Dear Friends and Colleagues,

On behalf of the ISMST Organization committee, Ihave the pleasure and privilege to invite you to the 14thISMST Congress that will be held in Kiel, Germany, onthe 9th-11th June 2011.

The ISMST is the world’s largest organization withregards to medical shock wave treatment.

The broad field of shockwave treatment has beenexpanding rapidly world wide. Standard indicationsincluding musculo-skeletal disorders and bonepathologies such as non-union, avascular necrosis andtendon pathologies will be presented. Due to thebiological principles of shockwaves multiple newindications have developed. Recent research, scientificupdates and preliminary results in skin lesions,myofascial treatment and nerve injuries will be part ofthe conference as well as instructional hands-oncourses. International experts will talk about shoulder,foot, pain, sports and tendon injuries, technicaldevelopments, how-to-use-shockwaves and financialaspects.

The Instructional courses consisting of part 1 and 2are certified by the ISMST and the DIGEST.

The conference venue is the Atlantic hotel right inthe centre of Kiel, which is know as Germany´s sailingcity with all kinds of yachts, boats and large luxurycruise ships, nice weather, famous beaches, and manyother attractive options of entertainment.

I look forward to welcoming you to Kiel

Ludger Gerdesmeyer

Dear Colleagues Across the World,

This is now the 7th issue of the ISMSTnewsletter, published annually in conjunction withthe ISMST conference.

Once again a heartfelt thanks to Dr. PauloRoberto dos Santos in Brazil from the ISMST boardof directors. The ISMST newsletter publishes thestudy findings, basic research and views ofscientists we consider most relevant to the ISMSTcommunity. The newsletter with a print run of3,000 can as well be downloaded directly from ourWebsite. The articles published in the newsletter donot necessarily reflect the opinions of the ISMSTcommunity, but are specifically the views of theirrespective authors.

As you have no doubt noticed, not onlyevidenced-based studies are presented but also theintriguing science-based opinions and statements ofindividual researchers and scientists. They areintended to stimulate discussion and spur furtherresearch and investigation.

We would like to again point out the guidelinesfor the proper application of ESWT, which can beviewed on the new Website of the GermanShockwave Therapy Association (DIGEST,www.digest-ev.de ). These guidelines are constantlyrevised to accommodate the latest scientificfindings and knowledge. At the meeting of thecouncil of experts in January of this year, it wasdecided that the parameters to be published in theguidelines be adopted as the official parameters,which are drawn from published evidence-basedstudies. These parameters will vary according todevice and method of shockwave generation. Nocertifiable parameters will be issued in theguidelines for individual indications requiringindividual devices for which no previous studiesexist. The parameters moreover are biometricallyworked out before being incorporated into theguidelines. When completed, the guidelines willbecome the basis for ESWT treatments and theirsubsequent billing, primarily in the German-speaking countries and later worldwide.

For this reason, it is essential to continuecarrying out and compiling scientific studies and topresent them at conferences and in scientificjournals, so that knowledge on the efficacy ofESWT can be further accrued and their futurefunding ensured. ESWT must remain in the handsof medical doctors and physicians, otherwisedevelopment of this wonderful therapeutic methodwill risk ceasing and coverage by insurers risk beingdenied. Focused EWST has too many benefits, andis ultimately too dangerous, to be left in the handsof non-medical personnel, who will treat it as justanother electro-medical technology.

We look forward to the continual developmentof shockwave therapy in the fields of bonetreatment, cardio-surgery and skin ailments. Theemphasis of this particular newsletter is thetreatment of skin ailments and myofascial painsyndrome

We hope you will enjoy both the articles andthis year's conference in Kiel.

Yours,

Richard Thiele

Chief Editor• Paulo Roberto Dias dos Santos, MD

(Brazil) - prds@uol.com.br

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

w281211@adm.cgmh.org.tw

Editorial Board• Ana Claudia Souza, MD (Brazil)

anaclaudia@cortrel.com.br• Carlos Leal, MD (Columbia)

leal@owc.com.co• Heinz Kuderna, MD (Áustria)

kuderna-unfallchir.wien@aon.ato• John Furia, MD (USA)

jfuria@ptd.net• Leonardo Jaime Guiloff Waissbluth,

MD (Chile) - lguiloff@davila.ch• Ludger Gerdsmeyer, MD (Germany)

gerdesmeyer@aol.com• M. Cristina d’Agostino, MD (Italy)

frogg@tele2.it• Matthias Buch, MD (Germany)

matthiasbuch@aol.com• Paulo Rockett, MD (Brazil)

rockett@terra.com.br• Richard Thiele, MD (Germany)

rithi@t-online.de• Robert Gordon, MD (Canada)

gordon@skockwavedoc.com• Sergio Russo, MD (Italy)

serghiey@hotmail.com• Vinzenz Auersperg, MD (Áustria)

vinzenz.auersperg@gespag.at• Weil Lowel Jr, MD (USA)

lweiljr@weil4feet.com • Wolfgang Schaden, MD (Austria)

med.eswt.schaden@aon.at

Veterinary Committee • Scott Mc Clure, DVM (USA)

mcclures@iastate.edu• Ana Liz Garcia Alves, DVM (Brazil)

anaalves@fmvz.unesp.br• Ana Cristina Bassit, DVM (Brazil)

anafbassit@uol.com.br

Editorial OfficeRua Monte Alegre, 428 - conj. 56Perdizes - São Paulo - Brazil CEP 05014-000 Fone: 55-11-3825·8699E mail : prds@uol.com.br

website: www.ismst.com

LudgerGerdesmeyer

Editorial · Editorial comments

Richard Thiele, MD

Member of the ISMSTSupervisory Board

2

IntroductionEPAT (Extracorporal Pulse Activation

Therapy) is used to describe theapplication of radial pressure waves,sometimes also referred to as radial shockwaves. For the application of focusedshockwave is the term ESWT mostcommon. EPAT and ESWT can be used totreat the musculo-skeletal complexeffectively. The application of focusedshockwaves applied to muscle triggerpoints are used for diagnostic andtherapeutic purposes according to Dr.Gleitz (1). Manual examination of triggerpoints in combination with EPAT can beused for diagnostic and therapeuticpurposes with positive results. In ourpractice, EPAT is used for the localtreatment of muscular trigger point areas,tendon insertion pain and for smoothingof the myofascial structures. EPAT allowslarge muscle regions to be treatedeffectively and in a timely manner. Thefocused shock waves induce a reductionof nociceptive fibers whereas radialpressure waves (EPAT) seem to have acounter-irritation and pain modulatingeffect through GABAergic interneurons inthe dorsal horn (1). In addition to thisaction, the pressure and vibrations ofradial shock waves (EPAT) improve bloodcirculation and lymphatic drainage.

EPAT application to muscle triggerpoints, tendon insertion pain andmyo-fascial conditions represents anevolution of use within the musculo-skeletal system. In our practice therapy isapplied with an EPAT system developedby Storz Medical AG. The mode of actionis identical to that used by pneumaticjack-hammers: that is a ballistic source(air compressor) generates pressurewaves by means of a projectile impactinga solid applicator in the hand piece. Theapplicator (D-Actor with 20 mm diameter)has to be covered with coupling gel andthen fixed in tight contact with the skin.The pressure used to drive the projectilecan be varied continuously from 1 bar to 4bar using a dial on the front panel of thecontrol unit (2).

In our practice muscle shortening ortightness can be a risk factor fortendinosis. Reducing the tension withinthe Musculo-Skeletal Complex can lead toa reduction in pain. A completeFunctional Movement Screen (3) andClinical Orthopaedic Examination (4) willbe performed before an EPAT treatment isinitiated.

1. The effectiveness of EPAT on themuscle belly might be given by the triggerpoint therapy theory established byTravell and Simons work (5). Thepresence of trigger points in musclescause a significant motor dysfunction withthe clinical findings of a restriction of fullstretch motion, a palpable increase inmuscle tenseness and painful contractionknots. The contracture of the actin-myosin filaments caused by trigger points,due to the energy crisis of the motor end-plate, leads to muscle contractures whichresult in a measurable overall shorteningof the affected muscles and a limitation injoint range of motion.

