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Effects of genetic obesity on rat upper airway muscle and diaphragm contractile properties.

The contractile properties of pharyngeal respiratory muscle are altered in sleep apnoea and in conditions associated with sleep apnoea, such as ageing. We hypothesized that the contractile properties of the pharyngeal musculature are also altered by obesity, another factor associated with sleep apnoea. Studies compared a pharyngeal muscle, the sternohyoid, with the diaphragm. These were chosen as representative muscles whose contraction has opposing effects on upper airway patency. Both muscles were removed from nine lean and nine obese male Zucker rats (a genetic model of obesity), and isometric contractile properties were studied in vitro at 37 degrees C. For the sternohyoid muscle, in obese compared to lean animals there were no significant differences in isometric contraction time (15.2 +/- 0.3 vs 14.2 +/- 0.6 ms, respectively), half-relaxation time (13.6 +/- 0.5 vs 12.6 +/- 0.9 ms, respectively), twitch-to-tetanic tension ratio (0.22 +/- 0.02 vs 0.24 +/- 0.02, respectively), force-frequency relationship, fatigue resistance (2 min fatigue index 0.20 +/- 0.03 vs 0.18 +/- 0.02, respectively), or maximal degree of force potentiation during repetitive stimulation (52 +/- 11 vs 74 +/- 20% increase, respectively). For the diaphragm, the only significant effect of obesity was a lowering of the twitch-to-tetanic tension ratio (0.25 +/- 0.01 vs 0.29 +/- 0.02, respectively). In obese, as in lean animals, the sternohyoid had faster isometric twitch kinetics, a larger degree of force potentiation, and lower resistance to fatigue, than the diaphragm. In lean, but not obese, animals the sternohyoid twitch-to-tetanic tension ratio was lower than and the force frequency relationship was located to the right of that of the diaphragm. In this study, genetic obesity in rats was not associated with any significant alterations in the contractile properties of the pharyngeal muscle, and only small changes in the relationship between the contractile properties of the sternohyoid and diaphragm muscle.

Aging↗

Muscle fatigue and pain after eccentric contractions at long and short length.

1. The effect of muscle length on the development of muscle pain and fatigue has been studied. 2. Eight normal young adults performed maximal eccentric contractions of the elbow flexors. The muscles of one arm were exercised at short length, and the contralateral muscle at long length. Each contraction lasted approximately 1 s, and was repeated once every 10 s for 30 min. 3. Muscle strength and frequency-force characteristics were measured from isometric contractions before, immediately after and at 24 h intervals for the next 4 days. Muscle tenderness was assessed daily. 4. The muscle strength was reduced by approximately 10% by exercise at short length, and by 30% by exercise at long length. 5. The 20:100 ratio (force generated by stimulation at 20 Hz/force generated at 100 Hz) fell by 30% after exercise at short length and had recovered after 24 h. Exercise at long length reduced this ratio by 65% and the muscles had not fully recovered 4 days later. 6. Muscle pain developed after both exercise regimens, but was slightly worse after that at long length. 7. It is concluded that there is a length-dependent component in the development of pain and fatigue after eccentric exercise, which had previously been thought to be caused solely by high force generation.

Adolescent↗

Lead alters structure and function of mouse flexor muscle.

