skeletal muscle response to tenotomy - dr amir jamali · invited review abstract: tenotomy is a...

INVITED REVIEW ABSTRACT: Tenotomy is a commonly encountered clinical entity, whethertraumatic or iatrogenic. This article reviews the response of skeletal muscleto tenotomy. The changes are subdivided into molecular, architectural, andfunctional categories. Architectural disruption of the muscle includes myofi-ber disorganization, central core necrosis, Z-line streaming, fibrosis of fibersand Golgi tendon organs, changes in sarcomere number, and alterations inthe number of membrane particles. Molecular changes include transientchanges in myosin heavy chain composition and expression of neural celladhesion molecule (NCAM). Functionally, tenotomized muscle produces de-creased maximum tetanic and twitch tension. Alterations in normal skeletalmuscle structure and function are clinically applicable to the understandingof pathological states that follow tendon rupture and iatrogenic tenotomy.

© 2000 John Wiley & Sons, Inc. Muscle Nerve 23: 851–862, 2000

SKELETAL MUSCLE RESPONSETO TENOTOMY

AMIR A. JAMALI, MD, 1 POUYA AFSHAR, BS, 1 REID A. ABRAMS, MD, 1 and

RICHARD L. LIEBER, PhD 1,2

1Department of Orthopedics, University of California, San Diego, School ofMedicine and Veterans Administration Medical Center, 3350 La Jolla Village Dr.,La Jolla, California 92093-9151, USA2Department of Bioengineering, Biomedical Sciences Graduate Group, University ofCalifornia and Veterans Administration Medical Centers, San Diego, California,USA

Accepted 11 February 2000

The word “tenotomy,” as used in the surgical litera-ture, indicates surgical division of a tendon for reliefof a deformity that is caused by congenital or ac-quired shortening of a muscle. Loss of tendon con-tinuity applies to surgical manipulation, trauma, anddegenerative musculoskeletal diseases.59 There arevast clinical implications of the changes that occurboth in muscles and tendons after tenotomy. Al-though numerous studies have detailed biochemicaland architectural properties of tendons after tenot-omy and these results have been incorporated intothe clinical realm, little information is available re-garding the biological and mechanical response ofmuscles to surgical tenotomy and to traumatic ten-don injury. This has clinical implications in the fieldsof orthopedics, ophthalmology, and general surgery.By studying the response of muscle to therapeutic

and traumatic tenotomy, a better understanding ofskeletal muscle function and response to injury isachieved. In addition, new methods of interventionon muscle’s healing response may be investigated,leading to accelerated recovery from surgery andhealing after injuries.

There are numerous examples of tendon injuriesthat lead to debilitation. These include rotator cuffrupture, Achilles tendon injury, flexor or extensortendon laceration in the hand, and patellar tendonrupture. Additionally, surgical tenotomy is widelyused in ophthalmology for realignment of the opticaxis.56 Tenotomy is commonly performed in footand ankle surgery for treatment of hallux valgus, inhand surgery for tendon transfers and treatment ofmallet finger,15 in sports medicine for treatment oftendinitis,45 in the treatment of rheumatologic dis-eases such as hamstring tenotomy for hemophiliacarthropathy of the knee, in pediatric orthopedics forcorrection of deformities in cerebral palsy,20,53 andin traumatology for the management of compart-ment syndrome contractures.33 Thus, it is importantto understand the effects of tenotomy on skeletalmuscle both acutely, immediately after the surgery,

Abbreviations: CCD, central core disease; DMD, Duchenne musculardystrophy; EDL, extensor digitorum longus; EMG, electromyographic;MHC, myosin heavy chain; MLC, myosin light chain; NCAM, neural celladhesion molecule; Po, maximum tetanic tensionKey words: immobilization; muscle injury; muscle mechanics; sarcomerenumber; surgical tendon transfer; tenotomyCorrespondence to: R.L. Lieber; e-mail: [email protected]

© 2000 John Wiley & Sons, Inc.

Tenotomy and Skeletal Muscle MUSCLE & NERVE June 2000 851

as well as in the long term, after the muscle has hadthe chance to adapt to its new environment. Thepurpose of this review is to highlight several basicstudies of skeletal muscle tenotomy and to suggesttheir clinical implications.

