Modeling of steady-state and relaxation elastic properties of the papillary muscle at rest

The biomechanical modeling of a papillary muscle preparation as an adequate object for studying the properties of the myocardial tissue under uniaxial stretching has been performed. The steady-state and relaxation tests of the papillary muscle of laboratory animals (rabbit and rat) have been conducted in normal conditions and after the maceration of intracellular structures with high ionic strength solution. It has been shown that the main contribution to the viscoelastic properties in the initial range of physiological deformations is made by the connective tissue skeleton, whereas under large physiological deformations, by intracellular structures.     

Decreased passive stiffness of cardiac myocytes and cardiac tissue from copper-deficient rat hearts

Passive stiffness characteristics of isolated cardiac myocytes, papillary muscles, and aortic strips from male Holtzman rats fed a copper-deficient diet for approximately 5 wk were compared with those of rats fed a copper-adequate diet to determine whether alterations in these characteristics might accompany the well-documented cardiac hypertrophy and high incidence of ventricular rupture characteristic of copper deficiency. Stiffness of isolated cardiac myocytes was assessed from measurements of cellular dimensional changes to varied osmotic conditions. Stiffness of papillary muscles and aortic strips was determined from resting length-tension analyses and included steady-state characteristics, dynamic viscoelastic stiffness properties, and maximum tensile strength. The primary findings were that copper deficiency resulted in cardiac hypertrophy with increased cardiac myocyte size and fragility, decreased cardiac myocyte stiffness, and decreased papillary muscle passive stiffness, dynamic stiffness, and tensile strength and no alteration in aortic connective tissue passive stiffness or tensile strength. These findings suggest that a reduction of cardiac myocyte stiffness and increased cellular fragility could contribute to the reduced overall cardiac tissue stiffness and the high incidence of ventricular aneurysm observed in copper-deficient rats.     

Effect of emotional and pain stress on the contractile function of the hypertrophied heart muscle

Rats with compensatory hypertrophy of the heart and control animals were subjected to emotional painful stress (EPS). It was established that EPS led to the lowering of the main indicators of the contractile function of an isolated papillary muscle and reduced the resistance of the function under study to excess/Na+ and H+ forcing out Ca2+ from the binding sites on the sarcolemma. Compensatory hypertrophy of the heart itself was accompanied by a reduction of the myocardial contractility but the increase of the concentration of Na+ and H+ in the perfusate led to a far greater depression of the contractile parameters than in the myocardium of the control animals. Contractile function of the hypertrophied myocardium after stress turned out to be reduced to the level close to that seen in heart insufficiency.     

Skeletal muscle glucose uptake following overload-induced hypertrophy.

While endurance exercise training has been shown to enhance insulin action in skeletal muscle, the effects of high resistance strength training are less clear. The purpose of this study was to determine the rate of glucose uptake in skeletal muscle in which compensatory hypertrophy was induced by synergist muscle ablation. Basal and insulin mediated [3H] 2-deoxyglucose uptake were measured in soleus and EDL muscles using the perfused rat hindquarter preparation. Neither basal nor insulin mediated glucose uptake, when expressed per gram muscle, were enhanced in hypertrophied soleus muscles compared with control muscles, despite a twofold increase in mass (P less than 0.01). In the EDL, muscle mass increased 60% with synergist ablation (P less than 0.01), however insulin mediated glucose uptake was not different from that of control muscles. The basal rate of glucose uptake in hypertrophied EDL muscles was increased twofold over that of control muscles (P less than 0.05), possibly due to changes in neural input and/or loading. These results suggest that the stimulus for development of increased muscle mass is different from that for metabolic adaptations.     

肾性高血压大鼠肥大心肌的力速关系和收缩末...

