Transmurally differentiated measurement of ATP hydrolysis rates in the in vivo porcine hearts

Magn Reson Med. 2016 May;75(5):1859-66. doi: 10.1002/mrm.26162. Epub 2016 Feb 19.

Abstract

Purpose: Compare the transmural distribution of forward creatine kinase reaction (kf,CK ) and ATP hydrolysis rate (kr,ATPase ) in the myocardium of normal porcine heart. Rate constants were extracted from partially relaxed spectra by applying the T1nom method, effectively reducing data acquisition time by up to an order of magnitude.

Theory and methods: T1nom method for double saturation of PCr and Pi is introduced and validated through simulations. Bioenergetics was measured in vivo utilizing one-dimensional chemical shift imaging (1D-CSI) magnetic resonance (31) P spectroscopy.

Results: At basal conditions, there was no significant difference between subepicardial layers (EPI) vs. the subendocardial layers (ENDO) for both fluxf,CK and fluxr,ATPase . At high cardiac workload (HWL), where the rate pressure product increased 2.6-fold, PCr/ATP ratio and fluxf,CK showed no significant change in both EPI and ENDO layers, while fluxr,ATPase increased significantly (baseline: 1.11 ± 0.12 and 1.12 ± 0.13 μmol/g/s, EPI and ENDO, respectively; to HWL: 2.35 ± 0.27 and 2.21 ± 0.08 μmol/g/s, EPI and ENDO, respectively, each P < 0.01 vs. baseline).

Conclusion: In the normal heart, increase of cardiac work state is accompanied by an increase in ATP hydrolysis rate with no changes in CK flux rate. There are no significant differences between EPI vs. ENDO concerning the ATP hydrolysis rate or CK flux rate in both baseline and high cardiac work states.

Keywords: ATP hydrolysis rate; heart; high-energy phosphate; magnetic resonance spectroscopy; saturation transfer.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphate / metabolism*
  • Animals
  • Computer Simulation
  • Endocardium / metabolism
  • Female
  • Heart / physiology*
  • Hemodynamics
  • Hydrolysis
  • Kinetics
  • Magnetic Resonance Spectroscopy
  • Models, Theoretical
  • Myocardium / metabolism*
  • Oxygen / metabolism
  • Pericardium / metabolism
  • Swine

Substances

  • Adenosine Triphosphate
  • Oxygen