High-intensity Contractions Research Articles

Relationship between Torque and Angular Velocity of Human Dorsiflexors in vivo

Numerous studies have investigated torque-angular velocity relation of human muscles in vivo, by using isokinetic strength measurements. However, the experimental data in the low-torque, high-velocity region are typically missing, primarily because of large inertial mass and limited range of motion in the human limbs. PURPOSE: To describe the whole picture of torque-angular velocity relation of human dorsiflexors in vivo, by combining isokinetic strength measurement with the slack test, a method for determining unloaded shortening velocity of muscle (Edman, 1979; Sasaki & Ishii, 2005). METHODS: Fifteen healthy students (age: 19.5 ± 0.8 years, height: 164.4 ± 9.1 cm, body mass: 53.9 ± 8.4 kg) participated in this study. In the slack-test measurement, the quick release of ankle joint was applied while the subjects exerted an isometric torque at 15, 50, and 85% of maximal voluntary contraction (MVC). Since the relation between the angular displacement of quick release (ÄL) and the time required to redevelop the torque (Ät) was approximately linear, the unloaded shortening velocity of dorsiflexors was determined as the linear regression slope of ÄL-Ät relation. In the isokinetic measurement, peak torque was determined at angular velocities of 0, 0.26, 0.52, 1.05, 2.09, and 3.14 rad s−1. Surface electromyographic activities (EMGs) of tibialis anterior (TA) and soleus (SOL) muscles during contraction were also examined. RESULTS: The results from the slack test showed that the unloaded shortening velocity of dorsiflexors increased with the contraction intensity (R2 = 0.37, P < 0.0001), suggesting an additional recruitment of fast motor units at higher contraction intensities (i.e. 50 and 85% of MVC). When combined with the unloaded shortening velocity determined at 85% of MVC (13.6 ± 9.1 rad s−1), the isokinetic torque-angular velocity relation had a hyperbolic shape, in which the shape parameter ranged between 0.09 and 1.38. In addition, EMGs of TA and SOL during contraction were consistent across different contraction velocity (Friedman test: P < 0.24, TA; P < 0.26, SOL). CONCLUSION: Torque-angular velocity relation of human dorsiflexors in vivo had hyperbolic shape, in which the shape parameter was consistent with the other muscles of humans and animals.

Take two NSAIDs and call on your satellite cells in the morning

it is generally agreed that successful skeletal muscle regeneration following intense exercise or injury is facilitated by the protein synthesis machinery and the recruitment of myogenic stem (satellite) cells. Upstream activation of these processes, however, is poorly understood. A growing body of

Combating muscle fatigue: extracellular lactic acidosis and catecholamines

During strenuous exercise, contracting skeletal muscle fatigues at a high rate in part due to ionic imbalances occurring across the sarcolemma that contribute to decreased sarcolemmal excitatibility (Sjogaard, 1990). It is suspected that the reduced excitability contributes to a reduction in calcium release by the sarcoplasmic reticulum and a consequent decrease in the force of muscle contraction (Lindinger, 2006). The contribution of this membrane mechanism to the fatigue of high-intensity exercise has been proposed as a way of protecting contracting muscle cells against the damage that may occur if contraction were to continue (Sjogaard, 1990). The accumulation of lactate and especially associated protons, both within the cell and in the extracellular fluids surrounding cells (Lindinger et al. 2005), have also long been thought to contribute to the fatigue of high-intensity exercise. However, Nielsen et al. (2001) previously raised serious questions about the roles of lactate and acidosis in the fatigue process when they showed, in rat muscle in vitro, that acidosis counteracted the effects of increased extracellular [K+] ([K+]o) on sarcolemmal Vm. So, while the effects of increased [K+]o as a key contributor to the fatigue of high-intensity exercise remain unrefuted, the elevated extracellular [H+] of exercise appears to allow muscle to continue to contract despite a higher [K+]o. Further, the authors have gone on to state: ‘In many kinds of exercise, reduced excitability may never contribute to fatigue because endogenous protection via activation of the Na+–K+ pumps and/or development of acidosis is sufficient to maintain excitability’ (Nielsen & Overgaard, 2006). It is noteworthy that other ‘protective’ effects of lactate on sustaining muscle contraction are also recognized (Brooks, 2001; Cairns, 2006). In this issue of The Journal of Physiology, Nielsen and coworkers (de Paoli et al. 2007) provide support that extracellular lactate accumulation has a protective effect on muscle excitability. They demonstrated that an increased extracellular acidity (20 mmol l−1 lactic acid), similar to that seen during high-intensity exercise, is additive to the effects of elevated adrenaline on stabilizing membrane excitability. Most importantly, the combination of these two effects was able to fully restore muscle force production. In contrast, adrenaline without concurrent increase in extracellular acidity, through its effects of increasing sarcolemmal Na+–K+-ATPase activity and hence membrane potential, was not able to fully restore sarcolemmal excitability or muscle force production. Limitations of the studies to date is that they have been performed on isolated fibre bundles or fibres, typically at room temperature in vitro, and the manipulations performed only mimic a few of the key changes that occur during high-intensity muscle contractions. Another caveat is that the influence of elevated [H+]o on fatigue of muscle in vitro is pronounced at low temperature but not at physiological temperatures; however, this temperature effect is not pronounced at elevated intracellular [H+] (Knuth et al. 2006). It remains unknown if the mechanisms that operate in such controlled conditions in vitro occur to a similar degree within complex in vivo systems. In the exercising human, there occur simultaneous changes in both the intra- and extracellular ionic and metabolic environments. So while the in vitro studies provide insight as to what may occur, we should still ask the question: Why should we expect the results of the present study to be similar to what occurs in contracting muscle in vivo? I am sure that we all look forward to finding out the answers.

