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(Circulation. 2009;119:1918-1924.)
© 2009 American Heart Association, Inc.

Imaging

Reduced Myocardial Creatine Kinase Flux in Human Myocardial Infarction

An In Vivo Phosphorus Magnetic Resonance Spectroscopy Study

Paul A. Bottomley, PhD; Katherine C. Wu, MD; Gary Gerstenblith, MD; Steven P. Schulman, MD; Angela Steinberg, RN; Robert G. Weiss, MD

From the Division of MR Research, Department of Radiology (P.A.B.), and Cardiology Division, Department of Medicine (K.C.W., G.G., S.P.S., A.S., R.G.W.), The Johns Hopkins University, School of Medicine, Baltimore, Md.

Correspondence to Paul A. Bottomley, PhD, Park Bldg 310, The Johns Hopkins University, 600 N Wolfe St, Baltimore, MD 21287. E-mail bottoml{at}mri.jhu.edu

Received September 19, 2008; accepted February 10, 2009.

Background— Energy metabolism is essential for myocellular viability. The high-energy phosphates adenosine triphosphate (ATP) and phosphocreatine (PCr) are reduced in human myocardial infarction (MI), reflecting myocyte loss and/or decreased intracellular ATP generation by creatine kinase (CK), the prime energy reserve of the heart. The pseudo–first-order CK rate constant, k, measures intracellular CK reaction kinetics and is independent of myocyte number within sampled tissue. CK flux is defined as the product of [PCr] and k. CK flux and k have never been measured in human MI.

Methods and Results— Myocardial CK metabolite concentrations, k, and CK flux were measured noninvasively in 15 patients 7 weeks to 16 years after anterior MI using phosphorus magnetic resonance spectroscopy. In patients, mean myocardial [ATP] and [PCr] were 39% to 44% lower than in 15 control subjects (PCr=5.4±1.2 versus 9.6±1.1 µmol/g wet weight in MI versus control subjects, respectively, P<0.001; ATP=3.4±1.1 versus 5.5±1.3 µmol/g wet weight, P<0.001). The myocardial CK rate constant, k, was normal in MI subjects (0.31±0.08 s^–1) compared with control subjects (0.33±0.07 s^–1), as was PCr/ATP (1.74±0.27 in MI versus 1.87±0.45). However, CK flux was halved in MI [to 1.7±0.5 versus 3.3±0.8 µmol(g · s)^–1; P<0.001].

Conclusions— These first observations of CK kinetics in prior human MI demonstrate that CK ATP supply is significantly reduced as a result of substrate depletion, likely attributable to myocyte loss. That k and PCr/ATP are unchanged in MI is consistent with the preservation of intracellular CK metabolism in surviving myocytes. Importantly, the results support therapies that primarily ameliorate the effects of tissue and substrate loss after MI and those that reduce energy demand rather than those that increase energy transfer or workload in surviving tissue.

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CLINICAL PERSPECTIVE

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Clinical Summaries
Circulation 2009 119: 1843-1845. [Extract] [Full Text]