Journal of the Neurological Sciences, 1978, 37: 187-197
187
© Elsevier/North-Holland Biomedical Press
ANALYSIS OF T H E E L E C T R I C A L MUSCLE ACTIVITY D U R I N G M A X I M A L C O N T R A C T I O N A N D T H E I N F L U E N C E OF ISCHAEMIA
VOLKER DIETZ* The National Hospital, Queen Square, London WC1 3BG (Great Britain)
(Received 20 December, 1977) (Accepted 1 March, 1978)
SUMMARY (1) The mechanism underlying muscle fatigue has been studied in maintained isometric maximal contraction of the wrist flexor muscles under normal and ischaemic conditions. Automatic E M G analysis has been used to show the level of motor unit firing rates in fatiguing contractions. (2) Under non-ischaemic conditions the decay of force, turns and amplitude is about the same, whereas during ischaemia force and to a lesser extent amplitude pulses, decline steeply towards zero, while turns, representing the number of impulses, remain in the non-ischaemic range. (3) Depending on the duration of the ischaemia applied before contraction, force and amplitude are initially reduced but turns are nearly unchanged compared with the non-ischaemic values. It is suggested, that this is due to nerve blocking of high threshold motor units. (4) The results show that transmission failure at the neuromuscular junction is a minor factor in muscle fatigue and that this structure is not greatly affected by ischaemia. (5) It is believed that in the first phase of muscle fatigue the force decline is connected with a slowing of discharge rates. This change of firing frequencies with time must be considered optimal in respect to the force produced because higher as well as lower discharge rates would reduce the force development. In the later phase it is possible that contractile element fatigue, connected with a reduction of action potential amplitudes of single muscle fibres, predominates, especially when the blood supply is obstructed.
The author held a Research Fellowship of the Deutsche Forschungsgemeinschaft. * Present address: Neurologische Klinik mit Abteilung fi~r Neurophysiologie, Hansastr. 9, D-7800 Freiburg, West-Germany.
188 INTRODUCTION
The mechanism underlying muscle fatigue during maximal voluntary contraction (MVC) is still a matter of discussion. Investigations using conventional electrophysiological techniques in man have been controversial and not all questions have been answered by animal experiments (LiJttgau 1965; Hanson and Persson 197 I). The following phenomena have been considered to play an important part in muscle fatigue : (1) Cessation in central excitatory impulse drive (Bigland-Ritchie, Hoskin and Jones 1975), (2) Conduction failure of nerve fibres (Magladery, McDougal and Stoll 1950; Hershey 1966), (3) Impairment of neuromuscular transmission (Naess and Storm-Mathisen 1955; Stephens and Taylor 1972), (4) Impairment of contractile mechanism in the muscle (Merton 1954; Lippold, Redfearn and Vu~o 1960). This study on muscle fatigue is based on a method of automatic quantitative analysis of the electromyogram (EMG) described by Rose and Willison (1967) and Hayward (1977). The method was used to obtain an indirect estimation of the level of motoneurone discharges and the amplitudes of action potentials occurring in the EMG. This method was proved to be reliable by results obtained from patients with muscular dystrophy and neuropathy (Rose and Willison 1967). Ischaemia was included in these experiments to differentiate between the 4 major possible components because it was supposed by several authors that ischaemia is an important factor responsible for muscle fatigue during maximal voluntary contraction (Barcroft and Millen 1939; Humphreys and Lind 1963; Lundborg 1970). METHODS
In these experiments 3 normal subjects exerted a maximal voluntary isometric contraction, pressing the volar, distal metacarpals of one hand against a force transducer, while the forearm was fixed (hand-forearm angle 180 degree). The surface EMG of the flexor carpi ulnaris recorded over the muscle belly was amplified and analysed (Medelec MS6 oscilloscope with an APA6 analyser). The bandwidth of the amplifier ranged from 8 Hz to 40 kHz (3 db points). The EMG analysis was done with a method which was originally carried out graphically (Willison 1963). Subsequently an electronic system based on the same principles was developed by Fitch (1967). Its application in clinical electromyography has been described by Rose and Willison (1967), Hayward (1977) and Hayward and Willison (1977). Although designed for needle electromyography the system can be applied to surface EMG as a method of quantification. The output of the oscilloscope is processed by a pulse converter, which derives two serial pulse trains from the signal that is fed to it. Each time the signal changes from positive going to negative going and vice versa and the excursion exceeds the
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Fig. 1. Typical record of all parameters registered at the beginning of maximal voluntary contraction. A : n o r m a l condition. B: after a preceding period of 15 min ischaemia applied to the arm. Note the loss of large amplitudes but nearly unchanged turns in B. a -- turns, b -- total amplitude, c - surface m y o g r a m , d - D-C amplified force, ~- -- resting force level.
significance level of 100 #V, a "turn pulse" is generated. The turn pulses are effectively registering positive and negative spikes in the signal that exceed 100 #V without reference to a baseline. The amplitudes of the potential changes between each turn in the signal are measured by a second converter which generates an "amplitude pulse" each time 100 #V is reached. The pulses have also been displayed on the Medelec oscilloscope (Fig. 1). Every 10th turn pulse is displayed (upper beam, a), every 50th amplitude pulse is displayed, each now representing 5 mV, on the second beam (b). The primary E M G trace and the D-C amplified force are displayed on the third and fourth beams (c and d). It is assumed that by counting the number of turns/sec a measure of the impulses occurring in the recorded E M G can be obtained. This assumption is made because the potentials in a normal muscle do not differ very much in the number of their phases. Normally there is only a very small percentage of polyphasic potentials (Buchthal and Rosenfalck 1963; Caruso and Buchthal 1965) which could falsify the number of impulses as estimated by this technique. Each experiment included the 3 following contraction conditions (each interrupted by a 10-min relaxation): (1) Single contraction steps from 0 to a certain force level (until 70 % of maximal voluntary contraction) for turn and amplitude to force calibration. Each contraction step was maintained for 20 sec, before the figures were taken to avoid dynamic discharge components. (2) Maximal voluntary contraction over a period of 3 min. (3) Ischaemia of the arm by inflation of a pneumatic cuff above 200 mm Hg, applied at the upper arm. Ischaemia was maintained for 5, 10 or 15 min in the different experiments and was followed - - still during ischaemia - - by maximal voluntary contraction for 1.5 min.
