engleski

Exercise improves cardiac mitochondrial function in rats with chronic heart failure

Purpose. Mitochondrial dysfunction has been identified as one of the key players in the onset and progression of myocardial dysfunction in chronic heart failure (CHF). Exercise, especially aerobic interval training (AIT), was shown to improve the failing heart function in both animal model and humans. The aim of the current study was to investigate whether restitution of mitochondrial function following an 8-week AIT period can account for the exercise-induced improvement of the failing heart function. Methods. CHF was induced by coronary artery ligation in female Sprague-Dawley rats. One month after surgery, rats with echocardiographically assessed fraction of shortenage bellow 35% were selected either for subsequent 8-week AIT protocol or sedentary period. Upon completion of these protocols, respiratory function of isolated mitochondria was assessed by measuring oxygen consumption in Clark electrode using pyruvate/malate (5 mM each) and succinate (5 mM) and rotenone (1 µM) as substrates. Three groups of rats were assessed: CHF exercised, CHF sedentary (not subjected to exercise following ligation surgery) and Sham sedentary. Results. Cardiac mitochondria isolated from CHF sedentary rats exhibited significantly decreased rate of ADP-stimulated respiration (state 3) measured in the presence of pyruvate and malate (143.2 ± 51.4 nmolO2/min/mg protein vs. 239.7 ± 30.7 found in Shams). In CHF exercised animals the O2 consumption was restored (213.6 ± 20.9 nmolO2/min/mg). The control between O2 consumption and phosphorylation (coupling) calculated as the ratio of S3 and S4 respiration (respiratory control ratio) was better preserved in CHF exercised then CHF sedentary animals (4.2 ± 0.5 vs. 3.2 ± 0.8). When respiration was fueled with succinate and rotenone, no differences in state 3 respiration was observed between any of the CHF and the Sham animals. However, the respiratory control ratio was higher in mitochondria isolated from CHF exercised then CHF sedentary rats (2.1 ± 0.2 vs. 1.7 ± 0.5), indicating improved respiratory coupling in their myocardium. Conclusions. The rate of mitochondrial respiration and the phosphorylation coupling is impaired in mitochondria isolated from the failing myocardium of ischemic etiology. Exercise training lasting for 8 weeks significantly improved the mitochondrial function, restoring the respiratory rate and increasing the level of phosphorylation efficiency. Since energy depletion underlies the impaired myocardial performance in CHF, it is likely that beneficial effects of exercise in CHF are at least partially mediated through improvement of cardiac mitochondrial function.

exercise ; mitochondrial function ; chronic heart failure

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