Heiss W D, Graf R, Wienhard K
Max-Planck-Institut für neurologische Forschung, Gleueler Strasse 50, D-50931 Köln, Germany.
Cerebrovasc Dis. 2001;11(2):73-81. doi: 10.1159/000047616.
Repeat studies in animal models of acute focal ischemia can be compared to incidental studies in the course of ischemic stroke in order to shed light on the development of changes causing ischemic infarcts or recovery of critically perfused tissue. Positron emission tomography (PET) studies of regional cerebral blood flow, cerebral metabolic rate for oxygen, oxygen extraction fraction (OEF), cerebral metabolic rate of glucose and flumazenil (FMZ) binding in the cat middle cerebral artery occlusion (MCAO) model and in patients with acute ischemic hemispheric stroke were reviewed. After permanent MCAO, the development of "misery-perfused" penumbral tissue and its centrifugal conversion into necrosis could be demonstrated, resembling focal pathophysiological changes in patients with ischemic attacks. In the experimental model and in vascular insults in humans, a chance of recovery existed if collateral perfusion developed spontaneously within the first hours. In transient MCAO, reperfusion was only effective in preventing infarction when it was initiated as long as misery perfusion persisted; in these cases tissue was salvaged and large infarcts did not develop. In the other instances when oxygen metabolism broke down, and an increased OEF was no longer seen, reperfusion even at levels above preocclusion had no effect, and large space-occupying infarcts developed. These experimental findings are comparable to the variable outcome after thrombolytic therapy; if reperfusion is achieved within the therapeutic window of tissue viability, large infarcts are prevented and complete or partial recovery can be achieved. In the experimental model of focal ischemia and in human stroke, FMZ can be utilized as a marker of neuronal integrity. If FMZ binding in the cortex is decreased below 4 times the mean value of white matter in the acute stage, permanent infarcts were observed on late CT/MRI; this irreversible damage could not be prevented by thrombolytic therapy. These results demonstrated that PET studies in suitable ischemia models in cats can help to explain various courses and diverging outcomes of acute ischemic stroke. Comparable findings from experimental ischemia and human stroke may affect the selection of appropriate therapeutic strategies.
急性局灶性缺血动物模型的重复研究可与缺血性中风过程中的偶然研究进行比较，以阐明导致缺血性梗死或严重灌注不足组织恢复的变化发展情况。回顾了正电子发射断层扫描（PET）对猫大脑中动脉闭塞（MCAO）模型和急性缺血性半球中风患者的局部脑血流量、脑氧代谢率、氧摄取分数（OEF）、脑葡萄糖代谢率和氟马西尼（FMZ）结合情况的研究。永久性MCAO后，可证明“灌注不良”半暗带组织的发展及其向坏死的离心性转化，这类似于缺血性发作患者的局灶性病理生理变化。在实验模型和人类血管损伤中，如果在最初几小时内自发形成侧支循环灌注，就存在恢复的机会。在短暂性MCAO中，只要灌注不良持续存在，再灌注仅在开始时对预防梗死有效；在这些情况下，组织得以挽救，未形成大面积梗死。在其他氧代谢分解且不再出现OEF升高的情况下，即使再灌注水平高于闭塞前水平也无效，会形成大面积占位性梗死。这些实验结果与溶栓治疗后的不同结果相当；如果在组织存活的治疗窗口内实现再灌注，可预防大面积梗死并实现完全或部分恢复。在局灶性缺血实验模型和人类中风中，FMZ可作为神经元完整性的标志物。如果急性期皮质中的FMZ结合低于白质平均值的4倍，后期CT/MRI上会观察到永久性梗死；这种不可逆损伤无法通过溶栓治疗预防。这些结果表明，在合适的猫缺血模型中进行PET研究有助于解释急性缺血性中风的各种病程和不同结果。实验性缺血和人类中风的类似发现可能会影响适当治疗策略的选择。