TENOTOMY EFFECTS ON MUSCLE

The immediate effects of tenotomy or tendon rup-ture on muscle are straightforward. Because normalmuscles are typically under resting tension, there isan immediate decrease in the tension across themuscle as well as sarcomere shortening after themuscle loses one of its attachments. Additionally, thespecialized neural sensors are affected with respectto the length and tension information that they re-ceive and relay (see below).

Tenotomy Decreases Muscle Mass and Force-Generation Capacity. Tenotomy, studied across awide range of species, results in decreased musclemass (Table 1). The specific effect of tenotomy de-pends both on the species and on the muscle stud-ied. For example, in the rat soleus muscle, 12 daysafter tenotomy, muscle mass decreased by approxi-mately 50% compared to a normal muscle.16,37,40 Ithas been shown, in general, that the antigravitymuscles (composed primarily of slow fibers) atrophyto a greater extent than their antagonists (composedprimarily of fast fibers). Additionally, tenotomy leadsto greater atrophy of the slow-twitch fibers in catgastrocnemius and soleus.30 Calcium-activated neu-tral proteases are upregulated after tenotomy in therat soleus, reaching the maximum level at 1 week.This time course corresponds to maximum musclefiber disorganization. These enzymes may be in-volved in the degenerative events that occur in te-notomized myofibers.8

In contrast to the relatively rapid response of therat soleus muscle, atropy of the rabbit soleus muscledoes not reach a significant level until 4 weeks post-tenotomy.10 In the rabbit model, reformation of adistal attachment of the muscle to either the tendonstump or surrounding connective tissue with subse-quent application of tension decreases atrophy andimproves maximum tension production, a measureof muscle strength.65,66

Tenotomy, with intact innervation, leads to sev-eral changes in muscle contractile function. Bullerand Lewis completely tenotomized all muscles sur-rounding the rabbit ankle and showed significantlydecreased twitch tensions in the tenotomized group(Table 1) to approximately 5–10% of the control

values within only 3 weeks.16 Additionally, they notedan increase in the speed of muscle contraction,which they attributed to conversion of slow fibers tofast fibers. This is similar to the conversion of slowfibers to fast fibers that occurs with other decreased-use models, such as spinal cord injury46 or hindlimbsuspension.13,63

Active tenotomy is defined as tenotomy of amuscle while it is undergoing active contraction. Pas-sive tenotomy is tenotomy of a muscle while at rest.Tsai et al. hypothesized that active tenotomy wouldbe more injurious to muscle based on a more violentrelease of tension. In the rabbit extensor digitorumlongus muscle (EDL), they compared active to pas-sive tenotomy over 3 weeks to determine whetheractive contraction during a tenotomy (simulatingtraumatic rupture) would lead to greater muscle in-jury. They found that, after 1 week, the active te-notomy group produced lower maximum tetanictension compared to passive tenotomy, possibly in-dicating greater damage to the contractile elements(Fig. 1). By 21 days, however, the active tenotomygroup had recovered to a significantly greater de-gree than the passive tenotomy group.66 They hy-pothesized that the active tenotomy initially caused agreater muscle injury leading to a greater regenera-tive response, allowing more complete restoration ofthe contractile function.

Tenotomy Causes Alterations in Sarcomeres andSupporting Structures. Tenotomy leads to an in-crease in the connective tissue content of a muscle.40

Within 1 week of tenotomy in rat soleus and gastroc-nemius muscles, a qualitative increase in both theepimysial and perimysial connective tissue layers wasseen (Figs. 2, 3). By 3 weeks after tenotomy, the vol-ume density of connective tissue had increased by afactor of 10, with a greater increase in the soleusmuscle compared to the gastrocnemius. In parallelto the connective tissue increase, there was a loss inthe number of capillaries. By 3 weeks post-tenotomy,only 47% of the soleus capillaries remained. Thecapillary effect was more pronounced in the soleuscompared to the gastrocnemius.

Tenotomy also plays a role in the organization ofsarcomeres in series within a muscle. It has beendemonstrated that tenotomy of the proximal anddistal tendons of rat soleus muscle not only leads tomuscle belly shortening, as expected, but that thisshortening is distributed to the sarcomeres in such away that they shorten proportionally from an averagelength of 2.6 µm to 1.8 µm.5,6 It was further shownthat over the course of the following 4 weeks, sarco-

852 Tenotomy and Skeletal Muscle MUSCLE & NERVE June 2000

Table 1. Summary of experimental tenotomy studies.*

Ref.no.

