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Biomedical subjects

Richard L Lieber

Publications and source records attributed to Richard L Lieber.

At least 19 recordsLinked to original sources
PubMed2007

Muscle adaptation by serial sarcomere addition 1 year after femoral lengthening.

A common complication of reconstructive surgery is muscle contracture and consequent loss of joint motion. This particularly occurs in surgical lengthening procedures where the muscle adaptive capacity seems to limit the extent of possible lengthening. We used intraoperative laser diffraction to determine the skeletal muscle adaptation that occurred in a 16-year-old girl who had 4-cm femoral lengthening for a leg-length discrepancy secondary to posttraumatic growth arrest. Fascicle length changed dramatically during distraction from a starting value of approximately 9 cm to a new length of 19 cm. In vivo vastus lateralis sarcomere length measured intraoperatively at the initial surgery was 3.64 microm, whereas sarcomere length measured 8 months later was 3.11 microm. The fact that fascicle length increased dramatically and in vivo sarcomere length decreased slightly reveals an increase in serial sarcomeres from 25,000 to 58,650. This direct measurement of fascicle length and sarcomere length confirms sarcomerogenesis in human skeletal muscle secondary to chronic length change, and shows the capacity of human muscle to adapt to length changes.

Adaptation, Physiological↗
PubMed2006

High stiffness of human digital flexor tendons is suited for precise finger positional control.

The objective of this study was to define the biomechanical properties of the human digital flexor tendons and to compare these biomechanical properties to other muscle-tendon units in the forearm. Mechanical measurements were performed on fresh-frozen tendons under physiological load and temperature conditions. Loads were determined by first measuring the physiological cross-sectional area of each digital belly of the flexor digitorum superficialis (FDS) and flexor digitorum profundus (FDP) and estimating maximum tension (P(o)) of that specific muscle head. Loading each tendon to the appropriate P(o) resulted in no significant difference in tendon strain among any of the tendons within each muscle (P > 0.05; digits 2-5) or between muscle types (FDP vs. FDS). The one exception to this finding was that a significantly higher strain at Po was observed in the FDP tendon to the small finger (P < 0.05). Average absolute strains observed for the FDP and FDS tendons (1.20 +/- 0.38%, mean +/- SD; n = 39) were significantly lower than those observed previously in a study of the prime movers of the wrist. The measured strain of approximately 1.5% was less than half of that predicted to occur in muscles of this architectural design. Modeling sarcomere shortening magnitudes during FDP or FDS contraction yielded a value of only 0.10 microm, which would have a negligible effect on the force generating capacity of these muscles. Thus the high stiffness of the digital flexor tendons suits them well for fine positional control and would render their muscle spindles quite sensitive to length perturbations at the fingertips.

Algorithms↗
PubMed2006

Nebulin-deficient mice exhibit shorter thin filament lengths and reduced contractile function in skeletal muscle.

Nebulin is a giant modular sarcomeric protein that has been proposed to play critical roles in myofibrillogenesis, thin filament length regulation, and muscle contraction. To investigate the functional role of nebulin in vivo, we generated nebulin-deficient mice by using a Cre knock-in strategy. Lineage studies utilizing this mouse model demonstrated that nebulin is expressed uniformly in all skeletal muscles. Nebulin-deficient mice die within 8-11 d after birth, with symptoms including decreased milk intake and muscle weakness. Although myofibrillogenesis had occurred, skeletal muscle thin filament lengths were up to 25% shorter compared with wild type, and thin filaments were uniform in length both within and between muscle types. Ultrastructural studies also demonstrated a critical role for nebulin in the maintenance of sarcomeric structure in skeletal muscle. The functional importance of nebulin in skeletal muscle function was revealed by isometric contractility assays, which demonstrated a dramatic reduction in force production in nebulin-deficient skeletal muscle.

Actin Cytoskeleton↗
PubMed2006

Passive muscle-tendon amplitude may not reflect skeletal muscle functional excursion.

