Cardiac structure and function during ageing in energetically compromised Guanidinoacetate N-methyltransferase (GAMT)-knockout mice – a one year longitudinal MRI study

Measurements of cardiac structure (left ventricular mass and volumes) and function (ejection fraction, stroke volume, cardiac output) were obtained using high-resolution cine-MRI at 9.4 T under isoflurane anaesthesia.There were no physiologically significant differences in cardiac function between wild type and GAMT knockout mice at any time point for male or female groups, or for both combined (for example ejection fraction: 6 weeks (KO vs. WT): 70 ± 6% vs. 65 ± 7%; 4 months: 70 ± 6% vs. 62 ± 8%; 8 months: 62 ± 11% vs. 62 ± 6%; 12 months: 61 ± 7% vs. 59 ± 11%, respectively).These findings suggest the presence of comprehensive adaptations in the knockout mice that can compensate for a lack of creatine. Furthermore, this study clearly demonstrates the power of cine-MRI for accurate non-invasive, serial cardiac measurements. Cardiac growth curves could easily be defined for each group, in the same set of animals for all time points, providing improved statistical power, and substantially reducing the number of mice required to conduct such a study. This technique should be eminently useful for following changes of cardiac structure and function during ageing.Magnetic resonance imaging (cine-MRI) is 3D-capable, non-invasive, with high spatial resolution, and represents the most sophisticated tool to determine cardiac structure and function in normal, genetically or surgically manipulated mice [1-4]. Hearts of juvenile or adult transgenic mouse models are commonly examined and compared to wild type littermates at a single time point to identify and characterize the effect of the genetic alteration(s) on global cardiac performance. However, due to the non-invasiveness of MRI, mice can be investigated in a longitudinal fashion in order to follow-up after an intervention such as myocardial infarction [5], transverse aortic constriction [6], or to identify phenotypes that may occur as a function of ageing.Here we report on the longitudinal application of cine-MRI on a mouse