T.R. Leonard

DEPRESSION OF CAT SOLEUS FORCES FOLLOWING ISOKINETIC SHORTENING

The purpose of this study was to test the hypothesis that force depression following muscle shortening is caused by stress-induced inhibition of the cross-bridges in the zone of new overlap between thick and thin filaments. Force depressions following shortening were assessed in five separate tests on the cat soleus. It was found that force depressions following shortening were inversely related to the speed of shortening and were directly related to the amount of shortening, which is in agreement with published results on muscles and fibre preparations. It was further observed that the force depressions were directly related to the force produced during the shortening phase, and that the force depressions were systematically reduced by relaxing the stress on the muscle following shortening. These latter results could not be compared with corresponding literature values for lack of systematic testing of these properties in mammalian skeletal muscle. All results of this study supported the predictions which were made based on our working hypothesis proposed above. The results also confirmed that there are long-lasting, time-dependent properties of skeletal muscle which are not part of the cross-bridge theory of muscular force production and which are ignored in Hill-type models of skeletal muscle.

Validation of optimization models that estimate the forces exerted by synergistic muscles

The purpose of this study was to validate the mathematical predictions of individual muscle forces obtained using optimization models. Mathematical muscle force predictions were made using linear and nonlinear optimization models proposed in the literature. Actual muscle forces were measured experimentally from soleus, gastrocnemius and plantaris muscles of an adult male cat during a variety of locomotor tasks. Mathematically predicted muscle forces did not agree well with the experimentally determined muscle forces, because changes in force sharing during given step cycles and for different locomotor speeds were largely ignored in the theoretical models tested. It is suggested that changes in force sharing during given step cycles may be caused by differences in force-velocity characteristics or small time delays of onset of activation between muscles; whereas changes in force sharing associated with different speeds of locomotion may be caused by corresponding changes in the magnitude of centrally controlled activation. Theoretical simulations testing the feasibility of these suggestions were encouraging. In view of the findings of this study, it is suggested that future models should be developed and validated based on experimental findings.

Force-length properties and functional demands of cat gastrocnemius, soleus and plantaris muscles.

The purpose of this study was to measure isometric force-length properties of cat soleus, gastrocnemius and plantaris muscle-tendon units, and to relate these properties to the functional demands of these muscles during everyday locomotor activities. Isometric force-length properties were determined using an in situ preparation, where forces were measured using buckle-type tendon transducers, and muscle-tendon unit lengths were quantified through ankle and knee joint configurations. Functional demands of the muscles were assessed using direct muscle force measurements in freely moving animals. Force-length properties and functional demands were determined for soleus, gastrocnemius and plantaris muscles simultaneously in each animal. The results suggest that isometric force-length properties of cat soleus, gastrocnemius and plantaris muscles, as well as the region of the force-length relation that is used during everyday locomotor tasks, match the functional demands.

Residual force enhancement in myofibrils and sarcomeres

Residual force enhancement has been observed following active stretch of skeletal muscles and single fibres. However, there has been intense debate whether force enhancement is a sarcomeric property, or is associated with sarcomere length instability and the associated development of non-uniformities. Here, we studied force enhancement for the first time in isolated myofibrils (n=18) that, owing to the strict in series arrangement, allowed for evaluation of this property in individual sarcomeres (n=79). We found consistent force enhancement following stretch in all myofibrils and each sarcomere, and forces in the enhanced state typically exceeded the isometric forces on the plateau of the force–length relationship. Measurements were made on the plateau and the descending limb of the force–length relationship and revealed gross sarcomere length non-uniformities prior to and following active myofibril stretching, but in contrast to previous accounts, revealed that sarcomere lengths were perfectly stable under these experimental conditions. We conclude that force enhancement is a sarcomeric property that does not depend on sarcomere length instability, that force enhancement varies greatly for different sarcomeres within the same myofibril and that sarcomeres with vastly different amounts of actin–myosin overlap produce the same isometric steady-state forces. This last finding was not explained by differences in the amount of contractile proteins within sarcomeres, vastly different passive properties of individual sarcomeres or (half-) sarcomere length instabilities, suggesting that the basic mechanical properties of muscles, such as force enhancement, force depression and creep, which have traditionally been associated with sarcomere instabilities and the corresponding dynamic redistribution of sarcomere lengths, are not caused by such instabilities, but rather seem to be inherent properties of the mechanisms of contraction.

