Editorial · Editorial comments

The use of shockwaves to crush uricconcrements instead of removing them bysurgical procedures has become a generallyrecognized tool in the hand of urologist in the8th decade of the last century - less than thirtyyears ago! The effect to bony structures firsthas been recognized as an awkward side effectof this treatment and has become in at firsttimid use for the treatment of delayed fracturehealing not even twenty years ago, but withthe very quickly recognized side effect toreduce also the concomitant chronic pain.In comparison to other physical methods andeven to many surgical methods shockwavetreatment in general is an extraordinarilyyoung procedure. This fact always should bekept in mind expecting strong rules for welldefined indications and a standardisation ofthe treatment in those indications with theassessment by the means of evidence basedmedicine. It was painful to learn that most ofthe clinical trials performed with the commonscientific approach failed to prove the efficacyof shockwave treatment by statistic meanswithout any doubt. The results of differentclinical trials for the same indications havebeen very contradictory. But should this factreally take wonder? Up to now we don´t havethe last answer to the question, howshockwaves are effecting living tissue. Howshould it be possible to define the properappliance in defined indications under thesecircumstances?

Nevertheless the experimental work hasbrought a fascinating progress in the last yearsby a change of mind on principle. In the lastyears of the last century the shockwave effectto the tissue was regarded as a kind of newtrauma similar the demolition of the uricconcrements, initiating somehow again thehealing process. The interpretation of theconcomitant pain release has been purespeculation as for example the input gatecontrol theory. But then we got aware of theimprovement of soft tissue condition also

outside the focus for example in chronicallyinfected bony non unions. We got aware of theeffects of radial shockwave, transferring onlysmall energy amounts to the tissue asphysically possible. We have learned that it isnot the physical damage, needing a highenergy level, but a very subtle stimulus to thenormal regeneration process by theimprovement of blood supply, by increase ofgrowth factors, stimulation and differentiationof stem cells, needing much less energy for anoptimal effect. than a „trauma“ dosis. This viewopened chances for shockwave treatmentindications we never have taken inconsideration before. Therefore formerindications and quality standards ofshockwave treatment had to be revised.

It is the merit of the ISMST President 2008,Roland Hamisultane, to initiate a consensuspaper of experts concerning the actualindications of ESWT. You can find thisconsensus paper in the in hand issue of theISMST Newsletter. It may be a basis forrecommendations to patients as well as fornegotiations with cost bearers and last notleast for your guidance in legal conflicts.

Nevertheless the use of this tool does notmean that shockwave treatment indicationsmay be delivered by other users than doctors. Ihope You will understand this recommendationas long as we are far away of understandingthe mechanism of ESWT effects to the livingtissue in total. The application may be done bymedical personnel as well but also undersupervision of a doctor who is familiar with theindications.

The publication of the consensus paperunderlines also the necessity for the ISMSTof having a print matter like this ISMSTNewsletter and I want to thank once morethe founder and chief editor Paolo RobertoDias dos Santos for his efforts to the benefitfor all of us.

Editorial · Editorial comments

Inside this Issue

Chief Editor• Paulo Roberto Dias dos Santos, MD

(Brazil) - [email protected]

Associate Editor• Ching-Jen Wang, MD (Taiwan)

[email protected]

Editorial Board• Ana Claudia Souza, MD (Brazil)

[email protected]• Carlos Leal, MD (Columbia)

[email protected]• Heinz Kuderna, MD (Áustria)

[email protected]• Helmut Neuland, MD (Germany)

[email protected]• Kimberly Eickmeier, MD (USA)

[email protected]• Leonardo Jaime Guiloff Waissbluth,

MD (Chile) - [email protected]• Ludger Gerdsmeyer, MD (Germany)

[email protected]• Matthias Buch, MD (Germany)

[email protected]• Richard Thiele, MD (Germany)

[email protected]• Robert Gordon, MD (Canada)

[email protected]• Sergio Russo, MD (Italy)

[email protected]• Vinzenz Auersperg, MD (Áustria)

[email protected]• Weil Lowel Jr, MD (USA)

[email protected] • Wolfgang Schaden, MD (Austria)

[email protected]

Veterinary Committee • Scott Mc Clure, DVM (USA)

[email protected]• Ana Liz Garcia Alves, DVM (Brazil)

[email protected]• Ana Cristina Bassit, DVM (Brazil)

[email protected]

Editorial Office Avenida Pacaembú,1024CEP 01234-000 - São Paulo - Brazil Fone: 55-11-3825·8699E mail : [email protected]

website: www.ismst.com

Heinz Kuderna, M.D.

Honorary Presidentem. Dozent Medical Universityem. Medical Director Trauma Center MeidlingMedical Chief Viennese Red CrossVienna, Austria

Editorial comments .............................................................................. 1Consensus statement Recommendations forthe use of extracorporeal shockwave technology inmedical indications .............................................................................. 2Extracorporeal Shockwave in Hip Necrosis .................................... 3When is the right time for ESWT?Influence of ESWT on Ischemia Induced Tissue Necrosisand Its Correlation with Application Time...................................... 6Mid-portion Achilles tendinopathy -What role is there for shock wave treatment? ............................... 9Extracorporal Shock Waves Influences Migration, Proliferationand Growth of Human Mesenchymal Stem Cells....................... 13Improvement of Active Ankle Joint Dorsiflexion by the Useof Extracorporeal Pulse Activation Therapy (EPAT) in Patientswith Chronic Achilles Tendinosis: A New Approach ................... 17

2 3

The authors group of the DIGEST The ISMST Managing Board

Vinzenz Auersperg Roland Hamisultane

Matthias Buch Robert Gordon

Ludger Gerdesmeyer Sergio Russo

Markus Gleitz Heinz Kuderna

Rolf Rädel Vinzenz Auersperg

Jan-Dirk Rompe Wolfgang Schaden

Wolfgang Schaden Richard Thiele

Richard Thiele Richard Coombs

Andreas Waubke

Georg Wille

IntroductionBuilding on the experience gained

over the past 15 years, the scientificboard of the ISMST and experts fromNational Shockwave Societies aroundthe world, have put together a set ofrecommendations for the use ofshockwave therapy.

Purposefully the experts did notapply Cochrane standards for theassessment of the level of evidence.The most recent meta-analysespublished by Cochrane shows"platinum evidence” that shockwavetreatment has little or no effect at all.But Cochrane researchers simplycannot ignore the results of severalwell-designed studies from the pastwhich failed to show any efficacy ofESWT for various disorders. Byanalysing those studies it could beshown that inclusion criteria,treatment parameters or otherconditions are afflicted with systemicbiases which turn the results of thestudies completely into the opposite.Therefore, as long as the situation is soincoherent the idea of a ranking due tothe level of evidence is not reasonableor feasible.

PrerequisitesIn order to prevent improper

treatment the following areprerequisites for administering thetechnology:

In addition to a clinicalexamination, radiological imaging,neurological and/or laboratory-diagnostic tests may be necessary tocorroborate the diagnosis.

Only a qualified (certified byNational or International Societies)physician may use shockwave therapyto treat pathologies, which have beendetermined by diagnostic testing.

For the treatment of bone ailments,a high-energy, focused shockwave withpositioning technology is to be used.To treat superficial soft tissueconditions, devices with or withoutfocusing technology may be utilized;close attention must be paid to thedepth of penetration of the shockwavesource when treating deep tissuestructures.

Approved standardindications

Chronic tendinopathies:- Plantar fasciitis with or without heel

spur- Achilles tendon- Radial epicondylopathy (tennis elbow)- Rotator cuff with or without

calcification- Patella tendon- Greater trochanteric pain syndrome

Impaired bone healingfunction:- Delayed bone healing- Stress fractures- Early stage of avascular bone necrosis

(native X-ray without pathology)- Early stage osteochondritis dissecans

(OD) post-skeletal maturity

Urology:- Lithotripsy (extracorporeal and

endocorporeal)

Common empirically-tested clinical uses

Tendinopathy:- Ulnar epicondylopathy- Adductor syndrome- Pes anserinus syndrome- Peroneal tendon syndrome

Muscular pathologies:- Myofascial syndrome (fibromyalgia

excluded)- Injury without discontinuity

Impaired wound healing

Burn injuries

Salivary stones

Exceptionalindications/expertindications

Spasticity

Early stage osteochondritisdissecans (OD) pre-skeletalmaturity

Apophysitis (Osgood Schlatterdisease)

Peyronie's disease (IPP)

Uses underexperimentalconditions

Myocardial ischemia(extracorporeal/endocorporeal)

Peripheral nerve lesions

Abacterial prostatitis

Periodontal disease

Osteoarthritis

Consensus statementRecommendations for the use of extracorporealshockwave technology in medical indications

Treatment of osteonecrosis of thefemoral head is stage dependent (1-4). For symptomatic hips, theprinciple is to preserve the femoralhead in early cases (5). Conservativetreatments are usually not successful,and core decompression with orwithout bone grafting is consideredthe gold standard (6-8). However, theresults of core decompression areirregular and inconsistent, and manystudies reported less satisfactoryoutcomes. Many patients eventuallyundergo total hip replacement(THR). The complications of THR inyoung active patients are highincluding thigh pain, polyethylenewear, mechanical loosening andinfection (9).

Recently, extracorporealshockwave (ESWT) (10-13),hyperbaric oxygen therapy (HBO)(14,15) and oral alendronate (16-19)were reported to be effective in earlyONFH. We have investigated theresults of single modality andmultiple modalities in the treatmentof early ONFH.

