EFFECTS OF ELECTRICAL STIMULATION PATTERN ON QUADRICEPS ISOMETRIC FORCE AND FATIGUE IN INDIVIDUALS WITH SPINAL CORD INJURY GAELLE DELEY, PhD,1,2 JEREMY DENUZILLER, MS,1 NICOLAS BABAULT, PhD,1 and JOHN ANDREW TAYLOR, PhD2 1
INSERM - U1093 Cognition, Action, et Plasticit e Sensorimotrice, Universit e de Bourgogne, Dijon, France Cardiovascular Research Laboratory, Spaulding Rehabilitation Hospital, and Department of Physical Medicine and Rehabilitation, Harvard Medical School, Boston, Massachusetts, USA Accepted 25 November 2014
2
ABSTRACT: Introduction: Variable frequency trains (VFT) or train combinations have been suggested as useful strategies to offset the rapid fatigue induced by constant frequency trains (CFT) during electrical stimulation. However, most studies have been of short duration with limited functional application in those with spinal cord injury (SCI). We therefore tested force and fatigue in response to VFT, CFT, and combined patterns in strength training-like conditions (6-s contractions). Methods: Ten SCI individuals underwent either CFT or VFT patterns until target torque was no longer produced and then switched immediately to the other pattern. Results: Target torque was reached more times when VFT was used first (VFT: 6.7 6 0.8 vs. CFT: 3.5 6 0.2 contractions, P < 0.05) and when it was followed by the CFT pattern (VFT-CFT: 10.3 6 1.2 vs. CFT-VFT: 6.9 6 1.2 contractions, P < 0.05). Conclusions: These findings suggest that for the same initial forces the VFT pattern is less fatiguing than CFT and that when combining train types, VFT should be used first. Muscle Nerve 52: 260–264, 2015
Electrical stimulation can be used to activate nerve branches to trigger skeletal muscle contraction.1,2 Depending on the stimulation pattern applied, it can be used for a variety of purposes including postexercise recovery, muscle strengthening, pain management, and muscle atrophy prevention.3–6 In addition, functional electrical stimulation (FES) has been used to facilitate exercise in individuals with spinal cord injury (SCI). It can produce functionally useful movements such as leg flexion/extension, standing, walking, cycling, and even rowing.2,7–9 However, despite its utility,10,11 rapid fatigue limits its effectiveness in those with SCI. The ideal FES pattern for muscle activation would be one that produces sufficiently high forces while minimizing fatigue. FES has traditionally consisted of constant-frequency trains (CFT): brief tetanic pulses of stimulation separated by constant interpulse intervals that produce a rapid rate of muscle tension but also rapid fatigue.12 It has been Abbreviations: CFT, constant-frequency trains; FES, functional electrical stimulation; SCI, spinal cord injury; SD, standard deviation; VFT, variablefrequency trains. Key words: constant frequency trains; FES; functional electrical stimulation; muscle fatigue; variable frequency trains des Sciences du Sport, Correspondence to: G. Deley; Faculte de Bourgogne, BP 27877, 21078 Dijon Cedex, France; Universite e-mail: [email protected] C 2014 Wiley Periodicals, Inc. V
Published online 27 November 2014 in Wiley Online Library (wileyonlinelibrary. com). DOI 10.1002/mus.24530
260
Stimulation Pattern and Fatigue
suggested that a stimulation pattern with variablefrequency trains (VFT) may limit fatigue development compared to the CFT pattern.13 VFT begins with 2 or 3 pulses separated by brief interpulse intervals, followed by regularly spaced pulses with longer interpulse intervals. This pattern is based on the “catchlike phenomenon”; tension is enhanced when an initial brief interpulse interval is added to the beginning of a subtetanic, less-fatiguing, train of pulses.14 In addition, the VFT pattern has been demonstrated to be better than the CFT pattern at generating force in fatigued muscles.15 There are also data that suggest switching stimulation patterns may be the best approach to offset the rapid fatigue that occurs with electrical stimulation in those with SCI.16 However, most of these data were derived from short (167-ms) stimulation patterns, whereas functional contractions require longer stimulation patterns of usually between 2 and 6 s.8,17,18 If FES is to be used to facilitate exercise in those with SCI, it is important to find a stimulation pattern that minimizes fatigue and allows exercise at high intensities for longer durations (i.e., to perform more contractions before being fatigued). The aim of this study was to measure force and fatigue development in response to a stimulation pattern which has been proposed for strengthening in SCI people (CFT)8 as compared with a VFT pattern which has never been tested in “strengthening like” conditions. In addition, this study aimed to determine if a combination of stimulation patterns (i.e., CFT followed by VFT or vice versa) is more effective at generating force in fatigued muscle. MATERIAL AND METHODS
Ten adults with spinal cord injury (8 men, 2 women, age 34.0 6 4.0, 9.8 6 2.7 years postinjury, American Spinal Injury Association motor score A or B, Table 1) at the neurological level of C5-T12 participated in the study. All volunteers were: (1) medically stable, (2) able to follow simple directions, (3) able to reach a certain range of motion in their legs, (4) able to respond to electrical stimulation of the quadriceps muscles, and (5) able to transfer from their chair to the isokinetic dynamometer. At the time of the study, all subjects
Subjects.
