[Evaluation of the management of COPD exacerbations: an audit in French emergency services]. / Prise en charge des exacerbations de BPCO : audit de pratique aux urgences.

INTRODUCTION: Acute exacerbations of chronic obstructive pulmonary disease (COPD) patients are major events in the history of this chronic respiratory disease. Their management in French emergency services is unknown, although national guidelines exist. METHODS: This is a descriptive audit study, over a 10 weeks period (12/01-22/03/2009), of the management of COPD exacerbations in the RESUVal (Réseau des Urgences de la Vallée du Rhône, France) network emergency departments. RESULTS: The enrollement of 16 emergency units allowed the analysis of 221 exacerbations of COPD. Measurement of respiratory rate and description of the sputum were mentioned in only 99 (45%) medical records. The rest of the initial assessment was generally satisfactory. Regarding the therapeutic management, 215 (97%) patients received oxygen, beta-2-agonist aerosols were administrated for 209 (95%) patients and anticholinergic aerosols were used for 176 (80%) patients. A systemic corticosteroid and antibiotics were respectively prescribed for 116 (52%) and 123 (56%) patients. Non-invasive ventilation (NIV) was used in only 59% of patients presenting a pH<7.35. CONCLUSIONS: These findings demonstrate that management of exacerbations of COPD could be improved through systematic patients' respiratory rate and sputum characteristics recording or NIV utilization reinforcement.

Effect of food restriction on lactate sarcolemmal transport.

The objective of this study was to investigate the effects of 6 weeks of food restriction (FR) on sarcolemmal lactate transport in rats. The daily food consumption of rats was monitored for 10 days, after which they were assigned to either a control group (CTL, n = 7) that consumed food ad libitum or an FR group (n = 7) that received a daily ration equal to 60% of their predetermined baseline food intake. After the 6-week period, we observed in red gastrocnemius (RG) a fall of 48% in glycogen content (P <.01) and a reduction in glutathione peroxidase activity (P <.05), confirming that the FR program was well executed. FR resulted in a reduction in muscle lactate (P <.05) and liver glycogen contents (P <.01). Moreover, hyperlactatemia was noted in the FR group: 1.77 +/- 0.24 versus 2.67 +/- 0.29 mmol/L (P <.05). Lactate transport capacity was significantly increased (P <.05) in FR rats, although monocarboxylate transporter isoforms (MCT1 and MCT4) did not change significantly. We conclude that FR alters sarcolemmal lactate transport activity without affecting MCT1 and MCT4 expression.

Streptozotocin-induced diabetes decreases rat sarcolemmal lactate transport.

Impaired lactate metabolism is a metabolic disorder, which is not fully understood in the diabetic state including streptozotocin (STZ)-induced diabetes. We investigated whether STZ-induced diabetes results in altered lactate exchanges using the rat muscle sarcolemmal vesicles (SV) model. Fifteen days after diabetes onset (1 STZ-injection, 65 mg/kg, intraperitoneal [IP]), rats had higher blood and muscle lactate concentrations compared with normal rats (1.50 +/- 0.09 v 1.95 +/- 0.21 mmol/L (not significant [NS]) and 21.02 +/- 1.26 v 25.53 +/- 0.98 mmol/kg wet weight (ww); P < .05). The initial rate of lactate uptake was measured at various external lactate concentrations using SV of both group in zero-trans conditions. STZ-induced diabetes decreased the initial rate of total lactate influx at external lactate concentrations from 1 to 100 mmol/L (P < .05). This decrease in lactate transport was found in addition to an increased free radical production, as indicated by a significant increase in malonedialdehyde (MDA) concentration (64.3 +/- 8.7 v 100.3 +/- 13.5 nmol. g(-1) ww, P < .05), coupled with a higher glutathione peroxidase (Gpx) activity (48.03 +/- 3.13 v 84.7 +/- 15.01 micromol. min(-1). mg(-1) protein, P < .05) in red gastrocnemius. We concluded that STZ-induced diabetes decreases total lactate transport activity in rat SV and is associated with increased muscular oxidative stress.

Lactate transport in rat sarcolemmal vesicles after a single bout of submaximal exercise.