(1). We compared 23 patients with29 hips treated with ESWT with 25patients with 28 hips treated withcore decompression and non-vascularized bone graft. Theevaluations included pain score,Harris hip score, radiograph and MRimaging. At 25 to 35 months offollow-up, the results showed 79%improved, 10% unchanged and 10%worse for ESWT group; and 19%improved, 36% unchanged and 36%worse after surgery. THR wasperformed in 10% of ESWT groupand 29% of surgical group. Weconcluded that ESWT appeared to bemore effective than coredecompression and bone grafting inearly ONFH (12).

(2). We compared 25 patients with30 hips treated with ESWT with 23patients with 30 hips treated withcombined ESWT and oral

alendronate. At 28 to 36 months offollow-up, the results were improvedin 83%, unchanged in 7% and worsein 10% for ESWT group; and 77%improved, 13% unchanged and 10%worse for ESWT plus alendronategroup. THR was performed in 10% ofESWT group and 10% of ESWT plusalendronate group (P = 1.000). Weconcluded that combined ESWT andalendronate produced comparableresults as ESWT without alendronate.The joint effects of alendronate andESWT are not realized in short-term(13).

(3). We compared 28 patients with50 hips treated with cocktail therapythat consists of ESWT, HBO andalendronate) with 35 patients with 48hips treated with ESWT. At aminimum of two years of follow-up,the results were improved in 74%,un-improved in 16% and worsened in10% for cocktail group; and 79.2%improved, 10.4% un-improved and10.4% worsened for ESWT group (P= 0.717). THR was performed in 10%of cocktail group and 10.4% of ESWTgroup (P = 0.946). No discernabledifferences between the two groupswere noted on X-rays and MR images.We concluded that ESWT is effectivewith or without the concomitant useof HBO and alendronate. Thesynergistic effects of HBO andalendronate over ESWT are notapparent in short-term.

Despite the good clinical results,the exact mechanism of ESWTremains unknown. Likewise, theworking mechanism of ESWT inONFH is poorly understood. Toelucidate the working mechanism ofESWT in early ONFH, we havecompared the ESWT-treated femoralheads with non-ESWT-treated onesprior to surgery usinghistomorphological examination andimmunohistochemical analysis. TheESWT-treated femoral heads showedsignificantly more viable bone and

less necrotic bone, higher cellconcentration and more cellactivities includingphagocytosis than non-ESWT-treated specimens. Inimmunohistochemical analysis,the ESWT-treated femoralheads showed significantincreases in vWF (vonWillebrand factor) (P < 0.01),VEGF (vessel endothelialgrowth factor) (P = 0.0021),CD31 (PECAM-1 or plateletendothelial cell adhesionmolecule-1) (P = 0.0023), Wnt3

(Winless 3a) (P = 0.008) and PCNA(proliferating cell nuclear antigen) (P= 0.0011), and decreases in VCAM(vascular cell adhesion molecule) (P= 0.0013) and DKK1 (Dickkoph-1) (P= 0.0007) than non-ESWT-treatedhips (Fig. 1). It appears that ESWTsignificantly promotes angiogenesisand osteogenesis with boneremodeling in ONFH of the hip(Rheumatology in press).

In conclusion, ESWT showedsuperior results than coredecompression and non-surgicaltreatments such as HBO andalendronate in early ONFH. Itappears that ESWT triggers thebiological changes of angiogenesisand osteogenesis at the molecularlevel and results in tissueregeneration in hips with earlyONFH.

References

1. Mont MA, Jones LC, Hungerford DS.Nontraumatic Osteonecrosis of theFemoral Head: Ten Years Later. J BoneJoint Surg 2006; 88A:1117-1132.

2. Ficat RF. Idiopathic bone necrosis of thefemoral head: Early diagnosis andtreatment. J Bone Joint Surg 1985; 67B: 3-9.

3. Gardeniers JWM. ARCO (AssociationResearch Circulation Osseous)international classification ofosteonecrosis. ARCO Committee onTerminology and Staging. Report on thecommittee meeting at Santiago deCompostella. ARCO Newsletter 1993; 5:79-82.

4. Steinberg ME, Hayken GD and SteinbergDR. A quantitative system for stagingavascular necrosis. J Bone Joint Surg 1995;77B: 34-41.

5. Hungerford DS. Role of coredecompression as treatment method forischemic femur head necrosis. Orthopäde1990; 19: 219-223.

6. Iorio R. Healy WL. Abramowitz AJ. PfeiferBA. Clinical outcome and survivorshipanalysis of core decompression for earlyosteonecrosis of the femoral head. JArthroplasty 1998; 13: 34-41.

Extracorporeal Shockwave in Hip Necrosis

Ching-Jen Wang, M.D.

Department of Orthopedic SurgeryChang Gung University College of MedicineChang Gung Memorial Hospital Kaohsiung Medical CenterKaohsiung, TaiwanE-mail: [email protected]

4 5

7. Mont MA, Carbone JJ, Fairbank AC. Coredecompression versus non-operativemanagement for osteonecrosis of the hip.Clin Orthop 1996; 324: 169-178.

8. Scully SP, Aaron RK, Urbaniak JR. Survivalanalysis of hips treated with coredecompression or vascularized fibulargrafting because of avascular necrosis. JBone Joint Surg 1998; 80A: 1270-1275.

9. Wei SY, Kliemkiewicz JJ, Lai M, Garino JP,Steinberg ME. Revision total hiparthroplasty in patients with avascularnecrosis. Orthopedics 1999; 22(8): 747-57.

10. Ludwig J, Lauber S, Lauber HJ, et al. High-energy shockwave treatment of femoralhead necrosis in adults. Clin Orthop 2001;387: 119-126.

11. Lin PC, Wang CJ, Yang KD, Huang CC, KoJY, Wang FS. Extracorporeal ShockwaveTreatment for Osteonecrosis of the FemoralHead in systemic Lupus Erythematosis. JArthroplasty 2006; 21(6):911-915.

12. Wang CJ, Wang FS, Huang CC, Yang KD,Weng LH, Huang HY. Treatment ofosteonecrosis of the femoral head -Comparison of extracorporeal shockwaveand core decompression and bone grafting.J Bone Joint Surg 2005; 87A: 2380-2387.

13. Wang CJ, Wang FS, Yang KD, Huang CC,Lee M SS, Chan YS, Wang JW, Ko JY.Treatment of osteonecrosis of the hip:comparison of extracorporeal shockwavewith shockwave and alendronate. ArchOrthop Trauma Surg (in press).

14. Levin D, Norman D, Zinman C, et al.Treatment of experimental avascularnecrosis of the femoral head withhyperbaric oxygen in rats: histologicalevaluation of the femoral heads during theearly phrase of the reparative process.Experimental & Molecular Pathology 1999;67: 99-108.

15. Reis ND, Schwartz O, Militianu D, Romon Y,Levin D, Norman D, Melamed Y, Shupak A,Goldsher D, Zinman C. Hyperbaric oxygen

therapy as a treatment for stage-I avascularnecrosis of the femoral head. J Bone JointSurg (Br) 2003; 85: 371-5.

16. Agarwala S, Jain D, Joshi VR, Sule A.Efficacy alendronate, a bisphosphate, in thetreatment of AVN of the hip. A prospectiveopen-label study. Rheumatology (Oxford)2005; 44;352-9.

17. Agarwala S, Sule A, Pai BU, Joshi VR.Alendronate in the treatment of avascularnecrosis of the hip. Rheumatology (Oxford)2002; 41:346-7.

18. Desai MM, Sonone S, Bhasme V. Efficacy ofalendronate in the treatment of avascularnecrosis of the hip. Rheumatology (Oxford)2005; 44:1331-2.

19. Lai KA, Shen WJ, Yang CY, Shao CJ, Hsu JT,Lin RM. The use of alendronate to preventearly collapse of the femoral head inpatients with nontraumatic osteonecrosis.A randomized clinical study. J Bone JointSurg 2005; 87A: 2155-2159.

Legends:

Figure 1. Microscopic findings with H-Estain showed significantly more viablebone and cell concentration and cellactivity in study group than the controlgroup.

Study group with shockwavetreatment prior to THA

Control group with no shockwaveprior to THA

Histomorphological features

Figure 2. Microscopic findings with vonWillenbrand factor stain showedsignificantly more new vessels(angiogenesis) in the study group thanthe control group.



vWF

Figure 3. Microscopic features withimmunohistochemical stain showedsignificantly higher VEGF expressions inthe study group than the control group.



VEGF

Figure 4. Microscopic features withimmunohistochemical stain showedsignificantly more CD 31 expressionsin the study group than the controlgroup.



CD31

Figure 5. Microscopic features withimmunohistochemical stain showedsignificantly less VCAM expressions inthe study group than the controlgroup.



VCAM

Figure 6. Microscopic features withimmunohistochemical stain showedsignificantly more PCNA expressionsand cell proliferations in the studygroup than the control group.



PCNA

Figure 7. Microscopic features withimmunohistochemical stain showedsignificantly less DKK1 expressions inthe study group than the controlgroup.



DKK1

Figure 8. Microscopic features withimmunohistochemical stain showedsignificantly more Wnt3 expressionsin the study group than the control.



Wnt3

76

angiogenesis.1 Numerous angiogenicfactors have been studied for efficacy,for which an invasive approach withconcomitant application of exogenoussubstances is common.2-4 The mode ofadministration for angiogenic factorshas also been studied, as theintended clinical use and efficacy area concern when known adverseeffects occur with systemicadministration.5-7

Application of shockwaves indifferent medical indications hascontinuously expanded since itsintroduction in urology forconcrement disintegration. Sincethen, technique as well as applicationmode have been steadily modifiedand improved. Recently,extracorporeal shockwave therapy(ESWT) is being successfully used fortreating chronic or delayed/disturbedhealing wounds. Distinct advantagesover other clinical but alsoexperimental therapeutic approachesare the non-invasiveness and theavoidance of “exogenous medication”via various substances (e.g. growthfactors, vasodilators). Although themechanisms of ESWT in ischemic softtissue pathologies are still uncertain,it seems that shockwaves affect acomplex spectrum of cellular andbio-molecular functions.

