High-energy phosphate metabolism in normal, hypertrophied and failing human myocardium
This chapter examines the role of cardiac high-energy phosphate metabolism in normal, hypertrophied and failing human myocardium. Myocardial biopsies allow analysis of ATP, total adenine nucleotides, creatine kinase activity and total creatine content, while non-invasive 31 P-magnetic resonance spectroscopy can be used to determine phosphocreatine/ATP ratios and, most recently, absolute levels of ATP and phosphocreatine. The failing human myocardium is characterized by reduced phosphocreatine and total creatine levels, normal or slightly reduced ATP levels and reduced creatine kinase activity. These changes are consistent with, but do not prove, a role of high-energy phosphate metabolism as a contributing factor in heart failure. An answer to the precise functional role of high-energy phosphate metabolism necessitates analysis of free ADP levels, free energy change of ATP hydrolysis and creatine kinase reaction velocity; these measurements may become feasible in coming years. However, analysis of energy metabolism in a compartmentalized manner, i.e., in the compartments relevant for contractile function such as the perimyofibrillar space, will remain elusive for the foreseeable future.