PURPOSE: To quantify the gain in muscle mobility with progressive release of surrounding connective-tissue structures and to compare this property with the known architecture of each muscle. METHODS: Each of 5 different muscle tendon units (extensor carpi radialis brevis, extensor carpi radialis longus, flexor carpi ulnaris, flexor digitorum superficialis, pronator teres) was released from its insertion and secured into the jaws of a clamp attached to a servomotor that could be operated under length or force control to simulate the load placed on the tendon by a surgical assistant. A constant load of 5 N was applied to the tendon while the muscle-tendon unit was released surgically from the surrounding tissue in 1-cm increments. Mobility was plotted against release distance and analyzed by linear regression to yield mobility gain, the slope of the regression equation. One-way analysis of variance was used to compare mobility gain among muscles. RESULTS: In contrast to previous results from the brachioradialis muscle in which the mobility gain was large and highly nonlinear, mobility gain was small, consistent, and linear for all muscles studied. The smallest mobility gain was for the flexor digitorum superficialis and was highly linear. The largest gain was for the pronator teres and again was highly linear. In general, the mobility gain for the extensor carpi radialis brevis was similar to that of the extensor carpi radial longus. The flexor carpi ulnaris muscle was difficult to mobilize, and its gain was modest. There was no significant correlation between mobility gain of the forearm muscles during progressive release and the length of their fibers. CONCLUSIONS: The small mobility and complete lack of correlation with fiber length provide strong evidence that mobility gain does not accurately reflect muscle excursion as it is typically described. This calls into question the general practice of tensioning muscles by first passively extending the muscle and then choosing the attachment length as a particular portion of that passive relationship.

Aged, 80 and over↗
PubMed2006

Variability in surgical technique for brachioradialis tendon transfer. Evidence and implications.

BACKGROUND: Transfer of the tendon of the brachioradialis muscle to the tendon of the flexor pollicis longus restores lateral pinch function after cervical spinal cord injury. However, the outcomes of the procedure are unpredictable, and the reasons for this are not understood. The purpose of this study was to document the degree of variability observed in the performance of this tendon transfer. METHODS: The surgical technique used for the brachioradialis tendon transfer was assessed in two ways. First, the surgical attachment length of the brachioradialis was quantified, after transfer to the flexor pollicis longus, with use of intraoperative laser diffraction to measure muscle sarcomere length in eleven individuals (twelve limbs) with tetraplegia. Second, ten surgeons who regularly performed this procedure were surveyed regarding their tensioning preferences. Using a biomechanical model of the upper extremity, we investigated theoretically the effect of different surgical approaches on the active muscle-force-generating capacity of the transferred brachioradialis in functionally relevant elbow, wrist, and hand postures. RESULTS: The average sarcomere length (and standard deviation) of the transferred brachioradialis was 3.5 +/- 0.3 mum. That length was significantly correlated to the in situ sarcomere length (r(2) = 0.53, p < 0.05). Surgical tensioning preferences varied considerably; however, six of the ten surgeons positioned the patient's elbow between full extension (0 degrees of elbow flexion) and 50 degrees of flexion when selecting the attachment length, and six of the ten stated that their goal was to tension the transfer slightly tighter than its resting tension. The computer simulations suggested that a "tighter" brachioradialis transfer would produce its peak active force in an elbow position that is more flexed than the elbow position in which a "looser" transfer would produce its peak active force. CONCLUSIONS: This study provides evidence that experienced surgeons perform this tendon transfer differently from one another. Biomechanical simulations suggested that these differences could result in substantial variability in the active force that the transferred brachioradialis can produce in functionally relevant postures. CLINICAL RELEVANCE: The surgical attachment length and the position of the patient's limb at the time of tendon transfer are both controllable and measurable parameters. Understanding the relationship between surgical technique and postoperative muscle function may provide surgeons with more control of clinical outcomes.

Biomechanical Phenomena↗
PubMed2005

Stress-dependent and -independent expression of the myogenic regulatory factors and the MARP genes after eccentric contractions in rats.

