Exercise can induce temporary mitochondrial and contractile dysfunction linked to impaired respiratory chain complex activity

Exercise is considered to elicit a physiological response of the heart. Previous studies investigated the influence of repetitive exercise only at the end of the training period. We assessed the impact of 2 exercise protocols, differing in their treadmill inclination, on cardiac and mitochondrial function at different times during the training period. Within 10 weeks, animals trained with 16% incline developed hypertrophy (left ventricular posterior wall thickness: 1.6 ± 0.1 vs 2.4 ± 0.1 mm; P < .05) with normal function (ejection fraction: 75.2% ± 2.5% vs 75.6% ± 2.1%). However, at 6 weeks, there was temporary impairment of contractile function (ejection fraction: 74.5% ± 1.67% vs 65.8% ± 2.3%; P < .05) associated with decreased mitochondrial respiratory capacity (state 3 respiration: 326 ± 71 vs 161 ± 22 natoms/[min mg protein]; P < .05) and a gene expression shift from the adult (α) to the fetal (β) myosin heavy chain isoform. Although peroxisome proliferator-activated receptor gamma coactivator–1α expression was normal, nuclear respiratory factors (NRFs)–1 and –2 were significantly reduced (NRF-1: 1.00 ± 0.16 vs 0.55 ± 0.09; NRF-2: 1.00 ± 0.11 vs 0.63 ± 0.07; P < .05) after 6 weeks. These findings were associated with a reduction of electron transport chain complexes I and IV activity (complex I: 1016 ± 67 vs 758 ± 71 nmol/[min mg protein]; complex IV: 18768 ± 1394 vs 14692 ± 960 nmol/[min mg protein]; P < .05). Messenger RNA expression of selected nuclear encoded subunits of the electron transport chain was unchanged at all investigated time points. In contrast, animals trained with 10% incline showed less hypertrophy and normal function in echocardiography, normal maximal respiratory capacity, and unchanged complex activities at all 3 time points. Repetitive exercise may cause contractile and mitochondrial dysfunction characterized by impaired respiratory chain complex activities. This activity reduction is temporary and intensity related.