Summary:The purpose of this study was the develop ment of a model of embolic stroke with high reproduci bility concerning infarct volume. In 37 male Sprague Dawley rats, the internal carotid artery was embolized with in vitro preformed suspensions of autologous micro emboli resembling arterial thrombi. With a method of continuous flow through the carotid arterial catheter, re flux of blood with uncontrolled clotting and embolization was avoided, thereby providing control animals free of ischemic damage. The embolized animals had arterial oc clusions on angiograms immediately after embolization and no spontaneous recanalization on angiograms 2 h later. The cerebral blood flow measured by the intra-A growing interest in thrombolytic therapy in acute cerebral ischemia has increased the need for an animal model of thrombotic embolization with reproducible infarcts. Experimental studies have demonstrated that neuronal damage does not occur in the first few minutes after the onset of ischemia (Hossman and Kleihues, 1973). The time interval between the onset of ischemia and neuronal death varies according to species, model (focal or global ischemia), and severity and duration of ischemia (Sundt et aI., 1969; Crowell et aI., 1970; DeGirolami et aI., 1984). It is unknown whether in human stroke institution of a treatment within that interval will result in a reduction in infarct size. It is important to test whether early recanalization with thrombolytic agents may result in neuronal recovery. Most of the knowledge, however, concerning the pathophysiol ogy of cerebral ischemia has been established from models of global ischemia and of focal ischemia by means of surgical occlusion of an intracranial ex tracerebral artery such as the middle cerebral artery (MCA). These models, however, are not suitable for the study of the pathophysiology of ischemic infarction treated by thrombolytic agents.In this report, we describe a model of embolic occlusion in rats. In the development of the model, we were inspired by Kudo et aI. (1982), who de scribed a model of embolization with autologous rat whole blood clots formed in vitro. A blood clot pro duced by extravascular coagulation is histologically different, more fragile, and softer than a thrombus formed in an artery during high pressure and normal circulation of blood (Robbins and Cotran, 1974). This might explain why distal fragmentation and spontaneous reperfusion frequently occurred in em bolization models using whole blood clots formed in
Background and Purpose: Thrombolytic therapy with recombinant tissue plasminogen activator was tested in a rat embolic stroke model.Methods: The rat carotid territory was embolized with arterial-like microthrombi formed under pressure. Hemispheric cerebral blood flow before and after embolization was measured by the intraarterial Xenon-133 injection method. Fifteen minutes after embolization, 24 rats were treated with 3 mg/kg or 10 mg/kg tissue plasminogen activator, and 27 were treated with saline. Carotid angiography displayed the rate of occlusion of the cerebral arterial supply before and after treatment. Brains were fixed and evaluated neuropathologically and infarct volume was measured.Results: Cerebral blood flow was reduced 70-86% after embolization. The comparison of pretreatment and posttreatment angiography showed significant (p=0.0005) reperfusion in the treated rats. Thrombolytic therapy significantly reduced the infarct volume from 55.1% to 24.4% of embolized hemisphere volume (p=0.007) and increased the survival rate from 0.48 to 0.96 (p=0.0004). Fifty-three percent of the embolized rats recanalized completely after thrombolytic treatment and developed almost no infarction (median volume 2.8%), and all survived. No hemorrhagic complications were observed.Conclusions: Early thrombolytic therapy induced recanalization and reduced mortality and infarct volume after embolic stroke in this model. (Stroke 1992;23:1167-1174 KEY WORDS • cerebral blood flow • cerebral ischemia • thrombolytic therapy • rats
Summary:The effect of delayed thrombolysis with re combinant tissue plasminogen activator was tested in an embolic stroke model. The carotid territory was embo lized in 103 rats with fibrin-rich clots formed and washed in polyethylene tubes. Hemispheric cerebral blood flow before and after embolization was measured by the intra arterial 133Xe injection method. At five delay times, 15-240 min after embolization, 69 animals were treated with tissue plasminogen activator, 20 mg/kg, and 34 animals with saline. Carotid angiography displayed the grade of occlusion of the cerebral arterial supply before and after treatment. Brains were fixed after 2 days, evaluated neu ropathologically, and infarct volume measured. Cerebral blood flow was reduced by 56-71% after embolization.
Background and Purpose: The effects of delayed thrombolysis with alteplase and neuroprotection with an excitatory amino acid receptor antagonist and their combination were tested in an embolic stroke model.Methods: In 61 rats the carotid artery territory was embolized with arterial-like fibrin-rich clots. Hemispheric cerebral blood flow before and after embolization was measured by intra-arterial '33Xe injection method. The animals were assigned to one of the following treatments: (1) vehicle-treated controls (n= 15); (2) dizocilpine 1 mg/kg IV 5 minutes after embolization (n= 16); (3) alteplase 20 mg/kg as an intravenous continuous infusion starting 2 hours after embolization (n=16); and (4) both agents
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