To evaluate the effect of long-term exposure to heavy metals on skeletal muscle, chronic subcutaneous injections for 7 days of two level treatments (low dose, 0.1 mg/kg and high dose, 1 mg/kg) of lead acetate were investigated. Comparative analyses of in situ dorsiflexor muscle isometric contractile characteristics were studied in urethane-anesthetized (2 mg/g, i.p.) control and lead-exposed male mice. Control muscle-twitch tension reached an average of 1.81 +/- 0.06 g. Chronic lead (Pb2+) treatments did not affect muscle contractile speed, but reduced significantly the twitch tension in both high and low doses when compared to control animals. This effect was in a dose-dependent manner; 1.21 +/- 0.07 g for low dose and 0.90 +/- 0.05 g for high dose. These chronic Pb2+ treatments accelerated muscle fatigue after 250 stimuli (25 Hz for 10 sec) in both the low and high doses equally. However, marked elevation in tetanic (25 Hz) specific tension were observed in the high-dose, chronically treated animals, indicating some changes in contractile apparatus function. The high dose of chronic Pb2+ treatment induced ultrastructural changes, including reduced number of synaptic vesicles, disruption of mitochondria and increased number of smooth endoplasmic reticulum and myelin-like figures in the intramuscular axons and neuromuscular junctions. Chronic Pb2+ treatment caused extensive disruption of the sarcoplasmic mitochondria and increased the number of myelin-like figures in the muscle. These results suggest that exposure to Pb2+ at a low concentration can compromise the in situ skeletal muscle isometric contraction.

Animals↗

Strength training by electrostimulation conditions for efficacy.

The overload imposed on the neuromuscular system under Electrostimulation (ES) can be expressed by applied current intensity or by Electrically Evoked Torque (EET). The aim of this study was to discern which of these two parameters is the one which is determinant for the efficacy of training by ES. Test and training involved isometric contraction of the flexion maintained at a joint angle of 25 degrees (0 degree = extension). The 16 trained subjects received 15 sessions of 25 electrically evoked contractions, using a monophasic rectangular waveform current at a frequency of 2500 Hz modulated at 90 Hz. Each stimulation lasted for 5 sec at the maximal tolerable current. Contrary to the control group (n = 16), the trained group significantly increased their MVIC (15.6%). The individual strength gains ranged from -5% to 49%. No correlation was found between current level and strength modifications. A direct relation was established between the EET and the strength gains (a minimum threshold of EET must be reached during at least 8 sessions to induce strength increases). The "overload principle", previously described for voluntary contraction strengthening, seems to be suitable for electrical stimulation and concerns the EET shown on the ergometer as the effect of the contraction of agonist and antagonist muscles.

Adult↗

Sex differences in human skeletal muscle fatigue are eliminated under ischemic conditions.

Several studies have suggested that women may be more resistant to muscle fatigue than men (Fulco CS, Rock PB, Muza SA, Lammi E, Cymerman A, Butterfield G, Moore, LG, Braun B, and Lewis SF. Acta Physiol Scand 167: 233-239, 1999) possibly because of differences in muscle oxidative metabolism. We evaluated muscle fatigue produced by intermittent, maximal volitional isometric contractions of the dorsiflexor muscles of healthy young (21-34 yr) men (n = 8) and women (n = 8) under two conditions: free-flow (FF) circulation and ischemia. Measures of voluntary and stimulated (10- and 50-Hz) force, central activation ratio (CAR), and compound muscle action potential (CMAP) were collected in each session. The ischemic protocol induced greater fatigue than the FF protocol, in both sexes, and was associated with greater reductions in CAR, CMAP, stimulated force, and the ratio of 10- to 50-Hz force compared with the FF condition. Women fatigued less than men in FF but not during ischemia, and this difference was roughly paralleled by a difference in CAR. No sex effects on the CMAP, tetanic force, and measures of excitation-contraction coupling function were found in the FF condition, suggesting that the primary mechanism behind the difference in fatigue was a relatively greater impairment of central activation in men. The observation that ischemia eliminated the sex differences in fatigue is consistent with a number of studies (Kent-Braun JA, Ng AV, Doyle JW, and Towse TF. J Appl Physiol 93: 1813-1823, 2002) relating fatigue to muscle metabolism and might be the result of sex-based differences in metabolic pathway utilization during muscle contraction.

Action Potentials↗

Influences of repetitive drop jump and isometric leg press exercises on tendon properties in knee extensors.

