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Biomedical subjects

R L Lieber

Publications and source records attributed to R L Lieber.

At least 73 records · Page 4Linked to original sources

Contractile and cellular remodeling in rabbit skeletal muscle after cyclic eccentric contractions.

The time course of muscle contractile and cellular properties was studied in rabbit ankle flexor muscles after injury produced by eccentric exercise. Cyclic eccentric exercise was produced by increasing the tibiotarsal angle of the rabbit while activating the peroneal nerve by use of transcutaneous electrodes. Muscle properties were measured 1, 2, 3, 7, 14, and 28 days after exercise to define the time course of muscle changes after injury. A control group receiving only isometric contraction was used to study the effect of cyclic activation itself. The magnitude of the torque decline after 1 day was the same with use of isometric or eccentric exercise, but eccentric exercise resulted in a further decrease in torque after 2 days, at which time isometrically exercised muscles had fully recovered. The most prominent morphological changes in the injured muscle fibers were the loss of antibody staining for the desmin cytoskeletal protein and deposition of intracellular fibronectin, even when the injured muscle fibers retained their normal complement of contractile and enzymatic proteins. The presence of fibronectin inside the myofibers indicated a loss of cellular integrity. Invasion by inflammatory cells was apparent on the basis of localization of embryonic myosin. Thus eccentric exercise initiates a series of events that results in disruption of the cytoskeletal network and an inflammatory response that could be the mechanism for further deterioration of the contractile response.

Animals↗

In vivo measurement of human wrist extensor muscle sarcomere length changes.

1. Human extensor carpi radialis brevis (ECRB) sarcomere length was measured intraoperatively in five subjects using laser diffraction. 2. In a separate cadaveric study, ECRB tendons were loaded to the muscle's predicted maximum tetanic tension, and tendon strain was measured to estimate active sarcomere shortening at the expense of tendon lengthening. 3. As the wrist joint was passively flexed from full extension to full flexion, ECRB sarcomere length increased from 2.6 to 3.4 microns at a rate of 7.6 nm/deg joint angle rotation. Correcting for tendon elongation during muscle activation yielded an active sarcomere length range of 2.44 to 3.33 microns. Maximal predicted sarcomere shortening accompanying muscle activation was dependent on initial sarcomere length and was always < 0.15 microns, suggesting a minimal effect of tendon compliance. 4. Thin filament lengths measured from electron micrographs of muscle biopsies obtained from the same region of the ECRB muscles were 1.30 +/- .027 (SE) microns whereas thick filaments were 1.66 +/- .027 microns long, suggesting an optimal sarcomere length of 2.80 microns and a maximum sarcomere length for active force generation of 4.26 microns. 5. These experiments demonstrate that human skeletal muscles can function on the descending limb of their sarcomere length-tension relationship under physiological conditions. Thus, muscle force changes during joint rotation are an important component of the motor control system.

Adult↗

Cloning and in situ hybridization of type 2A and 2B rat skeletal muscle myosin tail region: implications for filament assembly.

Changes in fast myosin expression play a critical role in skeletal muscle adaptation. Two fast myosin isoforms, type 2A and type 2B, are commonly expressed by fast muscle fibers but their sequences have not been determined to allow mRNA expression studies. A complete set of rat skeletal muscle myosins was amplified by PCR of cDNAs derived from skeletal muscle mRNA, cloned in a TA cloning vector, and sequenced. Specificity was demonstrated by in situ hybridization against skeletal muscle and myosin protein identification using monoclonal antibodies. Two novel sequences were cloned: A type 2A myosin which consisted of a 642 bp segment from the 3' end and a type 2B myosin which consisted of a 624 bp segment also from the 3' end. This region encodes that portion of the myosin molecule implicated in the control of filament assembly. The two fast myosins showed 88% homology in the open reading frame and 95% homology at the amino acid level. Based on this homology, it is unlikely that selective myosin filament assembly occurs during muscle fiber type transformation between type 2A and 2B.

Amino Acid Sequence↗

Torque history of electrically stimulated human quadriceps: implications for stimulation therapy.

