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 (alpha) to the fetal (beta) myosin heavy chain isoform. Although peroxisome proliferator-activated receptor gamma coactivator-la 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 land 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. (C) 2012 Elsevier Inc. All rights reserved.