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Biomedical subjects

R L Lieber

Publications and source records attributed to R L Lieber.

At least 55 records · Page 3Linked to original sources

Intraoperative measurement and biomechanical modeling of the flexor carpi ulnaris-to-extensor carpi radialis longus tendon transfer.

Sarcomere length was measured intraoperatively in five patients undergoing tendon transfer of the flexor carpi ulnaris (FCU) to the extensor carpi radialis longus (ECRL) for radial nerve palsy. All measurements were made with the elbow in 20 deg of flexion. Prior to tendon transfer, FCU sarcomere length ranged from 2.84 +/- .12 microns (mean +/- SEM) with the wrist flexed to 4.16 +/- .15 microns with the wrist extended. After transfer into the ECRL tendon, sarcomere length ranged from 4.82 +/- .11 microns with the wrist flexed (the new longest position of the FCU) to 3.20 +/- .09 microns with the wrist extended, resulting in a shift in the sarcomere length operating range to significantly longer sarcomere lengths (p < 0.001). At these longer sarcomere lengths, the FCU muscle was predicted to develop high active tension only when the wrist was highly extended. A biomechanical model of this tendon transfer was generated using normative values obtained from previous studies of muscle architectural properties, tendon compliance, and joint moment arms. Predicted sarcomere lengths pre- and post-tendon transfer agreed well with intraoperative experimental measurements. The theoretical wrist extension moment-wrist joint angle relationship was also calculated for a variety of values of FCU muscle length. These different lengths represented the different conditions under which the FCU could be sutured into the ECRL tendon. Variation in FCU muscle length over the range 200 mm to 260 mm resulted in large changes in absolute peak moment produced as well as the angular dependence of peak moment. This was due to the change in the region of FCU operation on its sarcomere length-tension curve relative to the magnitude of the ECRL moment arm. These data demonstrate the sensitivity of a short-fibered muscle such as the FCU to affect the functional outcome of surgery. In addition, we demonstrated that intraoperative sarcomere length measurements, combined with biomechanical modeling provide the surgeon with a powerful method for predicting the functional effect of tendon transfer surgery.

Adult↗

Muscle fiber length and moment arm coordination during dorsi- and plantarflexion in the mouse hindlimb.

The purpose of this study was to test the hypothesis that muscle fiber length and joint moment arm are combined in such a way that maximum muscle force is produced during locomotion. Plantarflexor (soleus, SOL and medial gastrocnemius, MG) and dorsiflexor (extensor digitorum longus, EDL and tibialis anterior, TA) muscle architecture in the mouse was measured along with their associated moment arms. Fiber length varied significantly between muscles ranging from 5.7 +/- 0.2 mm (MG) to 7.6 +/- 0.2 mm (TA). Plantarflexor moment arms were over twice as large as dorsiflexor moment arms (1.88 +/- 0.06 mm vs. 0.84 +/- 0.03 mm) suggesting a greater muscle length change with joint angle for plantarflexors compared to dorsiflexors. Using a simple muscle-joint model, the active sarcomere length range in these muscle groups was calculated and proved to be quite similar between functional groups. The active range for dorsiflexors was 2.2-2.4 microns, while the active range for plantarflexors was 2.2-2.5 microns, indicating that both muscle groups operate primarily near the plateau of their length tension-relation. Finally, when calculating force produced by muscles during locomotion, the combination of moment arm and fiber length measured in all muscle groups yielded muscle-joint systems that produced near maximal forces at the velocities modeled. These data indicate that fiber length and moment arm appear to be coordinated to yield the greatest possible force production during locomotion.

Animals↗

Skeletal muscle architecture and fiber-type distribution with the multiple bellies of the mouse extensor digitorum longus muscle.

