during cultivation, were investigated. Furthermore, different siRNA and PEI amounts, as well as nitrogen/phosphate ratios, were tested for their transfection efficiency. Gelatin coatings consisting of PEI and siRNA against an exemplary endothelial adhesion molecule receptor achieved a significant knockdown of around 70%. The transfection efficiency of the coatings was not influenced by the presence of serum. The results of this preliminary study support the expectation that this novel coating may be favorable for local in vivo gene silencing (for example, when immobilized on stents or balloons for percutanous transluminal coronary angioplasty). However, further animal experiments are needed to confirm the translation into clinical practice. This intriguing technology leads the way to more sophisticated and individualized coatings for the post-DES era, toward silencing of genes involved in the pathway of intimal hyperplasia.
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Prótesis Vascular , Stents Liberadores de Fármacos , Silenciador del Gen , ARN Interferente Pequeño/metabolismo , Células Cultivadas , Materiales Biocompatibles Revestidos/farmacología , Medios de Cultivo , Selectina E/metabolismo , Células Endoteliales/efectos de los fármacos , Células Endoteliales/metabolismo , Colorantes Fluorescentes , Técnicas de Silenciamiento del Gen , Silenciador del Gen/efectos de los fármacos , Humanos , Polietileneimina/química , ARN Mensajero/genética , ARN Mensajero/metabolismo , Reacción en Cadena en Tiempo Real de la Polimerasa , Suero/metabolismo , TransfecciónRESUMEN
Subacute stent thrombosis, caused by undesired interactions between blood and the stent surface, is a major concern in the first few weeks following coronary artery stent implantation. The aim of this study was to establish a novel in vitro model for hemocompatibility testing of coronary artery stents according to ISO 10993-4. The model consists of a modified Chandler-Loop design with closed heparin-coated PVC Loops and a thermostated water bath. The tests were performed with anticoagulated human whole blood. After incubation in the loop, blood was analyzed for coagulation and inflammatory activation markers (TAT, ß-TG, sP-selectin, SC5b-9 and PMN-elastase). Three different stent types with varying thrombogenicity were tested; statistically significant differences were found between the three stent types in measures of coagulation and platelet activation. The new Chandler-Loop model can be used as an alternative to animal and current in vitro models, especially for the determination of early events after stent implantation.
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Prótesis Vascular , Ensayo de Materiales/métodos , Stents , Anticoagulantes/administración & dosificación , Recuento de Células Sanguíneas , Células Sanguíneas/citología , Células Sanguíneas/efectos de los fármacos , Células Sanguíneas/fisiología , Coagulación Sanguínea/efectos de los fármacos , Coagulación Sanguínea/fisiología , Plaquetas/efectos de los fármacos , Plaquetas/fisiología , Materiales Biocompatibles Revestidos/química , Materiales Biocompatibles Revestidos/farmacología , Stents Liberadores de Fármacos , Heparina/administración & dosificación , Heparina/farmacología , Humanos , Técnicas In Vitro , Inflamación/metabolismo , Masculino , Ensayo de Materiales/normas , Microscopía Electrónica de Rastreo , Modelos Biológicos , Activación Plaquetaria/efectos de los fármacos , Activación Plaquetaria/fisiología , Estándares de ReferenciaRESUMEN
BACKGROUND: Cardioplegia and reperfusion of the myocardium may be associated with cardiomyocyte apoptosis and subsequent myocardial injury. In order to establish a pharmacological strategy for the prevention of these events, this study aimed to verify the reliability of our human cardiac model and to evaluate the pro-apoptotic properties of the sphingolipid second messenger ceramide and the anti-apoptotic properties of the acid sphingomyelinase inhibitor amitryptiline during simulated cardioplegia and reperfusion ex vivo. METHODS: Cardiac biopsies were retrieved from the right auricle of patients undergoing elective CABG before induction of cardiopulmonary bypass. Biopsies were exposed to ex vivo conditions of varying periods of cp/rep (30/10, 60/20, 120/40 min). Groups: I (untreated control, n = 10), II (treated control cp/rep, n = 10), III (cp/rep + ceramide, n = 10), IV (cp/rep + amitryptiline, n = 10) and V (cp/rep + ceramide + amitryptiline, n = 10). For detection of apoptosis anti-activated-caspase-3 and PARP-1 cleavage immunostaining were employed. RESULTS: In group I the percentage of apoptotic cardiomyocytes was significantly (p < 0.05) low if compared to group II revealing a time-dependent increase. In group III ceramid increased and in group IV amitryptiline inhibited apoptosis significantly (p < 0.05). In contrast in group V, under the influence of ceramide and amitryptiline the induction of apoptosis was partially suppressed. CONCLUSION: Ceramid induces and amitryptiline suppresses apoptosis significantly in our ex vivo setting. This finding warrants further studies aiming to evaluate potential beneficial effects of selective inhibition of apoptosis inducing mediators on the suppression of ischemia/reperfusion injury in clinical settings.