The relationship between muscle mechanical conditions and gene expression was investigated by varying both stress and contraction mode imposed upon rat dorsiflexors (n= 25), activating them at high or low frequencies (150 Hz or 40 Hz) either eccentrically or isometrically. Muscle physiological, immunohistochemical and gene expression changes were then measured 24 h after the exercise bout. Peak stress was the best predictor of muscle injury, independent of contraction mode (i.e. eccentric or isometric). When peak stresses were matched, no physiological or immunohistochemical differences were detected between isometric and eccentric contractions. The expression of certain myogenic regulatory and muscle ankyrin repeat protein (MARP) genes (myoD, myogenin, MLP and CARP) depended both on peak muscle stress achieved during contraction and contraction mode. In contrast, Arpp/Ankrd2 was dramatically upregulated only by eccentric contractions, but not by isometric contractions, even though the stress level of the eccentric contractions varied over a three-fold range and overlapped with that of the isometric group. The role that Arpp/Ankrd2 upregulation plays in the biological response to eccentric contraction remains to be determined, as does the control mechanism whereby the expression of certain genes (such as myoD, myogenin, MLP and CARP) is sensitive to muscle stress while another (Arpp/Ankrd2) is sensitive only to contraction mode.

Animals↗
PubMed2005

Muscle LIM protein plays both structural and functional roles in skeletal muscle.

Muscle LIM protein (MLP) has been suggested to be an important mediator of mechanical stress in cardiac tissue, but the role that it plays in skeletal muscle remains unclear. Previous studies have shown that it is dramatically upregulated in fast-to-slow fiber-type transformation and also after eccentric contraction (EC)-induced muscle injury. The functional consequences of this upregulation, if any, are unclear. In the present study, we have examined the skeletal muscle phenotype of MLP-knockout (MLPKO) mice in terms of their response to EC-induced muscle injuries. The data suggest that while the MLPKO mice recover completely after EC-induced injury, their torque production lags behind that of heterozygous littermates in the early stages of the recovery process. This lag is accompanied by decreased expression of the muscle regulatory factor MyoD, suggesting that MLP may influence gene expression. In addition, there is evidence of type I fiber atrophy and a shorter resting sarcomere length in the MLPKO mice, but no significant differences in fiber type distribution. In summary, MLP appears to play a subtle role in the maintenance of normal muscle characteristics and in the early events of the recovery process of skeletal muscle to injury, serving both structural and gene-regulatory roles.

Animals↗
PubMed2005

Biomechanical properties of the brachioradialis muscle: Implications for surgical tendon transfer.

PURPOSE: To understand the mechanical properties of the brachioradialis (BR) muscle and to use this information to simulate a BR-to-flexor pollicis longus (FPL) tendon transfer for restoration of lateral pinch. METHODS: The BR mechanical properties were measured intraoperatively. Passive elastic properties were measured by elongating BR muscles at constant velocity while they were attached directly to a dual-mode servomotor. Sarcomere length was measured intraoperatively and in situ by laser diffraction with the elbow fully extended. Then both the mechanical and structural properties were programmed into a surgical simulator to test the hand surgeon's decision making when tensioning muscles in a simulated BR-to-FPL tendon transfer. RESULTS: Passive mechanical BR properties were highly nonlinear. Under slack conditions sarcomere length (mean +/- standard deviation) was 2.81 +/- 0.10 microm (n = 4), corresponding to an active force of 93% maximum. Sarcomere length of the BR measured in situ with the elbow fully extended and the forearm in neutral rotation was 3.90 +/- 0.27 microm (n = 8), corresponding to an active force of only 23% maximum. Surgeons, who tensioned the BR for transfer into the FPL using only tactile feedback from the surgical simulator, attached the muscle at a passive tension of 5.87 +/- 0.97 N, which corresponded to a sarcomere length of 3.84 microm and an active muscle force of 27% maximum. Passive BR tension when both tactile and visual information were provided to the surgeon was significantly lower (2.42 +/- 0.72 N), corresponding to a sarcomere length of 3.56 mum and a much higher active muscle force of 45% maximum. CONCLUSIONS: When these data were used to model pretransfer and posttransfer function dramatic differences in predicted function were obtained depending on the tensioning protocol chosen. This emphasizes the point that the decision-making process used during muscle tensioning has a profound effect on the functional outcome of the transfer.

Adult↗
PubMed2005

Pronator teres is an appropriate donor muscle for restoration of wrist and thumb extension.