ESWT in experimentalflap surgery

Effectiveness of ESWT in reducingischemia-induced tissue necrosis wasalready shown experimentally in arodent epigastric flap model(Figure 1).8 After rendering a certainpart of the flap ischemic (ligation anddissecting a vascular bundle),shockwaves were immediatelyapplied to the ischemic challengedtissue. Seven days after, the area ofnecrosis was substantially reduced incomparison to the untreated controlgroup. Although this finding is ofenormous clinical interest, clinicians(especially reconstructive traumasurgeons) are regularly confrontedwith delayed (e.g. 24 hours) tissuenecrosis following reconstructive(flap) surgery. Thus, a treatmentoption to intervene in such cases withalready macroscopically visible failureis highly desirable. ESWT fulfills thisrequirement as seen in delayedtreatment of the above mentionedrodent epigastric flap performed inour institution. The study follow upshowed that the ischemic challenged

flap developed significantly lessnecrosis as compared with thecontrol group (Figure 2).A physiological process during woundhealing is the wound contraction andreflects in some manner the quality ofwound healing (collagen composition).Wound contraction should beminimal, especially for wound areasadjacent to joints which have to becovered by skin transplants or flaptransfer. Preventing or minimizingcontraction (extensive scarformation) results in less constrainedrange of motion in the involved jointsand avoids surgical revisions. But alsoareas adjacent to orifices (face,beside the aesthetic point of view)are vulnerable to contraction andshould be kept at a minimum. In thesame study set up, less flapcontraction concomitant with lessnecrotic area was observed.Encouraged by these findings, weaddressed a further issue in electivetreatment. Although in electivesurgery a broad spectrum of possiblecomplications can effectively beavoided, a residual risk which isincalculable exists especially inpatients with co-morbidities(e.g. disturbed wound healing indiabetic patients). A tremendousamount of professional care efforts(wound care, wound revision) andsocial financial burden could bereduced if an elective treatmentexisted which would prepare thetissue as needed for the anticipatedsurgical intervention. Surgicalprocedures in a two stage mannerwere evaluated to reduce necrosisand showed effectiveness.9

For instance, in the first stage of flapsurgery, only incisions will be made toinduce the following increased tissueperfusion and to prepare the tissuefor transfer in the second stage.Although this procedure shows apositive impact in the latter flapoutcome, it nevertheless representsan invasive approach with its sideeffects (e.g. infection risk). When weexperimentally applied shockwaves tothe flap prior to surgery, we wereable to see a reduction in necroticarea equal to the above mentioneddelayed treatment. This is of greatclinical relevance, because clinicianswould have the opportunity toselectively treat patients prior tointended surgery who are at high riskof suffering from wound healingdisturbances afterwards.

These findings in reducing tissuenecrosis by ESWT are comparablewith those studies which usedexogenous growth factors(e.g. therapeutic angiogenesis) in thesame indication.10,11 An enormousadvantage, however, over thesestudies is the non-invasiveness of ourapproach in the application ofshockwaves. Additionally, no adverseeffects over the entire study periodwere observed. Further advantagesare that the application is simple, it iswell-received by the patients, and iscost effective.

Compromised tissueperfusion and theinfluence of ESWT

Probably one of the worstscenarios in reconstructive surgery(e.g. after free flap transfer withmicro-anastomosis) represent tissueloss due to hypoxia or ischemia, asalready mentioned above. Severalapparatuses and methods exist forearly detection of this unfavorablecondition. However, treatmentoptions after verification of this statusare scarce. In the described animalmodel, flap ischemia could be verifiedbeyond doubt by clear bluedemarcation 24 hours after vesselligation. In addition, a clinically used,non-contact, Doppler based systemcould confirm the clinicalmacroscopic finding. The principle isthat a low intensity laser light beamscans the surface of the skin andgenerates a 2-dimensional image offlap perfusion. With this technologythe ischemic impact was confirmed inall test animals by a distinctreduction in flap perfusion.

Recent studies, predominantlyexperimental ones, demonstratedthat ESW treated tissues, which werevulnerable to disturbed woundhealing, showed modified releasekinetics of essential growth factorsLIT and induced angiogenesis. Thisimproved circulation may havedistinct benefits in wounds subjectedto healing disturbances. Growthfactors which are of interest includedamong others angiogenesis relatedfactors and their early expressionpatterns. It was shown that thesegrowth factors were up-regulated.This results in angiogenesis withconcomitant improved tissueperfusion, increased cell proliferationand accelerated tissue regeneration

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Delayed/Non-healing or chronicwounds are an enormous challenge(physically, but also mentally) to eachpatient affected. Such woundssignificantly impair the quality of life formillions of people. Intensive treatmentis required and imparts an enormousburden on society in terms of lostproductivity and health care costs.

Tissue ischemia/hypoxia is one ofthe major factors affecting anuncomplicated wound healing processpotentially resulting in a chronicwound condition. Numerous surgicalspecialties are confronted withcompromised tissue perfusion, oftenresulting in extensive operativerevisions. This is especially seen in

patients with co-morbiditiessuch as diabetes andperipheral ischemic diseases(e.g. arteriosclerosis).The intrinsic capacity forphysiological tissueregeneration is often severelyimpaired in these patients.If wounds require skin flapcoverage in this patientpopulation, then thetransferred flaps may also benegatively affected by theunderlying pathology. Skin flapsurgery using autologousdonor tissue is the treatmentof choice for patients withlarge wounds or tissue defects.Depending on the size of thedefect, either skin grafts,muscular flaps or composite

flaps may be used. Necrosis of skinflaps, either partial or complete,remains a serious complication in skinflap surgery. Insufficient arterial(in)flow with the accompanyingdecreased nutritional supply tohypoxic/ischemic tissues can bepotentially overcome by therapeutic

When is the right time for ESWT?Influence of ESWT on Ischemia Induced Tissue Necrosisand Its Correlation with Application Time

Rainer Mittermayr,1,2 Joachim Hartinger,1

Martina Hofmann,1 Wolfgang Schaden,2 Heinz Redl1

1 Ludwig Boltzmann Institute for experimental and clinical Traumatology AUVA Research CenterAustrian Cluster for Tissue Regeneration

2 AUVA Trauma Center MeidlingVienna, Austria

98

and healing.12,13 Using the Dopplerbased perfusion imaging system, aclear enhancement of circulation inthe experimental flaps was noticeableat the time point when shockwaveswere applied (Figure 3). Thissupports the hypothesis thatangiogenesis with concomitantimproved tissue perfusion/improvedblood supply is one of the mechanismsof ESWT in ischemic/hypoxic wounds.

Transplant surgery is oftenconfronted with limited healing oftransferred tissue to the wound bed.Possible causes are seroma formationwhich prevents the nutritional supplyfrom the wound bed to the overlyingtissue, ultimately resulting in flap loss.Additionally, the lack of full tissuecontact prevents the formation of newvessels (angiogenesis) which aremandatory for flap outcome, especiallywhen subjected to a certain degree ofhypoxia (ischemia). Macroscopicevaluation in our experiments showedthat transplanted flaps treated withshockwaves have better adherence tothe wound bed in the ischemicchallenged flap area in comparison tocontrols which were left untreated.Surprisingly, this was not due toreduced seroma formation (nearlyequal amounts between shockwavegroups and control group).

In summary ESWT was found as afeasible therapeutic tool in preventingnecrosis in ischemic challenged tissue.This therapeutic effect was seen astime-independent. This is of greatclinical relevance, because theclinicians have a certain therapeuticwindow in which ESWT shows itseffectiveness. Tissue subject tohypoxia/ischemia after surgery iseligible for this non-invasive, cost-effective approach and may helpreduce extensive surgical revisions andprolonged wound care. Likewise,patients susceptible to wound healingdisturbances could be treated prior tonecessary surgical interventions, thusminimizing postoperative complications.

References1. Hockel, M., Schlenger, K., Doctrow, S.,

Kissel, T. & Vaupel, P. Therapeuticangiogenesis. Arch. Surg. 128, 423-429(1993).

2. Pepper, M. S. Manipulating angiogenesis.From basic science to the bedside.Arterioscler. Thromb. Vasc. Biol. 17,605-619 (1997).

3. Zhang, F., Waller, W. & Lineaweaver, W. C.Growth factors and flap survival.Microsurgery 24, 162-167 (2004).

4. Vranckx, J. J. et al. In vivo gene delivery ofAd-VEGF121 to full-thickness wounds inaged pigs results in high levels of VEGFexpression but not in accelerated healing.Wound. Repair Regen. 13, 51-60 (2005).

5. Kryger, Z. et al. The effects of VEGF on

survival of a random flap in the rat:examination of various routes ofadministration. Br. J. Plast. Surg. 53,234-239 (2000).

6. Eppler, S. M. et al. A target-mediated modelto describe the pharmacokinetics andhemodynamic effects of recombinanthuman vascular endothelial growth factorin humans. Clin. Pharmacol. Ther. 72, 20-32(2002).

7. Yang, R. et al. Substantially attenuatedhemodynamic responses to Escherichiacoli-derived vascular endothelial growthfactor given by intravenous infusioncompared with bolus injection. J.Pharmacol. Exp. Ther. 284, 103-110 (1998).

8. Meirer, R., Kamelger, F. S., Huemer, G. M.,Wanner, S. & Piza-Katzer, H. Extracorporalshock wave may enhance skin flap survivalin an animal model. Br. J. Plast. Surg. 58,53-57 (2005).

