Biomedical subjects

R L Lieber

Publications and source records attributed to R L Lieber.

At least 19 recordsLinked to original sources

PubMed2001

Serum creatine kinase level is a poor predictor of muscle function after injury.

Serum creatine kinase and dorsiflexion torque levels were measured in New Zealand White rabbits 1, 2, 7, 14, or 28 days after a single bout of eccentric exercise (n=26). No significant correlation was observed between creatine kinase activity and torque across time periods (P>0.15) and the regression relationship described only about 8% of the experimental variability. These data demonstrate that there exists a poor correlation between serum creatine kinase levels and skeletal muscle function after eccentric exercise.

Animals↗

PubMed2001

Eccentric exercise-induced injuries to contractile and cytoskeletal muscle fibre components.

Exercise involving lengthening of an activated muscle can cause injury. Recent reports documented the mechanics of exercise-induced muscle injury as well as physiological and cellular events and manifestations of injury. Loss of the cytoskeletal protein desmin and loss of cellular integrity as evidenced by sarcolemmal damage occur early during heavy eccentric exercise. These studies indicate that the earliest events in muscle injury are mechanical in nature, while later events indicate that it may be more appropriate to conclude that intense exercise initiates a muscle remodeling process. We conclude that muscle injury after eccentric exercise is differently severe in muscles with different architecture, is fibre type-specific, primarily because of fibre strain in the acute phase, and is exacerbated by inflammation after the initial injury.

Cytoskeleton↗

PubMed2001

Quantitative evaluation of the posterior deltoid to triceps tendon transfer based on muscle architectural properties.

The architectural properties of the posterior deltoid muscle and the 3 heads of the triceps were measured using microdissection techniques to determine whether substitution of triceps function by the posterior deltoid is architecturally appropriate. Muscles from 10 fresh cadaver specimens were fixed by high-pressure perfusion using buffered formaldehyde. Muscle architectural properties, including pennation angle, fiber bundle length, sarcomere length, and physiologic cross-sectional area, were determined. Fiber bundle length varied significantly among the deltoid (123.1 +/- 7.8 mm), medial (64.5 +/- 3.8 mm), lateral (66.5 +/- 5.4 mm), and long (85.3 +/- 9.5) heads of the triceps. The physiologic cross-sectional area of the posterior deltoid was significantly less than the total triceps area and was predicted to provide only approximately 20% of the maximum isometric tension of the combined triceps heads. These data demonstrate that the long fibers of the posterior deltoid render it a very suitable transfer to provide elbow extension because of its tremendous excursion and also show why useful functional results seem relatively independent of posterior deltoid tension at the time of surgery.

Biomechanical Phenomena↗

PubMed2001

Clinical significance of skeletal muscle architecture.

Skeletal muscle architecture is one of the most important properties that determines a muscle's force and excursion capability. In the current review, basic architectural terms first are reviewed and then specific examples relevant to upper extremity anatomy are presented. Specific examples of anatomic considerations required for surgical reconstruction after radial nerve palsy also are detailed. Together, these data show not only the wide variety of architectural designs in human muscles, but the importance of considering architectural design when making surgical decisions.

Biomechanical Phenomena↗

PubMed2001

Biomechanical analysis of the brachioradialis as a donor in tendon transfer.

Anatomic and biomechanical properties of the passive brachioradialis muscle were investigated to understand the limited excursion of this muscle seen during tendon transfer surgery. First, architectural measurements were performed on three fiber bundles obtained from four regions of the brachioradialis (10 specimens) chosen to represent the range of muscle fiber lengths across the brachioradialis. Next, in separate specimens (eight specimens), passive excursion was measured by securing the distal tendon stump to a servomotor. A constant load of 4.9 N was applied to the tendon, while the distal tendon was released from the surrounding tissue in 3-cm increments. Within the four regions studied, muscle fiber length varied significantly from 104.2 +/- 6.2 mm to 179.8 +/- 6.1 mm. As the brachioradialis was released, an average of 3 mm of mobility was obtained for each interval whereas for the succeeding three intervals, an average of 5.3 mm of mobility was obtained. This resulted in 22.2 +/- 2.3 mm of mobility when each specimen was fully released. These data show that there is no intrinsic muscle fiber length limitation to excursion, but that excursion is limited by other intermuscular connections to adjacent connective tissue and other muscles.

