Rigorous swim training impairs mitochondrial function in post‐ischaemic rat heart

Abstract

The effect of rigorous swim training (6 h day-1, 5 days week-1 for an average of 191 h) on mitochondrial respiratory function was investigated in rat heart subjected to in vivo ischaemia reperfusion (I-R). Mitochondria was isolated from the risk region of the left ventricle subjected to 60 min occlusion of the main left coronary artery followed by 30 min reperfusion. Heart weight and heart-to-body weight ratio was increased by 21 and 28% (P < 0.01), respectively, in the trained (T, n = 15) vs. control rats (C, n = 20). I-R per se showed minimal effect on heart mitochondria regardless of training status. In sham, state 4 respiration rate was 26 and 32% (P < 0.05) lower in T vs. C rats, using malate-pyruvate (M-P) and 2-oxoglutarate (OG) as substrates, respectively. Training also reduced state 3 respiration by 28% (M-P) and 50% (OG) (P < 0.01). The respiratory control index (RCI) was unaltered in T with M-P, but decreased with OG (P < 0.01). In vitro exposure to superoxide radicals severely reduced state 4 and 3 respiration and RCI, but T hearts showed greater reductions of state 4 and 3 rates than C. Mitochondria from T hearts also revealed a greater state 4 inhibition by H2O2 and HO. compared with C. A lower glutathione content and a higher gamma-glutamyl transpeptidase activity (P < 0.05) was observed in T vs. C. It is concluded that rigorous swim training impairs heart mitochondrial function, making them more susceptible to in vivo and in vitro oxidative stress, and that this damaging effect may be related to a diminished glutathione reserve.

Glutathione deficiency intensifies ischaemia‐reperfusion induced cardiac dysfunction and oxidative stress

“…As Mn SOD represents an important antioxidant protection in heart mitochondria, a severe (˜40%) down‐regulation of this enzyme might render the organelle less protective thereby affecting its bioenergetic capacity. Glutathione depletion caused by rigorous swim‐training has been shown to decrease Mn SOD along with impaired state 43 respiration in rats (Leichtweis et al . 1997).…”

Cardiac Mitochondrial Respiratory Function and Oxidative Stress: The Role of Exercise

“…see [71]). However, much controversy has been noticed re- garding those effects on myocardial mitochondria, particularly with training-induced increased mitochondria volume/density indirectly measured by cardiac citrate synthase activity [45,53,56]. In contrast to skeletal muscle, in which adaptive changes in the volume fraction of mitochondria can readily occur, increases beyond 35% are not so frequent in cardiac muscle, possibly because this would encroach on the volumes of contractile myofibrils and sarcoplasmatic reticulum within the cardiomyocyte and hence, limit heart performance [29].…”

“…Data from Leichtweis et al [45] revealed a significant decrease in state 4 respiration of heart mitochondria from rats submitted to a vigorous swim training program (6 h´day ±1 ; 5 days´week ±1 , 8± 9 weeks) using malate-pyruvate and 2-oxoglutarate as respiratory energizer substrates. This unexpected change induced by training occurred in heart mitochondria from both sham and ischemia-reperfused (I-R) rats.…”

“…Vitamin E is a chain breaking antioxidant located in the lipid phase of the cell associated to membranes and acts as a powerful stabilizer, causing for example, inhibitory effects on the storage of heart lipofuscin-like particles [2]. Despite the absence of a close relationship between state 4 as an indirect sign of inner membrane permeability and oxidative stress, the supposed mitochondrial pro-oxidant redox state condition suggested in the study of Leichtweis [45] was confirmed by the enhanced susceptibility of the vigorously trained and I-R heart mitochondria to different conditions of ROS attack. Accordingly, notorious functional reductions were found in mitochondria treated with Hx + XO, H 2 O 2 and H 2 O 2 + Fe 2 + .…”

Physical Exercise and Antioxidant Defenses in the Hearta

“…Leichtweis et al 23 Rats One of the most comprehensive studies investigating the role of exercise training in regulating endogenous cardiac antioxidant defenses was reported by Powers and colleagues. 17 In this work, rats were treadmill-trained for 10 weeks at three different durations of daily run time (30,60, and 90 min).…”