The purpose of this study was to describe the extent to which architectural and fiber-type characteristics of the four bellies of the mouse extensor digitorum longus (EDL) suggest specialization of the digits, and to mathematically model the functional effects of the structural properties. Six mice were perfused in situ with glutaraldehyde while the lower limb was positioned approximately in the neutral position. After perfusion, lower limbs were removed and placed in glutaraldehyde until the EDL was dissected from the limb and separated into individual muscle bellies corresponding to each digit for architectural determination. The results showed that the muscle belly of digit 5 tended to be different from the muscle bellies of digits 2-4 for many architectural characteristics. Muscle mass, physiological cross-sectional area, muscle length, and fiber length were all significantly greater in digit 5. Proximal tendon length was also significantly longer in digit 5, and distal tendon length, as well as total tendon length, were significantly shorter in digit 5. Sarcomere length was shortest at the proximal end of the muscle and longest, 60-80%, toward the distal end. Fiber type distribution was about 60% FOG, 39% FG with only 1% SO fibers in all muscle bellies. Muscle-tendon modeling illustrated that peak force and maximal shortening velocity were greatest in digit 5. Inclusion of the tendon in the model resulted in a 10% shift of the force-length curve to longer lengths. Assuming muscle structure is matched to function, we speculate that digit 5 of the mouse EDL bears higher loads over a greater excursion during locomotion compared to the remaining digits.

Anatomy, Artistic↗

Intraoperative sarcomere length measurements reveal differential design of human wrist extensor muscles.

The design of the wrist extensor muscles was studied using a combination of intraoperative laser diffraction and biomechanical modelling of data obtained from human patients and previously published data. Intraoperatively, the change in sarcomere length per degree joint angle rotation (i.e. dSL/d omega) was measured as the wrist was moved from neutral to full flexion in both the extensor carpi radialis brevis (ECRB) and extensor carpi radialis longus (ECRL) muscles. Sarcomere length change per degree rotation was approximately twice as great for the ECRB compared with the ECRL muscle (9.06 +/- 1.06 versus 4.69 +/- 1.20 nm degree-1, mean +/- S.E.M., N = 7). Muscle fibre length and wrist extensor moment arms were obtained from published data and dSL/d omega calculated. The experimental values for dSL/d omega were extremely close to the calculated values. These data demonstrate that architectural differences between the ECRB and ECRL are accentuated by differences between their wrist extensor moment arms. This differential design may permit the extensor muscles, as a group, to generate high force over a wider range of velocities than would be possible with a single muscle or it may permit conservation of mass such that the two muscles together can generate approximately the same force and excursion as a single muscle but with approximately 30% less mass.

Humans↗

Sarcomere length in wrist extensor muscles. Changes may provide insights into the etiology of chronic lateral epicondylitis.

Since the etiology of tennis elbow (lateral epicondylitis) is poorly understood, we studied the anatomical changes in the extensor carpl radialis brevis (ECRB) muscle during elbow joint rotation. Specifically, we measured ECRB sarcomere length, using an intraoperative laser diffraction procedure that measures muscle sarcomere length with an accuracy of +/- 0.05 micron. We found an unexpected biphasic response in ECRB sarcomere length as the elbow was rotated from full extension to full flexion. The initial sarcomere length of 3.49 microns, with the elbow extended, was gradually changed to 3.68 microns, 3.34 microns, 3.81 microns, and 3.45 microns with progressive elbow flexion. Based on the very nonlinear mechanical properties of skeletal muscle, this "double lengthening" of the ECRB during progressive flexion would impose intense eccentric contractions on the muscle itself. Given that eccentric contractions cause muscle injury and subsequent inflammation, these findings may provide insights into the etiology of lateral epicondylitis.

Biomechanical Phenomena↗

Force transmission in skeletal muscle: from actomyosin to external tendons.

The actual path of force transmission in skeletal muscle from actomyosin interaction to tension at the tendinous insertion site is poorly understood. Within the muscle cell, endo- and exosarcomeric cytoskeletal proteins create series and parallel connections between contractile proteins resulting in a meshwork across which force can be transmitted in practically any direction with respect to the fiber axis. At the surface membrane, connections between the intermediate filament system, dystrophin, and specialized membrane complexes provide the route of force transmission to the extracellular matrix material. Finally, parallel and series connections between muscle fibers allow radial and longitudinal forces to converge on the connective tissue matrix. This complex pathway will certainly be the subject of future studies in muscle biology, biomechanics, and physiology.

Actomyosin↗

Equal effectiveness of electrical and volitional strength training for quadriceps femoris muscles after anterior cruciate ligament surgery.