9. Wong, M. S. et al. Basic fibroblast growthfactor expression following surgical delayof rat transverse rectus abdominismyocutaneous flaps. Plast. Reconstr. Surg.113, 2030-2036 (2004).

10. Michlits, W., Mittermayr, R., Schafer, R.,Redl, H. & Aharinejad, S. Fibrin-embeddedadministration of VEGF plasmid enhancesskin flap survival. Wound. Repair Regen.15, 360-367 (2007).

11. Mittermayr, R. et al. Abstract at TERMIS2005, Stutgart. Wound.Repair Regen. 2008.Ref Type: In Press

12. Wang, C. J. An overview of shock wavetherapy in musculoskeletal disorders.Chang Gung. Med. J. 26, 220-232 (2003).

13. Nishida, T. et al. Extracorporeal cardiacshock wave therapy markedly amelioratesischemia-induced myocardial dysfunctionin pigs in vivo. Circulation 110, 3055-3061(2004).

IntroductionThe incidence of midsubstance

Achilles tendinopathy has risen. Thecondition is common in recreationaland competitive athletes, particularlyamongst runners and athletesparticipating in racquet sports, trackand field, volleyball and soccer. Theincidence of Achilles tendinopathy intop level runners has been estimatedat between 7 and 9%. Of note, a10-fold increase in Achilles tendoninjuries has been reported in runnerscompared to age matched controls.However, Achilles tendinopathy is alsocommon in the sedentary population.In a recent study, 31% of 58 Achillestendinopathy patients did notparticipate in vigorous physical activity.

Aetiology andpathophysiology

Tendon injuries can be acute orchronic, and are caused by eitherintrinsic or extrinsic factors. In acutetrauma, extrinsic loads exceed thetensile strength of the tendon. Overuseinjuries generally have a multifactorialorigin. Gastrocnemius-soleusdysfunction, advanced age, body weight,pes cavus, and lateral ankle instabilityare common intrinsic risk factors.Changes in training pattern, poortechnique, previous lower extremityinjuries, footwear and environmentalfactors such as training on hard, slipperyor slanting surfaces are extrinsic factorswhich may also predispose the athlete toAchilles tendinopathy.

The relationship betweenexcessive tendon loading, clinicalsymptoms, and abnormalhistopathology remains unclear.Excessive loading of tendons duringvigorous physical training is generallyregarded as the main pathologicalstimulus for degeneration but not alldata supports this hypothesis. In onestudy on chronic Achilles tendinopathy(342 tendons), physical activity wasnot correlated to the extent ofhistopathological changes, suggestingthat physical activity may be moreimportant in evoking the symptomsthan being the root cause ofpathology. The lack of associationbetween activity, pain and structuralabnormality has also been reported inother tendons. Further pathologicalchanges are seen not uncommonlyseen on imaging studies inasymptomatic individuals who arephysically active.

Tendons respond to repetitiveoverload beyond physiologicalthreshold by either inflammation oftheir sheath, degeneration of theirbody, or a combination of both. Itremains unclear whether differentstresses induce different responses.Tendon damage may also occur from

Mid-portion Achilles tendinopathy -What role is there for shock wave treatment?

Jan D. Rompe MD

Professor of Orthopaedics, OrthoTrauma EvaluationCenter, Oppenheimer Str. 70, D-55130 Mainz, Germanye-mail: [email protected]

Figures:

Figure 3. Superficial flapperfusion assessed by LDI

system. Depicted are typicalperfusion images in the control

group and post-OP groupduring the 7 day interval.

An increase in perfusion on day7 postoperatively is evident in

the flaps which were treatedwith shockwaves. Each grouphad a drop in perfusion postsurgery caused by ligation ofthe neurovascular bundle (1h

post ischemia).

Figure 2. Necrosis of entireflap on day 7 after surgery.

Representative images ofeach group are depicted. A

clear reduction of tissuenecrosis is noticeable in all

shockwave treatment groupsin comparison to the control

group. Within the differenttreatment groups no

differences were found. (A)Control group (B) 24h pre-OPgroup (C) post-OP group (D)

24h post-OP group.

Figure 1.Application of

shockwaves in theischemic third of

the flap usingultrasound

conduction gel. Itis an epigastric flapwith dimensions ofapproximately 8x8

cm, divided intovital, transition and

ischemic areas(blue lines).

management of acute athletic injuries,often for analgesic purposes.The evidence to support enhancedhealing is limited. There is some datathat suggests that NSAIDs impairtendon healing. In one study, NSAIDswere shown to inhibit tendon cellmigration and proliferation. NSAIDs hadlittle or no effect on the clinicaloutcome.

Cryotherapy has been regarded as amost useful intervention in the acutephase of Achilles tendinopathy, as it hasan analgesic effect, reduces themetabolic rate of the tendon, anddecreases the extravasation of blood andprotein from new capillaries found intendon injuries. Intermittentcryotherapy of 3x10 min significantlydecreased local Achilles tendonmid-portion capillary blood flow by 71%.Postcapillary venous filling pressureswere reduced during cryotherapy,favouring capillary venous outflow of thehealthy Achilles tendon.

Peritendinous injections withcorticosteroids are still controversial,evidence for their effectiveness ismissing, and there are no good scientificreasons to support their use. The shortterm effect of corticosteroid injectionhas been shown in the Achilles withimprovement in walking pain andreduction in tendon diameter asmeasured by US. Intratendinousinjections of corticosteroids are to beavoided due to their catabolic effects.

Eccentric training is a populartreatment in Scandinavia. Severalcentres have reported good andexcellent results with this treatmentregime. Alfredson evaluated a 12-weekeccentric calf muscle trainingprogramme for painful midportionAchilles tendinopathy. Alfredson's modelof eccentric training involves noconcentric loading and emphasizes theneed for patients to complete theexercise protocol despite pain in thetendon. Good short- and long-termclinical results have been reported.This program was effective when otherconventional management modalities(rest, NSAIDs, change of shoes,orthoses, physical therapy, ordinarytraining programs) had failed, and thetraining was successful in approximately90% of patients.

Not all trials involving eccentrictraining have been favourable. Recently,a Danish group examined found nodifference when comparing the effect ofeccentric exercises with conventional

stretching exercises. In 2006 Sayana andMaffulli studied the effects of eccentricexercises in sedentary non-athleticpatients. Fourty-four percent of thethirty-four patients with a clinicaldiagnosis of unilateral tendinopathy ofthe main body of the Achilles tendon didnot improve with the eccentric exerciseregimen.

None of several possible explanationsfor the clinical effectiveness of eccentricexercise have been fully investigated.Volume and signal on MRI are increased.Type I collagen production is affected,and, in the absence of ongoing insult,this might increase the tendon volumeover the longer term. An influence of themechanical insult of the trainingprogram on the pain producing nervesand paratendinous blood flow has alsobeen discussed. In one observationalstudy, patients satisfied with the resultof the eccentric training regimen had noremaining neovascularisation, and allpatients with a poor clinical resultcontinued to demonstrateneovascularisation. This hypothesis wasnot supported by recent publications.

Alfredson and Cook suggestedinjection of a vascular sclerosant(Polidocanol) - an aliphatic non-ionisednitrogenfree substance with a sclerosingand anaesthetic effect - in the area withneovascularisation anterior to thetendon. Six months after this injection,eight of ten tendons were pain-free aftera mean of two treatments. Thosetendons that were painfree had noneovascularisation outside or inside thetendon, but vessels remained in the twonon-successfully treated patients. In alonger follow-up study color Dopplerultrasound showed no, or a few,remaining neovessels in the majority ofthe successfully treated tendons.As vessel number has been shown tocorrelate with tendon thickness,treatment that decreases vessel numberis likely to also affect tendon thickness.

Topical glyceryl trinitrate has beeninvestigated in randomised controlledtrials in the Achilles, elbow andsupraspinatus tendons as an adjunct toan eccentric exercise program. Thetopical glyceryl trinitrate was applied tothe tendon as a patch that was renewedeach day for six months. The treatmentwas compared to a placebo patch, andpain and function were measured over 6months. In the Achilles tendon, activitypain in the treatment group wasreduced at 12 and 24 weeks comparedto placebo and it also improvedoutcomes at six months. This study

supported the use of an eccentricexercise program, as 49% of the non-GTN group also reported excellentoutcomes.

Shock Wave Treatment (SWT) hasemerged as another effective treatmentfor Achilles tendinopathy. Pilot studiesinvestigating the effects of SWT onAchilles tendinopathy have beenpromising. Lohrer et al. reportedsignificant pain reduction and increasedfunctionality in patients with Achillestendinopathy who were treated withradial SWT. There was no control group,however. Perlick et al. compared SWTwith surgery as a treatment for chronicAchilles tendinopathy. At 1-year follow-up, there was a statistically significantreduction in pain in both groups.

In a small, randomized, double-blinded, placebo-controlled trialconsisting of 39 patients, Peers reportedhis experience using low-energy SWTfor the treatment of patients withchronic Achilles tendinopathy.At 12-week follow-up, the 20 treatedpatients had significantly improvedVAS when compared with an untreatedcontrol group. A 77% success rate wasreported.

Furia evaluated the effects of a singlehigh-energy SWT on a consecutiveseries of 35 patients with chronicAchilles tendinopathy that had notresponded to nonoperativemanagement, 33 patients with chronicinsertional Achilles tendinopathy werenot treated with SWT, but instead weretreated with additional forms ofnonoperative therapy (control group).At one month, 3 months, and 12 monthsfollowing treatment, the mean VASimproved significantly more in the SWTgroup. Patients in the SWT grouptreated under local anaesthesia had asignificant lower improvement in VASscore than the corresponding gain in thenon-local anesthesia subgroup.

