Human Limb Muscles Research Articles

Spasticity in rats with sacral spinal cord injury.

We have investigated sacral spinal cord lesions in rats with the goal of developing a rat model of muscular spasticity that is minimally disruptive, not interfering with bladder, bowel, or hindlimb locomotor function. Spinal transections were made at the S2 sacral level and, thus, only affected the tail musculature. After spinal transection, the muscles of the tail were inactive for 2 weeks. Following this initial period, hypertonia, hyperreflexia, and clonus developed in the tail, and grew more pronounced with time. These changes were assessed in the awake rat, since the tail is readily accessible and easy to manipulate. Muscle stretch or cutaneous stimulation of the tail produced muscle spasms and marked increases in muscle tone, as measured with force and electromyographic recordings. When the tail was unconstrained, spontaneous or reflex induced flexor and extensor spasms coiled the tail. Movement during the spasms often triggered clonus in the end of the tail. The tail hair and skin were extremely hyperreflexive to light touch, withdrawing quickly at contact, and at times clonus could be entrained by repeated contact of the tail on a surface. Segmental tail muscle reflexes, e.g., Hoffman reflexes (H-reflexes), were measured before and after spinalization, and increased significantly 2 weeks after transection. These results suggest that sacral spinal rats develop symptoms of spasticity in tail muscles with similar characteristics to those seen in limb muscles of humans with spinal cord injury, and thus provide a convenient preparation for studying this condition.

Human respiratory muscles: sensations, reflexes and fatiguability.

1. Given the importance of the ventilatory 'pump' muscles, it would not be surprising if they were endowed with both sensory and motor specializations. The present review focuses on some unexpected properties of the respiratory muscle system in human subjects. 2. Although changes in blood gas tension were long held not to influence sensation directly, studies in subjects who are completely paralysed show that increases in arterial CO2 levels elicit strong sensations of respiratory discomfort. 3. Stretch reflexes in human limb muscles contain a monosynaptic spinal excitation and a long-latency excitation. However, inspiratory muscles show an initial inhibition when tested with brief airway occlusions during inspiration. This inhibition does not depend critically on input from pulmonary or upper airway receptors. 4. Human inspiratory muscles (including the diaphragm) have been considered to fatigue during inspiratory resistive loading. However, recent studies using phrenic nerve stimulation to test the force produced by the diaphragm show that carbon dioxide retention (hypoventilation) and voluntary cessation of loading occur before the muscles become overtly fatigued.

Hyaluronan in human and rat muscle spindles.

Previous data on the composition of the periaxial fluid of muscle spindles have relied on indirect histochemical methods. We used a biotinylated hyaluronan-binding protein as a specific probe for the detection of hyaluronan in sections of human and rat limb muscles. Hyaluronan was identified in the axial and periaxial space of the muscle spindles as well as in the endoneurium and in the space in between individual axons. Hyaluronan was also present in the innermost layer of the spindle capsule in the A region and in all layers of the capsule in the B region.

Contractile properties of two human lower limb muscle groups: The quadriceps and triceps Surae

The purpose of this study was to differentiate between the contractile characteristics of the quadriceps femoris (QF) and triceps surae (TS) muscle groups within the same individual independently of volitional effort. Electrically evoked isometric contractions of the QF and TS muscle groups were recorded from the dominant leg of 13 men and women (28.8 ±2.1 years). The electrical stimulation protocol performed included: supramaximal twitches; contractions evoked at 10, 20, 50 and 100 Hz stimulation; and a two minute fatigue test. Compared with the QF, the TS contractile properties were found to have: (1) prolonged twitch TPT and ½RT; (2) a larger relative torque production at low frequencies of stimulation; and (3) a greater resistance to fatigue. These results indicate: (1) that the TS is a functionally slower and less fatiguable muscle group than the QF; and (2) that electrical stimulation is a sensitive and non‐invasive technique for determining the contractile characteristics of human muscle.

Ultra-high-resolution scanning electron microscopy of mitochondria and sarcoplasmic reticulum arrangement in human red, white, and intermediate muscle fibers.

