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BACKGROUND: Elderly patients are at increased risk of perioperative morbidity and mortality after conventional on-pump coronary artery bypass grafting (ONCABG). This study was to determine whether such high-risk population would benefit from off-pump coronary artery bypass grafting (OPCABG). METHODS: A retrospective analysis was performed on patients aged 65 years or older who underwent isolated coronary artery bypass grafting for the first time in Wuhan Union Hospital from January 2015 to January 2021. We used propensity score matching to adjust for differences in baseline characteristics between the ONCABG and OPCABG groups. Morbidity and mortality within 30 days after surgery were compared between the two groups. All operations were performed by experienced cardiac surgeons. RESULTS: A total of 511 patients (ONCABG 202, OPCABG 309) were included. After 1:1 matching, the baseline characteristics of the two groups were comparable (ONCABG 173, OPCABG 173). The OPCABG group had higher rate of incomplete revascularization (13.9% vs. 6.9%; P = .035) than the ONCABG group. However, OPCABG reduced the risk of postoperative renal insufficiency (15.0% vs. 30.1%; P = .001) and reoperation for bleeding (0.0% vs. 3.5%; P = .030). There were no significant differences in early postoperative mortality, myocardial infarction, stroke, and other outcomes between the two groups. CONCLUSIONS: OPCABG is an alternative revascularization method for elderly patients. It reduces the risk of early postoperative renal insufficiency and reoperation for bleeding.
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Puente de Arteria Coronaria Off-Pump , Puente de Arteria Coronaria , Complicaciones Posoperatorias , Puntaje de Propensión , Humanos , Masculino , Puente de Arteria Coronaria Off-Pump/métodos , Puente de Arteria Coronaria Off-Pump/efectos adversos , Femenino , Anciano , Estudios Retrospectivos , Complicaciones Posoperatorias/epidemiología , Puente de Arteria Coronaria/métodos , Puente de Arteria Coronaria/efectos adversos , Enfermedad de la Arteria Coronaria/cirugía , China/epidemiología , Factores de RiesgoRESUMEN
BACKGROUND: The objective of this study was to develop and validate a nomogram for the individualized prediction of adverse events in patients with Stanford type A aortic dissection (TAAD) undergoing hybrid total aortic arch repair. METHODS: From April 2019 to April 2022, we conducted a comprehensive review of the medical records of Stanford type A aortic dissection patients who underwent hybrid total aortic arch repair surgery at our hospital. Patients were separated into two groups based on whether or not a composite adverse event occurred following surgery. Using univariate and multivariate analyses of logistic regression, the prediction model was created. Construct risk prediction models utilizing nomograms and evaluate their precision, discrimination, and clinical utility. RESULTS: Age, platelets, serum blood urea nitrogen, and ascending aortic diameter were the variables included in the nomogram by univariate and multivariate analysis. The risk model performed well in internal validation, with an area under the curve (AUC) of 0.829. The calibration curve demonstrated good agreement between predicted and actual probabilities (Hosmer-Lemeshow test, P = 0.22). Clinical decision analysis curves demonstrate predictive nomograms' clinical utility. CONCLUSION: This study created and validated a nomogram for predicting the risk of composite endpoint events in TAAD patients undergoing hybrid total aortic arch repair. The nomogram can help determine the severity of a patient's condition and provide a more personalized diagnosis and treatment.
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Disección Aórtica , Humanos , Aorta Torácica/diagnóstico por imagen , Aorta Torácica/cirugía , Disección Aórtica/diagnóstico por imagen , Disección Aórtica/cirugía , Nomogramas , Estudios RetrospectivosRESUMEN
BACKGROUND AND AIM: Interrupted aortic arch (IAA) is defined as a complete interruption of aortic lumen between the ascending and descending aorta. It is an uncommon and complicated congenital heart disease. It is rare for patients with isolated IAA to survive to adulthood without operation. Here we present three rare cases with isolated IAA together with a review of the literature of IAA. Besides, we reviewed reported adult cases with isolated IAA in the last 20 years and summarized the relevant data of the isolated type. METHODS: We retrospectively searched the hospital databases for adult patients with isolated IAA diagnosed at the Wuhan Union Hospital over the past 10 years. Cases related to adult isolated IAA published in last 20 years were identified by searching Pubmed. RESULTS: Three adult patients with isolated IAA were identified. Two were referred to us for hypertension management and were diagnosed with IAA. They declined surgical treatments and took antihypertensive medications. One patient was referred to our hospital for further treatment options after diagnosed with IAA at another hospital. He received an extra-anatomic bypass surgery. But his hypertension did not well resolve after surgery, and was subsequently managed by anti-hypertensives medications. 25 published adult patients with isolated IAA were identified in Pubmed and relevant details were summarized. CONCLUSIONS: Adult patients with isolated IAA usually have extensive collateral vessels joining the descending aorta. Anti-hypertensives medical management with long-term follow-up appears to be a reasonable treatment option for these patients, although surgical intervention is a good choice.
