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Correlation between lactate dehydrogenase/pyruvate dehydrogenase activities ratio and tissue pH in the perfused mouse heart: A potential noninvasive indicator of cardiac pH provided by hyperpolarized magnetic resonance
NMR in Biomedicine ( IF 2.9 ) Pub Date : 2020-12-01 , DOI: 10.1002/nbm.4444
David Shaul 1 , Assad Azar 1 , Gal Sapir 1 , Sivaranjan Uppala 1 , Atara Nardi-Schreiber 1 , Ayelet Gamliel 1 , Jacob Sosna 1 , J Moshe Gomori 1 , Rachel Katz-Brull 1
Affiliation  

Cardiovascular diseases account for more than 30% of all deaths worldwide and many could be ameliorated with early diagnosis. Current cardiac imaging modalities can assess blood flow, heart anatomy and mechanical function. However, for early diagnosis and improved treatment, further functional biomarkers are needed. One such functional biomarker could be the myocardium pH. Although tissue pH is already determinable via MR techniques, and has been since the early 1990s, it remains elusive to use practically. The objective of this study was to explore the possibility to evaluate cardiac pH noninvasively, using in‐cell enzymatic rates of hyperpolarized [1‐13C]pyruvate metabolism (ie, moles of product produced per unit time) determined directly in real time using magnetic resonance spectroscopy in a perfused mouse heart model. As a gold standard for tissue pH we used 31P spectroscopy and the chemical shift of the inorganic phosphate (Pi) signal. The nonhomogenous pH distribution of the perfused heart was analyzed using a multi‐parametric analysis of this signal, thus taking into account the heterogeneous nature of this characteristic. As opposed to the signal ratio of hyperpolarized [13C]bicarbonate to [13CO2], which has shown correlation to pH in other studies, we investigated here the ratio of two intracellular enzymatic rates: lactate dehydrogenase (LDH) and pyruvate dehydrogenase (PDH), by way of determining the production rates of [1‐13C]lactate and [13C]bicarbonate, respectively. The enzyme activities determined here are intracellular, while the pH determined using the Pi signal may contain an extracellular component, which could not be ruled out. Nevertheless, we report a strong correlation between the tissue pH and the LDH/PDH activities ratio. This work may pave the way for using the LDH/PDH activities ratio as an indicator of cardiac intracellular pH in vivo, in an MRI examination.

中文翻译:

灌注小鼠心脏中乳酸脱氢酶/丙酮酸脱氢酶活性比与组织 pH 值之间的相关性:超极化磁共振提供的心脏 pH 值的潜在非侵入性指标

心血管疾病占全球所有死亡人数的 30% 以上,许多可以通过早期诊断得到改善。当前的心脏成像方式可以评估血流、心脏解剖结构和机械功能。然而,为了早期诊断和改进治疗,需要进一步的功能性生物标志物。一种这样的功能性生物标志物可能是心肌 pH 值。尽管组织 pH 值已经可以通过 MR 技术确定,并且自 1990 年代初就已经存在,但它仍然难以实际使用。本研究的目的是探讨非侵入性评估心脏pH值的可能性,使用细胞的超极化率酶促[1- 13C]丙酮酸代谢(即每单位时间产生的产物摩尔数)在灌注小鼠心脏模型中使用磁共振波谱直接实时测定。作为组织 pH 值的金标准,我们使用31 P 光谱和无机磷酸盐 (Pi) 信号的化学位移。使用该信号的多参数分析来分析灌注心脏的非均匀 pH 分布,从而考虑到该特征的异质性。与超极化 [ 13 C] 碳酸氢盐与 [ 13 CO 2的信号比相反],在其他研究中已经显示出与 pH 值的相关性,我们在这里研究了两种细胞内酶促速率的比率:乳酸脱氢酶 (LDH) 和丙酮酸脱氢酶 (PDH),通过确定 [1- 13 C] 乳酸的产生速率和[ 13 C]碳酸氢盐,分别。此处确定的酶活性是细胞内的,而使用 Pi 信号确定的 pH 值可能包含不能排除的细胞外成分。尽管如此,我们报告了组织 pH 值与 LDH/PDH 活性比之间的强相关性。这项工作可能为在 MRI 检查中使用 LDH/PDH 活性比作为体内心脏细胞内 pH 的指标铺平道路。
更新日期:2021-01-04
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