BACKGROUND: The intra-arterial thrombolytic therapy is one of main methods for more patients to obtain benefits. The percentage of arterial recanalization treated with intra-arterial therapy is higher than with intra-venous therapy, next, the dose of thrombolytic medicines is lower and the therapeutic time window may be possibly longer. Related researches are focus on intra-arterial thrombolysis combining with neuprotectant agents to treat acute ischemic stroke. The results show that combination of them can further prolong the therapeutic time window, improve the percentage of arterial recanalization and reduce cerebral infarction volume. OBJECTIVE: To observe the effect of single thrombolitic therapy combined with neuroprotectant agents in the treatment of acute ischemic stroke. DESIGN: Randomized block design. SETTING: Xinhua Hospital of Xixiang City, Henan Province. MATERIALS: Thirty-six adult male white rabbits, weighing 1.5-2.0 kg, clean grade, were provided by Experimental Animal Center of Xinxiang Medical College. All rabbits were randomly divided into three groups: intra-arterial thrombolysis control group, corenalin control group and combination group with 12 in each group. Urokinase was provided by Beijing Saisheng Pharmaceutical Co., Ltd. (batch number: 020923); corenalin by Sanjing Pharmaceutical Co., Ltd. of Harbin Pharmaceutical Group (batch number: 021106); nimodipine by Shandong Xihua Pharmaceutical Co., Ltd. (batch number: 020611); contrast medium IOPAMIRO300 by Bracco s.p.a, Milano Italian (batch number: 0584); 2,3,5-triphenyltetrazolium chloride (TTC) by Beijing Mashi Fine Chemical Product Co., Ltd. (batch number: 020926). METHODS: The experiment was carried out in the Department of Intervention, Second People’s Hospital of Xinxiang from September 2002 to May 2003. ① According to techniques of Benes et al and Zhu et al , animal models with acute ischemia were established. Two hours later, the therapy began. Intra-arterial thrombolysis control group: 5 000 U/kg urokinase was dripped in left common carotid artery for 30-60 minutes. Corenalin control group: Urokinase combined with corenalin was intraperitoneally injected into rabbits, and the procedures of thrombolysis were as the same as those in intra-arterial thrombolysis control group. And then, 125 g/L corenalin with the dosage of 250 mg per rabbit was slowly injected into abdominal cavity. Combination group: Urokinase combined with corenalin was intraperitoneally injected into rabbits, and the procedures of thrombolysis were as the same as those in corenalin control group. Meanwhile, nimodipine solution (0.2 mg per animal, 0.2 mg/25 mL 5% GS) was injected into right auricular vein for 60 minutes (0.4 mL/min). The contrast media was IOPAMIRO300 (0.4 mL per injection, 0.2 mL/s). ② Brain tissue was fixed with TTC staining. Modified TIMI classification was adopted as evaluation criteria of recanalization of vessels. ③ Enumeration data were compared with Chi-spuare test, and measurement data were compared with multivariate analysis of variance and t test. MAIN OUTCOME MEASURES: Recanalization ratio of obstructive vessels, and the ratio of total cerebral infarction volume to the non-infarction in the three groups. RESULTS: ① Recanalization ratio of obstructive vessels: The gross percentage of arterial recanalization in intra-arterial thrombolysis control group, corenalin control group and combination group was 75% (9/12); 83% (10/12); 90% (10/11), respectively. There was no significant difference among three groups (χ2=2.046, P = 0.727). ② Ratio of total cerebral infarction volume to the non-infarction: The percentage of the total cerebral infarction volume averaged (22.2±8.5)% in intra-arterial thrombolysis control group, (14.3±6.9)% in corenalin control group, and (17.7±8.7)% in combination group. There were significant statistics differences both in corenalin control group comparing with intra-arterial thrombolysis control group (t =4.759, P =0.001) and in combination group comparing with intra-arterial thrombolysis control group (t =5.587, P =0.000), which could significantly reduce the average percentage of the total cerebral infarction volume comparing with in intra-arterial thrombolysis control group. However, there was no significant difference for reducing the average percentage of the cerebral infarction volume between corenalin control group and combination group (t =-1.982, P =0.076). CONCLUSION: ① Intra-arterial thrombolytic therapy combined with neuroprotectant agents does not raised the recanalization ratio of vessels, but can accurately