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Influence of age on isometric, isotonic, and isokinetic force production characteristics in men.

BACKGROUND AND PURPOSE: Most previous studies have focused on the effects of age on muscle performance of a single type of contraction, usually isometric, and usually on only a single muscle group. Instead,we investigated the influence of age on isometric, isotonic, and isokinetic muscle performance in men aged 20-83 years and determined relationships between regional lean body mass and muscle performance. METHODS: Seventy-five volunteers were placed into designated 10-year age groups: 20-29 (n=13), 30-39 (n=14), 40-49 (n=15), 50-59 (n=10), 60-69 (n=14), and 70+ years (n=9). Muscle performance was characterized by a number of parameters, including strength, time, and rate for maximal voluntary contractions using all 3 contraction types and 4 muscle groups (elbow extensors, elbow flexors, knee extensors, and knee flexors). Measures of lean body mass were obtained by dual energy x-ray absorptiometry. RESULTS: There were significant age group differences in maximal force (P < or = 0.05) for each type of muscle contraction, and in maximal rates of isometric force production (P < or = 0.05), with declines beginning around 60 years of age. Differences in muscle performance between age groups remained when body composition differences were controlled statistically. CONCLUSION: Chronological age affected performance of both upper and lower extremity muscles, independent of muscle mass, and regardless of contraction type; however, isometric performance was the least affected.

Adult↗

Magnetic resonance imaging of isolated skeletal muscles. Osmotic influence.

RATIONALE AND OBJECTIVES: The authors evaluate the contribution of intracellular water to the change of T2 relaxation time. METHODS: Magnetic resonance images of frog muscles (n = 16) were obtained in hypotonic, isotonic, and hypertonic solutions, and their leg weights and T2 relaxation times were measured. Likewise, these values were measured after electric stimulation for 2 to 10 minutes in isotonic solution (n = 5). RESULTS: The muscle weights increased in the hypotonic solutions, whereas they showed no change in isotonic solution. T2 relaxation times, however, showed little change in either isotonic or hypotonic solutions. In electrically stimulated muscles, T2 relaxation times increased, accompanying the increase in muscle weight in isotonic solutions. CONCLUSION: Muscle contraction results in increased T2 relaxation time, but intracellular water hardly contributes to the increase in this value. Therefore, an increase in extracellular water may be the main cause of the increase in T2 relaxation time seen in exercised muscles.

Animals↗

Changes in surface EMG parameters during static and dynamic fatiguing contractions.

The effect of contraction types on muscle fiber conduction velocity (MFCV), median frequency (MDF) and mean amplitude (AMP) of surface electromyography was examined in the vastus lateralis of 19 healthy male adults. The subjects performed knee extension both statically and dynamically until they were exhausted. The static contraction was a sustained isometric extension of the knee at a joint angle of 90 degrees with 50% of the maximum voluntary contraction (MVC) load. The dynamic contraction was a repetitive isotonic extension of the knee between the angles of 90 degrees and 180 degrees with the same 50% MVC load at a frequency of 10 times per minute. MFVC during the static contraction significantly decreased during the exercise (p < 0.01). On the other hand, MFVC during the dynamic contraction did not significantly change throughout the exercise. MDF decreased and AMP increased during both types of contractions (p < 0.01). Because the blood flow within the muscle is maintained during the dynamic contraction by enhanced venous return from the contracting muscle, these results suggested that MFVC is affected by the metabolic state in the muscle and the changes in MDF cannot be explained only by that of MFVC.

Adult↗

The contraction induced by ethylenediaminetetracetic acid-4 sodium (EDTA-4Na) in guinea-pig isolated vas deferens kept in isotonic sucrose medium.