Effects of High Intensity&amp;thinsp;/&amp;thinsp;Low Volume and Low Intensity&amp;thinsp;/&amp;thinsp;High Volume Isokinetic Resistance Exercise on Postexercise Glucose Tolerance

The purpose of this study was to determine the effects of high intensity/ low volume (HILV) and low intensity/high volume (LIHV) isokinetic resistance exercise on postexercise glucose tolerance. Subjects (n = 10) participated in a counterbalanced, randomized design of 2 separate isokinetic resistance exercise trials (HILV and LIHV) of reciprocal concentric knee flexion and knee extension in a fasted state. Each bout was followed by a 45-minute oral glucose tolerance test (OGTT; 1.8 g.kg fat free mass(-1)). Blood samples were obtained every 15 minutes to determine glucose and insulin concentrations. There was no difference in total work between the 2 trials (p = 0.229). Blood glucose was significantly higher at all time points compared with time 0 following the LIHV trial (p < 0.05). Following the HILV trial, blood glucose was significantly elevated at 15 and 30 minutes (p < 0.05), but returned to resting values by 45 minutes. Insulin concentration was significantly elevated following both trials at all time points (p < 0.05). Blood glucose and insulin were significantly higher following the LIHV at 30 and 45 minutes compared with the HILV trial (p < 0.05). These results demonstrate that although the total work output was similar across trials, high intensity muscle contraction is associated with an enhanced normalization of glucose homeostasis following a large postexercise oral glucose feed.

Knee extensor muscle oxygen consumption in relation to muscle activation

Recently, fatigability and muscle oxygen consumption (mVO(2)) during sustained isometric contractions were found to be less at shorter (30 degrees knee angle; 0 degrees = full extension) compared to longer knee extensor muscle lengths (90 degrees ) and, at low torques, less in the rectus femoris (RF) muscle than in the vastus lateralis and medialis. In the present study we hypothesized that these findings could be accounted for by a knee angle- and a muscle-dependent activation respectively. On two experimental days rectified surface EMG (rsEMG) was obtained as a measure of muscle activation in nine healthy young males. In addition, on day 1 maximal torque capacity (MTC) was carefully determined using superimposed nerve stimulation on brief high intensity contractions (> 70%MVC) at 30, 60 and 90 degrees knee angles. On day 2, subjects performed longer lasting isometric contractions (10-70%MTC) while mVO(2) was measured using near-infrared spectroscopy (NIRS). At 30 degrees , maximal mVO(2) was reached significantly later (11.0 s +/- 6.5 s) and was 57.9 +/- 8.3% less (average +/- SD, across intensities and muscles) than mVO(2) at 60 and 90 degrees (p < 0.05). However, rsEMG was on average only 18.0 +/- 11.8% (p = 0.062) less at the start of the contraction at 30 degrees . At 10%MTC at all knee angles, maximal mVO(2) of the RF occurred significantly later (28.8 +/- 36.0 s) and showed a significantly smaller increase in rsEMG compared to both vasti. In conclusion, it is unlikely that the tendency for less intense muscle activation could fully account for the approximately 60% lower oxygen consumption at 30 degrees , but the later increase in RFmVO(2) seemed to be caused by a less strong activation of the RF.