190 At the beginning of each experiment and during ischaemia, before and alter maximal voluntary contraction, the ulnar nerve was stimulated at the elbow with supramaximal electrical stimuli and the action potential and twitch tension were registered. RESULTS
(1) Relationship between turns/sec, total amplitude and contraction force during nonischaemic conditions A linear relationship was found between force and turns/sec, as shown in Fig. 2. A linear relationship between integrated E M G recorded during steady contraction and force was reported by Bigland en Lippold (1954), Edwards and Lippold (1956) and Kuroda, Klissouras and Milsum (1970), whereas a non-linear relationship in changing forces was observed by Zuniga and Simons (1969). During MVC the force falls immediately reaching 50 % of the initial tension after about 40 sec and 25 % in 2 min (Fig. 3) in the non-ischaemic condition. The level of 25% MVC could be maintained by all subjects over a longer time period. This observation has been previously reported by Stephens and Taylor (1972). A similar decay can be observed in turns/sec (Fig. 4) and in total amplitude (Fig. 5), so that the relationship between turns and force and also between amplitude and force remains constant. The amplitude curve decreases a little more steeply than the turn slope (ratio amplitude to turn after 30 sec 0.85, after 1 min 0.6). This could be due to a drop out of high-threshold phasic motor units but the similar reduction of the stimulated APamplitude during contraction which was observed by Stephens and Taylor (1972) suggests a reduction of the amplitude of single muscle fibres. After 1.5 min contraction there is a slight increase in the turns to force ratio whereas the ratio amplitude to force 100"
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Fig. 2. Relationship between turns/sec (×), total amplitude (©) and contraction force. Figures are obtained after 20 sec of a maintained contraction level and from the fatigue curve (9¢rand O) for the high force steps (> 80% MUC) (Ch.H. and V.D.). Turns/sec and total amplitude (mV) are expressed as percentages of the values reached at 100% maximal voluntary force. Fig. 3. Time course of fatigue under normal and isehaernic condition. The thick line with standard deviations represents the control values obtained in 4 different experiments of one subject (V.D.). The thin lines represent the figures obtained after 5 rain [ ), 10 min (- - - -) and 15 min (. . . . . ) of ischaemia before contraction. The figures of the isehaemic experiments are expressed as a percentage of the control value without isehaemia.
191
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Fig. 4. Relationship between turns/sec and fatigue, with and without ischaemia. Same symbols as in Fig. 3. remains constant (Figs. 6A and B). That means that the increase of turns per 1% force increment is raised from 1 to 1.7 %, whereas the ratio is kept constant for the total amplitude. A comparable increase of the integrated E M G was reported by Stephens and Taylor (1972).
(2) Stimulation of the ulnar nerve under ischaemic conditions The ulnar nerve was stimulated with the arm relaxed (a) at the beginning of the experiment, (b) during ischaemia before MVC (after 5, 10 or 15 min of ischaemia) and (c) after MVC. The amplitude of the muscle action potential (MAP) and the twitch tension are shown for the 3 conditions in Fig. 7. Curing ischaemia before MVC there is a moderate reduction of AP-amplitude and a less pronounced reduction of twitch tension. These reductions are dependent on the duration of the preceding ischaemia. After 11/2 rain of MVC both measurements are further reduced, but in the experiments with a preceding ischaemia of 10 and 15 min the reduction in the twitch tension is now much more marked than that of the APamplitude. This means, for example, that in the experiment with a circulation arrest of amp
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Fig. 6. Ratio of turns/force (A) and amplitude/force (B) during fatigue, with and without ischaemia. Same symbols as in Fig. 3. Fig. 7. Stimulation of the ulnar nerve. MAP-amplitude (A) and twitch tension (B) are plotted as percentages of their control values without ischaemia. (1) control value, (2) with ischaemia, before maximal voluntary contraction, (3) with ischaemia, after maximal voluntary contraction. The duration of the preceding ischaemia is indicated with the same symbols as in Fig. 3. 15 min the twitch tension is reduced twice as much as the AP-amplitude. A reduction of the AP-amplitude of individual muscle fibres after muscle fatigue during repeated stimulation has been observed in animal experiments and it was suggested that it is caused by reactions connected with the fibre contractions (Liittgau 1965). Failure of the neuromuscular junction, suggested by Stephens and Taylor (1972), is unlikely to be the cause of the moderately diminished AP response after MVC (under ischaemia): neither would it explain the greater reduction of twitch tension.
(3) Influence of ischaemia on turns, amplitude and force during maximal voluntary contraction There are some observations common to all the experiments under ischaemia, which do not depend upon the different periods ofischaemia applied to the arm before MVC. After about 1 min of contraction the force falls rapidly towards zero (Fig. 3) whereas the decline of the amplitude curves is less steep (Fig. 5). There is no decay of turns, the turn slope remaining in the range of the non-ischaemic controls during this period (Fig. 4). This is further illustrated in Figs. 6A and 6B: after 1 min of MVC the proportion of turns to force rises rapidly and reaches a ratio of 6 % turns to 1% force in the next 20-30 sec, before the force reaches the zero level. The ratio amplitude to force rises later and to a smaller extent (Fig. 6B). Consequently the striking observation in all ischaemic experiments is the persistence of turns in the range of the non-ischaemic controls, whereas force and amplitude decline at nearly the same rate.
