PT  - JOURNAL ARTICLE
AU  - Lydia M. Le Page
AU  - Oliver J. Rider
AU  - Andrew J. Lewis
AU  - Victoria Noden
AU  - Matthew Kerr
AU  - Lucia Giles
AU  - Lucy J. A. Ambrose
AU  - Vicky Ball
AU  - Latt Mansor
AU  - Lisa C. Heather
AU  - Damian J. Tyler
TI  - Assessing the effect of hypoxia on cardiac metabolism using hyperpolarized <sup>13</sup>C magnetic resonance spectroscopy
AID  - 10.1101/495069
DP  - 2018 Jan 01
TA  - bioRxiv
PG  - 495069
4099  - http://biorxiv.org/content/early/2018/12/13/495069.short
4100  - http://biorxiv.org/content/early/2018/12/13/495069.full
AB  - Hypoxia plays a role in many diseases and can have a wide range of effects on cardiac metabolism depending on the extent of the hypoxic insult. Non-invasive imaging methods could shed valuable light on the metabolic effects of hypoxia on the heart in vivo. Hyperpolarized carbon-13 magnetic resonance spectroscopy (HP 13C MRS) in particular is an exciting technique for imaging metabolism that could provide such information.The aim of our work was, therefore, to establish whether hyperpolarized 13C MRS can be used to assess the in vivo response of cardiac metabolism to systemic acute and chronic hypoxic exposure. Groups of healthy male Wistar rats were exposed to either acute (30 minutes), one week or three weeks of hypoxia. In vivo MRS of hyperpolarized [1-13C]pyruvate was carried out along with assessments of physiological parameters and ejection fraction. No significant changes in heart rate, respiration rate, or ejection fraction were observed at any timepoint. Haematocrit was elevated after one week and three weeks of hypoxia.Thirty minutes of hypoxia resulted in a significant reduction in pyruvate dehydrogenase (PDH) flux, whereas one or three weeks of hypoxia resulted in a PDH flux that was not different to normoxic animals. Conversion of hyperpolarized [1-13C]pyruvate into [1-13C]lactate was elevated following acute hypoxia, suggestive of enhanced anaerobic glycolysis. Elevated HP pyruvate to lactate conversion was also seen at the one-week timepoint, in concert with an increase in lactate dehydrogenase (LDH) expression. Following three weeks of hypoxic exposure, cardiac metabolism was comparable to that observed in normoxia.We have successfully visualized of the effects of systemic hypoxia on cardiac metabolism using hyperpolarized 13C MRS, with differences observed following 30 minutes and 1 week of hypoxia. This demonstrates the potential of in vivo hyperpolarized 13C MRS data for assessing the cardiometabolic effects of hypoxia in disease.AbbreviationsHPhyperpolarizedPDHpyruvate dehydrogenaseLDHlactate dehydrogenaseBOLDblood-oxygen-level dependentPETpositron emission tomographyPDKpyruvate dehydrogenase kinaseHIFhypoxia-inducible factor