Neuromuscular electrical stimulation and voluntary muscle contraction are two exercise modes widely used in rehabilitation to strengthen skeletal muscle. Since there is no debate as to which mode is most effective, we compared electrical stimulation with voluntary contraction performed at matched intensities following reconstructive surgery of the anterior cruciate ligament. Forty men and women, aged 15-44, were randomly assigned to either an electrical stimulation or a voluntary contraction group. None of the subjects had a previous history of neuromuscular injury. The subjects received treatment for 30 minutes a day, 5 days a week, for 4 weeks. Knee extension torque was monitored during treatment to try to match the absolute muscular tensions (quantified as "activity") achieved during therapy. To match the activity of the subjects in the electrical stimulation group, who were treated at the highest stimulation intensity they could tolerate, the subjects in the voluntary contraction group were paced at progressively increasing intensities corresponding to 15, 25, 35, and 45% of the injured limb's maximum voluntary torque during weeks 1, 2, 3, and 4, respectively. We found no significant difference between the groups in terms of maximum voluntary knee extension torque throughout the study period. In addition, 1 year after surgery, there was still no significant difference between groups with regard to knee extension torque (p > 0.4). These data suggest that neuromuscular electrical stimulation and voluntary muscle contraction treatments, when performed at the same intensity, are equally effective in strengthening skeletal muscle that has been weakened by surgical repair of the anterior cruciate ligament.

Adolescent↗

Stepwise regression is an alternative to splines for fitting noisy data.

In this study, we compared numerical methods that are used to fit noisy data. Comparisons included polynominal regression, stepwise polynomial regression and quintic spline approximation. The advantages and limitations of each method are discussed in terms of curve fit quality, computational speed and ease, and solution compactness. Overall, the spline approximation and stepwise polynomial regression provide the best fits to the data. Stepwise regression provides the added utility of providing a simple, unconstrained function which can be easily implemented in simulation studies.

Algorithms↗

Human wrist motors: biomechanical design and application to tendon transfers.

Moment arm, muscle architecture, and tendon compliance in cadaveric human forearms were determined and used to model the wrist torque-joint angle relation (i.e. wrist torque profile). Instantaneous moment arms were calculated by differentiating tendon excursion with respect to joint rotation. Maximum isometric tension of each wrist muscle-tendon unit was predicted based on muscle physiological cross-sectional area. Muscle forces were subsequently adjusted for sarcomere length changes resulting from joint rotation and tendon strain. Torque profiles were then calculated for each prime wrist motor (i.e. muscle-tendon unit operating through the corresponding moment arm). Influences of moment arm, muscle force, and tendon compliance on the torque profile of each motor were quantified. Wrist extensor motor torque varied considerably throughout the range of motion. The contours of the extensor torque profiles were determined primarily by the moment arm-joint angle relations. In contrast, wrist flexor motors produced near-maximal torque over the entire range of motion. Flexor torque profiles were less influenced by moment arm and more dependent on muscle force variations with wrist rotation and with tendon strain. These data indicate that interactions between the joint, muscle, and tendon yield a unique torque profile for each wrist motor. This information has significant implications for biomechanical modeling and surgical tendon transfer.

Biomechanical Phenomena↗

Sarcomere length changes after flexor carpi ulnaris to extensor digitorum communis tendon transfer.

