Zöllner Johann Philipp, Hattingen Elke, Singer Oliver C, Pilatus Ulrich
From the Department of Neurology, University Hospital Frankfurt, Goethe University, Frankfurt am Main, Germany (J.P.Z., O.C.S) and Institute of Neuroradiology, University Hospital Frankfurt, Goethe University, Frankfurt am Main, Germany (E.H., U.P.).
Stroke. 2015 Feb;46(2):441-6. doi: 10.1161/STROKEAHA.114.007896. Epub 2014 Dec 11.
In vivo changes in tissue pH and energy metabolism are key to understanding stroke pathophysiology. Our goal was to study pH changes in subacute ischemic stroke and their relation to energy metabolism, which, unlike acidosis in acute stroke, are not yet well understood.
We measured tissue pH and phospholipid as well as cell energy markers, including creatine, phosphocreatine, and N-acetyl-aspartate in subacute stroke with combined (1)H and (31)P magnetic resonance spectroscopy. We included 19 patients with first-ever ischemic stroke (mean time after stroke, 6 days). We then compared metabolite concentrations in the ischemic tissue to contralateral (healthy) tissue using multivariate ANOVA to assess significant differences in metabolite levels between both tissue compartments.
In subacute stroke, a tissue fraction with significantly increased tissue pH was observed as compared with healthy contralateral tissue (pH, 7.09 versus 7.03; P=0.002) concurrent with splitting of the pH signal with 1 peak being more alkalotic. Furthermore, only a moderate decrease of energy-rich metabolites (phosphocreatine reduced by 17%, ATP reduced by 19%) was present, whereas total creatine was reduced by 51%.
The finding of an alkalotic pH split in subacute ischemia is unprecedented. The pH split and only incomplete energy loss in subacute stroke suggest 2 differently viable cellular moieties, best explained by active compensatory mechanisms after acute cerebral ischemia.
组织pH值和能量代谢的体内变化是理解中风病理生理学的关键。我们的目标是研究亚急性缺血性中风时的pH值变化及其与能量代谢的关系,与急性中风中的酸中毒不同,目前对其了解尚少。
我们采用联合氢质子磁共振波谱和磷-31磁共振波谱测量了亚急性中风患者的组织pH值、磷脂以及细胞能量标志物,包括肌酸、磷酸肌酸和N-乙酰天门冬氨酸。我们纳入了19例首次发生缺血性中风的患者(中风后平均时间为6天)。然后,我们使用多变量方差分析比较缺血组织与对侧(健康)组织中的代谢物浓度,以评估两个组织区域之间代谢物水平的显著差异。
在亚急性中风中,与对侧健康组织相比,观察到一个组织部分的组织pH值显著升高(pH值分别为7.09和7.03;P = 0.002),同时pH信号出现分裂,其中一个峰的碱性更强。此外,仅存在富含能量的代谢物适度降低(磷酸肌酸降低17%,三磷酸腺苷降低19%),而总肌酸降低了51%。
亚急性缺血中出现碱性pH值分裂的发现是前所未有的。亚急性中风中的pH值分裂和仅不完全的能量损失提示存在两种不同的存活细胞部分,这最好由急性脑缺血后的主动代偿机制来解释。