Clinical Investigation And Experimental Study Of Early Recanalization In Acute Superior Mesenteric Venous Thrombosis

Objective:The aim of this study is to solve the current clinic problems of early mesenteric recanalization therapy in acute superior mesenteric venous thrombosis (ASMVT) and provide more clinical and experimental evidences for optimal protocol and strategy of early recanalization in ASMVT patients. Then we can propose the novel management strategy of ASMVT based on early recanalization protocol by transcatheter thrombolysis.Methods:This study follws the concept of translational medicine. We explore the central issues of current early mesenteric recanalization therapy for ASMVT by preliminary literature review and clinical investigation. Then we build the ASMVT animal model to evaluate the early injury of intestinal mucosal epithelial barrier funtion and systemic response of oxidative stress, and compare the effect of different modalities of early transcatheter thrombolysis therapy. Based on the results of clinical investigation and experimental study, we develop the new schemes of early transcatheter thrombolysis therapy and multidisciplinary treatment system for two types of ASMVT patients.Results:First, the advances in moden treatment technique of early recanalization of ASMVT was analyzed and summarized by literature review. The transcatheter thrombolysis centered stepwise management strategy by systemic anticoagulation, endovascular therapy, damage control surgery, organ function support in intesive care unit was propsed. By a single-center retrospective study of ASMVT patients during 10 years, the clinical characters and epidemiology data were reviewed. The effectiveness and safety of initial transcatheter thrombolysis therapy were confirmed in Chinese ASMVT patients. The indication of early transcatheter thrombolysis therapy was extended to ASMVT patients with moderate and circumscribed peritonitis. The serum level of D-dimer during the first 3 days of admission was identified as sensitive serum marker of disease severity and prognosis factor of ASMVT patients, and can be used as an effective parameter of clinical outcome evaluation of different treatment for ASMVT.Then, according to the classic Virchow triad, the ASMVT animal models of two clinical types, the cental-type ASMVT model and peripheral-type ASMVT model, were instituted. These models could minic the real clinical condition of ASMVT patients and be used for experimental studies of mesenteric recanalization. Compared with peripheral-type ASMVT, the systemic hemodynamic alteration was more severe in cental-type ASMVT with more chances of circulatory failure. The injury of intestinal mucosal barrier function occurred in the very early phase of ASMVT. The injury was found to be more earlier and greater in peripheral-type ASMVT than that in cental-type ASMVT. The secondary superior mesenteric artery (SMA) spasm could be an important reason of complete disruption of intestinal mucosal barrier function. The optimal time to institue meenteric recanalization was before 9h in cental-type ASMVT model and before 6h in peripheral-type ASMVT model. The optimal time to institue meenteric recanalization was before 48h in cental-type ASMVT patient and before 36h in peripheral-type ASMVT patient. The imbalance of Thromboxane A2/Prostaglandin h was found in both tpyes of ASMVT. It was asscociated with microcirculation dysfuction in intestine and could trigger the oxidative stress and lipid peroxidation injury in early phase of ASMVT. The microcirculation dysfuction and oxidative stress were suggested to be important cause of disruption of intestinal mucosal barrier function because the time course of them was very consistent in the early phase of ASMVT. The oxidative stress injury in multiple organs could be an significant cause of high rete of multiple organ dysfunction syndrome in ASMVT. Early transcatheter thrombolysis therapy could significantly reduce the oxidative stress and injury of intestinal mucosal barrier function. The direct thrombolysis therapy via superior mesenteric vein (SMV) showed better treatment outcome than indirect thrombolysis via SMA in cental-type ASMVT. The indirect thrombolysis via SMA was better than direct thrombolysis therapy via SMV for peripheral-type ASMVT. Comapred with thrombolysis therpy only, thrombolyis plus infusion of low molecular weight heparin via catherter could significantly relieve the oxidative stress injury with no effect of intestinal mucosal barrier function injury.Finally, the transcatheter thrombolysis therapy by combined route of SMV plus SMA was developed for extensive ASMVT with high efficiency of thrombus removal. The transcatherter thrombolysis therapy was used as postoperative adjunctive therapy for ASMVT patients with emergent surgery. Moreover, a 10-year single center experience of "Multidisciplinary Stepwise Management Strategy for ASMVT" by establishment of intestinal stroke center and multidisciplinary treatment system was repoted.Conclusion:Early mesenteric renalization therapy by transcatheter thrombolysis showed great treatment outcome of ASMVT. The "Multidisciplinary Stepwise Management Strategy" with concept and technique of modern endovascular therapy, damage control surgery, multidisciplinary treatment, and multiple organ function support raise the hopes of significant improvement of overall suevival of ASMVT in the future.