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Biomedical subjects

J A Faulkner

Publications and source records attributed to J A Faulkner.

At least 73 records · Page 4Linked to original sources

Forces and powers of slow and fast skeletal muscles in mice during repeated contractions.

1. The normalized force or power developed during each of a series of repeated contractions was averaged over the entire cycle of activity and rest to provide a measure of performance referred to as sustained force or sustained power. We tested the hypotheses that compared with slow soleus muscles, fast extensor digitorum longus (EDL) muscles would attain lower maximum values of sustained force, but higher maximum values of sustained power. 2. During repeated contractions at a stimulation frequency of 150 Hz, forces and powers of soleus and EDL muscles of mice were determined in situ at 35 degrees C. The train rate of repeated contractions was incremented every 5 min to increase duty cycle until a maximum value for sustained force or power was reached. 3. In one set of repeated contractions, each contraction was preceded by a quick stretch and thereafter muscle length was held constant. The stretch minimized active shortening of muscle fibres. Sustained force was calculated from force at constant length. The maximum sustained force developed by soleus muscles of 4.58 +/- 0.31 N cm-2 (mean +/- S.E.M.) occurred at a duty cycle of 0.48. Compared with soleus muscles, EDL muscles attained a lower (P less than 0.05) maximum value of 1.38 +/- 0.15 N cm-2 at a 0.35 duty cycle. 4. During isovelocity shortening contractions, the maximum value for sustained power developed by soleus muscles of 7.4 +/- 0.5 W kg-1 occurred at a duty cycle of 0.18. Compared with soleus muscles, EDL muscles achieved a significantly greater maximum value of 9.1 +/- 0.4 W kg-1 at a 0.21 duty cycle.

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A simple Hill element-nonlinear spring model of muscle contraction biomechanics.

The purpose of this study was to develop a model to predict the mechanical response of muscles during isometric tetanic, afterloaded isotonic and isovelocity shortening contractions. Two versions of the model were developed. Both incorporated a contractile element that obeyed a Hill force-velocity relationship and a series elastic element. In a quadratic spring version, the series elastic element force was represented as proportional to the square of the stretch; in a cubic spring version, it was represented as proportional to the cube of the stretch. Both versions provided closed-form equations for response predictions that involved four independent parameters. Once the four parameters were chosen, each of these responses could be predicted. Model validity was established by comparing predicted and observed responses in slow and fast hindlimb muscles of rodents. Significant model-predicted responses seldom differed by more than 15% from experimental values. The model can provide insights into how changes in individual properties affect the overall mechanical behavior of muscles in a variety of circumstances and reduce the need for collection of experimental data.

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Free radical injury to skeletal muscles of young, adult, and old mice.

We tested the hypotheses that 1) muscles of old mice are more susceptible to injury than muscles of young and adult mice, and 2) secondary or delayed onset injury results from free radical damage. Extensor digitorum longus muscles were injured in situ by lengthening contractions. Injury was assessed by measurement of maximum isometric tetanic force (Po) expressed as a percentage of the control value and by morphological damage. Mice were treated with a free radical scavenger, polyethylene glycol-superoxide dismutase (PEG-SOD). Three days postinjury, the Po of 44% for muscles of nontreated old mice was significantly lower than the Po of 58 and 61% for those of young and adult mice. In each group, the secondary injury at 3 days was alleviated by treatment with PEG-SOD. For treated muscles of young, adult, and old mice, values for Po were 88, 80, and 70%, respectively. We conclude that muscles of old mice are more susceptible to injury than muscles of young or adult mice and that free radicals contribute to the secondary or delayed onset injury.

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Contraction-induced injury: recovery of skeletal muscles in young and old mice.

We tested the hypothesis that after the same amount of contraction-induced injury, skeletal muscles in old mice regenerate less well than muscles in young mice. Extensor digitorum longus (EDL) muscles in young and old mice were exposed to 15 min of lengthening contractions. The amount of injury was evaluated at 3, 7, 14, 28, and 60 days by measurements of maximum isometric tetanic force (Po) and number of fibers per cross section. When values 3 days after lengthening contractions were expressed as a percentage of control values, the Po (approximately 34%) and fiber number (approximately 80%) for muscles in old mice were not different from those in young mice, suggesting that muscles in old and young mice were injured to the same degree. By 28 days, injured muscles in young mice regained control values for Po and fiber number. In contrast, at 28 days, injured muscles in old mice recovered approximately 84 and approximately 87% of control values for Po and fiber number, respectively, and deficits in Po persisted at 60 days. We conclude that injured muscles regenerate less well in old mice than in young mice.

