P516Diastolic dysfunction in diabetic mice revealed by MRI

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Abstract

Purpose: Left ventricular diastolic dysfunction (LVDD) in diabetes is associated with high risk of heart failure [1]. New pharmaceutical strategies are being developed targeting LVDD in diabetes, but direct observation of their effect in mouse models is challenging [2]. In this study we used magnetic resonance imaging (MRI) to evaluate diastolic function in a streptozotocin-induced mouse model of diabetes.

Methods: Diabetes was induced in five male mice (C57/Bl6) with 100 mg/kg i.p. streptozotocin daily for three successive days and five control mice were injected with saline. Confirmation of disease onset was made at four weeks with blood sugar measurements and mice had free access to food and water throughout. MRI was performed at four weeks and eight weeks from the start of the experiment using a Bruker BioSpec 47/40 system at 4.7T.

For evaluation of systolic function, standard respiratory and ECG-gated acquisitions were performed on the whole heart in the short axis. To evaluate diastolic function, a single mid-ventricular short-axis slice was acquired with a flow-compensated gradient-echo sequence. We defined end-systolic and end-diastolic areas (ESA, EDA) as the smallest and largest areas of the slice respectively. The slice area measured at the time point occurring at 30% between end-systole and end-diastole (labelled d) was used to calculate a ‘diastolic index’ following [3]: (EDA-d)/(EDA-ESA).

Results: Blood measurements confirmed the onset of diabetes in four out of five induced mice. Systolic function was preserved in all mice both at four and at eight weeks after induction (left ventricular ejection fraction LVEF > 57% in all tested subjects). The diastolic index was lower at four weeks in the diabetic animals (diabetic: 22 ± 6 %; controls: 51 ± 3 %) and this did not change at eight weeks (diabetic: 27 ± 7 %; controls 54 ± 3 %).

Conclusions: We have shown that LVDD was present in mice four weeks after induction of diabetes and that it persisted at eight weeks, although systolic function was preserved. The data support the use of the LVDD MRI measurement for establishing diastolic dysfunction in mouse hearts.

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