Biomechanical Phenomena↗

PubMed2001

Sarcomere number regulation maintained after immobilization in desmin-null mouse skeletal muscle.

The serial sarcomere number of skeletal muscle changes in response to chronic length perturbation. The role of the intermediate filament desmin in regulating these changes was investigated by comparing the architectural adaptations of the tibialis anterior, extensor digitorum longus (EDL) and soleus from wild-type mice with those of homozygous desmin knockout mice after hindlimb immobilization. After 28 days, serial sarcomere number increased significantly in the lengthened wild-type tibialis anterior (by approximately 9%) and EDL (by approximately 17%). Surprisingly, muscles from desmin knockout mice also experienced significant serial remodeling, with the serial sarcomere number of the tibialis anterior increasing by approximately 10% and that of the EDL by approximately 27%. A consistent result was observed in the shortened soleus: a significant decrease in sarcomere number was observed in the muscles from both wild-type (approximately 26%) and knockout (approximately 12%) mice. Thus, although desmin is not essential for sarcomerogenesis or sarcomere subtraction in mouse hindlimb muscles, the results do suggest subtle differences in the nature of sarcomere number adaptation. We speculate that desmin may play a role in regulating the optimal arrangement of sarcomeres within the muscle or in sensing the magnitude of the immobilization effect itself.

Animals↗

PubMed2001

Identification of myosin light chains in Rana pipiens skeletal muscle and their expression patterns along single fibres.

Isoforms of myosin heavy chain (MHC) and myosin light chain (MLC) influence contractile kinetics of skeletal muscle. We previously showed that the four major skeletal muscle fibre types in Rana pipiens (type 1, type 2, type 3 and tonic; amphibian nomenclature) contain four unique MHC isoforms. In the present study we defined the MLCs expressed in each of these R. pipiens fibre types. The MLC composition of single MHC-typed fibres was determined from western blots using a panel of monoclonal MLC antibodies. A total of seven MLCs were identified, including four types of MLC1, two of MLC2 and a single MLC3. Twitch fibre types (types 1, 2 and 3) expressed MLC1(f) and MLC2(f), while tonic fibres contained a unique set of isoforms, MLC1(Ta), MLC1(Tb) and MLC2(T). MLC3 was expressed primarily in type 1, type 1-2 and type 2 fibres. Surprisingly, some frogs displayed a striking pattern of MLC expression where a unique isoform of MLC1 (MLC1(x)) was coexpressed along with the normal MLC1 isoform(s) in all fibre types. MLC1(x) was either expressed in all fibres of a given frog or was completely absent. The intraspecific polymorphism in MLC1 expression is likely to have a genetic basis, but is unlikely to be caused by allelic variation. The ratio of MLC3/MLC1 increased in direct proportion to the percentage of type 1 MHC, but was only weakly correlated. The variability in MLC3/MLC1 within a fibre type was extremely large. Both the MHC isoform and MLC3/MLC1 ratio varied significantly between 1 mm segments along the length of fibres. For all segments combined, MLC3/MLC1 increased with the percentage of type 1 MHC, but the correlation between segments was weaker than between fibres.

Alleles↗

PubMed2001

Sarcomere length operating range of vertebrate muscles during movement.

The force generated by skeletal muscle varies with sarcomere length and velocity. An understanding of the sarcomere length changes that occur during movement provides insights into the physiological importance of this relationship and may provide insights into the design of certain muscle/joint combinations. The purpose of this review is to summarize and analyze the available literature regarding published sarcomere length operating ranges reported for various species. Our secondary purpose is to apply analytical techniques to determine whether generalizations can be made regarding the "normal" sarcomere length operating range of skeletal muscle. The analysis suggests that many muscles operate over a narrow range of sarcomere lengths, covering 94+/-13 % of optimal sarcomere length. Sarcomere length measurements are found to be systematically influenced by the rigor state and methods used to make these measurements.

