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Biomedical subjects

A R Luff

Publications and source records attributed to A R Luff.

At least 37 records · Page 2Linked to original sources

Functional and structural changes of rat plantaris motoneurons following compensatory hypertrophy of the muscle.

The conduction velocity and histological structure of motoneurons innervating normal and hypertrophied rat plantaris muscles were investigated. Hypertrophy was produced by ablation of synergist muscles. Single motor units were obtained by ventral root dissection and conduction velocities measured. The structure of neurons was investigated following retrograde labeling with horseradish peroxidase. A combined silver, gold and cholinesterase staining method was developed to study the motor endplate. In addition, the peripheral nerve was fixed, embedded in Araldite, and sectioned for determination of axonal size and myelin thickness. Conduction velocity of motor axons decreased following hypertrophy of the skeletal muscle (control CV = 75.8 +/- 8.9 m s-1, n = 94, hypertrophy CV = 69.0 +/- 12.3 m s-1, n = 84). However, no alteration in the size of motor axons or myelin thickness could account for this alteration in conduction velocity. Mean motoneuronal soma size decreased following muscle hypertrophy (soma diameter: control 36.1 +/- 4.6 microns, n = 283, hypertrophy 32.9 +/- 4.5 microns, n = 294). The complexity of the motor endplate increased following hypertrophy with an increased occurrence of nodal sprouts. In addition, the area of cholinesterase staining increased following hypertrophy (control 588.1 +/- 297.2 microns 2, n = 269, hypertrophy 857.7 +/- 357.0 microns 2, n = 269). This study found that both the morphological and physiological parameters of motoneurons innervating a hypertrophied muscle were shifted toward those of normal rat slow motor units.

Adaptation, Physiological↗

Use of phenytoin to treat horses with Australian stringhalt.

Five horses with Australian stringhalt were treated with 15 mg/kg phenytoin orally for 2 weeks. During the second week of the trial, 3 of the horses were given an additional dose of 10 mg/kg phenytoin. The response to treatment was clinically assessed by grading the severity of the gait abnormality at the walk, trot, turning and backing twice daily. There was a significant (P less than 0.05) improvement in the gait abnormality when pre-treatment values were compared with the mean of the last 3 assessments before treatment stopped. When reassessed 2 weeks after treatment ceased, there remained a significant (P less than 0.05) improvement compared with pre-treatment values at the trot and on backing, but not at the walk or turning. Surface electromyographic recordings were made weekly from the long digital extensor muscle, and there was a change to a near normal recording by the end of treatment. Plasma phenytoin concentrations were monitored during the trial, and the dose rates used achieved a steady state with a mean plasma level of 37 +/- 7 mumol/l. There was wide variability between plasma concentrations in different horses, although there was no difference in absorption between administration of the phenytoin as a paste, or when it was mixed in the feed. Although mild tranquilization was seen after treatment, there were no clinical, haematological or biochemical signs of toxicity from the phenytoin therapy.

Administration, Oral↗

Effects of thyroidectomy on development of skeletal muscle in fetal sheep.

The influence of the thyroid gland on the functional and histochemical development of fast- and slow-twitch skeletal muscle of fetal sheep has been studied in euthyroid fetal sheep (n = 6) and athyroid fetuses (n = 4) surgically thyroid-ectomized at 70-75 days of gestation. Two fast-twitch muscles, the medial gastrocnemius and extensor digitorum longus, and the slow-twitch soleus muscle were studied at the fetal age of 140 days gestation. The athyroid fetuses had significantly slower twitch contraction and relaxation times in both the medial gastrocnemius and extensor digitorum longus muscles compared with the euthyroid fetuses. Twitch contraction and relaxation times of the soleus were not different in the two groups. Thyroidectomy resulted in an increase in the proportion of fast (type II) muscle fibers and myosin, as shown histochemically and by gel electrophoresis of heavy-chain myosins. These results indicate that the functional maturation of the fast-twitch muscles of sheep is influenced by the presence of an intact thyroid gland from at least 70 days of gestation. In contrast, the slow-twitch soleus muscle fiber diameter and twitch contraction and relaxation times were not different in the two groups.

