The safety and efficacy of intravenous tissue plasminogen activator (PA) on the condition of ruling out the significant risk were studied at 6 and 12 hours after cerebral artery embolization in rabbit mode. The time selection was chosen to
simulate
the
analogous clinical situation. The safety and effectiveness of tPA in experimental and clinical treatment of acute coronary thrombosis have been established. Tissue plasminogen activator is an endogenous fibrin-specific serine protease with the
potent
thrombolytic activity that has been produced recently by recombinant DNA technology.
The acute cerebral thromboembolic model was induced by injecting three 0.5×1.0mm fragments of autologous arterial thromi into internal carotid artery through the intra-arterial catheter. The autologous arterial thrombi was obtained from the
traumatized
arterial endothelium by scratching the lumen of auricular artery using modified spinal needle.
The experimental group was divided into four groups : ① group Ia : saline-treated (1 ml/kg) control group at 6 hours after embolization (n=10), ② group Ib : tPA-treated group (1 mg/kg) at 6 hours after embolization (n=10), ③ group IIa :
saline-treated control group at 12 hours after embolization (n=10), ④ group Iib : tPA-treated group at 12 hours after embolization (n=13).
The experimental rabbits were sacrificed at 24 hours after injection of tPA (1mg/kg) or asline (1ml/kg) in each group. Brain was cut into 0.5cm thick coronal sections, which were stained with triphenyltetrazolium chloride to define the areas of
infarction. The transparent plastic sheets were placed on the each section, and the total area of the brain slice and the area of infarction were measured by the plannimeter (as outlined by TTC staining). The percentage area of whole brain
infarction
was calculated as (the sum of infarcted area ÷the sum of brain slice areas) × 100% for each rabbit.
We also observed the pathologic findings with hematoxylin-eosin staining.
@ES The results were as follows:
@EN 1) only 1 rabbit treated with tPA at 12 hours after occlusion exhibited the gross hemorrhage.
2) The infarcted area was limited to the basal ganglia and cortex in all groups.
3) The mean percentage area of whole brain infarction averaged 18.6±1.94% in group Ia, 6.32±1.02% in group Ib, and 20.8±3.34% in group IIa, 6.78±1.40% in group IIb. One-way ANOVA test of infarction size showed the significant differences
(P<0.05)
between the tPA treated group and the saline-treated control group, but no difference between the groups treated with same agent.
4) Under the study of microscope, infarcted area of saline-treated control group was more extended than that of tPA-treated group. Coagulation necrosis and degeneration of neuronal cells could be seen. But the infarcted area of tPA-treated group
was
smaller than that of salinetreated control group. Only collection of foamy macrophages adjacent the necrotic area could be seen in tPA-treated group.
These results suggest that tPA therapy may be safe and efficacious during the interval of 6 to 12 hours after embolization.
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