OBJECTIVE: To compare the detailed architectural properties of the pronator teres (PT), extensor carpi radialis brevis (ECRB), and extensor pollicis longus (EPL) muscles to evaluate the suitability of PT-to-ECRB and PT-to-EPL surgical procedures. METHODS: Muscle physiologic cross-sectional areas and region-specific muscle fiber lengths were measured in cadaveric PT, ECRB, and EPL muscles (n = 10 muscles of each type). One-way repeated-analyses of variance measures and post hoc t tests with Bonferroni corrections were used for statistical comparisons. RESULTS: The ulnar head of the PT was present in 8 of 10 specimens. The average PT fiber length was similar to that of the ECRB (7.02 +/- 0.49 cm vs 6.17 +/- 0.27 cm) but was significantly longer than that of the EPL (5.44 +/- 0.25 mm). Fiber length in the humeral head of the PT was longer compared with the ulnar head (7.19 +/- 0.52 cm vs 4.14 +/- 0.25 cm). The average physiologic cross-sectional area of the PT was similar to that of the ECRB (3.5 +/- 0.4 cm2 vs 3.3 +/- 0.3 cm2) but was significantly larger than that of the EPL (3.5 +/- 0.4 cm2 vs 1.1 +/- 0.1 cm2). CONCLUSIONS: From an architectural point of view the PT is an excellent donor choice for transfer to the ECRB for restoration of wrist extension or to the EPL for restoration of thumb extension. Because there is fiber length heterogeneity within the PT, however, when the ulnar head is present it may limit the total excursion of the donor muscle. These data suggest that releasing the ulnar head of the PT before transfer may result in larger excursions of this important motor in tendon transfer surgery.

Aged↗
PubMed2005

Spastic wrist flexors are more severely affected than wrist extensors in children with cerebral palsy.

Morphological properties of skeletal muscle were compared between wrist flexors and extensors within the same children (n = 8, six females, two males; age range 4 to 9y, median age 7 y) with wrist muscle imbalance secondary to spastic cerebral palsy (CP). Five patients had hemiplegic CP, two diplegic CP, and one patient had tetraplegic CP. Muscle biopsies were taken during either tendon transfer or tendon lengthening procedures. Analyses included distribution of muscle fibre types, fibre sizes, and expression of developmental myosins. Extensor fibre area was significantly greater than flexor fibre area for type 2A fibres and type 2B fibres but not for type 1 fibres. Coefficient of variation (CV) of fibre size for all three fibre types was greater for flexors compared with extensors. The greatest CV was observed for the type 2A fibres in flexors (39.5 [3.6%]). A wide variation was observed for expression of developmental myosin with the magnitude of the expression being greater, but not statistically significant, in flexors compared with extensors (5.4/mm2 vs 0.53/mm2). These data demonstrate that significant secondary myopathy of wrist flexor muscles results from CP.

Age Factors↗
PubMed2005

Structural and mechanical alterations in spastic skeletal muscle.

Spasticity, a neurological problem secondary to an upper motor neuron lesion, has a significant effect on skeletal muscle. The upper motor neuron lesions may be secondary to a cerebral vascular accident, head injury, spinal cord injury, or degenerative diseases such as multiple sclerosis, or perinatal brain injuries such as cerebral palsy. Functional ability in these patients can be severely compromised but the basic mechanisms underlying these deficits are not clearly understood. In this review we evaluate the current evidence in the literature that suggests that skeletal muscle tissue itself is altered in spastic conditions. Experimental studies were evaluated that included a variety of methods encompassing joint mechanics, tissue mechanics, and muscle morphology. Taken together, the literature strongly supports the assertion that 'spastic muscles' are altered in a way that is unique among muscle plasticity models and inconsistent with simple transformation due to chronic stimulation or disuse. Further studies are required to detail the intra- and extracellular modifications of skeletal muscle that occur secondary to spasticity so that novel therapeutic treatments can be developed for this impairment.

Biomechanical Phenomena↗
PubMed2005

Sarcomere length measurement permits high resolution normalization of muscle fiber length in architectural studies.

