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

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


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bicarbonates / metabolism*
  • Carbon Dioxide / metabolism*
  • Carbon Isotopes
  • Carbonic Anhydrases / metabolism
  • Energy Metabolism / physiology
  • Hydrogen-Ion Concentration*
  • Magnetic Resonance Spectroscopy / methods*
  • Magnetic Resonance Spectroscopy / standards
  • Male
  • Models, Biological
  • Myocardial Ischemia / metabolism
  • Myocardium / metabolism*
  • Phosphorus Isotopes
  • Pyruvic Acid / pharmacokinetics
  • Rats
  • Rats, Wistar
  • Reproducibility of Results


  • Bicarbonates
  • Carbon Isotopes
  • Phosphorus Isotopes
  • Carbon Dioxide
  • Pyruvic Acid
  • Carbonic Anhydrases