【作者】 施海彬；

【导师】 黄峻；

【作者基本信息】 南京医科大学 ， 内科学， 2005， 博士

【摘要】 目的:①用介入栓塞技术建立一种能用于影像学诊断与溶栓治疗研究的犬急性脑栓塞动物模型,并评价其技术上的可行性和稳定性;②探讨多层螺旋CT脑灌注成像的注射速率及剂量;③研究r-Sak不同剂量、不同途径溶栓治疗犬急性脑栓塞的疗效和并发症,并与UK进行比较,以探讨r-Sak动脉内溶栓的合理剂量、安全性和有效性;④观察重组葡激酶对犬凝血和纤溶系统的影响。 方法:①成年毕格犬6条,抽取犬自体静脉血制作白色血栓,DSA透视下将4F猎人头导管插至左侧颈内动脉注入血栓,分别在栓塞前及栓塞后立即以及1、2、5h行脑血管造影观察所栓塞血管的通畅情况。24h后处死动物行病理检查;②25条毕格犬随机入组进行灌注成像扫描。实验采用配伍组设计。处理因素为对比剂注射速率,分别为3、4、5、6、8(ml/s);配伍因素为对比剂注射剂量,分别为0.5、0.75、1、1.25、1.5(ml/kg)。所得图像经后处理,测量上矢状窦内对比剂至峰值时间及升高CT值;③成年毕格犬36条,用介入技术建立犬脑栓塞动物模型,并随机分为对照组、r-Sak小剂量组、r-Sak中剂量组、r-Sak大剂量组、UK组和r-Sak静脉溶栓组。栓塞后5h行脑血管造影观察所栓塞血管的通畅情况,在30min内注射药物进行溶栓治疗(对照组:生理盐水10ml,动脉内;r-Sak小剂量组:r-Sak 5,000U/kg,更多还原

【Abstract】 Objectives: ① To establish a new canine model of focal cerebral infarction that be suit for the study of imaging diagnosis and thrombolytic therapy, and to evaluate the technique feasibility and stability; ② To investigate the suitable injection rate and dose of multislice CT perfusion imaging; ③ To study the effect and complications of r-Sak for acute cerebral infarction thrombolysis with different doses, different way in canine mode, and compare with UK, and then to investigate the fit dose, the safety and the efficacy of intraarterial r-Sak ;④ To observe the effect of r-Sak on plasma levels of coagulation and thrombolytic parameters in dogs.Methods: ① Six beagle dogs were selected into the study. The white thrombus was coagulated with dog’s self-venous blood. The 4F headhounter catheter was inserted into the left internal carotid artery and the thrombi was injected under fluoroscopic guidance. The cerebral angiography was performed before and after the embolization. The patency of the occluded cerebral arteries were examined by angiography at 1、 2 and 5h after the embolization. These dogs were sacrificed and the cerebrum was taken out for pathology study at 24h; ② Randomizedblock design was adopted in this study. The treatment factor-contrast medUm injection rate was classified into 3, 4, 5, 6 and 8(ml/s); the subjects were divided into 5 blocks grouped by contrast medUm injection dose: 0.5, 0.75, 1.0, 1.25 and 1.5(ml/kg). After post processing, time to peak (TTP) and rise value (RV) were measured in superior sagital venous; ③ The embolism model of acute cerebral infarction was established with interventional technique in 36 adult beagle dogs, which were randomly divided into control(saline, 10ml, IA), r-Sak low dose(r-Sak, 5,000U/kg, IA), r-Sak middle dose(r-Sak, 10,000U/kg, IA), r-Sak high dose(r-Sak, 20,000U/kg, IA), UK(UK, 10,000U/kg, IA) and intravenous r-Sak(r-Sak, 10,000U/kg, IV) groups. Angiography and thrombolysis within 30 minutes were performed 5 hours after embolization with different way, and angiography was repeated half, 1 and 2 hours after thrombolysis to observe recanalization. Blood samples were collected at a series of time pre- and post-thrombolysis to examine the plasma levels of PT, APTT and D-dimer. These canines were sacrificed, and their cerebri and vessels were taken out for pathologic study at 24 hours.Results: ①The middle cerebral artery occlusion occurred in all 6 dogs, 4 of which had other cerebral artery occlusion. All occluded arteries were not patent at 2h after embolization, but 1 posterior communicating artery was partly patent at 5h. All dogs were survived at 24h without any severe complications. The cerebral infarctions were found in dog’s deepcerebrum; (D Injection rate had a statistical significant effect on TTP of superior sagital venous. There was no significant difference among group 5, 6 and 8ml/s. Compared with 8ml/s, TTP of superior sagital venous was prolonged when injection rate 3, 4 ml/s were adopted. Injection dose had a statistical significant effect on RV of superior sagital venous. There was no significant difference among group 1, 1.25 and 1.5ml/kg. Compared with 1..5ml/kg, RV of superior sagital venous was prolonged when injection dose 0.5,0.75 ml/kg were adopted (D The rate of efficacy in 2 hours after thrombolysis was 10.0% (1/10) in control group, 40.0% (4/10) in low dose group, 90.9% (10/11) in middle dose group, 100% (9/9)in high dose group, 33.3% (3/9) in UK group and 45.5%(4/11) in intravenous group, respectively. There statistically are obvious differences among groups(p<0.05). The rate of complete recanalization was 0(0/10), 10% (1/10), 36.4% (4/11), 66.7% (6/9), 0(0/9), 9.09%(1/11), respectively. There are also statistically obvious differences among groups(p<0.05);(4) The death occurred in 1 canine of high dose group whin 24 hours after thrombolysis, the others were survived. The hemorrhage was found in puncture point with 6, 2 dogs respectively of the high dose and middle dose group after thrombolysis. There were better clinical re更多还原