Animals↗

PubMed2000

Myosin isoforms in anuran skeletal muscle: their influence on contractile properties and in vivo muscle function.

Functional studies on isolated single anuran skeletal muscle cells represent classic experiments from which much of our understanding of muscle contraction mechanisms have been derived. Because of their superb mechanical stability when isolated, single anuran fibers provide a uniquely powerful model system that can be exploited to understand the relationship between myosin heavy chain (MHC) and myosin light chain (MLC) composition and muscle fiber function. In this review, we summarize historic and recent studies of MHC and MLC expression patterns in the fiber types of anuran species. We extend the traditional classification scheme, using data from recent reports in which frog MHCs have been cloned, to reveal the molecular basis of frog muscle fiber types. The influence of MHC and MLC isoforms on contractile kinetics of single intact fibers is reviewed. In addition, we discuss more subtle questions such as variability of myosin coexpression along a single cell, and its potential influence on contractile function. The frog jump is used as a model system to elucidate principles of muscular system design, including the role of MHC isoforms on in vivo muscle function. Sequence information is used from cloned frog MHCs to understand the role of specific regions of the myosin motor domain in regulating contractile function and the evolutionary origins of fast and slow amphibian MHCs. Finally, we offer promising future possibilities that combine molecular methods (such as recombinant gene transfer) with single cell contractile measurements to address questions regarding myosin structure/function and gene regulation.

Animals↗

PubMed2000

Cloning and characterization of the S1 domain of four myosin isoforms from functionally divergent fiber types in adult Rana pipiens skeletal muscle.

The motor properties of myosin reside in the globular S1 region of the myosin heavy chain (MHC) subunit. All vertebrates express a family of MHC isoforms in skeletal muscle that have a major influence on the mechanical properties of the various fiber types. Differences in molecular composition of S1 among MHC isoforms within a species have not been studied to any great detail. Presently, we have isolated, cloned and sequenced the S1 subunit of four MHC isoforms from skeletal muscle in Rana pipiens that are specifically expressed in four mechanically divergent fiber types. Paired analysis showed that the overall amino acid identity was higher between the three S1 isoforms expressed in twitch fibers than between the twitch and tonic isoforms. Relatedness in amino acid composition was evaluated in regions reported to govern cross-bridge kinetics. Surface loops 1 and 2, thought to influence motor velocity and ATPase, respectively, were both highly divergent between isoforms. However, the divergence in the loops was roughly equal to that of the amino-terminal region, a domain considered less important for motor function. We tested the hypothesis that the loops are more conserved in pairs of isoforms with more similar kinetics. Comparisons including other vertebrate species showed no tendency for loops from pairs with similar kinetics to be more conserved. These data suggest that the overall structure of loops 1 and 2 is not critical in regulating the kinetic properties of R. pipiens S1 isoforms. Cloning of this family of frog S1 isoforms will facilitate future structure/function studies of the molecular basis of variability in myosin cross-bridge kinetics.

Amino Acid Sequence↗

PubMed2000

Skeletal muscle recovery after tenotomy and 7-day delayed muscle length restoration.

Rabbit extensor digitorum longus (EDL) tendons were cut with the muscle active (active tenotomy, AT) or with the EDL at rest (passive tenotomy, PT). One, 7, and 21 days after tenotomy, contractile testing was performed. A second experiment was performed in which EDL tendons underwent PT and, after a 7-day delay, muscle-tendon units were restored to their original length. Maximum isometric tension dropped precipitously 1 day after either AT or PT to approximately 50% of normal and continued to decline by day 7. In contrast to PT, where peak tension (P(0)) decreased further by 21 days, after AT, P(0) partially recovered. Differences in muscle mass, cross-sectional area, fiber type, and sarcomere number did not explain the differential response. One day after length restoration of muscles, P(0) rapidly increased by approximately 40%. These observations have implications for understanding the outcome of muscle-tendon unit injury and surgical repair.

