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A Ca2+-dependent mechanism for the positive inotropic response to an increase in afterload in cat papillary muscle.

In cat papillary muscles, under control conditions (1.25 mmol/L Ca2+ bathing solution, 25 degrees C), increasing the afterload by switching from isotonic to isometric contraction elicited a positive inotropic response. Halving the bath [Ca2+] resulted in a percentagewise similar or greater positive inotropic response to increased afterload, while doubling the bath [Ca2+] reduced and caffeine abolished or reversed this response, indicating [Ca2+]i predictably influences it. Since it was markedly reduced by verapamil and unaffected by propranolol, the positive inotropic response to increased afterload was concluded to be largely due to increased Ca2+ influx, unrelated to catecholamine release, caused by increased mean muscle length over time owing to the changing from isotonic to isometric contraction. While at 25 degrees C, increasing the afterload caused a positive inotropic response at 12 to 48 stimulations/min, at 37 degrees C and at similar frequencies, a negative inotropic response occurred. This reversed to a positive inotropic response at 86 stimulations/min, well below the normal cat heart rate, suggesting an increased afterload would cause a positive inotropic response via this mechanism in vivo, as observed for years in intact mammalian hearts. Similarities between positive inotropic responses to increased afterload in isolated cardiac muscle, isolated hearts, and intact animals indicate all may be examples of the same phenomenon (Anrep effect).

Animals↗

Proprioceptors and normal tremor.

The tremor of the hand, rotating about the wrist joint, was measured using an accelerometer, and groups of muscle action potentials were simultaneously recorded from the wrist extensor muscles using surface electrodes. The accelerometer signal and the rectified, demodulated electromyogram were submitted to Fourier analysis in order to quantify the tremor in terms of its frequency components and the amplitudes of those components. The amplitudes of the 8-12 Hz peak in the frequency spectrum obtained from muscle electrical activity were compared (a) when the hand was held raised against gravity (i.e. the contraction was isotonic) with (b) when it was held raised, with the same force and in the same position against a rigid bar (i.e. the contraction was isometric). In the isotonic condition (a) a prominent 8-12 Hz peak was observed in the spectrum. In the isometric condition (b) the peak was small or absent. The conclusion is drawn that the grouping (synchronization) of motor unit action potentials underlying tremor cannot be due to any process in the central nervous system generating them and they depend on cyclic alterations in muscle length activating proprioceptors.

Action Potentials↗

Effect of adenosine receptor blockade with caffeine on sympathetic response to handgrip exercise in heart failure.

Adenosine (Ado) increases muscle sympathetic nerve activity (MSNA) reflexively. Plasma Ado and MSNA are elevated in heart failure (HF). We tested the hypothesis that Ado receptor blockade by caffeine would attenuate reflex MSNA responses to handgrip (HG) and posthandgrip ischemia (PHGI) and that this action would be more prominent in HF subjects than in normal subjects. We studied 12 HF subjects and 10 age-matched normal subjects after either saline or caffeine (4 mg/kg) infusion during isometric [30% of maximal voluntary contraction (MVC)] and isotonic (10%, 30%, and 50%) HG exercise, followed by 2 min of PHGI. In normal subjects, caffeine did not block increases in MSNA during PHGI after 50% HG. In HF subjects, caffeine abolished MSNA responses to PHGI after both isometric and 50% isotonic exercise (P < 0.05) but MSNA responses during HG were unaffected. These findings are consistent with muscle metaboreflex stimulation by endogenous Ado during ischemic or intense nonischemic HG in HF and suggest an important sympathoexcitatory role for endogenous Ado during exercise in this condition.

Adenosine↗

Impact of heart failure and exercise capacity on sympathetic response to handgrip exercise.