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Coartación Aórtica , Hipertensión , Adulto , Antihipertensivos/uso terapéutico , Aorta Torácica/diagnóstico por imagen , Aorta Torácica/cirugía , Coartación Aórtica/diagnóstico por imagen , Coartación Aórtica/cirugía , Humanos , Hipertensión/tratamiento farmacológico , Masculino , Estudios RetrospectivosRESUMEN
BACKGROUND: To investigate the effects of tissue-type plasminogen activator (tPA) gene transfer with left-atrium local positioning on the fibrinolytic activity of rabbit left atrial blood. METHODS: A total of 48 rabbits were randomly divided into 3 groups (n = 16): gene therapy, vector control, and blank control groups. Each group was divided into 2 subgroups (8 rabbits in each subgroup) according to the sacrifice time on the postoperative 3(rd) and 14(th) days. The tPA mRNA transcriptional level and exogenous tPA protein expression within regional myocardial tissues of the left atrium were detected on the postoperative 3(rd) and 14(th) days. After excluding the animals that died, 6 samples of each subgroup were randomly selected for the statistics (n = 6). RESULTS: The tPA activities in rabbit left atrial blood and peripheral blood were also detected. The tPAmRNA and tPA protein expressions within regional myocardial tissues were detected on the postoperative 3(rd) and 14(th) days. The tPA activity in left atrial blood in the gene therapy group was higher than the tPA activity of other groups (p < 0.02). No significant differences were observed in the tPA activity of peripheral blood among the 3 groups before surgery. A gelatin-coated Dacron piece, which carried the tPA gene, was implanted in the left atrial appendage. CONCLUSIONS: The gelatin-coated Dacron piece could express and secrete tPA proteins in the region, thus enhancing the fibrinolytic activity of left atrial blood. KEY WORDS: Fibrinolytic activity; Gelatin coating; Gene; Left atrium; Tissue-type plasminogen activator.
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This case report described a patient of Behçet disease (BD)-related vascular lesions that initially presented as occlusion of superior vena cava (SVC) without any evidence of thrombosis. The patient was treated first by percutaneous transluminal angioplasty and stent implantation, and he developed thrombosis in the stent and then received open bypass operation. Pathologic examination of the SVC specimen and the postoperative manifestations revealed that the underlying cause of his symptoms as BD. Afterward, methylprednisolone plus anticoagulant therapy was routinely given, which relieved the symptoms of the patient.
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Síndrome de Behçet/complicaciones , Síndrome de la Vena Cava Superior/etiología , Vena Cava Superior , Adulto , Angiografía de Substracción Digital , Angioplastia de Balón/efectos adversos , Angioplastia de Balón/instrumentación , Anticoagulantes/uso terapéutico , Síndrome de Behçet/diagnóstico , Síndrome de Behçet/terapia , Biopsia , Implantación de Prótesis Vascular , Glucocorticoides/uso terapéutico , Humanos , Angiografía por Resonancia Magnética , Masculino , Metilprednisolona/uso terapéutico , Stents , Síndrome de la Vena Cava Superior/diagnóstico , Síndrome de la Vena Cava Superior/terapia , Trombosis/etiología , Trombosis/terapia , Tomografía Computarizada por Rayos X , Resultado del Tratamiento , Vena Cava Superior/diagnóstico por imagen , Vena Cava Superior/patología , Vena Cava Superior/cirugíaRESUMEN
Introduction: This study was to determine whether coronary artery bypass grafting without cardiopulmonary bypass (off-pump CABG, OPCAB) could reduce early postoperative mortality and major complications compared with conventional coronary artery bypass grafting with cardiopulmonary bypass (on-pump CABG, ONCAB) by experienced surgeons. Material and methods: From January 2016 to June 2020, isolated CABG was performed in 1200 patients (ONCAB 429, OPCAB 771) in Wuhan Union Hospital. The propensity score matching was used to adjust for differences in baseline characteristics between the ONCABG and OPCABG groups. After 1:1 matching, 404 pairs for each group were selected to compare outcomes within 30 days after surgery. All the operations were completed by experienced surgeons that had completed more than 500 on-pump and 200 off-pump CABG, respectively. Results: After propensity matching, the