Sarcomere length was measured intraoperatively on five patients undergoing tendon transfer of the flexor carpi ulnaris (FCU) to the extensor digitorum communis (EDC) for radial nerve palsy. The most significant result was that the absolute sarcomere length and sarcomere length operating range of the FCU increased after transfer into the EDC (p < .001). Preoperatively, with the wrist fully extended and fingers flexed, FCU sarcomere length was 4.22 +/- .24 microns and decreased to 3.19 +/- .05 microns as the wrist was fully flexed. This represented an overall sarcomere length range of 1.03 microns. After the tendon transfer using standard recommended techniques, all sarcomere lengths were significantly longer (p < .001). Specifically, sarcomeres were 0.74 +/- .14 microns longer with the muscle in its fully lengthened position (4.96 +/- .43 microns with the wrist and digits flexed) and 0.31 +/- .16 microns longer with the FCU in the fully shortened position (3.50 +/- .06 microns with the wrist and digits extended). At these sarcomere lengths, the FCU muscle was predicted to develop relatively high force only during movement involving synergistic wrist flexion and finger extension. Under the conditions of the procedures performed, the transferred FCU muscle was predicted to produce maximum force over the range of about 30 degrees of wrist flexion and 0 degree of finger flexion to 70 degrees of wrist extension and 90 degrees of finger flexion. While this is acceptable, a more desirable result was predicted to occur if the muscle was transferred at a longer length. In this latter case, greater stretch of the FCU during transfer (increasing sarcomere length to about 5 microns) was predicted to improve the transfer. The more highly stretched FCU was predicted to result in maximum force as the wrist and fingers progressed from about 60 degrees of wrist extension and 0 degree of finger flexion to 80 degrees of wrist extension and 70 degrees of finger flexion. These results quantify the relationship between the passive tension chosen for transfer, sarcomere length, and the estimated active tension that can be generated by the muscle. The results also demonstrate the feasibility of using intraoperative laser diffraction during tendon transfer as a guide for optimal placement of the transferred muscle.

Adolescent↗

Relationship between joint motion and flexor tendon force in the canine forelimb.

To increase in vivo tendon force and gliding after flexor tendon repair, a variety of modifications to the methods by which protective passive motion is administered have been advocated. To determine the relationship between the prime variables, wrist and digital position, muscle activation, and in vivo tendon force, a clinically relevant canine model was developed. Force was measured in the flexor tendon during several joint manipulation paradigms: single-finger flexion-extension with the wrist flexed (group 1F), single-finger flexion-extension with the wrist extended (group 1E), four-finger flexion-extension with the wrist flexed (group 4F), four-finger flexion-extension with the wrist extended (group 4E), and synergistic wrist and finger motion where wrist extension and finger flexion were performed simultaneously, followed by wrist flexion and finger extension (group SYN). In addition, tendon force was measured during electric stimulation of the proximal flexor muscle mass. Passive tendon force with the wrist extended (groups 1E and 4E) was two to three times greater than that measured with the wrist flexed, independent of the number of digits moved. With the wrist extended, peak tendon force reached 1,997 g +/- 194 g during single-digit manipulation (group 1E), compared to only 853 g +/- 104 g with the wrist flexed during the same maneuver (group 1F). Statistical comparison between means revealed that groups 1E and 4E were significantly different from groups 1F, 4F, and SYN (p < .005). There were no significant differences between groups 1E and 4E or between groups 1F, 4F, and SYN (p > .200). Active muscle force elicited by electrical stimulation and passive force varied dramatically as the wrist was flexed from full extension 3460 g +/- 766 g to full flexion 427 g +/- 239 g (p < .001). Simultaneously, passive tension decreased from 940 g +/- 143 g with wrist extended to 76 g +/- 37 g with the wrist flexed. These data indicate that wrist position has the greatest effect on flexor tendon force during motions that are commonly used to rehabilitate flexor tendon repairs. Thus, if force is to be controlled during passive motion, wrist-joint angle will have the dominant effect, while the number of digits manipulated will have much less of an effect. If the clinical goal is to minimize tendon force, rehabilitation could be carried out with the wrist flexed, whereas if the goal is to increase tendon force, rehabilitation could include exercise programs that use a greater degree of wrist extension.

Animals↗

Muscle cytoskeletal disruption occurs within the first 15 min of cyclic eccentric contraction.