Regulation of contraction-induced FA uptake and oxidation by AMPK and ERK1/2 is intensity dependent in rodent muscle

Muscle contraction activates AMP-activated protein kinase (AMPK) and extracellular signal-regulated kinase (ERK1/2), two signaling molecules involved in the regulation of muscle metabolism. The purpose of this study was to determine whether activation of AMPK and/or ERK1/2 contributes to the regulation of muscle fatty acid (FA) uptake and oxidation in contracting muscle. Rat hindquarters were perfused during rest (R) or electrical stimulation (E) of increasing intensity by manipulating train duration (E1 = 25 ms, E2 = 50 ms, E3 = 100 ms, E4 = 200 ms). For matched FA delivery, FA uptake was significantly greater than R during E1, E2, and E3 (7.8 +/- 0.7 vs. 14.4 +/- 0.3, 16.9 +/- 0.8, 15.2 +/- 0.5 nmol.min(-1).g(-1), respectively, P < 0.05), but not during E4 (8.3 +/- 0.3 nmol.min(-1).g(-1), P > 0.05). FA oxidation was significantly greater than R during E1 and E2 (1.5 +/- 0.1 vs. 2.3 +/- 0.2, 2.5 +/- 0.2 nmol.min(-1).g(-1), P < 0.05) before returning to resting levels for E3 and E4 (1.8 +/- 0.1 and 1.5 +/- 0.2 nmol.min(-1).g(-1), P > 0.05). A positive correlation was found between FA uptake and ERK1/2 phosphorylation from R to E3 (R(2) = 0.55, P < 0.05) and between FA oxidation and ERK1/2 phosphorylation from R to E2 (R(2) = 0.76, P < 0.05), correlations that were not maintained when the data for E4 and E3 and E4, respectively, were included in the analysis (R(2) = 0.04 and R(2) = 0.03, P > 0.05). A positive correlation was also found between FA uptake and FA oxidation and AMPK activity for all exercise intensities (R(2) = 0.57, R(2) = 0.65 respectively, P < 0.05). These results, in combination with previous data from our laboratory, suggest that ERK1/2 and AMPK are the predominant signaling molecules regulating FA uptake and oxidation during low- to moderate-intensity muscle contraction and during moderate- to high-intensity muscle contraction, respectively.

The Experimental Type 2 Diabetes Therapy Glycogen Phosphorylase Inhibition Can Impair Aerobic Muscle Function During Prolonged Contraction

Glycogen phosphorylase inhibition represents a promising strategy to suppress inappropriate hepatic glucose output, while muscle glycogen is a major source of fuel during contraction. Glycogen phosphorylase inhibitors (GPi) currently being investigated for the treatment of type 2 diabetes do not demonstrate hepatic versus muscle glycogen phosphorylase isoform selectivity and may therefore impair patient aerobic exercise capabilities. Skeletal muscle energy metabolism and function are not impaired by GPi during high-intensity contraction in rat skeletal muscle; however, it is unknown whether glycogen phosphorylase inhibitors would impair function during prolonged lower-intensity contraction. Utilizing a novel red cell-perfused rodent gastrocnemius-plantaris-soleus system, muscle was pretreated for 60 min with either 3 micromol/l free drug GPi (n=8) or vehicle control (n=7). During 60 min of aerobic contraction, GPi treatment resulted in approximately 35% greater fatigue. Muscle glycogen phosphorylase a form (P<0.01) and maximal activity (P<0.01) were reduced in the GPi group, and postcontraction glycogen (121.8 +/- 16.1 vs. 168.3 +/- 8.5 mmol/kg dry muscle, P<0.05) was greater. Furthermore, lower muscle lactate efflux and glucose uptake (P<0.01), yet higher muscle Vo(2), support the conclusion that carbohydrate utilization was impaired during contraction. Our data provide new confirmation that muscle glycogen plays an essential role during submaximal contraction. Given the critical role of exercise prescription in the treatment of type 2 diabetes, it will be important to monitor endurance capacity during the clinical evaluation of nonselective GPi. Alternatively, greater effort should be devoted toward the discovery of hepatic-selective GPi, hepatic-specific drug delivery strategies, and/or alternative strategies for controlling excess hepatic glucose production in type 2 diabetes.