2. The effectiveness of EPAT on thetendon insertion or the tenoperiostealjunction might be given by a transversefriction technique that was developed byDr. James Cyriax (4). The scar tissue orthickening is broken up by counterpressure of the EPAT head with asweeping motion moving in a transversedirection across the tendon.

3. The effectiveness of EPAT on themyofascial meridian system as describedby Thomas W. Myers in Anatomy Trains(6) can be shown through the use ofEPAT smoothing in the direction ofconnection. Once the particular patternsof these myofascial meridians arerecognized and the connectionsunderstood, they can be applied in EPATsmoothing treatment.

The use of EPAT has also been shownto have promising results in improvinglocal circulation (reactive hypermia) andreduce the concentration of vasoneuro-active substances within the generalizedtreatment area (2).

EPAT for Trigger Points and Myofascial Conditionsin Sport Medicine

Robert GORDON, M.D.

Chris Broadhurst, M.D.

Inside this Issue

Editorial comments ....................................................... 1

EPAT for Trigger Points and Myofascial Conditions in Sport Medicine ...................................... 2

What is cavitation? Destructive or useful ................ 4

ESWT in Myofascial Pain Syndromes ........................ 5

Influence of Shock-Wave-Treatmenton Migration, Proliferation andGenetic Expression of Fibroblasts .............................. 7

ESWT in Wound Care - Basic Research andClinical Experience.......................................................... 9

Instructions for Authors ............................................. 20

3

EPAT Treatment Guidelines of theShoulder Musculo-Skeletal Complex:

The goal is to reduce muscle shortening in themusculo-skeletal complex

The driving pressure (bars) is adjusted to the patient'spain threshold

500-1000 Pulses Decreases TP within muscle belly ormusclo-tendinous junction

1000-1500 Pulses Decreases insertion scar tissue orthickening

1000-2000 Pulses myofascial meridian smoothingTherapy frequency of one session per 3-10 days has

been shown to be ideal.

2.6 Bars or decrease to patient tolerance500-1000 Shocks

+TP in Supraspinatus/ Infraspinatus

EPAT Suggested Treatment Areas for Shoulder Pain:

2.6 Bars or patient tolerance500-1500 Shocks

+Supraspinatus, Supine Lying

3.0 Bars or patient tolerance500-1500 Shocks

+Infraspinatus, prone lying

2.6 Bars or patient tolerance500-2000 Shocks

+Myo-fascial Meridian Smoothing

Typical Complete Treatment:2000-6000 Shocks @ ~11 Hz

4

Post Treatment Recommendations:* Ice: Not to be used as it will affect the local circulation

(reactive hypermia)

* Heat: To aid in circulation

* Myofascial Release Techniques/ Active Stretching: i tissue memory

Symptoms Should Improve Within 1-2 TreatmentsSymptoms Should Resolve within 1-6 Treatments.

The common result of treatment is a reduction of muscletone along with a diminished extent of muscle shortening,improved mobility and pain reduction. EPAT for treatingmuscle shortening needs continued clinical protocols to beestablished for therapeutic benefit. EPAT shows promisingresults in a non-invasive solution to accelerate the recoveryfrom Trigger Points and Myofascial conditions (7). We lookforward to the future of EPAT and it's integration into theSport Medicine field and the development of powerfulintegrative therapeutic strategies.

References:1. Gleitz M, Dreisilker U, Rädel R, Orthopedic trigger point therapy with

focused and radial shockwaves: a review of the current situation.Luxemburg

2. Gleitz M, Improvement of Active Ankle Joint Dorsiflexion by the Useof Extracorporeal Pulse Activation Therapy (EPAT) in Patients withChronic Achilles Tendinosis: A New Approach

3. Gray, Movement: Functional Movement Systems-Screening,Assessment, Corrective Strategies, On Target Publications, 2010

4. Cyriax JH, Cyriax PJ, Illustrated Manual of Orthopaedic Medicine.London, Butterworths, 1984

5. Travell JG, Simons DG, Myofascial Pain and Dysfunction: the triggerpoint manual. Baltimore: Williams and Wilkins; 1992

6. Myers W. Thomas, Anatomy Trains: Myofascial Meridians for Manualand Movement Therapist, Churchill Livingstone, London, 2009

7. Shockwave Canada Inc., “New Medical Advances”,www.shockwavecanadainc.com, Toronto.

Lose fat without effort - this is what an increasing number of therapists promise to achieve with the help of a new generationof ultrasound systems that use the so-called cavitation technology. The question is, what do these systems really accomplish:cavitation, degassing, heat, or simply everything?

Physics defines cavitation as a local vaporisation of water molecules due to strong pressure changes. The tensile componentsof these pressure changes, caused during lithotripsy for instance, tear the water molecules successively apart (vaporisation). Thecavities generated by this process are cavitation bubbles, and the result of this sudden imbalance is a spontaneous implosion ofthe cavitation bubble. This spontaneous collapse produces a local shock wave or causes microjets. Cavitation requires highnegative pressures (Herbert et al., 2006: between 260 bar and 170 bar).

((Bildunterschrift: Creation of a micro-jet: Cavitation bubbles near obstacles cannot collapse in a spherically symmetrical way,since the obstacle hampers the flow of the fluid. This causes the development of micro-jets that hit the interface at severalhundred metres per second and lead to erosion or punch needle-like holes in vessels or membranes))

Bubble formation in an aqueous medium is referred to as noninertial or stable cavitation. Speaking purely physically, it has tobe clearly differentiated from inertial cavitation because the bubbles generated in this way cannot collapse spontaneously, have alow energy level and decompose or dissolve slowly in the medium. Consequently, tissue damage caused by stable cavitation ishighly improbable, which implies that effects on adipose cells are not to be expected.

So we have to distinguish between vaporising and degassing cavitation, the physical properties and cell-destructive effect ofwhich are blatantly different. The extremely high forces resulting from microjets (see illustration) out of the collapse of theinertial cavitation bubble is not observed with noninertial or stable cavitation.

Devices having all the capabilities of what is sold as cavitation would have to be able to generate the extreme negativepressures described above. However, there is reason to fear that maybe not a single one of the »cavitation devices« on the marketis capable of effecting cavitation in the proper physical sense described above. Therapeutic ultrasound, on the other hand, maycause local generation of heat, which may even result in cell destruction.

As a conclusion it can be said that in shock wave lithotripsy (ESWL), which works with high energy shock waves, cavitationexists and is useful. In the disciplines of Cardiac shock wave therapy (CSWT), Extracorporeal shock wave therapy (ESWT), andAcoustic Wave therapy (AWT®), which work with the application of low energy shock waves, cavitation does not exist and is notdesired as cavitation in soft tissue can cause lesion.

Dr. Pavel NovakDirector of International Product ManagementSTORZ MEDICAL

What is cavitation? Destructive or useful

5

IntroductionMuscle pain is common and presents

a major medical problem. As theunderstanding of its causes is stillincomplete treatment options varygreatly. One of the latest and fastestspreading treatment approaches inGermany is the use of ESWT. For the last10 years radial (r-ESWT) and focused(f-ESWT) shockwaves have been usedsystematically to treat myofascial triggerpoints (MTrP's), according to the triggerpoint theory of Travell and Simons(Travell & Simons, 1983).

Myofascial trigger pointsand muscle pain

The scientific understanding ofmuscle pain has changed within the last30 years (Mense & Simons, 2001a).Muscle pain differs in many wayssubjectively and objectively from pain inthe skin or viscera. One of the moststriking differences is the referral of paininto distant areas far away from theprimarily irritated muscle nociceptors.This phenomenon of a “Referred Pain” isone of the characteristic and best knownclinical sign of MTrP's and is explainedby the “Convergence-Projection-Theory”(Ruch, 1949). Accordingly, nociceptiveinformation is taking the wrong path inthe spinal cord and is reachingsomatotopically inappropriate dorsalhorn neurons. The referred painsymptoms often lead patients to localizetheir pain incorrectly. In these cases, thephysician must look for the actual sourceof the pain by exerting an externalpressure during strong palpation of themuscle, and then treat it accordingly.

