Cookies on this website

We use cookies to ensure that we give you the best experience on our website. If you click 'Accept all cookies' we'll assume that you are happy to receive all cookies and you won't see this message again. If you click 'Reject all non-essential cookies' only necessary cookies providing core functionality such as security, network management, and accessibility will be enabled. Click 'Find out more' for information on how to change your cookie settings.

<jats:p>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 <jats:sup>13</jats:sup>C 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 <jats:sup>13</jats:sup>C 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-<jats:sup>13</jats:sup>C] 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-<jats:sup>13</jats:sup>C] pyruvate into [1-<jats:sup>13</jats:sup>C] 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 <jats:sup>13</jats:sup>C MRS, with differences observed following 30 minutes and 1 week of hypoxia. This demonstrates the potential of in vivo hyperpolarized <jats:sup>13</jats:sup>C MRS data for assessing the cardiometabolic effects of hypoxia in disease.</jats:p>

Original publication

DOI

10.1101/495069

Type

Journal article

Journal

NMR in Biomedicine

Publisher

Wiley

Publication Date

27/03/2020