Blood flow and O2 extraction as a function of O2 uptake in muscles composed of different fiber types

We examined how the greater vasodilatory capacity of slow--(ST) versus fast-twitch (FT) muscles impacts the relationship between blood flow (Q ) and O2 uptake (VO2) and, consequently, the O2 extraction (a-vO2 diff.)-to-VO2 relationship. Q was measured with radiolabelled microspheres, while VO2 was calculated by the Fick principle using measurements of microvascular O2 pressure (phosphorescence quenching) at rest, low--(2.5 V) and high-intensity contractions (4.5 V) for soleus (Sol; ST, n=5), mixed-gastrocnemius (MG; FT, n=7) and white-gastrocnemius (WG; FT, n=7). The slope of the Q-to-VO2 relationship (delta Q/delta VO2] ) was not different among muscles (Sol = 5.5 +/- 0.2, MG = 6.0 +/- 0.11 and WG = 5.8 +/- 0.06; P > 0.05). In contrast, the intercept was greater (P < 0.05) for Sol (16.3 +/- 2.7 ml min(-1) 100 g(-1)) versus MG and WG (in ml min(-1) 100 g(-1): 1.39 +/- 0.26 and 1.45 +/- 0.23, respectively; MG and WG, P > 0.05). In addition, the a-vO2 diff.-to-VO2] relationship for Sol was shifted rightward compared to MG and WG. These data suggest that the increase in Q for a given change in VO2 is similar for slow- and fast-twitch muscles, at least for the range of metabolic rates and muscles studied herein and that a-vO2 diff. differences result from the lower resting Q in FT muscles.

Cardiovascular responses induced during high‐intensity eccentric and concentric isokinetic muscle contraction in healthy young adults

The purpose of this study was to determine the differences in cardiovascular response between high-intensity eccentric (ECC) and concentric (CON) contractions, and to obtain the basic data applicable to resistance training in middle-aged and elderly individuals. The subjects who participated in this study were nine healthy men (age 24.1 +/- 1.3 years). ECC and CON were randomly selected, as each test consisted of a high-intensity (80% of peak torque) bout of 60 s of ECC and CON isokinetic contractions of the flexor carpi radialis. Systolic pressure (SBP), diastolic pressure (DBP) and heart rate (HR) during ECC and CON were measured using a Finometer. Mean arterial pressure (MAP) was calculated by SBP and DBP. Rate-pressure product (RPP) was calculated by SBP and HR. SBP, DBP, MAP and RPP during ECC were significantly smaller compared with CON. It is clear that cardiovascular response by high-intensity contraction is smaller in ECC than in CON. High-intensity ECC has been suggested to exert only small stress to the cardiovascular system. Thus, being a contraction mode it may be applicable to resistance training.

Age-related changes in ATP-producing pathways in human skeletal muscle in vivo

Energy for muscle contractions is supplied by ATP generated from 1) the net hydrolysis of phosphocreatine (PCr) through the creatine kinase reaction, 2) oxidative phosphorylation, and 3) anaerobic glycolysis. The effect of old age on these pathways is unclear. The purpose of this study was to examine whether age may affect ATP synthesis rates from these pathways during maximal voluntary isometric contractions (MVIC). Phosphorus magnetic resonance spectroscopy was used to assess high-energy phosphate metabolite concentrations in skeletal muscle of eight young (20-35 yr) and eight older (65-80 yr) men. Oxidative capacity was assessed from PCr recovery after a 16-s MVIC. We determined the contribution of each pathway to total ATP synthesis during a 60-s MVIC. Oxidative capacity was similar across age groups. Similar rates of ATP synthesis from PCr hydrolysis and oxidative phosphorylation were observed in young and older men during the 60-s MVIC. Glycolytic flux was higher in young than older men during the 60-s contraction (P < 0.001). When expressed relative to the overall ATP synthesis rate, older men relied on oxidative phosphorylation more than young men (P = 0.014) and derived a smaller proportion of ATP from anaerobic glycolysis (P < 0.001). These data demonstrate that although oxidative capacity was unaltered with age, peak glycolytic flux and overall ATP production from anaerobic glycolysis were lower in older men during a high-intensity contraction. Whether this represents an age-related limitation in glycolytic metabolism or a preferential reliance on oxidative ATP production remains to be determined.

Intracellular [H+]: a determinant of cell volume in skeletal muscle

Intracellular [H⁺]: a determinant of cell volume in skeletal muscle

Protective role of extracellular chloride in fatigue of isolated mammalian skeletal muscle.