(4) Dependence of the neuromuscular system on the duration of ischaemia before contraction The difference between the recordings obtained at the beginning of MVC
193 without ischaemia and those with a preceding (15 min) and persisting ischaemia can be seen in Figs. 1A and lB. In the ischaemic condition (B) large potentials are lacking and the force is reduced, whereas the number of impulses as measured by the turn pulses is only slightly reduced compared with the control contraction. After a period of 5, 10 or 15 rain ischaemia the force is already reduced at the beginning of the contraction, the extent of the reduction depending on the duration of the preceding ischaemia. However, the duration of force maintenance is about the same for all 3 ischaemic conditions. As can be seen in Fig. 3 the slope of the fatigue curve obtained after 15 min ischaemia appears flatter than the curve after 5 rain ischaemia. The turn pulses remain within the range of 2 standard deviations of the control values (Fig. 4) during the first 70 sec in the 3 ischaemic conditions. That means the ratio turns to force is raised after a preceding ischaemic period (to 1.8 % turns to force) and is kept constant until the steep increase after about 1 min takes place (Fig. 5). The decline of turns parallels that of force at a higher level in this first rain of contraction. Only in the experiments with a 15 min preceding ischaemia were the amplitude values reduced in about the same proportion as the force (Fig. 5). Consequently the ratio of amplitude to force is not increased in the first min of MVC and after 1 min only slightly increased (Fig. 6B). In summary, the main influence of ischaemia before MVC consists in the reduction of the initial maximal force and to a lesser extent also of initial amplitude (depending on the duration of ischaemia) whereas the turns, representing the number of impulses, remain nearly unchanged in respect to the nonischaemic control values. DISCUSSION The present results suggest that there are two different mechanisms underlying muscle fatigue which are prominent at different phases of maximal voluntary contraction, as has also been suggested by other authors (Stephens and Taylor 1972). It is known, that during MVC the blood flow in the contracting muscle is restricted or arrested (Barcroft and Millen 1939; Naess and Storm-Mathisen 1955; Humphreys and Lind 1963; Mottram 1963) and it was suggested by several authors (Fox and Kenmore 1967; Dahlb~tck 1970; Lundborg 1970; Stephens and Taylor 1972) that impulse transmission in the neuromuscular system is the mechanism most sensitive to ischaemia and is therefore responsible for the initial decline of force. This hypothesis seems to be supported by the observation that the integrated EMG of the contracting muscle declines in the same way as the force and that the stimulated AP-amplitude is reduced in this phase (Stephens and Taylor 1972). But this reduction could also be explained by diminished fibre action potential amplitudes as reported by Lfittgau (1965) and which is supported by the diminished amplitude to turn relationship in our results. The results presented here clearly show that even if the contractile force and twitch tension amplitude nearly reach the zero level during ischaemia, impulses, as indicated by turns, remain in the "normal" non-ischaemic control range or are only slightly diminished in frequency. In accordance with this, stimulation of the ulnar
194 nerve under ischaemia after MVC also shows a much more reduced twitch tension than AP-amplitude. The single motor unit recordings of DahlNick, Ekstedt and Stalberg (1970) also show, that a blocking of impulses at the neuromuscular junction during ischaemia occurs only after the transmission of 3500-7000 impulses. Even if all motor units fire at the highest rates (about 100/sec), there should not be a neuromuscular blocking of impulses before 35 sec of maximal contraction. Thus the decline of force in the first 30 sec cannot be explained by this mechanism. However, these observations are not strictly relevant to maximal contractions, because the experiments were performed at discharge rates between 5-16/sec. Recent investigations on motor unit firing rates have shown that at the beginning of a strong contraction the motoneurone discharge frequency is usually raised to 80-150/sec (Marsden, Meadows and Merton 1971 ; Gillies 1972; Biidingen and Freund 1976) and that the neurons then slow down progressively during a prolonged effort to a rate of 20-25/sec within about 30 sec and stabilise at this rate (Marsden, Meadows and Merton 1971). At steady contractions the maximal firing rates reported by other authors are 20-30/sec (Tanji and Kato 1973; Freund, Btidingen and Dietz 1975). This change of firing rate from about 100 to 25/sec would explain the high-frequency decay related to muscle fatigue seen in the spectrum analysis of the E M G (Kadefors, Kaiser and Petersen 1968; Broman, Magnusson and Petersen 1973). An appropriate mechanical effect of these high discharge rates can be expected because an increase of force is reported for stimulation rates up to 50-60/sec (Rack and Westbury 1969; MitnerBrown, Stein and Yemm 1973; Bigland-Ritchie et al. 1975). Thus in the first phase of MVC the decline of discharge frequency and force take an optimal course because higher as well as lower discharge rates would reduce the force development as was established by Naess and Storm-Mathisen (1955) and confirmed by Marsden, Meadows and Merton (1976). It is suggested, that this represents the main mechanism underlying the first phase of muscle fatigue. Because of the stabilisation of motoneurone firing rates there must be a different mechanism for the second phase of muscle fatigue with a less marked loss of tension. The slow decrease of force and amplitude in our results suggests that reduction of the action potentials of single fibres, associated with contractile element fatigue, as shown during repetitive stimulation in animal preparations by Ltittgau (1965) and Hanson and Persson (1971) are predominant. The slight increase of turns during this phase would indicate that the loss of muscular force is partly compensated by an increase in discharge rate, possibly as a result of a reduced Goigi tendon organ inhibition on amotoneurones (c.f. Houk, Singer and Goldman 1970). Consequently the impulse transmission must be less fatiguable than the contractile elements of a muscle. It was suggested by Stephens and Taylor (1972) that motor units with a low threshold are more fatiguable than those with a high threshold. However, recent investigations of this group (Stephens and Usherwood 1975) have shown, that high threshold units are more fatiguable, which is supported by animal studies (Burke, Levine, Tsairis and Zajac 1973; Proske and Waite 1974). This would be an explanation for the common experience, that weak voluntary contraction force can be maintained without fatigue for much longer periods than strong contractions.
