Effects of 4 wk of hindlimb suspension on skeletal muscle mitochondrial respiration in rats.

We investigated in rats the effect of 4 wk of hypodynamia on the respiration of mitochondria isolated from four distinct muscles [soleus, extensor digitorum longus, tibial anterior, and gastrocnemius (Gas)] and from subsarcolemmal (SS) and intermyofibrillar (IMF) regions of mixed hindlimb muscles that mainly contained the four cited muscles. With pyruvate plus malate as respiratory substrate, 4 wk of hindlimb suspension produced an 18% decrease in state 3 respiration for IMF mitochondria compared with those in the control group (P < 0.05). The SS mitochondria state 3 were not significantly changed. Concerning the four single muscles, the mitochondrial respiration was significantly decreased in the Gas muscle, which showed a 59% decrease in state 3 with pyruvate + malate (P < 0.05). The other muscles presented no significant decrease in respiratory rate in comparison with the control group. With succinate + rotenone, there was no significant difference in the respiratory rate compared with the respective control group, whatever the mitochondrial origin (SS, or IMF, or from single muscle). We conclude that 4 wk of hindlimb suspension alters the respiration of IMF mitochondria in hindlimb skeletal muscles and seems to act negatively on complex I of the electron-transport chain or prior sites. The muscle mitochondria most affected are those isolated from the Gas muscle.

Effect of NaHCO3 on lactate kinetics in forearm muscles during leg exercise in man.

We investigated NaHCO3 infusion effects on plasma lactate removal by forearm muscles and performance during intensive leg exercise. Seven subjects performed the force-velocity (FV) test with placebo and NaHCO3 (2 mEq.min-1) with a double-blind crossover protocol. Blood samples for arterial ([LA]A) and venous ([LA]V) lactate determinations were taken 1) at rest before infusion, and 2, 6, 10, 14, 18, and 22 min following its start; and 2) at the end of each exercise bout. The arteriovenous difference ([LA]A-V) was determined for each sampling. NaHCO3 significantly increased arterial bicarbonate concentration and pH during rest (P < 0.001; P < 0.001) and the FV test (P < 0.001; P < 0.05). During the test, [LA]A and [LA]V were significantly higher with NaHCO3 (P < 0.05, P < 0.001). At test onset, [LA]A-V became positive and increased until the braking force of 6 kg, with NaHCO3 and placebo, with values significantly lower for NaHCO3 (P < 0.001). Peak anaerobic power (Wanae, peak) and the corresponding braking force (Fmax) were also determined. Fmax was significantly increased with NaHCO3 (P < 0.001). In conclusion, the increasing rise in [LA]A and [LA]V induced by NaHCO3 may be partly explained by a decreased rate of lactate uptake by forearm skeletal muscles. NaHCO3 did not improve Wanae, peak, but improved Fmax, thus increasing FV duration.

Cyclosporine A decreases rat skeletal muscle mitochondrial respiration in vitro.

Cyclosporine A (CsA) is a potent immunosuppressant used to decrease organ rejection after transplantation surgery. Reported limitations to use of CsA have been hepatotoxicity and nephrotoxicity. Additionally, exercise capacity is much less than expected following transplantation even if arterial oxygen transport capacity is repaired. Purposes of the present study were to determine the effects of CsA on skeletal muscle mitochondrial respiration in vitro and to determine the site of the CsA skeletal muscle mitochondrial lesion. Mitochondria were isolated from rat hind limb muscle homogenates after differential centrifugation. Mitochondrial respiration was determined using a Rank oxygen polarograph at 37 degrees C in a sucrose and mannitol respiration medium. CsA inhibited maximal respiration (ADP stimulated) in the presence of succinate and rotenone by 18.3% and in the presence of malate and pyruvate by 34.7%. CsA decreased the rate of uncoupled respiration (addition of carbonyl cyanide p-trifluoromethozyphenylhydrazone) by 19.6% and 32.0% for succinate and rotenone, or pyruvate plus malate, respectively. No significant effect of CsA on ADP/O for either substrate was observed. We conclude that CsA inhibits maximal coupled and uncoupled skeletal muscle mitochondrial respiration in vitro. Moreover, although the effects of CsA were greater on electron flux through Complex I, mitochondrial lesions caused by CsA were not specific to either Complex I or Complex II of the electron transport chain (ETC). Poor exercise performance despite adequate arterial oxygenation and systemic and regional oxygen deliveries in transplant patients may be attributed, in part, to the effects of immunosuppressive therapy on ETC capacity of skeletal muscle mitochondria.