A possible role of extracellular Cl(-) concentration ([Cl(-)](o)) in fatigue was investigated in isolated skeletal muscles of the mouse. When [Cl(-)](o) was lowered from 128 to 10 mM, peak tetanic force was unchanged, fade was exacerbated (wire stimulation electrodes), and a hump appeared during tetanic relaxation in both nonfatigued slow-twitch soleus and fast-twitch extensor digitorum longus (EDL) muscles. Low [Cl(-)](o) increased the rate of fatigue 1) with prolonged, continuous tetanic stimulation in soleus, 2) with repeated intermittent tetanic stimulation in soleus or EDL, and 3) to a greater extent with repeated tetanic stimulation when wire stimulation electrodes were used rather than plate stimulation electrodes in soleus. In nonfatigued soleus muscles, application of 9 mM K(+) with low [Cl(-)](o) caused more rapid and greater tetanic force depression, along with greater depolarization, than was evident at normal [Cl(-)](o). These effects of raised [K(+)](o) and low [Cl(-)](o) were synergistic. From these data, we suggest that normal [Cl(-)](o) provides protection against fatigue involving high-intensity contractions in both fast- and slow-twitch mammalian muscle. This phenomenon possibly involves attenuation of the depolarization caused by stimulation- or exercise-induced run-down of the transsarcolemmal K(+) gradient.

Effects of expiratory muscle work on muscle sympathetic nerve activity.

We hypothesized that contractions of the expiratory muscles carried out to the point of task failure would cause an increase in muscle sympathetic nerve activity (MSNA). We measured MSNA directly in six healthy men during resisted expiration (60% maximal expiratory pressure) leading to task failure with long [breathing frequency (f(b)) = 15 breaths/min; expiratory time (TE)/total respiratory cycle duration (TT) = 0.7] and short (f(b) = 30 breaths/min; TE/TT = 0.4) TE. Both of these types of expiratory muscle contractions elicited time-dependent increases in MSNA burst frequency that averaged +139 and +239%, respectively, above baseline at end exercise. The increased MSNA coincided with increases in mean arterial pressure (MAP) for both the long-TE (+28 +/- 6 mmHg) and short-TE (+22 +/- 14 mmHg) trials. Neither MSNA nor MAP changed when the breathing patterns and increased tidal volume of the task failure trials were mimicked without resistance or task failure. Furthermore, very high levels of expiratory motor output (95% maximal expiratory pressure; f(b) = 12 breaths/min; TE/TT = 0.35) and high rates of expiratory flow and expiratory muscle shortening without task failure (no resistance; f(b) = 45 breaths/min; TE/TT = 0.4; tidal volume = 1.9 x eupnea) had no effect on MSNA or MAP. Within-breath analysis of the short-expiration trials showed augmented MSNA at the onset of and throughout expiration that was consistent with an influence of high levels of central expiratory motor output. Thus high-intensity contractions of expiratory muscles to the point of task failure caused a time-dependent sympathoexcitation; these effects on MSNA were similar in their time dependency to those caused by high-intensity rhythmic contractions of the diaphragm and forearm muscles taken to the point of task failure. The evidence suggests that these effects are mediated primarily via a muscle metaboreflex with a minor, variable contribution from augmented central expiratory motor output.

Heart Rate and Blood Pressure Responses to Static Handgrip Exercise of Different Intensities: Reliability and Adult versus Child Differences

To determine the reliability of cardiovascular responses to isometric exercise of different intensities, and to compare adult versus child responses, 27 boys (7–9 years old) and 27 men (18–26 years old) performed static handgrip exercise at 10, 20, and 30% of previously determined maximal voluntary contraction (MVC) for three min each on different days, while heart rate (HR) and blood pressure (BP) were measured. HR reliability was moderately high at all intensities in both boys and men ranging from R = 0.52–0.87. BP reliability was moderate in men and boys at 30% MVC while at 10% and 20% MVC reliability was very low for boys and only moderate for men. HR response from pre- to 3-min of static exercise was not different between boys versus men at any intensity. At 30% MVC diastolic (20.2 vs. 29.3 mmHg), systolic (17.4 vs. 36.2 mmHg) and mean (19.2 vs. 31.6 mmHg) BP responses were lower in boys versus men, respectively. At 20% MVC SBP (6.8 vs. 14.3 mmHg) and MBP (8.4 vs. 12.6 mmHg) responses were lower in boys versus men, respectively. In conclusion, the reliability of cardiovascular response to isometric exercise is low at low contraction intensities and moderate at higher contraction intensities. Further, BP response in men at 30% MVC is higher than boys, while responses are similar at lower contraction intensities.

Lactate doesn't necessarily cause fatigue: why are we surprised?

