Abstract 278: Exercise Training Ameliorates LV Dysfunction in Mice with a Calcium Influx Mediated Cardiomyopathy

Abstract

Background— Ca 2+ influx through L-type Ca 2+ channels (LTCCs) induces Ca 2+ release from the SR to induce and regulate cardiac contraction. We have characterized a mouse model with cardiac-specific expression of the β2a subunit of the LTCC (β2a), leading to pathological hypertrophy due to excessive LTCC Ca 2+ entry. Chronic exercise causes physiological hypertrophy in normal hearts. We determined if swim training improved or further deranged the performance of β2a mice. Methods and Results— β2a (n=12) and WT (n=20) mice were swim trained for 21 consecutive days. ECHO was performed at beginning and end of swim training. Ejection fraction (EF) and fractional shortening (FS) increased significantly with swim training in WT animals. (EF pre-swim: 57±2.02% vs. post-swim: 70±2.88%; FS pre-swim: 30±1.34% vs. post-swim: 39±2.42%). β2a mice were hypercontractile before swimming and had no significant change after training (EF pre-swim: 70±1.75% vs. post-swim: 74.06±2.72%; FS pre-training: 38±2.38% vs. post-training: 42±2.22%). Contractile performance was significantly greater in β2a mice versus WT before but not after training. There was a significant increase in HW/BW [mg/gm] ratio in trained WT (n=8) versus sedentary WT (n=8) (swim: 5.75±0.19 vs. sed: 4.63±0.2) but training did not cause additional hypertrophy in β2a (n=8) versus sedentary (n=7) (swim: 5.98±0.31 vs. sed: 5.96±0.25). Isolated WT and β2a hearts were placed on a Langendorff apparatus and a balloon was inserted into the LV to record isovolumic pressure. Each heart underwent 15 min of ischemia followed by 30 min of reperfusion. End diastolic pressure (EDP) increased in all hearts during ischemia. There were no protective effects of training on ischemia-induced increases in EDP in WT hearts. EDP increased more in sedentary β2a during ischemia but this effect was eliminated in trained β2a hearts. LV developed pressure (LVDP) fell with ischemia and partially recovered with reperfusion. LVDP recovery was significantly greater in trained versus sedentary WT hearts. Swim training also significantly improved LVDP recovery in β2a hearts. Conclusions— Chronic exercise training reduces pathological hypertrophy and damaging effects of ischemia in a murine model of LTCC overexpression.