Moderate- and high-intensity exhaustive exercise in the heat induce a similar increase in monocyte Hsp72.

This study examined the relationship between exhaustive exercise in the heat at moderate and high intensities on the intracellular heat shock protein 72 (iHsp72) response. Twelve male subjects cycled to exhaustion at 60 and 75% of maximal oxygen uptake in hot conditions (40 °C, 50% RH). iHsp72 concentration was measured in monocytes before, at exhaustion and 24 h after exercise. Rectal temperature, heart rate and oxygen uptake were recorded during exercise. Volitional exhaustion occurred at 58.9 ± 12.1 and 27.3 ± 9.5 min (P < 0.001) and a rectal temperature of 39.8 ± 0.4 and 39.2 ± 0.6 °C (P = 0.002), respectively, for 60 and 75 %. The area under the curve above a rectal temperature of 38.5 °C was greater at 60 % (17.5 ± 6.6 °C min) than 75 % (3.4 ± 4.8 °C min; P < 0.001), whereas the rate of increase in rectal temperature was greater at 75 % (5.1 ± 1.7 vs. 2.2 ± 1.4 °C h(-1); P < 0.001). iHsp72 concentration increased similarly at exhaustion relative to pre-exercise (P = 0.044) and then increased further at 24 h (P < 0.001). Multiple regression analysis revealed no predictor variables associated with iHsp72 expression; however, a correlation was observed between exercise intensities for the increase in iHsp expression at exhaustion and 24 h (P < 0.05). These results suggest that iHsp72 expression increased in relation to the level of hyperthermia attained and sustained at 60 % and the higher metabolic rate and greater rate of increase in core temperature at 75 %, with the further increase in iHsp72 concentration 24 h after exercise reinforcing its role as a chaperone and cytoprotective agent.

Effects of type 1 diabetes, sprint training and sex on skeletal muscle sarcoplasmic reticulum Ca2+ uptake and Ca2+-ATPase activity.

Calcium cycling is integral to muscle performance during the rapid muscle contraction and relaxation of high-intensity exercise. Ca(2+) handling is altered by diabetes mellitus, but has not previously been investigated in human skeletal muscle. We investigated effects of high-intensity exercise and sprint training on skeletal muscle Ca(2+) regulation among men and women with type 1 diabetes (T1D, n = 8, 3F, 5M) and matched non-diabetic controls (CON, n = 8, 3F, 5M). Secondarily, we examined sex differences in Ca(2+) regulation. Subjects undertook 7 weeks of three times-weekly cycle sprint training. Before and after training, performance was measured, and blood and muscle were sampled at rest and after high-intensity exercise. In T1D, higher Ca(2+)-ATPase activity (+28%) and Ca(2+) uptake (+21%) than in CON were evident across both times and days (P < 0.05), but performance was similar. In T1D, resting Ca(2+)-ATPase activity correlated with work performed until exhaustion (r = 0.7, P < 0.01). Ca(2+)-ATPase activity, but not Ca(2+) uptake, was lower (-24%, P < 0.05) among the women across both times and days. Intense exercise did not alter Ca(2+)-ATPase activity in T1D or CON. However, sex differences were evident: Ca(2+)-ATPase was reduced with exercise among men but increased among women across both days (time × sex interaction, P < 0.05). Sprint training reduced Ca(2+)-ATPase (-8%, P < 0.05), but not Ca(2+) uptake, in T1D and CON. In summary, skeletal muscle Ca(2+) resequestration capacity was increased in T1D, but performance was not greater than CON. Sprint training reduced Ca(2+)-ATPase in T1D and CON. Sex differences in Ca(2+)-ATPase activity were evident and may be linked with fibre type proportion differences.

Heat exposure does not alter eccentric exercise-induced increases in mitochondrial calcium and respiratory dysfunction.

