The Effects of Frequency of Voluntary Exercise on Cardiac Function in Dilated Cardiomyopathy Model Mice

Abstract

Dilated cardiomyopathy (DCM) is one of major causes of heart failure (HF). Recent clinical guidelines take exercises up as one of therapy of HF. However, effects of exercise on patients with inherited DCM have not been established because DCM is associated with high risk of worsening HF and sudden death. A knock-in mouse model of human inherited DCM, TNNT2 ΔK210, shows similar characteristics to DCM patients and is useful model for evaluating therapeutic effects. We aimed to examine how the influence on cardiac function differs depending on amount of voluntary exercise using this model mouse. Homozygous ΔK210 (DCM) mice showed enlarged heart and frequent SD with t1/2 of ∼70 days. DCM mice were divided into 3 groups based on the frequency of voluntary exercise: no exercise control (no-ex), every 2 days (2D) and daily exercise (ED). The 2D and ED groups started running at 1 month of age. Following each dose of exercise for 1 month, cardiac function was assessed by echocardiography. Mice were sacrificed and their heart, lung, lower extremity muscles (soleus, plantaris and gastrocnemius) and body weights were measured. Gene expressions of HF- and arrhythmia-related genes in myocardium were quantified by qPCR analysis. The mortality rates up to 2 months of age decreased to 12% in 2D and ED groups from 39% in no-ex group (n=18-25).The weights of soleus muscles were significantly and similarly increased in 2D group and ED group. In the echocardiography, the cardiac contractility was more improved in ED group than 2D group. Expressions of HF- and arrhythmia-related genes were significantly improved by the voluntary exercise with dose dependent manner. The daily voluntary exercise appears to be most effective in preventing HF and SD in DCM mice.