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Muscle temperature of mammals: cooling impairs most functional properties.

Our purpose was to study the effect of a decrease in skeletal muscle temperature on single and repeated shortening, isometric, and lengthening contractions of mammalian skeletal muscles. Fast extensor digitorum longus muscles of mice were studied in situ and in vitro at 25 and 35 degrees C. No difference in isometric force was observed, but maximum and sustained powers were reduced by 40 and 62%, respectively. With cooling, maximum power absorption, which is proportional to the external work required to lengthen the muscle, increased significantly at each velocity of lengthening from 0.5 to 4.0 optimum fiber length/s. The 10 degrees C decrease in muscle temperature produced a decrease in power that was primarily a result of the decrease in the velocity of shortening, whereas the increase in power absorption was likely due to an increase in the number of strongly bound cross bridges resulting from a decreased rate of detachment. During voluntary exercise at decreased muscle temperatures, maximum and endurance performances are inevitably impaired by the decreases in maximum and sustained power of individual motor units.

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Power outputs of slow and fast skeletal muscles of mice.

The purpose of this study was to contrast the frequency-power relationship of slow soleus and fast extensor digitorum longus (EDL) muscles to their frequency-force relationships and to investigate factors involved in the development of maximum power during a single contraction. Stimulation frequency-force and stimulation frequency-power relationships were determined for soleus and EDL muscles of the mouse for single contractions in situ at 35 degrees C. Power was measured during isovelocity shortening contractions with displacement through 10% of fiber length at the optimum velocity. Optimum velocity was defined as the shortening velocity for the generation of maximum power for a given stimulation frequency. Both force (N/cm2) and power (watts/kg) increased with stimulation frequency until a plateau was reached. For the frequency-force relationship, the curve for soleus muscles was merely shifted to the left of that for EDL muscles. In contrast, the power developed by EDL muscles was greater than that of soleus muscles (P less than 0.05) at each stimulation frequency. The higher power was a direct consequence of higher optimum velocities for EDL muscles compared with soleus muscles.

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Injury to skeletal muscles of mice by forced lengthening during contractions.

Our purpose was to determine the amount of injury to extensor digitorum longus (EDL) and anterior tibial (ATB) muscles of mice from 1 h to 30 days following passive shortening and lengthening, shortening contractions and lengthening contractions. The shortening-lengthening cycle was of 600 ms duration and was repeated every 5 s for 30 min. Contractions were produced during either the shortening or lengthening phase with stimulation at 100 Hz for 300 ms. The amount of injury was evaluated by the decrease in the number of fibres in a cross-section of the muscle and in the maximum isometric tetanic force (Po). Passively shortened and lengthened and actively shortened EDL and ATB muscles showed no evidence of injury. At 3-5 days after lengthening contractions, EDL and ATB muscles showed an inflammatory response. At 3-5 days, the number of fibres in the cross-section of the injured EDL muscles was 65% of that of the contralateral control EDL muscle, whereas no change was observed in the number of fibres in the injured ATB muscles. By 3 days, the presence of myoblasts, myotubes and central nuclei indicated regeneration of fibres. One hour after shortening contractions, the Po of EDL and ATB muscles decreased to about 75% of the contralateral control value, but recovered completely by 3 days. In contrast, 1 h after lengthening contractions the Po of EDL and ATB muscles decreased to 52 and 40% respectively of the contralateral control value and then both recovered to about 65% within 3 h. For the ATB muscle, the Po showed a secondary decrease to 49% of the contralateral control value at 1 day and for the EDL muscle, to 47% at 3 days. Each muscle recovered gradually and by 30 days the number of fibres and the Po of the injured muscles were not significantly different from values for contralateral control muscles.

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The force-velocity relationship at high shortening velocities in the soleus muscle of the rat.

1. In intact skeletal muscle fibres, estimates of unloaded shortening velocity obtained from slack test measurements (V0) have been shown to exceed, by approximately 7%, estimates obtained from extrapolation of velocities measured during isotonic releases (Vmax). In contrast, published values for the V0 of whole soleus muscles of rats exceed Vmax by 56%. In the present study, we tested the hypothesis that this difference between whole muscles and single fibres is due to a difference in their respective force-velocity relationships at loads less than 5% of maximum isometric tetanic force (P0). In addition, we examined, by computer simulation, the effect of inter-fibre heterogeneity on the force-velocity characteristics of a whole muscle. 2. The force-velocity relationship of soleus muscles of rats was determined at low loads, in vitro at 20 degrees C, by recording force maintained during controlled shortening at constant velocities. The relationship was simulated by assigning a hyperbolic force-velocity curve to each motor unit and summing the force contributions of individual units at each of a series of velocities. 3. When measurements from low loads were included, the force-velocity relationship intersected the velocity axis at V0 (5.0 +/- 0.1 fibre lengths/s, mean +/- S.E.M., n = 10), not Vmax (3.1 +/- 0.1 fibre lengths/s). The simulated and measured force-velocity relationships agreed at all loads, supporting the premise that the deviation from hyperbolic form responsible for the large disparity between V0 and Vmax of whole muscles is a consequence of heterogeneity in shortening velocity among fibres.