1. Ethylenediaminetetracetic acid--4 sodium (EDTA--4Na) induced a contraction in guinea-pig isolated vas deferens kept in isotonic sucrose medium containing 0.07% Nahco3 and 0.1% glucose after preincubation in Locke's solution. The maximum contraction was 82.1 +/- 6.7% of that induced by added KCl. 2. EDTA--Ca--2Na (10(-7) to 10(-3) g/ml) induced no contraction in preparations kept in the sucrose medium. 3. The EDTA--4Na-induced contraction was also obtained when sucrose in the sucrose medium was replaced by glucose but not when the preparation was kept in Locke's solution. 4. The EDTA--4Na-induced contraction was decreased by reduction of the CaCl2 of KCl concentration of the Locke's solution in which the preparation had been preincubated before placing in the sucrose medium. 5. The EDTA--4Na-induced contraction was suppressed with increasing concentrations of NaCl used to partially replace sucrose in the sucrose medium. 6. When the preparation was kept in EDTA-free sucrose medium after pretreatment with 10(-4) g/ml of EDTA--4Na in the sucrose medium for 20 min, a contraction was induced by added CaCl2. The maximum contraction induced by CaCl2 was 30.1 +/- 11.8% of that of the EDTA--4Na-induced contraction, when CaCl2 was added at 20 min after the exchange of medium.

Animals↗

Muscarinic hyperresponsiveness of antigen-sensitized feline airway smooth muscle in vitro.

OBJECTIVE: To determine the effect of in vivo antigen sensitization (Ascaris suum) of cats on tracheal smooth muscle (TSM) and bronchial smooth muscle (BSM) muscarinic reactivity in vitro. ANIMALS: Healthy domestic shorthair cats of either sex. PROCEDURE: Cats were sensitized and were long-term antigen (or sham) challenge exposed for 6 weeks by aerosolization with soluble Ascaris suum. Tracheal and BSM preparations were obtained and stimulated in vitro by electrical field stimulation (EFS), acetylcholine (ACh, a muscarinic agonist), and physostigmine (an AChase inhibitor). Responses were compared with responses of comparable tissues from sham antigen challenge-exposed cats. RESULTS: Tracheal and BSM from sensitized, compared with sham-sensitized (control), cats had greater isometric contraction (expressed as percentage of the response observed for isotonic, 63 mM KCl-elicited contraction [% KCl]) in response to endogenous (EFS) and exogenous muscarinic receptor activation (ACh). Contractions in response to EFS by TSM from control cats were 74% KCl vs 97% KCl for antigen-sensitized TSM (P < 0.04). Muscarinic responses were augmented comparably by in vivo sensitization; TSM from control cats contracted to 190% KCl vs 230% KCl (P < 0.03) for TSM from immune-sensitized cats. Physostigmine augmented responses of all tissues to ACh so that TSM from control (290% KCl) and antigen-sensitized (257% KCl) cats were similar. Responses of BSM from antigen-sensitized cats had similar augmentation of contractile response to EFS and ACh. CONCLUSIONS: Long-term in vivo antigen sensitization increases numbers of muscarinic receptors on airway smooth muscle or decreases the availability or activity of AChase in cats. CLINICAL RELEVANCE: Modulation of muscarinic receptors may be useful for treatment of asthmatic cats with in vivo airway hyperreactivity.

Acetylcholine↗

Load clamp analysis of maximal force potential of mammalian cardiac muscle.

1. Abrupt alterations in load (load clamps) have been imposed on cat papillary muscle during isotonic shortening and relaxation of afterloaded twitch and tetanic contractions, to assess the maximal force potential for a given contractile state. 2. These load clamps were accompanied by an initial fast lengthening reflecting an undamped series compliance. Even when exceeding isometric twitch and tetanic force, these loads could be borne for a considerable time, accompanied by a slower lengthening after the initial extension of the series compliance. At sufficiently high loads the muscle was pulled out very rapidly; a maximal supra-isometric force potential was defined as the load the muscle could bear momentarily and this was measured at times throughout contraction and relaxation. 3. This maximal force potential was determined at different initial muscle lengths. Depending on the instantaneous loading conditions, various length-force relations were obtained from : (a) peak force values of isometric twitches at different starting lengths, (b) the shortest length reached during after loaded isotonic twitches, and (c) the forces obtained in overloaded isotonic twitch contractions. 4. These results are consistent with a crossbridge model in which the delayed lengthening during isotonic overloading is due to back rotation and detachment of attached crossbridges and in which the inital phase of spontaneous isotonic relaxation is governed by the same mechanism.

Animals↗

Sympathetic nerve activity during prolonged rhythmic forearm exercise.

