Journal
CARDIOVASCULAR RESEARCH
Volume 86, Issue 1, Pages 82-91Publisher
OXFORD UNIV PRESS
DOI: 10.1093/cvr/cvp396
Keywords
Magnetic resonance spectroscopy; Hyperpolarization; pH; Ischaemia; Carbonic anhydrase
Categories
Funding
- Newton Abraham Scholarship Foundation
- NIH [1-F31-EB006692-01A1]
- Wellcome Trust
- Medical Research Council
- Royal Society
- Cancer Research UK
- National Institute of Health Research Cambridge Biomedical Research Centre
- Medical Research Council [G0601490]
- British Heart Foundation [PG/07/070/23365]
- GE-Healthcare
- MRC [G0601490, G0700698] Funding Source: UKRI
- British Heart Foundation [RG/07/004/22659, PS/02/002/14893] Funding Source: researchfish
- Medical Research Council [G0700698, G0601490] Funding Source: researchfish
- National Institute for Health Research [CL-2008-14-009] Funding Source: researchfish
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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-C-13]pyruvate, coupled with C-13 magnetic resonance spectroscopy (MRS), to measure pH(i) in the healthy and diseased heart. Hyperpolarized [1-C-13]pyruvate was infused into isolated rat hearts before and immediately after ischaemia, and the formation of (CO2)-C-13 and (HCO3-)-C-13 was monitored using C-13 MRS. The HCO3-/CO2 ratio was used in the Henderson-Hasselbalch equation to estimate pH(i). We tested the validity of this approach by comparing C-13-based pH(i) measurements with P-31 MRS measurements of pH(i). There was good agreement between the pH(i) measured using C-13 and P-31 MRS in control hearts, being 7.12 +/- 0.10 and 7.07 +/- 0.02, respectively. In reperfused hearts, C-13 and P-31 measurements of pH(i) also agreed, although C-13 equilibration limited observation of myocardial recovery from acidosis. In hearts pre-treated with the carbonic anhydrase (CA) inhibitor, 6-ethoxyzolamide, the C-13 measurement underestimated the P-31-measured pH(i) by 0.80 pH units. Mathematical modelling predicted that the validity of measuring pH(i) from the (HCO3-)-C-13/(CO2)-C-13 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-C-13]pyruvate was also infused into healthy living rats, where in vivo pH(i) from the (HCO3-)-C-13/(CO2)-C-13 ratio was measured to be 7.20 +/- 0.03. Metabolically generated (CO2)-C-13 and (HCO3-)-C-13 can be used as a marker of cardiac pH(i) in vivo, provided that CA activity is at normal levels.
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