Animals↗

Effect of vertical jumping on the medial gastrocnemius and soleus muscles of rats.

Ten rats were trained to perform approximately 30 jumps/day, 5 days/wk for at least 8 wk, from a force platform that enabled the number and height of jumps to be quantified. There was considerable variation in height jumped during an activity session both within and between rats. The two highest-jumping rats attained a displacement of center of mass of approximately 30 cm, estimated to be approximately 67% of the maximum attainable. The two lowest-jumping rats jumped to approximately 30% of the estimated maximum. The activity was described as "habitual activity" rather than "training" because there were no significant increases in the height of jumping by any rat over the period of activity. The isometric properties of medial gastrocnemius (MG) and soleus muscles were studied in terminal experiments on anesthetised rats. Five significant effects on MG were evoked by this pattern of exercise ("habituation"): 1) a 15-18% increase in force at frequencies of stimulation between 60 and 150 Hz and a 15% increase in maximum tetanic tension to 14.9 N, 2) a 3% increase in the maximum rate of rise of tetanic force to 3.4% of maximum tetanic tension per millisecond, 3) an increase in fatigability expressed as a smaller fatigue index in active rats (33%) than in controls (58%), 4) a decrease of 4% in the percentage of type IIa muscle fibers, and 5) an increase of 6% in the percentage of type II fibers that could not be classified with certainty as IIa or IIb.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗

Long-term persistence of enlarged motor units in partially denervated hindlimb muscles of cats.

1. It was the aim of this study to determine the effect that regenerating motor axons would have on enlarged or sprouted motor units that had been established for a relatively long time. 2. The fast-twitch flexor digitorum longus (FDL) and slow-twitch soleus were partially denervated by unilateral section of the L7 ventral root in 12-wk-old kittens. After 200+ days single motor units were isolated, and their isometric contractile properties were determined. FDL units were also tested for their resistance to fatigue and categorized as fast-twitch-fatigable (FF), fast-twitch-fatigue-resistant (FR), and slow-twitch-fatigue-resistant (S). 3. It had been established previously that regenerating motor axons via L7 returned to the experimental muscles by approximately 100 days. Therefore from 100 to 200 days it was assumed that the sprouted units would be in competition with the regenerating axons. The extent of the original denervations was variable and was estimated from the contralateral side. In soleus most denervations ranged from 83 to 99%; in FDL, from 37 to 81%. 4. In both soleus and FDL there was no evidence that the motor units had sprouted to any less extent than found previously. Within some soleus muscles the largest motor units were developing substantially more force than was expected. However, determination of mean fiber cross-sectional area from muscles frozen, sectioned, and prepared for histochemical analysis showed that this was attributable to increased mean cross-sectional area of the type I fibers.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Australian Stringhalt--epidemiological, clinical and neurological investigations.

An investigation of 78 cases of typical Australian Stringhalt from 52 properties in Victoria was carried out from 1985 to 1987. Horses were either examined in the field (n = 52), referred to the Veterinary Clinical Centre (n = 13) or clinical details were obtained verbally (n = 13). In addition 10 cases of false or atypical stringhalt were examined. Detailed soil and pasture analysis was carried out on 14 properties where Australian Stringhalt had occurred. Information was also obtained on epidemiology of the condition from a survey of practitioners. Fifty of the 52 cases examined in the field occurred in horses that were dependent upon poor quality unimproved dry pasture. In all but a few cases, there was no pasture improvement or fertiliser application, leading to the development of weed-dominated pastures, particularly by flatweed, Hypochaeris radicata. The range of clinical signs exhibited by horses with Australian Stringhalt was described and a grading system proposed to classify horses according to severity of signs. Laryngeal abnormalities were present in 10 of 11 cases examined endoscopically and these horses exhibited increased electromyographic (EMG) activity in the long digital extensor muscle at rest and during hindlimb flexion. To a large extent, the EMG changes disappeared and digital extensor muscle atrophy improved in two horses that were monitored to recovery. Deep peroneal nerve conduction studies in four horses with Australian Stringhalt showed a substantial reduction in nerve conduction velocity and when stimulated at 50 Hz were unable to sustain activation of the long digital extensor muscle. EMG and evoked responses appeared to be sensitive indicators of the state of the disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Innervation of muscle receptors in the cross-reinnervated soleus muscle of the cat.

