Exploration Of The Surgical Treatment And Pathogenesis Of The Acute Stanford Type A Aortic Dissection

BackgroundAortic dissection is a very dangerous disease.There are two commonly used categories.First,it's the DeBakey classification.According to the starting position of the intimal rupture,it is divided into three types(Type ?:proximal to the ascending artery,extending beyond the left subclavian artery;Type ?:starting from the ascending artery but limited to below the innominate artery;Type ?:descending aorta(below the opening of the left subclavian artery).And the second is Stanford classification.According to the extent of the aortic dissection,it is divided into two types(Type A:ascending aorta involvement;Type B:ascending aorta is not involved).The mortality rate of type A aortic dissection is significantly higher than that of type B in 30 days.Therefore,once the patients with type A aortic dissection are diagnosed,emergency surgery or limited period of operation should be performed immediately.However,aortic surgery is still one of the most difficult surgical methods in cardiac surgery.Recently,most of the type A aortic dissection patients are treated by the Sun's procedure in China.Few experts will adopt the Y graft technique established by Spielvogel D.These two surgical methods have been recognized by experts at home and abroad.Both of methods are difficult,especially for the inexperienced surgeon.At present,there are few heart centers that can skillfully complete the operation and obtain satisfactory clinical results.According to this characteristic,our center has consulted a large number of literature on this technology,combined with Sun's procedure to put forward our modified idea,the Y graft technology combined with femoral artery bypass and one minute systemic circulatory arrest,and put it into practice.In recent years,aortic surgery has been widely carried out in all provinces and municipal hospitals,and the mortality of the aortic dissection has been greatly improved.But there is no doubt that the more fully understood the pathophysiological level of the aortic dissection,the better the prognosis of it.At present,the pathophysiological mechanism of aortic dissection has many research directions,most of which focus on genetic diversity,clinicopathology and hemodynamics.However,the underlying molecular mechanism of the disease is unclear.Therefore,on the one hand,we start from the technical level of surgery,improve the existing surgical methods,reduce the threshold of surgery,improve the survival rate;on the other hand,from the molecular mechanism level to explore its pathogenesis.In order to early warning and early intervention in the early onset of aortic dissection.The purpose of this study was to study the application of modified Y graft technique in the surgical treatment of Stanford A aortic dissection and to evaluate its effect on intraoperative indexes and short-term outcomes after the operation.At the same time,we explored the mechanism of lncRNA-Ftx regulating VEC function in Stanford A aortic dissection.This study was divided into two parts.PART 1 The Experience of the Treatment of Acute Type A Aortic Dissection using Modified Y-Graft TechniqueObjective:Aortic arch replacement in acute type A aortic dissection patients remains the most challenging cardiovascular operation.Herein,we described our modified Y-graft technique using the Femoral Artery Bypass(FAB)and the One Minute Systemic Circulatory Arrest(OSCA)technique,and assessed the short-term outcomes of the patients.Methods:Between February 2015 and November 2017,51 patients with acute type A aortic dissection underwent aortic arch replacement.Among them,23 patients underwent FAB while 28 patients underwent both FAB and OSCA.The intraoperative data and postoperative follow-up data were recorded.The follow-up data of patients with traditional Y-graft technique were collected from previously reported studies.Results:In the FAB group,two patients died due to pulmonary infection(30-day survival rate,91.3%),and two patients were paralyzed from the waist down.Hemodialysis was performed for five patients(21.7%)before hospital discharge.Fifteen patients(65.2%)received respiratory support for more than 2-days and eight patients(34.8%)for more than 5-days.These follow-up results were comparable or better than the patients with traditional Y-graft technique.Furthermore,compared to the FAB group,the morbidity due to neurological dysfunction and acute renal failure was significantly reduced in the FAB+OSCA group.Moreover,the respiratory support,length of postoperative stay and ICU stay were shortened.Conclusions:This study clarified the feasibility of FAB and OSCA technique in modifying Y-graft technique.The acute type A aortic dissection patients showed less surgical complications and favorable short-term outcomes after this surgery.PART 2 The Exploration of the Mechanism of Ftx Regulating VEC Function in Acute Type A Aortic DissectionObjective:The molecular pathogenesis of aortic dissection remains unclear.The destruction of vascular endothelial function is an important mechanism for the formation of aortic dissection.This study aims to investigate the role of lncRNA Ftx in the biological functions of vascular endothelial cells,as well as the key proteins it regulates,to explore the potential regulatory role of Ftx on the function of vascular endothelial cells in the pathogenesis of aortic dissection furtherly.Methods:12 cases of aortic dissection patients were enrolled,and the bypass surgery patients served as the control group.The whole-genome RNA of aortic dissection tissue and normal ascending aorta tissue was extracted.The expression of lncRNA Ftx was detected by real-time fluorescent quantitative PCR.Lentivirus was used as a vector to establish Ftx knockdown and overexpression human umbilical vein endothelial cell models and the empty plasmids were used as a model control.High-resolution liquid chromatography-tandem mass spectrometry analysis was performed to explore the regulatory effects of Ftx on endothelial cell function as well as relevant effector proteins.Cell experiments was conducted for valuable proteins to verify the regulatory effect by Ftx.Results:The results of clinical data showed that lncRNA Ftx in aortic dissection tissue was significantly up-regulated compared with normal aortic tissue.It was verified by qRT-PCR that the expression of Ftx in the human umbilical vein endothelial cell line cultured in vitro was successfully interfered or overexpressed.Proteomics analysis quantifies a total of 4348 proteins,which are involved in multiple biological processes,cell functions,and metabolism-related signal pathways.Among them,CBX1,a protein related to vascular cell proliferation and growth,is up-regulated when Ftx knocked down,and down-regulated when Ftx is over-expressed.This negative regulation has been further confirmed in cell experiments.Conclusions:This study showed that Ftx is abnormally highly expressed in aortic dissecting tissues.Interfering with the expression level of Ftx in the human umbilical vein endothelial cell line could regulate multiple biological functions of cells.CBX1 may be one of the key proteins.Ftx negatively regulates the expression of CBX1 to affect the growth and proliferation of vascular endothelial cells,thereby affecting the occurrence and development of aortic dissection.