Cardioprotective Effect of Exercise Training in Heart Failure Rats: Exercise Training Reduces Oxidative Stress Induced Nuclear Genomic Fragmentation

Abstract

Alterations in energy metabolism are hallmarks of heart failure (HF) following myocardial infarction (MI). The failing heart is commonly described as an energy-starved engine that has run out of fuel, and myocardial energetics is therefore a topic of considerable interest. Markers of oxidative stress are elevated in HF and have been correlated with myocardial dysfunction. Increased oxidative stress can induce DNA damage, and the main repair mechanism of oxidative DNA damage is Base excision repair (BER) and Single strand break repair (SSBR). Defects in SSBR in post-mitotic cells have been associated with human diseases. Exercise training is an effective treatment for HF. Therefore we aimed to investigate the effect of exercise training on the nuclear genomic integrity in HF rats.MI was induced in 30 female Sprague Dawley rats by surgical ligation of the descending coronary artery. HF was present 4 weeks after ligation. HF rats were then randomized to remain sedentary (n=10) or exposed to either moderate (n=10) or high intensity (n=10) aerobic interval training. Sham sedentary rats (n=10) acted as controls. After 6 weeks of exercise training, H2O2 induced genomic DNA fragmentation was studied in isolated left ventricular cardiomyocytes through an alkaline single cell gel electrophoresis assay. Cardiomyocytes from HF sedentary rats had an increase in H2O2 induced genomic fragmentation by 29% relative to sham, exercise training reduced the genomic fragmentation towards sham levels. 31P NMR experiments revealed reduced PCr concentration in HF and exercise training did not change the PCr levels. However, both moderate- and high intensity training resulted in an increase in cardiac ATP concentration in HF rats. Exercise training seems to induce a cardioprotective effect to increased oxidative stress in HF rats and possibly affects BER/SSBR pathways.