Latency Relaxation Research Articles

Análisis costo-efectividad de rocuronio y succinilcolina en tiroidectomías programadas

En el presente trabajo se realiza un análisis costo-efectividad de la succinilcolina y del rocuronio utilizados en la intubación de pacientes sometidos a tiroidectomía programada, mediante un estudio descriptivo prospectivo, donde se tuvo en cuentala calidad de intubación, los tiempos de latencia y de relajación muscular, necesidad de reversión farmacológica del bloqueo neuromuscular, parámetros hemodinámicos,reacciones adversas y costos directos e indirectos en 30 pacientes sometidos al procedimiento.El análisis económico evidenció la existencia de diferencias significativas entre los costos asociados al tiempo de latencia de la relajación muscular. En cuanto a los costos relacionados al bloqueo muscular, se observó que el grupo con succinilcolinapresentó unos costos totales de 10.972 ± 341,7 pesos colombianos, mientras que con rocuronio fueron de 63.088 ± 1.184 con valor P < 0,0001. La succinilcolinamostró mayor costo-efectividad al presentar menor tiempo de latencia, mejores condiciones de intubación, no provocar cambios hemodinámicos clínicamente significativos y bajo costo al ser comparado con rocuronio.

Minimum number of myosin motors accounting for shortening velocity under zero load in skeletal muscle.

Myosin filament mechanosensing determines the efficiency of the contraction by adapting the number of switched ON motors to the load. Accordingly, the unloaded shortening velocity (V0 ) is already set at the end of latency relaxation (LR), ∼10ms after the start of stimulation, when the myosin filament is still in the OFF state. Here the number of actin-attached motors per half-myosin filament (n) during V0 shortening imposed either at the end of LR or at the plateau of the isometric contraction is estimated from the relation between half-sarcomere compliance and force during the force redevelopment after shortening. The value of n decreases progressively with shortening and, during V0 shortening starting at the end of LR, is 1-4. Reduction of n is accounted for by a constant duty ratio of 0.05 and a parallel switching OFF of motors, explaining the very low rate of ATP utilization found during unloaded shortening. The maximum velocity at which a skeletal muscle can shorten (i.e. the velocity of sliding between the myosin filament and the actin filament under zero load, V0 ) is already set at the end of the latency relaxation (LR) preceding isometric force generation, ∼10ms after the start of electrical stimulation in frog muscle fibres at 4°C. At this time, Ca2+ -induced activation of the actin filament is maximal, while the myosin filament is in the OFF state characterized by most of the myosin motors lying on helical tracks on the filament surface, making them unavailable for actin binding and ATP hydrolysis. Here, the number of actin-attached motors per half-thick filament during V0 shortening (n) is estimated by imposing, on tetanized single fibres from Rana esculenta (at 4°C and sarcomere length 2.15μm), small 4kHz oscillations and determining the relation between half-sarcomere (hs) compliance and force during the force development following V0 shortening. When V0 shortening is superimposed on the maximum isometric force T0 , n decreases progressively with the increase of shortening (range 30-80nm per hs) and, when V0 shortening is imposed at the end of LR, n can be as low as 1-4. Reduction of n is accounted for by a constant duty ratio of the myosin motor of ∼0.05 and a parallel switching OFF of the thick filament, providing an explanation for the very low rate of ATP utilization during extended V0 shortening.

Acceleration and Force Reveal Different Mechanisms of Electromechanical Delay

Electromechanical delay (EMD) represents a series of complex processes of converting an electrical stimulus to a mechanical response. To quantify the contribution of electrochemical and mechanical processes of EMD in the human biceps brachii muscle over a wide range of elbow joint angles, we determined the onset of muscle contraction and the beginning of force development by recording acceleration of skin surface over the muscle and elbow flexion force, respectively. Ten healthy male volunteers underwent two experimental sessions, in which submaximal paired-pulse stimuli were applied percutaneously to the resting biceps brachii muscle at 10 different elbow joint angles from 40° to 130° (0° represents full extension). The electrical stimulation induced repeatable contractions, in which the test-retest reliability of time parameters was sufficiently high (intraclass correlation coefficient=0.84-0.88). The time for electrochemical process ranged between 3.1±0.8 and 3.6±0.9 ms and was independent of elbow joint angle (P=0.64). The time for mechanical process and the total duration of EMD, however, were significantly greater at elbow flexion positions than at 40°, the most extended position in this study (P<0.05). Regression analysis revealed that at elbow flexion positions, the time for mechanical process increased significantly with decreasing the muscle-tendon length of the biceps brachii calculated from a musculoskeletal model (R=0.54, P<0.001). These results suggest that, in the human biceps brachii muscle, the prolongation of EMD at short muscle-tendon length is not attributed to the impairment of the electrochemical process of muscle contraction but to the increased slack within the muscle-tendon unit.

