Using magnetic resonance spectroscopy for the first
time to examine energy production biochemistry in a beating
human heart, Johns Hopkins researchers have found
substantial energy deficits in failing hearts.
The findings, published in the Jan. 18 issue of the
Proceedings of the National Academy of Sciences,
confirm what many scientists have conjectured for years
about heart failure and suggest new treatments designed to
reduce energy demand and/or augment energy transfer.
"The heart consumes more energy per gram than any
other organ," said Paul A. Bottomley, lead researcher and
director of magnetic resonance research in the School of
of Radiology. "While scientists have long known that
nucleotide adenosine triphosphate is the chemical that
fuels heart contractions and that creatine kinase is the
enzyme for one of the sources of ATP, we believe this is
the first time someone has actually measured the flux of
ATP produced by CK reaction in the beating human heart."
Specifically, Bottomley and a team of cardiologists
and radiologists used MRS to provide direct molecular-level
measurements of the CK supply in normal, stressed and
failing human hearts. Other team members include Robert G.
Weiss and Gary Gerstenblith, both in the
Cardiology Division of the Department of Medicine.
For the study, the researchers used an MRI device that
combines conventional magnetic resonance imaging with
spectroscopy to provide not only images of the anatomy but
also direct measurements of the concentrations of various
important biochemicals and their chemical reaction rates
within the cells of various tissues. They first performed
MRS on 14 healthy volunteers to measure cardiac CK flux at
rest and with pharmaceutically induced stress to determine
whether increased energy demand during stress increases the
rate of ATP synthesis through CK.
Then, 17 patients with histories of heart failure were
similarly tested to measure the CK flux. Results showed
that CK flux in healthy hearts is adequate to supply energy
to the heart over a fairly wide normal range of rest and
However, in patients with mild to moderate heart
failure, there was a 50 percent reduction in the ATP energy
supplied by the CK reaction. "The failing hearts have an
energy supply deficit," Bottomley said. "The reduction is
sufficiently large that the supply may be insufficient to
match energy demands of the heart during stress or
exercise, which is often when symptoms appear. Many factors
may contribute to human heart failure, but a failure in the
energy supply would certainly affect the heart's function
if supply can't be met."