195 In a relaxed state the impulse conduction by the nerve fibres seems to be most affected by ischaemia. The observation, that the reduction of force and amplitude at the beginning of MVC depends on the duration of the preceding ischaemia suggests that there is an increasing loss of conducting nerve fibres. This is also reflected by a corresponding reduction of AP-amplitude under stimulation of the ulnar nerve. The minor reduction of the stimulated twitch amplitude is less crucial in this context because the twitch amplitude does not necessarily reflect the tetanic force level under ischaemia. The nearly normal impulse rate and the force decline, which proportionally stays the same in all ischaemic experiments, independent of the preceding duration of ischaemia, indicate that the initial force loss could not be due to neuromuscular transmission failure. The possibility of a selective failure of impulse transmission for the large phasic motor units from the beginning of contraction seems highly improbable but cannot be excluded. The latter result and the preserved twitch response also indicate that the contractile element functioning is scarcely affected at the beginning of contraction. The question arises which type, high or low threshold motor units, drop out. In the literature controversial observations are reported in this field. While Magladery et al. (1950) showed that motor nerve fibres with the highest conduction velocity are most sensitive to ischaemia, Hershey (1966) found a greater ischaemic effect on the smaller nerve fibres and Ruskin, Tanyag-Jocson and Rogoff (1967) observed a decrease in the conduction velocity of all fibres without significant differences between large and small motor units. Since there is a marked force and amplitude loss with only slight reduction of turns only a small number of motor units with high threshold, which produce a lot of force, can be affected and be responsible for the initial force reduction. Thus these results suggest that nerve fibres with a high conduction velocity are blocked first. In all experiments reported here neuro-muscular transmission seems to be the most resistant link to ischaemia within the neuromuscular system. This conclusion stands in contrast to those drawn in the papers by Fox and Kenmore (1967), Dahlb/ick (1970), Lundborg (1970) and Stephens and Taylor (1972) in which the hypothesis was put forward that the neuromuscular junction is the most sensitive structure in an ischaemic condition. This difference can be explained by the use of the method of automatic E M G analysis to give an indication of the number of motor units which are being activated and hence not affected by block of transmission. ACKNOWLEDGEMENTS The author thanks Dr. R. G. Willison for his encouragement in this study and critical review of the manuscript and Dr. P. A. Merton, Prof. A. Taylor, Dr. J. A. Stephens and Dr. Noth for helpful comments on the paper.
REFERENCES Barcroft, H. and J. L. E. Millen (1939) The blood flow through muscle during sustained contraction, J. Physiol. (Lond.), 97: 17-31.
196 Bigland, B. and O. C. J. Lippold (1954) The relation between force, velocity and integrated electrical activity in human muscles, J. Physiol. (Lond.), 123:214 224. Bigland-Ritchie, B., G. P. Hoskin and D. A. Jones (1975) The site of fatigue in sustained maximal contractions of the quadriceps muscle, J. Physiol. (Lond.), 250:45 46P. Broman, H., R. Magnusson, I. Petersen and R. Ortengren (1973) Vocational electromyography - Methodology of muscle fatigue studies. In: J. E. Desmedt (Ed.), New Developments in Electromyography and Clinical Neurophysiology, Vol. 1, Karger, Basel, pp. 656-664. Buchthal, F. and P. Rosenfalck (1963) Electrophysiological aspects of myopathy with reference to progressive muscular dystrophy. In : G. H. Bourne (Ed.), Muscular Dystrophy in Man and Animals, Hafner, New York, pp. 194-262. B/idingen, H. J. and H.-J. Freund (1976) The relationship between the rate of rise of isometric tension and motor unit recruitment in a human forearm muscle, Pfliigers Arch. ges. Physiol., 362: 61-67. Burke, R. E., D. N. Levine, P. Tsairis and F. E. Zajac (1973) Physiological types and histochemical profiles in motor units of cat medial gastrocnemius, J. Physiol. (Lond.), 234: 723-748. Caruso, G. and F. Buchthal (1965) Refractory period of muscle and electromyographic findings in relatives of patients with muscular dystrophy, Brain, 88 : 29-50. Dahlbfick, L. O. (1970) Effects of temporary tourniquet ischaemia on striated muscle fibers and motor end-plates, Scand. J. plast, reconstruct. Surg., Suppl. 7: 1-91. Dahlbfi.ck, L. O., J. Ekstedt and E. St',llberg (1970) Ischaemic effects on impulse transmission to muscle fibers in man, Electroenceph. clin. Neurophysiol., 29: 579-591. Edwards, R. G. and O. C. J. Lippold (1956) Relation between force and integrated electrical activity in fatigued muscle, J. Physiol. (Lond.), 132: 677-681. Fitch, P. (1967) An analyser for use in human electromyography, Electron. Engng., 39: 240-243. Fox, J. L. and P. 1. Kenmore (1967) The effect of ischaemia on nerve conduction, Exp. Neurol., 17: 403-419. Freund, H.