Animals↗

PubMed2000

Skeletal muscle response to tenotomy.

Tenotomy is a commonly encountered clinical entity, whether traumatic or iatrogenic. This article reviews the response of skeletal muscle to tenotomy. The changes are subdivided into molecular, architectural, and functional categories. Architectural disruption of the muscle includes myofiber disorganization, central core necrosis, Z-line streaming, fibrosis of fibers and Golgi tendon organs, changes in sarcomere number, and alterations in the number of membrane particles. Molecular changes include transient changes in myosin heavy chain composition and expression of neural cell adhesion molecule (NCAM). Functionally, tenotomized muscle produces decreased maximum tetanic and twitch tension. Alterations in normal skeletal muscle structure and function are clinically applicable to the understanding of pathological states that follow tendon rupture and iatrogenic tenotomy.

Animals↗

PubMed2000

Functional and clinical significance of skeletal muscle architecture.

Skeletal muscle architecture is the structural property of whole muscles that dominates their function. This review describes the basic architectural properties of human upper and lower extremity muscles. The designs of various muscle groups in humans and other species are analyzed from the point of view of optimizing function. Muscle fiber arrangement and motor unit arrangement is discussed in terms of the control of movement. Finally, the ability of muscles to change their architecture in response to immobilization, eccentric exercise, and surgical tendon transfer is reviewed. Future integrative physiological studies will provide insights into the mechanisms by which such adaptations occur. It is likely that muscle fibers transduce both stress and strain and respond by modifying sarcomere number in a way more suited to the new biomechanical environment.

Electromyography↗

PubMed2000

Interaction between series compliance and sarcomere kinetics determines internal sarcomere shortening during fixed-end contraction.

The interaction between contractile force and in-series compliance was investigated for the intact skeletal muscle-tendon unit (MTU) of Rana pipiens semitendinosus muscles during fixed-end contraction. It was hypothesized that internal sarcomere shortening is a function of the length-force characteristics of contractile and series elastic components. The MTUs (n=18) were dissected, and, while submerged in Ringer's solution, muscles were activated at nine muscle lengths (-2 to +6 mm relative to optimal length in 1 mm intervals), while measuring muscle force and sarcomere length (SL) by laser diffraction. The MTU was clamped either at the bone (n=6), or at the proximal and distal ends of the aponeuroses (n=6). Muscle fibers were also trimmed along with aponeuroses down to 5-20 fibers and identical measurements were performed (n=6). The magnitude of shortening decreased as MTU length increased. The magnitude of shortening ranged from -0.08 to 0.3 microm, and there was no significant difference between delta SL as a function of clamp location. When aponeuroses were trimmed, sarcomere shortening was not observed at L(0) and longer. These results suggest that the aponeurosis is the major contributor to in-series compliance. Results also support our hypothesis but there also appear to be other factors affecting internal sarcomere shortening. The functional consequence of internal sarcomere shortening as a function of sarcomere length was to skew the muscle length-tension relationship to longer sarcomere lengths.

Animals↗

PubMed2000

Effect of muscle tension during tendon transfer on sarcomerogenesis in a rabbit model.

Sarcomere number change was investigated in an animal model of tendon transfer. In 9 adult New Zealand white rabbits, the flexor digitorum longus muscle was cut distally and transferred and woven into the tibialis anterior tendon. Ankles were then immobilized for 3 weeks in 75 degrees flexion. Transferred flexor digitorum longus muscles were harvested and complete architectural analysis was performed. Sarcomere lengths were measured using laser diffraction. Serial sarcomere number in transferred flexor digitorum longus fibers was a strong function of the sarcomere length at the time of transfer. A highly significant negative correlation between these 2 parameters was approximated by a linear relationship. Based on this finding, we conclude that serial sarcomere number is significantly affected by the degree of stretch during the transfer itself. This could easily compromise the purpose of surgical tendon transfer by reducing the procedure to little more than a tenodesis. (J Hand Surg 2000; 25A:138-143.