Renovascular hypertension was induced in rats by left renal artery constriction. Force-velocity relation, end systolic tension-length relation (ESTLR) and responses to high extracellular calcium were investigated in hypertrophied myocardium with 4-week hypertension. The results showed that: (1) The myocardial hypertrophy was accompanied by increased peak active tension, decreased maximal velocity of shortening and prolonged contraction duration (P less than 0.01). (2) The ESTLR in hypertrophied myocardium was similar to that in the control, fitted well by an exponential curve and did not show significant alterations in all its regression parameters (P greater than 0.05). (3) No significant difference about the responses to high extracellular calcium (4 mmol/L) was observed between the control and the hypertrophied myocardium (P greater than 0.05). It is concluded that the mechanical properties of hypertrophied myocardium were characterized by a dissociation between force development and velocity of shortening and possibly these contractile abnormalities at the early stage of cardiac hypertrophy are not related to ability of calcium transport in cardiac plasma membrane. The indexes of myocardial mechanics are more sensitive to changes in contractility of hypertrophied myocardium as compared with the parameters of ESTLR.     

Limited resistance of hypertrophied skeletal muscle to glucocorticoids

Male hypophysectomized rats were initially assigned to a control or an overloaded group that underwent compensatory hypertrophy of plantaris muscles to steady-state levels following removal of synergistic musculature. Plantaris muscle mass of overloaded animals was higher than that of controls by 38% (391 +/- 8 vs 284 +/- 7 mg) and glucocorticoid cytosol specific binding concentrations, using [3H]triamcinolone acetonide (TA) as the labeled steroid, was also significantly higher in hypertrophied muscles (83.3 +/- 3.9 fmol . mg protein-1) than in control muscles 56.3 +/- 3.9 fmol . mg protein-1). Cortisone acetate (CA) was then administered daily subcutaneously in high, 100 mg; intermediate, 10 mg; or low, 1.0 mg . kg-1 body wt doses. Groups of rats were killed after 1/4, 2 days and 7 days. Absolute muscle mass losses after 7 days of CA treatment were approx 80 mg with high doses and 60 mg with intermediate doses in both hypertrophied and control muscles. The low CA dose did not produce atrophy. The absolute depletion of [3H]TA binding activity with CA treatment was always greater in hypertrophied muscles of high and intermediate dose treated than those of their respective controls, but TA binding capacities remained higher in hypertrophied muscles than in controls at almost all time points in all treatment groups. Unlike previous findings in which the simultaneous initiation of overload prevented glucocorticoid induced muscle wasting, no resistance to the effect of CA treatment was observed when treatment was begun after hypertrophy had occurred.     

The Viscoelastic Properties of Passive Eye Muscle in Primates. II: Testing the Quasi-Linear Theory

We have extensively investigated the mechanical properties of passive eye muscles, in vivo, in anesthetized and paralyzed monkeys. The complexity inherent in rheological measurements makes it desirable to present the results in terms of a mathematical model. Because Fung''s quasi-linear viscoelastic (QLV) model has been particularly successful in capturing the viscoelastic properties of passive biological tissues, here we analyze this dataset within the framework of Fung''s theory.We found that the basic properties assumed under the QLV theory (separability and superposition) are not typical of passive eye muscles. We show that some recent extensions of Fung''s model can deal successfully with the lack of separability, but fail to reproduce the deviation from superposition.While appealing for their elegance, the QLV model and its descendants are not able to capture the complex mechanical properties of passive eye muscles. In particular, our measurements suggest that in a passive extraocular muscle the force does not depend on the entire length history, but to a great extent is only a function of the last elongation to which it has been subjected. It is currently unknown whether other passive biological tissues behave similarly.     