-J., H. J. B0dingen and V. Dietz (1975) The activity of single motor units from human forearm muscles during voluntary isometric contractions, J. Neurophysiol., 38: 933-946. Gillies, J. D. (1972) Motor unit discharges during isometric contraction in man, J. Physiol. fLorid.), 223 : 36-37P. Hanson, J. and A. Persson (1971) Changes in the action potential and contraction of isolated frog muscle after repetitive stimulation, Acta physiol, stand., 81 : 340-348. Hayward, M. (1977) Automatic analysis of the electromyogram in healthy subjects of different ages, J. neurol. Sci., 33: 397-413. Hayward, M. and R. G. Willison (1977) Automatic analysis of the electromyogram in patients with chronic partial denervation, J. neurol. Sei., 33:415-423. Hershey, W. N. (1966) Effects of ischaemia on range of conduction velocities and on facilitation in human motor nerves, Trans. Amer. neurol. Ass., 91 : 246-248. Houk, J. C., J. J. Singer and M. R. Goldman (1970) An evaluation of length and force feedback to soleus muscles of decerebrate cats, J. Neurophysiol., 33:784-8 l 1. Humphreys, P. W. and A. R. Lind (1963) Blood flow through active and inactive muscles of the forearm during sustained hand grip contractions, J. Physiol. (Lond.), 166: 120-135. Kadefors, R., E. Kaiser and 1. Petersen (1968) Dynamic spectrum analysis ofmyopotentials with special reference to muscle fatigue, Electromyography, 8 : 39-74. Kuroda, A., V. Klissouras and J. H. Milsum (1970) Electrical and metabolic activities and fatigue in human isometric contraction, J. appl. Physiol., 29: 358-367. Lippold, O. C. J., J. W. T. Redfearn and J. Vu6o (1960) Electromyography of fatigue, Ergonomics, 3 : 121-131. Lundborg, G. (1970) lschaemic nerve injury, Stand. J. plast, reconstruct. Surg., Suppl. 6: 49-105. Ltittgau, H. C. (1965) The effect of metabolic inhibitors on the fatigue of the action potential in single muscle fibres, J. Physiol. (Lond.), 178: 45-67. Magladery, J. W., D. B. McDougal and J. Stoll (1950) Electrophysiological studies of nerve and reflex activity in normal man, Part 2 (The effects of peripheral ischaemia), Bull. Johns Hopk. Hosp., 86: 291-312. Marsden, C. D., J. C. Meadows and P. A. Merton (1971) Isolated single motor units in h u m a n muscle and their rate of discharge during maximal voluntary effort, J. Physiol. (Lond.), 217: 12P. Marsden, C. D., J. C. Meadows and P. A. Merton (1976) Fatigue in human muscle in relation to the number and frequency of motor impulses, J. Physiol. (Lond.), 258: 94-95P. Merton, P. A. (1954) Voluntary strength and fatigue, J. Physiol. (Lond.), 123 : 553-564.
197 Milner-Brown, H. S., R. B. Stein and R. Yemm (1973) Changes in firing rate of human motor units during linearly changing voluntary contractions, J. Physiol. (Lond.), 230:371-390. Mottram, R. F. (1963) The local blood-flow changes due to isometric contractions of the human forearm muscles, J. Physiol. (Lond.), 167: 57-58P. Naess, K. and A. Storm-Mathisen (1955) Fatigue of sustained tetanic contractions, Actaphysiol. scand., 34: 351-366. Proske, V. and P. M. E. Waite (1974) Properties of types of motor units in the medial gastrocnemius muscle of the cat, Brain Res., 67: 89-101. Rack, P. M. H. and D. R. Westbury (1969) The effects of length and stimulus rate on tension in the isometric cat soleus muscle, J. Physiol. (Lond.), 204: 443-460. Rose, A. L. and R. G. Willison (1967) Quantitative electromyography using automatic analysis - Studies in healthy subjects and patients with primary muscle disease, J. Neurol. Neurosurg. Psychiat., 30: 403-410. Ruskin, A. P., A. Tanyag-Jocson and B. Rogoff(1967) Effect of ischaemia on conduction of nerve fibers of varying diameters, Arch. Phys. Med., 48: 304-310. Stephens, J. A. and A. Taylor (1972) Fatigue of maintained voluntary muscle contraction in man, J. Physiol. (Lond.), 220: 1-18. Stephens, J. A. and T. P. Usherwood (1975) The fatiguability of human motor units, J. Physiol. (Lond.), 250: 37-38P. Tanji, J. and M. Kato (1973) Firing rate of individual motor units in voluntary contraction of abductor digiti minimi muscle in man, Exp. Neurol., 40: 771-783. Willison, R. G. (1963) A method of measuring motor unit activity in human muscle, J. Physiol. (Lond.), 168: 35-36P. Zuniga, N. E. and D. G. Simons (1969) Non-linear relationship between averaged electromyogram potential and muscle tension in normal subjects, Arch. Phys. Med., 50:613-620.
187
© Elsevier/North-Holland Biomedical Press
ANALYSIS OF T H E E L E C T R I C A L MUSCLE ACTIVITY D U R I N G M A X I M A L C O N T R A C T I O N A N D T H E I N F L U E N C E OF ISCHAEMIA
VOLKER DIETZ* The National Hospital, Queen Square, London WC1 3BG (Great Britain)
(Received 20 December, 1977) (Accepted 1 March, 1978)
SUMMARY (1) The mechanism underlying muscle fatigue has been studied in maintained isometric maximal contraction of the wrist flexor muscles under normal and ischaemic conditions. Automatic E M G analysis has been used to show the level of motor unit firing rates in fatiguing contractions. (2) Under non-ischaemic conditions the decay of force, turns and amplitude is about the same, whereas during ischaemia force and to a lesser extent amplitude pulses, decline steeply towards zero, while turns, representing the number of impulses, remain in the non-ischaemic range. (3) Depending on the duration of the ischaemia applied before contraction, force and amplitude are initially reduced but turns are nearly unchanged compared with the non-ischaemic values. It is suggested, that this is due to nerve blocking of high threshold motor units. (4) The results show that transmission failure at the neuromuscular junction is a minor factor in muscle fatigue and that this structure is not greatly affected by ischaemia. (5) It is believed that in the first phase of muscle fatigue the force decline is connected with a slowing of discharge rates. This change of firing frequencies with time must be considered optimal in respect to the force produced because higher as well as lower discharge rates would reduce the force development. In the later phase it is possible that contractile element fatigue, connected with a reduction of action potential amplitudes of single muscle fibres, predominates, especially when the blood supply is obstructed.
The author held a Research Fellowship of the Deutsche Forschungsgemeinschaft. * Present address: Neurologische Klinik mit Abteilung fi~r Neurophysiologie, Hansastr. 9, D-7800 Freiburg, West-Germany.