The myofascial trigger point is definedas a palpable local hardening of the muscletissue that is painful on palpation andmovement. According to a widespreadhypothesis it is the result of a sarcomerecontracture as a consequence of adysfunctional neuromuscular endplate(Simons, 2004). The resulting localischemia leads to a release of substancesinto the tissue that sensitize nociceptors(bradykinin, prostaglandin E2, serotonin),accounting for the tenderness of MTrP's topressure. Substances of this type have

been found within the MTrP's of patients(Shah et al., 2008). The nociceptorsthemselves release vasoactiveneuropeptides (substance P, CGRP) thatcreate a local neurogenic inflammationwith hyperemia and edema, thus starting avicious circle.

As clinical consequences MTrP's causea significant motor dysfunction with arestriction of full stretch range of motion, apalpable increase in muscle tenseness andpainful contraction knots.

For therapy a combination of deepfriction massage and stretching is used.The following reasons for its effectivenessare discussed: Disconnection of actin-myosin links within the contractedsarcomeres, improvement in localcirculation and the elimination of theischemia-induced energy crisis (Mense &Simons, 2001a).

ESWT in musclesThe first publications about the

successful use of focused shockwaves (f-ESWT) in muscular dysfunction describeda diminution of pain (Kraus, Reinhart,Krause, & Reuther, 1999) and muscle tone(Lohse-Busch, Kraemer, & Reime, 1997).Since the year 2000 radial shockwaves (r-ESWT) are used and have become themore popular treatment tool(Bauermeister, 2003), (Gleitz, 2003). Thebasic idea about using shockwaves inmuscles is the application of an externalmechanical energy, comparable to thetraditionally used technique of muscleknot compression (“Gelotrypsie”) (Lange,1931), followed by stretching exercises(Travell & Simons, 1983).

Although the mode of action ofshockwaves on muscles has not beenexamined in detail, the followinghypotheses are discussed, in analogy tothe proven mechanisms in non-muscular tissues:• Breaking Actin-Myosin-Links (Travell &

Simons, 1983), (Shah et al., 2008)• Hyperaemia + Neoangiogenesis (Wang,

2003), (Shah et al., 2008)• Dilution of vasoneuroactive substances

(Mense & Simons, 2001b), (Shah etal., 2008)

• Release of Substance P (Maier,

Averbeck, Milz, Refior, & Schmitz, 2003),(Hausdorf, Lemmens, & Kaplan, 2008)and CGRP (Hong, 1994)

• Selective degeneration of C-fibers(Hausdorf, Lemmens, & Heck, 2008)

• Gate-Control-Theory (Wall & Cronly-Dillon, 1960), (Gregor & Zimmermann,1972)

• Mechanotransduction (Neuland,Duchstein, & Mei, 2004), (Ingber, 2006)

• Release of NO (Neuland et al., 2004),(Mariotto et al., 2005)

• Muscle oscillation (Nazarov &Gorozhanin, 1988)

• Destruction of damaged fibers (Mense& Simons, 2001b)

Advantages anddisadvantages of r-ESWTand f-ESWT in muscles

According to their physicalcharacteristics radial and focused deviceshave different application profiles.

The advantages of the r-ESWT are thepossibility of treating large muscle areasand the easy handling of the narrow handpiece. Its disadvantages are the reducedpenetration depth (< 5 cm) and thediminished ability of provoking a referredpain, due to the radial (non-focused) wavepropagation in the tissue.

The advantages of the f ESWT are thehigh reliability to provoke a referred painpattern, due to focusing the energy in asmall muscle area and the greater depth ofpenetration (> 5-10 cm). Its disadvantagesare the small muscle area treated and thebulky, wide hand piece.

Treatment parameterswith r-ESWT and f-ESWT

The r-ESWT is used for a local triggerpoint treatment and for a large areatreatment (“smoothing”). The localtreatment is done with 500-1000 impulsesper trigger point at an intensity reaching amaximum pain level of VAS 8. The largearea treatment is done at lower intensitiesand maximum pain levels (VAS 4) with1000-4000 impulses, according to the seizeof the muscle. The impulse frequency ischosen between 4 and 20 Hz. Thetreatments are scheduled 1-2/week forchronic pathologies and daily for acuteinjuries. 6-8 treatments are mostly needed.

The f-ESWT is used locally fordiagnostic and therapeutic purposes. Asthe referred pain can be provokedregularly and easily, f-ESWT is first used tolocate the deep trigger points within themuscle and then to treat them afterwards.300-600 impulses are necessary per triggerpoint at an intensity of 0.05-0.35 mJ/mm2

and an impulse frequency of 4 Hz.

ESWT in Myofascial Pain Syndromes

Dr. med. Markus Gleitz

Médecin-Spécialiste en Orthopédie30, Grand-RueL-1660 Luxembourg / EuropeEmail: info@drgleitz.com

6

Treatment intervals and the total number oftreatments are identical to r-ESWT.

The choice of treatment intensity(mJ/mm2 or bar) is made according to thefollowing rules:• Stay below pain threshold (<VAS 8)• The higher the pain, the lower the energy• Adapting the energy to patient's reaction

after previous treatment• Continuous increase in energy if possible

Combined treatment:f-ESWT and r-ESWT

The best results are achieved with thecombination of both treatments: f-ESWT forthe search and local treatment of MTrP's,followed by a “smoothing” large areatreatment with r-ESWT.

Choice of muscles to betreated

The muscles are chosen according tothe probability of containing MTrP's. Withthe knowledge about muscle specificreferred pain patterns the description ofpain by the patients gives already an idea ofwhich muscles could be concerned.

The history about possible overload ofthe muscles (sport, trauma, posture,working position) makes the choicenarrower. Finally the clinical examinationwith testing the range of motion(shortening), manual palpation andshockwave provocation of the referred painthat should be recognized by the patientconfirms the choice.

Choice of treatment areaswithin the muscles1. MTrP's, that fulfill all diagnostic criteria

(Tender Spot, Taut Band, Referred Pain,Twitch Response)

2. Sensitive Pain Points with a strong localpain or a referred pain, that the patientrecognizes

3. “Smoothing” area treatment ofpainful, tense and shortenedmuscles with r-ESWT

Examinations neededAs muscle pain is often seen in context

with other pathologies outside the muscle(e.g. arthritis, radiculopathy, spinal andforaminal stenosis, neuropathy, myopathy,rheumatism, organ dysfunction, hormonedysregulation, psychiatric illness, infection,malnutrition, medicament induced) adifferential diagnosis is needed.

For the local structural diagnostic amanual examination is imperative and anultrasound examination is recommended.The ultrasound helps to measure themuscle thickness to choose the right focusfor f-ESWT and allows identifying musclepathologies such as tumors.

Empirically provenindications

Good results can be obtained in allacute or chronic muscle pathologies withpain, increased muscle tone and muscleshortening under the condition that there isno dominant pathology which irritates themuscle permanently or has structuraldamage to the muscle itself, such as

- Chronic neck pain with brachialgia,dorsalgia and cephalgia

- Periarticular shoulder pain anddysfunction

- Tendomyosis of the forearm extensorand flexor muscles without and withepicondylitis

- Dorsalgia- Chronic low back pain without or with

pseudosciatic irradiation - Tendopathy and shortening of the

adductor muscles- Shortening of the quadriceps and

hamstring muscles (chondropathiapatella, jumper's knee)

- Peroneal and tibial muscle syndrome- Shin Splint- Shortening of the calf muscles without

and with achillodynia- Shortening of the plantar foot muscles

without and with plantar fasciitis- Metatarsalgia- Sports injuries without discontinuity of

the muscle

Side-effectsUnder cautious and correct application

no major side-effects can be seen.A temporary increase in pain for 1-2

days is possible. Petechial bleedings areseen, especially with the r-ESWT afterthe first 2 treatments of the glutealmuscles.

ContraindicationsThe following structures should not be

in the focus of shockwaves:- Malign tumor- Lung tissue- Epiphyseal growth plate- Large vessels and nervesBlood thinning treatments are

considered as a relative contraindication.

ConclusionAfter 10 years of experience with this

treatment it can be accepted as effectiveand safe if all the steps have been followed.It is an enormous improvement of theknown trigger point therapy and offers newpossibilities in the functional treatment ofoverload pathologies of the locomotorsystem. Once the diagnosis is establishedthe treatment is easily applied and profitsfrom patient's tolerance as it is non-invasive.

