Combined intra-arterial thrombolysis and neuprotectant agents reduce cerebral infarction in rabbits with experimental acute cerebral ischemia

Pei Shi

摘要：BACKGROUND:The intra-arterial thrombolytic therapy is one of main methods for more patients to obtain bene-fits.The percentage of arterial recanalization treated with intre-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-artedal 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 thmmbolitic 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.dean grade.were provided by Expedmental 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.Urekinase was provided by Beijing Saisheng Pharmaceutical Co.,Ltd.(batch number:020923);corenalin by Sanjing Pharmaceutical Co.,Ltd.of Harbin Pharmacautical Group(batch number:021106):nimodipine by Shandong Xihua Pharmaceutical Co.,Ltd.(batch number:020611):contrast medium IOPAMlR0300 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 camed out in the Department of Intervention. Second People's Hospital of Xinxiang from September 2002 to May 2003.①According to techniques of Benes et al and Zhu et al,animal models with acute ischemia were established.Two hours later.the therapy began.Intra-artedal thrombolysis control group:5 000 U/kg urokinase was dripped in Ieft 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 intrapedtoneally 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 IOPAMIR0300(0.4 mL per injection,0.2 mL/s).②Brain tissue was fixed with TTC staining.Modified TIMI classification was adopted as evaluation criteria of recanalization of vessels.③Enumeration datawere compared with Chi-spuare test,and measurement data were compared with multivadate analysis of variaRCS 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:①Recanalization ratio of obstructive vessels:The gross percentaae of artedal 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).②Ratio 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 differencas 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-artedal 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:①Intra-artedal 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 thrembolytic therapy are more effective than single thrombolytic therapy.②However,there is no significant different efficacy in either alone citicoline or citicoline combined with nimodipine.