188 INTRODUCTION
The mechanism underlying muscle fatigue during maximal voluntary contraction (MVC) is still a matter of discussion. Investigations using conventional electrophysiological techniques in man have been controversial and not all questions have been answered by animal experiments (LiJttgau 1965; Hanson and Persson 197 I). The following phenomena have been considered to play an important part in muscle fatigue : (1) Cessation in central excitatory impulse drive (Bigland-Ritchie, Hoskin and Jones 1975), (2) Conduction failure of nerve fibres (Magladery, McDougal and Stoll 1950; Hershey 1966), (3) Impairment of neuromuscular transmission (Naess and Storm-Mathisen 1955; Stephens and Taylor 1972), (4) Impairment of contractile mechanism in the muscle (Merton 1954; Lippold, Redfearn and Vu~o 1960). This study on muscle fatigue is based on a method of automatic quantitative analysis of the electromyogram (EMG) described by Rose and Willison (1967) and Hayward (1977). The method was used to obtain an indirect estimation of the level of motoneurone discharges and the amplitudes of action potentials occurring in the EMG. This method was proved to be reliable by results obtained from patients with muscular dystrophy and neuropathy (Rose and Willison 1967). Ischaemia was included in these experiments to differentiate between the 4 major possible components because it was supposed by several authors that ischaemia is an important factor responsible for muscle fatigue during maximal voluntary contraction (Barcroft and Millen 1939; Humphreys and Lind 1963; Lundborg 1970). METHODS
In these experiments 3 normal subjects exerted a maximal voluntary isometric contraction, pressing the volar, distal metacarpals of one hand against a force transducer, while the forearm was fixed (hand-forearm angle 180 degree). The surface EMG of the flexor carpi ulnaris recorded over the muscle belly was amplified and analysed (Medelec MS6 oscilloscope with an APA6 analyser). The bandwidth of the amplifier ranged from 8 Hz to 40 kHz (3 db points). The EMG analysis was done with a method which was originally carried out graphically (Willison 1963). Subsequently an electronic system based on the same principles was developed by Fitch (1967). Its application in clinical electromyography has been described by Rose and Willison (1967), Hayward (1977) and Hayward and Willison (1977). Although designed for needle electromyography the system can be applied to surface EMG as a method of quantification. The output of the oscilloscope is processed by a pulse converter, which derives two serial pulse trains from the signal that is fed to it. Each time the signal changes from positive going to negative going and vice versa and the excursion exceeds the
189 A . . . . . . . . . . . . . . . . . . . . . . . . . . .
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Fig. 1. Typical record of all parameters registered at the beginning of maximal voluntary contraction. A : n o r m a l condition. B: after a preceding period of 15 min ischaemia applied to the arm. Note the loss of large amplitudes but nearly unchanged turns in B. a -- turns, b -- total amplitude, c - surface m y o g r a m , d - D-C amplified force, ~- -- resting force level.
significance level of 100 #V, a "turn pulse" is generated. The turn pulses are effectively registering positive and negative spikes in the signal that exceed 100 #V without reference to a baseline. The amplitudes of the potential changes between each turn in the signal are measured by a second converter which generates an "amplitude pulse" each time 100 #V is reached. The pulses have also been displayed on the Medelec oscilloscope (Fig. 1). Every 10th turn pulse is displayed (upper beam, a), every 50th amplitude pulse is displayed, each now representing 5 mV, on the second beam (b). The primary E M G trace and the D-C amplified force are displayed on the third and fourth beams (c and d). It is assumed that by counting the number of turns/sec a measure of the impulses occurring in the recorded E M G can be obtained. This assumption is made because the potentials in a normal muscle do not differ very much in the number of their phases. Normally there is only a very small percentage of polyphasic potentials (Buchthal and Rosenfalck 1963; Caruso and Buchthal 1965) which could falsify the number of impulses as estimated by this technique. Each experiment included the 3 following contraction conditions (each interrupted by a 10-min relaxation): (1) Single contraction steps from 0 to a certain force level (until 70 % of maximal voluntary contraction) for turn and amplitude to force calibration. Each contraction step was maintained for 20 sec, before the figures were taken to avoid dynamic discharge components. (2) Maximal voluntary contraction over a period of 3 min. (3) Ischaemia of the arm by inflation of a pneumatic cuff above 200 mm Hg, applied at the upper arm. Ischaemia was maintained for 5, 10 or 15 min in the different experiments and was followed - - still during ischaemia - - by maximal voluntary contraction for 1.5 min.
190 At the beginning of each experiment and during ischaemia, before and alter maximal voluntary contraction, the ulnar nerve was stimulated at the elbow with supramaximal electrical stimuli and the action potential and twitch tension were registered. RESULTS
(1) Relationship between turns/sec, total amplitude and contraction force during nonischaemic conditions A linear relationship was found between force and turns/sec, as shown in Fig. 2. A linear relationship between integrated E M G recorded during steady contraction and force was reported by Bigland en Lippold (1954), Edwards and Lippold (1956) and Kuroda, Klissouras and Milsum (1970), whereas a non-linear relationship in changing forces was observed by Zuniga and Simons (1969). During MVC the force falls immediately reaching 50 % of the initial tension after about 40 sec and 25 % in 2 min (Fig. 3) in the non-ischaemic condition. The level of 25% MVC could be maintained by all subjects over a longer time period. This observation has been previously reported by Stephens and Taylor (1972). A similar decay can be observed in turns/sec (Fig. 4) and in total amplitude (Fig. 5), so that the relationship between turns and force and also between amplitude and force remains constant. The amplitude curve decreases a little more steeply than the turn slope (ratio amplitude to turn after 30 sec 0.85, after 1 min 0.6). This could be due to a drop out of high-threshold phasic motor units but the similar reduction of the stimulated APamplitude during contraction which was observed by Stephens and Taylor (1972) suggests a reduction of the amplitude of single muscle fibres. After 1.5 min contraction there is a slight increase in the turns to force ratio whereas the ratio amplitude to force 100"
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Fig. 2. Relationship between turns/sec (×), total amplitude (©) and contraction force. Figures are obtained after 20 sec of a maintained contraction level and from the fatigue curve (9¢rand O) for the high force steps (> 80% MUC) (Ch.H. and V.D.). Turns/sec and total amplitude (mV) are expressed as percentages of the values reached at 100% maximal voluntary force. Fig. 3. Time course of fatigue under normal and isehaernic condition. The thick line with standard deviations represents the control values obtained in 4 different experiments of one subject (V.D.). The thin lines represent the figures obtained after 5 rain [ ), 10 min (- - - -) and 15 min (. . . . . ) of ischaemia before contraction. The figures of the isehaemic experiments are expressed as a percentage of the control value without isehaemia.
