| Objective:Acute cerebral infarction was a leading cause of death and disability for people in current society. On the early onset,thrombolytic therapy could timely restore blood flow of ischemic tissue and efficiently salvage the function of ischemic penumbra.Over all,many drawbacks of thrombolytic therapy still remain to be solved such as reperfusion injury and hemorrhagic transformation,which limited the clinical use of thrombolytic therapy.Recent experiment studies demonstrated that the inflammatory response played an important role in the development of reperfusion injury, and that inhibition of the early inflammatory response after reperfusion could reduce infarct size, improve neurological function in animals.Therefore thrombolytic therapy combined with preventing inflammatory response might contribute to relieving cerebral tissue damage after ischemia.Heparin has been established as an anticoagulant, having been used generally in clinical application.Until recently, it has been shown to inhibit the early inflammatory response.Our study have developed a model of cerebral embolic stroke in rabbit using autologus thrombus and the rabbits were treated with intravenousurokinase(UK) and heparin three hours later after embolization.The aim was to evaluate the efficacy and safety of this treatment on acute cerebral infarction.Methods:The left internal carotid artery of rabbit was injected with three fragments of autologous thrombus 0.5mm X 0.5mm in thickness.Three hours after embolization thirty rabbits were randomized into one of three treatment groups:UK(20,000U/kg) group,UK plus heparin (2,000U,per six hours,four times altogether) group and saline(30ml) group.Moreover, the activated partial thromboplastin time(APTT) was measured at the time of two hours before or after treatment.Twenty-four hours later, the neurological function of each animal was assessed .Then the brains were immediately removed and cut into five coronal sections approximately 5mm thick.The sections were carefully examined for evidence of hemorrhage, and stained with triphenytetrazolium chloride(TTC).Infarct size, as a percentage of hemisphere, was determined planimetrically using a computer image analyzer.Finally, the sections were stained with hematoxylin and eosin, and examined microscopically.Results:(l) The infarct size (percentage of hemisphere) of each group was 25.78+3.58(saline group), 18.04 + 2.69(UK group) and 14.75+3.03(UK plus heparin group).It had been shown that infarct size was significantly reduced in the UK and UK plus heparin group when compared with thesaline group (P<0.01),and there was a significant differece between the UK and UK plus heparin group (P<0.05).(2) Compared with saline group, admnistration of UK alone or plus heparin both resulted in a significant improvement in the neurological dysfunction(P<0.05), but the difference between UK and UK plus heparin groups was not significant(P>0.05).(3) No hemorrhage was found in autopsy in the saline group whereas two in UK group and one in UK plus heparin group, but there was no statistically significant difference in the incidence of hemorrhage among the groups(P=0.75).(4) In those animals that received UK plus heparin, the APTT was maintained at >120 seconds, but administration of UK and saline had no influence on APTT values.(5) Different sizes of cerebral infarction were found microscopically in each group through histological examination.Conclusions: (l)Different sizes of infarction and neurological dysfunction were found in all rabbits model which was simulated by injecting 0.5mm X 0.5mm fragments of autologous thrombus, so this model could be used to evaluate the efficacy of thrombolytic therapy.(2) Three hours after embolization thrombolytic therapy using intravenous UK could significantly reduce the infarct size and improve the neurological dysfunctions. Although two cases of hemorrhage were found in UK group, whereas none in saline group,this differece was not significant.(3)Administration of UK combined with heparin could result in a...
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