MUSCLE & NERVE
August 2015
Table 1. Characteristics of the study subjects. n Gender (M/W) Age (years) Weight (kg) Height (cm) ASIA classification (n) Level of lesion Time post-injury (yr)
10 8/2 33.9 6 1.2 74.0 6 4.9 176.0 6 3.5 A (9), B (1) C5 to T12 9.5 6 2.5
M, men; W, women; ASIA, American Spinal Injury Association.
were participating in an FES rowing exercise training program and were asked to refrain from training for at least 24 h before testing. The study was conducted according to the declaration of Helsinki, and approval for the project was obtained from the local Institutional Review Board. Each participant read and signed a written informed consent document outlining the procedures of the experiment. Experimental Design. Each subject underwent 2 testing sessions separated by at least 24 h. During each testing session, isometric muscle torque was measured under 2 sequential electrical stimulation train patterns. For the CFT pattern, this corresponded to 6 s of contraction generated by continuous 40 HZ stimulation with a pulse width of 450 ms (based on the strengthening protocol described by Taylor et al.8); for the VFT pattern, this corresponded to 6 s of contraction generated by an 80 HZ doublet followed by continuous 20 HZ stimulation with a pulse width of 450 ms. The characteristics of the VFT pattern were chosen based on results of preliminary studies (unpublished data and Deley et al.19). Stimulation was applied to the quadriceps of either the right or left leg, whichever had the greatest responsiveness to stimulation (highest visible contraction at a given intensity). Subjects were placed on an isokinetic dynamometer (Biodex corporation, Shirley, New York) with Velcro straps across the thorax for stability. The leg was fixed to the dynamometer lever-arm, and the axis of rotation of the dynamometer was aligned to the lateral femoral condyle that indicates the anatomical joint axis of the knee. The stimulation programs were applied at an angle of 90 (0 corresponding to full extension). Stimulation was achieved using biphasic square pulses, with a Compex 2 stimulator (Compex, Medicompex SA, Ecublens, Switzerland) attached to 2 10 3 5 cm adhesive electrodes. One electrode was placed over the muscle belly of the rectus femoris muscle and the other over the muscle belly of the vastus medialis. Following set-up, maximal evoked torque was determined with the 2 different stimuStimulation Pattern and Fatigue
lation patterns by recording the torque response of the paralyzed muscle to a series of 6-s stimulation trains increasing by 10 mA from 15 mA and up to maximal (120 mA). Trains were delivered at a rate of 1 every 10 s. There were at least 10 min of rest after maximal torque determination before the time to fatigue trial. After determination of maximal torque, the first stimulation pattern was applied to generate 50% of maximal CFT torque and was maintained to fatigue. Fatigue was defined as a 20% decline in torque to 40% of maximal torque observed over 2 consecutive contractions. At that point, the protocol switched immediately to the other stimulation pattern. The intensity of stimulation for the second pattern was set at a level that produced the original target torque (i.e., 50% of maximal CFT torque). Stimulation was stopped and the session was ended when the second pattern of stimulation failed to produce target torque for 3 consecutive contractions. The order in which each subject received the 2 stimulation patterns was randomized to different days. Data Analysis. Torque was digitized online at a 2 kHZ sampling frequency (Windaq, Dataq Instruments, Cambridge, Massachusetts) and stored for subsequent analysis (Biopac sytems, Inc., USA). The primary dependent variable was the number of contractions reaching target torque in response to either pattern (CFT and VFT), both alone and in combination (i.e., CFT followed by VFT and VFT followed by CFT). The peak torque developed during the first and last contractions of each stimulation pattern was measured, and the percentage change was calculated to quantify the magnitude of fatigue induced. Total work produced over each session was calculated by adding the torque / time integral obtained for each contraction.
Data are expressed as mean 6 SD. Paired t-tests were used to compare stimulation intensity, number of contractions, percentage of torque, and total work decreases obtained with each pattern. The normality of the data was tested using the Kolmogorov test for all studied parameters before statistical analysis. A 2-way analysis of variance (ANOVA) with repeated-measures (pattern 3 time) was then used to compare the peak torque. Time corresponded to the first or last contraction of a stimulation pattern. When the P-value of the ANOVA achieved significance, a post hoc Newman-Keuls test was used. Significant difference was accepted when P < 0.05.
Statistics.
RESULTS
When used as the first pattern of the session, CFT required lower stimulus intensity than VFT to MUSCLE & NERVE
August 2015
261
FIGURE 1. Evolution of the torque measured during the first (black symbols) and last (white symbols) contractions induced by constant frequency trains (CFT pattern) and variable frequency trains (VFT pattern) during the 2 testing sessions (left panel: CFT followed by VFT; right panel: VFT followed by CFT). * Significantly different from first contraction within stimulation pattern, # Significantly different from last contraction across stimulation patterns (P < 0.05).
generate 50% of maximal force (76 6 5 mA vs. 112 6 3 mA, P < 0.05). When used as the second program of the session, the CFT pattern required a stimulus intensity similar to VFT (113 6 5 mA vs. 110 6 9 mA, P 5 0.19). The VFT pattern required similar intensities to generate the target force regardless of whether it was the first or second pattern used in the session. Figure 1 shows the torque produced for the first and last stimulation for each pattern when it occurred first and when it occurred second. Initial stimulation with both CFT and VFT patterns resulted in significant fatigue with torque decreases between the first and last contractions (CFT: 41.8 6 7.2 to 21.4 6 3.0 N.m; VFT: 43.6 6 7.4 to 29.6 6 5.1 N.m, both P < 0.05). This decrease was significantly greater with the CFT pattern (244.3 6 3.3% vs. 231.7 6 1.8%, P < 0.05). When used as the second pattern of stimulation, both CFT and VFT patterns increased torque toward target, but the force produced by the VFT pattern tended to be lower than the initial force produced by the CFT pattern (35.3 6 5.0 vs. 41.8 6 7.2 N.m, P 5 0.06). However, both patterns evoked similar decreases in torque when applied second (VFT: 229.4 6 2.8%, P < 0.05; CFT: 226.3 6 3.5%, P < 0.05). Initial stimulation with the CFT pattern resulted in fewer contractions than initial stimulation with VFT before torque failed to reach target (3.5 6 0.2 vs. 6.7 6 0.8, P < 0.05; Fig. 1). Both patterns resulted in a similar number of target contractions when used as the second pattern of stimulation (3.4 6 1.1 and 3.6 6 0.8 for VFT and CFT, respectively; P 5 0.86). As a result, the total number of contractions performed over the entire session was significantly greater when starting with 262