It has recently been reported (Gregory et al., J. Physiol., 331:367-383, 1982) that cutting a muscle nerve and letting it grow back into the muscle or cross-uniting the muscle with a foreign nerve results in major disruption of the normal response patterns of muscle spindles and tendon organs. Here we report observations on the structure of muscle receptors in cross-reinnervated and self-reinnervated soleus muscles in an attempt to detect abnormalities that might account for their disturbed function. Eight soleus muscles were reinnervated with the extensor digitorum longus nerve for periods up to 449 days and two were self-reinnervated. Following the physiological investigation, the muscle was fixed and stained according to the method of Barker and Ip (J. Physiol., 69:73P-74P, 1963). Spindles and tendon organs were teased from the muscle and photographed. In one cross-reinnervated muscle an attempt was made to isolate all receptors. About two-thirds of the normal number of spindles and tendon organs were found. Three categories of receptor were identified: normal, abnormal, and those having no visible nerve endings. There appeared to be little difference in degree of abnormality of receptors in self- and cross-reinnervated muscles. Of the 180 spindles, 3% were normal, 43% had no visible endings, and 54% had abnormal endings. Of 80 tendon organs, 38% were normally innervated, 33% were without visible innervation, and 29% had abnormal endings. We conclude that following long-term cross-reinnervation and self-reinnervation of soleus there is extensive disruption of the normal innervation pattern of both spindles and tendon organs which could account for their functional abnormalities.

Animals↗

Contractile properties of cat skeletal muscle after repetitive stimulation.

The isometric and force-velocity properties of the fast-twitch flexor digitorum longus (FDL) and slow-twitch soleus muscles were investigated immediately after and during recovery from a fatiguing stimulus regime (40 Hz for 330 ms every second for 180 s) in the anesthetized cat. The amplitude of the isometric twitch of FDL was unaffected but in soleus it remained depressed for much of the recovery period. Immediately after stimulation the twitch time to peak of FDL increased to 140% of the control (prefatigue) value and then reverted to control values. The maximum isometric tetanic tension (Po) developed by FDL was reduced to 67% of control values immediately after the stimulus regime, whereas soleus declined to 93% of control. Recovery of maximum force development was achieved after 45 min in FDL and after 15 min in soleus. The maximum speed of shortening of FDL was reduced to 63% of control values immediately after fatigue; despite some recovery within the first 30 min, it remained depressed during the remainder of the recovery period (up to 300 min). Maximum speed of shortening was unaltered in soleus. The a/Po value transiently increased to 176% of control values in FDL immediately after the fatigue regime but promptly returned to control values. Force-velocity properties of soleus were not affected by the stimulus regime. It is concluded that in FDL changes in the maximum speed of shortening and maximum isometric tension as a result of the stimulus regime are attributable to changes in the intrinsic behavior of cross-bridges and the metabolic status of the fibers, particularly in the fast-twitch fatigue-resistant fibers.

Animals↗

Enlarged motor units resulting from partial denervation of cat hindlimb muscles.