Large-scale models reveal the two-component mechanics of striated muscle.

This paper provides a comprehensive explanation of striated muscle mechanics and contraction on the basis of filament rotations. Helical proteins, particularly the coiled-coils of tropomyosin, myosin and α-actinin, shorten their H-bonds cooperatively and produce torque and filament rotations when the Coulombic net-charge repulsion of their highly charged side-chains is diminished by interaction with ions. The classical “two-component model” of active muscle differentiated a “contractile component” which stretches the “series elastic component” during force production. The contractile components are the helically shaped thin filaments of muscle that shorten the sarcomeres by clockwise drilling into the myosin cross-bridges with torque decrease (= force-deficit). Muscle stretch means drawing out the thin filament helices off the cross-bridges under passive counterclockwise rotation with torque increase (= stretch activation). Since each thin filament is anchored by four elastic α-actinin Z-filaments (provided with force-regulating sites for Ca2+ binding), the thin filament rotations change the torsional twist of the four Z-filaments as the “series elastic components”. Large scale models simulate the changes of structure and force in the Z-band by the different Z-filament twisting stages A, B, C, D, E, F and G. Stage D corresponds to the isometric state. The basic phenomena of muscle physiology, i. e. latency relaxation, Fenn-effect, the force-velocity relation, the length-tension relation, unexplained energy, shortening heat, the Huxley-Simmons phases, etc. are explained and interpreted with the help of the model experiments.

A Structural Origin of Latency Relaxation in Frog Skeletal Muscle

A time-resolved x-ray diffraction study at a time resolution of 0.53 ms was made to investigate the structural origin of latency relaxation (LR) in frog skeletal muscle. Intensity and spacing measurements were made on meridional reflections from the Ca-binding protein troponin and the thick filament and on layer lines from the thin filament. At 16°C, the intensity and spacing of all reflections started to change at 4 ms, simultaneously with the LR. At 0°C, the intensity of the troponin reflection and the layer lines from the thin filament and the spacing of the 14.3-nm myosin meridional reflection, but not the spacing of other myosin meridional reflections, began to change at ∼15 ms, when the LR also started. Intensity of myosin-based reflections started to change later. When the muscle was stretched to nonoverlap length, the intensity and spacing changes of the myosin reflections disappeared. The simultaneous spacing change of the 14.3-nm myosin meridional reflection with the LR suggests that detachment of myosin heads that are bound to actin in the resting muscle is the cause of the LR.

An X-Ray Diffraction Study on Early Structural Changes in Skeletal Muscle Contraction

Structural changes in frog skeletal muscle were studied using x-ray diffraction with a time resolution of 0.53–1.02 ms after a single electrical stimulus at 8°C. Tension began to drop at 6 ms (latency relaxation), reached a minimum at 8 ms, and then twitch tension developed. The intensity of the meridional reflection at 1/38.5 nm −1, from troponin molecules on the thin filament, began to increase at 4–5 ms and reached a maximum at ∼12 ms. The meridional reflections based on the myosin 43-nm repeat began to decrease when the tension began to develop. The peak position of the third-order myosin meridional reflection began to shift toward the higher angle at ∼5 ms, reached a maximum shift (0.02%) at 10 ms, and then moved toward the lower angle. The intensity of the second actin layer line at 1/18 nm −1 in the axial direction, which was measured at 12°C, began to rise at 5 ms, whereas the latency relaxation started at 3.5 ms. These results suggest that 1), the Ca 2+-induced structural changes in the thin filament and a structural change in the thick filament have already taken place during latency relaxation; and 2), the Ca 2+ regulation of the thin filament is highly cooperative.

Do cross-bridges contribute to the tension during stretch of passive muscle?