The present study aimed to investigate the effects of repetitive drop jumps (DJ) and isometric leg presses (LP) on the tendon properties in knee extensors. Before and after each endurance test, the elongation (L) of the tendon and aponeurosis of the vastus lateralis muscle was measured directly by ultrasonography while the subjects performed ramp isometric knee extensions up to maximum voluntary isometric contraction. Eight men performed 100 repetitions of the DJ and 50 repetitions of the LP for 10 seconds with 10 seconds relaxation. In the DJ, there were no significant differences in L values at any force production levels before and after each endurance test. In LP, however, the L values above 500 N were significantly greater after the endurance test than before. These results suggest that the tendon properties in knee extensors change to become more compliant after the repeated longer-duration contractions, but not after repeated ballistic exercises.

Adult↗

The relation between blood lactate and ammonia in ischemic handgrip exercise.

Subjects with myopathies associated with certain enzyme defects often show abnormal concentrations of lactate (LA) and ammonia (NH3) in blood after ischemic exercise. Myoadenylate deaminase (MAD) deficient patients produce only small amounts of NH3, whereas LA rises to normal levels. On the other hand, patients with certain enzyme deficiencies in the glyco(geno)lytic pathway show the opposite. However, the concentrations in blood are dependent on the exercise performed. Standardization of tests for screening purposes, therefore, is necessary. For ischemic contractions, experiments were performed to find the optimal combination for force and frequency, using the highest LA and NH3 concentrations in blood as criteria. Eleven healthy subjects performed ischemic isometric contractions with a handgrip dynamometer at frequencies of 30 and 50/min(-1) and force levels of 50%, 65%, and 80% of maximal voluntary contraction (MVC). A combination of 30/min(-1) and 80% MVC was found to give the best results.

Adult↗

Effect of ethanol on spontaneous phasic contractions of cat gastric smooth muscle.

BACKGROUND: Ethanol is generally believed to inhibit extracellular Ca2+ influx, thereby inhibiting gastric muscle contraction. Recently, we observed that verapamil inhibited only the amplitude of spontaneous phasic contractions, whereas ethanol inhibited both amplitude and frequency. In our objective to investigate the mechanism of ethanol's inhibition of gastric motility, the involvement of various protein kinases in ethanol-inhibited spontaneous phasic contractions of the stomach muscle strips was tested. METHODS: Circular muscle strips (2.0 x 0.2 cm) were prepared from the corpus of cat stomach in order to measure isometric contraction in a chamber filled with Krebs-Ringer solution (pH 7.4, temperature 36 degrees C) bubbled with 5% CO2 in O2. RESULTS: Spontaneous phasic contraction was not affected by various receptor antagonists (I microM atropine, 1 microM hexamethonium, 1 microM phentolamine and 1 microM propranolol) or 1 microM tetrodotoxin. EGTA and verapamil dose-dependently inhibited only the amplitude of spontaneous phasic contractions and not the frequency. Ethanol dose-dependently inhibited both the amplitude and frequency of phasic contractions. The amplitude and frequency of spontaneous phasic contractions were significantly inhibited by protein kinase C and tyrosine kinase inhibitors. However, neither protein kinase C activator nor various phosphatase inhibitors blocked the inhibitory effect of ethanol. CONCLUSIONS: Ethanol appears to inhibit spontaneous phasic contractions by a mechanism other than the inhibition of protein kinase C or tyrosine kinase or the inhibition of extracellular Ca2+ influx.

Animals↗

Chloride ion currents contribute functionally to norepinephrine-induced vascular contraction.

