Regenerative defect in vastus lateralis muscle of patients with chronic obstructive pulmonary disease.

BACKGROUND: Impaired skeletal muscle regeneration could contribute to the progression of muscle atrophy in patients with chronic obstructive pulmonary disease (COPD). METHODS: Satellite cells and myogenesis-related proteins were compared between healthy subjects and patients with COPD, with or without muscle atrophy. Satellite cells were isolated and cultured to assess their proliferative and differentiation aptitudes. RESULTS: Although satellite cell numbers in muscle samples were similar between groups, the proportion of muscle fibers with central nuclei was increased in COPD. In muscle homogenates, increased expression of MyoD and decreased expression of myogenin and MRF4 were observed in COPD. In cultured satellite cells of patients with COPD, increased protein content was observed for Pax7, Myf5 (proliferation phase) and myogenin (differentiation phase) while myosin heavy chain protein content was significantly lower during differentiation. CONCLUSION: In COPD, the number of central nuclei was increased in muscle fibers suggesting a greater number of attempts to regenerate muscle tissue than in healthy subjects. Myogenesis signaling was also altered in muscle homogenates in patients with COPD and there was a profound reduction in the differentiation potential in this population as indicated by a reduced ability to incorporate myosin heavy chain into newly formed myotubes. Collectively, these results indicate that skeletal muscle regenerative capacity termination is impaired in COPD and could contribute to the progression of muscle atrophy progression in this population.

Preserved function and reduced angiogenesis potential of the quadriceps in patients with mild COPD.

BACKGROUND: Little is known about limb muscle abnormalities in mild COPD. Inactivity and systemic inflammation could play a role in the development of limb muscle dysfunction in COPD. The objective of the present study was to characterize quadriceps function, enzymatic activities and morphometry, levels of plasma inflammatory markers and physical activity levels in daily life (PAdl) in patients with mild COPD (GOLD 1). METHODS: Mid-thigh muscle cross-sectional area (MTCSA), quadriceps strength, endurance, fiber-type distribution, capillarity, pro-angiogenesis factors (VEGF-A, angiopoietin I and II) and muscle oxidative capacity were assessed in 37 patients with mild COPD and 19 controls. Systemic inflammatory markers (CRP, IL-6, TNF-α, Fibrinogen, SP-D) and PAdl were assessed. RESULTS: MTCSA, quadriceps strength and endurance were not different between COPD and controls. Capillarity and muscle oxidative capacity were all preserved in mild COPD. Reduced pro-angiogenesis factor mRNA expression was seen in COPD. The level of moderately active intensity (>3 METs) was significantly lower in mild COPD and, in multiple regression analyses, the level of physical activity was a determinant of muscle oxidative capacity and capillarization. No between-group differences were found regarding muscle oxidative stress while circulating IL-6 levels were elevated in mild COPD. CONCLUSIONS: The quadriceps muscle function was preserved in mild COPD although a reduced potential for angiogenesis was found. The reduced level of daily activities and evidence of systemic inflammation in these individuals suggest that these factors precede the development of overt limb muscle dysfunction in COPD.

MAPK signaling in the quadriceps of patients with chronic obstructive pulmonary disease.

Muscle atrophy in chronic obstructive pulmonary disease (COPD) is associated with reduced exercise tolerance, muscle strength, and survival. The molecular mechanisms leading to muscle atrophy in COPD remain elusive. The mitogen-activated protein kinases (MAPKs) such as p38 MAPK and ERK 1/2 can increase levels of MAFbx/Atrogin and MuRF1, which are specifically involved in muscle protein degradation and atrophy. Our aim was to investigate the level of activation of p38 MAPK, ERK 1/2, and JNK in the quadriceps of patients with COPD. A biopsy of the quadriceps was obtained in 18 patients with COPD as well as in 9 healthy controls. We evaluated the phosphorylated as well as total protein levels of p38 MAPK, ERK 1/2, and JNK as well as MAFbx/Atrogin and MuRF1 in these muscle samples. The corresponding mRNA expression was also assessed by RT-PCR. Ratios of phosphorylated to total level of p38 MAPK (P = 0.02) and ERK 1/2 (P = 0.01) were significantly elevated in patients with COPD compared with controls. Moreover, protein levels of MAFbx/Atrogin showed a tendency to be greater in patients with COPD (P = 0.08). mRNA expression of p38 MAPK (P = 0.03), ERK 1/2 (P = 0.02), and MAFbx/Atrogin (P = 0.04) were significantly elevated in patients with COPD. In addition, phosphorylated-to-total p38 MAPK ratio (Pearson's r = -0.45; P < 0.05) and phosphorylated-to-total ERK 1/2 ratio (Pearson's r = -0.47; P < 0.05) were negatively associated with the mid-thigh muscle cross-sectional area. These data support the hypothesis that the MAPKs might play a role in the development of muscle atrophy in COPD.