Human skeletal muscle fibers are the red, white, and intermediate fibers. They differ in their mitochondrial structure and enzyme activity. Scanning electron microscopy (SEM) was used on specially prepared specimens to determine the distinctive features of mitochondria and sarcoplasmic reticulum (SR) in each fiber type. Specimens of human limb muscles were glutaraldehyde fixed, frozen, fractured, and macerated by the aldehyde-osmium-DMSO-osmium procedure to expose large areas of mitochondria and SR. Osmium-hydrazine-impregnated tissues were examined without metal coating by ultra-high-resolution SEM. In white fibers, paired long, thin mitochondria encircled myofibrils at the I-band level. In red fibers, the paired rows of stubby mitochondria at the I-band level were often connected across the A-band to the next row of mitochondria by a slender mitochondrial stalk. Intermediate fiber mitochondria resembled those in red fibers but were longer and thinner. Intermyofibrillar mitochondrial columns were most common in red fibers. All three muscle types had T-tubules along the A-I junction level, and small periodic terminal cisternae formed triads or dyads. Sarcotubules from terminal cisternae formed continuous three-dimensional networks at the I-band level, but intermittent straight sarcotubules, narrow two-dimensional networks, and some axial tubules traversed the A-band. The subsarcolemmal space had continuous two-dimensional SR at the H-band level and a coarse SR network at the I-band. These two SR networks were connected by single A-band sarcotubules. Mitochondrial shape and configuration were distinctive for each human skeletal muscle fiber type, but the SR was similar in all muscles examined.

Ultra‐high‐resolution scanning electron microscopy of mitochondria and sarcoplasmic reticulum arrangement in human red, white, and intermediate muscle fibers

ABSTRACT Background: Human skeletal muscle fibers are the red, white, and intermediate fibers. They differ in their mitochondrial structure and enzyme activity. Scanning electron microscopy (SEM) was used on specially prepared specimens to determine the distinctive features of mitochondria and sarcoplasmic reticulum (SR) in each fiber type. Methods Specimens of human limb muscles were glutaraldehyde fixed, frozen, fractured, and macerated by the aldehyde-osmium-DMSO-osmium procedure to expose large areas of mitochondria and SR. Osmium-hydrazine-impregnated tissues were examined without metal coating by ultra-high-resolution SEM. Results In white fibers, paired long, thin mitochondria encircled myofibrils at the I-band level. In red fibers, the paired rows of stubby mitochondria at the I-band level were often connected across the A-band to the next row of mitochondria by a slender mitochondrial stalk. Intermediate fiber mitochondria resembled those in red fibers but were longer and thinner. Intermyofibrillar mitochondrial columns were most common in red fibers. All three muscle types had T-tubules along the A-I junction level, and small periodic terminal cisternae formed triads or dyads. Sarcotubules from terminal cisternae formed continuous three-dimensional networks at the I-band level, but intermittent straight sarcotubules, narrow two-dimensional networks, and some axial tubules traversed the A-band. The subsarcolemmal space had continuous two-dimensional SR at the H-band level and a coarse SR network at the I-band. These two SR networks were connected by single A-band sarcotubules. Conclusions Mitochondrial shape and configuration were distinctive for each human skeletal muscle fiber type, but the SR was similar in all muscles examined. © 1997 Wiley-Liss, Inc.

Moment arms and lengths of human upper limb muscles as functions of joint angles

Modeling of musculoskeletal structures requires accurate data on anatomical parameters such as muscle lengths (MLs), moment arms (MAs) and those describing the upper limb position. Using a geometrical model of planar arm movements with three degrees of freedom, we present, in an analytical form, the available information on the relationship between MAs and MLs and joint angles for thirteen human upper limb muscles. The degrees of freedom included are shoulder flexion/extension, elbow flexion/extension, and either wrist flexion/extension (the forearm in supination) or radial/ulnar deviation (the forearm in mid-pronation). Previously published MA/angle curves were approximated by polynomials. ML/angle curves were obtained by combining the constant values of MLs (defined by the distance between the origin and insertion points for a specific upper limb position) with a variable part obtained by multiplying the MA (joint radius) and the joint angle. The MAs of the prime wrist movers in radial/ulnar deviation were linear functions of the joint angle ( R 2 ≥ 0.9904), while quadratic polynomials accurately described their MAs during wrist flexion/extensions. The relationship between MAs and the elbow angle was described by 2nd, 3rd or 5th-order polynomials ( R 2 ≥ 0.9904), with a lesser quality of fit for the anconeus ( R 2 = 0.9349). In the full range of angular displacements, the length of wrist, elbow and shoulder muscles can change by 8.5, 55 and 200%, respectively.