Model andspecies Procedure Endpoint Measured results Conclusions

37 Rat soleus andgastrocnemius

Achilles tenotomy 4–120 days MHC distribution Shift in proportion of fast fibertypes (temporary). Noembryonic myosin expressionin tenotomized muscle.

71 Rat soleus Proximal anddistal tenotomy

5 days Histology, transmissionEM, energy dispersiveX-ray microanalysis

Cores found in type 1 fibers aftertenotomy; significant increasein Na+ and Cl− concentration.Decreased K+ and S contentin tenotomized fibers.

8 Rat soleus Achilles tenotomy 3,5,7,14,21and 42 days

Calcium protease activity Maximal protease activity within 1week after tenotomy. Persistentactivity at 2–3 weeks. Return tobaseline by 6 weeks.

38 Rabbit EDL Active andpassivetenotomy

1,7,21 days NCAM expression Molecular changes occur within24 h.

6 Rat gastrocnemiusand EDL

Passive tenotomy 1 day, 1,2,4weeks

Sarcomere lengths andlight microscopy

After 1 day, decreased averagesarcomere length. Central corefibers found after 1 week ingastrocnemius but not EDL.


2 days–6weeks

Light and electronmicroscopy

Central cores after tenotomyformed by addition of newlyformed myofibrils at theperiphery of the myofiber.

58 Rat soleus Tenotomy 1–4 weeks Light and electronmicroscopy

Central core necrosis, Z-bandstreaming, and nemaline rodsobserved.


1,2,3,4,6weeks aftertenotomy

Light and histochemistry Central core necrosis seen in allthree fiber types.


1,2,3,4,5,6,7days aftertenotomy

Light and electronmicroscopy

Segmental necrosis at fiber ends.Peripheral zone of central corefibers consists of normalmuscle cross-striations andcentral zone with theinterruption of striation pattern.


1 week aftertenotomy

Freeze fracture Decrease in number ofintramembranous particles.


1 day and 4weeks aftertenotomy

Light microscopy Muscle bellies and sarcomerelength shortened after 1 day.After 4 weeks, muscle belliesremain shortened, butsarcomere lengths return tonormal.

10 Rabbit soleus Tenotomy andimmobilization

4 weeks aftertenotomy

Muscle mass, length, fibertype and area, density,tetanic force, rate offorce generation

Achilles tenotomy resulted in a20% decreased and 50% dropin Po after 2 weeks. Tenotomyand immobilization resulted ina 90% drop in Po. Smallbeneficial effect of electricalstimulation.


Tenotomy andimmobilization

1,2, and 3weeks

Density of capillaries andconnective tissue byscanning EM

Increased endomysial andperimysial layers anddecreased capillary density.


Tenotomy andimmobilization

1,2, and 3weeks

Number of musclespindles, Golgi tendonorgans, and intrafusalfibers; diameter ofintrafusal fibers

Diameter of intrafusal fibersincreased after 1 week andthen decreased after 3 weeks.Spindle and Golgi capsulesthickened nearly two-fold 3weeks post-tenotomy.

39 Various humanmuscles

Spontaneoustendon rupture

1 day to 6months aftertendonrupture

Light microscopy,histochemistry, andelectron microscopy

Decreased SDH and CPKactivity. Decreased number oftype 1 fibers. Disruption anddisorientation of myofibrils;Z-line streaming anddisorganization. Enlargedmitochondria and sarcoplasmicreticulum dilatation.

42 Rat soleus Achilles tenotomy 24 h-40 days Light and electronmicroscopy

Nerve input is necessary for thedevelopment of central coresand nemaline rods. Lesionsprevented by sciatic neurotomyor cordotomy.


mere length returned to normal as the fibers de-creased serial sarcomere number. This suggests thatthe reduction of sarcomeres in series was made inorder to optimize the contractile function of eachsarcomere. If this is true, it would be analogous tostudies of immobilization in which sarcomere lengthreturns to optimal by changing sarcomere num-

ber.62,70 Baker sought to explain the mechanism ofsarcomere removal and noted preferential fiber ne-crosis in both the peripheral ends of the proximallyand distally tenotomized rat soleus with a significantinfiltration by inflammatory phagocytic cells, lyso-somes, and authophagic granules within 1 day aftertenotomy.2 This was termed “segmental necrosis.”