Stimulation Pattern and Fatigue
the VFT pattern and switching to the CFT pattern compared with the opposite (10.3 6 1.2 vs. 6.9 6 1.1 contractions, P < 0.05). Moreover, as shown in Figure 2, torque evolution during contractions is completely different with the 2 stimulation patterns. Thus, due to the different patterns of torque production and the greater number of total contractions, the total work produced over the trial with the VFT pattern followed by CFT was almost double that produced with the opposite pattern (764.8 6 118.4 for VFT and 518.0 6 113.7 Nm.s for a total work over the
FIGURE 2. Mechanical data from a representative subject with both 6-s contraction and 6-s relaxation stimulation patterns. A: Constant frequency trains (CFT pattern) followed by variable frequency trains (VFT pattern). B: VFT followed by CFT. The CFT followed by VFT pattern induced a total of 12 contractions, whereas the VFT followed by CFT pattern induced a total of 16 contractions. MUSCLE & NERVE
August 2015
session of 1218.1 6 211.0 vs. 418.5 6 65.7 for CFT and 445.1 6 84.5 for VFT for a total work over the session of 696.7 6 120.2 Nm.s, P 5 0.01). DISCUSSION
These data provide insight into a stimulation pattern that may minimize fatigue during FES training sessions and therefore allow those with SCI to exercise at higher intensities for longer durations. We found that the VFT pattern was more resistant to fatigue as compared with the CFT pattern, and that when combining train types, VFT should be used first to best offset rapid fatigue occurring during FES. Similarly, several authors previously showed that for the same initial forces, the VFT pattern induces lower declines in force than the CFT pattern.19,20 Although opposite results have also been reported,21,22 it may be difficult to compare our results with those in the literature, because no prior studies explored the potential of VFT stimulation patterns on quadriceps force and fatigue during functional contractions (lasting 2 to 6 s) in those with an SCI. There are several possible explanations for the greater resistance to fatigue with the initial VFT pattern as compared with the initial CFT pattern. The first hypothesis relates to motor unit recruitment which might be different when stimulation frequencies change. Electrical stimulation causes continuous contractile activity in the same population of superficial muscle fibers (i.e., those with axonal branches in proximity to the stimulating electrodes) irrespective of neuromuscular transmission-propagation failure,23 resulting in rapidly decreasing force production. Changes in stimulation characteristics (e.g., frequency, intensity) allow depolarization of new fibers located at a different distance from the electrode. Moreover, lower stimulation frequencies lead to less fatigue development.24 Thus, given that it incorporates both changes in and lower frequencies of stimulation, the VFT pattern should be less fatiguing than the CFT pattern. Indeed, it has been demonstrated that high and low frequencies induce different physiological events implicated in neuromuscular fatigue. In vitro or in situ stimulation of skeletal muscle with high-frequency patterns provokes force decline due to failure of muscle excitability, whereas stimulation with low-frequency patterns provokes force decline due to metabolic changes that influence excitation-contraction coupling.25 Denervated skeletal muscle in SCI may be more likely to fatigue due to the latter than the former. Indeed, Papaiordanidou et al.26 demonstrated that a low-frequency electrical stimulation session induced significant fatigue development in SCI people, which was attributed to impaired crossStimulation Pattern and Fatigue
bridge force-generating capacity, without modification of spinal excitability or muscle excitability. In addition, it can be hypothesized that the higher frequencies used during CFT may have induced changes in axonal excitability and, therefore, a greater loss of motor units. This might explain the greater torque decline after CFT as compared with VFT. Unfortunately, the methodology used in our study did not allow us to determine which of these mechanisms might explain the results. In a further study, it would be interesting to repeat this protocol and record mechanical and physiological responses to electrical twitches as well as 20 and 80 HZ tetanic contractions. This would allow us to learn more about the recruited motor units and to quantify low and high frequency fatigue.24 A second explanation for these results relates to the catch-like property of skeletal muscles.12,27,28 Catch-like stimulations (e.g., VFT pattern) deliver a second pulse when the muscle series elastic elements have been stretched by the response to the first pulse.18,29 The second pulse following closely after the first elicits a force response substantially greater than the sum of 2 twitches elicited separately.30 Moreover, if the force transmission in the muscle-tendon complex is more effective due to the fast stretch of series elastic elements during a VFT pattern, these contractions would have a lower metabolic cost, hence increasing the amount of work that can be produced before fatigue. Third, increased Ca21 release from the sarcoplasmic reticulum due to the initial high-frequency burst has been proposed as a potential mechanism for greater force maintenance with a VFT pattern.28 It has been suggested that the greater Ca21 release overcomes impairment in excitationcontraction coupling that results from progressively less Ca21 release from the sarcoplasmic reticulum with increasing fatigue. Ratkevicius and Quistorff,28 therefore, concluded that the major advantage of the VFT pattern is associated with the ability to produce more force in muscles affected by impairment of Ca21 release. However, this may be the least likely explanation, because the VFT pattern applied after the muscle had fatigued was no more effective than the CFT pattern. In fact, we were surprised to find that switching to a VFT stimulation pattern did not offset fatigue more than switching to a CFT pattern. The data showed that switching stimulation patterns once muscles were fatigued allowed for additional contractions. However, based on previous reports of the particular effectiveness of a VFT pattern on fatigued muscles, we expected more additional contractions when switching from CFT to VFT as compared with VFT followed by CFT.20 This might be due to the greater fatigue initially induced by MUSCLE & NERVE
August 2015
263
