Passive mechanics of muscle tendinous junction of canine diaphragm.

The diaphragmatic muscle tendon is a biaxially loaded junction in vivo. Stress-strain relations along and transverse to the fiber directions are important in understanding its mechanical properties. We hypothesized that 1) the central tendon possesses greater passive stiffness than adjacent muscle, 2) the diaphragm muscle is anisotropic, whereas the central tendon near the junction is essentially isotropic, and 3) a gradient in passive stiffness exists as one approaches the muscle-tendinous junction (MTJ). To investigate these hypotheses, we conducted uniaxial and biaxial mechanical loading on samples of the MTJ excised from the midcostal region of dog diaphragm. We measured passive length-tension relationships of the muscle, tendon, and MTJ in the direction along the muscle fibers as well as transverse to the fibers. The MTJ was slack in the unloaded state, resulting in a J-shaped passive tension-strain curve. Generally, muscle strain was greater than that of MTJ, which was greater than tendon strain. In the muscular region, stiffness in the direction transverse to the fibers is much greater than that along the fibers. The central tendon is essentially inextensible in the direction transverse to the fibers as well as along the fibers. Our data demonstrate the existence of more pronounced anisotropy in the muscle than in the tendon near the junction. Furthermore, a gradient in muscle stiffness exists as one approaches the MTJ, consistent with the hypothesis of continuous passive stiffness across the MTJ.

Passive mechanics of canine internal abdominal muscles.

The internal abdominal muscles are biaxially loaded in vivo, and therefore length-tension relations along and transverse to the directions of the muscle fibers are important in understanding their mechanical properties. We hypothesized that 1) internal oblique and transversus abdominis form an internal abdominal composite muscle with altered compliance than that of either muscle individually, and 2) anisotropy, different compliances in orthogonal directions, of internal abdominal composite muscle is less pronounced than that of its individual muscles. To test these hypotheses, in vitro mechanical testing was performed on 5 x 5 cm squares of transversus abdominis, internal oblique, and the two muscles together as a composite. These tissues were harvested from the left lateral side of abdominal muscles of eleven mongrel dogs (15-23 kg) and placed in a bath of oxygenated Krebs solution. Each tissue strip was attached to a biaxial mechanical testing device. Each muscle was passively lengthened and shortened along muscle fibers, transverse to fibers, or simultaneously along and transverse to muscle fibers. Both transversus abdominis and internal oblique muscles demonstrated less extensibility in the direction transverse to muscle fibers than along fibers. Biaxial loading caused a stiffening effect that was greater in the direction along the fibers than transverse to the fibers. Furthermore, the abdominal muscle composite was less compliant than either muscle alone in the direction of the muscle fibers. Taken together, our data suggested that the internal abdominal composite tissue has complex mechanical properties that are dependent on the mechanical properties of internal oblique and transversus abdominis muscles.

Genetic Models in Applied Physiology. Merosin deficiency leads to alterations in passive and active skeletal muscle mechanics.

The role of extracellular elements on the mechanical properties of skeletal muscles is unknown. Merosin is an essential extracellular matrix protein that forms a mechanical junction between the sarcolemma and collagen. Therefore, it is possible that merosin plays a role in force transmission between muscle fibers and collagen. We hypothesized that deficiency in merosin may alter passive muscle stiffness, viscoelastic properties, and contractile muscle force in skeletal muscles. We used the dy/dy mouse, a merosin-deficient mouse model, to examine changes in passive and active muscle mechanics. After mice were anesthetized and the diaphragm or the biceps femoris hindlimb muscle was excised, passive length-tension relationships, stress-relaxation curves, or isometric contractile properties were determined with an in vitro biaxial mechanical testing apparatus. Compared with controls, extensibility was smaller in the muscle fiber direction and the transverse fiber direction of the mutant mice. The relaxed elastic modulus was smaller in merosin-deficient diaphragms compared with controls. Interestingly, maximal muscle tetanic stress was depressed in muscles from the mutant mice during uniaxial loading but not during biaxial loading. However, presence of transverse passive stretch increases maximal contractile stress in both the mutant and normal mice. Our data suggest that merosin contributes to muscle passive stiffness, viscoelasticity, and contractility and that the mechanism by which force is transmitted between adjacent myofibers via merosin possibly in shear.

Risk assessment in liposarcoma patients based on FDG PET imaging.