Quadriceps metabolism during constant workrate cycling exercise in chronic obstructive pulmonary disease.

Impaired resting metabolism in peripheral muscles potentially contributes to exercise intolerance in chronic obstructive pulmonary disease (COPD). This study investigated the cytosolic energy metabolism of the quadriceps, from glycogen degradation to lactate accumulation, in exercising patients with COPD, in comparison to healthy controls. We measured, in 12 patients with COPD and 10 control subjects, resting and post-cycling exercise quadriceps levels of 1) energy substrates and end products of glycolysis (glycogen, glucose, pyruvate, and lactate) and intermediate markers of glycolysis (glucose-6-phosphate, glucose-1-phosphate, fructose-6-phosphate) and 2) the activity of key enzymes involved in the regulation of glycolysis (phosphofructokinase, lactate dehydrogenase). Exercise intensity (P < 0.01), duration (P = 0.049), and total work (P < 0.01) were reduced in patients with COPD. The variations in energy substrates and end products of glycolysis after cycling exercise were of similar magnitude in patients with COPD and controls. Glucose-6-phosphate (P = 0.036) and fructose-6-phosphate (P = 0.042) were significantly elevated in patients with COPD after exercise. Phosphofructokinase (P < 0.01) and lactate dehydrogenase (P = 0.02) activities were greater in COPD. Muscle glycogen utilization (P = 0.022) and lactate accumulation (P = 0.025) per unit of work were greater in COPD. We conclude that cycling exercise induced changes in quadriceps metabolism in patients with COPD that were of similar magnitude to those of healthy controls. These intramuscular events required a much lower exercise work load and time to occur in COPD. Our data suggest a greater reliance on glycolysis during exercise in COPD, which may contribute to exercise intolerance in COPD.

Cold-water immersion and the treatment of hyperthermia: using 38.6°C as a safe rectal temperature cooling limit.

CONTEXT: Cold-water immersion is recommended for the immediate field treatment of exertional heat stroke. However, concerns exist over potential overcooling of hyperthermic individuals during cold-water immersion. OBJECTIVE: To evaluate the recommendation that removing previously hyperthermic individuals from a cold-water bath at a rectal temperature (T(re)) of 38.6°C would attenuate overcooling. DESIGN: Controlled laboratory study. SETTING: University research laboratory. PATIENTS OR OTHER PARTICIPANTS: Participants included 6 men and 4 women (age  =  22 ± 3 years, height  =  172 ± 10 cm, mass  =  67.8 ± 10.7 kg, body fat percentage  =  17.1% ± 4.5%, maximum oxygen consumption  =  59.3 ± 8.7 mL·kg(-1)·min(-1)). INTERVENTION(S): After exercising at an ambient temperature of 40.0°C for 38.5 ± 9.4 minutes, until T(re) reached 39.5°C, participants were immersed in a 2.0°C circulated water bath until T(re) decreased to either 37.5°C or 38.6°C. Subsequently, participants were removed from the water bath and recovered for 20 minutes at an ambient temperature of 25°C. MAIN OUTCOME MEASURE(S): Rectal and esophageal temperatures were measured continuously during the immersion and recovery periods. RESULTS: Because of the experimental design, the overall time of immersion was greater during the 37.5°C trial (16.6 ± 5.7 minutes) than the 38.6°C trial (8.8 ± 2.6 minutes) (t(9)  =  -4.740, P  =  .001). During the recovery period after cold-water immersion, both rectal (F(1,9)  =  50.540, P < .001) and esophageal (F(1,6)  =  20.365, P  =  .007) temperatures remained greater in the 38.6°C trial than in the 37.5°C trial. This was evidenced by low points of 36.47°C ± 0.70°C and 37.19°C ± 0.71°C for rectal temperature (t(9)  =  2.975, P  =  .016) and of 35.67°C ± 1.27°C and 36.72°C ± 0.95°C for esophageal temperature (t(6)  =  3.963, P  =  .007) during the recovery period of the 37.5°C and 38.6°C trials, respectively. CONCLUSIONS: Immersion for approximately 9 minutes to a rectal temperature cooling limit of 38.6°C negated any risk associated with overcooling hyperthermic individuals when they were immersed in 2°C water.

