MRS studies of creatine kinase metabolism in human heart

The heart is the largest consumer of energy per gram of tissue and the creatine kinase (CK) reaction is its primary cellular energy reserve, providing adenosine triphosphate (ATP) to fuel contraction by shuttling phosphocreatine (PCR) from the mitochondria. For 30 years the measurement of the myocardial PCR/ATP ratio has been a common focus of human cardiac phosphorus (31P) magnetic resonance spectroscopy (MRS). Today, our ability to measure the absolute concentrations of PCR and ATP, the CK reaction rate and flux with 31P MRS, and the total creatine pool (CR) using proton (¹H) MRS, allows almost complete characterization of CK metabolism in the healthy and diseased human heart. The methods and limitations of human cardiac MRS for measuring CK metabolism are reviewed herein, along with the application and findings in 'normal' physiological processes including aging, diet, sedentary lifestyle, hypoxia, and obesity. The results from studies of patients with myocardial infarction, ischemia, dilated and hypertrophic cardiomyopathies, valve disease, heart failure, diabetes, and other disorders are summarized, with the quantitative findings tabulated. The myocardial PCR/ATP ratio is a sensitive indicator of cardiac energy reserve, existing in a meta-stable state that can be upset in many disorders. Reductions in metabolite concentrations and the forward flux for delivering ATP are associated with myocardial infarction, congestive heart failure, cardiomyopathy, and disease severity. Moreover, metrics of CK energy reserve and supply can independently predict long-term cardiovascular outcomes, and are now being used to quantify the effect of pharmaceutical and lifestyle intervention on the heart's energy budget.