Heat, mechanics, and myosin ATPase in normal and hypertrophied heart muscle

In this paper we review our previous work on the myothermic economy of isometric force production in compensated cardiac hypertrophy secondary to pulmonary artery constriction (pressure overload) and/or thyrotoxicosis (volume overload). Hypertrophy-induced changes in isotonic and isometric twitch mechanics are correlated with accompanying changes in actin-activated myosin ATPase and heat liberation. Heat measurements were made with rapid, high-sensitivity thermopiles on right ventricular papillary muscles from normal and hypertrophied rabbit hearts. Total activity-related heat was separated into initial and recovery heat. Initial heat was separated into a tension-dependent component (TDH) relating to cross-bridge activity, and a tension-independent component (TIH) relating to excitation-contraction coupling. There were oppositely directed changes in most parameters studied in pressure overload hypertrophy (P) as compared with thyrotoxic hypertrophy (T). Thus, in P there was depression (30-50% in the rate of isometric force production, mechanical Vmax, TDH and TDH rate, myosin ATPase, TIH, and prolongation in time-to-peak twitch tension, whereas in T all parameters were oppositely changed except for no change in TIH. Thyrotoxicosis following pressure overload reversed the P-induced changes in all parameters. There was a direct, linear relation between in vitro actin-activated myosin ATPase and in vivo TDH. However, TDH per unit twitch tension or tension-time integral varied inversely with ATPase, making force production more economical than normal in P muscles and less economical than normal in T muscles. These cellular changes beneficially equip P hearts for slow, high-pressure, economical pumping the T hearts for fast, high-volume, uneconomical pumping. The differences are similar to those between slow and fast skeletal muscle and between neonatal and adult skeletal muscle. The mechanism of these changes is discussed in terms of an enzyme kinetic scheme of chemomechanical coupling in actomyosin interaction.     

A dynamic model of mouth closing movements in clariid catfishes: the role of enlarged jaw adductors

Some species of Clariidae (air breathing catfishes) have extremely large (hypertrophied) jaw closure muscles. Besides producing higher bite forces, the enlarged muscles may also cause higher accelerations of the lower jaw during rapid mouth closure. Thus, jaw adductor hypertrophy could potentially also enable faster mouth closure. In this study, a forward dynamic model of jaw closing is developed to evaluate the importance of jaw adductor hypertrophy on the speed of mouth closure. The model includes inertia, pressure, tissue resistance and hydrodynamic drag forces on the lower jaw, which is modelled as a rotating half-ellipse. Simulations are run for four clariid species showing a gradual increase in jaw adductor hypertrophy (Clarias gariepinus, Clariallabes longicauda, Gymnallabes typus and Channallabes apus). The model was validated using data from high-speed videos of prey captures in these species. In general, the kinematic profiles of the fastest mouth closure from each species are reasonably well predicted by the model. The model was also used to compare the four species during standardized mouth closures (same initial gape angle, travel distance and cranial size). These simulations suggest that the species with enlarged jaw adductors have an increased speed of jaw closure (in comparison with the non-hypertrophied C. gariepinus) for short lower jaw rotations and when feeding at high gape angles. Consequently, the jaw system in these species seems well equipped to capture relatively large, evasive prey. For prey captures during which the lower jaw rotates freely over a larger distance before impacting the prey, the higher kinematic efficiency of the C. gariepinus jaw system results in the fastest jaw closures. In all cases, the model predicts that an increase in the physiological cross-sectional area of the jaw muscles does indeed contribute to the speed of jaw closure in clariid fish.     

Compensatory adaptations of skeletal muscle fiber types to a long-term functional overload

We investigated selected histochemical and histometrical characteristics of the heterogeneous fiber types of rat skeletal muscle following long-term compensatory muscle growth. Sixty days following surgical removal of the synergistic gastrocnemius muscle, the compensated ipsilateral plantaris and soleus muscles and the corresponding control muscles from the contralateral leg were excised and stained histochemically for myofibrillar ATPase and DPNH-diaphorase activities. The number of fibers per cross-section was determined by a direct count from transverse sections taken from the midportion of the muscles. Fiber area was determined by direct planimetry. The plantaris and soleus muscles hypertrophied 103% and 45%, respectively, within 60 days. Compensatory hypertrophy of the plantaris muscle was accompanied by a significant but disproportionate increase in the cross-sectional areas of the three muscle fiber types. There was an approximate 4-fold increase in the number of slow-twitch-oxidative (SO) fibers observed per transverse section. The hypertrophied plantaris muscle exhibited a significantly greater number of fibers per cross-section (29%) than the respective control muscle. The compensated soleus muscle consisted of nearly 100% SO fibers compared to 83% for the control soleus muscle.     