Table 1. Continued

Ref.no.

Model andspecies Procedure Endpoint Measured results Conclusions

16 Rabbit soleus Tenotomy ofdorsiflexors

17 to 85 days Twitch tension andisometric recordings

Shortened contraction time withno conversion from slow to fastmuscle fibers.

19 Human Achillestendon ruptures

Achilles tendonrepair patients

Measurementstaken at1,2,3,6,12,24,and 52weeks

Distance between ends ofthe tendon; ROM, andplantar flexion strength

Mobile cast postoperatively,increased ROM andplantarflexion strength, anddecreased tendon elongationand scar formation.

35 Rat soleus,gastrocnemius,EDL, TA

Tenotomy followedby dorsal rootsectioning

Musclesstudied 3and 7 daysaftertenotomy

Muscle shortening andcontracture aftertenotomy or tenotomyand deafferentation

Tenotomy alone caused greaterrate of atrophy than tenotomycombined with deafferentation.Atrophy more rapid in plantarflexors than dorsiflexors.


Achilles tendonrepair followedby early rangeof motion

Follow-up at 6weeks and3,6,12, and24 months

Pain evaluation, functionaldeficit, and return tosports

Suture technique provides rigidand stable fixation that allowsearly range of motion,strengthening, and functionalrehabilitation leading tominimal plantar flexion strengthdeficit.

49 Mouse soleus Achilles tenotomyand/or tibialnerve section

1,3,5,7,14days

Length and mass ofsoleus muscle aftertenotomy and/ordenervation

Muscle atrophy 24 h aftertenotomy. Simultaneoustenotomy and denervationafforded a temporary delay inatrophy for 2 days. By 7 days,there was equal atrophy in theexperimental groups.


Achilles tendonrepaired andpostop motion

Follow-upranged14–56months

Clinical evaluation,functional, testing andstrength testing

No increased risk of reruptureand good return of plantarflexion strength when treatingAchilles tendon repairs withearly range of motion.

52 Rabbit soleus andperoneuslongus

Tenotomy oftendonscrossing ankleand/or sciaticneurotomy

3 days to 3months

SDH activity, fiber sizeand type, histology

Denervation decreased SDHactivity. Tenotomy causeddegenerative changes insoleus but not peroneus.Denervation preventeddegenerative changes.

36 Rabbitgastrocnemius

Achilles tenotomy 9 days to 20months

Muscle spindlespontaneous sensoryactivity and histology ofmedial head ofgastrocnemius

Spindles react to muscle stretchwith increased dischargefrequency & by post-excitatoryinhibition on removal of stretch.Preservation of muscle spindlestructure and tendon organsdue to shortening of muscle.

67 Rabbit soleus andTA

EMG during reflexand activemovement

1,2 days, 6weeks, 3months

EMG activity TA shows continuous EMGactivity for 2 weeks aftertenotomy while soleus activityceases immediately.

66 Rabbit EDL Active or passivetenotomy

1,7,21 days Maximum tetanic tension After active tenotomy, maximumtension drops below that ofpassive tenotomy at 1 and 7days. By 21 days, activetenotomy produces highermaximum tension than passivetenotomy.

*CPK, creatine phosphokinase; EDL, extensor digitorum longus; EMG, electromyogram; MHC, myosin heavy chain; NCAM, neural cell adhesionmolecule; Po, maximum tetanic tension; ROM, range of motion; SDH, succinate dehydrogenase activity; TA, tibialis anterior.


The necrotic portion of the muscle fiber was seen incontinuity with the more normal part of the fiber,which was located toward the mid-belly. He hypoth-esized that this represented a key event leading tosarcomere number reorganization after tenotomy.

Theoretically, the muscle architecture probablyplays a role in the degree of sarcomere reorganiza-tion. Fibers that are parallel to the long axis of thefiber (low pennation angle) have the greater relativeshortening and greater degree of remodeling com-pared to those fibers with more oblique orientations(high penetration angle). The change in sarcomerenumber may represent a general theme of skeletalmuscle. Sarcomere number is a plastic value thatadapts to the new muscle environment. While this isa logical hypothesis based on the literature, the ex-tent to which such adaptations are characteristic ofmuscle is yet to be determined.