Material and functional properties of articular cartilage and patellofemoral contact mechanics in an experimental model of osteoarthritis

The purposes of this study were to determine the in situ functional and material properties of articular cartilage in an experimental model of joint injury, and to quantify the corresponding in situ joint contact mechanics. Experiments were performed in the anterior cruciate ligament (ACL) transected knee of the cat and the corresponding, intact contralateral knee, 16 weeks following intervention. Cartilage thickness, stiffness, effective Youngs modulus, and permeability were measured and derived from six locations of the knee. The total contact area and peak pressures in the patellofemoral joint were obtained in situ using Fuji Pressensor film, and comparisons between experimental and contralateral joint were made for corresponding loading conditions. Total joint contact area and peak pressure were increased and decreased significantly (alpha=0.01), respectively, in the experimental compared to the contralateral joint. Articular cartilage thickness and stiffness were increased and decreased significantly (alpha=0.01), respectively, in the experimental compared to the contralateral joint in the four femoral and patellar test locations. Articular cartilage material properties (effective Youngs modulus and permeability) were the same in the ACL-transected and intact joints. These results demonstrate for the first time the effect of changes in articular cartilage properties on the load transmission across a joint. They further demonstrate a substantial change in the joint contact mechanics within 16 weeks of ACL transection. The results were corroborated by theoretical analysis of the contact mechanics in the intact and ACL-transected knee using biphasic contact analysis and direct input of cartilage properties and joint surface geometry from the experimental animals. We conclude that the joint contact mechanics in the ACL-transected cat change within 16 weeks of experimental intervention.

Forces in gastrocnemius, soleus, and plantaris tendons of the freely moving cat

The purpose of this study was to gain an insight into the mechanisms of force sharing among muscles in a functional group. Tendon force measurements were obtained simultaneously from gastrocnemius, soleus, and plantaris muscles of 10 cats during a variety of different locomotor tasks using strain gauge based force transducers. In particular, tendon forces were measured for conditions where movement speed was altered systematically, and where movement speed was kept constant but external resistance to walking was varied systematically. The results show that forces in the gastrocnemius and plantaris tendons increase with increasing intensities of movement, independent of intensity being altered by varying speed or external resistance. In contrast, peak soleus forces, on an average, remained nearly the same for all conditions; however, substantial modulations in soleus force were observed for consecutive stride cycles. These results suggest that soleus forces are not limited by peripheral (contractile) conditions but by central mechanisms and, further, that these central mechanisms depend on speed of movement and resistance to movement.

The relationship between force depression following shortening and mechanical work in skeletal muscle.

Force depression following muscle shortening was investigated in cat soleus (n=6) at 37 degrees C for a variety of contractile conditions with the aim to test the hypotheses that force depression was independent of the speed of shortening and was directly related to the mechanical work produced by the muscle during shortening. Force depression was similar for tests in which the mechanical work performed by the muscle was similar, independent of the speed of shortening (range of speeds: 4-256mm/s). On the other hand, force depression varied significantly at a given speed of shortening but different amounts of mechanical work, supporting the hypothesis that force depression was not speed - but work dependent. The variations in the mechanical work produced by the muscle during shortening accounted for 87-96% of the variance observed in the force depression following shortening further supporting the idea that the single scalar variable work accounts for most of the observed loss in isometric force after shortening. The results of the present study are also in agreement with the notion that the mechanism underlying force depression might be associated with an inhibition of cross-bridge attachments in the overlap zone formed during the shortening phase, as proposed previously (Herzog and Leonard, 1997. Journal of Bimechanics 30 (9), 865-872; Maréchal and Plaghki, 1979.