Differences in capillary supply between human oro-facial, masticatory and limb muscles

In this report we show that immunostaining of the capillary basement membrane with an antibody directed against laminin is a useful alternative in detecting the capillaries in human muscle. Using this method, the capillary supply of three embryologically, morphologically and functionally different muscle groups, oro-facial, masticatory and limb muscles, were analysed. Significant differences in capillarization between muscles and muscle groups were found. The oro-facial and masseter muscles showed significantly higher density of capillaries than the limb muscles, taken in consideration the muscle cross-sectional area, with the masseter having the highest capillary density ever reported for human sedentary skeletal muscles. Judged from the number of capillaries per muscle fibre, the limb muscles showed the best capillarization. However, since the three muscle groups investigated differed with respect to fibre diameter, our evaluation of number of capillaries per muscle fibre was related also to fibre diameter. Thus, capillary constants were created which take fibre diameter into account. Based on these new parameters, the oro-facial and masseter muscles were found to be relatively better supplied by capillaries than the limb muscles. These results suggest differences in tasks and functional activity between muscles, and reflect a relatively higher need and demand for blood supply in the masticatory and oro-facial muscles than in limb muscles.

Muscle-specific enzyme activity patterns of the capillary bed of human oro-facial, masticatory and limb muscles.

Enzyme-histochemical methods were used to analyse the activities of alkaline phosphatase (AP), dipeptidylpeptidase IV (DPP IV) and adenosine triphosphatase (ATPase) in capillaries of four different human oro-facial muscles, the major and minor zygomatic, the orbicularis oris and buccinator, one masticatory, the masseter and two limb muscles, the biceps brachii and first dorsal interosseus muscles. In all muscles, except for the orbicularis oris, the majority of the capillaries lacked enzyme activity. Therefore, none of these enzymes seems to be reliable as a general marker for human muscle capillaries. In general, the capillaries of the limb muscles and the major and minor zygomatic and the buccinator, were similar in their staining pattern for AP and ATPase, but differed in DPP IV staining. The orbicularis oris muscle differed from the other muscles by showing the largest proportion of capillaries with AP and ATPase activity. The masseter muscle had the largest proportion of capillaries stained for DPP IV. The muscle specific differences in enzyme activity of the capillaries are in agreement with our previous findings of specific differences between limb, oro-facial and masticatory muscles with respect to capillary supply and composition of fibre types and myosins. The results reflect functional specialization of the capillary bed of human muscles.

Early and late motor evoked potentials reflect preset agonist–antagonist organization in lower limb muscles

A single transcranial magnetic stimulus can evoke two involuntary muscle responses in lower limb muscles of healthy humans. The purpose of the present study was to find out if these responses, when evoked during the processing period of a simple or choice reaction time task, such as ankle dorsiflexion, have specific characteristics related to the task. During the auditory reaction time, a transcranial magnetic stimulus was delivered to observe changes in the excitability of the central nervous system. A dual-cone coil was used, which effectively stimulated the fairly deep-lying lower limb motor cortex. Stimuli were delivered in a random order with 20-300-ms delays from the auditory go-signal. Motor evoked potentials (MEP) in right and left anterior tibial and soleus muscles were analyzed while early MEPs were observed invariably in both muscles; late MEPs occurred consistently only in soleus muscles. Both early and late MEP amplitudes were larger in simple reaction time trials than in choice reaction time trials. The late MEP appeared earlier in the simple reaction time task than in the choice reaction time task, reflecting faster central processing of simple reaction time tasks. The amplitude of the soleus late MEP in the simple reaction time task followed closely the amplitude of anterior tibial early MEP, suggesting a preset agonist-antagonist organization. This relationship was not present in the choice reaction time task.

Capillary Structure and Mitochondrial Volume Density in the Trapezius Muscle of Chronic Trapezius Myalgia, Fibromyalgia and Healthy Subjects

Objective: To better understand some of the pathophysiological mechanisms of chronic muscle pain. Methods: Muscle biopsies were obtained from myalgic areas in the trapezius muscle of female patients suffering from either chronic trapezius myalgia or fibromyalgia and from corresponding areas in healthy, symptom-free subjects. Electron microscopy and morphometric analysis were used to determine mean myofibrillar mitochondrial density and the capillary structure. Results: The mitochondrial fraction was higher in the patients with chronic trapezius myalgia than in those with fibromyalgia or in the healthy subjects. The mean volume density of mitochondria in the trapezius muscle fibers, however, was lower than that previously reported for human female limb muscle in all three groups. This indicates that the trapezius muscle in general has a lower capacity to tolerate endurance work than limb muscles. The morphometric analysis of the capillary structure revealed that the area and thickness of the endothelium wa...