The time course of knee extension torque was measured in human quadriceps muscles during 30 min of transcutaneous neuromuscular electrical stimulation (NMES). Ninety subjects were divided into six experimental groups (n = 15 per group), which received stimulation at one of the following frequency/duty cycle combinations: 10 Hz/50%, 30 Hz/50%, 50 Hz/50%, 10 Hz/70%, 30 Hz/70%, and 50 Hz/70%. Two-way analysis of variance revealed that the magnitude of the relative torque decrease (the percentage of decrease in torque relative to the initial value) was significantly different between frequencies (p < 0.005) and duty cycles (p < 0.02), with no significant interaction (p > 0.6). Increasing either frequency or duty cycle caused a greater decrease in torque. In spite of this result, there was no significant difference between groups in the total activity (torque-time integral) achieved during the 30 min treatment session. The magnitude of this activity corresponded to only about 7-14 maximum voluntary contractions. Finally, the average torque during the treatment session was significantly different among groups (p < 0.001), being greatest for the 50 Hz/50% group and least for the 10 Hz/70% group. Taken together, these data suggest that a smaller number of longer duration contractions produces the greatest muscle tension. They also suggest that the absolute torque levels achieved with NMES are relatively low compared with voluntary muscular activity.

Adult↗

Skeletal muscle mechanics: implications for rehabilitation.

Skeletal muscles are the primary organ system responsible for force generation and movement. As such, an improved understanding of normal movement can be obtained by understanding skeletal muscle mechanical properties. In this review, we present the basic mechanical properties of skeletal muscle in a way that relates to their normal function. First, isometric force production is discussed, followed by a presentation of isotonic force production. Then, skeletal muscle architectural properties are presented as a strategy for muscles to specialize in either force production or excursion. Finally, we discuss the relationship between muscles and joints and the significance of this relationship for understanding strength. Based on this presentation, the therapist will have an improved understanding of normal movement and may have insights into developing rehabilitation protocols that can improve function.

Actins↗

Relationship between Achilles tendon mechanical properties and gastrocnemius muscle function.

Strain was measured along the length of frog (Rana pipiens) gastrocnemius muscle-tendon units (MTU). Maximum muscle tension (P0) was measured, and the MTU was passively loaded to P0. Strain at P0 was measured at eight intervals along the tendon and aponeurosis and was approximately two percent for all regions except the aponeurosis region closest to the muscle fibers where it was about six percent. A computer model predicted sarcomere shortening of up to 0.5 micron due to tendon lengthening which demonstrates that tendons provide a more complex physiological function than simply transmitting muscle force to bones.

Achilles Tendon↗

Muscle damage is not a function of muscle force but active muscle strain.

Contractile properties of rabbit tibialis anterior muscles were measured after eccentric contraction to investigate the mechanism of muscle injury. In the first experiment, two groups of muscles were strained 25% of the muscle fiber length at identical rates. However, because the timing of the imposed length change relative to muscle activation was different, the groups experienced dramatically different muscle forces. Because muscle maximum tetanic tension and other contractile parameters measured after 30 min of cyclic activity with either strain timing pattern were identical (P > 0.4), we concluded that muscle damage was equivalent despite very different imposed forces. This result was supported by a second experiment in which the same protocol was performed at one-half the strain (12.5% muscle fiber length). Again, there was no difference in maximum tetanic tension after cyclic 12.5% strain with either strain timing. Data from both experiments were analyzed by two-way analysis of variance, which revealed a highly significant effect of strain magnitude (P < 0.001) but no significant effect of stretch timing (P > 0.7). We interpret these data to signify that it is not high force per se that causes muscle damage after eccentric contraction but the magnitude of the active strain (i.e., strain during active lengthening). This conclusion was supported by morphometric analysis showing equivalent area fractions of damaged muscle fibers that were observed throughout the muscle cross section. The active strain hypothesis is described in terms of the interaction between the myofibrillar cytoskeleton, the sarcomere, and the sarcolemma.

Animals↗

Quantitative method for comparison of skeletal muscle architectural properties.

A numerical method is presented which calculates the architectural difference index between two muscles. This index is based upon the parameters, identified using statistical discriminant analysis, which best characterize the various muscles. This index can be used to reduce multiple architectural properties into a single value and may be useful in selecting donor muscles which are required to perform a substitute function for another muscle which has been lost or injured.

Animals↗

Model of muscle-tendon interaction during frog semitendinosis fixed-end contractions.