the CFT pattern. The decline in force was greater with the initial CFT stimulation than with the initial VFT stimulation. Moreover, individuals with SCI tend to have a higher proportion of fast-twitch fibers, thereby making skeletal muscle highly susceptible to fatigue.31 It may be that when stimulated fast-twitch muscles fibers fatigue, they become unresponsive to stimulation, regardless of current characteristics. In addition, whereas in nonparalyzed people, switching from CFT to VFT supposedly recruits less fatigable slow-twitch fibers, it is likely that, given the SCI-induced myotypological modifications, other fast-twitch fibers will be recruited in those with SCI. In conclusion, this study showed that denervated human skeletal muscle is more fatigue resistant in response to a VFT pattern as compared with a CFT pattern. Moreover, switching from a VFT pattern to a CFT pattern results in greater overall work production. Although this should be explored further, these results are of particular interest for training and rehabilitation after SCI. Indeed, it may be possible to adapt a stimulation switching protocol for FES to allow for production of sufficiently high forces while minimizing fatigue. This work was supported by the National Institutes of Health grant HL117037. REFERENCES 1. Hultman E, Sj€ oholm H. Energy metabolism and contraction force of human skeletal muscle in situ during electrical stimulation. J Physiol 1983;345:525–532. 2. Rattay F, Resatz S, Lutter P, Minassian K, Jilge B, Dimitrijevic MR. Mechanisms of electrical stimulation with neural prostheses. Neuromodulation 2003;6:42–56. 3. Babault N, Cometti C, Maffiuletti NA, Deley G. Does electrical stimulation enhance post-exercise performance recovery? Eur J Appl Physiol 2011;111:2501–2507. 4. Babault N, Cometti G, Bernardin M, Pousson M, Chatard JC. Effects of electromyostimulation training on muscle strength and power of elite rugby players. J Strength Cond Res 2007;21:431–437. 5. Deley G, Cometti C, Fatnassi A, Paizis C, Babault N. Effects of combined electromyostimulation and gymnastics training in prepubertal girls. J Strength Cond Res 2011;25:520–526. 6. Deley G, Kervio G, Verges B, Grassi B, Casillas JM. Comparison of low-frequency electrical myostimulation and conventional aerobic exercise training in patients with chronic heart failure. Eur J Cardiovasc Prev Rehabil 2005;12:226–233. 7. Belanger M, Stein RB, Wheeler GD, Gordon T, Leduc B. Electrical stimulation: can it increase muscle strength and reverse osteopenia in spinal cord injured individuals? Arch Phys Med Rehabil 2000;81: 1090–1098. 8. Taylor JA, Picard G, Widrick JJ. Aerobic capacity with hybrid FES rowing in spinal cord injury: comparison with arms-only exercise and preliminary findings with regular training. PM R 2011;3:817–824. 9. Wheeler GD, Andrews B, Lederer R, Davoodi R, Natho K, Weiss C, et al. Functional electric stimulation-assisted rowing: increasing cardi-
264
Stimulation Pattern and Fatigue
10.
11. 12.
13.
14. 15.
16.
17.
18.
19.
20.
21.
22.
23.
24.
25.
26.
27.
28.
29.
30. 31.
ovascular fitness through functional electric stimulation rowing training in persons with spinal cord injury. Arch Phys Med Rehabil 2002; 83:1093–1099. Isakov E, Mizrahi J, Najenson J. Biomechanical and physiological evaluation of FES-activated paraplegic patients. J Rehabil Res Dev 1986;23:9–19. Peckham PH, Knutson JS. Functional electrical stimulation for neuromuscular adaptations. Annu Rev Biomed Eng 2005;7:327–360. Binder-Macleod SA, Barker CB III. Use of a catchlike property of human skeletal muscle to reduce fatigue. Muscle Nerve 1991;14:850– 857. Binder-Macleod SA, Scott WB. Comparison of fatigue produced by various electrical stimulation trains. Acta Physiol Scand 2001;172: 195–203. Burke RE, Rudomin P, Zajac FE. Catch property in single mammalian motor units. Science 1970;168:122–124. Binder-Macleod SA, Lee SCK, Russ DW, Kucharski LJ. Effects of activation pattern on human skeletal muscle fatigue. Muscle Nerve 1998; 21:1145–1152. Scott WB, Binder-Macleod SA. Changing stimulation patterns improves performance during electrically elicited contractions. Muscle Nerve 2003;28:174–180. Crameri RM, Weston AR, Rutkowski S, Middleton JW, Davis GM, Sutton JR. Effects of electrical stimulation leg training during the acute phase of spinal cord injury: a pilot study. Eur J Appl Physiol 2000;83:409–415. Sabatier MJ, Stoner L, Mahoney ET, Black C, Elder C, Dudley GA, et al. Electrically stimulated resistance training in SCI individuals increases muscle fatigue resistance but not femoral artery size or blood flow. Spinal Cord 2006;44:227–233. Deley G, Laroche D, Babault N. Effects of electrical stimulation pattern on quadriceps force production and fatigue. Muscle Nerve 2014; 49:760–763. Bigland-Ritchie B, Zijdewind I, Thomas CK. Muscle fatigue induced by stimulation with and without doublets. Muscle Nerve 2000;23: 1348–1355. Bickel SC, Slade JM, VanHiel LR, Warren GL, Dudley GA. Variable frequency train stimulation of skeletal muscle after spinal cord injury. J Rehab Res Dev 2004;41:33–40. Scott WB, Lee SCK, Johnston TE, Binkley J, Binder-Macleod SA. Effect of electrical stimulation pattern on the force responses of paralyzed human quadriceps muscles. Muscle Nerve 2007;35:471–478. Zory R, Bo€ erio D, Jubeau M, Maffiuletti NA. Central and peripheral fatigue of the knee extensor muscles induced by electromyostimulation. Int J Sports Med 2005;26:847–853. Martin V, Millet GY, Martin A, Deley G, Lattier G. Assessment of lowfrequency fatigue with two methods of electrical stimulation. J Appl Physiol 2004;97:1923–1929. Darques JL, Bendahan D, Roussel M, Giannesini B, Tagliarini F, Le Fur Y, et al. Combined in situ analysis of metabolic and myoelectrical changes associated with electrically induced fatigue. J Appl Physiol 2003;95:1476–1484. Papaiordanidou M, Varray A, Fattal C, Guiraud D. Neural and muscular mechanisms of electrically induced fatigue in patients with spinal cord injury. Spinal Cord 2014;52:246–250. Duchateau J, Hainaut K. Nonlinear summation of contractions in striated muscle. II. Potentiation of intracellular Ca21 movements in single barnacle muscle fibers. J Muscle Res Cell Motil 1986;7: 18–24. Ratkevicius A, Quistorff B. Metabolic costs of force generation for constant-frequency and catchlike-inducing electrical stimulation in human tibialis anterior muscle. Muscle Nerve 2001;25:419–426. Parmiggiani F, Stein RB. Nonlinear summation of contractions in cat muscles. II. Later facilitation and stiffness changes. J Gen Physiol 1981;78:295–311. Binder-Macleod SA, Lee SC. Catchlike property of human muscle during isovelocity movements. J Appl Physiol 1996;80:2051–2059. Dudley-Javoroski S, Shields RK. Muscle and bone plasticity after spinal cord injury: review of adaptations to disuse and to electrical muscle stimulation. J Rehabil Res Dev 2008;45:283–296.