The time course of loss of the 55,000-Da intermediate filament protein desmin was measured in rabbit muscles subjected to cyclic eccentric contraction. Rabbit extensor digitorum longus (EDL) and tibialis anterior (TA) muscles were examined 5 or 15 min after eccentric exercise and 1 h or 1 day after 30 min of an eccentric exercise protocol (n = 16 rabbits). The earliest change noted was a significant loss of desmin labeling in 2.5 +/- 0.63% of the rabbit EDL muscle fibers (P < 0.005) 5 min after initiation of eccentric exercise. Some loss of TA fiber desmin was also apparent at this time period (0.24 +/- 0.19%), but the magnitude was not significantly different from zero (P > 0.2). Fifteen minutes after initiation of exercise, desmin loss was more pronounced, increasing to 7.4 +/- 1.4 and 4.6 +/- 1.0% in the EDL and TA, respectively (P < 0.005). Finally, 1 day after 30 min of eccentric exercise, the percentage of fibers without desmin staining rose to 23.4 +/- 3.7 and 7.7 +/- 2.4% in the EDL and TA, respectively (P < 0.001). Loss of desmin staining occurred in the absence of contractile or metabolic protein disruption. Increased staining intensity of the intrasarcomeric cytoskeletal protein titin and an inability to exclude plasma fibronectin were also observed in most but not all fibers that had lost desmin staining. Desmin disruption thus represents a very early structural manifestation of muscle injury during eccentric contraction. Cytoskeletal disruption may predispose the contractile apparatus to previously reported structural damage.

Animals↗

Tendon biomechanical properties enhance human wrist muscle specialization.

Biomechanical properties of human wrist tendons were measured under loads predicted to be experienced by those tendons under physiological conditions. This was accomplished by measuring the architectural properties of the five prime wrist movers--extensors carpi radialis brevis (ECRB), extensor carpi radialis longus (ECRL), extensor carpi ulnaris (ECU), flexor carpi radials (FCR), flexor carpi ulnaris (FCU)--and predicting their maximum tension (P0) using a specific tension value (22.5 N cm-2. Loading the corresponding tendons to P0 resulted in significantly different strain among tendons (p < 0.01) with the largest strain observed in the FCU (3.68 +/- 0.31%) and the smallest strain observed in the ECRL (1.78 +/- 0.14%). Further, strain magnitude was significantly positively correlated with the tendon length-to-fiber length ratio of the muscle-tendon unit, a measure of the intrinsic compliance of the muscle-tendon unit. Theoretical modeling of the magnitude of muscle sarcomere shortening expected based on the measured biomechanical properties revealed a maximum sarcomere length decrease of about 0.6 micron for the FCU to a minimum of about 0.2 micron for the ECRB at P0. Thus, tendon compliance may, but does not necessarily, result in significant modification of muscle force generation. The significant variation in tendon biomechanical properties was not observed using traditional elongation-to-failure methods on the same specimens. Thus, the use of elongation-to-failure experiments for determination of tendon properties may not be reasonable when the purpose of such studies is to infer physiological function. These data indicate that muscle-tendon units show remarkable specialization and that tendon intrinsic properties accentuate the muscle architectural specialization already present.

Biomechanical Phenomena↗

Anti-inflammatory medication after muscle injury. A treatment resulting in short-term improvement but subsequent loss of muscle function.

We studied the effect of flurbiprofen, a non-steroidal anti-inflammatory drug, on muscles that had been subjected to exercise-induced injury. The muscles of the anterior compartment in the limbs of rabbits were cyclically activated as the ankle was simultaneously moved through passive plantar flexion every two seconds for thirty minutes. This treatment imposed acute passive lengthening (eccentric contractions) of the maximally contracted muscles of the anterior compartment. After the eccentric contraction-induced muscle injury, one group of rabbits was treated with oral administration of flurbiprofen, two times a day for six days, while the other group of rabbits served as untreated controls. The contractile, histological, and ultrastructural properties of the muscles were measured before the initial exercise and at three, seven, and twenty-eight days afterward. The group that was treated with flurbiprofen demonstrated a more complete functional recovery than the untreated controls at three and seven days but had a deficit in torque and force generation at twenty-eight days. The administration of flurbiprofen also resulted in a dramatic preservation of the intermediate filament protein desmin. After three days, the proportion of fibers of the extensor digitorum longus that lost desmin-staining was significantly greater in the untreated controls than in the treated animals (34 +/- 4.1 compared with 2.9 +/- 1.7 per cent) (p < 0.001), a finding that supports the concept of a short-term protective effect. However, the muscles in the treated animals still mounted a dramatic regenerative response, as indicated by the expression of embryonic myosin. Early in the recovery period (at three days), significantly fewer fibers of the extensor digitorum longus (2.2 +/- 1.4 per cent) expressed embryonic myosin in the treated animals than in the untreated controls (11.8 +/- 1.9 per cent) (p < 0.001). However, at seven days, the expression of embryonic myosin by the muscles from the treated animals (19.5 +/- 11.9 per cent) actually exceeded that of the muscles from the untreated controls (16.2 +/- 4.1 per cent). This finding suggests either a delayed or an ineffectual regenerative response by the muscles in the treated animals.