Mechanical deficit persists during long-term muscle hypertrophy

Hypotheses were tested that the deficit in maximum isometric force normalized to muscle cross-sectional area (i.e., specific Po, N/cm2) of hypertrophied muscle would return to control value with time and that the rate and magnitude of adaptation of specific force would not differ between soleus and plantaris muscles. Ablation operations of the gastrocnemius and plantaris muscles or the gastrocnemius and soleus muscles were done to induce hypertrophy of synergistic muscle left intact in female Wistar rats (n = 47) at 5 wk of age. The hypertrophied soleus and plantaris muscles and control muscles from other age-matched rats (n = 22) were studied from days 30 to 240 thereafter. Po was measured in vitro at 25 degrees C in oxygenated Krebs-Ringer bicarbonate. Compared with control values, soleus muscle cross-sectional area increased 41-15% from days 30 to 240 after ablation, whereas Po increased 11 and 15% only at days 60 and 90. Compared with control values, plantaris muscle cross-sectional area increased 52% at day 30, 40% from days 60 through 120, and 15% at day 240. Plantaris muscle Po increased 25% from days 30 to 120 but at day 240 was not different from control value. Changes in muscle architecture were negligible after ablation in both muscles. Specific Po was depressed from 11 to 28% for both muscles at all times. At no time after the ablation of synergistic muscle did the increased muscle cross-sectional area contribute fully to isometric force production.     

Mibefradil improves beta-adrenergic responsiveness and intracellular Ca(2+) handling in hypertrophied rat myocardium

The present study investigated the effects of mibefradil, a novel T-type channel blocker, on ventricular function and intracellular Ca(2+) handling in normal and hypertrophied rat myocardium. Ca(2+) transient was measured with the bioluminescent protein, aequorin. Mibefradil (2 microM) produced nonsignificant changes in isometric contraction and peak systolic intracellular Ca(2+) concentration ([Ca(2+)](i)) in normal rat myocardium. Hypertrophied papillary muscles isolated from aortic-banded rats 10 weeks after operation demonstrated a prolonged duration of isometric contraction, as well as decreased amplitudes of developed tension and peak Ca(2+) transient compared with the sham-operated group. Additionally, diastolic [Ca(2+)](i) increased in hypertrophied rat myocardium. The positive inotropic effect of isoproterenol stimulation was blunted in hypertrophied muscles despite a large increase in Ca(2+) transient amplitude. Afterglimmers and corresponding aftercontractions were provoked with isoproterenol (10(-5) and 10(-4) M) stimulation in 4 out of 16 hypertrophied muscles, but were eliminated in the presence of mibefradil (2 microM). In addition, hypertrophied muscles in the presence of mibefradil had a significant improvement of contractile response to isoproterenol stimulation and a reduced diastolic [Ca(2+)](I), although a mild decrease of peak Ca(2+)-transient was also shown. However, verapamil (2 microM) did not restore the inotropic and Ca(2+) modulating effects of isoproterenol in hypertrophied myocardium. Mibefradil partly restores the positive inotropic response to beta-adrenergic stimulation in hypertrophied myocardium from aortic-banded rats, an effect that might be useful in hypertrophied myocardium with impaired [Ca(2+)](i) homeostasis.     