Norepinephrine (NE) increases Cl- efflux from vascular smooth muscle (VSM) cells. An increase in Cl- conductance produces membrane depolarization. We hypothesized that if Cl- currents are important for agonist-induced depolarization, then interfering with cellular Cl- handling should alter contractility. Isometric contraction of rat aortic rings was studied in a bicarbonate buffer. Substitution of extracellular Cl- with 130 mM methanesulfonate (MS; 8 mM Cl-) did not cause contraction. NE- and serotonin-induced contractions were potentiated in this low-Cl- buffer, whereas responses to K+, BAY K 8644, or NE in the absence of Ca2+ were unaltered. Substitution of Cl- with I- or Br- suppressed responses to NE. Inhibition of Cl- transport with bumetanide (10(-5) M) or bicarbonate-free conditions (10 mM HEPES) inhibited NE- but not KCl-induced contraction. The Cl--channel blockers DIDS (10(-3) M), anthracene-9-carboxylic acid (10(-3) M), and niflumic acid (10(-5) M) all inhibited NE-induced contraction, whereas tamoxifen (10(-5) M) did not. Finally, disruption of sarcoplasmic reticular function with cyclopiazonic acid (10(-7) M) or ryanodine (10(-5) M) prevented the increase in the peak response to NE produced by low-Cl- buffer. We conclude that a Cl- current with a permeability sequence of I- > Br- > Cl- > MS is critical to agonist-induced contraction of VSM.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗

Force during stretch and shortening of frog sartorius muscle: effects of intracellular acidification due to increased carbon dioxide.

The force-velocity relation of frog sartorius muscle was observed during slow stretch and during shortening in solutions with and without CO2 at extracellular pH (pHo) 6.9 and pHo 7.5 (5 degrees C). Less force was produced with CO2 than without CO2 during stretch, during shortening, and under isometric conditions. Compared with pHo 7.5, the effects were greater at pHo 6.9, where the concentration of CO2, a permeant acid, was greater and would cause a greater acidification of intracellular pH (pHi). The reduction of force caused by CO2 was smaller during stretch than during shortening or isometric contraction. This result indicates that the crossbridge states specific to stretch retain their ability to produce force better under acidic conditions than those characteristic of shortening and isometric conditions. This difference between stretch and shortening suggests that there may be compensating changes in the pattern of motor unit activity during fatigue in vivo.

Animals↗

Correlation between autoregressive moving-average model parameters of electromyogram of human jaw closing muscles and maximum clenching time at intercuspal position.

During maximum clenching in the intercuspal position, surface electromyograms of left masseter and anterior temporal muscles were sampled in 16 healthy subjects with natural dentitions to establish a four-order, autoregressive (AR) moving-average (MA) model of the myoelectrical signals. The correlation coefficients and the linear regression between the model parameters and the clenching time were calculated. The model parameters had the positive or the negative correlation, and AR model parameters had the higher correlation than MA model parameters. The model parameters relate to muscular fatigue and the slope of the regressive equation relates to the endurance time of the isometric contraction.

Adult↗

Two years of growth hormone (GH) treatment increase isometric and isokinetic muscle strength in GH-deficient adults.

GH deficiency in adults is associated with reduced muscle mass and muscle strength. The objective of this trial was to follow the effect of 2 yr of GH treatment in GH-deficient adults on muscle performance in relation to a reference population. Knee extensor and flexor strengths for isometric and isokinetic concentric muscle strength were measured using a Kin-Com dynamometer. Hand-grip strength was measured in both hands. The fatigue index was calculated as the percent reduction in peak torque at 50 repeated isokinetic knee extensions. Superimposed, single twitch electrical stimulation was performed. The GH-deficient subjects had lower isometric knee extensor, knee flexor, and hand-grip strength than the reference population. Two years of GH treatment increased and normalized the mean isometric knee extensor and flexor strengths. The concentric knee flexor and extensor strength at an angular velocity of pi rad/s increased, as did the concentric knee flexor strength at an angular velocity of pi/3 rad/s. The increase in muscle strength was more marked in younger patients and in patients with lower initial muscle strength than predicted. Quadriceps endurance decreased, whereas the effect of superimposing single twitches on isometric contraction and hand-grip strength was unaffected by the GH treatment. Two years of GH therapy in GH-deficient adults increased and normalized isokinetic and isometric muscle strength studied in proximal muscle groups. Hand-grip strength and the degree of lack of maximal motor unit activation on voluntary isometric knee extensor force did not change. The dynamic local muscle fatigue index decreased.

Adult↗

Effect of exercise conditioning on excitation-contraction coupling in aged rats.

