U74389G prevents vasospasm after subarachnoid hemorrhage in dogs.
U74389G prevents vasospasm after subarachnoid hemorrhage in dogs.
复制标题
U74389G 可预防狗蛛网膜下腔出血后的血管痉挛。
DOI：
10.1097/00006123-199806000-00089
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发表时间：
1998
期刊：
影响因子：
4.8
通讯作者：
Andrus,PK
中科院分区：
文献类型：
--
作者：
Macdonald,RL;Bassiouny,M;Johns,L;Sajdak,M;Marton,LS;Weir,BK;Hall,ED;Andrus,PK
目的：氧源性自由基可能通过动脉壁内发生的直接血管收缩效应或继发性血管收缩引起蛛网膜下腔红细胞脂质过氧化而导致颅内动脉瘤破裂后的血管痉挛。U 74389 G是一种有效的脂质过氧化抑制剂和氧自由基清除剂。本研究确定了氧自由基和脂质过氧化作用的相对贡献，在双出血狗model.METHODS：16只狗进行了基线（第0天）脑血管造影和诱导蛛网膜下腔出血的两次注射血液到枕大池2天分开。他们随机接受药物载体（n= 8）或U 74389 G（n= 8，3 mg/kg体重/d）静脉注射。药物给药和终点分析均设盲。终点是血管造影性血管痉挛，通过比较蛛网膜下腔出血前和出血后7天的血管造影片以及丙二醛和水杨酸羟化产物的水平来评估结果：脑出血后7天，脑脊液中二羟基苯甲酸类物质含量及蛛网膜下腔血凝块和基底动脉中丙二醛含量均明显升高。第0天和第7天血管造影组内以及第7天获得的血管造影组间的比较，在载体组中的动物中显示出显著的血管痉挛（平均值±标准误差，51%±4），但在U 74389 G组中没有（25%±11，P< 0.05，未配对t检验）。高压液相色谱法测定丙二醛和二羟基苯甲酸在脑脊液，蛛网膜下腔血凝块，基底动脉组之间没有显着差异。结论：U 74389 G的显著预防血管痉挛的自由基反应的指标水平没有变化表明，该药物的效果与其他过程中发生的动脉壁和脑脊液水平的氧自由基和脂质过氧化物是没有有用的标志物的血管痉挛。
OBJECTIVE:Oxygen-derived free radicals may contribute to vasospasm after the rupture of an intracranial aneurysm through direct vasoconstricting effects occurring within the arterial wall or, secondarily, by causing lipid peroxidation in the subarachnoid erythrocytes with secondary induction of vasoconstriction. U74389G is a potent inhibitor of lipid peroxidation and a scavenger of oxygen-derived free radicals. This study determined the relative contributions of oxygen-derived free radicals and lipid peroxidation to vasospasm in the double-hemorrhage dog model.METHODS:Sixteen dogs underwent baseline (Day 0) cerebral angiography and induction of subarachnoid hemorrhage by two injections of blood into the cisterna magna 2 days apart. They were randomized to receive drug vehicle (n= 8) or U74389G (n= 8, 3 mg/kg of body weight/d) intravenously. Drug administration and end point analysis were blinded. The end points were angiographic vasospasm, as assessed by comparison of angiograms obtained before and 7 days after subarachnoid hemorrhage, and the levels of malondialdehyde and salicylate hydroxylation products (dihydroxybenzoic acids) in cerebrospinal fluid and of malondialdehyde in subarachnoid blood clots and basilar arteries 7 days after hemorrhage.RESULTS:Comparisons within groups of Day 0 and Day 7 angiograms and between groups of angiograms obtained at Day 7, showed significant vasospasm in animals in the vehicle group (mean±standard error, 51%±4) but not in the U74389G group (25%±11, P< 0.05, unpairedt test). High-pressure liquid chromatographic assays of malondialdehyde and dihydroxybenzoic acids in cerebrospinal fluid, subarachnoid blood clots, and basilar arteries showed no significant differences between groups.CONCLUSION:The significant prevention of vasospasm by U74389G without change in levels of indicators of free radical reactions suggests that the effect of the drug is related to other processes occurring in the arterial wall and that cerebrospinal fluid levels of oxygen radicals and lipid peroxides are not useful markers of vasospasm.