【摘要】 目的比较动脉内注射不同剂量重组葡激酶(r-Sak)溶栓治疗犬急性脑梗死的疗效和并发症,以探讨其相对合理的治疗剂量。方法成年比格犬24条,用介入技术建立犬脑栓塞动物模型,随机分为对照组(生理盐水10 ml)、小剂量组(r-Sak 5 000 u/kg)、中剂量组(r-Sak 10 000u/kg)和大剂量组(r-Sak 20 000 u/kg)。栓塞后5 h行脑血管造影观察所栓塞血管的通畅情况,插管至左颈内动脉分别在30 min内注入药物行溶栓治疗,在溶栓后0．5、1及2 h复查DSA,观察栓塞血管的再通情况,并分别在溶栓前0．5 h、溶栓后0．5 h、1 h及2 h抽取犬静脉血检测PT、APTT和D-二聚体。24 h后处死动物行病理检查。结果溶栓后2 h内造影显示对照组、r-Sak小剂量、中剂量和大剂量组的有效率分别为10．0%(1/10)、40．0%(4/10)、90．9%(10/11)和100%(9/9),各组间比较有显著性差异(P＜0．001);完全通畅的比率分别为0、10%(1/10)、36．4%(4/11)、66．7%(6/9),也有统计学差异(P=0．005)。溶栓后PT、APTT在r-Sak各剂量组均显著延长(P＜0．001);各组的D-二聚体在溶栓前后没有明显变化(各组P＞0．05)。溶栓后r-Sak大剂量组有1例死亡,病理检查在其顶叶脑实质见出血灶,其余动物均存活。结论①在犬脑梗死的超急性期,r-Sak动脉内溶栓治疗有效、可行,r-Sak对含少量血小板的白色血栓有显著溶栓作用,剂量大或等于10 000 u/kg时血管再通率高,剂量再增加出血风险加大;②r-Sak在有效剂量范围内不激活犬的系统纤溶,但对犬的凝血系统影响较大。更多还原

【Abstract】 Objective To compare the effect and complications of intraarterial thrombolysis with different doses of recombinant-staphylokinase(r-Sak)in canine model with acute cerebral infarction,and then to find out the most properly appropriate effective dose.Methods The model with left cerebral embolism was established with interventional technique in 24 beagle adult dogs.They were randomly divided into 4 groups including control group(saline,10 ml),group of low dose(r-Sak,5 000 u/kg),middle dose(r-Sak,10 000 u/kg)and high dose(r-Sak,20 000 u/kg).Angiography and intraarterial thrombolysis were performed within 30 minutes after the embolization.Microcatheter was superselectively inserted into left carotid artery.Five hours later with a repeated angiography at half,1 and 2 hours after thrombolysis to observe the recanalizafion.Blood samples were collected at a series of time pre-and post-thrombolysis to test the plasma levels of PT,APTT and D-dimer.These canines were sacrificed,and their cerebri were taken out for pathologic study by the end of 24 hours.Results The rates of efficacy within 2 hours after thrombolysis were 10.0%(1/10)in control group, 40.0%(4/10)in low dose group,90.9%(10/11)in middle dose group and 100%(9/9)in high dose group. The rates of complete recanalization were 0,10%(1/10),36.4%(4/11)and 66.7%(6/9),correspondingly and respectively.There were statistically obvious differences between the 3 groups(P＜0.05).PT and APTF prolonged markedly in all r-Sak groups(P＜0.001 )after thrombolysis.There was no obvious change of D-dimer after thrombolysis in all groups(P＞0.05).Death occurred in 1 canine(high dose group)within 24 hours after thrombolysis with hemorrhagic lesion in parietal lobe of brain.No other severe complications ocurred. Conclusions①Intraarterial thrombolysis with r-Sak within 5 hours after onset of thrombosis is effective and feasible.Intraarterial r-Sak shows strong thrombolytic effect for white thrombus including a few platelets.There is relative high rate of recanalization with no less than 10 000U/kg of r-Sak but accompanied with high risk of hemorrhage following dose increase.②The systemic fibrinolysis is not significantly affected by r-Sak with no more than effective dosage.But there is apparent effect on coagulation in dogs.更多还原