We investigated the effects of a single bout of non-exhaustive exercise (25 m x min(-1), 10% grade, for 30 min) on the initial rates of lactate uptake in rat skeletal muscle sarcolemmal vesicles and the monocarboxylate transporter 1 (MCT1) content in isolated hindlimb muscles in relation to the exercise-induced oxidative stress. The exercise led to a decrease in red gastrocnemius and red vastus lateralis muscle glycogen content by 74% and 83%, respectively, and an increase in blood lactate concentration from 1.67 +/- 0.15 to 3.44 +/- 0.47 mM (p < 0.05). Initial rates of lactate uptake were measured in zero-trans conditions, at pH 7.4, for 1, 10, 30 and 100 mM external lactate concentrations. Lactate transport capacity was significantly decreased at 1 mM in the exercised group (p < 0.05), while a non-significant trend towards an increase was observed at 10, 30 and 100 mM. We failed to obtain any change in soleus, red tibialis anterior and white gastrocnemius muscle MCT1 content (p>0.05), and no evidence of exercise-induced oxidative stress in terms of muscle malondialdehyde content and glutathione peroxidase and superoxide dismutase activities was observed after the 30 min exercise bout. These results indicate that a single bout of submaximal exercise, which did not induce an increase in muscle MCT1 content and apparent oxidative stress, decreased lactate transport capacity at low physiological concentration. Although the changes are small and independent of a MCT1-facilitated lactate transport regulation, we suggest that another MCT isoform with different kinetic properties from MCT1 could be present in the sarcolemma and responsible for lactate exchange alterations.

Training does not protect against exhaustive exercise-induced lactate transport capacity alterations.

The effects of endurance training on lactate transport capacity remain controversial. This study examined whether endurance training 1) alters lactate transport capacity, 2) can protect against exhaustive exercise-induced lactate transport alteration, and 3) can modify heart and oxidative muscle monocarboxylate transporter 1 (MCT1) content. Forty male Wistar rats were divided into control (C), trained (T), exhaustively exercised (E), and trained and exercised (TE) groups. Rats in the T and TE groups ran on a treadmill (1 h/day, 5 days/wk at 25 m/min, 10% incline) for 5 wk; C and E were familiarized with the exercise task for 5 min/day. Before being killed, E and TE rats underwent exhaustive exercise (25 m/min, 10% grade), which lasted 80 and 204 min, respectively (P < 0.05). Although lactate transport measurements (zero-trans) did not differ between groups C and T, both E and TE groups presented an apparent loss of protein saturation properties. In the trained groups, MCT1 content increased in soleus (+28% for T and +26% for TE; P < 0.05) and heart muscle (+36% for T and +33% for TE; P < 0.05). Moreover, despite the metabolic adaptations typically observed after endurance training, we also noted increased lipid peroxidation byproducts after exhaustive exercise. We concluded that 1) endurance training does not alter lactate transport capacity, 2) exhaustive exercise-induced lactate transport alteration is not prevented by training despite increased MCT1 content, and 3) exercise-induced oxidative stress may enhance the passive diffusion responsible for the apparent loss of saturation properties, possibly masking lactate transport regulation.

Lactate transport activity in rat skeletal muscle sarcolemmal vesicles after acute exhaustive exercise.

The effect of a single bout of exhaustive exercise on muscle lactate transport capacity was studied in rat skeletal muscle sarcolemmal (SL) vesicles. Rats were assigned to a control (C) group (n = 14) or an acutely exercised (E) group (n = 20). Exercise consisted of treadmill running (25 m/min, 10% grade) to exhaustion. SL vesicles purified from C and E rats were sealed because of sensitivity to osmotic forces. The time course of 1 mM lactate uptake in zero-trans conditions showed that the equilibrium level in the E group was significantly lower than in the C group (P < 0.05). The initial rate of 1 mM lactate uptake decreased significantly from 2.44 +/- 0.22 to 1.03 +/- 0.08 nmol. min(-1). mg protein(-1) (P < 0.05) after exercise, whereas that of 50 mM lactate uptake did not differ significantly between the two groups. For 100 mM external lactate concentration ([lactate]), exhaustive exercise increased initial rates of lactate uptake (219.6 +/- 36.3 to 465.4 +/- 80.2 nmol. min(-1). mg protein(-1), P < 0.05). Although saturation kinetics were observed in the C group with a maximal transport velocity of 233 nmol. min(-1). mg protein(-1) and a Michealis-Menten constant of 24.5 mM, saturation properties were not seen after exhaustive exercise in the E group, because initial rates of lactate uptake increased linearly with external [lactate]. We conclude that a single bout of exhaustive exercise significantly modified SL lactate transport activity, resulting in a decrease in 1 mM lactate uptake and was associated with alterations in the saturable properties at [lactate] above 50 mM. These results suggest that changes in sarcolemmal lactate transport activity may alter lactate and proton exchanges after exhaustive exercise.