Eccentric exercise can lead to muscle damage including dramatic changes to mitochondrial calcium content (MCC) and impaired respiratory function. Heat acclimation can create a cross-tolerance to a number of stresses including eccentric exercise but little is known about any protection to mitochondria. We hypothesised that intermittent heat exposure will lead to improved control of MCC and to preserved mitochondrial function following eccentric exercise. Sprague-Dawley rats were exposed to 3 weeks of intermittent heat exposure (36°C, 40% relative humidity, 6 h/day, 5 days a week) or kept in cool conditions (20°C). Animals were then assigned to a control or exercise group (-14°C decline treadmill exercise for 90 min). MCC, mitochondrial respiration and mitochondrial permeability transition pore opening (mPTP) were measured in mitochondria isolated from the red quadriceps in animals killed immediately, 2 h and 48 h post-exercise. Results showed that heat exposure was associated with lower plasma creatine kinase levels (p < 0.05) post-exercise suggesting lower levels of muscle damage. There was a significant (~500%) rise in MCC (p < 0.001) and a reduction in mitochondrial respiratory control ratio (p < 0.001) 48 h post-exercise. mPTP displayed increased (p < 0.05) sensitivity to calcium immediately and 48 h post-exercise. Thus, decline running led to significant impairment of mitochondria respiration and calcium loading which was more pronounced 48 h post-exercise compared with earlier time points. MCC levels and mitochondrial function were not altered by heat exposure. In conclusion, intermittent heat exposure does not appear to provide protection against mitochondrial dysfunction resulting from eccentric exercise.

Creatine supplementation does not enhance submaximal aerobic training adaptations in healthy young men and women.

The benefits of dietary creatine supplementation on muscle performance are generally related to an increase in muscle phosphocreatine content. However, creatine supplementation may benefit endurance sports through increased glycogen re-synthesis following exercise. This study investigated the effect of creatine supplementation on muscle glycogen content, submaximal exercise fuel utilisation and endurance performance following 4 weeks of endurance training. Thirteen healthy, physically active, non-vegetarian subjects volunteered to take part and completed the study. Subjects were supplemented with either creatine monohydrate (CREAT, n = 7) or placebo-maltodextrin (CON, n = 6). Submaximal fuel utilisation and endurance performance were assessed before and after a 4 week endurance training program. Muscle biopsies were also collected before and following training for assessment of muscle creatine and glycogen content. Training increased quadriceps glycogen content to the same degree (approximately 20%) in both groups (P = 0.04). There was a significant training effect on submaximal fuel utilisation and improved endurance performance. However, there was no significant treatment effect of creatine supplementation. Creatine supplementation does not effect metabolic adaptations to endurance training.

Plasma Hsp72 is higher in runners with more serious symptoms of exertional heat illness.

Exertional heat illness is a potentially fatal disorder that primarily affects fit young men. Plasma Hsp72 may be important in the aetiology of this disorder, acting as a danger signal to the organism and leading to an inflammatory response. The aim of this study was to determine whether patients with exertional heat illness following a 14 km run show a difference in their plasma Hsp72 concentration compared with control subjects who completed the event without incident. Patients (n = 22) and controls (n = 7) were all male. The patients were subdivided into two groups, one of which exhibited more serious symptoms indicating neurological impairment such as confusion (n = 13) (CNS) while the other group exhibited mild symptoms (MILD) (n = 9). The CNS group had a higher rectal temperature (T(rec)) compared with the control group (41.0 +/- 0.3 vs. 39.8 +/- 0.2 degrees C, P < 0.05, mean +/- SE). Immediately after the run plasma Hsp72 was higher in the CNS group compared to controls and patients with mild symptoms (37.9, 17.0, and 20.9 ng/ml, respectively, P < 0.005). There was a correlation between plasma Hsp72 and T(rec) measured immediately after the race (r = 0.597, P < 0.001, n = 29). However, core temperature was not the only factor leading to increased plasma Hsp72 immediately post race. Plasma Hsp72 was still higher in CNS patients compared with the control group (P < 0.05) when T(rec )was included as a covariate. In conclusion, plasma Hsp72 was elevated immediately after a 14 km run with higher levels in patients with more serious symptoms of heat illness.