two groups were comparable in terms of preoperative characteristics. The OPCAB group had less vein graft (2.5 ± 1.0 vs. 2.7 ± 0.9; P < 0.001) and a higher rate of incomplete revascularization (12.4 vs. 8.2%; P < 0.049) than the ONCAB group. There was no significant difference in early postoperative mortality between ONCAB and OPCAB groups (2.2 vs. 2.2%; P = 1.00). However, patients in the OPCAB group had a lower risk of postoperative stroke (1.5 vs. 4.7%; P = 0.008), new-onset renal insufficiency (8.9 vs. 18.8%; P < 0.001), respiratory failure (2.2 vs. 7.2%; P = 0.001), reoperation for bleeding (0.5 vs. 2.7%; P = 0.001), and required less ventilator assistance time (33.4 ± 37.9 h vs. 51.0 ± 66.1 h; P < 0.001) and intensive care unit (ICU) time (3.7 ± 2.7 days vs. 4.8 ± 4.3 days; P < 0.001). Conclusions: In our study, patients undergoing OPCAB had fewer postoperative complications and a faster recovery. It is a feasible and safe surgical approach to achieve revascularization when performed by experienced surgeons.
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INTRODUCTION: No previous studies comparing the outcomes between off-pump coronary artery bypass grafting (off-pump CABG, OPCAB) and on-pump CABG (ONCAB) have been performed in patients with severe left ventricular dysfunction (LVD) and a giant left ventricle. We aimed to investigate whether such patients could benefit from OPCAB. METHODS: From January 2011 to January 2021, a total of 98 patients with severe LVD and a giant left ventricle underwent isolated CABG (ONCAB 46, OPCAB 52) in Wuhan Union Hospital. The clinical data were collected retrospectively and propensity score matching was performed to adjust baseline characteristics. RESULTS: After propensity matching, the two groups were comparable in baseline variables. The OPCAB group had a higher rate of incomplete revascularization than the ONCAB group (25.0% vs. 9.1%; p = 0.047). The 30-day mortality was similar between the matched groups (4.5% vs. 4.5%; p = 1.000) but the OPCAB group had a lower risk of postoperative IABP usage (9.1% vs. 25.0%; p = 0.047) and renal insufficiency (11.4% vs. 29.5%; p = 0.034). The long-term probability of survival (log-rank test, p = 0.450) was similar between the two groups but the OPCAB group had a lower probability of major adverse cardiovascular events (log-rank test, p = 0.038). CONCLUSIONS: For patients with severe LVD and a giant left ventricle, OPCAB reduced early postoperative complications while sacrificing long-term quality of life compared to those having ONCAB.
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[This corrects the article DOI: 10.3389/fcvm.2022.965648.].
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Background: Many countries and regions have established multicenter registration studies to improve the outcomes of acute type A aortic dissection (ATAAD). Objectives: The aims of this study were to report actual preoperative management, surgery type, and early outcomes of surgical treatment for ATAAD in China. Methods: This cohort study uses data from the China Registry of Type A Aortic Dissection, a national clinical registry to investigate management of patients with Stanford type A aortic dissection. The data, including surgical management and outcomes of patients with ATAAD, were analyzed from January 2018 to December 2021. Results: A total of 1,058 patients with ATAAD were enrolled in this study between January 2018 and December 2021. The mean age of all patients was 51.6 ±11.7 years. The median interval from onset to hospital was 10.65 hours (IQR: 6-24 hours), and the median interval from entering the emergency room to starting operation was 13 hours (IQR: 4.08-28.7 hours). Total arch repair was performed in 938 patients (88.7%), and frozen elephant trunk repair was performed in 800 patients (75.6%). The incidence of early mortality was 7.6%. Conclusions: The population of patients with ATAAD in China experienced a longer interval from onset to arrival at the hospital, received more extensive aortic arch repair, and showed a relatively lower early mortality. These findings suggest that there may be a huge survivor bias in patients with ATAAD in China, more efforts should be made to promote prehospital emergency care and preoperative management of Chinese ATAAD patients. (A multicenter registration study of aortic dissection in China; ChiCTR1800015338).