Exercise is a potent stimulus to activate the sympathetic nervous system. Previous work suggests that metabolite-sensitive muscle afferents are activated near the point of fatigue, and, when activated, they determine the muscle sympathetic nerve activity (MSNA) response to isometric forearm exercise. Yet, studies using a more prolonged rhythmic exercise paradigm suggest that the sympathetic nervous system can be activated in a more graded fashion. The purpose of this study was to determine whether metaboreceptor stimulation would also be responsible for MSNA responses to prolonged rhythmic isotonic forearm exercise. Subjects (n = 16) performed rhythmic isotonic forearm exercise at 25% maximal voluntary contraction for 30 min as we measured MSNA (microneurography). We observed progressive increases in MSNA with a peak increase of 161 units from a baseline value of 180 units. We also performed posthandgrip circulatory arrest (PHG-CA) in nine of these subjects. This maneuver isolates the metaboreceptor contribution to MSNA. During PHG-CA, delta MSNA values were not different from those observed during a freely perfused recovery period (n = 7). We also compared MSNA responses during the rhythmic paradigm with those seen during a static protocol at 40% of maximal voluntary contraction in five subjects. The two types of exercise caused similar increases in MSNA, but only the static paradigm was associated with a sustained MSNA response during PHG-CA. Finally, 31P-nuclear magnetic resonance was used to evaluate muscle metabolic responses during rhythmic and static forearm exercise (n = 6). Static exercise caused muscle acidosis and an increase in H2PO4-, whereas rhythmic exercise had no effect on muscle metabolism.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Isotonic relaxation of control and sensitized airway smooth muscle.

Smooth muscle relaxation has most often been studied in isometric mode. However, this only tells us about the stiffness properties of the bronchial wall and thus only about wall capacitative properties. It tells us little about airflow. To study the latter, which of course is the meaningful parameter in regulation of ventilation and in asthma, we studied isotonic shortening of bronchial smooth muscle (BSM) strips. Failure of BSM to relax could be another important factor in maintaining high airway resistance. To analyze relaxation curves, we developed an index of isotonic relaxation, t1/2(P, lCE), which is the half-time for relaxation that is independent of muscle load (P) and of initial contractile element length (lCE). This index was measured in curves of relaxation initiated at 2 s (normally cycling crossbridges) and at 10 s (latch-bridges). At 10 s no difference was seen for adjusted t1/2(P, lCE) between curves obtained from control and sensitized BSM, (8.38 +/- 0.92 s vs. 7.78 +/- 0.93 s, respectively). At 2 s the half-time was almost doubled in the sensitized BSM (6.98 +/- 0.01 s (control) vs. 12.74 +/- 2.5 s (sensitized)). Thus, changes in isotonic relaxation are only seen during early contraction. Using zero load clamps, we monitored the time course of velocity during relaxation and noted that it varied according to 3 phases. The first phase (phase i) immediately followed cessation of electrical field stimulation (EFS) at 10 s and showed almost the same velocity as during the latter 1/3 of shortening; the second phase (phase ii) was linear in shape and is associated with zero load velocity, we speculate it could stem from elastic recoil of the cells' internal resistor; and the third phase (phase iii) was convex downwards. The zero load velocities in phase iii showed a surprising spontaneous increase suggesting reactivation of the muscle. Measurements of intracellular calcium (Fura-2 study) and of phosphorylation of the 20 kDa myosin light chain showed simultaneous increments, indicating phase iii represented an active process. Studies are under way to determine what changes occur in these 3 phases in a sensitized muscle. And of course, in the context of this conference, just what role the plastic properties of the muscle play in relaxation requires serious consideration.

Animals↗

Stereospecific effects of ketamine enantiomers on canine tracheal smooth muscle.