MUSCLE & NERVE
August 2015
INSERM - U1093 Cognition, Action, et Plasticit e Sensorimotrice, Universit e de Bourgogne, Dijon, France Cardiovascular Research Laboratory, Spaulding Rehabilitation Hospital, and Department of Physical Medicine and Rehabilitation, Harvard Medical School, Boston, Massachusetts, USA Accepted 25 November 2014
2
ABSTRACT: Introduction: Variable frequency trains (VFT) or train combinations have been suggested as useful strategies to offset the rapid fatigue induced by constant frequency trains (CFT) during electrical stimulation. However, most studies have been of short duration with limited functional application in those with spinal cord injury (SCI). We therefore tested force and fatigue in response to VFT, CFT, and combined patterns in strength training-like conditions (6-s contractions). Methods: Ten SCI individuals underwent either CFT or VFT patterns until target torque was no longer produced and then switched immediately to the other pattern. Results: Target torque was reached more times when VFT was used first (VFT: 6.7 6 0.8 vs. CFT: 3.5 6 0.2 contractions, P < 0.05) and when it was followed by the CFT pattern (VFT-CFT: 10.3 6 1.2 vs. CFT-VFT: 6.9 6 1.2 contractions, P < 0.05). Conclusions: These findings suggest that for the same initial forces the VFT pattern is less fatiguing than CFT and that when combining train types, VFT should be used first. Muscle Nerve 52: 260–264, 2015
Electrical stimulation can be used to activate nerve branches to trigger skeletal muscle contraction.1,2 Depending on the stimulation pattern applied, it can be used for a variety of purposes including postexercise recovery, muscle strengthening, pain management, and muscle atrophy prevention.3–6 In addition, functional electrical stimulation (FES) has been used to facilitate exercise in individuals with spinal cord injury (SCI). It can produce functionally useful movements such as leg flexion/extension, standing, walking, cycling, and even rowing.2,7–9 However, despite its utility,10,11 rapid fatigue limits its effectiveness in those with SCI. The ideal FES pattern for muscle activation would be one that produces sufficiently high forces while minimizing fatigue. FES has traditionally consisted of constant-frequency trains (CFT): brief tetanic pulses of stimulation separated by constant interpulse intervals that produce a rapid rate of muscle tension but also rapid fatigue.12 It has been Abbreviations: CFT, constant-frequency trains; FES, functional electrical stimulation; SCI, spinal cord injury; SD, standard deviation; VFT, variablefrequency trains. Key words: constant frequency trains; FES; functional electrical stimulation; muscle fatigue; variable frequency trains des Sciences du Sport, Correspondence to: G. Deley; Faculte de Bourgogne, BP 27877, 21078 Dijon Cedex, France; Universite e-mail: [email protected] C 2014 Wiley Periodicals, Inc. V
Published online 27 November 2014 in Wiley Online Library (wileyonlinelibrary. com). DOI 10.1002/mus.24530
260
Stimulation Pattern and Fatigue
suggested that a stimulation pattern with variablefrequency trains (VFT) may limit fatigue development compared to the CFT pattern.13 VFT begins with 2 or 3 pulses separated by brief interpulse intervals, followed by regularly spaced pulses with longer interpulse intervals. This pattern is based on the “catchlike phenomenon”; tension is enhanced when an initial brief interpulse interval is added to the beginning of a subtetanic, less-fatiguing, train of pulses.14 In addition, the VFT pattern has been demonstrated to be better than the CFT pattern at generating force in fatigued muscles.15 There are also data that suggest switching stimulation patterns may be the best approach to offset the rapid fatigue that occurs with electrical stimulation in those with SCI.16 However, most of these data were derived from short (167-ms) stimulation patterns, whereas functional contractions require longer stimulation patterns of usually between 2 and 6 s.8,17,18 If FES is to be used to facilitate exercise in those with SCI, it is important to find a stimulation pattern that minimizes fatigue and allows exercise at high intensities for longer durations (i.e., to perform more contractions before being fatigued). The aim of this study was to measure force and fatigue development in response to a stimulation pattern which has been proposed for strengthening in SCI people (CFT)8 as compared with a VFT pattern which has never been tested in “strengthening like” conditions. In addition, this study aimed to determine if a combination of stimulation patterns (i.e., CFT followed by VFT or vice versa) is more effective at generating force in fatigued muscle. MATERIAL AND METHODS
Ten adults with spinal cord injury (8 men, 2 women, age 34.0 6 4.0, 9.8 6 2.7 years postinjury, American Spinal Injury Association motor score A or B, Table 1) at the neurological level of C5-T12 participated in the study. All volunteers were: (1) medically stable, (2) able to follow simple directions, (3) able to reach a certain range of motion in their legs, (4) able to respond to electrical stimulation of the quadriceps muscles, and (5) able to transfer from their chair to the isokinetic dynamometer. At the time of the study, all subjects
Subjects.
MUSCLE & NERVE
August 2015
Table 1. Characteristics of the study subjects. n Gender (M/W) Age (years) Weight (kg) Height (cm) ASIA classification (n) Level of lesion Time post-injury (yr)
10 8/2 33.9 6 1.2 74.0 6 4.9 176.0 6 3.5 A (9), B (1) C5 to T12 9.5 6 2.5
M, men; W, women; ASIA, American Spinal Injury Association.
