Effect Of Intra-arterial Urokinase Or/and Neuprotect Agents On Autologous Arterial Emboli In Rabbits Of Acute Ischemic Stroke

Objectives: A randomized controlled trial was conducted to test the efficacy of single thrombolisis therapy with urokinase or combined with neuroprotectant thrapy in the treatment of acute embolic stroke-Materials and Methods: Embolic stroke which the middle cerebral artery of 36 rabbits was embolized with autologous emboli, which was devided into three paired groups(the number of per group is 12). The obstruction of the middle cerebral artery of each brain was examined by digital sbtraction angiography. Two hours after embolization the rabbits were blindly treated with urokinase (n =12), urokinase and citicoline(n = 12), or urokinase, citicoline and nimodipine (n = 12). At 3 hours after the embolization was completed, the rabbits were sacrificed. The brain was then cut into 3-mm-thick coronal sections, and stained with triphenyltetrazolium chloride to define volumes of infarction. Recanaled vessels were identified with the use of the modified TIMI grading. Image Tool procession system was used to evaluate the volumes of infarction. The final data was analyzed using the x,2 test corrected for multiple comparisons, paired-sample t-test and multivariate test.Results: The percentages of rabbits with vessels of recanlization in the 3 groups were as follows: 75%(9/12) in the urokinase-treated group, 83.3%(10/12) in the group treated with urokinase and citicoline-treated group, 90.1%(10/11) in the group treated with citicoline and with urokinase and citicoline and nimodipine, respectively. x2=2.046, P=0.727>0.05. Overall, there was not a diffenrence in recanalation rates of vessels in three groups. Infarct volumes were 22.2+/-8.5% (mean+/-SD) of the ischemic hemisphere, 14.3+/-6.9%(mean+/-SD)with urokinase and citicoline and 17.7+/-8.7%(mean+/-SD) with urokinase and citicoline and nimodipine, respectively. Treatment with either urokinase with citicoline or urokinase with citicoline and nimodipine significantly reduced the incidence of infarction than with single urokinase (Hotelling=3.339, P=0.001<0.05). However, reduction of area of infarction between the rabbits treated with urokinase combined with citicoline and treated with urokinase combined with citicoline and nimodipine was not developed t=-l .982, P=0.076>0.05(95%CI, -0.4106--0.3743).Conclusions: Compared with single thrombolysis therapy, early thrombolysis therapy combined with neuroprotect agents didn't raised the recalization ratio of vessels, but it improved the outcome. Either the combination of urokinase and citicoline or urokinase, citicoline and nimodipine showed a decreased infarction volume compared with urokinase group. Neuroprotect agents combined with thrombolysis therapy are more effective than single thrombolysis therapy. Howerver, there was no significant difference in either alone citicoline or citicolinein combination with nimodipine on infarct volume of infarction.