1. Ketamine is a potent bronchodilator which relaxes airway smooth muscle (ASM). Clinically, ketamine is used as a 1:1 racemic mixture of enantiomers that differ in their analgesic and anaesthetic effects. The aim of this study was to determine whether there was a difference between the enantiomers in their ability to relax isolated ASM and to explore mechanisms responsible for any observed differences. 2. Canine tracheal smooth muscle strips were loaded with fura-2 and mounted in a photometric system to measure simultaneously force and [Ca2+]i. Calcium influx was estimated by use of a manganese quenching technique. 3. In strips stimulated with 0.1 microM ACh (EC50) R(-)-ketamine (1-100 microM) caused a significantly greater concentration-dependent decrease in force (P<0.0001) and [Ca2+]i than S(+)-ketamine (1-100 microM) (P<0.0005). In contrast, there was no significant difference between the enantiomers in their ability to inhibit calcium influx (45% decrease in influx rate for R(-)-ketamine and 44% for S(+)-ketamine, P =0.782). In strips contracted with 24 mM isotonic KCI (which activates voltage-operated calcium channels), the enantiomers modestly decreased force and [Ca2+]i; there was no significant difference between the enantiomers in their effects on force (P=0.425) or [Ca2+]i (P=0.604). 4. The R(-)-enantiomer of ketamine is a more potent relaxant of ACh-induced ASM contraction than the S(+)-enantiomer. This difference appears to be caused by differential actions on receptor-operated calcium channels.

Acetylcholine↗

Calcium dependence of myosin phosphorylation and airway smooth muscle contraction and relaxation.

The time course and the steady-state calcium dependence of myosin phosphorylation and isotonic shortening velocity were studied during contraction and relaxation of canine tracheal smooth muscle. Dephosphorylation of myosin coincided with the decay of isotonic shortening velocity during rapid relaxation following agonist washout. However, the decay of shortening velocity preceded dephosphorylation during a slow relaxation induced by Ca2+-free physiological salt solution (PSS). Carbachol dose-response curves for isometric stress development and myosin phosphorylation were superimposable but shifted to the left of the shortening velocity dose-response. The steady-state Ca2+ dependence of myosin phosphorylation was defined using carbachol and K+ as agonists. There was a significant dissociation of dephosphorylation and relaxation following a stepwise reduction of extracellular CaCl2 concentration. This result was related to muscarinic activation because the dissociation of relaxation and dephosphorylation was reduced by atropine in muscles stimulated with K+. Myosin phosphorylation was completely dissociated from contraction when muscles were stimulated with carbachol in Ca2+-free PSS and contracted by readmission of CaCl2. Mechanisms in addition to myosin phosphorylation appear to regulate airway muscle tone and shortening velocity, and two possibilities are discussed.

Acetylcholine↗

Involvement of Ca2+ influx-induced Ca2+ release in contractions of intact vascular smooth muscles.

Application of Ca2+ (0.1-2.5 mM) to guinea pig aortas incubated in Ca(2+)-free isotonic KCl solution induced a contraction (Ca contraction), a part of which depended on preloading the intracellular stores with Ca2+ and which was sensitive to 3 x 10(-5) M ryanodine. Because 45Ca2+ influx from the external fluid upon the addition of Ca2+ was not modified either by the state of filling of the Ca2+ store or by the presence of ryanodine, the ryanodine-sensitive component of the contraction could be attributed to the Ca2+ influx-induced Ca2+ release from the Ca2+ store. Supporting the possibility of involvement of Ca(2+)-induced Ca2+ release, the Ca contraction due to 0.1 mM Ca2+ was enhanced either by decreasing Mg2+ in the medium or by low temperature. The ratio of the ryanodine-sensitive fraction in the Ca contraction was inversely related to the concentration of Ca2+ added and also to the extent of 45Ca2+ influx. When the Ca2+ influx was decreased by verapamil or cadmium, the ratio of ryanodine-sensitive fraction increased. On the contrary, an increase of Ca2+ influx by CGP-28392 decreased the ratio. These results suggest that Ca2+ influx at a physiological level triggers Ca2+ release from the Ca2+ store, resulting in the amplification of contractile force.

Animals↗

Nonexcised papillary muscle preparation: force and length measurement and control.

An electromechanical servocontrol system was developed to analyze mechanical properties of a nonexcised, blood-perfused papillary muscle. A miniature load cell mounted on the moving arm of a pen motor measured muscle force, and a shaft angle sensor built in the motor measured the length. The pen motor was actuated by a servocontrol command signal. A papillary muscle was exposed in the right ventricle of an excised, cross-circulated canine heart. The tendinous end of the papillary muscle was connected to the load cell. The intact root of the muscle was fixed by a metal ring. The preparation was stable over 5 h heating at a regular spontaneous heart rate (95-150/min) at 37 degrees C. The system allowed the muscle to contract in various modes such as isometric, isotonic, auxotonic, afterloaded isotonic, quick released, lengthening, etc. Changes in the contraction mode, preload, and afterload could be achieved at the investigator's disposal simply by turning switches and potentiometers, or by feeding external command signals of desired wave forms.