were participating in an FES rowing exercise training program and were asked to refrain from training for at least 24 h before testing. The study was conducted according to the declaration of Helsinki, and approval for the project was obtained from the local Institutional Review Board. Each participant read and signed a written informed consent document outlining the procedures of the experiment. Experimental Design. Each subject underwent 2 testing sessions separated by at least 24 h. During each testing session, isometric muscle torque was measured under 2 sequential electrical stimulation train patterns. For the CFT pattern, this corresponded to 6 s of contraction generated by continuous 40 HZ stimulation with a pulse width of 450 ms (based on the strengthening protocol described by Taylor et al.8); for the VFT pattern, this corresponded to 6 s of contraction generated by an 80 HZ doublet followed by continuous 20 HZ stimulation with a pulse width of 450 ms. The characteristics of the VFT pattern were chosen based on results of preliminary studies (unpublished data and Deley et al.19). Stimulation was applied to the quadriceps of either the right or left leg, whichever had the greatest responsiveness to stimulation (highest visible contraction at a given intensity). Subjects were placed on an isokinetic dynamometer (Biodex corporation, Shirley, New York) with Velcro straps across the thorax for stability. The leg was fixed to the dynamometer lever-arm, and the axis of rotation of the dynamometer was aligned to the lateral femoral condyle that indicates the anatomical joint axis of the knee. The stimulation programs were applied at an angle of 90 (0 corresponding to full extension). Stimulation was achieved using biphasic square pulses, with a Compex 2 stimulator (Compex, Medicompex SA, Ecublens, Switzerland) attached to 2 10 3 5 cm adhesive electrodes. One electrode was placed over the muscle belly of the rectus femoris muscle and the other over the muscle belly of the vastus medialis. Following set-up, maximal evoked torque was determined with the 2 different stimuStimulation Pattern and Fatigue
lation patterns by recording the torque response of the paralyzed muscle to a series of 6-s stimulation trains increasing by 10 mA from 15 mA and up to maximal (120 mA). Trains were delivered at a rate of 1 every 10 s. There were at least 10 min of rest after maximal torque determination before the time to fatigue trial. After determination of maximal torque, the first stimulation pattern was applied to generate 50% of maximal CFT torque and was maintained to fatigue. Fatigue was defined as a 20% decline in torque to 40% of maximal torque observed over 2 consecutive contractions. At that point, the protocol switched immediately to the other stimulation pattern. The intensity of stimulation for the second pattern was set at a level that produced the original target torque (i.e., 50% of maximal CFT torque). Stimulation was stopped and the session was ended when the second pattern of stimulation failed to produce target torque for 3 consecutive contractions. The order in which each subject received the 2 stimulation patterns was randomized to different days. Data Analysis. Torque was digitized online at a 2 kHZ sampling frequency (Windaq, Dataq Instruments, Cambridge, Massachusetts) and stored for subsequent analysis (Biopac sytems, Inc., USA). The primary dependent variable was the number of contractions reaching target torque in response to either pattern (CFT and VFT), both alone and in combination (i.e., CFT followed by VFT and VFT followed by CFT). The peak torque developed during the first and last contractions of each stimulation pattern was measured, and the percentage change was calculated to quantify the magnitude of fatigue induced. Total work produced over each session was calculated by adding the torque / time integral obtained for each contraction.
Data are expressed as mean 6 SD. Paired t-tests were used to compare stimulation intensity, number of contractions, percentage of torque, and total work decreases obtained with each pattern. The normality of the data was tested using the Kolmogorov test for all studied parameters before statistical analysis. A 2-way analysis of variance (ANOVA) with repeated-measures (pattern 3 time) was then used to compare the peak torque. Time corresponded to the first or last contraction of a stimulation pattern. When the P-value of the ANOVA achieved significance, a post hoc Newman-Keuls test was used. Significant difference was accepted when P < 0.05.
Statistics.
RESULTS
When used as the first pattern of the session, CFT required lower stimulus intensity than VFT to MUSCLE & NERVE
August 2015
261
FIGURE 1. Evolution of the torque measured during the first (black symbols) and last (white symbols) contractions induced by constant frequency trains (CFT pattern) and variable frequency trains (VFT pattern) during the 2 testing sessions (left panel: CFT followed by VFT; right panel: VFT followed by CFT). * Significantly different from first contraction within stimulation pattern, # Significantly different from last contraction across stimulation patterns (P < 0.05).
generate 50% of maximal force (76 6 5 mA vs. 112 6 3 mA, P < 0.05). When used as the second program of the session, the CFT pattern required a stimulus intensity similar to VFT (113 6 5 mA vs. 110 6 9 mA, P 5 0.19). The VFT pattern required similar intensities to generate the target force regardless of whether it was the first or second pattern used in the session. Figure 1 shows the torque produced for the first and last stimulation for each pattern when it occurred first and when it occurred second. Initial stimulation with both CFT and VFT patterns resulted in significant fatigue with torque decreases between the first and last contractions (CFT: 41.8 6 7.2 to 21.4 6 3.0 N.m; VFT: 43.6 6 7.4 to 29.6 6 5.1 N.m, both P < 0.05). This decrease was significantly greater with the CFT pattern (244.3 6 3.3% vs. 231.7 6 1.8%, P < 0.05). When used as the second pattern of stimulation, both CFT and VFT patterns increased torque toward target, but the force produced by the VFT pattern tended to be lower than the initial force produced by the CFT pattern (35.3 6 5.0 vs. 41.8 6 7.2 N.m, P 5 0.06). However, both patterns evoked similar decreases in torque when applied second (VFT: 229.4 6 2.8%, P < 0.05; CFT: 226.3 6 3.5%, P < 0.05). Initial stimulation with the CFT pattern resulted in fewer contractions than initial stimulation with VFT before torque failed to reach target (3.5 6 0.2 vs. 6.7 6 0.8, P < 0.05; Fig. 1). Both patterns resulted in a similar number of target contractions when used as the second pattern of stimulation (3.4 6 1.1 and 3.6 6 0.8 for VFT and CFT, respectively; P 5 0.86). As a result, the total number of contractions performed over the entire session was significantly greater when starting with 262
Stimulation Pattern and Fatigue
the VFT pattern and switching to the CFT pattern compared with the opposite (10.3 6 1.2 vs. 6.9 6 1.1 contractions, P < 0.05). Moreover, as shown in Figure 2, torque evolution during contractions is completely different with the 2 stimulation patterns. Thus, due to the different patterns of torque production and the greater number of total contractions, the total work produced over the trial with the VFT pattern followed by CFT was almost double that produced with the opposite pattern (764.8 6 118.4 for VFT and 518.0 6 113.7 Nm.s for a total work over the
FIGURE 2. Mechanical data from a representative subject with both 6-s contraction and 6-s relaxation stimulation patterns. A: Constant frequency trains (CFT pattern) followed by variable frequency trains (VFT pattern). B: VFT followed by CFT. The CFT followed by VFT pattern induced a total of 12 contractions, whereas the VFT followed by CFT pattern induced a total of 16 contractions. MUSCLE & NERVE
August 2015
session of 1218.1 6 211.0 vs. 418.5 6 65.7 for CFT and 445.1 6 84.5 for VFT for a total work over the session of 696.7 6 120.2 Nm.s, P 5 0.01). DISCUSSION
