2018 Volume 64 Issue Suppl.1 Pages 52
Background: Exercise is known to have beneficial effects on therapy for heart failure (HF). However, the effects of exercise on patients with dilated cardiomyopathy (DCM), one of major causes of progressive HF, have not been established because DCM is associated with high risk of sudden death (SD) at compensated stage and deterioration in HF. Our aim is to examine the impacts of voluntary and forced exercise on cardiac function of DCM using a knock-in mouse model of DCM.
Methods: We used a knock-in mouse model having one of human inherited DCM mutation, TNNT2 Δ210, which decreases Ca2+ sensitivity of myofilaments and show enlarged heart and frequent SD with t1/2 of ~70 days (Du et al: Circ Res, 2007). Homozygous Δ210 mice (below are called DCM mice) in a voluntary exercise (V-Ex) group were housed with a wheel at 1 month of age and daily running distance was recorded. DCM mice in a forced exercise (F-Ex) group underwent a forced treadmill exercise every 1-2 days from 1 month of age. Following each exercise until 2 monthold, cardiac function was assessed by echocardiography and ECG. Heart, lung and lower extremity muscle (soleus, plantaris and gastrocnemius muscles) were excised and their weights were measured together with body weight (BW). Heart failure-related genes (ANP, αMHC, βMHC) were quantified by q-PCR analysis.
Results and Discussion: In case that DCM mice start running exercise before onset of detriorateion in HF, V-Ex significantly prolonged t1/2 of DCM mice, from 77 days to 128 days. At 2 month of age, after each exercise for a month, V-Ex group showed significantly attenuated deterioration of left ventricular systolic function and F-Ex group showed similar tendency. Gene expression of αMHC was consistently higher in F-Ex group. Though the relative soleus muscle weights were significantly greater in V-Ex group than in those of F-Ex group and control (V-Ex: 0.40±0.05 mg/g BW, F-Ex: 0.32±0.05 mg/g BW, control: 0.34±0.05 mg/g BW), the relative gastrocnemius muscle weights of V-Ex group were slightly smaller compared with F-Ex and control groups (V-Ex: 4.83±0.3 mg/g BW, F-Ex: 5.01±0.3 mg/g BW, control: 5.04±0.6 mg/g BW), suggesting the effects of both exercises on whole body may be somewhat different. These results suggest that voluntary and forced exercises are beneficial for cardiac function of DCM mice and would give different means for the future therapy of DCM patients.