1. It was the aim of this study to determine the extent to which a mammalian motoneuron can sprout in a partially denervated muscle, which motor unit types are involved in sprouting, and whether polyneuronal innervation exists between sprouted units. 2. The fast-twitch flexor digitorum longus (FDL) and slow-twitch soleus were partially denervated by unilateral section of the L7 ventral root in 12-wk-old kittens. After approximately 100 days single motor units were isolated, and their isometric contractile characteristics were determined. FDL units were also tested for their resistance to fatigue and categorized as fast-twitch, fatiguing fibers (FF), fast-twitch, fatigue-resistant fibers (FR), and slow-twitch, fatigue-resistant fibers (S). The presence of polyneuronal innervation was investigated between pairs of like and unlike units. 3. The extent of the original denervation was variable and was estimated from the distribution of motor axons innervating the muscle via the L7 and S1 (soleus) or L6 and L7 (FDL) ventral roots on the contralateral side. In soleus, denervations ranged from 75 to 98%; in FDL, 60 to 97% (denervations less than 60% were not investigated). In general, motor-unit force increased in proportion to the extent of the denervation. 4. Within soleus, unit force increased to over 2 N, which was about 16 times greater than the average for a normal muscle (133 mN). However, most units increased in force to between five and 12 times normal. 5. Within FDL, the force development of type S units was unaffected by partial denervation. Type FF units increased by up to 11 times (4.3 N) compared with normal FF units (395 mN) with most increasing between two and four times. FR units exhibited the greatest relative increase in force [up to 19 times (4.3 N) compared with normal (225 mN)]. Most units were two to seven times the normal. 6. A few FDL units were glycogen depleted, the muscles frozen, and cross sections prepared for histochemical analysis. This indicated that the largest units contained approximately 5,000 fibers, and there was little fiber hypertrophy. In the extensively denervated soleus muscle, large numbers of small, presumably denervated fibers were observed. The innervation ratio of several large units was determined indirectly using mean fiber area. This gave estimates of 3,000-4,000 fibers for the largest units. Again, fiber hypertrophy contributed little to the increase in unit force. It was concluded that the increased force of units in both muscles was largely attributable to terminal and axonal sprouting of the intact motor axons. 7. No evidence for polyneuronal innervation was found in either FDL or soleus muscle.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Force-velocity properties of fatigue-resistant units in cat fast-twitch muscle after fatigue.

The isometric and force-velocity properties of an identified and uniform population of fast-twitch, fatigue-resistant (FR) fibers within the flexor digitorum longus (FDL) muscle were investigated before, immediately after, and during recovery from a fatiguing repetitive isometric stimulus regime (40 Hz for 330 ms every s for 180 s) in the anesthetized cat. It was necessary to determine the smallest fraction of muscle that had the same force-velocity properties as the whole muscle. This was approximately 15% for FDL; if the fraction was less, the maximum speed of shortening was depressed and the a/Po value increased. Motor units were enlarged by partial denervation of the muscle, causing the intact motoneurons to sprout and incorporate more muscle fibers; FR units showed the greatest increase. Immediately after the fatigue regime, maximum isometric tetanic tension declined to 67% but subsequently recovered to 90% of the control value by the end of the 60-min recovery period. Maximum speed of shortening dropped to 71% of the control but after 30 min had recovered and did not differ significantly from control values. It is concluded that the capacity for recovery from fatigue is greater for FR units than for a whole muscle, which also contains fast-fatiguable units, and that the mechanisms involved in the recovery of the maximum isometric tension and maximum speed of shortening are independently regulated.

Animals↗

The effect of initial length on the shortening velocity of cat hind limb muscles.

The effect of initial muscle length on the speed of shortening at different relative loads has been determined for the soleus and flexor digitorum longus (FDL) muscles of the cat. Isometric tetanic force-length relationships for both muscles were similar to those shown previously. The functional length range for FDL occurred at relatively long lengths, from optimum (100%) to 135% of optimum length; however, soleus worked at relatively short lengths from 60% to 110% of optimum length. In FDL the speed of shortening at any given load was relatively constant within the functional range, but at very short muscle lengths the speed of shortening declined. Soleus also showed a decline in the speed of shortening at all loads at short muscle lengths, which included the functional working range of the muscle. Speed of shortening at any given load was maximal at optimum length but tended to decline at low loads and long muscle lengths. It is concluded that in FDL even when the toes are at the extremity of their range, speed of muscle shortening is unaffected. Soleus may be relatively disadvantaged because its functional range extends over short muscle lengths. The results indicate that soleus is capable of making a significant contribution in standing and a slow walk, but that at faster gaits the contribution of soleus may be negligible.

Animals↗

Contractile properties of cat motor units enlarged by motoneurone sprouting.

The fast-twitch flexor digitorum longus (FDL) muscle was partially denervated by a unilateral section of the L7 ventral root. After approximately 100 days the isometric, force-velocity and histochemical properties of single motor units from the partially denervated muscle were determined. The diameter of the nerve axons supplying the muscle were also examined. The extrapolated maximum speed of sarcomere shortening (Vmax) of the enlarged motor units was significantly less than that of the control whole muscle Vmax. It is concluded that the motoneurone is capable of expanding its territory and therefore its tension generating capability without any apparent change in axonal diameter. In addition, the intrinsic properties of the muscle fibres are altered.