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Apoptosis/efectos de los fármacos , Ceramidas/farmacología , Isquemia Miocárdica/patología , Miocitos Cardíacos/patología , Cuidados Preoperatorios/métodos , Anciano , Biopsia , Células Cultivadas , Puente de Arteria Coronaria , Estudios de Seguimiento , Paro Cardíaco Inducido/métodos , Humanos , Inmunohistoquímica , Persona de Mediana Edad , Isquemia Miocárdica/metabolismo , Isquemia Miocárdica/cirugía , Miocitos Cardíacos/efectos de los fármacos , Miocitos Cardíacos/metabolismo , Proyectos PilotoRESUMEN
OBJECTIVE: The patency of venous conduits after aortocoronary bypass grafting is still not satisfactory and needs to be improved. Atherosclerotic alterations mediated by adhesion molecules triggering the transmigration of leukocytes are regarded as one of the major causes for venous graft failure. This study deals with short interfering RNA (siRNA)-mediated silencing of adhesion molecule expression on venous endothelial cells, which could lead to a new therapeutic strategy, resulting in improved patency rates by inhibiting early graft alterations. METHODS: Primary human venous endothelial cells (HVECs) were cultured in a newly developed perfusion model and subsequently transfected with specific siRNAs targeting three different adhesion molecules (the E-selectin (ESELE), the intercellular adhesion molecule 1 (ICAM-1), and the vascular adhesion molecule (VCAM-1)), followed by stimulation with tumor necrosis factor-alpha (TNF-α). Isolated leukocytes were perfused under physiological shear stress conditions, and their attachment to HVEC after single and triple transfection was quantified. RESULTS: siRNA transfection effectively knocks down adhesion molecule expression on venous endothelial cells, which subsequently reduces leukocyte attachment. Leukocyte adhesion to activated HVEC was significantly reduced after transfection by specific siRNAs in each case compared to the controls (p<0.05). Transfection with a mixture of all three siRNA sequences improved this effect even more (p<0.05). CONCLUSION: For the first time, a functional protection of HUEC in a model simulating physiologic vascular conditions by using nonviral transfection of the cells in a setup with high relevance for clinical applicability was demonstrated. Therefore, siRNA transfection of bypass material may develop into a new therapeutic option to improve the quality of venous graft material in the future.
Asunto(s)
Moléculas de Adhesión Celular/genética , Puente de Arteria Coronaria/métodos , Endotelio Vascular/metabolismo , Silenciador del Gen , Adhesión Celular/genética , Moléculas de Adhesión Celular/metabolismo , Células Cultivadas , Células Endoteliales/efectos de los fármacos , Células Endoteliales/metabolismo , Endotelio Vascular/citología , Endotelio Vascular/efectos de los fármacos , Terapia Genética/métodos , Humanos , Neutrófilos/fisiología , ARN Interferente Pequeño/genética , Vena Safena/citología , Vena Safena/metabolismo , Vena Safena/trasplante , Transfección , Factor de Necrosis Tumoral alfa/farmacología , Grado de Desobstrucción VascularRESUMEN
Thoracic mobile aortic mural thrombus (TAMT) of the aortic arch is a rare condition. We report 3 cases of symptomatic TAMT treated with systemic alteplase (tissue plasminogen activator [t-PA]) thrombolysis. The first patient was symptomatic with repetitive thromboembolism to the left brachial artery. She was treated with repetitive thrombolysis after surgical embolectomy of the brachial artery. The second patient was symptomatic with splenic infarction and mesenteric ischemia. She was treated with a single cycle of systemic thrombolysis followed by ileocoecal resection. The third patient presented with a TAMT obstructing the left common carotid artery, causing ischemic stroke. After systemic thrombolysis, a reduction in thrombus size was documented; however, the patient died later, of acute heart failure, during the clinical course. On follow-up 6 months after the incidences, the 2 surviving patients were in good condition and free of thromboembolic events. We show that systemic thrombolytic therapy can be performed successfully in patients with TAMT.