Tenotomy Causes Alterations in Muscle Fiber Fine

Structure. Structural changes that appear in te-notomized muscle involve the basic structure of thefibers themselves. Central muscle fiber cores are aclassic pathological sign in histological sections. Cen-tral core disease (CCD) and nemaline myopathy aretwo of the most common of the congenital myopa-thies in patients who often present as a “floppy in-fant.”17,48 In the tenotomy literature, the term cen-tral core was originally used to describe the centralfiber disorganization seen at the light and electronmicroscopic level. Further work since that time hasseparated the pathological entities of central cores

from that of target fibers. Target fibers are fibersconsisting of three zones: a central zone with de-creased oxidative capacity analogous to the centralcore in CCD, an intermediate zone of increased oxi-dative enzyme activity, and a peripheral zone consist-ing of normal muscle microscopic structure. The tar-get fiber is brought about by denervation andreinervation. According to De Coster et al., they aredemonstrated when the “trophic influence of thenervous system” is interrupted.23 Central cores canbe multiple in the same fiber and can extend alongthe entire length of the fiber whereas targets areusually central and localized within the fiber.17,23,29

Histological changes have been demonstrated in te-notomized muscle in both the cat and rat, initially

FIGURE 2. In normal muscle, a few delicate collagen fibers (ar-row) are seen with minimal connective tissue by SEM. Bar = 10µm. From Josza et al.40

FIGURE 3. In the soleus, 3 weeks post-tenotomy, there is adense connective tissue envelope separating the muscle fibers.Bar = 10 µm. From Josza et al.40

FIGURE 1. After active and passive tenotomy, there is initially agreater decline in maximum tetanic tension in the active group at7 days, with improved recovery by 21 days, possibly indicating agreater regenerative response. From Tsai et al.66


described as central cores.17,30 At the light micro-scopic level, these regions consisted of a peripheralnormal region and a central region of disorganizedmyofibrils.2 They were seen in tenotomized ratmuscle within 7 days.58 Most of these fibers lost theirmyosin ATPase and succinate dehydrogenase activitywithin the cores, indicating not only structural butalso metabolic derangement. Although the specificfunction of these fibers was not explicitly measured,given the inability to generate force using myosincross-bridges and the lack of oxidative capacity, itcan be expected that the function of these fibers iscompromised. The so-called cores as described inthe early tenotomy literature represent target fibersbased on the mechanism of their formation andtheir microscopic appearance. According to DeReuck et al., target fiber formation can be inhibitedby performing simultaneous neurectomy in the ratgastrocnemius model, suggesting the need formuscle activation in order to manifest these histo-logical and structural changes.24–26

The mechanism of sarcomere structural reorga-nization that follows tenotomy and the formation ofthe central cores themselves is poorly understood.Baker showed that normal muscle fibers (Fig. 4) be-gin to show morphological changes within 1 day af-ter tenotomy, including mitochondrial swelling andZ-line dissolution.2 Using electron microscopy, heshowed that myofibrils along the entire length of thefiber underwent destruction. His findings indicatedthat the peripheral normal region of the central corefibers was actually the region of new myofibril pro-liferation. In this respect, fiber rebuilding recapitu-lated the developmental process.44 Nemaline rods

are characteristic findings in nemaline myopathy, amyopathy of either sporadic or autosomal inheri-tance.31,54 These structures are ascribed to excessivecollections of Z-band components. These same ne-maline rods have been demonstrated in animalmodels of tenotomy.55 Other structural changes intenotomized muscle include mitochondrial degen-eration with autophagic vacuoles and Z-band stream-ing (Fig. 5). As early as 1 day after tenotomy, there isswelling of the sarcoplasmic reticulum, especially theterminal cisternae. Based on these results, Baker hy-pothesized that these changes are analogous to thoseseen in Duchenne muscular dystrophy (DMD).4

Of interest to many investigators are the molecu-lar factors responsible for changes in muscle struc-ture and function. Baker used the freeze-fracturetechnique to examine the membrane morphologicalresponse to tenotomy in rats 1 week after soleus te-notomy.4 Previous studies on DMD muscle showed adecrease in intramembranous particles on both thecytoplasmic and external faces of the freeze fracturespecimens.57 The authors speculated that the de-crease in intramembranous particles affected mem-brane permeability, which may have lead to the de-generative changes observed. Wroblewski andEdstrom performed X-ray microanalysis to quantifythe amounts of sodium, chloride, and potassiumwithin central core fibers after tenotomy in rats (Fig.6).71 In the core fibers studied, they found increasedsodium, increased chloride, and decreased potas-sium compared to contralateral controls. This wasattributed to an inability of the plasma membrane tomaintain normal ionic electrochemical gradients. A

FIGURE 4. Electron micrograph of control skeletal muscle dem-onstrating linear arrangement of Z-bands. Bar = 1 µm.

