Kumar K, White B C, Krause G S, Indrieri R J, Evans A T, Hoehner T J, Garritano A M, Koestner A
Department of Pathology, College of Human Medicine, Michigan State University, East Lansing 48824-1316.
Neurol Res. 1988 Sep;10(3):136-40. doi: 10.1080/01616412.1988.11739830.
The effect of the combination of two drugs, i.e. lidoflazine (a calcium antagonist), and deferoxamine (an iron chelator) was evaluated following 15 min global brain ischaemia (GBI) and reperfusion in dogs in a randomized blind study. GBI was produced by complete cardiac arrest of 15 min duration. Histopathological analysis performed on in situ fixed brains 40 h post-resuscitation revealed diffuse microhaemorrhages in the control group. These were noted rarely in the treatment group, the mean value of foci of microhaemorrhages/20 low power fields (LPF) being 5.2 in the treatment group versus 28 in the control group (p less than 0.001). Diffuse coagulative necrosis of neurons (ischaemic cell change) in the cerebral cortex, especially lamina 3, hippocampus, striatum, brain stem and cerebellum was present in all cases. Quantitation of the degree of cellular damage obtained by counting the number of anoxic neurons (in consistent regions of the brain) with the use of an image analysis system, revealed no significant difference between the 2 groups. The mean percentages of the ischaemic neurons in the control group in the various areas studied were: parietal cortex, 22.25; hippocampus, 50.37 and cerebellum (Purkinje cells), 66.75; and in the treatment group 25.3, 55.04 and 70.6 respectively. Thus, the lidoflazine-deferoxamine regimen significantly reduced the incidence of microhaemorrhages in the brain, but it did not have any protective effect against anoxic neuronal injury 40 h post-ischaemia in this experimental model of GBI of 15 min duration.
在一项随机双盲研究中，对利多氟嗪（一种钙拮抗剂）和去铁胺（一种铁螯合剂）联合用药的效果进行了评估，该研究观察了犬在经历15分钟全脑缺血（GBI）及再灌注后的情况。通过持续15分钟的完全心脏骤停造成GBI。复苏后40小时对原位固定的大脑进行组织病理学分析，结果显示对照组出现弥漫性微出血。在治疗组中很少观察到这种情况，治疗组微出血灶/20个低倍视野（LPF）的平均值为5.2，而对照组为28（p<0.001）。所有病例均出现大脑皮质（尤其是第3层）、海马体、纹状体、脑干和小脑的神经元弥漫性凝固性坏死（缺血性细胞改变）。使用图像分析系统通过计数（大脑一致区域内的）缺氧神经元数量来定量细胞损伤程度，结果显示两组之间无显著差异。对照组在各个研究区域中缺血神经元的平均百分比分别为：顶叶皮质22.25%、海马体50.37%、小脑（浦肯野细胞）66.75%；治疗组分别为25.3%、55.04%和70.6%。因此，在这个持续15分钟的GBI实验模型中，利多氟嗪 - 去铁胺方案显著降低了大脑微出血的发生率，但对缺血后40小时的缺氧神经元损伤没有任何保护作用。