Peak oxygen uptake (VO(2 peak)) in patients with heart failure (HF) is inversely related to muscle sympathetic nerve activity (MSNA) at rest. We hypothesized that the MSNA response to handgrip exercise is augmented in HF patients and is greatest in those with low VO(2 peak). We studied 14 HF patients and 10 age-matched normal subjects during isometric [30% of maximal voluntary contraction (MVC)] and isotonic (10%, 30%, and 50% MVC) handgrip exercise that was followed by 2 min of posthandgrip ischemia (PHGI). MSNA was significantly increased during exercise in HF but not normal subjects. Both MSNA and HF levels remained significantly elevated during PHGI after 30% isometric and 50% isotonic handgrip in HF but not normal subjects. HF patients with lower VO(2 peak) (<56% predicted; n = 8) had significantly higher MSNA during rest and exercise than patients with VO(2 peak) > 56% predicted (n = 6) and normal subjects. The muscle metaboreflex contributes to the greater reflex increase in MSNA during ischemic or intense nonischemic exercise in HF. This occurs at a lower threshold than normal and is a function of VO(2 peak).

Blood Pressure↗

Blood flow in "red" and "'white" calf muscles in cats during isometric and isotonic exercise.

Muscle blood flow was measured with the radioactive microspheres technique in plantar flexors of seven cats. Right leg performed rhythmic isotonic and left leg sustained isometric contractions. Flows were determined at rest, during stimulation periods, and immediately after 90 sec of high frequency stimulation. During isotonic contraction, flow to m. soleus (a "red muscle") increased progressively as stimulation increased: 0.06 +/- 0.02, 0.21 +/- 0.05, 0.42 +/- 0.12, and 0.26+/- 0.06 ml/min/g during rest, 10 Hz, 50 Hz, and after 50 Hz stimulation frequencies, respectively. Corresponding values for gastrocnemius medialis were 0.06 +/- 0.01, 0.38 +/- 0.05, 0.27 +/- 0.03, and 0.28 +/- 0.06 (x +/- S.E.). These last values were characteristic also for the other "'white" muscles investigated: gastrocnemius lateralis, and plantaris. During sustained isometric exercise at 5 and 25 Hz stimulation frequency the patterns were similar, except that higher flows were observed, and during recovery flows actually increased again in the "white" muscles. Blood pressure did not change. Resting flows were similar in innervated and denervated muscles. These data demonstrate that during isotonic as well as isometric exercise there is an increased resistance to flow with increasing muscle tension in "white" but not in "red" muscles. This supports the notion that a condition of relative ischaemia exists in "white" muscles during both isometric and isotonic contractions which is more pronounced during isometric exercise. The results corroborate previous studies on isometric exercise and suggest that the pattern during isotonic exercise is similar.

Animals↗

Comparison of serotonin agonistic and antagonistic activities of a new antidepressant agent Trelibet (EGYT-475) and its metabolite EGYT-2760 on isolated rat fundus.

The effects of Trelibet (EGYT-475, N-benzyl-piperazine-picolinyl-fumarate) and its active metabolite (EGYT-2760, N-benzyl-piperazine) on the serotoninergic responses of rat stomach fundus were investigated and compared with those of MCPP (m-chlorophenyl-piperazine) which is the common metabolite of the arylpiperazine antidepressants Trazodone and Etoperidone. The contraction inhibitory potencies of the agents were determined on the equipotent contractions (EC50) to serotonin (5-HT) and prostaglandin F2 alpha (PGF2 alpha). Isotonic contractile responses to 5-HT were not affected by EGYT-475, however, both EGYT-2760 and MCPP produced concentration related and reversible inhibition of the serotoninergic responses. The IC50 values for EGYT-2760 and MCPP were 40.5 +/- 7.5 mumol/l and 125 +/- 35 nmol/l, respectively. The inhibition was selective for the serotoninergic responses, as the equipotent responses to PGF2 alpha were not affected. EGYT-2760 and MCPP displayed not only 5-HT antagonistic, but also partial agonistic activities on the rat fundus preparation. Maximum contractile response of the fundus preparation to MCPP was approximately 25%, to EGYT-2760 was 10% of the maximum response to 5-HT.

Animals↗

[Study of postinhibitory "rebound" in individual motor units of human hand muscles].

Analysis of poststimulus histograms and interspike intervals of firing motor units showed that the burst following the silent period under evoked muscle contraction is the result of synchronous motoneuron escape from inhibition. Under strong evoked isotonic muscle contraction a true facilitation was revealed. The latency of this facilitation was too long for spinal monosynaptic reflex related to spindles elongation at the muscle relaxation stage.

Electric Stimulation↗

Effects of shortening velocity and of oxygen consumption on efficiency of contraction in dog gastrocnemius.