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BACKGROUND: A hybrid surgery method, on-pump beating heart coronary artery bypass graft (ON-BH CABG), is supposed to be a promising technology for coronary artery revascularization. Here, we conducted a comprehensive meta-analysis of the data derived from published studies on ON-BH CABG and conventional on-pump coronary artery bypass graft (C-CABG) to compare their short-term and long-term clinical outcomes. METHODS: We searched major electronic databases and 24 studies incorporating 6,862 patients (1,847 ON-BH CABG and 5,015 C-CABG) were included eventually, and 9 studies of them were focusing on high-risk patients. RESULTS: Compared with ON-BH CABG, C-CABG was associated with a higher risk in early mortality [odds ratio (OR), 1.45; 95% confidence interval (CI), 1.09 to 1.93; P=0.01], myocardial infarction (MI) (OR, 2.60; 95% CI, 1.41 to 4.78; P<0.01), low output syndrome (LOS) (OR, 2.56; 95% CI, 1.55 to 4.23; P<0.01), renal failure (OR, 1.84; 95% CI, 1.38 to 2.44; P<0.01). In contrast, there was no significant difference in long-term survival [hazard ratio (HR), 1.08; 95% CI, 0.81 to 1.43; P=0.60]. In systematic analysis of the studies in high-risk patients, ON-BH CABG showed a lower risk in terms of early mortality, intra-aortic balloon pump (IABP) usage, renal failure, hemodialysis, MI and pulmonary complication. No significant difference was observed in the long-term survival between ON-BH CABG and C-CABG. CONCLUSIONS: With experienced and adept surgical team and mature ON-BH technology, ON-BH CABG may reduce the risk of postoperative death and complications in some patients. It might be an attractive alternative for high-risk patient populations.
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ETHNOPHARMACOLOGY RELEVANCE: In folkloric medicine of many cultures, one of the medical uses of Valeriana officinalis Linn is to treat heart-related disease. Recently, it was shown that the ethanol extracts from V. officinalis could effectively prevent auricular fibrillation, and 8-hydroxypinoresinol-4-O-ß-D-glucoside (HPG) from the extracts is one of the two active compounds showing antiarrhythmia activities. AIM OF THE STUDY: The human Kv1.5 channel (hKv1.5) has potential antiarrhythmia activities, and this study arms at investigating the current blocking effects of HPG on hKv1.5 channel. MATERIAL AND METHODS: HPG was obtained from V. officinalis extracts, and hKv1.5 channels were expressed in HEK 293 cells. HPG was perfused while recording the current through hKv1.5 channels. Patch-clamp recording techniques were used to study the effects of HPG at various concentrations (10 µM, 30 µM, and 50 µM) on hKv1.5 channels. RESULTS: The present study demonstrated that HPG inhibited hKv1.5 channel current in a concentration-dependent manner; the higher the concentration, the greater is the inhibition at each depolarization potential. During washout, the channels did not full recover indicating that the un-coupling between HPG and hKv1.5 channels is a slow process. CONCLUSION: HPG may be an effective and safe active ingredient for AF having translational potential.
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Antiarrítmicos/farmacología , Canal de Potasio Kv1.5/antagonistas & inhibidores , Extractos Vegetales/farmacología , Bloqueadores de los Canales de Potasio/farmacología , Valeriana/química , Potenciales de Acción/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Células HEK293 , Humanos , Canal de Potasio Kv1.5/genética , Técnicas de Placa-Clamp , Factores de Tiempo , Verapamilo/farmacologíaRESUMEN
Form 2008 to 2009, four patients with complex thoracic aortic disease, including aortic aneurysms and dissections, were successfully treated in our department with a new treatment approach: hybrid procedure. Combined open surgery and endovascular repair were performed in these patients without deep hypothermia or circulatory arrest. Compared to those who underwent traditional open surgery in the same period, time of mechanical ventilation and ICU stay was decreased in these four patients. All of them were discharged soon after operation without postoperative complications or death. The result suggests that this new approach could be an option for thoracic aortic disease, but long-term and large-population studies are still required to demonstrate the safety and validity.