Everyone knows that lactic acidosis causes fatigue. But is it in fact true that the fatigue associated with severe exercise is caused by lactate? And, moreover, how did this received opinion come to be? In many instances our teachers instructed us in this fact as they challenged us to read classical works of the progenitors of biochemistry and muscle physiology. Subsequently, we faithfully transferred this knowledge to our students. Routinely, the association between acidosis and fatigue is reinforced in our minds and psyches by sports journalists and commentators who reiterate what we previously conveyed through our teachings and writings. However, with the results of Nielsen et al. (2001) reported in this issue of The Journal of Physiology, as well as other recent findings, we need to reconsider the appropriateness of this Homeric transfer of knowledge concerning lactic acidosis and muscle fatigue. Since the work of Fletcher & Hopkins (1907), Meyerhof (1920) and A. V. Hill (1932) it has been known that isolated muscles made to contract until fatigue accumulate lactic acid. Further, it was observed that if oxygen was present in recovery, lactic acid level declined while glycogen concentration and contractile function were restored (Meyerhof, 1920; Hill, 1932). Hence, the associations between oxygen insufficiency, lactic acidosis and disrupted function have been presumed by physiologists and clinicians alike (Brooks, 1991; Wasserman & McIlroy, 1964). More recently, beneficial effects of lactate anions in providing oxidizable substrate and gluconeogenic precursors, as well as in cell-cell signalling such as in glutamate-mediated synaptic transmission have been recognized (Brooks, 1991; Pellerin et al. 1998). Moreover, lactic acid (lactate and associated proton) clearance through oxidation and gluconeogenesis during human exercise has been thought to provide a beneficial, alkalizing, effect on blood pH (Brooks, 1991). Cell-cell and intracellular lactate transport across membrane barriers are now known to be facilitated by lactate transport proteins that co-transport lactate and hydrogen ions. Further, several lactate (monocarboxylate; MCT) transporter isoforms are expressed in different tissues and MCTs occupy specific cell domains (Price et al. 1998). Still, despite recognition of the beneficial effects of lactate production and exchange, popular concern persists over the consequences of hydrogen ion production and accumulation during exercise. Given the results of Nielsen et al. (2001) we should relax a bit about the hazardous consequences of acidosis, but we need again to acknowledge that Nature is smarter, and things are more complex than we mortals imagine. Specifically, results of the paper of Nielsen et al. require us to once again reevaluate our notions of lactic acidosis and muscle fatigue. As elegantly described in their paper on electrically stimulated isolated rat soleus muscles, Nielsen and colleagues describe how contractions cause both lactic acidosis and loss of intracellular K+ with accumulation of extracellular K+ ([K+]o). In their experiments high [K+]o led to loss of tetanic force. However, first with lactic acid, then with propionic and carbonic acids (from addition of high CO2) Nielsen and colleagues observed that acidification counteracts the effects of elevated [K+]o that are associated with muscle fatigue. Certainly, repeated, high intensity contractions lead to muscle fatigue. Glycogenolysis and glycolysis can lead to lactic acidosis and disturbances to muscle and plasma pH. Furthermore, contractions also precipitate a variety of other disturbances to cell homeostasis including perturbations to energy charge and ion balances. Whether K+ imbalances always, sometimes or hardly ever lead to fatigue during exercise in vivo is uncertain at this point. Certainly, muscles can be made to contract to fatigue in vivo without loss of the M-waves in EMG. However, isn't it interesting to observe, at least on muscles studied in vitro, that one consequence of repeated forceful muscle contraction (i.e. H+ accumulation) offers a degree of protection against another consequence of contraction (i.e. increased [K+]o)? As we look forward to learning more about the role of potassium ion imbalance and lactic acidosis in muscle function in normal and pathological situations we are given cause to wonder how robust are other notions of physiology that we have long held.

Murine muscles deficient in creatine kinase tolerate repeated series of high-intensity contractions.

