NMR STUDIES OF ISCHEMIC INJURY IN THE PERFUSED HEART

Project: Research project

Project Details

Description

The uniquely diagnostic and noninvasive advantages of NMR spectroscopy will
be employed to investigate the regulation of transarcolemmal cation
gradients during ischemia and reperfusion, and their role in cell damage
and recovery, in the perfused isovolumic rate heart model. Intracellular
Na+ will be continuously monitored with 23Na NMR using the recently
developed 23Na NMR shift reagent Tm(DOTP)5-. This unique reagent not only
provides excellent resolution of the intracellular Na+ resonance, but is
compatible with acquisition of high quality 31P spectra. Taking advantage
of this, a specially designed NMR probe will be used to collect interleaved
23Na and 31P NMR spectra on the same preparation. High energy phosphates
and intra- and extracellular pH will be monitored from the 31P NMR spectra,
using the chemical shifts of inorganic phosphate and phenylphosphate, an
extracellular pH marker. Additionally, free intracellular Ca2+ will be
measured with 19F NMR by using loading the fluorinated Ca2+ indicator, 5F-
BAPTA. These methodologies will ultimately be combined; Na+ and Ca2+ will
be measured in the same preparation for the first time by NMR. The
specific aims of this project are to determine the mechanisms which alter
the sarcolemmal Na+ and Ca2+ gradients during ischemia and reperfusion, and
to determine how these two gradients are coupled together, and to the
energy supply. The relation of cation homeostasis to functional recovery
will be investigated. The importance of glycolytic energy production in
maintaining cation gradients during ischemia and reperfusion will be
investigated. Two different models of ischemia will be employed, both low-
flow and zero-flow global ischemia. The role of Na+/H+ exchange will
investigated directly by using the specific inhibitor
ethylisopropylamiloride. These issues will be addressed in the
hypertensive animal model, the Spontaneously Hypertensive Rat, using age-
matched Wistar-Kyoto rats as controls, to investigate the sensitivity of
the hypertrophied heart to ischemia. The role of Ca2+ as a mediator of
cell damage could be elucidated, leading to a better understanding of
myocardial ischemia with regard to possible treatments.
StatusFinished
Effective start/end date8/1/916/30/02

Funding

  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health

ASJC

  • Medicine(all)

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