Marinov M, Wassmann H, Natschev S
Department for Neurosurgery, Medical Academy, Sofia, Bulgaria.
Neurol Res. 1991 Jun;13(2):77-83. doi: 10.1080/01616412.1991.11739970.
Despite the voluminous current literature the potential of nimodipine to modify the outcome in experimental cerebral ischaemia remains a controversial matter. The authors have evaluated in controlled double blind experiments the influence of a continuous i.v. infusion of the drug (1 microgram kg-1 min-1) upon infarct size, histopathology and neurological outcome in rats with permanent middle cerebral artery (MCA) occlusion. The infusion was started 20 min before induction of ischaemia and continued 4 hours thereafter. The nimodipine treated animals were subdivided into hypotensive (MABP lower than 85 mmHg for more than 5 min after arterial occlusion) and normotensive groups. Infarction size, documented by TTC, H&E and Nissl staining was significantly smaller (p less than 0.001) in nimodipine normotonic rats than the lesions in placebo and saline treated rats, as well compared with hypotonic nimodipine animals (largest infarction). These differences were found to be entirely at the expense of the cortical (frontoparietal) component of the lesion, suggesting 'penumbra' action of the drug. Moreover, nimodipine normotonic rats displayed lower cortical neuronal injury in the periinfarct zone. These findings were corroborated by corresponding better neurological scores. Our results indicate that nimodipine is effective in reducing focal cerebral ischaemia, provided the MABP is maintained higher than 85 mmHg.
尽管目前有大量文献，但尼莫地平在实验性脑缺血中改变预后的潜力仍是一个有争议的问题。作者在对照双盲实验中评估了持续静脉输注该药物（1微克/千克/分钟）对永久性大脑中动脉（MCA）闭塞大鼠梗死灶大小、组织病理学和神经功能结局的影响。在缺血诱导前20分钟开始输注，并在其后持续4小时。将接受尼莫地平治疗的动物分为低血压组（动脉闭塞后平均动脉压（MABP）低于85 mmHg超过5分钟）和正常血压组。通过TTC、苏木精-伊红（H&E）和尼氏染色记录的梗死灶大小，尼莫地平正常血压大鼠明显小于安慰剂和生理盐水治疗的大鼠，与低血压尼莫地平组动物（梗死灶最大）相比也更小（p<0.001）。发现这些差异完全是由于病变的皮质（额顶叶）部分减小，提示该药物具有“半暗带”作用。此外，尼莫地平正常血压大鼠在梗死灶周围区域的皮质神经元损伤较轻。相应更好的神经功能评分证实了这些发现。我们的结果表明，只要将MABP维持在高于85 mmHg，尼莫地平在减轻局灶性脑缺血方面是有效的。