Animals↗

Correlation of contractions and transit in rat small intestine.

A single strain gauge was implanted chronically in the proximal jejunum of the rat to record contractions. FAsted pentobarbital-anesthetized animals received glucagon, caerulein, or isotonic saline control infusions intravenously while contractions were recorded. In control animals, the distribution of contractions in time showed clusters, with peaks at intervals of 14.24 +/-5.6 (SD) min. Glucagon produced dose-related inhibition of contractions. Caerulein at two lower doses produced a more uniform distribution of contractions in time; a higher dose caused inhibition. In other fasted rats, an isotopically labeled bolus was given through a chronically implanted duodenal cathether, and its distribution along the small intestine was examined in animals receiving the same doses of glucagon, caerulein, and saline. Glucagon caused a dose-related delay in transit. Those doses of caerulein that produced a uniform distribution of contractions accelerated transit; the dose that inhibited contractions delayed transit. Doses of glucagon and caerulein known to affect both motility and transit did not significantly affect water movement. The fasted rat resembles the fasted go in respect to the temporal distributions of jejunal contractions at a single point. Both quantitative and qualitative changes in contractions induce changes in transit.

Animals↗

Effects of palytoxin on isolated intestinal and vascular smooth muscles.

Palytoxin (PTX), the most potent marine toxin isolated from the Zoanthid, Palythoa tuberculosa, was studied to determine the effect on isolated smooth muscles. In guinea pig taenia coli PTX at above 3 X 10(-10) g/ml caused a contraction which slowly subsided under isotonic recording. Under isometric recording PTX at above 1 X 10(-10) g/ml caused a contraction which depended on the spontaneous activity. The PTX-induced contraction was not affected by atropine, tripelenmamine or tetrodotoxin but was inhibited by 5 mM Mg, norephinrphrine, isoprenaline or papaverine. PTX at above 1 X 10(-9) g/ml induced an increase in spike frequency and a slight depolarization accompanied with a contraction when measured using a sucrose gap method. In some cases the spike generation was almost abolished after a long exposure to higher dose of PTX and the developed tension gradually decreased. Under isometric recording PTX caused a sustained contraction in rabbit aorta, dog mesenteric and coronary arteries at above 1 X 10(-10) and 1 X 10(-11) g/ml, respectively, in a dose-dependent manner. The coronary artery was most sensitive among the preparation used. PTX-induced contraction in aorta was irreversible, was not influenced by phentolamine but diminished with 5 mM Mg and disappeared in a D-600 or Ca-free medium. PTX is thus an extremely potent and direct stimulant which acts on smooth muscles.

Acrylamides↗

Autonomic energy conversion. II. An approach to the energetics of muscular contraction.

All discussions of muscle energetics concern themselves with the Hill force-velocity relation, which is also the general output relation of a class of self-regulated energy converters and as such contains only a single adjustable parameter -the degree of coupling. It is therefore important to see whether in principle muscle can be included in this class. One requirement is that the muscle should possess a working element characterized by a dissipation function of two terms: mechanical output and chemical input. This has been established by considering the initial steady phase of isotonic and isometric tetanic contraction to represent a stationary state of the fibrils (a considerable body of evidence supports this). Further requirements, which can be justified for the working element, are linearity and incomplete coupling. Thus the chemical input of the muscle may be expected to follow the inverse Hill equation (see Part I). The relatively large changes in activities of reactants which the equation demands could only be controlled by local operation of the regulator, and a scheme is outlined to show how such control may be achieved. Objections to this view recently raised by Wilkie and Woledge rest on at least two important assumptions, the validity of which is questioned: (a) that heat production by processes other than the immediate driving reaction is negligible, which disregards the regulatory mechanism (possibly this involves the calcium pump), and (b) that the affinity of the immediate driving reaction is determined by over-all concentrations. The division of heat production into "shortening heat" and "maintenance heat" or "activation heat" is found to be arbitrary.

