Hossmann K A
Max-Planck-Institut für neurologische Forschung, Abteilung für experimentelle Neurologie, Köln.
Arzneimittelforschung. 1991 Mar;41(3A):292-8.
In vivo NMR (nuclear magnetic resonance) spectroscopy allows for non-invasive measurement of the intracellular pH and the concentration of different metabolites in defined areas of the brain. Phosphocreatine, ATP and lactic acid are of prime interest in ischaemia research. Moreover, a distinction can be made between glycolysis and the oxidative breakdown of glucose after administering C-13-labelled glucose. Finally, spectroscopy of fluorine-containing inert gases such as Freon-23 allows for measuring cerebral blood flow and for directly relating the metabolic alterations to the changes in cerebral blood flow. Given the non-invasive character of NMR spectroscopy all metabolic process occurring throughout one experiment can for the first time be followed up. Thus metabolic alterations during ischaemia can directly be correlated with post-ischaemic recovery processes. It has been shown with the cerebral ischaemia model in the cat that recovery after circulatory failure rather depends on post-ischaemic changes such as the recirculation rate or the speed of high-energy phosphate formation than on the speed of energy metabolism breakdown or acidosis occurring during ischaemia. The future of nuclear magnetic resonance spectroscopy in experimental ischaemia research certainly lies in the therapeutic range. As the exact extent of ischaemic damage can be determined in each experiment it is possible for the first time to define the effect of a drug substance on metabolic dysfunction in each individual experiment. This method is not only expected to reduce the number of laboratory animals but also to dramatically improve statistical variability compared to group comparisons.
体内核磁共振光谱法可对大脑特定区域的细胞内pH值和不同代谢物浓度进行无创测量。磷酸肌酸、三磷酸腺苷和乳酸是缺血研究中最受关注的物质。此外,在给予C-13标记的葡萄糖后,可区分糖酵解和葡萄糖的氧化分解。最后,对含氟惰性气体(如氟利昂-23)进行光谱分析,可测量脑血流量,并直接将代谢改变与脑血流量变化联系起来。鉴于核磁共振光谱法具有无创性,在整个实验过程中发生的所有代谢过程首次得以跟踪。因此,缺血期间的代谢改变可直接与缺血后恢复过程相关联。在猫的脑缺血模型中已表明,循环衰竭后的恢复更多地取决于缺血后的变化,如再循环率或高能磷酸盐形成的速度,而非缺血期间能量代谢分解或酸中毒的速度。核磁共振光谱法在实验性缺血研究中的未来无疑在于治疗领域。由于在每个实验中都能确定缺血损伤的确切程度,首次有可能在每个单独实验中确定药物物质对代谢功能障碍的影响。预计这种方法不仅能减少实验动物的数量,而且与组间比较相比,还能显著提高统计变异性。