Effect of temperature and duration of hyperthermia on HSP72 induction in rat tissues.

The aim of the present study was to determine whether heat shock protein 72 (HSP72) is induced in a heated rat model at rectal temperatures below 42 degrees C. Rats were divided into a control group and six groups (n = 6) heated to different rectal temperatures: 39 degrees C for 1 h (39), 40.0 degrees C for either 15 min (40S) or 1 h (40L), 41.0 degrees C for either 15 min (41S) or 1 h (41L) and 42.0 degrees C for 15 min (42). Tissues were sampled 4 h after heating. Following 1 h at 40.0 degrees C, HSP72 was significantly elevated in heart (p < 0.005), but not in gut or liver tissue. In all three tissues, HSP72 was significantly elevated under the conditions 41L and 42 compared to control tissue (p < 0.005). Marked differences were found in the amount of HSP72 induced in different tissues in response to the same heat stress. Duration of heating was important in modulating HSP72 induction, with a significantly greater induction of HSP72 following 1 h compared to 15 min at 41 degrees C in all three tissues (p < 0.02). A correlation was found between thermal load and HSP72 content in liver, heart (both p < 0.01) and gut (p < 0.001) for the rats heated to 41 and 42 degrees C. These data show that HSP72 is induced at temperatures below 42 degrees C, with striking differences between tissues.

Effect of 10-day cast immobilization on sarcoplasmic reticulum calcium regulation in humans.

This study investigated the effects of 10-day lower limb cast immobilization on sarcoplasmic reticulum (SR) Ca2+ regulation. Muscle biopsies were analysed in eight healthy females for maximal rates of SR Ca2+ release, Ca2+ uptake and Ca2+ ATPase activity at control, during immobilization at day 3 (IM 3), day 6 (IM 6) and day 10 (IM 10). Quadriceps muscle cross-sectional area (CSA) and 1-repetition maximum (1RM) leg extension strength were measured to determine the extent of muscle size and strength adaptations. Muscle CSA and strength decreased following 10 days of immobilization (11.8 and 41.6%, respectively, P < 0.01). A decrease in SR Ca2+ uptake rate (analysed per g wet wt) was found at IM 3 (13.2%, P=0.05), with a further decrease at IM 10 (19.8% from control, P < 0.01). At IM 10, a decrease in SR Ca2+ uptake rate (per mg protein) also occurred (19.9%, P < 0.01). Sarcoplasmic reticulum Ca2+ ATPase activity and rate of Ca2+ release were not altered with 10 days of immobilization. This study observed a decrease in SR Ca2+ uptake rate, muscular atrophy and strength loss over 10 days of immobilization in humans.

Sarcoplasmic reticulum function and muscle contractile character following fatiguing exercise in humans.

1. This study examined the alterations in calcium release, calcium uptake and calcium ATPase activity of skeletal muscle sarcoplasmic reticulum in response to a bout of intense dynamic knee extensor exercise, and the relationship between these changes and alterations in muscle contractile characteristics in the human quadriceps. 2. In biopsy samples taken from the vastus lateralis, sarcoplasmic reticulum calcium release and calcium uptake were significantly depressed (P < 0.01 and 0.05, respectively) immediately following the exercise with no alteration in the sarcoplasmic reticulum Ca2+-ATPase activity. 3. A 33 % reduction in the maximum voluntary isometric torque was found following the exercise, with reduced torques from electrically evoked isometric contractions at low frequencies of stimulation (10 and 20 Hz) but not at higher frequencies (50 and 100 Hz). 4. The depressed calcium release was correlated (P < 0.05) with a decreased ratio of torques generated at 20:50 Hz, indicating an involvement in low frequency fatigue; however, no correlations between the muscle relaxation times or rates of change of torque and calcium uptake were observed.