Viscous elements have little impact on measured passive length-tension properties of human gastrocnemius muscle-tendon units in vivo

Several studies have measured the elastic properties of a single human muscle-tendon unit in vivo. However the viscoelastic behavior of single human muscles has not been characterized. In this study, we adapted QLV theory to model the viscoelastic behavior of human gastrocnemius muscle-tendon units in vivo. We also determined the influence of viscoelasticity on passive length-tension properties of human gastrocnemius muscle-tendon units. Eight subjects participated in the experiment, which consisted of two parts. First, the stress relaxation response of human gastrocnemius muscle-tendon units was determined at a range of knee and ankle angles. Subsequently, passive ankle torque and ankle angle were collected during cyclic dorsiflexion and plantarflexion at a range of knee angles. Viscous parameters were determined by fitting the stress relaxation experiment data with a two-term exponential function, and elastic parameters were estimated by fitting the QLV model and viscous parameters to the cyclic experiment data. The model fitted the experimental data well at slow speeds (RMSE: 1.7 ± 0.5N) and at fast speeds (RMSE: 1.9 ± 0.2N). Muscle-tendon units demonstrated a large amount of stress relaxation. Nonetheless, viscoelastic passive length-tension curves estimated with the QLV model were similar to elastic passive length-tension curves obtained using a model that ignored viscosity. There was little difference in the elastic passive length-tension curves at different loading rates. We conclude that (a) the QLV model can be used to quantify viscoelastic behaviors of relaxed human gastrocnemius muscle-tendon units in vivo, and (b) over the range of velocities we examined, the velocity of loading has little effect on the passive length-tension properties of human gastrocnemius muscle-tendon units.     

Regulation of myosin heavy-chain gene expression during skeletal-muscle hypertrophy.

Changes in the myosin phenotype of differentiated muscle are a prominent feature of the adaptation of the tissue to a variety of physiological stimuli. In the present study the molecular basis of changes in the proportion of myosin isoenzymes in rat skeletal muscle which occur during compensatory hypertrophy caused by the combined removal of synergist muscles and spontaneous running exercise was investigated. The relative amounts of sarcomeric myosin heavy (MHC)- and light (MLC)-chain mRNAs in the plantaris (fast) and soleus (slow) muscles from rats was assessed with cDNA probes specific for different MHC and MLC genes. Changes in the proportion of specific MHC mRNA levels were in the same direction as, and of similar magnitude to, changes in the proportion of myosin isoenzymes encoded for by the mRNAs. No significant changes in the proportion of MLC proteins or mRNA were detected. However, high levels of MLC3 mRNA were measured in both normal and hypertrophied soleus muscles which contained only trace amounts of MLC3 protein. Small amounts of embryonic and neonatal MHC mRNAs were induced in both muscles during hypertrophy. We conclude that the change in the pattern of myosin isoenzymes during skeletal-muscle adaptation to work overload is a consequence of changes in specific MHC mRNA levels.     

Sarcomere shortening in pressure overload hypertrophy

Sarcomere shortening during contraction was measured by using laser diffraction, in thin, rabbit right ventricular (RV) trabeculae from normal hearts (N) (n = 5) and from hearts subjected to RV pressure overload by pulmonary banding (H) (n = 5). Banding resulted in substantial RV hypertrophy after 2 wk. Hypertrophied preparations had the same resting muscle length (H = 3.15 +/- 0.29 mm) and resting sarcomere lengths (H = 2.16 +/- 0.005 micron) as the normal preparations (3.10 +/- 0.37 mm, 2.16 +/- 0.008 micron, respectively). Total tension at the peak of isometric twitches was the same as normal in the hypertrophied muscles (N = 8.06 +/- 1.20, H = 8.51 +/- 1.95 g/mm2). However, the amount of auxotonic sarcomere shortening was much less than normal in the hypertrophied preparations (N = 0.39 +/- 0.028, H = 0.19 +/- 0.034 micron; P less than 0.001). In isotonic contractions in which the ratio of muscle shortening to resting muscle length was the same in both the normal and hypertrophied muscles (ratio of 0.05 in both groups), the extent of sarcomere shortening relative to resting sarcomere length was less in the hypertrophied muscles than in the normal preparations (N = 0.14 +/- 0.01), H = 0.07 +/- 0.01; P less than 0.01). Series elasticity was the same as normal in the hypertrophied muscle P less than 0.05). Less auxotonic sarcomere shortening for a given level of isometric tension development and less isotonic sarcomere shortening per unit muscle shortening indicate that there is less than normal work per sarcomere during contraction in hypertrophied myocardium. These findings may have important implications for intracellular compensatory adaptation in pressure overload cardiac hypertrophy.     