191
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(2) Stimulation of the ulnar nerve under ischaemic conditions The ulnar nerve was stimulated with the arm relaxed (a) at the beginning of the experiment, (b) during ischaemia before MVC (after 5, 10 or 15 min of ischaemia) and (c) after MVC. The amplitude of the muscle action potential (MAP) and the twitch tension are shown for the 3 conditions in Fig. 7. Curing ischaemia before MVC there is a moderate reduction of AP-amplitude and a less pronounced reduction of twitch tension. These reductions are dependent on the duration of the preceding ischaemia. After 11/2 rain of MVC both measurements are further reduced, but in the experiments with a preceding ischaemia of 10 and 15 min the reduction in the twitch tension is now much more marked than that of the APamplitude. This means, for example, that in the experiment with a circulation arrest of amp
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192
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Fig. 6. Ratio of turns/force (A) and amplitude/force (B) during fatigue, with and without ischaemia. Same symbols as in Fig. 3. Fig. 7. Stimulation of the ulnar nerve. MAP-amplitude (A) and twitch tension (B) are plotted as percentages of their control values without ischaemia. (1) control value, (2) with ischaemia, before maximal voluntary contraction, (3) with ischaemia, after maximal voluntary contraction. The duration of the preceding ischaemia is indicated with the same symbols as in Fig. 3. 15 min the twitch tension is reduced twice as much as the AP-amplitude. A reduction of the AP-amplitude of individual muscle fibres after muscle fatigue during repeated stimulation has been observed in animal experiments and it was suggested that it is caused by reactions connected with the fibre contractions (Liittgau 1965). Failure of the neuromuscular junction, suggested by Stephens and Taylor (1972), is unlikely to be the cause of the moderately diminished AP response after MVC (under ischaemia): neither would it explain the greater reduction of twitch tension.
(3) Influence of ischaemia on turns, amplitude and force during maximal voluntary contraction There are some observations common to all the experiments under ischaemia, which do not depend upon the different periods ofischaemia applied to the arm before MVC. After about 1 min of contraction the force falls rapidly towards zero (Fig. 3) whereas the decline of the amplitude curves is less steep (Fig. 5). There is no decay of turns, the turn slope remaining in the range of the non-ischaemic controls during this period (Fig. 4). This is further illustrated in Figs. 6A and 6B: after 1 min of MVC the proportion of turns to force rises rapidly and reaches a ratio of 6 % turns to 1% force in the next 20-30 sec, before the force reaches the zero level. The ratio amplitude to force rises later and to a smaller extent (Fig. 6B). Consequently the striking observation in all ischaemic experiments is the persistence of turns in the range of the non-ischaemic controls, whereas force and amplitude decline at nearly the same rate.
(4) Dependence of the neuromuscular system on the duration of ischaemia before contraction The difference between the recordings obtained at the beginning of MVC
193 without ischaemia and those with a preceding (15 min) and persisting ischaemia can be seen in Figs. 1A and lB. In the ischaemic condition (B) large potentials are lacking and the force is reduced, whereas the number of impulses as measured by the turn pulses is only slightly reduced compared with the control contraction. After a period of 5, 10 or 15 rain ischaemia the force is already reduced at the beginning of the contraction, the extent of the reduction depending on the duration of the preceding ischaemia. However, the duration of force maintenance is about the same for all 3 ischaemic conditions. As can be seen in Fig. 3 the slope of the fatigue curve obtained after 15 min ischaemia appears flatter than the curve after 5 rain ischaemia. The turn pulses remain within the range of 2 standard deviations of the control values (Fig. 4) during the first 70 sec in the 3 ischaemic conditions. That means the ratio turns to force is raised after a preceding ischaemic period (to 1.8 % turns to force) and is kept constant until the steep increase after about 1 min takes place (Fig. 5). The decline of turns parallels that of force at a higher level in this first rain of contraction. Only in the experiments with a 15 min preceding ischaemia were the amplitude values reduced in about the same proportion as the force (Fig. 5). Consequently the ratio of amplitude to force is not increased in the first min of MVC and after 1 min only slightly increased (Fig. 6B). In summary, the main influence of ischaemia before MVC consists in the reduction of the initial maximal force and to a lesser extent also of initial amplitude (depending on the duration of ischaemia) whereas the turns, representing the number of impulses, remain nearly unchanged in respect to the nonischaemic control values. DISCUSSION The present results suggest that there are two different mechanisms underlying muscle fatigue which are prominent at different phases of maximal voluntary contraction, as has also been suggested by other authors (Stephens and Taylor 1972). It is known, that during MVC the blood flow in the contracting muscle is restricted or arrested (Barcroft and Millen 1939; Naess and Storm-Mathisen 1955; Humphreys and Lind 1963; Mottram 1963) and it was suggested by several authors (Fox and Kenmore 1967; Dahlb~tck 1970; Lundborg 1970; Stephens and Taylor 1972) that impulse transmission in the neuromuscular system is the mechanism most sensitive to ischaemia and is therefore responsible for the initial decline of force. This hypothesis seems to be supported by the observation that the integrated EMG of the contracting muscle declines in the same way as the force and that the stimulated AP-amplitude is reduced in this phase (Stephens and Taylor 1972). But this reduction could also be explained by diminished fibre action potential amplitudes as reported by Lfittgau (1965) and which is supported by the diminished amplitude to turn relationship in our results. The results presented here clearly show that even if the contractile force and twitch tension amplitude nearly reach the zero level during ischaemia, impulses, as indicated by turns, remain in the "normal" non-ischaemic control range or are only slightly diminished in frequency. In accordance with this, stimulation of the ulnar
