Dose-related Efficacy Of A Intracisternal Irrigation Using Recombinant Tissue-type Plasminogen Activator Treatment On Cerebral Vasospasm In The Rabbit Double Subarachnoid Hemorrhage Model

Objective: To establish a rabbit model of cerebral vasospasm following subarachnoid hemorrhage and study the effect of intracisternal irrigation using recombinant tissue-type plasminogen activator(rt-PA) in prevention of cerebral vasospasm, and to discuss the dose-related efficacy of rt-PA.Methods: 50 New Zealand white rabbits, were made into cerebral vasospasm model by percutaneous puncture and inject auto fresh arterial blood into the cisterna magna twice, and randomly divided into subarachnoid hemorrhage group(n=10),four treatment groups(including 0.25mg,0.50mg,0.75mg and 1.00mg, each group has 10 rabbits), and then four dosages of rt-PA(0.25mg,0.50mg,0.75mg,1.00mg) were injected respectively into cisterna magna of each treatment group, within 48h after the second blood injection to prevent cerebral vasospasm. The cerebral vasospasm of before and 7 days after treatment were assessed by the change of diameter of the basilar artery measured by cerebral angiography and pathological section, and the SUVmean measured by PET-CT.Results: The results showed a trend suggesting that cerebral vasospasm occurred just at 1 day after double subarachnoid hemorrhage, and became serious gradually, reached a peak at about 7 days. Cerebral angiography suggested that the vessel cavity of BA was narrowing, the average value of CVS was 30.83% at 1 day, 48.33% at 3 days, 65.83% at 7 days; the average value of SUVmean was also reducing, from 2.03±0.08 before SAH to 0.81±0.01 at 7 days after SAH; the histological examination showed some morphological changes in the arterial wall of BA, such as the thickening of medical smooth muscle layer and the whole arterial wall, the narrowness of vessel cavity and so on. By the treatment of rt-PA, the CVS palliated in all groups, except the 0.25mg group still existed and deteriorated, but a little better than untreatment group; both of 0.75mg and 1.00mg groups were more efficient than 0.50mg group, but there wasn't any dramatic statistic differences between 1.00mg and 0.75mg group.Conclusion: The occurrence of cerebral vasospasm can be reduced by intracisteral irrigation using recombinant tissue-type plasminogen activator within 48h after subarachnoid hemorrhage, the efficacy of 0.75mg was most significant in four dosage groups.