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Muscle transplantation between young and old rats: age of host determines recovery.

As compared with age-matched controls, extensor digitorum longus (EDL) muscles autografted in young rats regenerated significantly greater mass (1.8 times) and developed greater maximum contractile force (2.6 times) than EDL muscles autografted in old rats. A cross-age transplantation study showed that the mass and maximum force of old muscles grafted into young hosts were not significantly different from those of young muscles grafted into the same young hosts. Conversely, young muscle grafted into old hosts regenerated no better than old muscles grafted into the same old hosts. We conclude 1) that chronological age alone is not a factor that limits the intrinsic ability of a muscle to regenerate and 2) that the poor regeneration of muscles in old animals is a function of the environment for regeneration provided by the old host.

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Force deficit of vascularized skeletal muscle grafts in rabbits.

Through autografting experiments on 9-g rectus femoris (RFM) muscles in rabbits, we substantiated a previous observation that the maximum isometric tetanic force (Po) and specific Po (N/cm2) of neurovascular-intact grafts are not different from grafts made with neurovascular repair. We then tested the hypotheses that the specific Po of vascularized grafts is significantly less than that of control RFM muscles and the deficit in the specific Po is associated with increases in connective tissue and interstitial space. The specific Po of the grafts was 65% of the value for control RFM muscles. Connective tissue protein concentration of grafts was 3.8 times greater than the control value of 16.6 +/- 3 micrograms/mg wet mass, but this only accounted for a 5% correction in specific Po. The volume of interstitial space did not differ between grafts and control muscles. We conclude that the deficit of 35% in specific Po of vascularized grafts compared with control values is partially explained by an increase in connective tissue, but a 30% unresolved deficit remains.

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Aminophylline enhances contractility of frog skeletal muscle: an effect dependent on extracellular calcium.

The effects of aminophylline (10-500 microM) on isometric twitch and tetanic forces were studied in vitro on frog semitendinosus muscle. Two hypotheses were tested: 1) that micromolar concentrations of aminophylline enhanced contractility of isolated skeletal muscle and 2) that the potentiating effect of aminophylline was dependent on the presence of extracellular calcium ions. Muscles were removed, placed in aerated Ringer solution at 20 degrees C, attached to a force transducer, and stimulated directly. Muscles in normal Ringer and aminophylline Ringer were compared throughout the frequency-force relationship from twitches to maximum tetanic force. Aminophylline increased twitch force significantly at concentrations as low as 25 microM. Over a range of stimulation frequencies, but especially at 10 and 20 Hz, aminophylline increased tetanic force. The potentiating effect of aminophylline (100 microM) was reduced or eliminated in calcium-free Ringer containing 10 mM magnesium. We conclude that aminophylline, at therapeutic concentrations, enhances muscle contractility, and the enhancement is dependent on the presence of extracellular calcium. These findings support the concept that aminophylline is effective in improving respiration in humans with airway obstruction by enhancing diaphragmatic contractility.

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Properties of motor units in nerve-intact autografts of cat extensor digitorum longus muscles.

1. In cats, isometric contractile properties were measured on five extensor digitorum longus (EDL) muscles and four EDL muscle grafts 150-270 days after autografting with nerves intact. Comparisons were made between the properties of whole muscles and grafts and between 36 motor units in control EDL muscles and 41 motor units in grafts. 2. The time-to-peak twitch force (TPT) of 23 +/- 1.7 (SE) ms for grafts was significantly prolonged compared with the value of 17 +/- 0.7 ms observed for whole EDL muscles. The mean values for the TPT of motor units were not different from the respective values for whole grafts or for whole muscles. The maximum specific force of whole grafts of 19.7 +/- 0.6 (SE) N/cm2 was significantly less than the control value of 23.6 +/- 0.6 N/cm2, an observation consistent with all previous data on the maximum specific force of grafts and control muscles. 3. Based on the presence or absence of sag and an index of fatigue, motor units were classified as fast fatigable (FF), fast intermediate (FI), fast fatigue-resistant (FR), and slow (S). Motor units were classified 33% FF, 22% FI, 27% FR, and 17% S in control muscles and 17% FF, 43% FI, 29% FR, and 12% S in autografted muscles. Compared with control muscles, the number of small FF units increased significantly in the autografts, but no significant difference was observed in the fatigue properties of motor units.(ABSTRACT TRUNCATED AT 250 WORDS)

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Transplantation and transposition of skeletal muscles into the faces of monkeys.

