The Comparison of Voluntary and Forced Exercises on Cardiac Function of DCM Model Mice

Abstract

Background:Recent studies have demonstrated that exercise has beneficial effects as therapy for heart failure (HF). However, effects of exercise on patients with inherited dilated cardiomyopathy (DCM), one of major causes of HF, has not been established because DCM is associated with high risk of sudden death (SD) by lethal arrhythmia. Recently, a knock-in mouse model of inherited DCM was created. They show similar characteristics to DCM patients and are useful model for evaluating therapeutic effects. We compared effects of voluntary exercise and forced exercise on this model mouse.Methods: We used a knock-in mouse model having one of human inherited DCM mutation, TNNT2 ΔK210, which have decreased Ca2+ sensitivity of myofilaments and show enlarged heart and frequent SD with t1/2 of ∼70 days. Homozygous ΔK210 mice (DCM mice) at 1 month-old were housed with a running wheel (diameter = 12 cm), and daily voluntary running distance was recorded. Other group of DCM mice underwent a forced treadmill exercise every 1-2 days (4 times a week) from 1 month of age. Running period and speed were gradually increased from 11m/min of speed for 15 min to 20m/min for 60 min in initial 2 weeks and kept constant for the rest of the weeks. Following each exercise until 2 month-old, cardiac function was assessed by echocardiography and ECG. Heart, lung and body weights were excised and weighed. Gene expressions of heart failure-related genes were quantified by q-PCR analysis.Results and discussion: Voluntary exercise significantly prolonged t1/2 of DCM mice (from 77 days to 128 days) and attenuated deterioration of left ventricular systolic function. Forced exercise also similarly attenuated the deterioration of systolic function, though the left ventricular wall was significantly thicker than that of voluntary exercise group. Gene expression of αMHC was consistently higher in forced exercise group. We will also discuss other differences between two exercise groups.