Abstract #4769

Quantitative modeling and detection of flux through pyruvate dehydrogenase in human myocardium

Jeffry R. Alger¹, Jian-xiong Wang¹, Jeannie Baxter¹, Jeff Liticker², Crystal Harrison¹, Vlad Zaha³, Albert Chen⁴, Salvador Pena¹, Lucy Christie¹, Richard Martin¹, Kelley Derner¹, Carol Parcel¹, A. Dean Sherry¹, and Craig R. Malloy¹

¹Advanced Imaging Research Center, UT Southwestern Medical Center, Dallas, TX, United States, ²Simmons Cancer Center, UT Southwestern Medical Center, Dallas, TX, United States, ³Internal Medicine, UT Southwestern Medical Center, Dallas, TX, United States, ⁴University of Toronto, Toronto, ON, Canada

Flux through pyruvate dehydrogenase, a key regulatory enzyme, may be detected in human myocardium by hyperpolarization (HP) technology. A previously-validated model for quantitation of pyruvate metabolism in isolated hearts was extended to human myocardium. HP [¹³C]bicarbonate and HP[1-¹³C]lactate were detected from heart muscle after injection of ~0.43 mL/kg of 250mM HP[1-¹³C]pyruvate in four healthy subjects. All subjects tolerated the procedure well. Kinetic modeling yielded a rate constant for oxidation of pyruvate to bicarbonate of 0.005 sec^-1, lower than that reported for isolated rodent hearts. Assessment of PDH flux in human myocardium is feasible with hyperpolarization technology.

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