Effects of cyclosporine A on skeletal muscle mitochondrial respiration and endurance time in rats.

We investigated the effects of 14 d of cyclosporine A (CsA) administration on skeletal muscle mitochondrial respiration and submaximal running endurance time in rats. Eight experimental (CsA) and eight control rats followed a 14-d feeding protocol of CsA (20 mg/kg/d) oral administration or placebo. Submaximal endurance exercise time (EET) was measured on a treadmill on Day 13 and mitochondria were isolated from the hind limb muscles homogenate on Day 15. The results showed (1) a significant decrease of EET in CsA versus control rats (29 +/- 8 min versus 60 +/- min, p < 0.001), (2) significantly lower state 3 and uncoupled mitochondrial respiration in CsA compared with control rats with pyruvate plus malate (p < 0.001, p < 0.01) as well as succinate plus rotenone (p < 0.01) as substrates, (3) no differences in coupling efficiency (ADP/O ratios), and (4) significant linear correlation between EET and state 3 respiration (r = 0.71, p < 0.05; r = 0.92, p < 0.001), and strong curvilinear relationship between EET and CsA state 3/mean control state 3 (r2 = 0.81, p < 0.001; r2 = 0.82, p < 0.001), respectively, with pyruvate plus malate and succinate plus rotenone. We conclude that 14 d of CsA oral administration decreases skeletal muscle mitochondrial electron chain capacity without changing coupling efficiency in rats. Results suggest that immunosuppressive therapy is responsible, in part, for poor exercise performance in transplant patients.

Individualized aerobic and high intensity training for asthmatic children in an exercise readaptation program. Is training always helpful for better adaptation to exercise?

In order to define the role of individualized training intensity in a conditioning program for asthmatic children, we have trained seven asthmatics (age = 11.4 +/- 1.8 years) at their ventilatory threshold (VTh) intensity level for a three-month period (aerobic training) and at maximal intensity also for three months (high intensity training). VTh is the point at which a nonlinear increase of VE occurs. Another group of seven asthmatics (age = 11.4 +/- 1.5) served as control subjects. Cardiopulmonary fitness was determined on a cycle ergometer before and after each training session. This study demonstrated that aerobic training, correctly adapted to the child's physical ability, induces the following: (1) a rapid and marked cardiovascular fitness increase; and (2) a decrease in VE over a given work range so that VTh is increased. This is of great importance because hyperventilation is a major determinant of exercise-induced bronchospasm. In contrast, even if high intensity training is well tolerated in an indoor swimming pool, the long-term effects are unsuitable for asthmatic children because the decrease of VTh will involve an increase of hyperventilation, even when exercise is performed at submaximal intensity.

Ventilatory control during exercise in children with mild or moderate asthma.

The aim of this study was to specify whether during exercise the neural response to increased resistive load in asthmatic children corresponds to a modification of the neuromuscular inspiratory drive, to a modification of the breathing pattern, or to both. Thus, nine children with mild or moderate asthma (aged 10-15 yr) and nine normal children (aged 11-16 yr) were studied during an incremental load exercise with a cyclic ergometer, the load of which was increased by steps of 30 W.3 min-1. During the 3rd min of each workload, we measured the following parameters: O2 consumption (VO2), CO2 production (VCO2), ventilation (VE), tidal volume (VT), respiratory frequency (f), ratio of inspiratory to total time of respiratory cycle (T1/TTOT), mean inspiratory flow (VT/T1) as well as mouth occlusion pressure measured at 100 ms (P0.1), and inspiratory power for breathing (W). At maximum level, the two groups showed identical values for heart rate, ventilation divided by weight (VEBW), T1/TTOT), VT/T1, P0.1, and W. However, asthmatic children had lower maximal power (P less than 0.02), higher tidal volume divided by weight (VTBW) (P less than 0.05), and lower f (P less than 0.01). At a same level of exercise (60, 90, or 120 W), in both groups, we found identical values for P0.1, VEBW, VO2, T1/TTOT, and VTBW/T1. However, asthmatic patients exhibited higher VTBW and lower f(limit of significance). This resulted from higher inspiratory and total time durations. Furthermore, they showed a higher inspiratory power for breathing. It was the same for f and VTBW if the results were expressed in relation to the VO2 in ml.kg-1.(ABSTRACT TRUNCATED AT 250 WORDS)