N-acetylcysteine inhibits muscle fatigue in humans.

N-acetylcysteine (NAC) is a nonspecific antioxidant that selectively inhibits acute fatigue of rodent skeletal muscle stimulated at low (but not high) tetanic frequencies and that decreases contractile function of unfatigued muscle in a dose-dependent manner. The present experiments test the hypothesis that NAC pretreatment can inhibit acute muscular fatigue in humans. Healthy volunteers were studied on two occasions each. Subjects were pretreated with NAC 150 mg/kg or 5% dextrose in water by intravenous infusion. The subject then sat in a chair with surface electrodes positioned over the motor point of tibialis anterior, an ankle dorsiflexor of mixed-fiber composition. The muscle was stimulated to contract electrically (40-55 mA, 0.2-ms pulses) and force production was measured. Function of the unfatigued muscle was assessed by measuring the forces produced during maximal voluntary contractions (MVC) of ankle dorsiflexor muscle groups and during electrical stimulation of tibialis anterior at 1, 10, 20, 40, 80, and 120 Hz (protocol 1). Fatigue was produced using repetitive tetanic stimulations at 10 Hz (protocol 1) or 40 Hz (protocol 2); intermittent stimulations subsequently were used to monitor recovery from fatigue. The contralateral leg then was studied using the same protocol. Pretreatment with NAC did not alter the function of unfatigued muscle; MVC performance and the force-frequency relationship of tibialis anterior were unchanged. During fatiguing contractions stimulated at 10 Hz, NAC increased force output by approximately 15% (P < 0.0001), an effect that was evident after 3 min of repetitive contraction (P < 0.0125) and persisted throughout the 30-min protocol. NAC had no effect on fatigue induced using 40 Hz stimuli or on recovery from fatigue. N-acetylcysteine pretreatment can improve performance of human limb muscle during fatiguing exercise, suggesting that oxidative stress plays a causal role in the fatigue process and identifying antioxidant therapy as a novel intervention that may be useful clinically.

Expression of myosin heavy chain isoforms in developing human muscle spindles.

We studied serial sections of human fetal limb muscles (10-25 weeks of gestation) by light microscopic (LM) immunocytochemistry, using specific antibodies against slow-tonic, slow-twitch, fetal, embryonic, and alpha-cardiac myosin heavy chain (MHC) isoforms, neurofilament protein, laminin, and myomesin. One set of the first-generation myotubes expressed slow-tonic MHCs, and slow-twitch, fetal, and embryonic MHCs from the tenth week of gestation. These primary myotubes were identified as developing nuclear bag fibers. Second-generation myotubes in close apposition to the primary nuclear bag myotubes initially expressed only fetal and embryonic MHCs. One or more of these secondary myotubes acquired expression of slow-tonic and slow-twitch MHCs and gave rise to nuclear bag fibers. Most of the nuclear bag precursors expressed alpha-cardiac MHC. The secondary myotubes that expressed fetal and embryonic MHC but not slow-tonic, slow-twitch, or alpha-cardiac MHCs gave rise to the nuclear chain fibers. This study shows that different populations of fiber precursors, each with a unique sequence of MHC expression, gave rise to the nuclear bag and chain fibers, despite the presence of a common afferent nerve, from the early stages.

Individual variation in contractile cost and recovery in a human skeletal muscle.