Previous observations have shown that, in isolated perfused dog gastrocnemii in situ, stimulated to aerobic rhythmic isotonic tetanic contractions (at about 40% of maximal isometric force), only about 20% of the overall metabolic power (proportional to the rate of O2 consumption, VO2) was converted into mechanical power (W). Here we report that, in the same preparation, the maximal velocity during the shortening phase of each tetanus (v, mm s(-1)) increased with the rate of energy dissipation, as given by the difference between VO2 and W (W kg(-1)). The relationship between these variables was described by: v=2.85(VO2-W)(1.24) (R2=0.85; n=17). A mathematical analysis of this equation shows that the overall mechanical efficiency (eta=WVO2(-1)) decreased with increasing v (at constant VO2), whereas it increased with increasing VO2 (at constant v). The net effect of this state of affairs was that the decrease of eta over the entire range of work intensities was relatively minor (from 0.22 to 0.15), in spite of a large increase of v, (from 40 to 120 mm s(-1)), thanks to the concomitant increase of VO2 (from 10 to 25 W kg(-1)). So, under these experimental conditions, the energetics of work performance seems to be governed by two conflicting needs. The need for a sufficiently high shortening speed (and hence power output), itself requiring a sufficiently large energy dissipation rate, which, however, brings about a fall in eta. This is counteracted by the increased VO2, which in turn leads to an increased efficiency at the expense of a fall in shortening speed.

Algorithms↗

Effects of catecholamines on lactic acid output during progressive working contractions.

Epinephrine and norepinephrine together (E + NE) and epinephrine (E) alone were infused intravenously in stepwise increasing doses during progressive isotonic tetanic contractions. The goal was to mimic, for in situ dog skeletal muscle, the concentrations of these catecholamines in the blood and the contractions during progressive exercise. The concentrations of lactate and O2 in arterial and muscle venous blood, the arterial plasma concentration of E and NE, PO2 in arterial and muscle venous blood, and the venous outflow were measured. The infusions caused a rise in plasma E and NE like those seen in progressive exercise. Compared with no-infusion controls, the E + NE infusions and the E alone infusion resulted in significant increases in maximal lactic acid output by the muscles during the contractions from 0.24 mumol X g-1 X min-1 in the controls to 0.44 and 0.54 mumol X g-1 X min-1 during E + NE and E alone infusions, respectively. The venous O2 concentrations and partial pressures were not reduced by the infusions. Both infusions resulted in a rise of arterial lactate concentration that could not be accounted for by the lactic acid output of the contracting muscles. The E alone infusions were associated with a rise in maximal O2 uptake during the contractions. Since the effects of the E + NE and E alone infusions were similar, it was suggested that E is more active than NE. It was suggested that E also increased lactic acid production in tissues other than the working muscles.

Animals↗

Pharmacological modulation of the mechanical response of airway smooth muscle to length oscillation.

Stretch and retraction of the airways caused by changes in lung volume may play an important role in regulating airway reactivity. We studied the effects of different pharmacological stimuli on airway smooth muscle to determine whether the muscle behavior during length oscillation can be modulated pharmacologically and to evaluate the role of different activation mechanisms in determining its behavior during the oscillation. Active force decreased below the static isometric force during the shortening phase of length oscillation, resulting in an overall depression of force during the length oscillation cycle. This pattern of response was unaffected by the contractile stimulus or level of activation, suggesting that it was caused by a mechanism that is independent of the level of activation of cross bridges. The normalized area of the length-force hysteresis loop (hysteresivity) differed depending on the stimulus used for contraction. Effects of different stimuli on hysteresivity were not correlated with their effects on isotonic shortening velocity or isometric force, suggesting that the pharmacological modulation of the behavior of airway smooth muscle during length oscillation at these amplitudes cannot be accounted for by the effects on the cross-bridge cycling rate.

(4-(m-Chlorophenylcarbamoyloxy)-2-butynyl)trimethy↗

[Effects of alpha adrenergic stimulation on the mechanical properties of the myocardium].