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Aneurisma de la Aorta Torácica/cirugía , Disección Aórtica/cirugía , Implantación de Prótesis Vascular/métodos , Procedimientos Endovasculares/métodos , Procedimientos Quirúrgicos Torácicos/métodos , Adulto , Anciano , Prótesis Vascular , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
OBJECTIVES: Our goal was to compare the short-term outcomes of Stanford type A aortic dissection (TAAD), during the coronavirus disease 2019 (COVID-19) pandemic with those during normal times and summarize our perioperative management experience of patients with TAAD in the context of COVID-19. METHODS: From 17 January 2020 to 8 March 2020, a total of 27 patients with TAAD were operated on in 8 cardiovascular surgery centres in Hubei Province (COVID-19 group). The data from 91 patients with TAAD from the same centres during the same period last year were extracted from the Hubei Cardiac Surgery Registration System (control group). A propensity score matched subgroup of 26 pairs (1:2) was identified. Perioperative data and short-term outcomes were assessed. RESULTS: Nine patients in the COVID-19 group were categorized as suspicious for the disease (9/27, 33.3%), and others were excluded (18/27, 66.7%). No one was laboratory confirmed preoperatively. The average waiting, cross-clamp and circulatory arrest times were longer in the COVID-19 group (22.9 ± 8.3 vs 9.7 ± 4.0 h, P < 0.001; 135 ± 36 vs 103 ± 45 min, P = 0.003; 24 ± 9 vs 17 ± 8 min, P < 0.001, respectively). The 30-day or in-hospital deaths were 3.8% in both groups (P = 1.0). The COVID-19 group was associated with longer ventilation and intensive care unit times (81 ± 71 vs 45 ± 19 h, P < 0.001; 7.4 ± 3.8 vs 4.5 ± 2.7 days; P < 0.001, respectively). There were no statistical differences between the 2 groups in the incidence of complications such as stroke, neurological deficit, acute kidney injury, pulmonary infection and reoperation. Serum antibody tests for those patients showed 7 out of 9 suspected cases were Immunoglobulin G positive. No cross-infection occurred in other patients or associated medical staff. CONCLUSIONS: With adequate preparation and appropriate protection, satisfactory early outcomes can be achieved after emergency operations for patients with TAAD during the COVID-19 pandemic.
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Disección Aórtica/cirugía , COVID-19/epidemiología , Pandemias , Puntaje de Propensión , SARS-CoV-2 , Procedimientos Quirúrgicos Vasculares/métodos , Disección Aórtica/epidemiología , China/epidemiología , Comorbilidad , Femenino , Humanos , Incidencia , Unidades de Cuidados Intensivos , Masculino , Persona de Mediana Edad , Reoperación , Estudios Retrospectivos , Factores de Riesgo , Tasa de Supervivencia/tendencias , Factores de Tiempo , Resultado del TratamientoRESUMEN
The study summarizes the clinical experience of surgical treatments of various types of thoracic aneurysm and aortic dissection. Clinical data of 122 patients with thoracic aneurysm and aortic dissection during July 2005 to July 2008 were retrospectively analyzed. The elective operations were performed in 107 patients while emergency surgery was done in 15 cases. Different surgical strategies were employed on the basis of diseased region, including simple ascending aortic replacement (n=3), aortic root replacement (n=43), hemi-arch replacement /total arch replacement+elephant trunk technique (n=32), thoracic/thoracoabdominal aortic replacement (n=8) and endovascular repair (n=36). In this series, there is 4 cases of perioperative death due to massive cerebral hemorrhage (n=1), respiratory failure (n=1) and multiple organ dysfunction syndrome (MODS) (n=2). Three cases developed post-operative massive cerebral infarction and the relatives of the patients abandoned treatment. Instant success rate of endovascular repair was 100%. The intimal rupture was sealed. Blood flow was unobstructed in true lumen and no false lumen was visualized. It was concluded that aggressive surgery should be considered in the patients with thoracic aneurysm and aortic dissection. Surgical procedures should vary with the location and the nature of the lesions.