Analysis of Variance↗

PubMed2000

Protection of the deltoid to triceps tendon transfer repair sites.

The posterior deltoid muscle was used to replace lost elbow extension in 11 patients with C5 or C6 level tetraplegia. During surgery stainless steel sutures were inserted into the donor muscle, graft, and tendon insertion sites. Over the succeeding time periods (1 month to 2 years) the distances between the various markers were measured. Significant tendon elongation of 23.1 +/- 4.8 mm (mean +/- SEM; n = 6) was observed in patients receiving traditional postoperative care. To reduce the tendon elongation observed, a specially designed armrest was developed and applied the first postoperative day. The armrest was designed to maintain the elbow in 20 degrees flexion and to prevent shoulder adduction. The addition of this armrest to the traditional postoperative protocol resulted in a dramatic decrease of tendon elongation to only 8.4 +/- 3.0 mm (n = 5). Elongation occurred within the first 6 postoperative weeks in the armrest group; in the nonprotected group, elongation continued for several additional months. The majority of the elongation in both groups occurred in the proximal portion of the tendon-graft-tendon unit. Although this study did not explicitly measure strength, we conclude that preventing excessive muscle length change is required to protect repair sites in posterior deltoid to triceps transfer. (J Hand Surg 2000; 25A:144-149.

Adult↗

PubMed2000

Desmin knockout muscles generate lower stress and are less vulnerable to injury compared with wild-type muscles.

The functional role of the skeletal muscle intermediate filament system was investigated by measuring the magnitude of muscle force loss after cyclic eccentric contraction (EC) in normal and desmin null mouse extensor digitorum longus muscles. Isometric stress generated was significantly greater in wild-type (313 +/- 8 kPa) compared with knockout muscles (276 +/- 13 kPa) before EC (P < 0.05), but 1 h after 10 ECs, both muscle types generated identical levels of stress ( approximately 250 kPa), suggesting less injury to the knockout. Differences in injury susceptibility were not explained by the different absolute stress levels imposed on wild-type versus knockout muscles (determined by testing older muscles) or by differences in fiber length or mechanical energy absorbed. Morphometric analysis of longitudinal electron micrographs indicated that Z disks from knockout muscles were more staggered (0.36 +/- 0. 03 microm) compared with wild-type muscles (0.22 +/- 0.03 microm), which may indicate that the knockout cytoskeleton is more compliant. These data demonstrate that lack of the intermediate filament system decreases isometric stress production and that the desmin knockout muscle is less vulnerable to mechanical injury.

Age Factors↗

PubMed2000

Effects of muscle contraction on the load-strain properties of frog aponeurosis and tendon.

The mechanical properties of the frog semitendinosus (ST) tendon and aponeurosis were measured during passive tensile loading to a force equal to ST maximum tetanic tension and during active isometric muscle contraction. During active contraction, both the tendon and aponeurosis regions initially strained at rates exceeding 400%/s while near the end of the muscle contraction, strain rates were nearly zero. At this point, the strain in the tendon region was equal to that observed during slow passive loading to the same tension level. However, for the aponeurosis, even near the zero strain rate, strain at the end of the active contraction was significantly below that observed during slow passive loading (p < 0. 001). Specifically, when aponeurosis strain rate was almost zero, aponeurosis strain was 13.8 +/- 3% (means +/- SEM, n = 10), which was significantly below that measured during passive loading (23.7 +/- 5%) suggesting that active contraction actually altered aponeurosis material properties. These data demonstrate that, while the tendon and aponeurosis regions have different passive biomechanical properties and both demonstrate viscosity typical of other connective tissues, the aponeurosis region of the frog ST actually changed its intrinsic properties during muscle contraction. Thus, extrapolation of biomechanical data obtained at nonphysiological strain rates or under conditions where the muscle-tendon junction has been interrupted should be made with caution.

Animals↗