Background: The impairment of cardiac diastolic function is essential for the development and progression of heart failure, regardless of the systolic performance of the heart. Novel methods of diagnosis of diastolic dysfunction in experimental animals are needed in order to validate the effectiveness of novel heart failure treatment.
Aim: The in vivo characterisation of diastolic and systolic function of the heart during heart failure progression in Tgaq*44 mice using magnetic resonance imaging (MRI) and original image analysis.
Methods: Cardiac function in vivo in both Tgaq*44 and FVB mice was analysed using MRI at 4.7 T. Magnetic resonance imaging was performed using an ECG triggered fast gradient echo (cine-like flow compensated FLASH) sequence. For the assessment of left ventricle (LV) dynamics at least 20 images per cardiac cycle were acquired in the midventricular short-axis projection at the level of papillary muscles. End-systolic (ESA) and end-diastolic (EDA) areas were estimated from the minimum and maximum values found in the area-time plot. Fractional area change (FAC) defined as (EDA-ESA)/EDA, ejection (ER) and filling (FR) rates defined as slope of the beginning part of the systolic and diastolic limbs were calculated. In addition, heart failure progression in Tgaq*44 mice was assessed by morphometric parameters (ventricular weight to body weight index and wet to dry lung weight index), level of BNP mRNA expression as well as survival.
Results: Systolic function assessed by FAC% and ER was stable but slightly impaired up to 10 months of age in Tgaq*44 mice as compared to the FVB mice. After 12 months of age of the Tgaq*44 mice there was a progressive deterioration of systolic function (ER at 10, 12, 14 months of age were 0.0188 ± 0.00434, 0.0140 ± 0.00474, 0.0115 ± 0.00469 1/ms, respectively). Diastolic function of the Tgaq*44 hearts was preserved or even slightly augmented between 4 and 10 months of age, then at the age of 12 months and later profoundly impaired (FR at 10, 12, 14 months of age were 0.0280 ± 0.01031, 0.0196 ± 0.01050, 0.0158 ± 0.00833 1/ms, respectively).
Conclusions: The MRI allows reliable in vivo assessment of the systolic and diastolic function in Tgaq*44 mice. In Tgaq*44 mice after few months of stable and compensated phase of the heart failure decompensation develops that involves impairment of both systolic and diastolic and leads to the fully symptomatic dilated cardiomyopathy. The precise molecular mechanisms of the systolic and diastolic dysfunction and their relative contribution to the heart failure progression in Tgaq*44 mice remain to be established.