Using magnetic resonance spectroscopy (MRS) 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 January 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," notes Paul A. Bottomley, Ph.D., lead researcher and director of magnetic resonance research at the Johns Hopkins Department of Radiology. "While scientists have long known that nucleotide adenosine triphosphate (ATP) is the chemical that fuels heart contractions and that creatine kinase (CK) 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 at Hopkins 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, M.D., and Gary Gerstenblith, M.D., both in the Cardiology Division of the Hopkins 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 stress conditions.
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," says Bottomley. "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."
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