The mechanical effects of phenylephrine at 2 x 10(-6) M (PE1, n = 8), 2 x 10(-5) M (PE2, n = 10) and 2 x 10(-4) M (PE3, n = 6) were studied on rat left ventricular papillary muscle, in the presence of propranolol (4 x 10(-7) M) and 0.5 mM of (Ca2+)e. The contraction-relaxation coupling was studied under isotonic and isometric conditions. The maximal velocity of contraction (max Vc) and relaxation (max Vr) were calculated during isotonic contraction with preload only at L max. The positive (+ dF/dt max) and negative (- dF/dt max) peaks of the derivative of the force were calculated during isometric contraction. Two coefficients, R1 = max Vc/max Vr and R2 (+ dF/dt max)/(- dF/dt max) provided an appreciation of the contraction-relaxation coupling at low and high loads respectively. The positive inotropic effect observed in the three groups was accompanied by a significant decrease of the coefficient R1 (PE1: - 11 +/- 2% p less than 0.001; PE2: - 15 +/- 2%, p less than 0.001; PE3: -20 +/- 2%, p less than 0.001). On the other hand, no significant variations of the coefficient R2 were observed (PE1: 3 +/- 3%; PE2: 1 +/- 4%; PE3: 5 +/- 3%). The proportionally greater improvement in the velocity of relaxation compared to the velocity of contraction at low loads suggests that the sarcoplasmic reticulum is involved in the expression of positive inotropic and positive lusitropic effects of alpha-adrenergic stimulation.

Adrenergic alpha-Agonists↗

Effects of ischemic and hypoxic hypoxia on VO2 and lactic acid output during tetanic contractions.

We measured O2 uptake (VO2), CO2 output (VCO2), and net lactic acid output (L) during a 30-min period of repetitive 1/s isotonic tetanic contractions of the dog gastrocnemius-plantaris muscle group. The conditions were modest ischemic hypoxia (ischemia), hypoxia hypoxia (hypoxia), and free-flow normoxia (control). The major goal was to assess the effects of these perturbations on L during contractions. Ischemia and hypoxia were initiated just before the start of the contractions and at minute 7 of contractions in separate groups of experiments. Whenever applied, both ischemia and hypoxia reduced VO2 compared with the control values. When ischemia was initiated at the start of contractions, L was reduced transiently compared with the controls. When ischemia began at minute 7, L was increased modestly but transiently compared with the controls. When hypoxia was initiated at the start of contractions, L was increased during the entire period of contractions. The L pattern was the same as in the controls, rising to a maximal value at 3 min and declining steadily to a lower value at 30 min. When hypoxia began at minute 7, L declined initially at a slower rate than it did in the controls and was thereby elevated above the controls from 9 to 30 min. Ischemia was associated with a more rapid reduction in mechanical performance than hypoxia. The data suggest that the mechanisms of the decreased mechanical performance and VO2 are different for ischemia and hypoxia.

Animals↗

A simple Hill element-nonlinear spring model of muscle contraction biomechanics.

The purpose of this study was to develop a model to predict the mechanical response of muscles during isometric tetanic, afterloaded isotonic and isovelocity shortening contractions. Two versions of the model were developed. Both incorporated a contractile element that obeyed a Hill force-velocity relationship and a series elastic element. In a quadratic spring version, the series elastic element force was represented as proportional to the square of the stretch; in a cubic spring version, it was represented as proportional to the cube of the stretch. Both versions provided closed-form equations for response predictions that involved four independent parameters. Once the four parameters were chosen, each of these responses could be predicted. Model validity was established by comparing predicted and observed responses in slow and fast hindlimb muscles of rodents. Significant model-predicted responses seldom differed by more than 15% from experimental values. The model can provide insights into how changes in individual properties affect the overall mechanical behavior of muscles in a variety of circumstances and reduce the need for collection of experimental data.

Animals↗

O2 uptake and work by in situ muscle performing contractions with constant shortening.

The oxygen uptake by the gastrocnemius-plantaris muscle group of the dog was measured during brief submaximal isotonic-tetanic contractions. Shortening in the contractions was kept constant while the load was altered by adjusting the stimulation voltage applied to the motor nerve. Incompletely fused tetanic contractions were produced by 200 msec trains of impulses at a frequency of 20/sec. The trains were delivered once a second. The rate of oxygen uptake (VO2) was linearly related to the external work rate (W). The relationship between VO2, microliter/g min, vs W, gM/g min, is described by the equation VO2 = 18.0 + 3.36 W. The average maximal gross efficiency was 12.5%. The major determinant of VO2 during contractions appeared to be the number of muscle fibers which were activated during the contractions.