The use of sarcomere length to normalize fiber length in architectural studies is commonly practiced but has not been explicitly validated. Using mouse hindlimb muscles as a model system, ankle joints were intentionally set to angles ranging from 30 degrees to 150 degrees and their muscles fixed. Tibialis anterior (TA), extensor digitorum longus (EDL) and soleus muscles were removed and their raw fiber length measured. Sarcomere length was then measured for each fiber length sample and fiber length was normalized to a standard sarcomere length. As expected, raw fiber length was dependent on tibiotarsal angle (P < 0.0005 for all muscles, r2 range 0.22-0.61), while sarcomere length normalization eliminated the joint-angle dependent variation in fiber length (P > 0.24, r2 range 0.001-0.028). Similarly, one-way ANOVA revealed no significant differences in normalized fiber length among ankle angles for any of the three muscles (P > 0.1), regardless of animal size. To determine the resolution of the method, power calculations were performed. For all muscles studied, there was >90% chance of detecting a 15% fiber length difference among muscles and >60% chance of detecting fiber length differences as small as 10%. We thus conclude that the use of sarcomere length normalization in architectural studies permits resolution of fiber length variations of 15% and may even be effective at resolving 10% fiber length variations.

Analysis of Variance↗
PubMed2004

Density and hydration of fresh and fixed human skeletal muscle.

The maximum tetanic tension of skeletal muscle (P(0)) is often estimated based on calculation of physiological cross-sectional area (PCSA). PCSA depends on muscle volume, pennation angle, and fiber length. Studies documenting PCSA in fixed human muscles usually compute muscle volume by dividing muscle mass by density. These studies use a density value of 1.0597 g/cm(3), which was originally based on unfixed rabbit and canine muscle tissue. Due to the dehydration effects of different fixation methods, the variable hydration that occurs when fixed tissue is stored in buffered saline, and the potential for species-specific muscle density, this value may be incorrect and an accurate value for fixed human muscle density is needed. To obtain an accurate density and water content values, 4% formaldehyde-fixed (n=54) and 37% formaldehyde-fixed (n=54) cadaveric human muscle samples were divided into 6 groups (0, 6, 12, 18, 24, or 30 h) for hydration in phosphate buffered saline (PBS). Measurements of volume, water content, and mass were made enabling calculation of muscle density. Additionally, water content was measured in living muscle (n=4) to determine the appropriate hydration time in PBS. Comparisons among groups demonstrated a significant increase in muscle water content and muscle volume over time, reaching living tissue levels after 24h, but, interestingly, the hydration process did not affect muscle density. These data yield a density value (mean+/-SE) of 1.112+/-0.006 g/cm(3) in 4% formaldehyde-fixed muscle and 1.055+/-0.006 g/cm(3) in 37% formaldehyde-fixed muscle. These results indicate that the use of inappropriate hydration times or density values can produce PCSA errors of 5-10%.

Adult↗
PubMed2004

Sarcomere strain and heterogeneity correlate with injury to frog skeletal muscle fiber bundles.

Sarcomere length and first-order diffraction line width were measured by laser diffraction during elongation of activated frog tibialis anterior muscle fiber bundles (i.e., eccentric contraction) at nominal fiber strains of 10, 25, or 35% (n = 18) for 10 successive contractions. Tetanic tension, measured just before each eccentric contraction, differed significantly among strain groups and changed dramatically during the 10-contraction treatment (P < 0.01). Average maximum tetanic tension for the three groups measured before any treatment was 203.7 +/- 6.8 kN/m2, but after the 10-eccentric contraction sequence decreased to 180.3 +/- 3.8, 125.1 +/- 7.8, and 78.3 +/- 5.1 kN/m2 for the 10, 25, and 35% strain groups, respectively (P < 0.0001). Addition of 10 mM caffeine to the bathing medium decreased the loss of tetanic tension in the 10% strain group but had only a minimal effect on either the 25 or 35% strain groups. Diffraction pattern line width, a measure of sarcomere length heterogeneity, increased significantly with muscle activation and then continued to increase with successive stretches of the activated muscle. Line width increase after each stretch was significantly correlated with the lower yield tension of the successive contractile record. These data demonstrate a direct association and, perhaps, a causal relationship between sarcomere strain and fiber bundle injury. They also demonstrate that muscle injury is accompanied by a progressive increase in sarcomere length heterogeneity, yielding lower yield tension as injury progresses.