Animals↗

Dynamic properties of fiber bundles from the rat sternomastoid muscle.

The sternomastoid muscle of the rat can be subdivided into a "white" and "red" portion. The red portion predominantly contains type IIA fibers and the white portion type IIB fibers. Fiber bundles were dissected from the two parts of the muscle and their dynamic properties determined; both showed "fast-twitch" type characteristics. Small, but significant, differences were found in their isometric properties. Their force-velocity relationships were identical, although the maximum speed of sarcomere shortening (about 40 microns s-1) was significantly less than that of other fast-twitch rat muscles. Other differences in the respective force-length relations at different temperatures were noted. The desirability of pursuing these investigations on identified single fibers is emphasized.

Animals↗

Electromyographic activity in the cross-reinnervated soleus muscle of unrestrained cats.

Electromyographic (e.m.g.) activity was recorded from cross- and self-reinnervated soleus and extensor digitorum longus (e.d.l.) muscles of the cat during normal activity, including standing, walking and jumping. Activity patterns of normal soleus, e.d.l., and lateral gastrocnemius (l.g.) were essentially similar to those shown by other investigators. The self-reinnervated soleus fired phasically and synchronously with l.g. during walking but the activity was not trimmed to the extent that is seen in normal soleus. This is attributed to the relatively limited amount of proprioceptive information arising from such muscles. The activity pattern of the cross-reinnervated soleus muscles was variable. During walking, the phase of activity was sometimes coincident with that of a normal e.d.l., at other times (even in the same animal) it would be approximately coincident with l.g. The phase of activity usually consisted of an initial burst which was not sustained. Reflex activity elicited from the cross-reinnervated soleus was very similar to that of normal e.d.l., indicating the rigidity of connexions for reflex responses. reinnervated e.d.l. muscles; the activity attributable to the cross-reinnervated portion was similar to that seen in a self-reinnervated soleus. The activity pattern of soleus, reinnervated by the nerve to e.d.l. (an effective antagonist) is unlike that of either a normal soleus or e.d.l. muscle. This is attributed to a combination of lack of proprioceptive information and/or some degree of central remodelling.

Action Potentials↗

Force-velocity properties of fast-twitch and slow-twitch muscles of the kitten.

The characteristics of the isometric and force-velocity properties of the fast-twitch flexor digitorum longus (f.d.l.) and the slow-twitch soleus muscles of the developing kitten were determined at post-natal ages of 2 days and 1,2,4 and 6 weeks. The contractile properties of the isometric twitch and tetanus were similar to those previously reported by other authors. The minimum stimulation frequency required for isotonic contractions to achieve the maximum speed of shortening at any given load was 200 Hz for f.d.l. and 150 Hz for soleus at all ages. The extrapolated maximum speed of sarcomere (sarc.) shortening (Vmax) was significantly different between the f.d.l. (22.3 microns s-1 sarc.-1) and soleus (13.1 microns s-1 sarc.-1) at 2 days of age. The f.d.l. Vmax achieved adult values by 4 weeks of age, while there was little or no change in the soleus Vmax. The force-velocity properties are discussed and compared to the changes which have been observed in other contractile properties of the cat f.d.l. and soleus muscles.

Animals↗

Force--sarcomere-length relation and filament length in rat extensor digitorum muscle.

