Endurance Exercise Training Reduces Cardiac Sodium/Calcium Exchanger Expression in Animals Susceptible to Ventricular Fibrillation

Abstract

Increased Na+/Ca2+ exchanger activity (NCX1, an important regulator of cardiomyocyte cystolic Ca2+) may provoke arrhythmias. Exercise training can decrease NCX1 expression in animals with heart failure, improve cytosolic Ca2+ regulation, and could thereby reduce the risk for ventricular fibrillation (VF). To test this hypothesis, a 2-min coronary occlusion was made during the last min. of exercise in dogs with healed myocardial infarctions; 23 had VF (S, susceptible) and 13 did not (R, resistant). The animals were randomly assigned to either 10-wk exercise training (progressively increasing treadmill running) (S n = 9; R n = 8) or 10-wk sedentary (S n = 14; R n = 5) groups. At the end of the 10-wk period, the exercise + ischemia test provoked VF in sedentary but not trained susceptible dogs. After euthanasia, cardiac tissue was harvested and NCX1 protein expression was determined by Western blot. In the sedentary group, NCX1 expression was 4 fold higher in susceptible (4.2 ± 1.3 AU) compared to resistant (1.0 ± 0.1 AU) dogs. In contrast, post-training NCX1 levels were similar in the resistant and susceptible animals (S = 1.7 ± 0.3 AU). Thus, exercise training can restore a more normal NCX1 level in VF susceptible dogs and could improve cystolic Ca2+ regulation reducing the risk for sudden death. (supported by NIH grant HL-68609)