The tension rise during stretch of passive skeletal muscle is biphasic, with an initial steep rise, followed by a subsequent more gradual change. The initial rise has been interpreted as being due to the presence of numbers of long-term, stable cross-bridges in resting muscle fibres. A point of weakness with the cross-bridge interpretation is that the initial stiffness reaches its peak value at muscle lengths beyond the optimum for myofilament overlap. To explain this result it has been suggested that despite the reduced overlap at longer lengths, the closer interfilament spacing and a higher sensitivity of the myofilaments to Ca2+ allows more stable cross-bridges to form. Recently the stretch responses of passive muscle have been re-examined and it has been suggested that it is not necessary to invoke cross-bridge mechanisms at all. Explanations based on a viscous resistance to interfilament sliding and mechanical properties of the elastic filaments, the gap filaments, were thought to adequately account for the observed tension changes. However, an important property of passive muscle, the dependence of stretch responses on the immediate history of contraction and length changes, thixotropy, cannot be explained simply in terms of viscous and viscoelastic properties. The review discusses the cross-bridge interpretation of muscle thixotropy and the relationship of passive stiffness to filament resting tension and latency relaxation. It is proposed that cross-bridges can exist in three states; one, responsible for the resting stiffness, requires resting levels of calcium. When, during activation, calcium levels rise, cross-bridges enter a low-force, high-stiffness state, signalled by latency relaxation, before they move to the third, force-generating state. It is concluded that, compared with viscoelastic models, a cross-bridge-based explanation of passive muscle properties is better able to accommodate the currently known facts although, as new information becomes available, this view may need to be revised.

The intracellular Ca2+ transient and tension in frog skeletal muscle fibres measured with high temporal resolution.

1. The purpose of this study was to determine, with high temporal resolution, the relationship between the intracellular Ca2+ transient (ICT) and the mechanical responses of intact, single skeletal muscle fibres of frogs following stimulation by a single, brief depolarization. 2. The time course of the ICT was monitored using the Ca(2+)-sensitive fluorescent dyes mag-fura-2 (furaptra) and mag-fura-5. The mag-fura dyes have a low affinity for Ca2+ and have been shown to track the ICT with no appreciable kinetic delay. Continuous records of mag-fura fluorescence, tension and stiffness responses were obtained simultaneously at high time resolution at a sarcomere length of 2.9 microns. Experimental temperature was 3 degrees C. 3. When a delay of 0.4 ms due to the low-pass filter associated with the photodetector was included, the onset of the fluorescence response preceded the onset of latency relaxation (the small fall in tension that precedes positive tension generation) by 3.1 +/- 0.2 ms (mean +/- S.E.M., n = 8). After its onset, the mag-fura fluorescence signal continued to change rapidly (indicating increasing intracellular [Ca2+]) to an extreme level that occurred 1.5 +/- 0.5 ms (mean +/- S.E.M., n = 7) before tension had recovered to its resting level following latency relaxation. The time delay from the extreme of the fluorescence signal to the peak of the tension signal was 239 +/- 27 ms (mean +/- S.E.M., n = 6).(ABSTRACT TRUNCATED AT 250 WORDS)

Tension in frog single muscle fibers while shortening actively and passively at velocities near Vu

Experiments were undertaken to determine the contribution of passive tension to total tension during rapid shortening in a stimulated muscle fiber. Results were obtained by applying shortening movements at constant velocities slightly less than Vu (the velocity of unloaded shortening) to intact twitch fibers isolated from the frog (Rana temporaria). The tension maintained by unstimulated fibers during such shortening movements ("dynamic passive tension") from moderately long lengths was greater than zero but much less than the passive tension measured under static conditions ("static passive tension") at the same lengths. Fibers maximally activated by electrical stimulation and then shortened at the same velocity over the same range of average sarcomere lengths maintained tension that was greater than zero but less than the dynamic passive tension. For average sarcomere lengths up to approximately 3.1 microns, the dynamic passive tension appeared to be substantially abolished by activation. The onset of the apparent disappearance of dynamic passive tension was studied by initiating the stimulation and the shortening movement simultaneously. The resulting tension response exhibited a latency relaxation that was increased in amplitude compared with the isometric case, followed by a brief tension rise, giving way to a steady tension level equal to that expected if stimulation had been initiated well before the release. These changes are qualitatively explained in terms of the establishment of a steady state distribution of deformations of attached cross-bridges.