In a recent randomized, controlledtrial, Rompe compared the effectivenessof three management strategies for thetreatment of noninsertional Achillestendinopathy. Group one was treatedwith eccentric loading exercises, grouptwo was treated with repetitivelowenergy radial SWT, and group 3 wastreated with a 'wait-and-see' approach.All of the 75 enrolled patients hadreceived unsuccessful management withtraditional nonoperative methods for aminimum of 3 months. At 4 monthsfrom baseline, the VISA A Scoreincreased in all groups, pain ratingdecreased in all groups. For all outcomemeasures, groups 1 and 2 did not differ

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stresses within physiological limits, asfrequent cumulative microtrauma maynot allow enough time for repair.

Free radical damage occurring onreperfusion after ischaemia, hypoxia,hyperthermia and impaired tenocyteapoptosis have been linked withtendinopathy, as have been localadministration of cytokines andinflammatory agents. Ciprofloxacincauses enhanced interleukin-1-mediated MMP3 release, inhibitedtenocyte proliferation, and reducedcollagen and matrix synthesis. Changesin the expression of genes, regulatingcell-cell and cell-matrix interactions inAchilles tendinopathy, have beenreported, with down-regulation ofmatrix metalloproteinase 3 (MMP 3)and up-regulation of MMP2 mRNA intendinopathic Achilles tendon samples.

HistopathologyThe pathologic label 'tendinosis' is

used to describe the disorganizedimpaired healing response intendinopathy. Despite that, mostclinicians still use the term “tendonitis” or“tendonitis”, thus implying that thefundamental problem is inflammatory.I advocate the use of the termtendinopathy as a generic descriptor ofthe clinical conditions in and aroundtendons arising from overuse, andsuggest that the terms tendinosis,tendonitis and tendinitis only be usedafter histopathological examination.

Various types of degeneration may beseen in tendons, but in the Achillestendon 'mucoid' or 'lipoid' degeneration isusually seen. In mucoid degeneration,light microscopy reveals large mucoidpatches and vacuoles between fibres.In lipoid degeneration, abnormalintratendinous accumulation of lipidoccurs, with disruption of collagen fibrestructure.40 In general, tendinopathy ischaracterized by cellular activation andincrease in cell numbers, increase inground substance, collagen disarray andneovascularisation, with an appearanceof a failed healing response. Histologicalevaluation of Achilles tendon biopsies,intratendinous microdialysis andcontemporary molecular biologytechniques (cDNA-arrays, real-timequantitative PCR) of appropriatelyprepared biopsy tissue, all failed to showevidence of prostaglandin-mediatedinflammation.

Clinical PresentationPain is the cardinal symptom of

Achilles tendinopathy. Pain occurs at thebeginning and a short while after the endof a training session, with a period of

diminished discomfort in between. As thepathological process progresses, pain mayoccur during the entire exercise session,and, in severe cases, it may interfere withactivities of daily living.

In the acute phase, the tendon isdiffusely swollen and edematous, and onpalpation tenderness is usually greatest 2to 6 cm proximal to the tendon insertion.Crepitation is common. In chronic cases,exercise-induced pain is still the cardinalsymptom, but crepitation and edemadiminish. The tendon becomes thick,firm, and nodular.

The first priority of the clinicalexamination is to exclude acute rupture.The calf squeeze test is easy to performand has excellent validity. Afterdemonstrating that the tendon is intact,the examination should aim to provoketendon pain during tendon-loadingactivity. In most patients, simple single-leg heel raises will be sufficient to causepain. In more active individuals, however,it may be necessary to ask the patient tohop on the spot, or hop forward, tofurther load the tendon and reproducepain. The differential diagnoses includetenosynovitis or dislocation of theperoneal or other plantar flexor tendons,irritation or neuroma of the sural nerve,and systemic inflammatory disease.Although these conditions may causepain in and also around the Achillestendon; true Achilles tendon pain isnearly always confined to the tendonitself.

Imaging methodsAchilles tendinopathy is a clinical

diagnosis mainly based on a carefulhistory and detailed clinical examination.At times, however, however, diagnosticimaging may be required to verify aclinical suspicion or, occasionally, toexclude other musculoskeletal disorders.

Ultrasonography is widely used inEuropean countries. It is easily available,quick, safe, and inexpensive. However,ultrasound is operator-dependent, hassomewhat limited soft tissue contrast,and is not as sensitive as MRI.

Colour and power Doppler haverecently added a new dimension tostandard ultrasound tendon imaging. Thisimaging demonstrates blood flow intissues. Alfredson´s group reports that, innormal Achilles tendons, blood flow wasnot detectable, but colour Doppler oftenreveals blood flow in pathologicaltendons. Such blood flow was linked togreater pain scores, poorer function andlonger standing symptoms in the Achillestendon, compared with controlparticipants who have no visible flow.The association, however, was not

absolute. The long term clinicalimportance of blood vessels inpathological tendon is not clear, especiallyas more refined examinationsdemonstrated vascularization also innon-tendinopathic Achilles tendons.Koenig ultrasonically detected arteriesin all normal tendons with Doppler aftercontrast injection. Accordingly,abnormalities in vascularity might beage-related, and age-stratified normalmaterials is needed to define normality.

MRI is also a helpful diagnostic study.MRI provides extensive information onthe internal morphology of tendon andthe surrounding structures, and is usefulto evaluate various stages of chronicdegeneration and for differentiationbetween peritendinitis and tendinosis.Excellent correlation between MRI andpathological findings at surgery has beenreported. Areas with increased signalintensity seen on MRI correspond withareas of altered collagen fiber structureand increased interfibrillar groundsubstance (proteoglycans and hydrophilicglycosaminoglycans). Signal intensity onMR has been associated with clinicaloutcome.

TreatmentBoth conservative and nonoperative

treatment have a role in the managementof Achilles tendinopathy. The initialtreatment is nonoperative. Earlyintervention is paramount.

Seeking medical attention at an earlystage may improve outcome, astreatment becomes more complicatedand less predictable when the conditionbecomes chronic.

Unfortunately, the scientific level ofevidence for most of conservative andsurgical treatments remains low.

Initial conservative management mostcommonly consists of a combination ofstrategies, including abstention from theactivities that caused the symptoms, andcorrection of training errors, footmalalignments, decreased flexibility, andmuscle weakness.

Treatments that have beeninvestigated with randomised controlledtrials include nonsteroidal anti-inflammatory medication (NSAID),eccentric exercise, glyceryl trinitratepatches, electrotherapy (microcurrentand microwave), sclerosing injections,and shock wave treatment. There are norandomized or prospective studies thatcompare different conservative andsurgical treatment regimens.

Nonsteroidal antiinflammatory drugs(NSAIDs) are frequently used in the

12 13

significantly. For all outcome measures,groups 1 and 2 showed significantlybetter results than group 3.

Costa, in an earlier publication, haddeviated from the protocols used by Furiaand Rompe. In the Costa trial, 49 patientswere treated once a month for 3 months.The primary outcome measure was areduction in Achilles tendon pain duringwalking at 4 weeks after the lastSWT/sham SWT. No difference in painrelief was found between the shock wavetherapy group and the control group.

None of several possible explanationsfor the clinical effectiveness of shockwave treatment have been fullyinvestigated. The rationale for SWT inclinical use is inhibition of pain receptorsand stimulation of soft-tissue healing. Inthe periphery, SWT leads to selectivedysfunction of sensory unmyelinatednerve fibres without affecting the largemyelinated nerve fibres responsible formotor function. For high energytreatment, this selective destruction ofsensory unmyelinated nerve fibres withinthe focal zone of SWT may contribute toclinically evident long-term analgesia.For low-energy application, analgesia mayresult from shock wave-induceddestruction of sensory nerve fibres withliberation of neuropeptides, such ascalcitonin gene related peptide (CGRP),resulting in a local neurogenicinflammation in the focal area withsubsequent prevention of sensory nerveendings from re-innervating this area.Centrally, the findings of a reduction inthe number of neurons immunoreactiveto CGRP and substance P without areduction in the total number of neuronswithin the lower lumbar dorsal rootganglia (DRG) probably are a secondaryeffect following the decrease in thenumber of sensory nerve fibres in thefocal zone of shock wave application.Similar results were reported for neuronsimmunoreactive for CGRP within theDRG of the mouse after transaction of thesciatic nerve. Therefore, both theperipheral and central nervous systemmay play a pivotal role in mediating shockwave-induced long-term analgesia.

In the only human experiment,Klonschinski investigated whether thebiological effects of SWT differedbetween application with and without anLA. SWT was applied to the skin eitherafter local pre-treatment with lidocaincream LA or without LA to thecorresponding location of thecontralateral limb. Increasing energy fluxdensity led to a significant increase ofpain. LA significantly attenuated this painand significantly inhibited C-fibre activity,

with a significant reduction in localvasodilation. Reduction in vasodilationcorrelated positively with the amount ofenergy flux density applied. SWT withoutLA resulted in a dose-dependent lowerpressure pain threshold, i.e. sensitization,than did SWT with LA.

With regard to soft-tissue healing,Taiwanese research groups investigatedthe effect of low-energy SWT onneovascularization at the tendon-bonejunction in rabbits. Low-energy SWT(LESWT) produced a significantly highernumber of neo-vessels and angiogenesis-related markers, including endothelialnitric oxide synthase, vessel endothelialgrowth factor and proliferating cellnuclear antigen than the control withoutSWT. Only an optimal number of200-500 impulses of LESWT promotedclinical resolution of Achillestendinopathy by inducing TGF-beta1 andIGF-I and increased the contact betweenbone and tendon as well as tensilestrength.