We studied aged (24-26 mo) Fischer 344 rats after they underwent 8 wk of moderate exercise conditioning. Right ventricular papillary muscles were loaded with the calcium indicator aequorin. Electrophysiological recordings were also performed. Time to peak isometric tension in muscles from exercised aged rats (EAR) was shorter than in those from unexercised aged rats (UAR) (126 +/- 7 vs. 167 +/- 7 ms; P less than 0.01). Time to 50% relaxation from peak isometric tension was also shorter in EAR than in UAR (88 +/- 3 vs. 119 +/- 12 ms; P less than 0.05). There was a trend toward decrease in time to peak light and a significant decrease in time to 50% decline from peak light (33 +/- 4 ms in EAR vs. 59 +/- 17 ms in UAR; P = 0.001). Action potential amplitude was smaller in EAR than in UAR (67 +/- 4 vs. 82 +/- 3 mV; P = 0.003); however, action potential duration was longer (137 +/- 6 ms in EAR vs. 100 +/- 10 ms in UAR; P = 0.005). Right ventricular-to-body weight ratios revealed no evidence of hypertrophy in EAR compared with UAR. Cardiac tissue norepinephrine content was significantly greater in EAR than in UAR (1,212 +/- 25 vs. 630 +/- 105 ng/tissue; P = 0.02). In summary, exercise reversed the age-related prolongation of isometric contraction and associated intracellular calcium transient in the aged rat while it prolonged the transmembrane action potential. In addition, exercise in aged rats resulted in an increase in cardiac norepinephrine content.

Aequorin↗

Physiological alterations of maximal voluntary quadriceps activation by changes of knee joint angle.

The purpose of this study was to investigate the influence of different angles of the knee joint on voluntary activation of the quadriceps muscle, estimating the ability of a subject to activate a muscle maximally by means of voluntary contraction. Isometric torque measurement was performed on 6 healthy subjects in 5 degrees intervals between 30 degrees and 90 degrees of knee joint flexion. Superimposed twitches at maximal voluntary contraction (MVC) and at a level of 60% and 40% of the MVC were applied and the voluntary activation estimated. At between 30 degrees and 75 degrees of knee flexion, the maximal extension torque increased at an average rate of 2.67 +/- 0.6 Nm/degree, followed by a decline with further flexion. However, throughout the joint-angle range tested, voluntary activation increased on average by 0.37%/degree with a maximum at 90 degrees of flexion. Due to the influence of joint position it is not possible to generalize results obtained at the knee joint angle of 90 degrees of flexion, which is usually used for the quadriceps twitch-interpolation technique. Consequently, it is useful to investigate voluntary activation deficits in knee joint disorders at a range of knee joint angles that includes, in particular, the more extended joint angles used frequently during daily activity.

Adult↗

Modulation of motor unit discharge rate and H-reflex amplitude during submaximal fatigue of the human soleus muscle.

Declining motor unit discharge rates and H-reflex amplitude have been observed in separate experiments during fatiguing submaximal contractions in humans. The purpose of this experiment was to investigate motor unit discharge rate, H-reflex amplitude, and twitch contractile properties concurrently during a fatiguing submaximal isometric contraction of the ankle plantarflexors. Eleven healthy subjects performed fatiguing contractions of low force (25% maximal voluntary contraction (MVC)) or high force (42-66% MVC). Hoffmann (H)-reflexes, muscle compound action potentials (M-waves), twitch contractile properties, and motor unit discharges were recorded from the soleus muscle. In the low-force fatigue task, motor unit firing rate increased gradually over time, whereas the resting H-reflex was significantly depressed at 15% of endurance time and remained quasiconstant for the rest of the task. This suggests that the processes mediating the resting H-reflex depression are relatively independent of those modulating the motor unit firing rate during a low-force fatigue task. In the high-force fatigue task, a decline in the average motor unit discharge rate was accompanied by a decrease in the resting H-reflex amplitude and a prolongation of the twitch half-relaxation time (HRT) at the completion of the fatigue task. Overall, motor unit firing rate was modulated in parallel with changes in the twitch HRT, consistent with the muscle wisdom hypothesis.