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Aneurisma de la Aorta Torácica/cirugía , Disección Aórtica/cirugía , Adolescente , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Procedimientos Quirúrgicos Vasculares/métodos , Adulto JovenRESUMEN
In order to study the effects of ethyl pyruvate on cardiomyocyte apoptosis following ischemia/reperfusion (I/R) in vitro and the expression of Bcl-2 and Bax proteins, isolated rat hearts were perfused in a Langendorff model. Twenty-four rats were randomly divided into 3 groups (n=8 in each group): control group was perfused for 120 min. In the I/R group, after 30 min stabilization the injury was induced by 30 min global ischemia followed by 60 min reperfusion. Ethyl pyruvate (EP) group was set up with the same protocol as I/R group except that it was supplied with 2 mmol/L EP 15 min before ischemia and throughout reperfusion. Myocardial malonaldehyde (MDA) content was measured. Myocardial apoptotic index (AI) was tested by terminal deoxynucleotidyl transferase mediated dUTP nick end labeling (TUNEL) method. The expression of anti-apoptotic protein Bcl-2 and pro-apoptotic protein Bax in cardiac myocytes was detected by immunohistochemistry. As compared with control group, the content of MDA, myocardial AI and the expression of Bcl-2, Bax proteins were increased significantly in I/R group, but the content of MDA, myocardial AI and the expression of Bax protein were decreased obviously and the expression of Bcl-2 protein was up-regulated in EP group (P<0.05). These results demonstrate that EP could inhibit apoptosis of cardiac myocytes possibly via alleviating oxidative stress, up-regulating Bcl-2 and down-regulating Bax proteins.
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Apoptosis , Miocardio/patología , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Piruvatos/farmacología , Daño por Reperfusión , Proteína X Asociada a bcl-2/metabolismo , Animales , Etiquetado Corte-Fin in Situ , Masculino , Malondialdehído/farmacología , Miocitos Cardíacos/citología , Estrés Oxidativo , Ratas , Ratas Sprague-Dawley , Distribución TisularRESUMEN
To develop a more efficient antithrombotic way after coronary artery bypass grafting (CABG), the anticoagulant effects were compared of human tissue factor pathway inhibitor (TFPI) gene transfection and aspirin oral administration (traditional method) on vein grafts. An eukaryotic expression plasmid pCMV-(Kozak) TFPI was prepared. Animal model of carotid artery bypass grafting was constructed. In operation, endothelial cells of vein grafts in TFPI group and empty plasmid control group were transfected with pCMV-(Kozak) TFPI and empty plasmid pCMV respectively, while no transfection was conducted in aspirin control group. After operation, aspirin (2 mg.kg(-1).(-1)) was administered (i.g.) in aspirin control group. Three days later, grafts (n=10) were harvested for RT-PCR, Western blotting and immunohistochemical analyses of exogenous gene expression and for pathological, scanning electron microscopic observation of thrombus. Thirty days later, the patency rates of remnant grafts (n=10) were recorded by vessel Doppler ultrasonography. Human TFPI gene products were detected in gene transferred vein grafts. Three days later, thrombi were found in 7 animals of aspirin control group and in 8 animals of empty plasmid control group, but in only 1 of TFPI group (P<0.01). Thirty days later, 5 grafts were occluded in empty plasmid control group, but none of grafts was occluded in the other groups (P<0.05). The endothelial surfaces of grafts in both of the control groups were covered with aggregated erythrocytes and platelets, and it were not seen in TFPI group. It was suggested that the anticoagulant effects on vein grafts of human TFPI gene transfection are better than those of aspirin.
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Anticoagulantes/metabolismo , Aspirina/administración & dosificación , Lipoproteínas/metabolismo , Trasplante de Tejidos/métodos , Venas/trasplante , Administración Oral , Animales , Aspirina/metabolismo , Puente de Arteria Coronaria , Modelos Animales de Enfermedad , Humanos , Plásmidos/metabolismo , Conejos , Transfección , Ultrasonografía Doppler/métodos , Trombosis de la Vena/metabolismoRESUMEN
BACKGROUND: Mutation of the ACTA2 (α-2 smooth muscle actin) gene accounts for ~15% of all cases of familial thoracic aortic aneurysms and dissections. Surprisingly, no severe vascular phenotypes were observed at baseline in mice carrying this gene mutation. Our aim was to explore whether mutation of ACTA2 promotes the development of aneurysms or dissections in the presence of angiotensin II (AngII) and to determine whether this mutation has an impact on the phenotypic modulation and apoptosis mediated by AngII in vascular smooth muscle cells (VSMCs). METHODS: Mice were divided into three groups: AngII stimulated-wild-type (WT) (AngII) and ACTA2-/- mice (ACTA2) group, in which AngII were administered subcutaneously into 8-week-old C57 mice and ACTA2-/- mice, respectively, for 4 weeks using osmotic minipumps, and the control group (WT), in which the WT mice were infused with normal saline (NS). Ultrasound was performed to quantify lumen diameters. RT-qPCR and Western blot were used to assess gene expression, and histobiochemistry was used to evaluate the pathological changes in the thoracoabdominal aortas. TUNEL was used to assess apoptosis in VSMCs. RESULTS: Compared with the AngII- group, the ACTA2 mice exhibited more severity of dilated lumena of the aortas, a significantly increased expression of osteopontin (OPN), an elevated ratio of Bax/Bcl-2, increased apoptosis, and a decreased expression of α-smooth muscle actin (α-SMA). CONCLUSIONS: Knockout of ACTA2 promoted AngII induced progressive lumen dilation of the aortas, apoptosis, and the phenotypic modulation in VSMCs in mice.