This study determined the variation among individuals in ATP use during contraction and ATP synthesis after stimulation in a human limb muscle. Muscle energetics were evaluated using a metabolic stress test that separates ATP utilization from synthesis by 31P NMR spectroscopy. Epicutaneous supramaximal twitch stimulation (1 Hz) of the median and ulnar nerves was applied in combination with ischemia of the finger and wrist flexors in eight normal subjects. The linear creatine phosphate (PCr) breakdown during ischemic stimulation defined ATP use (delta PCr per twitch or approximately P/twitch) and was highly reproducible as shown by the relative standard deviation [(standard deviation/mean) x 100] of 11% in three repeated measures. The time constant of the monoexponential PCr change during aerobic recovery represented ATP synthesis rate and also showed a low relative standard deviation (9%). Individuals were found to differ significantly in both mean approximately P/twitch (PCr breakdown rates, 0.29-0.45% PCr per sec or % PCr per twitch; ANOVA, p < 0.001) and in mean recovery time constants (41-74 sec; ANOVA, P < 0.001). This range of approximately P/twitch corresponded with the range of fiber types reported for a flexor muscle. In addition, approximately P/twitch was negatively correlated with a metabolite marker of slow-twitch fiber composition (Pi/ATP). The nearly 2-fold range of recovery time constants agreed with the range of mitochondrial volume densities found in human muscle biopsies. These results indicate that both components involved in the muscle energy balance--oxidative capacity and contractile costs--vary among individuals in human muscle and can be measured noninvasively by 31 P NMR.

Thyroarytenoid intramuscular pressures.

The aim of this research has been to investigate the measurement of laryngeal intramuscular fluid pressures as a technique for assessment of laryngeal muscle activity for diagnostic or experimental purposes. Simultaneous measurements of contractile force, intramuscular fluid pressure, and electromyographic signals were made under isometric conditions in the vocal fold muscles of anesthetized dogs during supramaximal stimulation of the recurrent laryngeal nerve. Covariation of force and pressure was studied in twitch and tetanic contractions, over a range of stimulation frequencies. Tetanic pressure rises were usually smaller than in human limb muscles, but were of sufficient magnitude that effects on blood flow and muscle metabolism are probable. Analysis of relations between pressure and force records demonstrated that intramuscular pressure variations correlated closely to isometric force in their time course. This finding suggests the potential significance of this measure as a relatively nonintrusive indicator of the level of force of muscles involved in laryngeal function, and as a physiological measure of importance.

Central and peripheral fatigue of human diaphragm and limb muscles assessed by twitch interpolation.

1. This study used a sensitive modification of the twitch interpolation technique to compare the extent of voluntary neural drive to the diaphragm and the elbow flexors during fatigue. For the diaphragm both inspiratory and expulsive efforts were tested, and fatigue was induced by expulsive efforts which were either maximal voluntary contractions (MVCs, 10 s duration, 50% duty cycle) or submaximal contractions (50% MVC, 3 s duration, 60% duty cycle). 2. Over the series of thirty MVCs peak elbow torque declined to 57.9 +/- 3.0% (mean +/- S.E.M.) of the initial value while maximal inspiratory pressure declined to 78.7 +/- 7.3% (P < 0.05). For the diaphragm the relative decline in voluntary peak inspiratory (and expulsive) force was similar to the decline in twitch responses to single and twin (10 ms interval) stimuli. However, for the elbow flexors the decline in twitch force was disproportionately greater than the decline in maximal voluntary force. The decline in twitch force for the diaphragm could not be attributed to failure at the neuromuscular junction. 3. At the start of the exercise, twitch potentiation (following three brief MVCs) was significantly less for the diaphragm than for the elbow flexors (20% versus 61%, P < 0.01). 4. In the unfatigued state maximal voluntary efforts by subjects activated 98.4 +/- 0.4% of the stimulated elbow flexors compared with 95.0 +/- 1.5% of the diaphragm (P < 0.05). During the exercise period there was a progressive failure in the ability to activate the limb muscle ('central fatigue'; voluntary drive declined from 98.4 +/- 0.4 to 86.8 +/- 2.2%, P < 0.01) whereas the decline in voluntary activation during inspiratory contractions was not significant (from 95.0 +/- 15 to 91.5 +/- 2.5%). 5. Voluntary activation during attempted maximal efforts was less complete for both muscles when stimuli were delivered without warning. The index of voluntary activation for unwarned stimuli was lower for the diaphragm (performing expulsive efforts, 81.0 +/- 2.8%) than for the limb muscle (89.9 +/- 1.5%, P < 0.01). 6. During repeated submaximal expulsive efforts we confirmed that subjects develop a marked inability to contract the diaphragm voluntarily, but when the diaphragm performed inspiratory manoeuvres at the same level of contractile fatigue, the index of voluntary drive was greater than 94%. 7. In conclusion, when tested with inspiratory efforts the diaphragm developed less central fatigue than the limb muscle over the same exercise period.(ABSTRACT TRUNCATED AT 400 WORDS)

Presence of homonymous recurrent inhibition in motoneurones supplying different lower limb muscles in humans

