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KMID : 0350519940470020837
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Journal of Catholic Medical College
1994 Volume.47 No. 2 p.837 ~ p.848
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Effect of the Combined Treatment of Tissue Plasminogen Activator and 21-Aminosteroid U-74389F on Embolic Stroke in Rabbits
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Abstract
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The term "cerebral ischemia" has long been used to describe a state of disrupted cerebral blood flow and metabolism. After interruption of the blood supply, some tissues probably suffer irreparable damage within minutes, but a variable amount
remains in
a "shut-down" but viable state for several hours. Neutralization of toxic metabolites released from infarcted cells or restoration of the blood supply might save the ischemic tissue and improve the outcome.
Authers aimed to evaluate the combined treatment with thrombolytic agent, tPA and a potent inhibitor of lipid peroxidation, U-74389F in embolic stroke using autologous arterial thrombus in rabbits.
Thirty rabbits were divided into three groups: one control group(saline-treated group) and two treatment groups(tPA-treated group and combined treatment group with tPA and U-74389F). There were 10 rabbits in each group. The acute cerebral
thromboembolic
model was induced by injecting three fragments of autologus arterial thrombi, which were obtained from the traumatized auricular arterial endothelium by scratching, through internal carotid artery. Immediately after embolization, carotid
angiography was
performed. The animals with no visible occluson on the angiography were excluded from the study.
In tPA-treated group, tPA 1mg/kg was given intravenously 4 hours after embolization and in combined treated group, U-74389F 3mg/kg given 5 minutes and 2 hours after tPA administration. In control group, 1m/kg of saline was given 4 hours after
embolization.
The animals were sacrificed at 24 hours after the embolization. The brain was cut into five coronal sections of 0.5 cm thickness. The sections were stained with 2% solution of triphenyltetrazolium chloride(TTC) for measurement of infarct size.
The
percentage area of whole brain infarction was calculated as(sum of infarcted areas÷sum of brain slice areas)×100%.
@ES The results were as follows;
@EN 1. The area of ischemic injury was significantly reduced in treatment groups compared with control group(P<0.01), especially in combined treatment group.
2. Compared with tPA-treated group, there was a significant reduction of infarcted area in combined treatment group(P<0.05).
These reaults suggest that the combined treatment of tPA and U-74389 may be more effective in treatment of rabbit embolic stroke compared to that of tPA only.
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