Autonomic Nervous System↗

The inhibition of rabbit skeletal muscle contraction by hydrogen ions and phosphate.

1. The effects of phosphate and protons on the mechanics and energetics of muscle contraction have been investigated using glycerinated rabbit psoas muscle. 2. Fibres were fully activated by addition of Ca2+ (pCa 4-5) at 10 degrees C. The velocities of contraction were measured in isotonic load clamps, and the velocities of unloaded fibres were measured by applying a series of step changes in fibre length. Fibre ATPase activity was monitored using an enzyme system to couple ADP production to reduced nicotinamide-adenine dinucleotide (NADH) and measuring the depletion of NADH by optical density. 3. At pH 7.0 and 3 mM-phosphate, isometric tension (P0) was 13.2 +/- 0.9 N/cm (mean +/- S.E.M., n = 10 observations), the maximum contraction velocity (Vmax) was 1.63 +/- 0.05 lengths/s (n = 5) and the ATPase activity was 1.27 +/- 0.12 s-1 myosin head-1 (n = 35). Increasing phosphate from 3 to 20 mM at pH 7.0 does not affect Vmax, causes a small decrease in the ATPase activity (15-20%) and decreases P0 by approximately 20%. Changing pH from 7 to 6 at 3 mM-phosphate decreases P0 by 45% and both Vmax and ATPase activity by 25-30%. The effects of changing both pH and phosphate were approximately additive for all parameters measured. The inhibition of these parameters by low pH and high concentration of phosphate was reversible. 4. The force-velocity relation was fitted by the Hill equation using a non-linear least-squares method. The value of the parameter which describes the curvature, a/P0, was 0.20. The curvature of the force-velocity relation was not changed by addition of phosphate or by changes in pH. 5. These data provide information on both the kinetics of the actomyosin interaction and on the process of muscle fatigue. The data are consistent with models of cross-bridge kinetics in which phosphate is released within the powerstroke in a step involving a rapid equilibrium between states. The inhibition by protons is more complex, and may involve less specific effects on protein structure. 6. During moderate fatigue of living skeletal muscle, MgATP concentration is known to remain approximately constant at 4 mM, phosphate to increase from 3 to 20 mM, and protons from 0.1 to 1 microM. The data suggest that much of the inhibition of P0 observed during moderate fatigue can be explained by the increased levels of phosphate and protons, and that much of the inhibition of fibre Vmax and ATPase activity can be explained by the increase in protons.

Adenosine Triphosphatases↗

The effects of dantrolene on the contraction, relaxation, and energetics of the diaphragm muscle.

UNLABELLED: Dantrolene is used in patients with muscle spasticity and is the only known effective treatment for malignant hyperthermia. However, its effects on muscle relaxation and energetics are unknown and may have important consequences in diaphragmatic function. We studied the effects of dantrolene (10(-8) to 10(-4) M) on diaphragm muscle strips (n = 12) in the hamster in vitro (Krebs-Henseleit solution, 29 degrees C, 95% oxygen/5% carbon dioxide) in response to tetanic stimulation (50 Hz). We studied contraction and relaxation under isotonic and isometric conditions, as well as energetics. Data are mean +/- SD. Dantrolene induced a negative inotropic effect in the hamster diaphragm (active force at 10(-4) M: 34% +/- 7% of baseline; P < 0.05) but did not significantly modify the curvature of the force-velocity relationship. Dantrolene did not significantly modify isotonic relaxation. Dantrolene, up to 10(-5) M, did not significantly impair isometric relaxation. In conclusion, dantrolene induced a marked negative inotropic effect on diaphragm muscle without affecting myothermal efficiency and relaxation. IMPLICATIONS: Dantrolene induced a significant and concentration-dependent negative inotropic effect on diaphragm muscle but did not modify isotonic relaxation, which suggests no alteration of the calcium reuptake by the sarcoplasmic reticulum; up to 10(-5) M dantrolene did not alter isometric relaxation, i.e., myofilament calcium sensitivity. Dantrolene did not modify the energetics of diaphragm muscle.

Animals↗