These data provide insight into a stimulation pattern that may minimize fatigue during FES training sessions and therefore allow those with SCI to exercise at higher intensities for longer durations. We found that the VFT pattern was more resistant to fatigue as compared with the CFT pattern, and that when combining train types, VFT should be used first to best offset rapid fatigue occurring during FES. Similarly, several authors previously showed that for the same initial forces, the VFT pattern induces lower declines in force than the CFT pattern.19,20 Although opposite results have also been reported,21,22 it may be difficult to compare our results with those in the literature, because no prior studies explored the potential of VFT stimulation patterns on quadriceps force and fatigue during functional contractions (lasting 2 to 6 s) in those with an SCI. There are several possible explanations for the greater resistance to fatigue with the initial VFT pattern as compared with the initial CFT pattern. The first hypothesis relates to motor unit recruitment which might be different when stimulation frequencies change. Electrical stimulation causes continuous contractile activity in the same population of superficial muscle fibers (i.e., those with axonal branches in proximity to the stimulating electrodes) irrespective of neuromuscular transmission-propagation failure,23 resulting in rapidly decreasing force production. Changes in stimulation characteristics (e.g., frequency, intensity) allow depolarization of new fibers located at a different distance from the electrode. Moreover, lower stimulation frequencies lead to less fatigue development.24 Thus, given that it incorporates both changes in and lower frequencies of stimulation, the VFT pattern should be less fatiguing than the CFT pattern. Indeed, it has been demonstrated that high and low frequencies induce different physiological events implicated in neuromuscular fatigue. In vitro or in situ stimulation of skeletal muscle with high-frequency patterns provokes force decline due to failure of muscle excitability, whereas stimulation with low-frequency patterns provokes force decline due to metabolic changes that influence excitation-contraction coupling.25 Denervated skeletal muscle in SCI may be more likely to fatigue due to the latter than the former. Indeed, Papaiordanidou et al.26 demonstrated that a low-frequency electrical stimulation session induced significant fatigue development in SCI people, which was attributed to impaired crossStimulation Pattern and Fatigue
bridge force-generating capacity, without modification of spinal excitability or muscle excitability. In addition, it can be hypothesized that the higher frequencies used during CFT may have induced changes in axonal excitability and, therefore, a greater loss of motor units. This might explain the greater torque decline after CFT as compared with VFT. Unfortunately, the methodology used in our study did not allow us to determine which of these mechanisms might explain the results. In a further study, it would be interesting to repeat this protocol and record mechanical and physiological responses to electrical twitches as well as 20 and 80 HZ tetanic contractions. This would allow us to learn more about the recruited motor units and to quantify low and high frequency fatigue.24 A second explanation for these results relates to the catch-like property of skeletal muscles.12,27,28 Catch-like stimulations (e.g., VFT pattern) deliver a second pulse when the muscle series elastic elements have been stretched by the response to the first pulse.18,29 The second pulse following closely after the first elicits a force response substantially greater than the sum of 2 twitches elicited separately.30 Moreover, if the force transmission in the muscle-tendon complex is more effective due to the fast stretch of series elastic elements during a VFT pattern, these contractions would have a lower metabolic cost, hence increasing the amount of work that can be produced before fatigue. Third, increased Ca21 release from the sarcoplasmic reticulum due to the initial high-frequency burst has been proposed as a potential mechanism for greater force maintenance with a VFT pattern.28 It has been suggested that the greater Ca21 release overcomes impairment in excitationcontraction coupling that results from progressively less Ca21 release from the sarcoplasmic reticulum with increasing fatigue. Ratkevicius and Quistorff,28 therefore, concluded that the major advantage of the VFT pattern is associated with the ability to produce more force in muscles affected by impairment of Ca21 release. However, this may be the least likely explanation, because the VFT pattern applied after the muscle had fatigued was no more effective than the CFT pattern. In fact, we were surprised to find that switching to a VFT stimulation pattern did not offset fatigue more than switching to a CFT pattern. The data showed that switching stimulation patterns once muscles were fatigued allowed for additional contractions. However, based on previous reports of the particular effectiveness of a VFT pattern on fatigued muscles, we expected more additional contractions when switching from CFT to VFT as compared with VFT followed by CFT.20 This might be due to the greater fatigue initially induced by MUSCLE & NERVE
August 2015
263
the CFT pattern. The decline in force was greater with the initial CFT stimulation than with the initial VFT stimulation. Moreover, individuals with SCI tend to have a higher proportion of fast-twitch fibers, thereby making skeletal muscle highly susceptible to fatigue.31 It may be that when stimulated fast-twitch muscles fibers fatigue, they become unresponsive to stimulation, regardless of current characteristics. In addition, whereas in nonparalyzed people, switching from CFT to VFT supposedly recruits less fatigable slow-twitch fibers, it is likely that, given the SCI-induced myotypological modifications, other fast-twitch fibers will be recruited in those with SCI. In conclusion, this study showed that denervated human skeletal muscle is more fatigue resistant in response to a VFT pattern as compared with a CFT pattern. Moreover, switching from a VFT pattern to a CFT pattern results in greater overall work production. Although this should be explored further, these results are of particular interest for training and rehabilitation after SCI. Indeed, it may be possible to adapt a stimulation switching protocol for FES to allow for production of sufficiently high forces while minimizing fatigue. This work was supported by the National Institutes of Health grant HL117037. REFERENCES 1. Hultman E, Sj€ oholm H. Energy metabolism and contraction force of human skeletal muscle in situ during electrical stimulation. J Physiol 1983;345:525–532. 2. Rattay F, Resatz S, Lutter P, Minassian K, Jilge B, Dimitrijevic MR. Mechanisms of electrical stimulation with neural prostheses. Neuromodulation 2003;6:42–56. 3. Babault N, Cometti C, Maffiuletti NA, Deley G. Does electrical stimulation enhance post-exercise performance recovery? Eur J Appl Physiol 2011;111:2501–2507. 4. Babault N, Cometti G, Bernardin M, Pousson M, Chatard JC. Effects of electromyostimulation training on muscle strength and power of elite rugby players. J Strength Cond Res 2007;21:431–437. 5. Deley G, Cometti C, Fatnassi A, Paizis C, Babault N. Effects of combined electromyostimulation and gymnastics training in prepubertal girls. J Strength Cond Res 2011;25:520–526. 6. Deley G, Kervio G, Verges B, Grassi B, Casillas JM. Comparison of low-frequency electrical myostimulation and conventional aerobic exercise training in patients with chronic heart failure. Eur J Cardiovasc Prev Rehabil 2005;12:226–233. 7. Belanger M, Stein RB, Wheeler GD, Gordon T, Leduc B. Electrical stimulation: can it increase muscle strength and reverse osteopenia in spinal cord injured individuals? Arch Phys Med Rehabil 2000;81: 1090–1098. 8. Taylor JA, Picard G, Widrick JJ. Aerobic capacity with hybrid FES rowing in spinal cord injury: comparison with arms-only exercise and preliminary findings with regular training. PM R 2011;3:817–824. 9. Wheeler GD, Andrews B, Lederer R, Davoodi R, Natho K, Weiss C, et al. Functional electric stimulation-assisted rowing: increasing cardi-
264
Stimulation Pattern and Fatigue
10.
