Zumkeller M, Dietz H
Neurosurgical Clinic, University Hannover, Medical School, Fed. Rep. of Germany.
Neurosurg Rev. 1996;19(4):253-60. doi: 10.1007/BF00314841.
The idea of using induced hypertension to treat the symptomatic ischaemia resulting from vasospasm after subarachnoidal hemorrhage, and the effect of this therapy on the blood-brain barrier, is checked in animal experiments. This therapy is combined with the application of nimodipine, which is recognised as the standard medication for prophylaxis of vasospasm. The effects of the induced hypertension combination with Nimodipine and in combination with another calcium antagonist, Flunarizine are compared. Seventy-four narcotised rats, one group with 22 animals treated with Nimodipine and 22 with placebo, and a second group 20 animals treated with Flunarizine and 10 with placebo, are evaluated. The blood pressure is raised to 150-180 mmHg by i.v. application of norfenephrine and measured continuously. The standard tracer, horseradish peroxidase, is applied as indicator for the blood-brain barrier function. 15 minutes later the experimental animals are exsanguinated by perfusion with saline, then perfused with Karnovsky's solution. After removal, the brains are stained for peroxidase to visualise extravasation of the horseradish peroxidase, and after evaluation of the results each brain is assigned to its experimental group. In the Nimodipine group, a significant accumulation (p < 0.001) of perivascular deposits of peroxidase reaction product were found, these were not found in the placebo group. The Flunarizine group does not differ from its placebo group in the number of extravasates, and thus, with respect to protein extravasation, appears better than the Nimodipine group. In electron micrographs of the extravasates one sees intact tight junctions and a neuroendothelial transport, and also vesicles, filled with horseradish peroxidase in the endothelium, the muscle cells, and the brain parenchyma, which arise from pinocytosis. The vesicles, which transport the high-molecular-weight protein, horseradish peroxidase, also transport other proteins and can, therefore, cause a brain edema. It follows from these morphological results that Nimodipine can disrupt the blood brain barrier function and can, therefore, also interfere with cerebral autoregulation, which depends on the resistance of vessels.
在动物实验中检验了使用诱导性高血压治疗蛛网膜下腔出血后血管痉挛所致症状性缺血的想法以及该疗法对血脑屏障的影响。该疗法与尼莫地平联合应用，尼莫地平被公认为预防血管痉挛的标准药物。比较了诱导性高血压联合尼莫地平以及联合另一种钙拮抗剂氟桂利嗪的效果。评估了74只麻醉大鼠，一组22只动物用尼莫地平治疗，22只用安慰剂，另一组20只动物用氟桂利嗪治疗，10只用安慰剂。通过静脉注射去甲肾上腺素将血压升至150 - 180 mmHg并持续测量。使用标准示踪剂辣根过氧化物酶作为血脑屏障功能的指标。15分钟后，通过用生理盐水灌注使实验动物放血，然后用卡诺夫斯基溶液灌注。取出后，对大脑进行过氧化物酶染色以观察辣根过氧化物酶的外渗情况，结果评估后将每个大脑归入其实验组。在尼莫地平组中，发现血管周围过氧化物酶反应产物有显著积聚（p < 0.001），而安慰剂组未发现。氟桂利嗪组在外渗物数量上与其安慰剂组无差异，因此，就蛋白质外渗而言，似乎比尼莫地平组更好。在外渗物的电子显微照片中，可以看到完整的紧密连接和神经内皮转运，并且在内皮、肌肉细胞和脑实质中也有充满辣根过氧化物酶的小泡，这些小泡源于胞饮作用。转运高分子量蛋白质辣根过氧化物酶的小泡也转运其他蛋白质，因此可能导致脑水肿。从这些形态学结果可以看出，尼莫地平会破坏血脑屏障功能，因此也可能干扰依赖血管阻力的脑自动调节。
