Effects of augmented delivery of pyruvate on myocardial high-energy phosphate metabolism at high workstate

K. Ochiai, J. Zhang, G. Gong, Y. Zhang, J. Liu, Y. Ye, X. Wu, H. Liu, Y. Muraka-Mi, Robert J Bache, Kamil Ugurbil, Arthur H From

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Abstract

This study was performed to determine whether the fall in myocardial high-energy phosphates (HEP) that occurs during high workstates can be ascribed to either inadequate glycolytic pyruvate generation and conversion to acyl-CoA or limitation of long-chain fatty acid transport into the mitochondria. This was tested by using infusions of either pyruvate or butyrate in anesthetized dogs. Pyruvate was used because it bypasses the glycolytic sequence of reactions, activates pyruvate dehydrogenase, and increases mitochondrial NADH concentration ([NADHm]) in isolated myocardium, whereas butyrate enters the mitochondria without need for transport by the rate-limiting, palmitoyl-carnitine transporter. Increasing blood pyruvate from 0.16 ± 0.016 mM to >3 mM did not alter baseline HEP levels determined with 31P nuclear magnetic resonance, but caused an increase in the rate-pressure product and a modest increase in myocardial oxygen consumption (MV̇o2). Infusion of dobutamine + dopamine (each 20 μg·kg-1. min-1 iv) increased MV̇o2 and caused decreases of myocardial phosphocreatine (PCr)/ATP. Pyruvate partially reversed the decrease of HEP levels produced by catecholamine stimulation, whereas butyrate had no effect. Neither pyruvate nor butyrate caused an increase of MV̇o2 during catecholamine infusion. Deoxymyoglobin was not detected by 1H magnetic resonance spectroscopyy in any group. The data demonstrate that carbon substrate availability to the mitochondria is not the only cause of the reduction of PCr/ATP that occurs at high workstates. Supplemental pyruvate (but not butyrate) attenuated the reduction of PCr/ATP during the high workstates; this may have resulted from direct effects on intermediary metabolism or from other effects such as the free radical scavenging activity of pyruvate.

Original languageEnglish (US)
Pages (from-to)H1823-H1832
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume281
Issue number4 50-4
DOIs
StatePublished - Jan 1 2001

Keywords

  • Catecholamines
  • Magnetic resonance spectroscopy
  • Oxygen consumption

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    Ochiai, K., Zhang, J., Gong, G., Zhang, Y., Liu, J., Ye, Y., Wu, X., Liu, H., Muraka-Mi, Y., Bache, R. J., Ugurbil, K., & From, A. H. (2001). Effects of augmented delivery of pyruvate on myocardial high-energy phosphate metabolism at high workstate. American Journal of Physiology - Heart and Circulatory Physiology, 281(4 50-4), H1823-H1832. https://doi.org/10.1152/ajpheart.2001.281.4.h1823