A structural model was developed to explain sarcomere shortening at the expense of tendon lengthening in the frog semitendinosis (ST) muscle-tendon system. The model was based on the data of Lieber et al. [Am. J. Physiol. 261, C86-C92 (1991)], who determined the relationship between the sarcomere length, tendon load (as a fraction of maximum isometric tension) and tendon, bone-tendon junction (BTJ), and aponeurosis strain. The model was generated assuming a finite time-course of cross-bridge attachment [Huxley, Prog. Biophys. 7,255-318 (1957)], an ideal sarcomere length-tension relationship [Gordon et al., J. Physiol. 184, 170-192 (1966)] and an ideal force-velocity relationship [Katz, J. Physiol. 96, 45-64 (1939); Edman, J. Physiol. 291, 143-159 (1979)]. Functionally, sarcomeres operated on three distinct regions of the length-tension curve: (1) regions where the muscle force decreased as sarcomeres shortened (the shallow and steep ascending limbs); (2) regions where the muscle force increased as sarcomeres shortened and there was little passive tension (descending limb, where sarcomere length greater than or equal to 3.0 microns); and (3) regions where the muscle force increased as sarcomeres shortened and there was a significant passive tension (descending limb where sarcomere length greater than 3.0 microns). Using such a physiological model, it was found that the effect of tendon compliance was to 'skew' the sarcomere length-tension curve to the right and to increase the operating range of the muscle-tendon unit.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Architecture of selected muscles of the arm and forearm: anatomy and implications for tendon transfer.

The architectural features of twenty-one different forearm muscles (n = 154 total muscles) were studied. Muscles included the extensor digitorum communis to the index, middle, ring, and small fingers, the extensor digit quinti, the extensor indicis proprius, the extensor pollicis longus, the flexor digitorum superficialis, the flexor digitorum profundus, the flexor pollicis longus, the pronator quadratus, the palmaris longus, the pronator teres, and the brachioradialis. Muscle length, mass, fiber pennation angle, fiber length, and sarcomere length were determined with the use of laser diffraction techniques. From these values, physiologic cross-sectional area and fiber length/muscle length ratio were calculated. The individual digital extensor muscles were found to be relatively similar in architectural structure. Similarly, the deep and superficial digital flexors were very similar architecturally, with the exception of the small finger flexor digitorum superficialis, which was much smaller and shorter than the rest of the digital flexors. The brachioradialis and the pronator teres had dramatically different architectural properties. While the masses of the two muscles were nearly identical, the muscles had significantly different predicted contractile properties based on their different fiber arrangement. The brachioradialis, with its long fibers arranged at a small pennation angle, had a physiologic cross-sectional area that was only one third that of the pronator teres, with its short fibers that were more highly pennated. Using these architectural data and the statistical method of discriminant analysis, we provide additional information that might be useful in the selection of potential donor muscles to restore thumb flexion, thumb extension, finger extension, and finger flexion.

Arm↗

Architectural design of the human intrinsic hand muscles.

The architectural features of twenty different muscles (18 intrinsics and 2 thumb extrinsics, n = 180 total muscles) were studied. Muscle length, mass, fiber pennation angle, fiber length, and sarcomere length were determined. From these values, physiologic cross-sectional area and fiber length/muscle length ratio were calculated. Intrinsic muscle lengths were relatively similar to one another, which we interpreted as representing a space constraint within the hand. However, several specialized architectural designs were observed: lumbrical muscles had an extremely high fiber length/muscle length ratio, implying a design toward high excursion. The first dorsal interosseous and adductor pollicis had physiologic cross-sectional areas comparable to those of extrinsic muscles and much greater than those of the other intrinsic muscles. The interosseous muscles had relatively high physiologic cross-sectional areas with low fiber length/muscle length ratios, suggesting their adaptation for high force production and low excursion. Taken together, these observations illustrate the underlying structural basis for the functional capacities of the intrinsic muscles.

Hand↗

Muscle, joint, and tendon contributions to the torque profile of frog hip joint.

The relative contributions of muscle force, moment arm, and tendon compliance were determined as a function of joint angle in the frog semitendinosus-hip joint system. Muscle, joint, and tendon properties were individually measured and then combined to predict the torque generated at the hip joint as a function of joint angle (i.e., the hip torque profile). Predicted torques were then compared to experimentally measured torques using a stepwise regression model to quantify the relative importance of muscle, joint, and tendon contributions to the hip torque profile. Variation in moment arm accounted for 74% of the variability observed in the hip torque profile, while addition of the muscle's intrinsic sarcomere length-tension property accounted for an additional 19% of the torque profile variability. Tendon compliance, which permitted a small amount of sarcomere shortening, accounted for only about 4% of the torque profile variability. We conclude that in this muscle-joint system, the relative fiber length-to-moment arm ratio is the major determinant of the shape of the isometric joint profile. The fiber length-to-moment arm ratio in other mammalian systems is also discussed.

