Cardiac Metabolism Research Group, Department of Physiology, Anatomy and Genetics, University of Oxford, Sherrington Building, Parks Road, Oxford OX1 3PT, UK.
Cardiovasc Res. 2010 Apr 1;86(1):82-91. doi: 10.1093/cvr/cvp396. Epub 2009 Dec 15.
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.
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.
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.
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。
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。
只要 CA 活性正常，代谢产生的 (13)CO2 和 H13CO3(-) 可作为体内心脏 pH(i)的标志物。
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