The influence of menstrual cycle phase on skeletal muscle contractile characteristics in humans.

The influence of the different phases of the menstrual cycle on skeletal muscle contractile characteristics was studied in 19 regularly menstruating women. Muscle function was measured when (i) oestrogen and progesterone concentrations were low (menstruation), (ii) oestrogen was elevated and progesterone was low (late follicular phase), and (iii) oestrogen and progesterone were both elevated (luteal phase).Maximal isometric quadriceps strength, fatiguability and electrically stimulated contractile properties were measured. Isokinetic knee flexion and extension strength and fatiguability were also assessed as well as handgrip strength. Menstrual cycle phases were confirmed through measurement of oestrogen, progesterone, follicle stimulating hormone and luteinising hormone. No significant changes were found in any of the muscle function parameters throughout the menstrual cycle (n = 15). The muscle function measurements showed no significant correlations with any of the female reproductive hormone concentrations. These results suggest that the fluctuations in female reproductive hormone concentrations throughout the menstrual cycle do not affect muscle contractile characteristics.

Skeletal muscle metabolic and ionic adaptations during intense exercise following sprint training in humans.

The effects of sprint training on muscle metabolism and ion regulation during intense exercise remain controversial. We employed a rigorous methodological approach, contrasting these responses during exercise to exhaustion and during identical work before and after training. Seven untrained men undertook 7 wk of sprint training. Subjects cycled to exhaustion at 130% pretraining peak oxygen uptake before (PreExh) and after training (PostExh), as well as performing another posttraining test identical to PreExh (PostMatch). Biopsies were taken at rest and immediately postexercise. After training in PostMatch, muscle and plasma lactate (Lac(-)) and H(+) concentrations, anaerobic ATP production rate, glycogen and ATP degradation, IMP accumulation, and peak plasma K(+) and norepinephrine concentrations were reduced (P<0.05). In PostExh, time to exhaustion was 21% greater than PreExh (P<0.001); however, muscle Lac(-) accumulation was unchanged; muscle H(+) concentration, ATP degradation, IMP accumulation, and anaerobic ATP production rate were reduced; and plasma Lac(-), norepinephrine, and H(+) concentrations were higher (P<0.05). Sprint training resulted in reduced anaerobic ATP generation during intense exercise, suggesting that aerobic metabolism was enhanced, which may allow increased time to fatigue.

Human skeletal sarcoplasmic reticulum Ca2+ uptake and muscle function with aging and strength training.

This study investigated the adaptations of skeletal muscle sarcoplasmic reticulum (SR) Ca2+ uptake, relaxation, and fiber types in young (YW) and elderly women (EW) to high-resistance training. Seventeen YW (18-32 yr) and 11 EW (64-79 yr) were assessed for 1) electrically evoked relaxation time and rate of the quadriceps femoris; and 2) maximal rates of SR Ca2+ uptake and Ca2+-ATPase activity and relative fiber-type areas, analyzed from muscle biopsies of the vastus lateralis. EW had significantly slower relaxation rates and times, decreased SR Ca2+ uptake and Ca2+-ATPase activity, and a larger relative type I fiber area than did YW. A subgroup of 9 young (YWT) and 10 elderly women (EWT) performed 12 wk of high-resistance training (8 repetition maximum) of the quadriceps and underwent identical testing procedures pre- and posttraining. EWT significantly increased their SR Ca2+ uptake and Ca2+-ATPase activity in response to training but showed no alterations in speed of relaxation or relative fiber-type areas. In YWT none of the variables was altered after resistance training. These findings suggest that 1) a reduced SR Ca2+ uptake in skeletal muscle of elderly women was partially reversed with resistance training and 2) SR Ca2+ uptake in the vastus lateralis was not the rate-limiting mechanism for the slowing of relaxation measured from electrically evoked quadriceps muscle of elderly women.

