Impaired ATP Kinetics in Failing In Vivo Mouse Heart

The hypothesis that the failing heart may be energy-starved is supported in part by observations of reduced rates of adenosine 5'-triphosphate (ATP) synthesis through the creatine kinase (CK) reaction, the primary myocardial energy reservoir, in patients with heart failure (HF). Although murine models have been used to probe HF pathophysiology, it has not been possible to noninvasively measure the rate of ATP synthesis through CK in the in vivo mouse heart. The purpose of this work was to exploit noninvasive spatially localized magnetic resonance spectroscopy techniques to measure ATP flux through CK in in vivo mouse hearts and determine the extent of any reductions in murine HF. The Triple Repetition Time Saturation Transfer (TRiST) magnetic resonance spectroscopy method of measuring ATP kinetics was first validated in skeletal muscle, rendering similar results to conventional saturation transfer magnetic resonance spectroscopy. In normal mouse hearts, the in vivo CK pseudo-first-order-rate constant, k(F), was 0.32±0.03 s(-1) (mean±SD) and the rate of ATP synthesis through CK was 3.16±0.47 μmol/g/s. Thoracic aortic constriction reduced k(F) by 31% (0.23±0.03 s(-1), P