Murine muscles lacking both mitochondrial (Mi-CK) and cytoplasmic (MM-CK) creatine kinase (CK-/-) show depressed mechanical performance in association with low muscle ATP and enhanced IMP content. The aims of the present study were to elucidate the possible role of low ATP and high IMP content in impairment of mechanical performance in CK-/- mice and to establish whether CK-/- muscles are able to sustain repeated series of high-intensity contractions. The dorsal flexors of CK-/- and control mice were subjected in situ to two series of 12 tetanic contractions using a custom-made mouse isometric dynamometer. The muscle content of high-energy phosphates was analysed by HPLC. ATP content declined from 20.6+/-1.9 to 15.5+/-2.4 micromol x g(-1) dry weight (d.w.); IMP content increased from 1.2+/-0.4 to 2.4+/-1.1 micromol x g(-1) d.w. during the first contraction series in CK-/- muscle. Despite these unfavourable changes, maximal torque developed during the first contraction of either series did not differ, indicating that the altered content of ATP and IMP does not play a decisive role in impaired mechanical performance in CK-/- mice. The relative decline in torque during the two series did not differ in CK-/- (-20.4+/-6.6 vs. -23.8+/-9.9%). In contrast, wild-type (WT) muscles showed a significantly more pronounced decline during the second series (-12.3+/-7.4 vs. -20.1+/-6.8%). Muscle ATP and IMP content did not change in CK-/-, whereas in WT IMP content increased significantly during the second contraction series. These findings indicate that CK-/- tolerate repeated series of high-intensity contractions better than WT, while in CK-/- muscle an additional source of energy is mobilised to regenerate ATP during the second series.

Reversibility of exercise-induced translocation of Na+-K+ pump subunits to the plasma membrane in rat skeletal muscle.

Exercise-induced translocation of Na+-K+ pump subunits to the sarcolemmal membrane was studied using sarcolemmal giant vesicles as a membrane purification procedure. The subunit content was quantified by Western blotting or by ouabain labeling. Low-intensity treadmill running increased (P<0.01) the alpha1, alpha2, beta1, and beta2 subunit contents by 19-32% in membranes from oxidative muscle fibers and the alpha1, alpha2, and beta2 contents increased by 13-25% in membranes from glycolytic muscle fibers. Ouabain labeling of membranes from mixed fibers was increased by 29% after exercise. A similar increase in subunit content could be induced by 5 min of fatiguing, high-intensity electrical stimulation of isolated soleus muscles. An increased subunit content was just detectable in vesicles produced 30 min after exercise, and the content was completely back to control levels 3 h after exercise. It is concluded that both low-intensity long-lasting running and short-lasting high-intensity contractions are able to induce a translocation of pump subunits to the sarcolemmal membrane. The post-exercise disappearance of the extra subunits (half-time approximately 20 min) from the membrane demonstrates the reversible nature of the translocation process.

Creatine kinase, myosin heavy chains and magnetic resonance imaging after eccentric exercise

The aim of this study was to examine the relationship between myosin heavy chain (MHC) release as a specific marker of slow-twitch muscle fibre breakdown and magnetic resonance imaging (MRI) of skeletal muscle injury after eccentric exercise. The effects of a single series of 70 high-intensity eccentric contractions of the quadriceps femoris muscle group (single leg) on plasma concentrations of creatine kinase and MHC fragments were assessed in 10 young male sport education trainees before and 1 and 4 days after exercise. To visualize muscle injury, MRI of the loaded thigh was performed before and 4 days after the eccentric exercise. All participants recorded an increase ( P ≪ 0.05) in creatine kinase after exercise. In five participants, T2 signal intensity was unchanged post-exercise compared with pre-exercise and MHC plasma concentration was normal; however, they showed an increase ( P ≪ 0.05) in creatine kinase after exercise. For the remaining five participants, there was an increase in T2 signal intensity of the loaded vastus intermedius and vastus lateralis. These changes in MRI were accompanied by an increase in MHC plasma concentration ( P ≪ 0.01) as well as an increase in creatine kinase ( P ≪ 0.01). We suggest that changes in MRI T2 signal intensity after muscle damage induced by eccentric exercise are closely related to damage to structurally bound contractile filaments of some muscle fibres. Additionally, MHC plasma release indicates that this damage affects not only fast-twitch fibres but also some slow-twitch fibres.

Static contraction causes a reflex-induced release of arginine vasopressin in anesthetized cats

We tested the hypothesis that brief static contraction of the triceps surae muscle causes reflex-induced increases in plasma arginine vasopressin (AVP) in anesthetized cats. Arterial blood samples, for measurement of plasma AVP, were taken before and after 30 s of electrically stimulated static contraction performed at a low intensity (<20% of maximal; n = 5), a high intensity (>70% of maximal; n = 7), and a high intensity after denervation of the triceps surae ( n = 5). The low intensity contraction protocol was repeated during α-adrenergic blockade ( n = 7) to minimize potential baroreflex-induced inhibition of AVP release. Passive stretch of the triceps surae was conducted ( n = 5) to determine effects of muscle mechanoreceptor stimulation on the release of AVP. Low intensity contraction had no effect on plasma AVP. During α-adrenergic blockade, this same contraction intensity caused this peptide to increase from12.8 ± 2.1 to 17.7 ± 2.6 pg/ml. High intensity contraction caused an increase in AVP (13.2 ± 3.5 to 26.1 ± 6.6 pg/ml) that was abolished by denervation (14.4 ± 3.7 vs. 17.1 ± 6.6 pg/ml). Passive stretch had no effect on plasma AVP. These findings suggest that brief static contraction causes increases in plasma AVP that are reflex in nature, intensity dependent, opposed by the arterial baroreflex, and probably unrelated to muscle mechanoreceptor activation.