Animals↗
PubMed2004

Structural and functional changes in spastic skeletal muscle.

This review summarizes current information regarding the changes in structure or function that occur in skeletal muscle secondary to spasticity. Most published studies have reported an increase in fiber size variability in spastic muscle. There is no general agreement regarding any shift in fiber type distribution secondary to spasticity. Mechanical studies in whole limbs as well as in isolated single cells support the notion of an intrinsic change in the passive mechanical properties of muscle after spasticity in addition to the more widely reported neural changes that occur. Evidence is presented for changes within both the muscle cell and extracellular matrix that contribute to the overall changes in the tissue. Taken together, the literature supports the notion that, although spasticity is multifactorial and neural in origin, significant structural alterations in muscle also occur. An understanding of the specific changes that occur in the muscle and extracellular matrix may facilitate the development of new conservative or surgical therapies for this problem.

Animals↗
PubMed2004

Predicted effects of metacarpal shortening on interosseous muscle function.

PURPOSE: Metacarpal fractures are common in hand surgery. Metacarpal shortening ranging from 2 mm to as much as 10 mm has been deemed acceptable in the literature. We examined the effect of metacarpal shortening on interosseous muscle architecture and predicted force production capacity based on the standard muscle length-tension curve (commonly known as the Blix curve). METHODS: The dorsal interosseous muscles between the middle and ring finger metacarpals from 9 adult human cadaver hands were exposed and studied. The ring finger metacarpal was translated proximally in 2-mm increments in relation to a stationary middle finger metacarpal. Digital images were obtained and analyzed to define the length and orientation of individual muscle fibers with each incremental change in position. RESULTS: Interosseous muscle fiber length increased and pennation angle decreased uniformly with increasing proximal translation of the ring finger metacarpal. At 10 mm of shortening the fiber length had increased to 20.8 +/- 1.8 mm, or to approximately 125% of optimum fiber length, and the pennation angle had decreased to 6.7 degrees +/- 2.2 degrees or by approximately 50%. CONCLUSIONS: The interosseous muscles have been shown to have a high fiber-to-muscle length ratio. This ratio indicates that these muscles function optimally over a short range of lengths, leaving them vulnerable to derangement in function owing to alteration in the surrounding bony architecture. Based on the standard muscle length--tension relationship we had predicted a steady linear decrease in interosseous power with proximal translation of the metacarpal. The results indicate an initial linear progression with a plateau at approximately 8 mm of shortening. At 2 mm of shortening there is an approximately 8% loss of power generation, at 10 mm of metacarpal shortening we predict the interosseous muscle to be capable of only approximately 55% of its optimum power compared with the resting position.

Biomechanical Phenomena↗
PubMed2004

Fiber length variability within the flexor carpi ulnaris and flexor carpi radialis muscles: implications for surgical tendon transfer.

PURPOSE: The purpose of this study was to understand the detailed architectural properties of the human flexor carpi radialis (FCR) and flexor carpi ulnaris (FCU) muscles and their implications for tendon transfer surgery. METHODS: Muscle fiber length was measured in 6 separate regions of the FCU and FCR from 10 cadaveric specimens. Sarcomere length was measured by laser diffraction for normalization. Moment arms were estimated by measuring tendon excursion with respect to joint angle. The position of entry of the motor nerve branches into each muscle also was measured to establish limits for the safe length of muscle mobilization. RESULTS: Muscle fiber length varied significantly along both the FCU and FCR. Fiber length variability in the FCU was twice that of the FCR. Although the average fiber length for both muscles across all regions was similar (62.6 +/- 2.1 mm for the FCR and 63.1 +/- 4.0 mm for the FCU), the proximal fibers of the FCU were longer compared with the proximal fibers of the FCR and the distal fibers of the FCU were shorter compared with the distal fibers of the FCR. The 99% confidence interval for the second nerve branch entry into the muscles was located approximately 69 mm distal to the medial epicondyle for the FCU and approximately 73 mm distal for the FCR. CONCLUSIONS: These data show different designs of both the FCU and the FCR. The functional significance of fiber length variability is not clear but imply that, when used in tendon transfer, the properly mobilized FCU has a much greater excursion.

Cadaver↗