FIGURE 5. Z-band streaming in tenotomized rat soleus muscle.Bar = 1 µm. From Shafiq et al.58


change in sodium and potassium of the same mag-nitude has been reported in human myopathicmuscle, including myotonic dystrophy and myotubu-lar myopathy.28

Tenotomy Causes Alterations in Myosin Heavy Chain

Expression. Myosin is the molecular motor thatpowers contraction in skeletal muscle. Myosin is thekey protein in fiber type determination. It has a vitalrole in muscle function as a result of its interactionwith actin. Each myosin molecule chain contains sixsubunits, two heavy chains (MHC) and four myosinlight chains (MLC). The heavy chains have impor-tant functional significance as they are related to themaximum muscle fiber speed of contraction.14 Manymuscles are a mosaic of these fibers, whereas othersare predominately slow or fast. The fiber type systemwas initially based on laboratory observations oftwitch time, peak torque, and degree of fatigability,and content of oxidative enzymes. With newer tech-niques such as immunohistochemistry, gel electro-phoresis, and molecular biology, more definitiveanalysis of muscle fiber type is now available. Addi-tionally, various species and specific muscles havevariable fiber typing, based on MHC isoforms. Muchof the tenotomy literature precedes many of thesenewer techniques and thus fibers are simply dividedinto slow, (type I) or fast, (type 2) fibers.16,58,67 Asmentioned earlier, the soleus, a classic posturalmuscle, is composed largely of slow fibers, whereasthe gastrocnemius muscle consists primarily of fastfibers. In addition, myosins expressed during em-

bryogenesis and in the neonatal period are also ex-pressed during muscle regeneration. During trau-matic injuries, toxin injection, and local anestheticinfusion, muscle fibers are destroyed, leading to for-mation of new fibers that express developmentalmyosins as they regenerate.22 These developmentalmyosins are also commonly expressed after denerva-tion injury to muscle. The effect of tenotomy com-pared to denervation alone on the expression ofmyosins has been studied in rat muscle.37 The totalMHC content, slow and fast MHC, embryonic MHC,and muscle mass were measured. Total soleus MHCcontent decreased to 15% of control values 10 daysafter tenotomy. The gastrocnemius seemed more re-sistant and only decreased its total MHC to 70% ofcontrol values. There was only a transient shift be-tween various MHC isoforms but no long-termchanges were noted (Figs. 7,8). In the active andpassive tenotomy model described by Tsai et al.,66

tenotomy did not bring about any expression of em-bryonic myosins, commonly expressed after dener-vation injury or traumatic injury, nor was any fibertype change noted based on immunohistochemis-try.1,38

Relationship between Tenotomy and Innervation.

The effect of tenotomy on neural function is com-plex, involving both the efferent and afferent path-ways. Tenotomy was traditionally used as a methodfor simulating immobilization of muscle,22 but, asmentioned earlier, this is probably not a straightfor-ward comparison since the magnitude and the du-

FIGURE 6. Bar graphs of the content of elements as determinedby X-ray microanalysis in the soleus muscle fibers after tenotomycompared with contralateral nontenotomized soleus and soleusfrom normal rats. From Wroblewski and Edstrom.71

FIGURE 7. SDS-PAGE quantification of myosin heavy-chaincomposition at various time periods after tenotomy of the ratsoleus. From Jakubiec-Puka et al.37


ration of muscle unloading are not explicitly known.Electromyographic (EMG) activity is reportedly de-creased or absent in animal tenotomy models.67 Thespecific muscle and its physiological role leads tovariable changes in response to tenotomy. Vrbovashowed that the soleus, a postural muscle, sustainsmarked alteration in its EMG profile whereas tibialisanterior, a phasic muscle, maintains its EMG profileafter tenotomy. Interestingly, within 1 day after spi-nal cord section, no reflex activity can be elicited inthe soleus, whereas the tibialis anterior maintains itsreflex activity on EMG analysis.67 This may representan inability of the muscle to be reflexly activated ormay truly represent decreased neural drive to themuscle itself.