Animals↗

Sarcomere length-joint angle relationships of seven frog hindlimb muscles.

The sarcomere length-joint angle relationship was measured in 7 different muscle-joint complexes (n = 43 muscles) of the frog hindlimb (Rana pipiens). Muscles studied included the cruralis, iliacus internus, gastrocnemius, gluteus magnus, gracilis major, semimembranosus and the semitendinosus. Muscle-joint complexes were mounted in a jig and submerged in chilled Ringer's solution. Joints were rotated throughout their range of motion, while sarcomere length was measured by laser diffraction. Muscles were then formalin fixed and architectural properties determined by microdissection of individual muscle fibers. Sarcomere length change per degree of joint rotation (dLs/d theta) ranged from a low of 3.7 nm/degree for the cruralis muscle acting at the knee to a high of 12.5 nm/degree for the semitendinosus muscle acting at the hip. Values for dLs/d theta were significantly different between all muscles (p < 0.001), and dLs/d theta values for muscles acting at the hip were significantly greater than those for muscles acting at the knee (p < 0.005). dLs/d theta was negatively correlated with fiber length, suggesting a balance between fiber length and moment arm in most muscle-joint systems. However, many exceptions to this generalization were noted. These data suggest that different muscle-joint systems are 'designed' for differential contribution of muscle force production to the joint torque profile. The low variability of these data also suggests that sarcomere number is tightly regulated in these muscle-joint systems but not simply as a result of the total in vivo muscle excursion.

Animals↗

Decreased muscle speed, strength and fatigability following two hours of tourniquet-induced ischaemia.

Contractile and morphological properties of the rabbit tibialis anterior muscle were measured 48 hours following a two-hour ischaemic episode. Ischaemia was induced using a specially-designed pneumatic tourniquet placed on the rabbit thigh. Maximum tetanic tension of muscle subjected to ischaemia (381 +/- 77 g) was only about 30% of the tension generated by control muscles (1,212 +/- 67 g). The rate of rise of tetanic tension of muscles subjected to ischaemia (15.9 +/- 3 g/ms) was only 33% of control values (44.5 +/- 5.9 g/ms). Muscle fatigue index increased significantly from 0.22 +/- 0.7 in control muscles to 0.55 +/- 0.09 in ischaemic muscles suggesting that muscles subjected to ischaemia had a greater endurance capacity than control muscles. Morphologically, focal necrotic regions and inflammatory cells were observed in ischaemic muscle fibers. Taken together, these data are consistent with selective damage to the fast glycolytic muscle fibers within the ischaemic tibialis anterior muscles. Thus, ischaemia results in overall decreased muscle speed, strength and fatigability.

Animals↗

Structural and mechanical basis of exercise-induced muscle injury.

It is well documented in both animal and human studies that unaccustomed, particularly eccentric, muscle exercise may cause damage of muscle fiber contractile and cytoskeletal components. These injuries typically include: Z-band streaming and dissolution, A-band disruption, disintegration of the intermediate filament system, and misalignment of the myofibrils. The mechanical basis for this damage is suggested to be due to the fiber strain magnitude rather than the absolute stress imposed on the fiber. We hypothesize that eccentric contraction-induced damage occurs early in the treatment period, i.e., within the first few minutes. The structural abnormalities predominate in the fast-twitch glycolytic fibers. In the final section of this paper, we hypothesize a damage scheme, based on the muscle fiber oxidative capacity as a determining factor.

Animals↗

Factors influencing quadriceps femoris muscle torque using transcutaneous neuromuscular electrical stimulation.

Quadriceps femoris muscle torque was measured in 40 subjects during transcutaneous neuromuscular electrical stimulation (NMES). Three different electrode types (carbonized rubber, sponge, and adhesive) were used on each subject, permitting determination of the factors that influenced the magnitude of quadriceps femoris muscle torque induced by NMES. This goal was accomplished by entering the various factors into a multiple-regression model. The electrodes differed significantly in their characteristics. The carbonized-rubber electrode delivered the greatest current with the lowest impedance, resulting in the highest knee extension torque. We found that the most important factor in determining torque generation level was the quadriceps femoris muscle's intrinsic ability to be activated (as opposed to electrode size, current, current density, or skin impedance). These data suggest that NMES efficacy is primarily determined by the intrinsic tissue properties of the individual (defined in this study as "efficiency") and is not dramatically changeable by using high stimulation currents or large electrode sizes. The precise physiological basis for interindividual differences in efficiency is not known.

Adult↗