Intracisternal Infusion Of Rt-PA And Urokonase In The Prevention Of DCVS After Subarachnoid Hemorrhage: A Preliminary Study

Objective: To establish a rabbit model of cerebral vasospasm following subarachnoid hemorrhage and study the effect of intracisternal irrigation using urokinase and recombinant tissue-type plasminogen activator(rt-PA) in prevention of cerebral vasospasm, and to discuss urokinase and rt-PA in control efficiency of DCVS.Methods: 40 New Zealand white rabbits,were randomly made into three groups: normal saline group(n=10),SAH group(n=10),treatment groups[including rt-PA (n=10), urokinase (n=10)]. Before the experiment, PET-CT and the angiogram of basilar artery(BA) were performed,cerebral vasospasm model by percutaneous puncture and inject auto fresh arterial blood into the cisterna magna twice,normal saline group inject equal normal saline. rt-PA(180ug/kg) and urokinase(24000U/kg) were injected respectively into cisterna magna of each treatment group, within 24h after the second blood injection to prevent cerebral vasospasm. The cerebral vasospasm was assessed by the SUVmean measured by PET-CT,the diameter of basilar artery measured by cerebral angiography and pathological section.Results: To compare the SUVmean and the diameter of the BA among the three groups (rt-PA group, urokinase group,SAH group), there was no significant difference before treatment(P>0.05).To compare with SAH group, the SUVmean and the diameter of the BA were increased in treatment groups(rt-PA group, urokinase group)after treatment, there was significant difference between treatment groups and SAH group (P<0.001). Comparison of the SUVmean and the diameter of the BA, there was significant difference between rt-PA group and urokinase group after treatment (P<0.05),and there was also significant difference both in rt-PA group and urokinase group before and after treatment(P<0.001). The blood clots around the BA was decreased in the second day and disappeared in the sixth day both in rt-PA group and urokinase group after treament,and the decreased clots were more in rt-PA group than urokinase.But there was a lot of blood clots around the BA in SAH group in the third day,decreased in the seventh day. The histopathological examination showed the thickening of smooth muscle layer, the narrowness of vessel cavity and the corrugation of intim in SAH group in seventh day,but the change was relieved in rt-PA group and urokinase group after treatment.Conclusion: Single intracisternal irrigation using recombinant tissue-type plasminogen activator and urokinase within 24h after subarachnoid hemorrhage could resolve blood clots and prevent DCVS, the efficacy of rt-PA was more significant than urokinase.