ReferencesBauermeister, W. (2003). Die Behandlungmyofaszialer Schmerzsyndrome durch Trigger-ESWTam Beispiel chronischer Lumbalgien undLumboischialgien. Paper presented at the 51.Jahrestagung der Vereinigung SüddeutscherOrthopäden e.V.

Gleitz, M. (2003). Stosswellen zur Behandlungmyofaszialer Schmerzen in der Orthopädie: Eineneue Therapiemöglichkeit. Paper presented at the 51.Jahrestagung der Vereinigung SüddeutscherOrthopäden e.V.

Gregor, M., & Zimmermann, M. (1972).Characteristics of spinal neurones responding tocutaneous myelinated and unmyelinated fibres. JPhysiol, 221(3), 555-576.

Hausdorf, J., Lemmens, M. A., Heck, K. D.,Grolms, N., Korr, H., Kertschanska, S., et al.(2008a). Selective loss of unmyelinated nerve fibersafter extracorporeal shockwave application to themusculoskeletal system. Neuroscience, 155(1), 138-144.

Hausdorf, J., Lemmens, M. A., Kaplan, S.,Marangoz, C., Milz, S., Odaci, E., et al. (2008b).Extracorporeal shockwave application to the distalfemur of rabbits diminishes the number of neuronsimmunoreactive for substance P in dorsal root gangliaL5. Brain Res, 1207, 96-101.

Hong, C. Z. (1994). Lidocaine injection versus dryneedling to myofascial trigger point: the importance ofthe local twitch response. American Journal ofPhysical Medicine Rehabilitation, 73(4), 256.

Ingber, D. E. (2006). Cellular mechanotransduction:putting all the pieces together again. FASEB J, 20(7),811-827.

Kraus, M., Reinhart, E., Krause, H., & Reuther, J.(1999). [Low energy extracorporeal shockwave therapy(ESWT) for treatment of myogelosis of the massetermuscle]. Mund Kiefer Gesichtschir, 3(1), 20-3.

Lange, M. (1931). Die Muskelhärten (Myogelosen).München: J.F. Lehmann's Verlag.

Lohse-Busch, H., Kraemer, M., & Reime, U.(1997). [A pilot Investigation into the Effects ofExtracorporeal Shock Waves on Muscular Dysfunctionin Children with Spastic Movement Disorders].Schmerz, 11(2), 108-112.

Maier, M., Averbeck, B., Milz, S., Refior, H. J., &Schmitz, C. (2003). Substance P and prostaglandinE2 release after shock wave application to the rabbitfemur. Clin Orthop Relat Res(406), 237-245.

Mariotto, S., Cavalieri, E., Amelio, E., Ciampa,A. R., de Prati, A. C., Marlinghaus, E., et al.(2005). Extracorporeal shock waves: from lithotripsyto anti-inflammatory action by NO production. NitricOxide, 12(2), 89-96.

Mense, S., & Simons, D. G. (2001a). Muscle pain :Understanding its nature, diagnosis, and treatment.Philadelphia: Lippincott Williams & Wilkins.

Mense, S., & Simons, D. G. (2001b). Muscle pain :Understanding its nature, diagnosis, and treatment.Philadelphia: Lippincott Williams & Wilkins.

Nazarov, S. B., & Gorozhanin, L. S. (1988). [Useof a quantitative method for optimizing a muscletraining regimen in experimental research]. Fiziol ZhSSSR Im I M Sechenova, 74(7), 1041-1043.

Neuland, H., Duchstein, H., & Mei, W. (2004).Grundzüge der molekularbiologischen Wirkung derextrakorporalen Stosswellen am menschlichenOrganismus - In-vitro- und In-vivo-Untersuchung.Orthopädische Praxis, 40(9), 488-492.

Ruch, T. (1949). Visceral sensation and referred pain.In J. Fulton (Ed.), Howell's Textbook of Physiology (16ed., pp. 385-401). Philadelphia: Saunders.

Shah, J. P., Danoff, J. V., Desai, M. J., Parikh,S., Nakamura, L. Y., Phillips, T. M., et al. (2008).Biochemicals associated with pain and inflammationare elevated in sites near to and remote from activemyofascial trigger points. Arch Phys Med Rehabil,89(1), 16-23.

Simons, D. G. (2004). Review of enigmatic MTrPs asa common cause of enigmatic musculoskeletal pain anddysfunction. J Electromyogr Kinesiol, 14(1), 95-107.

Travell , J., & Simons, D. G. (1983). Myofascialpain and dysfunction. The Trigger Point Manual.The upper Extremities ( Vol. 1). Baltimore: Williams &Wilkins.

Wall, P. D., & Cronly-Dillon, J. R. (1960). Pain,itch, and vibration. Arch Neurol, 2, 365-375.

Wang, C. J. (2003). An overview of shock wavetherapy in musculoskeletal disorders. Chang GungMed J, 26(4), 220-232.

7

IntroductionThe meaning of extracorporal

shock wave thearapy (ESWT) fortreatment of different skin lesions hadincreased during the last years.Starting with poor healing woundswhich were treated with great success[1] several indications followed.Currently application of shock wavesis for instance done in case of necrosis[2], burns [3] and wounds in veterinarymedicine [4]. In all studies the factthat the treated area totally remodelsto healthy and smooth skin of fullintegrity is common. This notice wasalso done in treatment of intact tissue,where tightness increased [5].

For these macro visual effectsfibroblasts play a crucial role. They areone of the most important connectivetissue cells of the dermis which isresponsible for the elasticity andappearance of skin (Figure1).Fibroblasts produce the connectivetissue fibers collagen, elastin andfibronectin. They are incorporated inthe extracellular matrix mainly formedby hyaluronan. Hyaluronancontributes to tissue hydrodynamicswhat facilitates movement andproliferation of cells. Collagen andelastin are responsible for skinstrength and elasticity, whereasfibronectin supports tissue repaireither [6].

Examining the influence of shock-waves to proliferation, migration andgenetic expression of fibroblasts invitro may help to understand theunderlying mechanism of ESWT.

Materials and MethodsNormal human dermal fibroblasts

(NHDF) provided by PromoCell werecultivated in low serum medium(2%V/V). Treatment was carried outusing the IVSWT Water Bath 2.0 [7],filled with degassed, thermostatically

controlled water. During treatmentculture flasks were filled withphosphate buffered saline of 37°C.Cells were treated using Orthowave180c CP-155, MTS Europe GmbH andPiezoson 100plus, Richard Wolf GmbH.For Orthowave an energy flux densityof 0,07mJ/mm2 or 0.15mJ/mm2,frequency 5Hz, 300 pulses and deviceto cell distance 7cm was chosen. Cellstreated by Piezoson 100plus wereplaced as near as possible toapplication membrane due to the smalldepth of penetration. Devices: FP4(energy level 0,06mJ/mm2) and IP20(0,20mJ/mm2) with 1000 pulses either.

For observing cell migration woundand heal assay was carried out. Across was scratches into a confluentmonolayer of cells growing in petridishes. The closure of the wound wasmeasured after 6, 12 and 24 hours.Based on fewer cells in wound andheal assay specified lower energylevels were used in that case.

Proliferation was measured 1 hour,day 3 and 5 after treatment carryingout cell counting with coulter counter,BCA protein assay and MTT assay.

Genetic expression of hyaluronansynthase (HAS2), collagen (COL1A2and COL3A1), elastin (ELN) andfibronectin (FN1) was determined 6,12, 24 hours as well as 3 and 5 daysafter treatment performing qRT-PCR.Housekeeping gene used wasglyceraldehyde-3-phosphatedehydrogenase (GAPDH). Cells werecultivated in T12,5 for proliferationand T25 flasks for genetic expressionmeasurements.

ResultsCompared to non-treated cells

migration is already visibly enhanced 6hours after shock wave application.Over a period of 24 hours the woundof the treated cells is nearly closed

whereas in the control cells it is stillvisible (Figure2a and 2b).

Cell Proliferation didn’t show anydifference between control and lowerenergy level treatment. Using higherlevels cell viability decreased causedby treatment. Surviving cells showedslightly higher proliferation rate in cellcounting than control group after 3and 5 days. However MTT assay andBCA protein assay showed higherresults for treated cells than cellcounting. MTT increased especiallystraight after treatment, whereas theamount of protein rose after 3 days(Figure3). For shown data cells werescaled to 2,5x103 cells per flask aftertreatment.