Aural canal, esophageal, and rectal temperatures during exertional heat stress and the subsequent recovery period.

CONTEXT: The measurement of body temperature is crucial for the initial diagnosis of exertional heat injury and for monitoring purposes during a subsequent treatment strategy. However, little information is available about how different measurements of body temperature respond during and after exertional heat stress. OBJECTIVE: To present the temporal responses of aural canal (T(ac)), esophageal (T(es)), and rectal (T(re)) temperatures during 2 different scenarios (S1, S2) involving exertional heat stress and a subsequent recovery period. DESIGN: Randomized controlled trial. SETTING: University research laboratory. PATIENTS OR OTHER PARTICIPANTS: Twenty-four healthy volunteers, with 12 (5 men, 7 women) participating in S1 and 12 (7 men, 5 women) participating in S2. INTERVENTION(S): The participants exercised in the heat (42 degrees C, 30% relative humidity) until they reached a 39.5 degrees C cut-off criterion, which was determined by T(re) in S1 and by T(es) in S2. As such, participants attained different levels of hyperthermia (as determined by T(re)) at the end of exercise. Participants in S1 were subsequently immersed in cold water (2 degrees C) until T(re) reached 37.5 degrees C, and participants in S2 recovered in a temperate environment (30 degrees C, 30% relative humidity) for 60 minutes. MAIN OUTCOME MEASURE(S): We measured T(ac), T(es), and T(re) throughout both scenarios. RESULTS: The T(es) (S1 = 40.19 +/- 0.41 degrees C, S2 = 39.50 +/- 0.02 degrees C) was higher at the end of exercise compared with both T(ac) (S1 = 39.74 +/- 0.42 degrees C, S2 = 38.89 +/- 0.32 degrees C) and T(re) (S1 = 39.41 +/- 0.04 degrees C, S2 = 38.74 +/- 0.28 degrees C) (for both comparisons in each scenario, P < .001). Conversely, T(es) (S1 = 36.26 +/- 0.74 degrees C, S2 = 37.36 +/- 0.34 degrees C) and T(ac) (S1 = 36.48 +/- 1.07 degrees C, S2 = 36.97 +/- 0.38 degrees C) were lower compared with T(re) (S1 = 37.54 +/- 0.04 degrees C, S2 = 37.78 +/- 0.31 degrees C) at the end of both scenarios (for both comparisons in each scenario, P < .001). CONCLUSIONS: We found that T(ac), T(es), and T(re) presented different temporal responses during and after both scenarios of exertional heat stress and a subsequent recovery period. Although these results may not have direct practical implications in the field monitoring and treatment of individuals with exertional heat injury, they do quantify the extent to which these body temperature measurements differ in such scenarios.

Differences between sexes in rectal cooling rates after exercise-induced hyperthermia.

PURPOSE: We evaluated differences between sexes in core cooling rates during cold water immersion after exercise-induced hyperthermia. METHODS: Ten male (M) and nine female (F) participants, matched for body surface area-to-mass ratio (AD/M) (F: 268 +/- 19 vs M: 261 +/- 16 cm2 x kg(-1)), were recruited for the study. Participants exercised until rectal temperature reached 39.5 degrees C and were subsequently immersed in a 2.0 degrees C circulated water bath until rectal temperature decreased to 37.5 degrees C. Rectal and mean skin temperatures and the relative rate of nonevaporative heat loss (W x m(-2)) were measured continuously during the immersion period. RESULTS: Males were heavier, had a lower body fat percentage, and had a greater amount of lean body mass compared with females (P < or = 0.05). Significant differences were found in the overall cooling rate for rectal temperature (F: 0.22 +/- 0.07 vs M: 0.12 +/- 0.03 degrees C x min(-1), P = 0.001) and in the overall immersion times (F: 10.89 +/- 4.49 vs M: 18.13 +/- 4.47 min, P = 0.003). Mean skin temperature was lower in females compared with that in males during the immersion period (P < 0.001), although there were no differences between sexes in the rate of nonevaporative heat loss (P = 0.180). CONCLUSIONS: Although females had a similar AD/M and greater body adiposity, they had approximately 1.7-fold greater rectal cooling rate. Because AD/M and body adiposity do not seem to influence rectal cooling rates in previously hyperthermic individuals, the greater cooling rates in females may be attributed to physical differences in lean body mass.