Earliest mechanical evidence of cross-bridge activity after stimulation of single skeletal muscle fibers

The stiffness of single fibers from frog skeletal muscle was measured by the application of small 2-kHz sinusoidal length oscillations during twitch and tetanic contractions at a range of initial sarcomere lengths. The earliest mechanical signs of activation were a fall in tension (latency relaxation) and a rise in stiffness. The earliest stiffness increase and the earliest tension fall occurred simultaneously at all sarcomere lengths. This suggests a cross-bridge origin for the latency relaxation. The lead of stiffness over tension seen during the rise of tension was substantially established during the latent period. Reducing the size of the twitch by reducing calcium release with D-600 (methoxyverapamil) reduced the latency relaxation and the stiffness development during latency much less than it reduced the twitch tension. For very small twitches the peak of the stiffness response occurred during the latent period and the times of onset of both latency relaxation and stiffness rise were delayed, but remained coincident. This suggests a strong connection between the latency relaxation and the rise of stiffness during the latent period, whereas the connection between these events and positive tension generation appears to be less strong.

The theory of sliding filament models for muscle contraction. I. The two-state model

The mechanical and thermal properties of Huxley's 1957 sliding filament model for striated muscle contraction are reconsidered, with emphasis on general relationships between two-state models and muscle behaviour. New empirical forms for the rate functions f(x) and g(x) are proposed, which give an improved fit to experiments. A specific procedure, based on the shortening heat, for determining model parameters is described and applied to various choices of rate functions. The change in slope of the tension-velocity curve observed by Katz is shown to require at least one discontinuity in the binding rate f(x), and a general formula is given. The two-state model also gives a symmetric cusp in the ATP-rate vs velocity curve at v = 0. The theory is extended to time-varying situations and applied to transient responses following isometric activation by tetanus (including latency relaxation), and unloaded and after-loaded contractions. The early burst of heat production can also be fitted by assigning appropriate values to the heats of binding and dissociation.

Functional property of the masseter muscle in man

The purpose of this paper is to investigate the functional property of the masseter muscle at the motor unit level in man. The responses of the surface EMG and the bite force were studied by averaging technique, with the following results.1. The higher threshold units with large twitch tensions were found in the superficial layer of the muscle, the lowers were throughout the muscle.2. Positive correlation was found between voluntary threshold force and peak twitch tension, linear correlation coefficient was 0.76.3. The motor units with a larger twitch tension tended to have shorter contraction time, but those of smaller had the wide range.4. There was a tendency for deeper-layer units to contribute less to the wave form of the surface EMG than did the superficial units.5. There was a significant tendency for the units recruited with larger forces to contribute extensively to the surface EMG. The linear correlation coefficient was 0.70.6. In 106 force records, DEM (the discrepancy between electrical activity and mechanical contraction) was observed. It seemed that DEM was similar phenomenon to the latency relaxation.

New optical spike in frog twitch muscle fibers injected with a potential probe dye NK2935.

Absorbance responses posterior to action potentials were recorded from frog twitch fibers loaded by an impermeant potential probe dye NK2935 that was chemically identical with WW781. Extracellularly loaded NK2935-related responses (EOS) increased in absorbance around 640nm wavelengths and were like action potential in waveform but were slightly preceded by action potential. Model analysis showed that EOS consisted of two components, namely 39% non-delay component reflected with sarcolemma action potential and 61% first-order delay component reflected with transverse tubule (T) action potential (delay-constant tau 1 = 0.48 ms). The T-disrupted fibers showed only the non-delayed response. Intracellularly injected NK2935-related responses (IOS) were also composed of a single spike of the same direction swing as in the EOS case described by the term "ipsidirection," but were clearly preceded by EOS and followed by Ca transient, birefringence, transparency and latency relaxation responses. The T-disrupted fibers showed a small "sidedness" response characterized by both opposite direction swing, namely "contradirection" and non-delay against EOS. Model analysis showed that IOS consisted of two main components, namely second-order delay component with ipsidirection (tau 2 = 0.8 ms) and the further high-order delay component with contradirection. Based on spatio-temporal heterogeneity of NK2935 binding inside fibers and potential-absorbance relation in sarcolemma, the former origin was thought to be in junctional sarcoplasmic reticulum (jSR) responding to T excitation with a transient "positive polarization" estimated roughly 20 mV. Similarly, the latter was possibly in free SR where a slow "negative polarization" estimated -0.9 mV might appear associated with Ca release.