Sensory outflow from the cat gastrocnemius asmeasured by electromyography increases after tenot-omy.36 There is an increase in the amplitude ofmonosynaptic reflex as a result of stimulation of theafferent nerve of the tenotomized muscle.11,12,43 De-generative changes are less severe in animals withinterruption of sensory outflow from the tenoto-mized muscle.35,49 This could mean that neural ac-tivity may in some way be responsible for theseevents.

The occurrence of central fiber degenerationand formation of nemaline rods requires intact in-nervation in the rat soleus. According to Karpati etal., the absence of innervation brought about by cor-dotomy or sciatic neuropathy leads only to muscleatrophy.42 However, according to De Reuck, the for-mation of target fibers after tenotomy could be in-hibited in the rat gastrocnemius by performing con-current neurotomy.24 It may be that subsequent

neural stimulation of an already shortened muscleleads to these changes or that the neural input hassome trophic influence on the involved muscle fi-bers. Afferent pathways are probably very importantin the degenerative effects of tenotomy. Cat soleusmuscles immobilized in a shortened position, simu-lating tenotomy, underwent equal atrophy regard-less of cordotomy or deafferentiation.27 Dorsal rootsection decreased the degree of tenotomy-inducedatrophy in rat soleus, indicating that some abnormal-ity in the afferent pathways may play a role in theetiology of muscle atrophy.42

The presence of changes in the afferent outflowfrom muscle has been demonstrated using bothphysiological and histological studies. Coordinationis affected by the output of Golgi tendon organs andmuscle spindle receptors. They respond to both ac-tive contractions and passive stretch of muscle.Muscle spindle length is decreased in length in te-notomized muscle.36 Tenotomized muscle has alsobeen shown to have increased stretch sensitivity, in-dicating possible alteration in the output frommuscle spindle receptors and Golgi tendon organs.72

The shortened state of tenotomized muscle does notfully explain these alterations in receptor output.Jozsa et al. demonstrated that there is decreasedperiaxial space as well as fibrosis of the capsules ofboth muscle spindles and of Golgi tendon organs,with some receptors becoming completely fibrosed.They hypothesized that the changes in elasticity andfluid content result in diminished responses to peri-organ pressure changes required for activation.41

Nerve–Muscle Communication after Tenotomy.Neural cell adhesion molecule (NCAM) was ex-

pressed in the rabbit EDL within 1 day after bothactive and passive tenotomy.38 NCAM is a cell-surfacemolecule that is involved in embryogenesis with theestablishment of muscle–nerve and nerve–nerveconnections.32 It is also expressed on the surface ofdenervated muscle cells21 and regenerating musclecells.18 It is expressed neither in necrotic nor degen-erating muscle fibers. NCAM has been used as amodel to quantify muscle injury by determining thepercentage of cells expressing the molecule.50,51 Theexpression of NCAM in the rabbit model may rep-resent molecular evidence of denervation as well asregeneration after atrophy within tenotomizedmuscle or may simply represent acute shock to theneuromuscular junction that accompanies dramaticunloading with possible functional disruption of theneuromuscular junction. In a different model ofmuscle injury, eccentric contraction injury, Warren

FIGURE 8. SDS-PAGE quantification of myosin heavy-chaincomposition at various time periods after tenotomy of the ratgastrocnemius. From Jakubiec-Puka et al.37


et al. demonstrated changes typically associated withdenervation in mechanically injured muscle. Theyreported a 79% increase in acetylcholine receptorlevel within 3 days after eccentric injury, which isanalogous to that seen in a “transiently denervatedmuscle.”68 The acute changes seen with tenotomywithin 1 day as well as the expression of NCAM inthis time course may represent similar early chemicalalterations in the muscle (Fig. 9).

