Central activation, metabolites, and calcium handling during fatigue with repeated maximal isometric contractions in human muscle.

PURPOSE: To determine the roles of calcium (Ca2+) handling by sarcoplasmic reticulum (SR) and central activation impairment (i.e., central fatigue) during fatigue with repeated maximal voluntary isometric contractions (MVC) in human muscles. METHODS: Contractile performance was assessed during 3 min of repeated MVCs (7-s contraction, 3-s rest, n = 17). In ten participants, in vitro SR Ca2+-handling, metabolites, and fibre-type composition were quantified in biopsy samples from quadriceps muscle, along with plasma venous [K+]. In 11 participants, central fatigue was compared using tetanic stimulation superimposed on MVC in quadriceps and adductor pollicis muscles. RESULTS: The decline of peak MVC force with fatigue was similar for both muscles. Fatigue resistance correlated directly with % type I fibre area in quadriceps (r = 0.77, P = 0.009). The maximal rate of ryanodine-induced Ca2+-release and Ca2+-uptake fell by 31 ± 26 and 28 ± 13%, respectively. The tetanic force depression was correlated with the combined reduction of ATP and PCr, and increase of lactate (r = 0.77, P = 0.009). Plasma venous [K+] increased from 4.0 ± 0.3 to 5.4 ± 0.8 mM over 1-3-min exercise. Central fatigue occurred during the early contractions in the quadriceps in 7 out of 17 participants (central activation ratio fell from 0.98 ± 0.05 to 0.86 ± 0.11 at 1 min), but dwindled at exercise cessation. Central fatigue was seldom apparent in adductor pollicis. CONCLUSIONS: Fatigue with repeated MVC in human limb muscles mainly involves peripheral aspects which include impaired SR Ca2+-handling and we speculate that anaerobic metabolite changes are involved. A faster early force loss in quadriceps muscle with some participants is attributed to central fatigue.

Plasma and lymphocyte Hsp72 responses to exercise in athletes with prior exertional heat illness.

We investigated the effect of exercise in the heat on both intracellular and extracellular Hsp72 in athletes with a prior history of exertional heat illness (EHI). Two groups of runners, one consisting of athletes who had a previous history of EHI, and a control group (CON) of similar age (29.7 ± 1.2 and 29.1 ± 2 years CON vs. EHI) and fitness [maximal oxygen consumption [Formula: see text] 65.7 ± 2 and 64.5 ± 3 ml kg(-1) min(-1) CON vs. EHI] were recruited. Seven subjects in each group ran on a treadmill for 1 h at 72 % [Formula: see text] in warm conditions (30 °C, 40 % RH) reaching rectal temperatures of ~39.3 (CON) and ~39.2 °C (EHI). Blood was collected every 10 min during exercise and plasma was analysed for extracellular Hsp72. Intracellular Hsp72 levels were measured in both monocytes and lymphocytes before and immediately after the 60-min run, and then after 1 h recovery at an ambient temperature of 24 °C. Plasma Hsp72 increased from 1.18 ± 0.14 and 0.86 ± 0.08 ng/ml (CON vs. EHI) at rest to 4.56 ± 0.63 and 4.04 ± 0.45 ng/ml (CON vs. EHI, respectively) at the end of exercise (p < 0.001), with no difference between groups. Lymphocyte Hsp72 was lower in the EHI group at 60 min of exercise (p < 0.05), while monocyte Hsp72 was not different between groups. The results of the present study suggest that the plasma Hsp72 response to exercise in athletes with a prior history of EHI remained similar to that of the CON group, while the lymphocyte Hsp72 response was reduced.

Noninvasive assessment of hepatic lipid composition: Advancing understanding and management of fatty liver disorders.

UNLABELLED: Nonalcoholic fatty liver is frequently observed in obese individuals, yet the factors that predict its development and progression to liver disease are poorly understood. We proposed that proton magnetic resonance spectroscopy ((1)H-MRS) might allow noninvasive assessment of hepatic lipid composition. Lipid saturation (SI) and polyunsaturation (PUI) indices measured by (1)H-MRS were in agreement with those expected in oils of known composition. Hepatic triglyceride concentration (HTGC) and composition were then measured in healthy lean (LEAN) men, obese men with normal HTGC (OB), and obese men with hepatic steatosis (OB+HS). The effect of marked changes in dietary fat consumption on hepatic lipids were also compared in lean men after 67 hours of a normal mixed (NM) diet versus a low-carbohydrate, high-saturated-fat (LCHF) diet. SI was significantly higher in OB+HS (0.970 +/- 0.004) and OB (0.944 +/- 0.008) versus LEAN (0.818 +/- 0.025) (P < 0.01 for both). PUI was significantly lower in OB+HS (0.003 +/- 0.001) and OB (0.022 +/- 0.005) versus LEAN (0.120 +/- 0.021) (P < 0.01), and significantly lower in OB+HS versus OB (P < 0.05). LCHF diet did not alter HTGC, SI, or PUI (P > 0.05). The (1)H-MRS method provides for rapid, qualitative assessment of lipid composition. Application of this technique in the liver produces results that are consistent with biopsy-based approaches demonstrating that relative hepatic lipid saturation increases and polyunsaturation decreases with obesity. Obesity-related hepatic steatosis is characterized by further depletion of polyunsaturated hepatic lipids. CONCLUSION: This readily available and noninvasive approach should promote further study into interactions between hepatic and whole-body lipid metabolism and help to elucidate the pathogenesis of disorders characterized by lipid accumulation within the liver.

Effects of sprint training on extrarenal potassium regulation with intense exercise in Type 1 diabetes.