Acoustic phenomena in the latent period of skeletal muscle: a simple method for in-vivo measurement of the electro-mechanic latency (EML).

An in-vivo method for the assessment of the latency of muscular contraction is presented. It is based on acoustic registration of muscular thickening by a microphone. It was found that the recorded sound wave is often preceded by a small wave of opposite polarity (flattening of the muscle belly) which is an acoustic correlate of the latency relaxation. Strong direct stimulation produced another small sound wave at the beginning of the latent period. The physiological significance of these findings is discussed.

Arsenazo III calcium transients and latency relaxation in frog skeletal muscle fibres at different sarcomere lengths.

Single, intact, frog muscle fibres were injected electrophoretically with a Ca2+-sensitive metallochromic dye, Arsenazo III, to a local concentration of 1.2-1.5 mmol/l. The intracellular concentration of free Mg2+, estimated photometrically in the presence of approximately millimolar Arsenazo III, was 3-4 mmol/l in fibres at rest. Ca2+-related changes in dye absorbance were characterized in vitro using 1 mM-Arsenazo III in solutions approximating the intracellular ionic environment. Isometric twitch contractions and related changes in light transmittance of dye-injected regions of fibre were recorded at 2.4 and 3.0 micron sarcomere lengths, at 15 degrees C. A method was developed for separating Ca2+ transients from larger, movement-related optical changes recorded as compound signals during fibre contraction. Decreases in twitch amplitude by about one-third following dye injection, together with the in vitro characteristics of the dye, suggested that millimolar intracellular Arsenazo III acted as a major Ca2+ buffer and inhibited the activation of contractile filaments. The onset of both the Ca2+ transient and latency relaxation occurred at virtually the same time in the twitch response and neither of those transition times was altered significantly with changes in sarcomere length from 2.4 to 3.0 micron. The amount of activation Ca2+ released in dye-injected regions of fibres following a single stimulus was about 0.3 mmol/l at 2.4 micron sarcomere length. The rate of rise and the amplitude of the Ca2+ transient were reversibly decreased with increase in sarcomere length from 2.4 to 3.0 micron. That finding is reviewed in relation to other evidence indicating length dependence of the intracellular release and distribution of activation Ca2+ up to 3.9 micron sarcomere length.

Birefringence signal and early mechanical changes at normal and increased tonicities in frog skeletal muscle.

Simultaneous measurements of the time course of early mechanical events and the early large birefringence signal were performed during activation of isolated frog skeletal muscle fibres bathed in iso- and hypertonic media. A piezo-electric transducer was used which had a resonance frequency of 3.3 kHz and a sensitivity of 740 mV/mN (0.5 mV noise peak to peak) and a compliance of 0.6 mu/mN. The delay from stimulus onset to the onset of the birefringence signal was estimated to be 0.78 +/- 0.03 ms in normal Ringer solution at room temperature (20-23 degrees C). The beginning of latency relaxation appeared subsequent to the birefringence signal after a delay of 0.36 +/- 0.03 ms. Increasing the tonicity retarded the time course of both birefringence signal and latency relaxation. In solutions of twofold greater tonicity an increase in tension (denoted pre-relaxation contraction) was observed to precede latency relaxation. Pre-relaxation contraction became more prominent with increasing tonicity and appeared to coincide with its onset with the onset of the birefringence signal. The pre-relaxation contraction was shown not to be a stimulus artifact and was not reduced in amplitude by D 600 or calcium-poor solutions. Lowering the temperature to 2.2 degrees C in normal Ringer solution delayed the onsets of the birefringence signal and latency relaxation, and increased the interval between the two signals but did not result in a tension increase before latency relaxation. The coincidence of the birefringence signal onset with the onset of pre-relaxation contraction suggests a common aetiology. The aetiology remains speculative but seems to require hypertonicity for expression of the mechanical signal.