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We have established a human umbilical vein endothelial cell (HUVEC) line monoclonal cells with the stable expression of human tissue-type plasminogen activator (t-PA) gene to provide a basis for further study on the vascular tissue engineering. Recombinant plasmid pcDNA3. 1-Myc-His B (-)/t-PA was constructed by insertion of t-PAcDNA originated from PBS/t-PA into eukaryotic expression vector pcDNA3. 1-Myc-His B(-) and transfected into hUVEC line cells mediated by lipofectamine. The positive clones were obtained by the screen of G418. The transcription and expression of t-PA gene were investigated by RT-PCR and Western blotting respectively. The t-PA activity was measured by chromogenic substrate assay. The positive clone cells which transcripted the mRNA of t-PA gene was obtained by RT-PCR. Immunoreactive human t-PA of the medium was significantly increased in the group of transfected gene when compared with that in the controlled and transfected plasmid without t-PA gene group. The biological activity of the protein of the t-PA in the media was increased significantly in the positive clone cells with t-PA gene transfected. The HUVEC line monoclonal cells with the stable expression of t-PA gene was established successfully.
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Células Endoteliales de la Vena Umbilical Humana/metabolismo , Lípidos/farmacología , Activador de Tejido Plasminógeno/biosíntesis , Línea Celular , Humanos , ARN Mensajero/biosíntesis , ARN Mensajero/genética , Proteínas Recombinantes/biosíntesis , Proteínas Recombinantes/genética , Ingeniería de Tejidos , Activador de Tejido Plasminógeno/genética , TransfecciónRESUMEN
The effects of in vivo local expression of recombined human tissue-type plasminogen activator (t-PA) gene on the thrombosis and neointima formation of vein grafts were explored. Jugular vein-to-artery bypass grafting was performed on 72 New Zealand white rabbits. The rabbits were divided into 3 groups according to the different processing methods: transfected t-PA gene group (n = 24), vector group (n = 24) and blank control group (n = 24). Samples of vein grafts were harvested at different time points after surgery. The expression of t-PA gene in vein graft was detected by RT-PCR and the synthesis of t-PA protein by Western-Blot assay. The t-PA activity was measured by chromogenic substrate assay. The Cr51 labeled platelets accumulation in vein grafts was counted. The histopathological changes were compared in intima hyperplasia index among the three groups after operation. The results showed that at the 2nd, 5th, 14th and 28th day after operation, RT-PCR and Western-blot confirmed the expression of t-PA mRNA and protein at the site of gene transfer. The t-PA activity detected on the 2nd, 5th, 14th and 28th day in experimental group was 370.63 +/- 59.44, 344.13 +/- 48.47, 252.87 +/- 51.80 and 161.75 +/- 68.94 U/g respectively, and disappeared on the 60th day and undetected in the control groups. The number of platelets accumulated in the vein grafts in gene group, vector group and blank control group was (85.04 +/- 21.58) 10(6), (225.87 +/- 85.13) 10(6) and (211.7 +/- 78.02) 10(6) respectively. The number of platelets accumulated in gene group was significantly fewer than that in the control groups. Morphometric analysis revealed that intimal hyperplasia was markedly reduced in the t-PA gene group as compared with that in the control groups. It was suggested that the local expression of t-PA gene in vein graft significantly inhibited the accumulation of platelets, thrombosis and concomitant intimal hyperplasia, by which stenosis of bypass graft could be prevented effectively.