Animals↗

In vivo force-velocity relation of human muscle: a modelling from sinusoidal oscillation behaviour.

Isokinetic tests performed on human muscle in vivo during plantar flexion contractions lead to torque-angular velocity relationships usually fitted by Hill's equation expressed in angular terms. However, such tests can lead to discrepant results since they require maximal voluntary contractions performed in dynamic conditions. In the present study, another way to approach mechanical behaviour of a musculo-articular structure was used, i.e. sinusoidal oscillations during sub-maximal contractions. This led to the expression of (i). Bode diagrams allowing the determination of a damping coefficient (B(bode)); and (ii). a viscous parameter (B(sin)) using an adaptation of Hill's equation to sinusoidal oscillations. Then torque-angular velocity relationships were predicted from a model based on the interrelation between B(bode) and B(sin) and on the determination of optimal conditions of contraction. This offers the possibility of characterizing muscle dynamic properties by avoiding the use of isokinetic maximal contractions.

Ankle↗

Criterion validation of surface EMG variables as fatigue indicators using peak torque: a study of repetitive maximum isokinetic knee extensions.

A number of studies have been published that have used variables of the electromyogram (EMG) power spectrum during dynamic exercise. Despite these studies there is a shortage of studies of the validity of surface EMG registrations during repetitive dynamic contractions with respect to fatigue. The aim of this study was to investigate if the surface EMG variables mean frequency (MNF [Hz]) and the signal amplitude (RMS [microV]) are valid indicators of muscular fatigue (defined as "any exercise-induced reduction in the capacity to generate force or power output") during maximum repeated isokinetic knee extensions (i.e. criterion validity using peak torque). Twenty-one healthy volunteers performed 100 isokinetic knee extensions at 90 degrees s(-1). EMG signals were recorded from the vastus lateralis, the rectus femoris and the vastus medialis of the right thigh by surface electrodes. MNF and RMS of the EMG together with peak torque (PT [Nm]) were determined for each contraction. MNF showed consequently higher correlation coefficients with PT than RMS did. Positive correlations generally existed between MNF and PT. The majority of the subjects had positive correlations between RMS and PT (i.e. decreases both in PT and in RMS). In conclusion, at the individual level MNF generally - in contrast to RMS - showed good criterion validity with respect to biomechanical fatigue during dynamic maximum contractions.

Adult↗

Effects of eccentrically and concentrically induced unilateral fatigue on the involved and uninvolved limbs.

This study extended findings of others related to the fatigue resistance of maximum voluntary knee extension contractions performed eccentrically on an isokinetic dynamometer. Twelve subjects performed either 75 unilateral isokinetic concentric MVCs or 75 unilateral isokinetic eccentric MVCs at 30 degrees s(-1). A uniquely-configured dynamometer provided the opportunity to describe the effect of the concentric or eccentric fatigue protocol on the concentric or eccentric MVC force of the contralateral limb, which was not involved in the fatigue protocol, immediately following the conclusion of the fatigue protocol. Eccentric MVC of the eccentrically fatigued group decreased significantly (13%, p = 0.001) although the decrease was significantly smaller than that of the concentric MVC of the concentrically fatigued group (39%). Concentric MVC of the contralateral limb was unaffected following the concentric fatigue protocol but the eccentric MVC of the contralateral limb increased 11% (p = 0.028) following the eccentric fatigue protocol. These results suggest that eccentric MVCs are not resistant to fatigue but do follow a different time course than fatigue induced with concentric contractions. The extent to which eccentrically performed MVCs fatigue may reflect the influence of protocol parameters such as the isokinetic speed, the number of repetitions, the criteria by which the protocol is terminated and the subject selection. However, the explanations for why eccentric MVCs fatigue to such a smaller extent necessitate further systematic investigation including electrophysiologic methods, as do the results relative to the contralateral leg. Both results can be considered within the framework of current thought about the disparate nature of nervous system control of eccentric contractions.

Adult↗