Action Potentials↗

ATP splitting by half the cross-bridges can explain the twitch energetics of mouse papillary muscle.

The aim of this study was to quantify the fraction of cross-bridges that cycle during a cardiac twitch. Measurements of the energetics of contracting left ventricular mouse papillary muscle were made in vitro (27 degrees C) using the myothermic technique. Enthalpy output was partitioned into force-dependent and force-independent components using 2,3-butanedione monoxime (BDM) to selectively inhibit cross-bridge cycling. For isometric contractions and a contraction frequency of 2 Hz the net enthalpy output was 5.7 +/- 0.8 mJ g(-1) twitch(-1) and initial enthalpy output was 2.3 +/- 0.3 mJ g(-1) twitch(-1) (n = 11). Assuming that low concentrations of BDM did not affect Ca2+ cycling, force-independent enthalpy output was 18.6 +/- 1.9% (n = 7) of the initial enthalpy output. Enthalpy output decreased with increased contraction frequency but was independent of shortening velocity. On the basis of these values, it was calculated that the twitch energetics were consistent with ATP splitting by half the cross-bridges and the pumping of one Ca2+ into the sarcoplasmic reticulum for every three cross-bridge cycles. The simplest interpretation is that half the cross-bridges completed one ATP-splitting cycle in each twitch. The lack of influence of shortening velocity on energy cost supports the idea that the amount of energy to be used is determined early in a twitch and is not greatly influenced by events that occur during the contraction.

Adenosine Triphosphate↗

The time-course of contractions induced by acetylcholine and barium in the vas deferens of normal and castrated guinea-pigs.

1. The influence of castration on contraction of the guinea pig vas deferens induced by acetylcholine was investigated regarding facilitation of endogenous neurotransmitter release, changes in post-synaptic events and modification in acetylcholine metabolization. 2. Castration prolonged the duration of the isometric contraction of the vas deferens induced by acetylcholine (3 mM) but not the duration of that induced by barium chloride (10 mM). 3. Reserpinization (0.5 mg/kg) of normal and castrated guinea pigs did not change the time-course of acetylcholine-induced contraction in the vas deferens. 4. 4-Aminopyridine (0.05 mM) prolonged the contraction induced by acetylcholine and barium chloride. This effect was blocked by reserpine pretreatment, indicating that in the presence of 4-AP, both acetylcholine and barium release endogenous noradrenaline. Since there was no difference between the effects of 4-AP on organs from normal and castrated animals, prolongation of the acetylcholine-induced contraction is not related to an increase in neutransmitter release. 5. Total cholinesterase and acetylcholinesterase activities were reduced after castration and the time-course of carbachol contraction was not changed. Thus, this decrease in enzyme activity appears to play a relevant role in the prolongation of acetylcholine-induced contraction.

Acetylcholine↗

Electromyogram median power frequency in dynamic exercise at medium exercise intensities.

The electromyogram (EMG) median power frequency of the calf muscles was investigated during an exhausting treadmill exercise and a 20-min recovery period. The exercise was an uphill run at a speed of 5 km.h-1 and a gradient of 20%. During exercise there was no decrease of EMG median power frequency. In contrast, EMG median power frequency in isometric contractions of the same muscles decreased by 7% for the soleus muscle and 16 to 18% for gastrocnemius muscles immediately after the exercise. During the recovery period the isometric median power frequency of the gastrocnemius muscles increased to pre-exercise levels in about 5 min. The isometric median power frequency of the soleus muscle also increased but had not reached pre-exercise values by 20 min. The observations from this study and from a previous uphill treadmill investigation at a steeper gradient gave evidence that two types of exhaustion can be distinguished during dynamic exercise; exhaustion at lower exercise intensities without a decrease in frequency during exercise and exhaustion at high intensities accompanied by a decline of frequency. The reason for this difference remains unclear.

Adult↗