使用超极化二氧化碳和碳酸氢盐测量心脏细胞内 pH 值：一项 13C 和 31P 磁共振波谱研究。

Measuring intracellular pH in the heart using hyperpolarized carbon dioxide and bicarbonate: a 13C and 31P magnetic resonance spectroscopy study.

机构信息

Cardiac Metabolism Research Group, Department of Physiology, Anatomy and Genetics, University of Oxford, Sherrington Building, Parks Road, Oxford OX1 3PT, UK.

出版信息

Cardiovasc Res. 2010 Apr 1;86(1):82-91. doi: 10.1093/cvr/cvp396. Epub 2009 Dec 15.

DOI:10.1093/cvr/cvp396

PMID:20008827

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2836261/

Abstract

AIMS

Technological limitations have restricted in vivo assessment of intracellular pH (pH(i)) in the myocardium. The aim of this study was to evaluate the potential of hyperpolarized [1-(13)C]pyruvate, coupled with (13)C magnetic resonance spectroscopy (MRS), to measure pH(i) in the healthy and diseased heart.

METHODS AND RESULTS

Hyperpolarized [1-(13)C]pyruvate was infused into isolated rat hearts before and immediately after ischaemia, and the formation of (13)CO(2) and H(13)CO(3)(-) was monitored using (13)C MRS. The HCO(3)(-)/CO(2) ratio was used in the Henderson-Hasselbalch equation to estimate pH(i). We tested the validity of this approach by comparing (13)C-based pH(i) measurements with (31)P MRS measurements of pH(i). There was good agreement between the pH(i) measured using (13)C and (31)P MRS in control hearts, being 7.12 +/- 0.10 and 7.07 +/- 0.02, respectively. In reperfused hearts, (13)C and (31)P measurements of pH(i) also agreed, although (13)C equilibration limited observation of myocardial recovery from acidosis. In hearts pre-treated with the carbonic anhydrase (CA) inhibitor, 6-ethoxyzolamide, the (13)C measurement underestimated the (31)P-measured pH(i) by 0.80 pH units. Mathematical modelling predicted that the validity of measuring pH(i) from the H(13)CO(3)(-)/(13)CO(2) ratio depended on CA activity, and may give an incorrect measure of pH(i) under conditions in which CA was inhibited, such as in acidosis. Hyperpolarized [1-(13)C]pyruvate was also infused into healthy living rats, where in vivo pH(i) from the H(13)CO(3)(-)/(13)CO(2) ratio was measured to be 7.20 +/- 0.03.

CONCLUSION

Metabolically generated (13)CO(2) and H(13)CO(3)(-) can be used as a marker of cardiac pH(i) in vivo, provided that CA activity is at normal levels.

摘要

目的

技术限制限制了对心肌细胞内 pH 值（pH(i)）的体内评估。本研究旨在评估极化 [1-(13)C]丙酮酸与 (13)C 磁共振波谱 (MRS) 相结合，测量健康和患病心脏中 pH(i)的潜力。

方法和结果

在缺血前和缺血后立即将极化 [1-(13)C]丙酮酸注入离体大鼠心脏，并使用 (13)C MRS 监测 (13)CO2 和 H13CO3(-)的形成。使用 Henderson-Hasselbalch 方程中的 HCO3(-)/CO2 比来估计 pH(i)。我们通过比较基于 (13)C 的 pH(i)测量值与基于 (31)P MRS 的 pH(i)测量值来验证这种方法的有效性。在对照心脏中，使用 (13)C 和 (31)P MRS 测量的 pH(i)之间存在良好的一致性，分别为 7.12 +/- 0.10 和 7.07 +/- 0.02。在再灌注心脏中，(13)C 和 (31)P 测量的 pH(i)也一致，尽管 (13)C 平衡限制了观察心肌从酸中毒中恢复的情况。在用碳酸酐酶 (CA)抑制剂 6-乙氧唑胺预处理的心脏中，(13)C 测量值比 (31)P 测量值低估 pH(i) 0.80 pH 单位。数学模型预测，从 H13CO3(-)/(13)CO2 比测量 pH(i)的有效性取决于 CA 活性，并且在 CA 受到抑制的情况下，例如在酸中毒情况下，可能会给出错误的 pH(i)测量值。极化 [1-(13)C]丙酮酸也被注入健康的活体大鼠体内，从 H13CO3(-)/(13)CO2 比测量体内 pH(i) 为 7.20 +/- 0.03。