Surgical treatmentIn 24% - 45.5% of patients with

Achilles tendinopathy, conservativemanagement is unsuccessful, and surgeryis recommended after exhaustingconservative methods of management,often tried for at least six months. For theAchilles tendon, frequency of surgery hasbeen shown to increase with patient age,duration of symptoms, and occurrence oftendinopathic changes.

The objective of surgery is to excisefibrotic adhesions, remove degeneratenodules and make multiple longitudinalincisions in the tendon to detectintratendinous lesions and to restorevascularity and possibly stimulate theremaining viable cells to initiate cellmatrix response and healing. Recentinvestigations show that multiplelongitudinal tenotomies triggerneoangiogenesis at the Achilles tendon,with increased blood flow. This would bedue to the fact that, in the failed healingresponse typical of tendinopathy,vascularisation, though present, ishaphazard and non-functional. Thiswould result in improved nutrition and amore favourable environment for healing.Patients are encouraged to weight bear assoon as possible after surgery. Mostauthors report excellent or good resultsin up to 85% of cases, although this is notalways observed in routine non-specialised clinical practice. Percutaneoustenotomy resulted in 75% reporting goodor excellent results after 18 months.Open surgery for Achilles tendinopathyhas shown that the outcomes are better

for those tendons without a focal lesioncompared with those with a focal area oftendinopathy. At seven months aftersurgery, 67% had returned to physicalactivity, 88% in the no lesion group and50% in the group with a focal lesion.

It is difficult to compare the results ofstudies as most studies do not reporttheir assessment procedure. Also, noprospective randomized studiescomparing operative and conservativetreatment of Achilles tendinopathy havebeen published. Thus, most of ourknowledge on treatment efficacy is basedon clinical experience and descriptivestudies. Under all circumstances, Achillestendon surgery requires extensive post-surgical rehabilitation, and the resultsafter surgery may only as good as thestrength and functional capacity that isregained. Adequate attention torehabilitation is likely to improveoutcomes for those that are surgicallytreated.

ConclusionsAlthough Achilles tendinopathy has

been extensively studied, there is a clearlack of properly conducted scientificresearch to clarify its etiology, pathologyand optimal management. Most patientsrespond to conservative measures if thecondition is recognised early, whilecontinuing the offending activities leadsto chronic changes which are moreresistant to non-operative management.

Teaching patients to control thesymptoms may be more beneficial thanleading them to believe that Achillestendinopathy is fully curable. Inrandomised controlled studies, painfuleccentric heavy loading exercises andshock wave treatment have shownencouraging outcomes. Surgery usuallyinvolves removal of adhesions anddegenerated areas, and longitudinaltenotomy may influence the localcirculation in a beneficial way. It is stilldebatable why tendinopathic tendonsrespond to surgery. For example, we donot know whether surgery inducesrevascularization, denervation or both,resulting in pain reduction. It is alsounclear how longitudinal tenotomyimproves vascularization. As the biologyof tendinopathy is being clarified, moreeffective management regimens maycome to light, improving the successrate of both conservative and operativemanagement.

IntroductionPreviously the Extracorporal Shock Wave Therapy

(ESWT) was established for example for disintegratingrenal caculi and gallstones. Currently the ESWT issuccessfully used in therapy against pseudoarthrosis,plantar fascitis, tendinosis calcarea and wound healingdisorders. Numerous in vivo studies underline the goodresults of this method of therapy. Our studies arefocused on cellular effects of extracorporal shock waveson migration, proliferation and growth of isolated humanmesenchymal stem cells (MSCs). MSCs have beendiscussed for a very long time as being a useful tool forthe treatment of various disfunctions. For therapeuticapplication of MSCs different invasive methods havebeen described before. Shock waves are generatedextracorporal and would represent a first non-invasiveway to influence and guide MSCs to the target area.

Extracorporal ShockWaves InfluencesMigration, Proliferationand Growth of HumanMesenchymal Stem Cells

The Effectiveness andImportance ofMechanotransduction withinDifferentiated Human ConnectiveTissue and Adult Stem Cells(in vitro study)

H. Neuland*,

Y. Delhase **,

H.-J. Duchstein***,

A. Schmidt**, W. Bloch **

* ZES, Centre for Extracorporal Shock Wave Therapy,Kronberg im Taunus

** Institute for Cell- and Molecularbiology, German Sports University Cologne

*** Pharmaceutical Insitute University Hamburg

Characteristics of the ESW

For our studies we use the piezoelectricextension of Piezoson 100 (Wolf Inc.Knittlingen, Germany)

• High peak pressure(100 MPa)

• Short lifecycle (10 ms)• Rapid pressure rise time

(< 10 ns)• Broad spectrum of

frequencies(16 Hz – 20 Mhz)

• High shear stress atthe interface

14 15

MechanotransductionThe Mechano Transduction leads to the

transformation of mechanical sensations into cellularimpulses. The routes of these impulses are time-dependent in different supporting connective tissue.These routes induce a certain flow direction ofinformation. There after arising follow-up signals, whichare considered as biological information units, lead tovery specific signals and thus to equally specificbiological transformation within the cellular structure.

The adherence to precise method of application bymeans of mechanical stimulus is of utmost importance.

For the first time we were able to prove thatmechanical activation of stem cells is possible with thehelp of extra corporal shock waves.

Hereby establishing further therapy methods.

Adult Stem CellsWithin the grown-up body stem cells are found during the whole life. These so-called

adult stem cells mainly occur in the bonemarrow, but also in the liver and brain. Until todayit is not exactly clear as to whether they might exist in other organs as well.

As opposed to embryonic stem cells which can diversify into all types of tissue, adult orspecific stem cells exhibit a limited potential for differentiation.

Adult or tissue specific stem cells differentiate into different types of tissue.The bone marrow contains two types of stem cells:

the haematopoetic (HSC) andthe mesenchymale (MSC) stem cells

Embryonic Stem CellsStem cells first appear during in the early embryonic

development. The fertilized ovum (Zygote) alreadyrepresents a totipotent stem cell, which is able todevelop all kinds of human tissue.

Mesenchymal Stem Cells (MSCs)The MSCs are omnipotent, they are able to differentiate

not only in vivo but also ex vivo in special tissue cells:heart and skeleton muscle cells, bone and cartilage cells,connective and fat tissue.

Ways of Differentiation of MSCsThe purpose of the MSCs is the regeneration and

reparation of tissue.

This means:Stem cells are necessary for the reparation and

regeneration within living tissue.

Furthermore:Aging is a process of imbalance between degeneration

and regeneration.

Putting it differently:The loss of self-renewal in adult stem cells describes

one of the most important reasons for growing old.

The question of the following study was:Are extracorporal shock waves able to influence the

activity, proliferation and growth of MSCs?

The study was approved by the local ethicscommitee and conforms to the declaration of Helsinki.

Some pictures are to find by internet http://stemcells.nih.gov/info

The Influence of Extracorporal Shock Waveson Migration Activity of Mesenchymal Stem Cells(MSCs)

* ECM: Extra Cellular Matrix

Cell Culture and ManipulationPurification and Selection of Marrow-Derived Stroma

Cells

MSCs Cell Culture and Quality Control

Microscopic assessment of the morphology– Flow cytometry– CFU-Assay– Differentiation assay

The differentiation potential of MSCs was controlled byculturing the cells under conditions that were favourablefor adipogenic, osteogenic and chondrogenic differentiation.

Before migration wasstarted, cells were treatedwith shock waves Piezoson100, Company Wolf,Germany.

Materials and Methods

Application of Shock Waves

Shock waves were applied toadherent MSCs. In order to imitatenatural application in in vivo culturedishes were completely filled with mediaand covered with freshly prepared porkskin.

Ultrasound gel was placed on top ofthe pork skin to ensure best adjustmentto the shock wave system.

Ficoll

16 17

Results1. Boyden Chamber Assay

Migration Assay was performed in a modified Boyden-Chamber assay. 5 x 104 single cells were put onto the top ofa Falcon® HTS Fluoro Blok™ inserted and incubated for 8hours in 20 % alpha-MEM.

For the shock wave treatment 3 parameters were altered:• Number of applications

(500 or 1000 applications)• Frequency

(2 or 4 applications per second)• Density of energy

(from 0,048 mJ/mm2 to 0,238 mJ/mm2)

Shock waves significantly increase the migratory activityof MSCs.

2. Growth rate

Equal amounts of freshly isolated MSCs were plated ontotwo culture dishes. After grown to a confluent monolayerone dish was treated with singular shock waves, the otheruntreated dish served as control. Afterwards MSCs weredetached by AccutaseTM, counted and replated onto freshdishes (5 x 104 cells/dish). The amount of MSCs wasmonitored until passage 5.

Growth of MSCs significantly increased in the firstpassage after the shock wave treatment. In later passagesMSC growth was not influenced compared to the controlreference.

3. Proliferation Assay with Anti-Ki67

MSCs were fixed and used for immunhistochemistryby using rabbit anti-Ki67 (1:200, abcam,Cambridge, UK) to detect proliferative nuclei.Immunhistochemistry was developed by DAB.Positive and negative nuclei were microscopicallyquantified.

Shock waves significantly increase the proliferation ofMSCs.

In the case of more than 1000 impulses the activity of alltested parameters is reduced.

Summary and Conclusions• Shock waves increase the migratory activity of MSCs when using distinct conditions.• The results of shock wave treatment depend on number of applications, frequency and

density of energy.• Shock waves significantly increase MSC growth in the first passage after treatment.• Shock waves significantly increase MSC proliferation.• Shock waves might be the first approach to mobilise stem cells without invasion.• The strong effects of shock waves onto MSCs indicate that these cells can be

influenced by mechanic stimuli.