Relations between sarcomere length (SL) and force (F) were studied in ten fiber bundles (six to twenty fibers) from rat extensor digitorum muscles. A bundle (60 micron by 200-300 microns) was mounted in a glass covered perfusion chamber containing modified Krebs Henseleit buffer at 25 degrees C, oxygenated with 95% O2, 5% CO2 and pancuronium bromide (8 mg/1). F ( Disa 51E 01 transducer) and SL (laser diffraction and light microscopy) were measured; the latter could be controlled by a servomotor system. 200-500 ms tetanic stimulus trains were applied via platinum electrodes parallel to the muscle with 20% above maximal intensity, 160 Hz frequency and 1 ms duration of pulses. Tetani were at 2 min intervals. F attained a steady value 100 ms after the start of the tetanus at 2.0-2.5 microns SL and 350 ms at 3.5 microns SL. Active force, measured during tetani in which sarcomere length was held constant, was maximal between SL = 2.15 microns and 2.65 microns and declined in linear fashion with SL to zero at SL = 3.90 microns. Active force at SL = 2.00 microns was 95% of maximal force. Passive force was manifest above SL = 3.10 microns and was 10% of maximal force at 3.80 microns. Eight similar bundles were processed conventionally for electron microscopy (Philips EM 201A ) while SL was measured during the processing steps. Measurements were made from micrographs of longitudinal sections. SL measured from the micrographs were consistent with the observed shrinkage (5%). Actin periodicity was 41.5 +/- 0.19 nm; twenty-seven periods per actin filament were found. Filament lengths were corrected for an assumed actin periodicity of 39 nm. Actin length was 1.13 +/- 0.013 micron; myosin length was 1.53 +/- 0.015 micron. Bare zone was 0.17 micron +/- 0.01 micron. These filament lengths would give optimum overlap at SL between 2.26 and 2.43 microns and a linear decrease to zero with increasing SL from 2.43 microns to 3.79 microns. Actual force was consistently higher than predicted by overlap and force was maintained to both the left and the right of the predicted plateau.

Animals↗

The transformation of cross-reinnervated slow-twitch muscle after deafferentation in the cat.

Cross-reinnervations were effected between the extensor digitorum longus and soleus muscles in the cat hind limb. At the same time dorsal root section or ganglionectomy was performed over segments L6-S1. Completeness of the deafferentation was subsequently confirmed either by dissection or by dorsal root recording. The isometric and force-velocity properties of the muscles were measured. In animals with a unilateral cross plus deafferentation the conversion of the contractile properties of the normally slow-twitch soleus to those resembling a fast-twitch muscle was typical of that seen with an intact afferent supply. In cats with a bilateral cross-reinnervation and unilateral deafferentation there was no significant difference in the degree of transformation between the two sides. It is concluded that at least for the conversion of a slow-twitch to a fast-twitch muscle afferent feedback does not play a major role.

Afferent Pathways↗

Muscle receptors in the cross-reinnervated soleus muscle of the cat.

1. Discharges have been recorded from afferents of the soleus muscle following reinnervation by the nerve of a fast twitch muscle, extensor digitorum longus. Recordings were made 227-449 d post-operatively.2. The gross afferent discharge from the cross-reinnervated soleus suggested the presence of fewer mechanosensitive receptors than in normal muscles, as judged by discharges seen during a maximal muscle twitch.3. A comparison of receptors in the cross-reinnervated muscle with afferents from a self-reinnervated muscle showed that many of the responses in the self-reinnervated muscle were also abnormal. It was concluded that much of the disruption resulted from the surgical interference and that rather less could be attributed to the foreign nerve.4. A detailed analysis of response characteristics of receptors in cross-reinnervated soleus muscles of five cats showed that afferent conduction velocities of identified spindles and tendon organs were generally lower than normal and responses to muscle stretch or vibration were often atypical. A large number of afferents which could not be classified as muscle spindles or tendon organs included a group called contraction receptors. These responded generally only during maximal muscle contractions and with a rather feeble discharge. A second group consisted of afferents in which impulses could be elicited by electrical stimulation of the nerve but not by any mechanical activity in the muscle.5. In a further five animals a detailed study was made of the motor supply of muscle spindles. A fusimotor innervation was common, but invariably stimulation of the gamma fibre had a static action on the spindle. No purely dynamic fusimotor fibres were encountered. There were many static beta fibres (skeletofusimotor) no dynamic betas and three axons conducting in the alpha range, which developed no tension, yet produced specific intrafusal effects. Two of these had a mixed static-dynamic action while the third was purely static.6. It was concluded that in the cross-reinnervated soleus muscle the majority of afferents were abnormal in one or other respect. The central action of such abnormal receptors would have to be taken into account when seeking explanations of the transformation of a muscle's mechanical properties following reinnervation by a foreign nerve.

Action Potentials↗