In vivo cardiac P-31 MRS in a mouse model of heart failure

Objective: To investigate myocardial energy status in a mouse model of heart failure using in vivo31P magnetic resonance spectroscopy (MRS). Methods: Male C57BL/6 mice underwent thoracic aortic constriction (TAC) surgery, inducing pressure-overload cardiomyopathy, and were measured seven weeks after surgery (n = 5). Healthy wild-type mice served as controls (n = 4). Cardiac cine 1H MR images were made for reference purposes and to quantify left ventricular (LV) function. Cardiac 31P MR spectra were measured from a ~6 mm cubic voxel enclosing the end-diastolic LV myocardium using ECG triggered, respiratory gated 3D Image-Selected In vivo Spectroscopy (ISIS). Results: LV end-diastolic volume and LV mass normalized to body weight were higher in TAC mice compared to controls (91.7 ± 19.0 versus 61.8 ± 6.0 µL and 4.4 ± 0.6 versus 3.1 ± 0.2 mg/g, P <0.01), whereas LV ejection fraction was reduced in TAC mice (45.4 ± 20.0 versus 64.4 ± 5.2 %, P <0.05). Myocardial phosphocreatine-to-ATP ratio was lower in TAC mice when compared to healthy controls (0.8±0.2 versus 1.2±0.2, P <0.05). Conclusion: Decreased EF in TAC mice is accompanied by decreased phosphocreatine-to-ATP ratio, indicating a disturbed energy homeostasis in this mouse model of heart failure. This research was funded by a VIDI grant from the Netherlands Organisation for Scientific Research (NWO)