Effects of sprint training on plasma K+ concentration ([K+]) regulation during intense exercise and on muscle Na+-K+-ATPase were investigated in subjects with Type 1 diabetes mellitus (T1D) under real-life conditions and in nondiabetic subjects (CON). Eight subjects with T1D and seven CON undertook 7 wk of sprint cycling training. Before training, subjects cycled to exhaustion at 130% peak O2 uptake. After training, identical work was performed. Arterialized venous blood was drawn at rest, during exercise, and at recovery and analyzed for plasma glucose, [K+], Na+ concentration ([Na+]), catecholamines, insulin, and glucagon. A vastus lateralis biopsy was obtained before and after training and assayed for Na+-K+-ATPase content ([3H]ouabain binding). Pretraining, Na+-K+-ATPase content and the rise in plasma [K+] ([K+]) during maximal exercise were similar in T1D and CON. However, after 60 min of recovery in T1D, plasma [K+], glucose, and glucagon/insulin were higher and plasma [Na+] was lower than in CON. Training increased Na+-K+-ATPase content and reduced [K+] in both groups (P < 0.05). These variables were correlated in CON (r = -0.65, P < 0.05) but not in T1D. This study showed first that mildly hypoinsulinemic subjects with T1D can safely undertake intense exercise with respect to K+ regulation; however, elevated [K+] will ensue in recovery unless insulin is administered. Second, sprint training improved K+ regulation during intense exercise in both T1D and CON groups; however, the lack of correlation between plasma delta[K+] and Na+-K+-ATPase content in T1D may indicate different relative contributions of K+-regulatory mechanisms.

Sprint training increases muscle oxidative metabolism during high-intensity exercise in patients with type 1 diabetes.

OBJECTIVE: To investigate sprint-training effects on muscle metabolism during exercise in subjects with (type 1 diabetic group) and without (control group) type 1 diabetes. RESEARCH DESIGN AND METHODS: Eight subjects with type 1 diabetes and seven control subjects, matched for age, BMI, and maximum oxygen uptake (Vo(2peak)), undertook 7 weeks of sprint training. Pretraining, subjects cycled to exhaustion at 130% Vo(2peak). Posttraining subjects performed an identical test. Vastus lateralis biopsies at rest and immediately after exercise were assayed for metabolites, high-energy phosphates, and enzymes. Arterialized venous blood drawn at rest and after exercise was analyzed for lactate and [H(+)]. Respiratory measures were obtained on separate days during identical tests and during submaximal tests before and after training. RESULTS: Pretraining, maximal resting activities of hexokinase, citrate synthase, and pyruvate dehydrogenase did not differ between groups. Muscle lactate accumulation with exercise was higher in type 1 diabetic than nondiabetic subjects and corresponded to indexes of glycemia (A1C, fasting plasma glucose); however, glycogenolytic and glycolytic rates were similar. Posttraining, at rest, hexokinase activity increased in type 1 diabetic subjects; in both groups, citrate synthase activity increased and pyruvate dehydrogenase activity decreased; during submaximal exercise, fat oxidation was higher; and during intense exercise, peak ventilation and carbon dioxide output, plasma lactate and [H(+)], muscle lactate, glycogenolytic and glycolytic rates, and ATP degradation were lower in both groups. CONCLUSIONS: High-intensity exercise training was well tolerated, reduced metabolic destabilization (of lactate, H(+), glycogenolysis/glycolysis, and ATP) during intense exercise, and enhanced muscle oxidative metabolism in young adults with type 1 diabetes. The latter may have clinically important health benefits.

Ultrastructural changes and sarcoplasmic reticulum Ca2+ regulation in red vastus muscle following eccentric exercise in the rat.

This study examined the effects of a bout of low-intensity, prolonged downhill exercise on sarcoplasmic reticulum (SR) Ca(2+)-ATPase activity, Ca(2+) uptake and release in rat red vastus muscle. Ionophore stimulation was determined to assess vesicle integrity by measuring the ratio of Ca(2+)-ATPase activities in the presence and absence of A23187. Observations of the muscle ultrastructure were made to evaluate muscle damage at the level of the myofibrils and SR. Adult male Sprague-Dawley rats (weight, 395 +/- 5.9 g) were either assigned as non-exercise controls or subjected to 90 min of downhill treadmill exercise (-16 deg; 15 m min(-1)), and then killed immediately, 4, 24, 48, 72 or 144 h after exercise (n = 7). Calcium uptake was significantly lower (P < 0.05) compared with control values (19.25 +/- 1.38 nmol min(-1) (mg protein)(-1)), by 29 and 36% immediately and 4 h postexercise, respectively, and remained depressed (P < 0.05) 24 h postexercise. Calcium release was also significantly lower (P < 0.05) compared with control values (31.06 +/- 2.36 nmol min(-1) (mg protein)(-1)), by 37 and 39% immediately and 4 h postexercise, respectively, and remained depressed (P < 0.05) 24 h postexercise. Ca(2+)-ATPase activity measured with ionophore was 31% lower (P < 0.05) 4 h postexercise, and remained lower (P < 0.05) 24 h postexercise. The ratio of Ca(2+)-ATPase activities in the presence and absence of A23187 was not significantly changed after exercise, indicating that membrane integrity was not altered by the exercise. Focal dilatations of the SR were observed immediately and 4 h following exercise, implying that SR may be susceptible to damage in the localized regions of overstretched sarcomeres. The results demonstrate that a bout of low-intensity, prolonged downhill exercise results in a long-lasting depression of SR function that is not fully restored after 2 days of recovery, which may underlie some functional impairments induced by eccentric exercise.