PURPOSE: Tumor grade and subtype are considered standard parameters for risk assessment in patients with liposarcoma. The aim of this study was to assess the clinical value of [(18)F]fluorodeoxyglucose (FDG) PET-derived maximum standardized uptake value (SUV(max)) for prediction of outcome in liposarcoma patients. METHODS: (18)F-FDG PET was performed in 54 patients with liposarcoma prior to therapy. SUV(max) was calculated for each tumor and results were correlated with tumor grade, subtype, and relapse-free survival. RESULTS: SUV(max) ranged from 0.4 to 15.9 (mean 3.6) and was significantly lower in grade I than in grade II and grade III tumors. SUV(max) was 2.3+/-1.7, 3.5+/-1.5, 4.8+/-2.5, and 5.6+/-5.8 in well-differentiated, myxoid/round cell, dedifferentiated, and pleomorphic subtypes, respectively. Borderline differences (p=0.059) were found between tumor SUV(max) in patients with and without relapse. Using a SUV of 3.6 as cut-off, the accuracy in predicting a relapse was 75%. Tumor grade yielded a lower accuracy for predicting relapse (50%), as did tumor subtype (35%). In Kaplan-Meier survival analysis, patients with a SUV(max) >3.6 had a significantly shorter disease-free survival of 21 months compared with 44 months in patients with a SUV(max)

Shape and tension distribution of the active canine diaphragm.

Both diaphragm shape and tension contribute to transdiaphragmatic pressure, but of the three variables, tension is most difficult to measure. We measured transdiaphragmatic pressure and the global shape of the in vivo canine diaphragm and used principles of mechanics to compute the tension distribution. Our hypotheses were that 1) tension in the active diaphragm is nonuniform with greater tension in the central tendon than in the muscular regions; 2) maximum tension is essentially oriented in the muscle fiber direction, whereas minimum tension is orthogonal to the fiber direction; and 3) during submaximal activation change in the in vivo global shape is small. Metallic markers, each 2 mm in length, were implanted surgically on the peritoneal surface of the diaphragm at 1.5- to 2.0-cm intervals along the muscle bundles at the midline, ventral, middle, and dorsal regions of the left costal diaphragm and along a muscle bundle of the crural diaphragm. Postsurgery, a biplane videofluoroscopic system was used to determine the in vivo three-dimensional coordinates of the markers at end expiration and end inspiration during quiet breathing as well as at end-inspiratory efforts against an occluded airway at lung volumes of functional residual capacity and at one-third maximum inspiratory capacity increments in volume to total lung capacity. A surface was fit to the marker locations using a two-dimensional spline algorithm. Diaphragm surface was modeled as a pressurized membrane, and tension distribution in the active diaphragm was computed using the ANSYS finite element program. We showed that the peak of the diaphragm dome was closer to the ventral surface than to the dorsal surface and that there was a depression or valley in the crural region. In the supine position, during inspiratory efforts, the caudal displacement of the dorsal region of the diaphragm was greater than that of the dome, and the valley along the crural diaphragm was accentuated. In contrast, at lower lung volumes in the prone posture, the caudal displacement of the dome was greater than that of the crural region. At end of inspiration, transdiaphragmatic pressure was approximately 6.5 cmH2O, and tensions were nonuniform in the diaphragm. Maximum principal stress sigma(1) of central tendon was found to be greater than sigma(1) of the costal region, and that was greater than sigma(1) of the crural region, with values of 14-34, 14-29, and 4-14 g/cm, respectively. The corresponding data of the minimum principal stress sigma(2) were 9-18, 3-9, and 0-1.5 g/cm, respectively. Maximum principal tension was approximately parallel to the muscle fibers, whereas minimum tension was essentially orthogonal to the longitudinal direction of the muscle fibers. In the muscular region, sigma(1) was approximately 3-fold sigma(2), whereas in the central tendon, sigma(1) was only approximately 1.5-fold sigma(2.).

Altered muscle force and stiffness of skeletal muscles in alpha-sarcoglycan-deficient mice.

Alpha-sarcoglycan (ASG) is a transmembrane protein of the dystrophin-associated complex, and absence of ASG causes limb-girdle muscular dystrophy. We hypothesize that disruption of the sarcoglycan complex may alter muscle extensibility and disrupt the coupling between passive transverse and axial contractile elements in the diaphragm. We determined the length-tension relationships of the diaphragm of young ASG-deficient mice and their controls during uniaxial and biaxial loading. We also determined the isometric contractile properties of the diaphragm muscles from mutant and normal mice in the absence and presence of passive transverse stress. We found that the diaphragm muscles of the null mutants for the protein ASG show 1) significant decrease in muscle extensibility in the directions of the muscle fibers and transverse to fibers, 2) significant reductions in force-generating capacity, and 3) significant reductions in coupling between longitudinal and transverse properties. Thus these findings suggest that the sarcoglycan complex serves a mechanical function in the diaphragm by contributing to muscle passive stiffness and to the modulation of the contractile properties of the muscle.