Influence of energy nearly equalsfocusing gene expression. Littleincrease in collagen expression is seenwithin 24 hours. Positive change inelastin amount can be observed from 12to 73 hours after treatment. Fibronectinand hyaluronan synthase remained atthe control level during observationperiod of 24 hours. Afterwardsespecially hyaluronan synthase showedsignificant progression.

DiscussionInfluence of ESWST on tissue

influences many different pathwayswherein the influence on fibroblastsmay be just another brick in the wall.In vitro effects are not directlycomparable to in vivo results what isespecially shown in case of focusedshock waves. Different devices weretried in this research. For treatment ofadherent growing cells it isadvantageous to use unfocused shockwaves. Due to focused high energy celldetachment increases. Proliferationand migration cannot be determinedin a satisfactory manner.

Currently using the IVSWT WaterBath 2.0 is the state of scientificknowledge for treating cells in culture.Nevertheless genetic expression iscomparable to other devices.Acceptance of higher energy levelscorrelates with amount of treated cellsfor which reason migration had to beexamined with lower levels.

The difference in MTT assay valuescompared to cell counting can imply ahigher metabolic activity of treatedcells especially after cell treatmentwhat could be another reason forESWT effects. It is well known that allinfluences of ESWT cannot be shownuntil a longer period than it’s possibleto cultivate cells without subcultivating. This might be anotherlimiting factor for in vitro research.

Influence of Shock-Wave-Treatment on Migration,Proliferation and Genetic Expression of Fibroblasts

Kerstin Neumann

Hans-Jürgen Duchstein

Helmut Neuland

Institute for PharmacyUniversity of HamburgHamburg, Germany

8

AcknowledgementWe thank Prof. Stephan Baldus for

the possibility to work in hislaboratories at the university hospitalHamburg-Eppendorf. Special thanks goto Dr. Anna Klinke and Dr. Denise Laufor their capable support.

References

1. Schaden Wolfgang; Thiele Richard; KolplChristine; Pusch Michael; Nissan Aviram;Attinger Christopher E; Maniscalco-Theberge Mary E; Peoples George E; ElsterEric A; Stojadinovic Alexander. Shock wavetherapy for acute and chronic soft tissuewounds: a feasibility study. The Journal ofsurgical research (2007), 143(1), 1-12

2. Jankovic Danilo. Case study: shock wavestreatment of diabetic gangrene.International wound journal (2011), 8(2),206-9

3. Arno A; Garcia O; Hernan I; Sancho J;Acosta A; Barret J P.Extracorporeal shockwaves, a new non-surgical method to treatsevere burns. Burns: journal of theInternational Society for Burn Injuries(2010), 36(6), 844-9

4. Silveira, Andressa. Effects ofextracorporeal shock wave therapy(ESWT) for the healing of distal limbwounds in horses. Dissertation (2010), 129pp.

5. Siems, Werner; Grune, Tilman; Voss, Peter;Brenke, Rainer. Anti-fibrosclerotic effectsof shock wave therapy in lipedema andcellulite. BioFactors (2005), 24(1-4), 275-282

6. Grinnell, Frederick. Fibronectin and woundhealing. Journal of Cellular Biochemistry(1984), 26(2), 107-16

7. Holfeld, Johannes. IVSWT – In Vitro ShockWave Treatment. ISMST Newsletter 2010May; Vol1, Issue1:6-7.

8. Geback, Tobias; Schulz, Martin MichaelPeter; Koumoutsakos, Petros; Detmar,Michael. TScratch : a novel and simplesoftware tool for automated analysis ofmonolayer wound healing assays.BioTechniques (2009), 46(4), 265-266, 268,270, 272, 274

Figures:

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Abstract

Background: Non-healing wounds are a significant burden to both the healthcare system and the patient, oftenrequiring protracted, intensive and quality-of-life-altering treatment. A novel approach to chronic wound management,extracorporeal shockwave therapy (ESWT) addresses the pathophysiological aspects of tissue ischemia and bioburdenaffecting chronic wounds.

Aim: To review the collective experimental and clinical data with ESWT from a translational research partnership(Austrian Cluster for Tissue Regeneration) and relevant published literature.

Methods: ESWT was applied in the context of animal and human studies: 1. Rodent ischemic epigastric flap model(0.1mJ/mm2, 0.10-0.30 pulses/cm2 immediately and 24 hours before/after ischemic challenge); 2. Patients with complicated,non-healing sub-acute and chronic wounds despite standard management, treated over 53-months in a prospective clinicalstudy (100 pulses/cm2, 0.1mJ/mm2, initially bi-weekly then weekly in conjunction with wound debridement and moistdressings).

Results: Immediate and delayed post-surgical ESWT was associated with equally superior flap outcome (reducedplanimetry-determined ischemic necrosis) compared to untreated controls. Tissue response to treatment was dose-dependent having maximum effect between 0.14 and 0.28 impulses/cm2 at an energy level of 0.1mJ/mm2. Induction ofangiogenesis with up-regulation of the VEGF-R2 and increased quantitative tissue perfusion were found to play a pivotalrole. Of 390 patients treated with ESWT, 72% demonstrated 100% wound epithelialization. Advanced patient age and woundsize negatively impacted response to ESWT. There was no treatment-related toxicity.

Conclusions: Extracorporeal shock wave therapy has a protective, pro-angiogenic influence on experimental ischemicflaps, and has beneficial effects on wounds unresponsive to standard treatment.

ESWT in Wound Care - Basic Research and Clinical Experience

Rainer Mittermayr, 1,2,3 Joachim Hartinger,1

Heinz Redl, 1 Wolfgang Schaden, 2,3

1 Ludwig Boltzmann Institute for Experimental and Clinical Traumatolgyin AUVA Research Center, Austrian Cluster for Tissue Regeneration2 AUVA Trauma Center Meidling, Vienna, Austria3 shockwavetherapy-vienna.at

Correspondence:Rainer Mittermayr, MDLudwig Boltzmann Institute for Experimental and Clinical TraumatolgyDonaueschingenstrasse 13A-1200 ViennaAustriaoffice: +43 (1) 33110 464FAX: +43 (1) 33110 460Email: rainer.mittermayr@trauma.lbg.ac.at

IntroductionThe incidence of patients suffering

from chronic wounds is continuouslyrising worldwide and constitutes anextraordinary burden to patients’quality of life but also to health careexpenses. The etiology is in themajority of cases multifaceted andtreatment is often insufficient andlimited to surgical intervention orspecial wound dressings 1-5.Furthermore, treatment isdisproportionally prolonged and ofteninsufficient eventually resulting intherapy refractory wounds. Patientdiscomfort concomitant with immensehealth care expenses make thesechronic wounds subject of intensiveresearch. Alternative (effective)

treatment options are highly desirableto reduce both cost expenses andpatients discomfort.

Normally, uncomplicated soft tissuewound healing is a complex, wellcoordinated cascade of interdigitateprocesses on the cellular but alsomolecular level 2,3. Ultimately, thisphysiological process leads to fulltissue regeneration with completerestored tissue integrity andfunctionality. Hypoxia is known to be astrong inducer of a broad spectrum ofmechanisms (adaptation of supply,metabolic and growth adaptation)facing tissue restoration 6,7. However,depending on severity and duration,the diminished oxygen supply can alsoresult in wound healing problems. This

is aggravated especially in the elderlybut also by co-morbidities such asdiabetes and hypercholesterolemia.Studies have shown that in these casesthe angiogenic response as a key eventin the physiological wound healingprocess is remarkably reduced 8,9. Thisleads to disturbed healing (chronicwounds, delayed healing wounds) butalso patient psychological strain andextraordinary economical health careexpenses.