194 nerve under ischaemia after MVC also shows a much more reduced twitch tension than AP-amplitude. The single motor unit recordings of DahlNick, Ekstedt and Stalberg (1970) also show, that a blocking of impulses at the neuromuscular junction during ischaemia occurs only after the transmission of 3500-7000 impulses. Even if all motor units fire at the highest rates (about 100/sec), there should not be a neuromuscular blocking of impulses before 35 sec of maximal contraction. Thus the decline of force in the first 30 sec cannot be explained by this mechanism. However, these observations are not strictly relevant to maximal contractions, because the experiments were performed at discharge rates between 5-16/sec. Recent investigations on motor unit firing rates have shown that at the beginning of a strong contraction the motoneurone discharge frequency is usually raised to 80-150/sec (Marsden, Meadows and Merton 1971 ; Gillies 1972; Biidingen and Freund 1976) and that the neurons then slow down progressively during a prolonged effort to a rate of 20-25/sec within about 30 sec and stabilise at this rate (Marsden, Meadows and Merton 1971). At steady contractions the maximal firing rates reported by other authors are 20-30/sec (Tanji and Kato 1973; Freund, Btidingen and Dietz 1975). This change of firing rate from about 100 to 25/sec would explain the high-frequency decay related to muscle fatigue seen in the spectrum analysis of the E M G (Kadefors, Kaiser and Petersen 1968; Broman, Magnusson and Petersen 1973). An appropriate mechanical effect of these high discharge rates can be expected because an increase of force is reported for stimulation rates up to 50-60/sec (Rack and Westbury 1969; MitnerBrown, Stein and Yemm 1973; Bigland-Ritchie et al. 1975). Thus in the first phase of MVC the decline of discharge frequency and force take an optimal course because higher as well as lower discharge rates would reduce the force development as was established by Naess and Storm-Mathisen (1955) and confirmed by Marsden, Meadows and Merton (1976). It is suggested, that this represents the main mechanism underlying the first phase of muscle fatigue. Because of the stabilisation of motoneurone firing rates there must be a different mechanism for the second phase of muscle fatigue with a less marked loss of tension. The slow decrease of force and amplitude in our results suggests that reduction of the action potentials of single fibres, associated with contractile element fatigue, as shown during repetitive stimulation in animal preparations by Ltittgau (1965) and Hanson and Persson (1971) are predominant. The slight increase of turns during this phase would indicate that the loss of muscular force is partly compensated by an increase in discharge rate, possibly as a result of a reduced Goigi tendon organ inhibition on amotoneurones (c.f. Houk, Singer and Goldman 1970). Consequently the impulse transmission must be less fatiguable than the contractile elements of a muscle. It was suggested by Stephens and Taylor (1972) that motor units with a low threshold are more fatiguable than those with a high threshold. However, recent investigations of this group (Stephens and Usherwood 1975) have shown, that high threshold units are more fatiguable, which is supported by animal studies (Burke, Levine, Tsairis and Zajac 1973; Proske and Waite 1974). This would be an explanation for the common experience, that weak voluntary contraction force can be maintained without fatigue for much longer periods than strong contractions.
195 In a relaxed state the impulse conduction by the nerve fibres seems to be most affected by ischaemia. The observation, that the reduction of force and amplitude at the beginning of MVC depends on the duration of the preceding ischaemia suggests that there is an increasing loss of conducting nerve fibres. This is also reflected by a corresponding reduction of AP-amplitude under stimulation of the ulnar nerve. The minor reduction of the stimulated twitch amplitude is less crucial in this context because the twitch amplitude does not necessarily reflect the tetanic force level under ischaemia. The nearly normal impulse rate and the force decline, which proportionally stays the same in all ischaemic experiments, independent of the preceding duration of ischaemia, indicate that the initial force loss could not be due to neuromuscular transmission failure. The possibility of a selective failure of impulse transmission for the large phasic motor units from the beginning of contraction seems highly improbable but cannot be excluded. The latter result and the preserved twitch response also indicate that the contractile element functioning is scarcely affected at the beginning of contraction. The question arises which type, high or low threshold motor units, drop out. In the literature controversial observations are reported in this field. While Magladery et al. (1950) showed that motor nerve fibres with the highest conduction velocity are most sensitive to ischaemia, Hershey (1966) found a greater ischaemic effect on the smaller nerve fibres and Ruskin, Tanyag-Jocson and Rogoff (1967) observed a decrease in the conduction velocity of all fibres without significant differences between large and small motor units. Since there is a marked force and amplitude loss with only slight reduction of turns only a small number of motor units with high threshold, which produce a lot of force, can be affected and be responsible for the initial force reduction. Thus these results suggest that nerve fibres with a high conduction velocity are blocked first. In all experiments reported here neuro-muscular transmission seems to be the most resistant link to ischaemia within the neuromuscular system. This conclusion stands in contrast to those drawn in the papers by Fox and Kenmore (1967), Dahlb/ick (1970), Lundborg (1970) and Stephens and Taylor (1972) in which the hypothesis was put forward that the neuromuscular junction is the most sensitive structure in an ischaemic condition. This difference can be explained by the use of the method of automatic E M G analysis to give an indication of the number of motor units which are being activated and hence not affected by block of transmission. ACKNOWLEDGEMENTS The author thanks Dr. R. G. Willison for his encouragement in this study and critical review of the manuscript and Dr. P. A. Merton, Prof. A. Taylor, Dr. J. A. Stephens and Dr. Noth for helpful comments on the paper.
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