Analgesics↗

Relationship between muscle fiber types and sizes and muscle architectural properties in the mouse hindlimb.

Skeletal muscle fiber and architectural properties both contribute to the functional behavior of a muscle. This study uses discriminant analysis and mathematical modeling to identify the structurally and functionally significant properties. The architectural properties of fiber length, muscle length, and pennation angle are found to be the most structurally significant parameters, whereas fiber length, muscle length, and fiber type distribution are found to be most functionally determining. Architectural speed and fiber type do not appear to be complimentary (i.e., the architectural determinant of speed, fiber length, is not associated with fibers of high intrinsic velocity). However, there does seem to be a synergistic relation between the two property classes and force production. Muscles with large physiological cross sectional areas (PCSAs) tend to contain a greater proportion of larger, faster fibers. Structurally or morphologically significant parameters are not always found to have a large functional effect. Pennation angle, though one of the most structurally significant variables, was found to have very little functional effect.

Animals↗

Physiologic consequences of surgical lengthening of extensor carpi radialis brevis muscle-tendon junction for tennis elbow.

Sarcomere length was measured intraoperatively using a laser diffraction method before and after surgical lengthening of the human extensor carpi radialis brevis muscle (ECRB) in five subjects treated for lateral epicondylitis. Based on measured sarcomere and filament lengths, we previously established the length-tension curve for this muscle and the normal sarcomere length range as a function of wrist joint angle. Preoperative measurements indicated that the ECRB developed near-maximal isometric force at full wrist extension, decreasing to 20% maximum at full wrist flexion. Stair-step surgical tendon lengthening of the ECRB by 9.1 mm resulted in mean ECRB sarcomere shortening of 0.30 microns. This 0.30 microns shortening was predicted to have two primary biomechanical effects: (1) a 25% decrease in muscle passive tension that could lead to reduced insertional tension and decreased pain and (2) a 25% increase in active muscle force that opposes the notion that tendon lengthening necessarily results in muscle weakness.

Adult↗

Myosin and actin filament lengths in diaphragms from emphysematous hamsters.

In vitro studies of the diaphragm from emphysematous animals have, in some instances, shown an alteration in its sarcomere length-tension relationship and a decreased maximal specific tension. To our knowledge, it has never been determined whether such functional changes may be indicative of ultrastructural adaptations, e.g., changes in filament lengths and thus cross-bridge number. To address this, we compared filament lengths in diaphragms from hamsters in which emphysema was induced by endotracheal instillation of elastase (E) 5 mo before the hamsters were killed with those from control hamsters (C; saline instillation). Diaphragms were then fixed by vascular perfusion with buffered glutaraldehyde in situ at airway pressures set to approximate the physiological range of lung volumes from residual volume (RV) to total lung capacity (TLC). Ultrathin sections (50-70 nm) were taken parallel to the muscle fiber axis and examined by electron microscopy (x33,000). Sarcomere and filament length measurements were calibrated using an actin periodicity of 39 nm and an M-band width of 86 nm to correct for dimensional changes during preparation. Emphysema increased the change in lung volume from -20 to +25 cmH2O airway pressure (from RV to TLC) by approximately 88%, and the displacement volume of excised lung at 0 cmH2O airway pressure was increased by approximately 138% on average. Neither myosin (C = 1.592 +/- 0.027; E = 1.572 +/- 0.035 micron; P = 0.72) nor actin (C = 1.210 +/- 0.035; E = 1.221 +/- 0.014 micron; P = 0.76) filament lengths were affected by emphysema. Thus, filament length changes do not underlie the diaphragm functional adaptations observed previously in emphysema.

Actin Cytoskeleton↗