SCOPE OF A TECHNIQUE FOR ELECTRICAL STIMULATION OF HUMAN BRAIN, SPINAL CORD, AND MUSCLE

Brief high-voltage electrical shocks from a special low-output-resistance stimulator, delivered through electrodes on the skin, can excite human muscle directly (not by way of the nerves) and can also excite the motor cortex, the visual cortex, and the spinal cord. Possible applications of the technique include measurement in muscle disorders of the latency relaxation and of the excitability and contractility of muscle without the interposition of nerve fibres or the neuromuscular junction; measurement of conduction velocity in the pyramidal tract; and the detection of neuropathy in the nerves to the external sphincter ani.

Latency relaxation in frog skeletal muscle under hypertonic conditions.

The effect of exposure to hypertonic conditions on latency relaxation (LR), twitch tension and resting tension in frog toe muscle was studied. Measurements were carried out in standard and hypertonic conditions (1 to 3.6 times standard tonicity) and following transversal stimulation. In hypertonic conditions, the LR showed increased duration and decreased amplitude. Both time course and amplitude showed the same dependency on sarcomere length as in standard conditions. The fall in amplitude and extension of the time course was proportional to the increase in tonicity up to 2.2 times the tonicity of the standard. At higher tonicities the time course extended earlier and diverged from the linear dependency, the amplitude falling later with increasing tonicity. The LR was abolished at tonicities exceeding 3 times the standard. In hypertonic conditions the twitch tension was reduced and extended, but showed the same dependency on sarcomere length as in standard conditions. The amplitude showed the same dependency on tonicity as the LR amplitude. The time course extended in a non-linear way with growing tonicity. In hypertonic conditions the resting tension was higher than or the same as in standard conditions, and the dependency on sarcomere length was the same.

Activation heat and latency relaxation in relation to calcium movement in skeletal and cardiac muscle.

Measurements of activation heat, initial heat, twitch tension, and latency relaxation were made using thin-layer, vacuum-deposited thermopiles and isometric force transducers, respectively. Experiments were performed on frog skeletal muscle fiber bundles and on rabbit right ventricular papillary muscles at 0, 15, ans 21 degrees C in normal and 1.75X to 2.5X mannitol hyperosmotic bathing solutions. In skeletal muscle, activation heat, obtained by stretching to zero overlap, was only slightly affected by 1.75X hyperosmotic solution and consisted of a fast and a slow component. Both components have a refractory period and a relatively refractory period which can be demonstrated by double pulse stimulation. The twitch potentiators Zn2+ and caffeine increase the total activation heat and the magnitude and rate of the fast component. The temporal relation between the latency relaxation and activation heat is demonstrated. The latency relaxation is independent of the number of sarcomeres in series in a muscle. Activation heat and latency relaxation records from heart muscle are obtained in 2.5X hyperosmotic bathing solution. A model of excitation--contraction coupling is presented which indicates that (1) the downstroke of the latency relaxation monitors the functioning of the Ca2+-permeability or debinding mechanism in the terminal cisternae, (2) the fast component of activation heat monitors the amount of Ca2+ bound to troponin C, and (3) the total amplitude of activation heat is a measure of the total quantity of Ca2+ cycled in a twitch.

Increase of resistance to stretch during the latent period in single muscle fibres of the frog.

The time from stimulation to the first change of the extensibility in an isolated skeletal muscle fibre was measured by subjecting the fibre to a rapid, small stretch at various times during the latent period. The experiments were performed at constant temperatures in the range 1-16 degrees C. Irrespective of the temperature, the first increase of the resistance to stretch occurred after the onset of the latency relaxation. At a temperature or 10 degrees C and a sarcomere length of 3 microgram the resistance started to increase 5.5 ms after stimulation, i.e. 1.5-2 ms after the onset of the drop in tension, and then increased nearly linearly with time. Corresponding to the end of the latent period, i.e. when the tension recrosses the resting level, the amplitude of the response was about 1.5 times its resting value. There was an interval between the onset of increase f the resistance to stretch and the time when the rate of drop in tension had passed its maximum value. The results are compatible with the hypothesis that the latency relaxation arises from a minute lengthening of the thin filaments as proposed by Haugen & Sten-Knudsen, and that attachment and generation of force take place at separate steps of the cross-bridge cycle.