A quantitative morphological assessment of the effect of lidoflazine and deferoxamine therapy on global brain ischaemia

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.