11. 12.
13.
14. 15.
16.
17.
18.
19.
20.
21.
22.
23.
24.
25.
26.
27.
28.
29.
30. 31.
ovascular fitness through functional electric stimulation rowing training in persons with spinal cord injury. Arch Phys Med Rehabil 2002; 83:1093–1099. Isakov E, Mizrahi J, Najenson J. Biomechanical and physiological evaluation of FES-activated paraplegic patients. J Rehabil Res Dev 1986;23:9–19. Peckham PH, Knutson JS. Functional electrical stimulation for neuromuscular adaptations. Annu Rev Biomed Eng 2005;7:327–360. Binder-Macleod SA, Barker CB III. Use of a catchlike property of human skeletal muscle to reduce fatigue. Muscle Nerve 1991;14:850– 857. Binder-Macleod SA, Scott WB. Comparison of fatigue produced by various electrical stimulation trains. Acta Physiol Scand 2001;172: 195–203. Burke RE, Rudomin P, Zajac FE. Catch property in single mammalian motor units. Science 1970;168:122–124. Binder-Macleod SA, Lee SCK, Russ DW, Kucharski LJ. Effects of activation pattern on human skeletal muscle fatigue. Muscle Nerve 1998; 21:1145–1152. Scott WB, Binder-Macleod SA. Changing stimulation patterns improves performance during electrically elicited contractions. Muscle Nerve 2003;28:174–180. Crameri RM, Weston AR, Rutkowski S, Middleton JW, Davis GM, Sutton JR. Effects of electrical stimulation leg training during the acute phase of spinal cord injury: a pilot study. Eur J Appl Physiol 2000;83:409–415. Sabatier MJ, Stoner L, Mahoney ET, Black C, Elder C, Dudley GA, et al. Electrically stimulated resistance training in SCI individuals increases muscle fatigue resistance but not femoral artery size or blood flow. Spinal Cord 2006;44:227–233. Deley G, Laroche D, Babault N. Effects of electrical stimulation pattern on quadriceps force production and fatigue. Muscle Nerve 2014; 49:760–763. Bigland-Ritchie B, Zijdewind I, Thomas CK. Muscle fatigue induced by stimulation with and without doublets. Muscle Nerve 2000;23: 1348–1355. Bickel SC, Slade JM, VanHiel LR, Warren GL, Dudley GA. Variable frequency train stimulation of skeletal muscle after spinal cord injury. J Rehab Res Dev 2004;41:33–40. Scott WB, Lee SCK, Johnston TE, Binkley J, Binder-Macleod SA. Effect of electrical stimulation pattern on the force responses of paralyzed human quadriceps muscles. Muscle Nerve 2007;35:471–478. Zory R, Bo€ erio D, Jubeau M, Maffiuletti NA. Central and peripheral fatigue of the knee extensor muscles induced by electromyostimulation. Int J Sports Med 2005;26:847–853. Martin V, Millet GY, Martin A, Deley G, Lattier G. Assessment of lowfrequency fatigue with two methods of electrical stimulation. J Appl Physiol 2004;97:1923–1929. Darques JL, Bendahan D, Roussel M, Giannesini B, Tagliarini F, Le Fur Y, et al. Combined in situ analysis of metabolic and myoelectrical changes associated with electrically induced fatigue. J Appl Physiol 2003;95:1476–1484. Papaiordanidou M, Varray A, Fattal C, Guiraud D. Neural and muscular mechanisms of electrically induced fatigue in patients with spinal cord injury. Spinal Cord 2014;52:246–250. Duchateau J, Hainaut K. Nonlinear summation of contractions in striated muscle. II. Potentiation of intracellular Ca21 movements in single barnacle muscle fibers. J Muscle Res Cell Motil 1986;7: 18–24. Ratkevicius A, Quistorff B. Metabolic costs of force generation for constant-frequency and catchlike-inducing electrical stimulation in human tibialis anterior muscle. Muscle Nerve 2001;25:419–426. Parmiggiani F, Stein RB. Nonlinear summation of contractions in cat muscles. II. Later facilitation and stiffness changes. J Gen Physiol 1981;78:295–311. Binder-Macleod SA, Lee SC. Catchlike property of human muscle during isovelocity movements. J Appl Physiol 1996;80:2051–2059. Dudley-Javoroski S, Shields RK. Muscle and bone plasticity after spinal cord injury: review of adaptations to disuse and to electrical muscle stimulation. J Rehabil Res Dev 2008;45:283–296.
MUSCLE & NERVE
August 2015