Pathophysiologically, chronicwound conditions often result due totissue ischemia/hypoxia which is wellknown to be one of the major factorscomplicating the normal woundhealing process 10. The surgical dailyroutine is regularly confronted with

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such compromised tissue perfusion.Once surgical treated, it often ends up inextensive operative revisions. Inparticular, this is seen in patients withco-morbidities such as diabetes andperipheral ischemic diseases (e.g.arteriosclerosis, peripheral arterialocclusive disease). The intrinsic capacityfor physiological tissue regeneration isoften severely impaired in thesepatients. If wounds require skin flapcoverage in this patient population, thenthe transferred flaps may also benegatively affected by the underlyingpathology. Skin flap surgery usingautologous donor tissue is the treatmentof choice for patients with large woundsor tissue defects 11. Depending on thesize of the defect, skin grafts, muscularflaps or composite flaps may be used.Necrosis of skin flaps, either partial orcomplete, remains a seriouscomplication in skin flap surgery.Insufficient arterial (in-)flow with theaccompanying decreased nutritionalsupply to hypoxic/ischemic tissues canbe potentially overcome by therapeuticangiogenesis 12. Numerous angiogenicfactors have been studied for efficacy,for which an invasive approach withconcomitant application of exogenoussubstances is common 13-15. The mode ofadministration for angiogenic factors hasalso been studied, as the intendedclinical use and efficacy are a concernwhen known adverse effects occur withsystemic administration 16-18.

The therapy concept of chronicwounds (e.g. venous ulcers, diabeticulcers, pressure sores) is up to nowlimited in both quantity and efficacy.Clinical standards include sufficientsurgical and non-surgical (e.g.enzymatic) debridement withsubsequent application of specializeddressings providing the wound with amoist environment 4,19. However, severalexperimental approaches are currentlyevaluated to further improve chronicwound care. Studies show efficacy usinggene therapy, recombinant growth factorapplication, bio-engineered skin (tissueengineering), and stem cell therapy 20-22.However, these (experimental)treatment approaches target primarilyonly a single scope in the complexmechanism of pathological woundhealing processes.

Shock waves were first clinicallyused in lithotripsy and are a potentmeans in disintegrating urinary stoneshardly without side effects 23. Since then,technique as well as application modeshave been steadily modified andimproved. In the last decades, shock

wave application became attractive inthe orthopedic and traumatic fieldtreating (chronic) tendinopathies,pseudoarthrosis 24,25 but also chronicwounds 26,27. Distinct advantages overother clinical but also experimentaltherapeutic approaches are the non-invasiveness and the avoidance of“exogenous medication” via varioussubstances (e.g. growth factors,vasodilators). Although this encouragingproceedings, the biomolecular basis bywhich shock wave exerts its positiveeffects remains widely unclear. Fewexperimental studies suggest thatvascular endothelial growth factor – apivotal player in new vessel formation(angiogenesis) – is affected in terms ofup-regulation 28,29. Some studies alsodemonstrate the involvement of thenitric oxide system improving tissueperfusion 30,31.

In this work a brief overview of theexperimental and clinical experiencesusing extracorporeal shock wavetherapy in soft tissue wound care isprovided. Own results in conjunctionwith recent publications in this field arediscussed.

Basic ResearchBackground:

To better understand the(biomolecular) mechanism by whichshock wave therapy influences andsupport impaired soft tissue woundhealing, several investigators useischemia models. Iatrogenic occlusion ofblood flow (ischemia) constantly endsup in tissue necrosis accessible forvarious treatment modalities. One of thepromising approaches inreducing/avoiding post-ischemicnecrosis is “therapeutic angiogenesis”first mentioned by Hockel in 1993 12. Theprimary target is to stimulate local out-growth of vessels which are able to re-establish adequate perfusion. Severalinvestigators hypothesized thatinduction of angiogenesis is also one ofthe key events in the biomechanisms ofshock wave therapy.

Tissue Necrosis:Effectiveness of ESWT in reducing

ischemia-induced tissue necrosis wasalready shown experimentally indifferent rodent flap models 28,31-34. In ourlaboratory, several flap models areestablished 35-38. The rodent epigastricflap model (Figure 1) enablesinvestigating ischemia induced necrosisand potential therapies along withperfusion measurements reflectingdifferent degree of ischemia. In our

opinion, it is a feasible model evaluatingshock wave associated mechanisms andwas used therefore in several ESWTstudies. After short learning curve,surgery could be performed easily andflap outcome is highly reproducible.

After rendering a certain part of theflap ischemic (ligation and dissecting ofan epigastric vascular bundle), 300shock waves at 0.1 mJ/mm2 wereimmediately applied to the ischemicchallenged tissue. Attention was drawnthat over the distal parts of the lungs(proximal flap) no direct perpendicularapplication was administered. Sevendays after surgery and treatment, thearea of necrosis was substantiallyreduced in comparison to the untreatedcontrol group assessed by a planimetricanalyzing tool. This is in accordancewith multiple other experimental studiesusing flap models and ESWT 31,32,34,39-41. Allof them showed a significantly reducedarea of flap necrosis in the shock wavegroups compared to non-treatedcontrols. However, studies differed inthe total amount of applied pulses(range: 500 – 2500 pulses) and theenergy flux density (range: 0.09 – 0.15mJ/mm2). In addition, within these 6studies, three different shock waveapparatus were used (one study missingapparatus specification). Our owninvestigations on dosage optimizationshowed that tissue response totreatment is dose dependent havingmaximum effects between 0.14 and 0.28impulses/cm2 at 0.1 mJ/mm2 (manuscriptin preparation). Althoughinhomogeneities between the studies(including our findings) exist, looking atthe results on flap outcome a broad andsafe treatment modality could beimplied.

Influence of Treatment Time Point:Even though this findings are of

enormous clinical interest, clinicians(especially reconstructive traumasurgeons) are particularly confrontedwith delayed (e.g. 24 hours) tissuenecrosis following reconstructive (flap)surgery. Thus, a treatment option tointervene in such cases with alreadymacroscopically visible failure is highlydesirable. ESWT fulfills this requirementas seen in delayed treatment (24 hourspost ischemia) of the above mentionedrodent epigastric flap performed in ourinstitution 42. The 7 days follow-upshowed that the ischemic challengedflap developed significantly less necrosisas compared with the untreated controlgroup (Figure 2; manuscript acceptedfor publication in Annals of Surgery). In

11

contrast to our study, where we singletreated the flaps 24 hours post-ischemia Kuo et al. 34,43 applied shockwaves twice (immediately aftersurgery and 1 day thereafter). Contraryto our significantly reduction ofnecrosis after delayed treatment, theflaps treated twice in the study of Kuoand colleagues showed also reducedbut insignificant difference in areas offlap failure in comparison to controls.Possible explanations were given bythe authors that additional treatmentresults in too high local energy densitythus blocking blood perfusion andneovascularization. However, one ofour clinical cases supports the thesisthat ESWT might have the therapeuticpotential to rescue established tissuenecrosis (Figure 3) which we werealso able to demonstrateexperimentally.

A physiological process duringwound healing is the woundcontraction and reflects in somemanner the quality of wound healing(e.g. collagen composition). Woundcontraction should be minimal,especially for wound areas adjacent tojoints which have to be covered by skintransplants or flap transfer. Preventingor minimizing contraction (extensivescar formation) results in lessconstrained range of motion in theinvolved joints and avoids surgicalrevisions. But also areas adjacent toorifices (face, beside the aestheticpoint of view) are vulnerable tocontraction and should be kept at aminimum. In the same study set-up,less flap contraction concomitant withless necrotic area was observed.

Encouraged by these findings, weaddressed a further issue in electivetreatment. Although in elective surgerya broad spectrum of possiblecomplications can effectively beavoided, a residual risk which isincalculable exists especially in patientswith co-morbidities (e.g. disturbedwound healing in diabetic patients). Atremendous amount of professionalcare efforts (wound care, woundrevision) and social financial burdencould be reduced if an electivetreatment would be available toprepare the tissue as needed for theanticipated surgical intervention.Surgical procedures in a two stagemanner were already evaluated toreduce necrosis and showedeffectiveness 44. For instance, in thefirst stage of flap surgery, only incisionswill be made to induce the followingincreased tissue perfusion and to

prepare the tissue for transfer in thesecond stage. Although this procedureshows a positive impact in the latterflap outcome, it neverthelessrepresents an invasive approach withits side effects (e.g. infection risk).When shock waves were appliedexperimentally to the flap prior tosurgery, an equal reduction in necroticflap area was found as compared to theabove mentioned therapy groups(treatment immediately and 24 hoursafter surgery) where shock waves wereapplied delayed regarding ischemia.This is of great clinical relevance,because clinicians would have theopportunity to selectively treat patientsprior to intended surgery who are athigh risk of suffering from woundhealing disturbances. A clinical studyperformed in 2008 45 used thisapproach to treat surgical wounds aftervein harvesting for coronary bypassgrafts and had less woundcomplications in the shock wavetreated group. However, treatment wasperformed after surgery beingprophylactic but not really reflecting anelective intervention.

