ATP flux through creatine kinase in the normal, stressed, and failing human heart

Research output: Contribution to journalArticle

Abstract

The heart consumes more energy per gram than any other organ, and the creatine kinase (CK) reaction serves as its prime energy reserve. Because chemical energy is required to fuel systolic and diastolic function, the question of whether the failing heart is "energy starved" has been debated for decades. Despite the central role of the CK reaction in cardiac energy metabolism, direct measures of CK flux in the beating human heart were not previously possible. Using an image-guided molecular assessment of endogenous ATP turnover, we directly measured ATP flux through CK in normal, stressed, and failing human hearts. We show that cardiac CK flux in healthy humans is faster than that estimated through oxidative phosphorylation and that CK flux does not increase during a doubling of the heart rate-blood pressure product by dobutamine. Furthermore, cardiac ATP flux through CK is reduced by 50% in mild-to-moderate human heart failure (1.6 ± 0.6 vs. 3.2 ± 0.9 μmol/g of wet weight per sec, P < 0.0005). We conclude that magnetic resonance strategies can now directly assess human myocardial CK energy flux. The deficit in ATP supplied by CK in the failing heart is cardiac-specific and potentially of sufficient magnitude, even in the absence of a significant reduction in ATP stores, to contribute to the pathophysiology of human heart failure. These findings support the pursuit of new therapies that reduce energy demand and/or augment energy transfer in heart failure and indicate that cardiac magnetic resonance can be used to assess their effectiveness.

Original languageEnglish (US)
Pages (from-to)808-813
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume102
Issue number3
DOIs
StatePublished - Jan 18 2005

Keywords

  • Heart failure
  • Magnetic resonance spectroscopy
  • Metabolism

ASJC Scopus subject areas

  • General

Fingerprint Dive into the research topics of 'ATP flux through creatine kinase in the normal, stressed, and failing human heart'. Together they form a unique fingerprint.

  • Cite this