reduce the volume of infarction areas, furthermore, improve the outcome. Neuroprotectant agents combined with thrombolytic therapy are more effective than single thrombolytic therapy. ② However, there is no significant different efficacy in either alone citicoline or citicoline combined with nimodipine. BACKGROUND: The percentage of arterial recanalization treated with intra-arterial therapy is higher than with intra-venous therapy, next, the dose of thrombolytic medicines is lower and the results show that combination of them can further prolong the therapeutic time window, improve the percentage of arterial recanalization and reduce cerebral infarction volume. OBJECTIVE: To observe the effect of single thrombolitic therapy combined with neuroprotectant agents in the treatment of acute ischemic stroke. DESIGN: Randomized block design. SETTING: Xinhua Hospital of Xixiang City, Henan Province. MATERIALS: Thirty-six adult Male white rabbits, weighing 1.5-2.0 kg, clean grade, were provided by Experimental Animal Center of Xinxiang Medical College. All rabbits were divided into three groups: intra-arterial thrombolysis control group, corenalin control group and combination group with 12 in each group. Urokinase was provided by Beijing Saisheng Pharmaceutical Co., Ltd. (batch number: 020923); corenalin by Sanjing Pharmaceutical Co., Ltd. of Harbin Pharmaceutical Group (batch number: 021106); nimodipine by Shandong Xihua Pharmaceutical Co., Ltd. (batch number: 020611); contrast medium IOPAMIRO300 by Bracco spa, Milano Italian batch number: 0584); 2,3,5-triphenyltetrazolium chloride (TTC) by Beijing Mashi Fine Chemical Product Co., Ltd. (batch number: 020926). METHODS: The experiment was carried out in the Department of Intervention, Second People’s Hospital of Xinxiang from September 2002 to May 2003. ① According to techniques of Benes et al and Zhu et al, animal models with acute ischemia were established. Two hours later, the therapy began. Intra-arterial thrombolysis control gr ouCorenalin control group: Urokinase combined with corenalin was intraperitoneally injected into rabbits, and the procedures of thrombolysis were as the same as those in intra-arterial Thrombolysis control group. And then, 125 g / L corenalin with the dosage of 250 mg per rabbit was slowly injected into abdominal cavity. Combination group: Urokinase combined with corenalin was intraperitoneally injected into rabbits, and the procedures of thrombolysis were as same as as those in corenalin control group. Meanwhile, nimodipine solution (0.2 mg per animal, 0.2 mg / 25 mL 5% GS) was injected into the right auricular vein for 60 minutes injection, 0.2 mL / s). ② Brain tissue was fixed with TTC staining. Modified TIMI classification was adopted as evaluation criteria of recanalization of vessels. ③ Enumeration data were compared with Chi-spuare test, and measurement data were compared with multivariate analysis of variance and t test. MAIN OUTCOME MEASURES: Recanalization ratio of obstructive vessels, and the ratio of total cerebral infarction volume to non-infarction in the three groups. The gross percentage of arterial recanalization in intra-arterial thrombolysis control group, corenalin control group and combination group was 75% (9/12); 83% (10/12); 90% (10/11), respectively. There was no Significant differences among three groups (χ2 = 2.046, P = 0.727). ② Ratio of total cerebral infarction volume to the non-infarction: The percentage of the total cerebral infarction volume averaged (22.2 ± 8.5)% in intra-arterial thrombolysis control group (14.3 ± 6.9)% in corenalin control group, and (17.7 ± 8.7)% in combination group. There were significant statistics differences both in corenalin control group comparing with intra-arterial thrombolysis control group (t = 4.759, P = 0.0 01) and in combination group comparing with intra-arterial thrombolysis control group (t = 5.587, P = 0.000), which could significantly reduce the average percentage of the total cerebral infarction volume comparing with in intra-arterial thrombolysis control group. However, there was no significant difference for reducing the average percentage of the cerebral infarction volume between corenalin group and combination group (t = -1.982, P = 0.076) CONCLUSION: Intra-arterial thrombolytic therapy combined with neuroprotectant agents does not raise the recanalization ratio of vessels, but can accurately reduce the volume of infarction areas, than, improve the outcome. Neuroprotectant agents combined with thrombolytic therapy are more effective than single thrombolytic therapy.