CLINICAL IMPLICATIONS

As mentioned above, tendon injury is a commonclinical entity, whether traumatic, degenerative, orsurgically induced. Tenotomy results in decreasedmuscle length and corresponding sarcomere length,a change in the neural output from muscle receptorsaltering EMG activity. From a clinical standpoint,early tendon repair and mobilization is the bestmethod to avoid pathological changes in the corre-sponding muscle by restoring the muscle to its origi-nal length. The idea of early primary tendon repairand mobilization to permit a smooth gliding surfacehas become a standard part of management of ten-don injuries.34,60,61 As knowledge of the changes thattake place in tenotomized muscle increases, it is in-creasingly apparent that the timing of tendon repairis extremely important to prevent these molecularand structural events. Delay in tendon repair mayaffect the ability to achieve normal length and func-tion as a result of muscle contracture and atrophy.To investigate this, Tsai et al. performed tenotomy ofrabbit EDL muscles. Maximum tetanic tension (Po)

is a commonly used measure of muscle motor activityand function.9,69 Within 1 day after tenotomy, therewas a 50% decline in maximum muscle tension pro-duction which continued to decrease over the ensu-ing 3 weeks (Fig. 10). In another experiment, rabbitEDL tendons were cut and then restored to theiroriginal length by suturing to the ankle retinaculumat 1 week, a time-course consistent with many flexortendon repairs after injury. It was found that over thefirst 3 weeks after the repair, the previously observeddecline was averted and maximum tension produc-tion increased precipitously by 1 day and then pro-gressively to 21 days after repair, consistent with aregenerative process (Fig. 11). It was expected that

FIGURE 9. NCAM expression increases within 1 day after tenot-omy in rabbit EDL muscle with further increases by 7 and 21days. From Jamali et al.38

FIGURE 10. Maximum tetanic tension decreases to 50% of nor-mal within 1 day after passive tenotomy, and this trend pro-gresses at 7 days and at 21 days. From Tsai et al.66

FIGURE 11. After simulated tendon repair, the maximum tetanictension reverses its trend and instead progressively increasesdemonstrating the importance of tension in the myotendinousunit. From Tsai et al.65


the rabbit muscles would respond by gaining sarco-meres after being pulled out to length. However,there was no change in the sarcomere number orsarcomere length in these groups. These data indi-cate that in the rabbit EDL, within 1 week, there isno significant change in sarcomere number. This isencouraging from a clinical standpoint, as it vali-dates the 1 week window for performing delayed ten-don repair.65

Other modalities have also been shown to pre-vent muscle degeneration after tendon injury. Barryet al., using a rabbit soleus model, performed anAchilles tenotomy in the rabbit. They then main-tained the leg immobilized for 2 weeks. After thispoint, the animals were either removed from thesplint or maintained for another 2 weeks. In this“mobilized” group, some animals were treated withelectrical stimulation. Thus, they compared the ef-fect of natural recovery from immobilization, fol-lowed by natural recovery augmented by electricalstimulation using implanted electrodes attached to amini-stimulator.10 In their immobilization groups,they confirmed similar myopathic changes seen withtenotomy, demonstrating decreased fiber area, de-creased fiber occupancy per field, increased num-bers of transitional and fast fibers, decreased tetanictension, and increased rate of contraction and relax-ation. The time of total immobilization was directlycorrelated with the degree of the above changes.The stimulation groups showed significant improve-ment in all of the above parameters compared to thenonstimulated animals. Thus, electrical stimulationmay have a clinical role in preventing some of thesedegenerative changes. Multiple clinical studies haveadvocated a limited period of immobilization fol-lowed by early passive remobilization and earlyweightbearing after Achilles tendon repairs.19,47,64

Cetti et al. demonstrated in a prospective study thatplantarflexion strength, gait, range of motion, andpatient satisfaction were better after treatment ofAchilles tendon rupture with a mobile cast that al-lowed early limited motion. These studies and othersreflect the new awareness of muscle preservation us-ing electrical stimulation, range of motion, and ac-tivity to minimize the degeneration and atrophy thataccompany tenotomy.

It seems clear that muscle response to tendoninjury is an area of interest beyond that of basic sci-ence alone. It is a common entity encountered inmedical clinics on a daily basis. Whether seen in apatient with a traumatic injury such as a biceps orAchilles tendon rupture or in a postoperative patientrecovering from a tendon transfer procedure, thereare multiple structural and molecular events at play

within the muscular compartment. With this ongo-ing research, it is becoming increasingly apparentthat long-term atrophy and architectural changescan be averted by early restoration of a point of at-tachment. This philosophy, combined with the mo-dalities of electrical stimulation and early range ofmotion, will lead to lower levels of postinjury atrophyand shorter duration of rehabilitation.

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skeletal muscle response to tenotomy - dr amir jamali · invited review abstract: tenotomy is a...

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