title: Application of hyperpolarized [1-¹³C]lactate for the in vivo investigation of cardiac metabolism.
abstract: In addition to cancer imaging, (13) C-MRS of hyperpolarized pyruvate has also demonstrated utility for the investigation of cardiac metabolism and ischemic heart disease. Although no adverse effects have yet been reported for doses commonly used in vivo, high substrate concentrations have lead to supraphysiological pyruvate levels that can affect the underlying metabolism and should be considered when interpreting results. With lactate serving as an important energy source for the heart and physiological lactate levels one to two orders of magnitude higher than for pyruvate, hyperpolarized lactate could potentially be used as an alternative to pyruvate for probing cardiac metabolism. In this study, hyperpolarized [1-(13) C]lactate was used to acquire time-resolved spectra from the healthy rat heart in vivo and to measure dichloroacetate (DCA)-modulated changes in flux through pyruvate dehydrogenase (PDH). Both primary oxidation of lactate to pyruvate and subsequent conversion of pyruvate to alanine and bicarbonate could reliably be detected. Since DCA stimulates the activity of PDH through inhibition of PDH kinase, a more than 2.5-fold increase in bicarbonate-to-substrate ratio was found after administration of DCA, similar to the effect when using [1-(13) C]pyruvate as the substrate.
authors.affiliation: SRI International, Neuroscience Program, 333 Ravenswood Ave, Menlo Park, CA 94025, USA. dirk.mayer@stanford.edu
authors.forename: Dirk
authors.initials: D
authors.lastname: Mayer
authors.forename: Yi-Fen
authors.initials: YF
authors.lastname: Yen
authors.forename: Sonal
authors.initials: S
authors.lastname: Josan
authors.forename: Jae Mo
authors.initials: JM
authors.lastname: Park
authors.forename: Adolf
authors.initials: A
authors.lastname: Pfefferbaum
authors.forename: Ralph E
authors.initials: RE
authors.lastname: Hurd
authors.forename: Daniel M
authors.initials: DM
authors.lastname: Spielman
mesh_terms: D000818:Animals; D002247:Carbon Isotopes; D003999:Dichloroacetic Acid / Q000008:administration & dosage; D019344:Lactic Acid / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D055442:Metabolome; D009206:Myocardium / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
chemical_list: D002247:Carbon Isotopes; D019344:Lactic Acid; D003999:Dichloroacetic Acid