One-year changes in hind limb kinematics, ground reaction forces and knee stability in an experimental model of osteoarthritis

Long-term changes in the three-dimensional external loading, hind limb kinematics and knee stability were assessed in an anterior cruciate ligament (ACL)-transected cat model of osteoarthritis (OA). Seven skeletally mature cats (mean mass 4.6+/-1.4 kg) were studied before ACL transection (ACLT) and at 1 and 3 weeks, and at 3, 6, 9 and 12 months following ACLT. One week following ACLT, significant changes from the normal locomotion pattern were observed: peak vertical and anterior posterior ground reaction forces were decreased, particularly the peak posterior forces in the early phase of stance. Furthermore, knee angles were reduced by about 15 degrees throughout the whole gait cycle, while ankle and hip angles were reduced at paw off in the experimental compared to the contralateral hind limbs. Ground reaction forces and hind limb kinematics recovered to near pre-surgical patterns over the one year period assessed. ACLT was also associated with an increased knee instability which improved over time. X-rays suggested that there was a continued degeneration in the experimental knee over the one year period; there was osteophyte formation at the joint margins and an increase in cartilage thickness throughout the joint. It was speculated that the more flexed knee angles and the reduced anterior-posterior ground reaction forces in the ACL-transected compared to the intact hind limb represent an adaptive strategy aimed at avoiding excessive anterior displacement of the tibia in the early phase of stance. The recovery of the locomotion pattern with time might be related to the corresponding improvement of knee stability.

Muscle weakness causes joint degeneration in rabbits.

OBJECTIVE The objective of this study was to investigate the effects of botulinum toxin type-A (BTX-A) induced quadriceps weakness on micro-structural changes in knee cartilage of New Zealand White (NZW) rabbits. DESIGN Fifteen rabbits were divided randomly into an experimental and a sham control group. Each group received a unilateral single quadriceps muscle injection either with saline (sham control; n=4) or BTX-A (experimental; n=11). RESULTS BTX-A injection produced significant quadriceps muscle weakness (P<0.05) and loss of quadriceps muscle mass (P<0.05). Degenerative changes of the knee cartilage, assessed with the Mankin grading system, were the same for the injected and non-injected hind limbs of the experimental group animals. Sham injection had no effect on joint degeneration but all control animals showed some degenerative changes in the knee. Degenerative changes of the retro-patellar cartilage were more severe in the experimental compared to sham control group rabbits (P<0.05). The distal region of the retro-patellar cartilage was more degenerated than the proximal part in the experimental and control group rabbits (P<0.05). The Mankin grades for the tibiofemoral region were not significantly different between experimental and control group rabbits (P>0.05). CONCLUSION Quadriceps muscle weakness caused increased degeneration in the retro-patellar cartilage of NZW rabbits, providing evidence that muscle weakness might be a risk factor for the onset and progression of osteoarthritis (OA). Future work needs to delineate whether muscle weakness directly affects joint degeneration, or if changes in function and movement execution associated with muscle weakness are responsible for the increased rate of OA onset and progression observed here.

In vivo knee joint loading and kinematics before and after ACL transection in an animal model

Osteoarthritis (OA) is typically diagnosed in humans in its final stage when joint movement becomes painful. Clinical information about the onset and the mechanisms triggering the degenerative responses are virtually non-existent. However, research on animal models of experimental OA shows that joint adaptations associated with the onset of OA can be detected as early as two to four weeks following disruption of the normal joint mechanics. Transection of the anterior cruciate ligament (ACL) has been shown to cause OA-like symptoms in various animal models including the cat. However. the changes in joint loading responsible for the early tissue responses have not been quantified in vivo. Consequently, the relationship between abnormal joint loading and the onset of OA remains unknown. The purpose of this study was to quantify knee loading before and early after ACL transection in the cat. Knee mechanics were assessed by measuring patellar tendon forces, gastrocnemius forces, knee flexor and extensor EMGs, and hindlimb kinematics before and 5, 7, and 9 days following ACL transection in six experimental and two sham-operated animals. The knee mechanics were not affected by sham-surgery but the muscular forces. knee extensor EMGs, and knee range of motion were reduced following ACL transection compared to corresponding pre-intervention values. These results suggest that ACL transection causes a general unloading and changed kinematics of the knee. We speculate that the decrease in loading and the altered kinematics are responsible for the onset of biologic adaptations of the knee. Precise data about the local joint contact mechanics before and after ACL transection are now required to further relate the detailed changes in the knee mechanics to the early joint changes.