AUTORADIOGRAPHIC LOCALIZATION OF NEW RNA SYNTHESIS IN HYPERTROPHYING SKELETAL MUSCLE

Work-induced growth of rat soleus muscle is accompanied by an early increase in new RNA synthesis. To determine the cell type(s) responsible for the increased RNA synthesis, we compared light autoradiographs of control and hypertrophying muscles from rats injected with tritiated uridine 12, 24, and 48 h after inducing hypertrophy. There was an increased number of silver grains over autoradiographs of hypertrophied muscle. This increase occurred over connective tissue cells; there was no increase in the number of silver grains over the muscle fibers. Quantitative studies demonstrated that between 70 and 80% of the radioactivity in the muscle that survived fixation and washing was in RNA. Pretreatment of the animals with actinomycin D reduced in parallel both the radioactivity in RNA and the number of silver grains over autoradiographs. Proliferation of the connective tissue in hypertrophying muscle was evident in light micrographs, and electron micrographs identified the proliferating cells as enlarged fibroblasts and macrophages; the connective tissue cells remained after hypertrophy was completed. Thus, proliferating connective tissue cells are the major site of the increase in new RNA synthesis during acute work-induced growth of skeletal muscle. It is suggested that in the analysis of physiological adaptations of muscle, the connective tissue cells deserve consideration as a site of significant molecular activity.     

TGF-beta(1) and prepro-ANP mRNAs are differentially regulated in exercise-induced cardiac hypertrophy.

The induction of transforming growth factor (TGF)-beta and prepro-atrial natriuretic peptide (ANP) mRNAs represent hallmark features of pathological cardiac hypertrophy. The present study examined whether this pattern of mRNA expression was conserved in a physiological model of cardiac hypertrophy. To address this thesis, female Sprague-Dawley rats were individually housed and permitted to run freely. Voluntary exercise for 3 and 6 wk resulted in biventricular hypertrophy and increased cytochrome c oxidase activity in the triceps muscle. In the hypertrophied left ventricle, the steady-state mRNA level of the cardiac fetal gene prepro-ANP and the extracellular matrix proteins preprocollagen-alpha(1) and fibronectin were similar in exercise-trained and sedentary rats. By contrast, an increased expression of TGF-beta(1) mRNA was observed, whereas TGF-beta(3) mRNA level was unchanged in the hypertrophied left ventricle of exercise-trained compared with sedentary rats. These data highlight a heterogeneity in the regulation of TGF-beta isoforms, and the increased expression of ventricular TGF-beta(1) mRNA in physiological cardiac hypertrophy may contribute to myocardial remodeling.     

Diameter changes of muscle fiber types of the inferior oblique muscle of the rabbit following denervation]

Changes in fibre diameters of extraocular muscles of the rabbit were studied at different times after denervation. The whole inferior oblique muscle hypertrophied, while some of the muscle fibres hypertrophied and others showed atrophy, depending on the fibre type. Fibre types have been determined by their histochemical enzyme profile. In the central layer of the muscle the phasic muscle fibres, which are rich in mitochondria, exhibited a transient hypertrophy being maximal 4-5 weeks after denervation and afterwards they atrophied; other phasic muscle fibres, which are poor in mitochondria, atrophied without having shown any sign of hypertrophy. Special, putatively slow tonic muscle fibres, which have low enzyme activities, underwent small long-lasting increases of their diameters. In the superficial layer of extraocular muscle there are two types of extremely thin muscle fibres rich in mitochondira. Both these fibre types hypertrophied to the greatest degree and for a very long time. Comparable changes in fibre diameters as described here for the muscle fibre types of an extraocular muscle are known from special muscle fibres in other vertebrate