Restoration of normal facial movement after long-term facial paralysis with muscle atrophy has not yet been achieved reliably by either free grafts, in which fibers degenerate and regenerate, or by grafts made with microneurovascular repair, in which most fibers survive. Our purpose was to compare the structural and functional properties of free muscle grafts and continuously perfused muscle flaps transplanted into the faces of monkeys. In adult monkeys, the facial muscles were replaced by either a free graft of a donor muscle from the lower limb or a denervated flap of ipsilateral temporalis muscle. Each graft or flap was reinnervated with the preserved buccal branch of the facial nerve. The control muscles, grafts, and flaps were examined 90 days later for gross appearance, contractile properties, and fiber areas. Compared with muscle flaps, free grafts showed greater adaptability to the new location and innervation and a closer approximation to the structural and functional properties of the original facial musculature.

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Neurovascular-anastomosed muscle grafts in rabbits: functional deficits result from tendon repair.

In rabbits, 9 g rectus femoris (RFM) muscles were grafted with tendon repair and with (1) nerves and blood vessels intact, (2) nerves intact and blood vessels anastomosed, or (3) nerves and blood vessels anastomosed. The influences of tendon, nerve, and vascular repair on the functional capabilities of grafts were compared 15-120 days after grafting. Data were collected on the mass, total protein content, oxidative capacity, maximum force development, and fatigability of grafts and control RFM muscles. When stabilized 90-120 days after grafting, mean values for the three types of grafts were not significantly different. Compared with values for control RFM muscles, each type of graft had significantly lower mean values for mass, total protein content, and maximum force, but the grafts were more resistant to fatigue. In RFM grafts, nerve and vascular repair do not contribute significantly to the impairments. Consequently, tendon repair appears to be responsible for the major functional deficits.

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Reinnervation of long-term denervated rat muscle freely grafted into an innervated limb.

This experiment was designed to test the hypothesis that in the presence of regenerating nerve fibers long-term denervated skeletal muscle does not become reinnervated. This hypothesis was tested in rats by the transplantation of 22-month denervated extensor digitorum longus (EDL) muscles into the sites of EDL muscles in the contralateral, normally innervated legs. Two months after transplantation, the muscles contracted when stimulated via the motor nerve, and based on silver-acetylcholinesterase staining, all grafts possessed innervated motor end plates. Compared to values for control EDL muscles in old rats, the maximum force developed by standard free grafts in old rats was 19% and that of long-term denervated grafts was 7%. For standard free grafts, nerve stimulation produced a maximum force that was 81% of that produced by direct stimulation, and for control EDL muscles in young and old rats, the values were 96 and 90%, respectively. These results show that after long-term denervation rat muscles are capable of becoming functionally reinnervated, even though by the time of reinnervation the animals have attained an advanced age of 26 months.

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Contractile properties of skeletal muscles from young, adult and aged mice.

1. Comparisons were made in vitro at 25 degrees C among soleus and extensor digitorum longus (EDL) muscles from young (2-3 months), adult (9-10 months), and aged (26-27 months) male mice. We tested the hypotheses that, compared with soleus and EDL muscles of young and adult mice, those from aged mice develop decreased maximum tetanic force (P0, mN) and specific P0 (N/cm2), and that no significant differences occur for contraction time, half-relaxation time, or force-velocity relationship. 2. For the aged mice, the P0 of the soleus muscles and EDL muscles were 78 and 73% respectively of the values for adult mice. The specific P0 of EDL muscles of aged mice was 78% of the value of 23 N/cm2 obtained for young and adult mice. For soleus muscles, the specific P0 of 21 N/cm2 did not change with age. 3. Compared to values for young and adult mice, the contraction and half-relaxation times of soleus muscles from aged mice were increased, but the overall force-velocity relationships of soleus and EDL muscles did not change. The pooled values for the maximum velocity of unloaded shortening extrapolated from the force-velocity relationship of soleus and EDL muscles were 4.6 and 10.1 fibre lengths/s, respectively. 4. The decrease in the specific P0 of the EDL muscle with ageing must result from either a decrease in the number of cross-bridges in the driving stroke or a decrease in the force developed by each cross-bridge.

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