These findings in reducing tissuenecrosis by ESWT are comparable withthose studies which used exogenousgrowth factors (e.g. therapeuticangiogenesis) in the same indication37,38. An enormous advantage, however,over these studies is the non-invasiveness of our approach in theapplication of shock waves.Additionally, no adverse effects overthe entire study period were observed.Further advantages are that theapplication is simple, it is well-receivedby the patients and is cost effective.

Influence of ESWT onCompromised Tissue Perfusion:

Probably one of the worst scenariosin reconstructive surgery (e.g. afterfree flap transfer with micro-anastomosis) represent tissue loss dueto hypoxia or ischemia, as alreadymentioned above. Several differentinstruments and methods exist forearly detection of this unfavorablecondition. However, treatment optionsafter verification of this status arescarce. In the described animal model,flap ischemia could be verified beyonddoubt by clear blue demarcation 24hours after vessel ligation. In addition,a clinically used, non-contact, Dopplerbased system could confirm the clinicalmacroscopic finding. The principle isthat a low intensity laser light beamscans the surface of the skin and

generates a 2-dimensional image of flapperfusion. With this technology theischemic impact was confirmed in alltest animals by a distinct reduction inflap perfusion.

In addition, using the Doppler basedperfusion imaging system a clearenhancement of circulation in theexperimental flaps was noticeable atthe time point when shock waves wereapplied. Moreover, superficial tissueperfusion was maintained at a higherlevel during the entire study period (7days) when compared to controls. Thisis confirmed by perfusion studies in adorsal random flap model, whichshowed significantly increased bloodflow following ischemic impact 34,46.

Two reasonable mechanisms couldexplain this finding. Nitric oxide (NO),a small ubiquitous molecule withvasoactive properties, causes vesseldilation which results in improvedperfusion. Production and release isdependent on endogenous activity ofits synthase. A study by Yan et al. 31

demonstrated a higher level of bothnitric oxide and endothelial nitric oxidesynthase (eNOS) in response to shockwaves 8 hours after application. Oi etal. 30 confirmed eNOS up-regulation inan ischemic hindlimb model. Thus, thisinitial higher NO content stimulated byshock wave treatment could improveearly perfusion and reduces earlyischemia induced tissue damage.

Physiologically, angiogenesis takesplace within 24 to 48 hours afterimpact. Vascular endothelial growthfactor (VEGF) is the pivotal player inthe angiogenic response, stronglyinduced by hypoxia. It is noteworthythat VEGF and NO influence eachother 47. Improved perfusion, initiallyaccomplished by shock waves via NOas mentioned above, could then bemaintained by shock wave inducedangiogenesis. In fact, a number ofstudies showed up-regulation of VEGF31,34,48-50. Our own investigations intransgenic VEGF-R2 mice, revealed adistinct up-regulation of the mainangiogenesis-related receptor VEGF-R2due to ESWT, directly or indirectlythrough NO generation. Numeroushistological and immunohistochemicalanalyses further showed enhancedlevels of VEGF expression and highercontent of capillaries. This improvedcirculation may have distinct benefitsin wounds subjected to healingdisturbances. All of this supports thehypothesis that angiogenesis withconcomitant improved tissueperfusion/improved blood supply is one

12

of the mechanisms of ESWT inischemic/hypoxic wounds.

Furthermore, recent experimentalstudies demonstrate that ESW treatedtissues, which were vulnerable todisturbed wound healing, show modifiedrelease kinetics of essential growthfactors 51. Treatment resulted inincreased cell proliferation, suppressionof pro-inflammatory cytokines, andaccelerated tissue regeneration andhealing 52-54.

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 withshock waves have better adherence tothe wound bed in the ischemicchallenged flap area in comparison tountreated controls. Surprisingly, this wasnot due to reduced seroma formation(nearly equal amounts between shockwave groups and control). Therefore, astrong induction of angiogenesis had tobe induced by shock wave therapyoriginating primarily from thecontralateral (perfused) side withoutnecessitating the contact to recipientwound bed.

Clinical Experiences Background:

Since the first clinical use of ESWTto disintegrate urinary stones decadesago 55, a series of clinical observationslead to expanded treatment indications.One of the first new fields of applicationwas the treatment of non-union in bonefractures 24,25. Nowadays extracorporealshock wave therapy is used in the clinicto treat further different pathologicalconditions of the musculoskeletalsystem such as plantar fasciitis, (non-)calcifying tendinosis, and epicondylitis56-58.

The serendipitous finding of chronicwound healing concomitant with theconsolidation of non-union attracted theinterest also to chronic woundconditions which are refractory toconventional therapy.

The Trauma Center Meidling is oneof the largest trauma-clinics in Austriaand Europe with around 70.000 trauma

patients treated per year. More than7.000 as indoor patients and more than300 needing intensive care (166 beds / 8ICU-beds).

The Trauma Center Meidling usesshock wave technology to treat non-union in bones already for 15 years.Furthermore, ESWT is used indelayed/non-healing or chronic woundssince 2004.

Patients and Etiology:At regular intervals (initially

biweekly, then weekly) patients aretreated in our hospital primarily in anoutpatient setting.

The etiologies of the treated softtissue wounds are wide-ranging andinclude failure of primary wound closureafter trauma and surgical intervention,disturbed wound healing after trauma,venous or arterial ulcers, pressure sores,and burns.

Those patients were enrolled whovolunteered to participate in the studyor refused standard therapy in order toavoid hospitalization. Exclusion criteriawere as follows: pregnancy, patientswith stage I (intact skin with signs ofimpending ulceration) and stage IV (full-thickness loss of skin and subcutaneoustissue and extension into muscle, bone,tendon, or joint capsule) decubitusulcers (stage II and III decubital ulcerswere included), superficial first degree,superficial second degree orcircumferential burns requiringescharotomy, compartment syndrome,necrotizing fasciitis, or lymphedema.Patients with current participation inanother clinical investigation of amedical device or a drug therequirements of which precludedinvolvement in the current study andthose with active or previous (within 60days prior to the study screening visit)systemic chemotherapy and/or radiationto the affected extremity to be treatedby investigational shock wave therapywere excluded from this study. Inaddition, patients with physical ormental disability or geographicalconcerns (residence not withinreasonable travel distance) that wouldhamper compliance with required studyvisits were also excluded. The study wasapproved by the Institutional ReviewBoard of the AUVA Trauma CenterMeidling.

Focused versusUnfocused/Defocused Shock Wave:

Shock wave devices based on theelectro-hydraulic technology which areused routinely in various pathological

musculoskeletal conditions consist of aunder water spark plug with opposingelectrodes. Shock waves generated bycharging the opposing electrodes withmaximum voltage concomitant withabrupt discharge are focused via a halfellipsoid shaped piece (reflector). Dueto the geometric properties of thisreflector all shock waves are reflected toan area (secondary focus – F2) at adefined distance away from the primaryfocal point (opposing electrodes – F1).Therefore, during treatment the exactalignment of the therapy head and thearea to be treated (e.g. non-union = F2)is mandatory to gain maximum peak-positive acoustic pressure at this point.

Other than in lithotripsy or non-unions an unfocused or defocused shockwave in wound care indications ispreferable due to the typically largersurface area of soft tissue wounds. Toachieve such shock waves which areroughly plane to the treatment area thedevice which we use in our hospital hasa parabolic instead of an ellipsoidreflector. Positioning the opposingelectrodes at the primary focus F1 in aparabolic reflector will result in a planarwave which is emitted after thereflection of the primary spherical wave.The focal point (F2) of these planewaves is, by definition, “unfocused” or“defocused”, which means that asecondary focal point F2 is found in theendless distance. Therefore the shockwave characteristics for the parabolicreflector could be defined as planarwaves comprised of parallel rays ofacoustic energy. The generalizedparabolic reflector allows the planewaves to be bent slightly towards thecentral acoustical axis. Therefore thewaves are unfocused, nearly parallel,and the energy density realized by thisreflector configuration is higher thanwith an exact parabolic reflector and alarge area is stimulated by the acousticalfield.