The pattern of recurrent inhibition to motoneurones (MNs) innervating different lower limb muscles was investigated in ten healthy subjects. Three complementary experimental designs, all based on the electrophysiological method introduced by Bussel and Pierrot-Deseilligny in 1977, were used in Quadriceps (Qu), Pretibial (Pt), Soleus (Sol) and Abductor hallucis (Abh) motornuclei: 1) measurement of the relationship between the amplitude of conditioning H (H1) and test (H') reflexes; 2) measurement of the effect of the intravenous administration of L-Acetylcarnitine (L-Ac) on the amplitude of the test H' reflex after a constant H1 conditioning reflex; 3) measurement of the modifications of the test H' reflex in relation to a reference H (Ref H) reflex during a weak tonic voluntary contraction of the homonymous muscle. A complete agreement among results obtained with the different experimental paradigms was observed. Similarly to the Sol, both Pt and Qu MNs were found to be recurrently inhibited: a) the test H' reflex exhibited a progressive and consistent depression with increasing amplitude of the H1 conditioning reflex beyond a specific value; b) an additional decrement of the test H' reflex was obtained after intravenous administration of L-Ac; c) a decrease in the size of the test H' reflex, with respect to its value at rest, was observed during a weak tonic voluntary contraction, in spite of the enhanced MN excitability (as shown by the increase in the Ref H). By contrast, no evidence of recurrent inhibition to the Abh MNs was found.(ABSTRACT TRUNCATED AT 250 WORDS)

Recovery from fatigue of human diaphragm and limb muscles

This study was designed to compare the recovery from fatigue of human inspiratory and limb muscles using repeated maximal static contractions. Series of 18 maximal contractions of 10 sec duration were performed with a duty cycle of 50% for maximal inspiratory efforts (against a shutter at FRC), and with duty cycles of 5%, 10%, 20% and 50% for the elbow flexors in repeated studies on 6 subjects. The peak inspiratory pressure at the end of the series declined to 86.7% ± 5.3% (mean ± S.D.) of its initial value; maximal force of the elbow flexors declined to 83.5% ± 7.0% (5% duty cycle), 80.0% ± 5.5% (10% duty cycle), 70.0% ± 9.3% (20% duty cycle),and required approximately a 10-fold reduction in duty cycle to maintain over a series of contractions a force generating capacity comparable to that of the diaphragm. A small degree of ‘central’ fatigue developed progressively during all series of contractions but did not correlate with duty cycle. Fatigue-induced changes in twitch contraction properties varied with changes in duty cycle. Our major conclusions are that the human diaphragm has a marked capacity to recover from fatigue and that this may have been underestimated in previous studies from this and other laboratories.

The precision of motor control in human jaw and limb muscles during isometric contraction in the presence of visual feedback

Experiments showed that the human capacity to maintain a particular isometric force in the presence of visual feedback during a force-level, pursuit-tracking experiment is less developed for the jaw-closing muscles than for the limb muscles. This finding may indicate that the projection on the trigeminal motoneurone pool from visual inputs is poor, or that the trigeminal effector system itself is less finely tuned.

Cytochrome c oxidase deficient fibres in the limb muscle and diaphragm of man without muscular disease: An age-related alteration

Cytochrome c oxidase (complex IV of the respiratory chain) was studied histochemically in human limb muscle (n = 109) and diaphragm (n = 115) obtained at autopsy revealing randomly distributed muscle fibres without enzyme activity. The defects were present both in normal type I and type II fibres and in ragged red like fibres with increased content of mitochondria. In both organs an age associated manifestation of the defect was observed. First defects occurred sporadically in the 3rd and 4th decade, but were present from the 6th to 9th decade in 66-83% of the limb muscles and 75-100% of the diaphragms. Also the number of defects/cm2 (defect density) increased with age from approx. 5, and 7 in limb muscle and diaphragm below the 6th decade to 54 and 60 defects in the 8th-9th decade (P = 0.000). Between both muscles no statistically significant difference in defect density (P greater than 0.15) existed. Irrespective of the defect density the defect typically affected isolated fibres showing normal histochemical reactivity for succinate dehydrogenase (complex II). The results indicate that cytochrome c oxidase deficient muscle fibres in normal skeletal muscle represent an age related phenomenon which probably results from cellular ageing and might be involved in the reduction of muscle mass and strength during senescence.