CONTACT:

ZESCentre for Extracorporal Shock WaveTherapy

Dr. Helmut NeulandE-mail: [email protected]ße 23F61476 Kronberg/Ts., GermanyTel. +49 (0)61 73/94 05 80Fax +49 (0)61 73/94 05 82

SummaryCalf muscle tightness and

restricted dorsiflexion of the anklejoint are risk factors for many lowerlimb disorders, especially Achillestendinosis. The origin of the muscletightness remains unclear, butreducing the tension within themusculo-tendinous system leadsgenerally to a reduction of pain.

The aim of this retrospective studywas to investigate the possibility ofimproving active calf muscleextensibility by the use ofExtracorporeal Pulse ActivationTherapy (EPAT) in patients withchronic Achilles tendon pain andrestricted dorsiflexion in the anklejoint. Therefore, pressure pulse waveswere applied to the shortened calfmuscles in 78 patients, and activedorsiflexion of the affected ankle jointwas measured before and aftertherapy. The mean active dorsiflexionmeasured prior to ExtracorporealPulse Activation Therapy was 3.6°(SD 3.7°; range -3° to 10°). After anaverage of 4.6 sessions with 6000pressure waves per session, asignificant increase in activedorsiflexion to 11.5° (SD 5.1°; range -2° to 21°) was found. Follow-upexaminations conducted after anaverage of 4.2 months (range 3 to 6months) after the end of therapyshowed a persistent increase inmaximal active dorsiflexion to 11.7°(SD 5.6°; range -2° to 22°). As thepain in the treated muscle indurationsdecreased, pulse intensity could beincreased from 1.8 bar to 3.4 barduring therapy.

The mode of action of acousticpulse waves in muscles is inaccordance with the trigger pointtheory, but needs to be investigatedin more detail by experimentalstudies.

Key Words:EPAT, calf muscle shortening,stretching, muscle extensibility,Achilles tendinosis, trigger points.

IntroductionShortened calf muscles are one of

the main risk factors for recurrentAchilles tendinosis.1-3 The anamnesticinformation provided by patientsreveals that many of them had beensuffering from limited ankle jointdorsiflexion for years (e.g. heel up offthe ground when in squat position).The cause of the muscle shorteningremains unclear.

In most cases, stretching exercisesare not sufficient to provide pain reliefand to produce a lasting improvementin calf muscle extension.4-6 In contrastthe use of heel lifts leads to a rapiddecrease in pain, which demonstratesthat the reduction of tension withinthe Achilles tendon is crucial in curingAchilles tendon pain.7

A possible cause of calf muscleshortening may be the presence oftrigger points 8 in the calf muscles.The permanent contracture of theactin-myosin filaments caused bytrigger points, due to the energy crisisof the motor end-plate, leads tocircumscribed muscle contractureswhich, in the presence of a sufficientnumber of trigger points, result in ameasurable overall shortening of theaffected muscles and in a limiteddorsiflexion of the ankle joint. Thereare numerous causes for trigger pointdevelopment, ranging frommechanical overstrain, trauma or poorposture to articular, neurogenic orremote muscular disorders (satellitetrigger points). Rest and medicaments(NSAID) help in pain relief, but donot eliminate the underlyingcontracture, which persists for yearsand leads to recurrent injuries. With

time the trigger pathologyoften increases, as themalfunction induces apermanent overload ofneighboring muscle areas.

One of the most effectivetherapies in use is theapplication of manuallyadministered mechanicalpressure on the triggerpoints.8 This is generally doneby using the friction massagetechnique, followed by musclestretching. Examinations intothe effectiveness of classicaltrigger point therapy inimproving active calf muscleextensibility are not dealt

within the citable literature. Theeffectiveness of calf muscle stretchingalone is discussed controversially,4,6,9

as this therapy approach is consideredto induce only a temporary and littleimprovement in flexibility.5,10

In the last few years, the use oflow to medium energy ExtracorporealPulse Activation Therapy (EPAT) hasbecome increasingly established inthe treatment of myofascial pain,especially in the German speakingEuropean countries (Germany,Austria, and Switzerland). On thebasis of the aforementioned pressureapplication theory in the treatment oftrigger points, the question is,whether acoustic pulse waves are ableto provide an improvement in theextensibility of shortened calf muscles.

Material and Methods

SubjectsA retrospective study was

conducted on 78 patients of anorthopedic practice (56 men and22 women), mean age 45.3 years (SD11.2; range 23 to 58 years), withunilateral chronic (> 6 months)Achilles tendon pain (mean 21.2months; range 6 to 137 months).69 patients complained about amid-portion tendon pain, 9 about aninsertional pain. All patients wererecreational athletes and had a historyof failed conservative treatments forAchilles tendon pain with NSAIDs,local cortisone injections, andphysiotherapy. Physiotherapy includedstretching exercises but they were notexecuted regularly and were not partof a specific stretching program. Theinclusion criterion was a reduction inactive ankle joint dorsiflexion equal orless than 10°, due to shortened calfmuscles when examined at full hip andknee extension.

Improvement of Active Ankle Joint Dorsiflexion by the Useof Extracorporeal Pulse Activation Therapy (EPAT) in Patientswith Chronic Achilles Tendinosis: A New Approach

Dr. med. Markus Gleitz

Médecin-Spécialiste en Orthopédie[Orthopedic Surgery]30, Grand Rue L-1660 LuxembourgTel.: (+352) 22 91 92 - Fax: (+352) 22 91 94e-mail: [email protected]

18 19

Device for ExtracorporealPulse Activation Therapy(EPAT)

Therapy was carried out with theD-Actor® 100 system (Fig. 1) developedby Storz Medical AG* for orthopedicpain therapy in humans. The machineproduces acoustic pulses with an energyflux density (EFD) up to 0.23 mJ/mm_and a maximal pulse frequency of 15 Hz.

The mode of action is identical to thatused by pneumatic jack-hammers: aballistic source (air compressor)generates stress waves by means of aprojectile impacting a solid applicator inthe handpiece (Fig. 2). The face of theapplicator (20-mm diameter, Fig. 3) hasto be covered with coupling gel and thenfixed in tight contact with the skin. Thepressure used to drive the projectile canbe varied continuously from 1 bar to4 bar using a dial on the front panel ofthe control unit (1 bar = 105 Pa).

The generated pulse of this type ofdevice is a pressure wave and not ashock wave. It consists of a fast leadingpositive phase with a peak positivepressure as high as 5-8 MPa, followedby a negative phase. The -6 dB regionof the pressure field is not a cigar-shaped focal volume, as typically foundin extracorporeal shock wave therapy(SWT) derived from shock wavelithotripters, but rather a region of

space that extends radialy from theapplicator surface (maximum energy atthe skin level), decreasing into thetissue with a penetration depth of 3-4cm. The distance and the width of the -6 dB pressure field are consistent withthe Rayleigh distance that bounds thenear field of a piston source.11

Procedure of ExtracorporealPulse Activation Therapy (EPAT)

All patients underwent 4 to 6Extracorporeal Pulse Activation Therapy(EPAT) sessions of the calf muscles atweekly intervals, in addition to receiving4 local treatments with focusedExtracorporeal Shock Waves (ESW) inthe distal Achilles tendon (maximum 5cm above the calcaneus). During eachsession, 6000 pressure pulse waves wereapplied to the calf muscles, with thepatient lying in the prone position on thetreatment table (Fig. 4). Pressure waveswere mainly administered locally to the

proximal gastrocnemiusmuscles, where most palpableindurations were found. Themiddle part of the soleusmuscle was treated throughthe gastrocnemius muscles,whereas the distal muscleportion, often indurate as well,was freely accessible medialand lateral to the proximalAchilles tendon.

The palpable muscleindurations were considered asareas of trigger points andwere therefore in the focus ofthe therapy. These areas werealways more painful during thepressure wave treatment than

the rest of the calf muscles. They weretreated locally with 500-1000 pulseseach, until the pain diminished. Afterchoosing 4-6 trigger areas per session,the remaining 1500-2000 pulse waveswere administered widely spread overthe rest of the calf muscles (smoothingtechnique).

The maximum driving pressure as ameasure for the pulse intensity wasadjusted to the patient's pain threshold

and was tried to be increased duringtherapy. The pulse repetition frequencywas 15 Hz. The number of sessions wasdetermined according to thedisappearance of pain during thetreatment, with a maximum of 6sessions. Application of pressure waveswas strictly avoided over vessels andnerves. All therapies were executed bythe same orthopedic physician (MG),who has an experience of severalthousand pressure wave and shock wavetreatments.

Instrumentation andMeasurement of Ankle JointDorsiflexion

The active dorsiflexion of the anklejoints was measured by means of aBROM gravity goniometer** made oftransparent plastic.

The examiner (MG) sat at the levelof the ankle and held the goniometeragainst the patient's foot sole withoutexerting any pressure. Patients layprone on a standard treatment table,both hip and knee joints extended. Thisis the position in which thegastrocnemius is maximally stretched.The foot was hanging over the table'sedge with the hip in neutral rotation.Before measurement patients wereasked to actively dorsiflex and plantarflex the ankle through the available ROM4 times for the purpose ofpreconditioning the soft tissues,according to the procedure recommendedby Zito et al 12. After this preparationthe next maximum active dorsiflexionangle was taken as the measurement.Measurements were taken beforetreatment, 1 week after the lasttreatment and as a follow-up 3 to 6months later.

Instrumentation andStatistical evaluation

The statistical evaluation wasperformed using the SPSS*** software(version 11.5.0). The results of anklemobility are expressed as mean withstandard deviation (SD). Differences inactive ankle joint dorsiflexion before andafter treatment were calculated with anon-parametric test for paired samplesusing the Wilcoxon signed ranks test.A p-value less than 0.05 was consideredsignificant.