Antioxidants and mitochondrial respiration in lung, diaphragm, and locomotor muscles: effect of exercise.

Previous studies have shown that exhaustive exercise may increase reactive oxygen species (ROS) generation in oxidative muscles that may in turn impair mitochondrial respiration. Locomotor muscles have been extensively examined, but there is few report about diaphragm or lung. The later is a privileged site for oxygen transit. To compare the antioxidant defense system and mitochondrial function in lung, diaphragm and locomotor muscles after exercise, 24 young adult male rats were randomly assigned to a control (C) or exercise (E) group. E group rats performed an exhaustive running test on a motorized treadmill at 80-85% VO2max Mean exercise duration was 66+/-2.7 min. Lung, costal diaphragm, mixed gastrocnemius, and oxidative muscles (red gastrocnemius and soleus: RG/SOL homogenate) were sampled. Mitochondrial respiration was assessed in tissue homogenates by respiratory control index (RCI: rate of uncoupled respiration/rate of basal respiration) measurement. Lipid peroxidation was evaluated by malondialdehyde concentration (MDA) and we determined the activity of two antioxidant enzymes: superoxide dismutase (SOD) and glutathione peroxidase (GPX). We found elevated basal (C group data) SOD and GPX activities in both lung and diaphragm compared to locomotor muscles (p<.001). Exercise led to a rise in GPX activity in red locomotor muscles homogenate (GR/SOL; C = 10.3+/-0.29 and E = 14.4+/-1.51 micromol x min(-1) x gww(-1); p<.05), whereas there was no significant change in lung and diaphragm. MDA concentration and mitochondrial RCI values were not significantly changed after exercise. We conclude that lung and diaphragm had higher antioxidant protection than locomotor muscles. The exercise test did not lead to significant oxidative stress or alteration in mitochondrial respiration, suggesting that antioxidant function was adequate in both lung and diaphragm in the experimental condition.

Effect of 2-chloropropionate on initial lactate uptake by rat skeletal muscle sarcolemmal vesicles.

2-Chloropropionate (2-CP) is a halogenated monocarboxylic acid generally used to decrease blood lactate concentration in various metabolic states. To investigate whether it has an inhibitory effect on sarcolemmal lactate transport, we compared the initial rate of lactate transport in sarcolemmal membrane vesicles purified from 20 male Wistar rats with and without 2-CP. Transport by these vesicles was measured as uptake of L-(+)-[U-14C]lactate under pH gradient-stimulated cis inhibition. The time courses of 1 mM L-(+)-lactate uptake into vesicles both with and without 10 mM 2-CP (L- or D-) displayed saturation kinetics. Lactate uptake values were lower with 10 mM L-2-CP and 10 mM D-2-CP in comparison to the control values. Both 10 mM L-2-CP and 10 mM D-2-CP significantly inhibited 1 mM L-(+)-lactate uptake (55.8 +/- 9.1 and 53.5 +/- 12.1%, respectively; P < 0.001), whereas a smaller inhibition was observed with a higher lactate concentration of 50 mM (40.2 +/- 11.2 and 38.7 +/- 12.4%; P < 0.001 and P < 0.05, respectively). However, a higher D-2-CP concentration (50 mM) increased the inhibition of pH-stimulated 1 mM L-(+)-lactate uptake (77.0 +/- 9.4%; P < 0.001). D-2-CP had a trans-stimulation effect on the initial rate of lactate efflux of 1 mM L-(+)-lactate compared with baseline efflux (9.5 +/- 0.8 vs. 5.1 +/- 0.4 nmol.min-1.mg protein-1; P < 0.05). 2-CP significantly inhibited the initial rate of lactate uptake in skeletal muscle sarcolemmal membrane vesicles. This result suggests that 2-CP is a nonstereoselective substrate of the lactate muscle carrier that impairs lactate transport.