Impaired calcium pump function does not slow relaxation in human skeletal muscle after prolonged exercise.

This study examined the effects of prolonged exercise on human quadriceps muscle contractile function and homogenate sarcoplasmic reticulum Ca2+ uptake and Ca2+-adenosinetriphosphatase activity. Ten untrained men cycled at 75 +/- 2% (SE) peak oxygen consumption until exhaustion. Biopsies were taken from the right vastus lateralis muscle at rest, exhaustion, and 20 and 60 min postexercise. Peak tension and half relaxation time of the left quadriceps muscle were measured during electrically evoked twitch and tetanic contractions and a maximal voluntary isometric contraction at rest, exhaustion, and 10, 20, and 60 min postexercise. At exhaustion, homogenate Ca2+ uptake and Ca2+ adenosinetriphosphatase activity were reduced by 17 +/- 4 and 21 +/- 5%, respectively, and remained depressed after 60 min recovery (P

Measurement of sarcoplasmic reticulum function in mammalian skeletal muscle: technical aspects.

Two recently developed methods for measuring the maximal rate of Ca2+ uptake and Ca2+ ATPase activity (EC 3.1.6.38) in vitro use muscle homogenate rather than isolated sarcoplasmic reticulum (SR). In this study we investigated technical aspects of these assays, including specificity and variability of the assays, the effect of different freezing treatments on maximal Ca2+ uptake and Ca2+ ATPase activity of human and rat muscle homogenate, stability of the homogenate, and the modification of the Ca2+ uptake assay to measure Ag(+)-induced Ca2+ release. Addition of cyclopiazonic acid (20 microM) blocked Ca2+ uptake, demonstrating specificity of the assay. Using frozen muscle homogenate, the inter- and intraassay variation for both assays was less than 9%. Whereas homogenates were stable to freezing for both Ca2+ uptake and Ca2+ ATPase activity, there was a significant (P < 0.05) decrease in activity when muscle was freeze-dried or quickly frozen in small pieces. After 1 h on ice, rat muscle homogenate Ca2+ uptake and Ca2+ ATPase activity had decreased by 6.0% (ns) and 3.6% (P < 0.05), respectively; after 3 h, activity had decreased by 15.3 and 14.7%, respectively (P < 0.01). The Ca2+ uptake assay was modified to allow measurement of Ag(+)-induced Ca2+ release. Following homogenate addition, after the SR vesicles were loaded with Ca2+ and [Ca2+] had declined to a plateau, AgNO3 (141 microM) was added, initiating release of Ca2+ into the assay solution. Addition of dithiothreitol (4 mM) blocked the Ag(+)-induced Ca2+ release, demonstrating specificity of the assay.

Intermittent claudication. The effect of physical training on walking tolerance and venous lactate concentration.

Twenty-one patients with intermittent claudication underwent a physical exercise program lasting 8 weeks. The patients were classified on the basis of maximal walking tolerance (MWT) and diagnosis at the initial examination. Seven of the patients had a MWT less than 1,000 m and no symptoms of chronic obstructive airways disease (COAD) or angina (group A), seven had a MWT less than 1,000 m plus angina and/or COAD (group B) and seven had an unlimited (greater than 1,250 m) MWT (group C). At the completion of the training program all three groups showed a significant improvement in walking distance to pain and stress test capacity. During the post-training walking tolerance test, the venous lactate concentrations in group A were lower after 2 min and 4 min of exercise, and at exhaustion (P less than 0.05). Group A patients showed a significant correlation between an increase in MWT after training and a decrease in maximum lactate concentration measured during walking. Although the patients in group B had a significant increase in MWT, blood lactate concentrations in this group were not always decreased by physical training. Group C lactate concentrations were lower after 8 min, 15 min, and 30 min of walking (P less than 0.05). It is concluded that a physical training program increases walking tolerance in different categories of claudicants, and possible mechanisms for the improvement are discussed.