ResultsThe mean active dorsiflexion

measured prior to ExtracorporealPulse Activation Therapy was 3.6°(SD 3.7°; range -3° to 10°). After anaverage of 4.6 sessions (range 4 to

* Storz Medical AG, 8274 Tägerwilen, Switzerland ** Performance Attainment Associates, P.O. Box 528, Lindstrom, MN 55045 *** SPSS Inc., Chicago, USA

6 sessions) a significant increase(p=0.016) in active dorsiflexion to11.5° (SD 5.1°; range -2° to 21°) wasfound. Follow-up examinationsconducted after an average of 4.2months (range 3 to 6 months) afterthe end of pressure wave therapyshowed a significant increase(p=0.013) in maximal activedorsiflexion to 11.7° (SD 5.6°; range -2° to 22°). No significant differencewas identified between the resultsimmediately after the end of therapyand at follow-up4.2 months later (p = 0.86).

During therapy the pressure waveintensity could be increased in allpatients. The average intensity at thefirst session was 1.8 bar (range 1.6 to2.6 bar) and at the last session 3.4 bar(range 3.0 to 4.0 bar). Palpation aftertherapy showed a much softer muscletissue and a disappearance of mostindurations. Patients reported thefeeling of more flexible calf musclesand an easier gait or running.

Side effects included smallsubcutaneous hematomas during the firsttwo sessions. Sonographic examinationsexcluded any deeper-sited lesion in themuscles. Treatments could be continuedat weekly intervals. Temporary musclesoreness for 1-3 days after the first twosessions was common. These symptomswere treated with paracetamol. None ofthe patients required early termination ofthe therapy.

DiscussionExtracorporeal Pulse Activation

Therapy (EPAT) for treating muscleshortening is a new approach. Thegain of ankle joint dorsiflexion afterEPAT is more than 8° and lasts atleast for 4 months. Consequently, thistherapy seems to be superior toconventional stretching therapy, bothin terms of the degree ofimprovement and in terms of theduration of its effectiveness. Radfordet al10 reported in their literaturereview after meta-analyses from 5trials a weighed mean difference(WMD) between 2° and 3° for theoutcome of ankle dorsiflexion afterstatic calf muscle stretches for up to 6weeks. These results were obtainedeither immediately to maximal 72hours after the end of a stretchingtherapy. Results weeks or monthsafter stretching therapy are notreported.

Compared to the recommendeddaily stretching exercises, which needto be performed over a period of

several weeks, EPAT requiresrelatively little time as 4 to 6 therapysessions are sufficient to achieve thedescribed results. Because of thelasting improvement in calf muscleextensibility, EPAT seems a viablealternative to heel lifts in thetreatment of chronic achillodyniasince it allows the tension on theAchilles tendon to be reduced withoutrunning the risk of additional muscleshortening by heel elevation.Moreover, the treatment of a shortenedmuscle in overuse pathology of therelated tendon represents a causal andmore functional approach than theclassic local Extracorporeal ShockWave Therapy (ESWT) of the affectedtendon alone.

The additional local treatment ofthe Achilles tendon with ESWT is,according to the existing literatureand the author's knowledge, notknown to have any influence on thecalf muscle extensibility.

The mode of action of EPAT is indiscussion. Even for the focusedESWT the mode of action is not fullyunderstood and recent studies showthat shock waves can have both, ananalgesic effect13 and induce tissuerepair.14 A plausible explanation forthe effectiveness of EPTA might begiven by the trigger point theory.8 Thepresence of trigger points in musclescauses a significant motor dysfunctionwith the clinical findings of arestriction of full stretch range ofmotion, a palpable increase in muscletenseness and painful contractionknots.15 The histological findings in acontracture knot are segments ofmuscle fibers with extremelycontracted sarcomeres.16 According tothe energy crisis hypothesis17 aninadequate supply of ATP blocs theCa++ pump and a sustainedendogenous contracture develops as abeginning of a vicious cycle. Inaddition endogenous substancessensitize the muscle nociceptors andare responsible for the localtenderness of trigger points.

The following reasons for theeffectiveness of the historicallyaccepted combination of deep frictionmassage and stretching in thetreatment of trigger points arediscussed: disconnection of actin-myosin links within the contractedsarcomeres and improvement in localcirculation along with the eliminationof the ischemia-induced energy crisis.15

Extracorporeal Pulse ActivationTherapy applies a similar principle: itbrings mechanical energy into the

muscle. On the contrary to the classicmanual techniques, EPAT uses muchhigher energy levels and is appliedperpendicular to the longitudinalmuscle fibers. Therefore it might bemore efficient in interrupting localmuscle contractures than thelongitudinal stretching.

An argument for this theory is thatindurations found in the calf muscleswere very painful to EPAT during thefirst sessions and that they becamesoft and painless during therapy,together with the reportedimprovement of active ankledorsiflexion.

Although the trigger point theoryitself seems convincing, reduction ofthe treatment to the painful triggerpoints only is, in the opinion of theauthor, misleading and is not fullyconsistent with the practicalexperience of this study. In fact, theincrease in ankle dorsiflexionachieved by an exclusively localtreatment of the painful contractureknots within the muscle bellies of thegastrocnemius and soleus musclesremains far behind the improvementprovided by the combined treatmentof both individual spots and largermuscle areas described above(smoothing technique of the wholemuscle). This would mean that themuscle shortening is not only due tothe painful, active trigger points butalso due to painless latent triggerpoint areas within the whole muscle,which also respond to EPAT.

ConclusionThe results of this practical study

are encouraging, but need to beverified by means of methodicallymore valid studies and by conductingexperimental examinations of thespecific mode of action. Except forthe pain perceived during treatment,EPAT has only minimal side effectsand is indicated for almost all patientswith calf muscle shortening.

References1. Krivickas LS. Anatomical factors

associated with overuse sports injuries.Sports Med. 1997 Aug 1997; 24(2):132-146.

2. Kaufman KR, Brodine SK, Shaffer RA,Johnson CW, Cullison TR. The effect offoot structure and range of motion onmusculoskeletal overuse injuries. Am JSports Med. 1999 Sep-Oct 1999; 27(5):585-593.

3. McCrory JL, Martin DF, Lowery RB, et al.Etiologic factors associated with Achillestendinitis in runners. Med Sci SportsExerc. 1999 Oct 1999; 31(10):1374-1381.

Fig. 1

D-Actor unit

Fig. 2

Schematic view of D-Actorhand piece emitting radialpressure waves (no focus)

Fig. 3

20-mm D-Actor applicator ofhand piece

Fig. 4

Calf muscle treatment with pulse transmitter(D-Actor)

4. Alfredson H, Lorentzon R. ChronicAchilles tendinosis: recommendations fortreatment and prevention. Sports Med.2000 Feb 2000; 29(2):135-146.

5. Harvey L, Herbert R, Crosbie J. Doesstretching induce lasting increases in jointROM? A systematic review. PhysiotherRes Int. 2002 2002; 7(1):1-13.

6. Youdas JW, Krause DA, Egan KS,Therneau TM, Laskowski ER. The effectof static stretching of the calf muscle-tendon unit on active ankle dorsiflexionrange of motion. J Orthop Sports PhysTher. 2003 Jul 2003; 33(7):408-417.

7. Davis WL Jr, Singerman R, LabropoulosPA, Victoroff B. Effect of ankle and kneeposition on tension in the Achilles tendon.Foot Ankle Int. 1999 Feb 1999; 20(2):126-131.

8. Travell JG, 1901-, Simons DG. Myofascialpain and dysfunction : the trigger pointmanual. Baltimore: Williams & Wilkins;1983.

9. Porter D, Barrill E, Oneacre K, May BD.The effects of duration and frequency ofAchilles tendon stretching on dorsiflexionand outcome in painful heel syndrome: a

randomized, blinded, control study. Foot Ankle Int. 2002 Jul 2002; 23(7):619-624.

10. Radford JA, Burns J, Buchbinder R,Landorf KB, Cook C. Doesstretching increase ankledorsiflexion range of motion? Asystematic review. Br J Sports Med.2006 Oct 2006; 40(10):870-5;discussion 875.

11. Cleveland RO, Chitnis PV, McClureSR. Acoustic field of a ballisticshock wave therapy device.Ultrasound Med Biol. 2007 Aug2007; 33(8):1327-1335.

12. Zito M, Driver D, Parker C,Bohannon R. Lasting effects of onebout of two 15-second passivestretches on ankle dorsiflexionrange of motion. J Orthop SportsPhys Ther. 1997 Oct 1997; 26(4):214-221.

13. Ohtori S, Inoue G, Mannoji C, et al.Shock wave application to rat skininduces degeneration andreinnervation of sensory nervefibres. Neurosci Lett. 2001 Nov 232001; 315(1-2):57-60.

14. Wang CJ, Wang FS, Yang KD, et al.Shock wave therapy inducesneovascularization at the tendon-bone junction. A study in rabbits. JOrthop Res. 2003 Nov 2003;21(6):984-989.

15. Mense S, Simons DG. Muscle pain :understanding its nature, diagnosis,and treatment. Philadelphia:Lippincott Williams & Wilkins; 2001.

16. Simons DG, Stolov WC. Microscopicfeatures and transient contractionof palpable bands in canine muscle.Am J Phys Med. 1976 Apr 1976;55(2):65-88.

17. Simons DG, Travell J. Myofascialtrigger points, a possibleexplanation. Pain. 1981 Feb 1981;10(1):106-109.

Ankle Dorsiflexion(Degrees)

Before therapy

After therapy

P

Follow-up

P

Table 1. Results: Active Ankle Joint Dorsiflexion before and after EPAT

Treatment Group(n=78)

3.6 +- 3.7

11.5 +- 5.1

0.016a

11.7 +- 5.6

0.013b

a Comparison between before and after therapyb Comparison between before therapy and at 4.2-month follow-up

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