MAGNETIC-RESONANCE-IMAGING STUDY ON THE EFFECT OF LEVEMOPAMIL ON THE SIZE OF INTRACEREBRAL HEMORRHAGE IN RATS
MAGNETIC-RESONANCE-IMAGING STUDY ON THE EFFECT OF LEVEMOPAMIL ON THE SIZE OF INTRACEREBRAL HEMORRHAGE IN RATS
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DOI：
10.1161/01.str.25.9.1836
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发表时间：
1994-09-01
期刊：
影响因子：
8.3
通讯作者：
BRENDEL, R
中科院分区：
文献类型：
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作者：
ELGER, B;SEEGA, J;BRENDEL, R
背景和目的钙拮抗剂在脑缺血和脑外伤中的有益作用部分归因于改善脑血流量。然而，如果脑损伤合并脑出血，脑血流增强可加重病理情况。在这项研究中，我们在脑出血动物模型中使用高场磁共振成像来确定钙和5 -羟色胺拮抗剂左旋莫帕米[(S)-埃莫帕米的国际非专利名称]在以已知增加脑血流量的剂量（6mg /kg）输注时的无创作用。方法采用立体定向向尾状壳核微量注入胶原酶诱导大鼠脑出血。进行了两个系列的实验。(1)左旋帕米静脉滴注于胶原酶脑内灌注后30分钟（0.05 U），代表颅内出血时间。另一组动物给予肝素（55 IU）。公斤(1)。Min(-1))来评价该动物模型证明药物性脑出血恶化的能力。(2)超急性输注左炔帕米（0.5 U胶原酶输注后30分钟）与延迟2小时输注的效果进行比较。在两种实验环境中，通过注射胶原酶后24小时在体内冠状面和脑横面拍摄的t -1加权磁共振图像（自旋回声，重复时间400毫秒，回声时间23毫秒）来确定脑出血的程度。结果(1)对照组大鼠、左旋莫帕米组大鼠和肝素组大鼠冠状脑平面（距耳间线前方10mm）出血区分别为10.1+/-2.9 mm(2)、8.5+/-2.1 mm(2)和18.8+/-2.5 mm(2)（每组8只，平均+/- sd）。对照组大鼠、左旋帕米组大鼠和肝素组大鼠脑横面（耳间线背侧6mm）出血面积分别为11.5+/-3.6 mm(2)、9.7+/-2.4 mm(2)和19.9+/-3.3 mm(2)。(2)左旋帕米延迟输注2小时的脑出血大小与对照组相似。(3)左旋帕米对小、大出血灶均无增加作用。结论左旋莫帕米对脑出血的影响未见脑出血加重。然而，肝素输注引起了显著的(P
Background and Purpose Beneficial effects of calcium antagonists in cerebral ischemia and trauma have been attributed in part to improved cerebral blood flow. Enhancement of cerebral blood flow, however, could aggravate the pathological situation if brain injury is associated with intracerebral hemorrhage. In this study we used high-field magnetic resonance imaging in an animal model of intracerebral hemorrhage to determine noninvasively the effect of the calcium and serotonin antagonist levemopamil [international nonproprietary name for (S)-emopamil] when infused in a dose (6 mg/kg) that is known to increase cerebral blood flow.Methods Intracerebral hemorrhage was induced in rats by stereotaxic microinfusion of collagenase into the caudate putamen. Two series of experiments were performed. (1) Levemopamil was intravenously infused 30 minutes after intracerebral infusion of collagenase (0.05 U), which represents the time of intracranial bleeding. Another group of animals was given heparin (55 IU . kg(-1) . min(-1)) to evaluate the capability of this animal model to demonstrate drug-induced worsening of intracerebral hemorrhage. (2) The effects of hyperacute infusion of levemopamil (30 minutes after infusion of 0.5 U of collagenase) were compared with those of a 2-hour delayed administration. In both experimental settings, the extent of intracerebral hemorrhage was determined by T-1-weighted magnetic resonance images (spin-echo; repetition time, 400 milliseconds; echo time, 23 milliseconds) taken in vivo in a coronal and a transverse brain plane 24 hours after collagenase infusion.Results (1) Hemorrhagic brain areas measured 10.1+/-2.9 mm(2), 8.5+/-2.1 mm(2), and 18.8+/-2.5 mm(2) in the coronal brain plane (10 mm anterior to the interaural line) of control, levemopamil-, and heparin-infused rats, respectively (8 animals per group, mean+/-SD). In the transverse brain plane (6 mm dorsal to the interaural line) the hemorrhagic area was 11.5+/-3.6 mm(2), 9.7+/-2.4 mm(2), and 19.9+/-3.3 mm(2) in control, levemopamil-, and heparin-infused rats, respectively. (2) Animals with 2-hour delayed levemopamil infusion displayed intracerebral hemorrhage similar in size to that of control rats. (3) Neither small nor large hemorrhagic lesions were increased by levemopamil.Conclusions Aggravation of intracerebral hemorrhage was not observed by magnetic resonance imaging in levemopamil-infused animals. However, infusion of heparin caused a significant (P