Can exercise-induced muscle damage be avoided?

All athletes have experienced the discomfort and debilitating effects of exercise-induced muscle damage. Symptoms are most common at the beginning of the season when intense training is reintroduced after a period of relative inactivity. A plethora of scientific data describes exercise conditions that lead to muscle damage. It is well accepted that damage occurs with unfamiliar exercise, primarily involving eccentric contractions. For example, downhill running places a large eccentric stress on the quadriceps muscle group and commonly results in muscle damage.1 However, muscles that have been preconditioned with eccentric contractions are protected against damage from subsequent bouts of eccentric exercise. This muscle damage is known as the “repeated-bout effect” and has been shown with various forms of exercise in both humans and animal models.2 Despite the many studies describing muscle damage and its various clinical symptoms, few have identified intrinsic causative factors or suitable interventions for limiting the symptoms. Clinically, it is important to first identify people at risk of developing more severe symptoms and then to design interventions that might limit those symptoms. Three recent experimental studies provide clinically relevant information for athletes and physicians.3,4,5 Controlled experimental studies have shown wide variation in symptoms between subjects after a bout of unfamiliar eccentric exercise. These data indicate that some people are more susceptible to damage than others, but it is not clear why. Recently musculoskeletal flexibility has been shown to be an important factor affecting the severity of symptoms after eccentric exercise.3 Flexibility was quantified according to a measure of passive muscle stiffness, and subjects' muscles were categorized as “stiff,” “normal,” or “compliant.” After a bout of eccentric exercise, subjects with stiff muscles had significantly greater loss of strength, pain, muscle tenderness, and elevation of plasma creatine kinase activity than those with compliant muscles. Greater apparent muscle damage was attributed to the inability of the tendon and aponeurosis of stiffer muscles to absorb the lengthening imposed by the eccentric contractions. Warm-up and stretching are known to greatly reduce muscle stiffness.6 Because stiffness seems to predispose muscles to damage, it follows that appropriately warming up before exercise may reduce the severity of exercise-induced muscle damage. It has also been shown that warm-up reduces subsequent symptoms of muscle damage.4 Eccentric contractions of the elbow flexors preceded by a warm-up resulted in significantly less loss of strength and elevation of plasma creatine kinase activity than eccentric contractions without a prior warm-up. The protective effect was attributed to decreased passive muscle stiffness, although actual stiffness measurements were not made. Besides the possible role of warm-ups in limiting the symptoms of muscle damage, preconditioning the muscle with eccentric contractions clearly provides a protective effect (repeated-bout effect). Recent data suggest that it may not be necessary to damage the muscle with the initial bout to provide a protective effect.5 Brown and associates showed that as few as 10 maximal eccentric contractions of the knee extensors were sufficient to reduce symptoms appreciably after a subsequent bout of 50 maximal contractions performed three weeks later. There was a clear repeated-bout effect despite that 10 contractions did not result in appreciable muscle damage. These data indicate that preconditioning muscles with a few maximal eccentric contractions can considerably reduce symptoms after a subsequent, more intense, bout of eccentric exercise. The key elements for the repeated-bout effect are that the preconditioning contractions are eccentric, that high-intensity contractions are performed, and that the preconditioning contractions affect the same muscle groups that will be working eccentrically in the repeated bout. All dynamic sports activities involve a large component of high-intensity eccentric contractions, whether the activity is in a game or a practice. Athletes typically experience considerable symptoms of muscle damage when returning to these activities after a prolonged layoff because of injury or between seasons. The severity of these symptoms may be reduced by maintaining good flexibility, especially of the principal muscle groups involved in the given sport; preconditioning the principal muscle groups with a few high-intensity eccentric contractions one to two weeks before returning to full activities; and performing specific warm-up exercises for the principal muscle groups immediately before the first few training sessions or games. Increasing the athletes' awareness of the cause of symptoms will increase compliance with any intervention directed at limiting muscle damage. This is especially important in sports that do not place a large emphasis on warm-up or flexibility.