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  • Oral presentation
  • Open Access

Myocardial fatty acid metabolism probed with hyperpolarized [1-13C]octanoate

  • 1,
  • 2,
  • 3,
  • 3,
  • 4 and
  • 1
Journal of Cardiovascular Magnetic Resonance201517 (Suppl 1) :O101

https://doi.org/10.1186/1532-429X-17-S1-O101

  • Published:

Keywords

  • Octanoic Acid
  • Myocardial Metabolism
  • Myocardial Fatty Acid
  • Acetylcarnitine
  • Metabolite Peak

Background

The heart normally derives most of its energy from the oxidation of fatty acids. Myocardial metabolism can be monitored non-invasively by MRS using hyperpolarized (HP) 13C-labelled compounds; however, the vast majority of studies reported have used HP pyruvate and did not measure fatty acid catabolism. The myocardial metabolism of HP [1-13C]butyrate and [1-13C]acetate has been reported. The conversion of these short-chain fatty acids to acetyl-CoA does not involve successive rounds of beta-oxidation, as is the case for longer chain fatty acids, which are a more important source of cardiac energy. In this study we examined the applicability of hyperpolarized [1-13C]octanoate, a medium-chain fatty acid, as a probe of myocardial metabolism.

Methods

[1-13C]octanoic acid (4 M in DMSO, doped with stable trityl radical) was polarized by microwave irradiation (196.8 GHz) at 7 T & 1 K. After dissolution with superheated buffered D2O, ~0.04 mmol was infused via a femoral vein catheter into anesthetized Wistar rats in a 9.4 T horizontal bore scanner (Varian) and a series of single pulse (BIR-4, 300, TR ~3 s) gated 13C MRS acquisitions was performed with a surface coil positioned over the heart. To aid metabolite identification, HP [1-13C]acetate and/or 13C-urea were coinfused in several experiments.

Results

After dissolution, [1-13C]octanoate polarization level and T1 relaxation rate were ~11% and 29 ± 3 s, respectively. In vivo, the octanoate signal decayed rapidly and was no longer measurable 20-36 s after the start of infusion. Interactions with blood proteins such as serum albumin are likely responsible for the rapid loss of signal, and the T1 in blood ex vivo was ~9.6 ± 0.5 s. One metabolite peak at 175.4 ppm, was consistently observed (Fig 1). Summing the FIDs where octanoate was present and integrating the peaks, the metabolite had 1.49 ± 0.20% the area of octanoate C-1 (n=5). The chemical shift of the metabolite was assigned to [1-13C]acetylcarnitine. This was confirmed by infusing HP [1-13C]acetate and observing [1-13C]acetylcarnitine with the same chemical shift, as well as coinfusing HP [1-13C]acetate and [1-13C]octanoate and observing a single metabolite peak for [1-13C]acetylcarnitine.
Figure 1
Figure 1

Acetylcarnitine produced in the rat heart from hyperpolarized [1-13C]octanoate. Overlay of summed 13C MR spectra acquired in vivo, chemical shift referenced to coinfused 13C-urea, with hyperpolarized [1-13C]octanoate and [1-13C]acetate infused, separately or together, converted to [1-13C]acetylcarnitine.

Conclusions

This study demonstrates that in-vivo dissolution DNP metabolic experiments can be performed with 13C-labelled medium-chain fatty acids. Sufficient 13C polarization in octanoate survives circulation, tissue uptake, mitochondrial transport and conversion by beta-oxidation to acetyl-CoA to be detectible in the acetylcarnitine pool. HP octanoate can be used to directly probe the beta-oxidation of metabolically important fatty acids in the heart.

Funding

Work supported by the Swiss National Fund (grants #138146 & PPOOP1_133562).

Authors’ Affiliations

(1)
Dept. of Cardiology, Lausanne University Hospital (CHUV), Lausanne, Switzerland
(2)
Dept. of Radiology, Lausanne University Hospital (CHUV) and University of Lausanne (UNIL), Lausanne, Switzerland
(3)
Albeda Research ApS, Copenhagen, Denmark
(4)
Institute of Physics of Biological Systems, Swiss Federal Institute of Technology (EPFL), Lausanne, Switzerland

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