Brain high-energy phosphates and creatine kinase synthesis rate under graded isoflurane anesthesia: An in vivo (31) P magnetization transfer study at 11.7 tesla

Magn Reson Med. 2015 Feb;73(2):726-30. doi: 10.1002/mrm.25136. Epub 2014 Feb 12.

Abstract

Purpose: The creatine kinase rate of metabolic adenosine triphosphate (ATP) synthesis is an important metabolic parameter but is challenging to measure in vivo due to limited signal-to-noise ratio and long measurement time.

Theory and methods: This study reports the implementation of an accelerated (31) P Four Angle Saturation Transfer (FAST) method to measure the forward creatine kinase (CK) rate of ATP synthesis. Along with a high-field scanner (11.7 Tesla) and a small sensitive surface coil, the forward CK rate in the rat brain was measured in ∼5 min.

Results: Under 1.2% isoflurane, the forward CK rate constant and metabolic flux were, respectively, kf , CK =0.26 ± 0.02 s(-1) and Ff,CK =70.8 ± 4.6 μmol/g/min. As a demonstration of utility and sensitivity, measurements were made under graded isoflurane. Under 2.0% isoflurane, kf , CK =0.16 ± 0.02 s(-1) and Ff,CK =410.0 ± 4.2 μmol/g/min, corresponding to a 38% and 42% reduction, respectively, relative to 1.2% isoflurane. By contrast, the ATP and phosphocreatine concentrations were unaltered.

Conclusion: This study demonstrated the (31) P FAST measurement of creatine kinase rate of ATP synthesis in rat brain with reasonable temporal resolution. Different isoflurane levels commonly used in animal models significantly alter the CK reaction rate but not ATP and phosphocreatine concentrations.

Keywords: MRS; high fields; metabolic flux; rats.

Publication types

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

MeSH terms

  • Adenosine Triphosphate / biosynthesis*
  • Anesthetics, Inhalation / administration & dosage
  • Animals
  • Brain / drug effects
  • Brain / metabolism*
  • Creatine Kinase / biosynthesis*
  • Dose-Response Relationship, Drug
  • Image Interpretation, Computer-Assisted / methods*
  • Isoflurane / administration & dosage*
  • Magnetic Resonance Imaging
  • Magnetic Resonance Spectroscopy / methods*
  • Male
  • Metabolic Clearance Rate
  • Metabolic Flux Analysis / methods
  • Phosphorus Radioisotopes / pharmacokinetics
  • Radiopharmaceuticals / pharmacokinetics
  • Rats
  • Rats, Sprague-Dawley
  • Reproducibility of Results
  • Sensitivity and Specificity

Substances

  • Anesthetics, Inhalation
  • Phosphorus Radioisotopes
  • Radiopharmaceuticals
  • Adenosine Triphosphate
  • Isoflurane
  • Creatine Kinase