Apparatus and Configuration:Non-healing/chronic wounds are

treated with unfocused extracorporealshock waves. We used first theorthowave 180C (MTS Europe GmbH,Konstanz, Germany) to treat ourpatients. Since summer 2007 we useadditionally the ActiVitor (SwiTechMedical AG, Switzerland) in the sameclinical set-up (Figure 4). Consideringprevious experience treating variousmusculoskeletal disorders such astendinopathies we concluded to applyan average energy flux density of 0.1mJ/mm2 typically applied for theseindications in the range of 0.03 – 0.15

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mJ/mm2. Experimental dose-responsestudies indicated 100 pulses per cm2 asthe optimal dose for the proposedindication. Following configurations ofESWT were applied to each individual:

Orthowave 180C: 100 totalimpulses per squarecentimetre at anenergy flux intensity of 0.1 mJ/mm2

(level 5), frequency of 5 pulses/sec.ActiVitor: Equivalent parameters in

terms of impulses/cm2, energy fluxintensity and frequency were used.

Treatment Modalities andAdditional Wound Care:

We treat our patients (bi-)weeklyprimarily in an outpatient setting. Atpresentation and on each otherevaluation time points wounds areclinically described concerning woundarea, wound depth, wound cavitations,signs of inflammation, and exudationstate. Additionally, digital images aretaken for documentation. If necessary,wounds are debrided prior to shockwave treatment to removeavital/necrotic tissue as it will be alsoperformed in the daily clinical routine.

Until yet, no anesthesia wasnecessary in any of the patientsenrolled, as the delivered shock wavewas defocused and therefore notcausing relevant pain.

After adequate preconditioning ofthe wounds sterile ultrasound gel wasapplied on the wound surface as well ason adjacent tissue. Then, parameters ofthe shock wave device were adapted toeach individual treatment. Shock waveswere administered directly on thewounds but also on the surroundingtissue. Post treatment the gel wasremoved and special wound dressings(standard or advanced) were appliedaccording to wound needs. Betweenthe treatment sessions patientsreceived advanced wound dressingsaccording to wound needs. All pre-treatment data including digitalphotography were continuouslyupdated during each single-timesession.

Collected/Evaluated Parametersand Study Readout:

Patient variables analyzed includedage at presentation and gender.Anatomic sites were classified as softtissue wound of the upper and lowerextremity, trunk or head. Wound-specific variables included etiology(disturbed healing, post-traumaticnecrosis, venous stasis ulcer, decubitalstage II/III ulcer, plaster cast pressureulcer, arterial insufficiency ulcer, or

second or third degree burn), woundsize in cm2, wound depth (superficial ordeep), and wound cavitations (none, ≤1cm, or > 1 cm). Shock wave therapyrelated factors analyzed were numberof shock wave treatments and shockwave pulses delivered. In addition, inwounds responsive to ESWT the meantime from first treatment to completehealing was assessed.

Primary study endpoint was toevaluate the feasibility of shock wavetreatment in sub-acute/chronic woundsof various etiologies failing standardwound care. Secondly, the overallhealing rate in response to treatmentwas evaluated and referred to differentvariables such as patients’ age, woundetiology, and wound size. Treatmentparameters were assessed also withrespect to the healing rate.

Definitions:Wounds of the head were those

located on at or above the skull base orinvolving the face.

Wounds lower the groin weredefined as lower extremity wounds.Wounds lower the shoulder werecategorized as upper extremitywounds. Wounds of the superficialtrunk including the gluteal and sacralregions were defined as truncal.

Disturbed healing was defined aspartial or complete failure to heal afterprimary closure of a

surgical wound. Skin grafts or flapswere not included in this study. Softtissue wounds resulting from directpenetrating or blunt trauma associatedwith necrosis of epithelial and non-epithelial extra-skeletal structures (e.g.fibrous and adipose tissue, skeletalmuscle, vasculature, etc.) werecategorized as posttraumatic.

Venous stasis ulcers were non-healing sores or wounds of the lowerleg near the medial malleolous inpatients with known dysfunction of theperforating draining veins of the legapparent by duplex ultrasound. Thesewere typically characterized by ashallow, exuding ulcer with diffuseedges, brown pigmentation,surrounding skin scaling andgeneralized edema of the affectedextremity.

Decubitus ulcers were defined assores resulting from pressure exertedon the skin, soft tissue, muscle andbone by the weight of the patientagainst a surface beneath them. Forthe purpose of this trial, decubitusulcers demonstrating partial-thicknessloss of skin involving epidermis and

dermis as well as decubitus ulcersshowing full-thickness loss of skin withextension into subcutaneous tissue, butnot through the underlying fascia wereincluded. Pressure sores in this studycharacterized by partial thickness lossof skin involving epidermis, dermisand/or subcutaneous tissue, but notsuperficial investing muscular fascia,resulting from skin necrosisattributable to localized pressure fromthe inner aspect of a plaster cast over abony prominence were defined asplaster cast pressure ulcers. An arterialinsufficiency ulcer was defined bychronic, non-healing, distal limbulceration in patients with knownatherosclerotic peripheral vasculardisease unable to receiverevascularization due to medical co-morbidity or lack of suitable outflowartery in the affected extremity.

These ulcers were typically deepwith localized edema and shiny,hairless surrounding skin. Burn woundsin this study were defined as non-circumferential deep second or thirddegree burns typically characterized bypresence of blisters, mottled/patchyappearance and diminished or nosensation.

Wound depth was defined relativeto the dermis. Soft tissue woundsextending beyond the dermis into theunderlying subcutaneous tissue weredefined as deep. Those woundsconfined to the epidermis and dermiswere regarded as superficial. Woundcavity or soft tissue defect was definedas absent, < 1cm, or > 1 cm relative tothe epidermis. Wound duration wasdefined from the date of diagnosis ofthe soft tissue wound under study tothe date of first shock wave application.No patients received antibiotic therapyduring shock wave treatment.

Results and Discussion:Study Summary:During August 2004 and December

2008 (= 53 months), patients with sub-acute and chronic wound conditionswere enrolled as part of clinical routine.They underwent treatment withunfocused shock wave therapy in thisprospective non-randomized singlearmed study. Parts of this open studywith 208 patients were published in2007 by Schaden et al. 26.

During the 53 months, 390 patientswere included (summary of patient,wound, and treatment related factorsin Table 1) for shock wave treatment.The mean age of the patient cohortwas 59.4 years ranging from 11 to 102

14

years (median: 60 years). It is notablethat of these 390 patients 57.4% weremale and 42.6% were female. Thisgender distribution could be due toour trauma centers´ prevalence oftreating working accidents. Comparingage and gender the mean age in themales was 60.8 ranging from 11 to 102years (median: 50) while the age offemales was in mean 57.6 within 20and 97 years (median: 76).

Most common comorbidies werediabetes mellitus type II, and vascularhypertension which is typicallyassociated with chronic ordelayed/non-healing wounds(“diabetic foot ulcer”). A largenumber of patients reported smokingbehavior which also negativelyinfluences wound healing 59,60.Therefore it is more interesting,whether diabetes mellitus type II norsmoking affected adversely treatmentoutcome although patients concernedmaintained smoking during therapyduration.

The most common location ofwounds treated was the lowerextremity (79.7%) followed by theupper extremity (14.9%). Residualwounds were distributed to the trunkand the head. Most frequentlyobserved wound etiology in thiscohort were wound healingdisturbances of primary acute (directpenetrating or blunt trauma) wounds(43.3% = 169 patients). Posttraumaticnecrosis (epithelial and non-epithelialextraskeletal structures) was found in31.3% (122 patients) of the patientsrepresenting the second main woundetiology. Treatment of the variousulcers was performed in 83 patients.Delayed/non-healing burn woundswere treated in 16 patients.

The mean wound size independentof wound etiology was 11.6 cm2

ranging from 0.24 to 375 cm2 (median:5cm2). Looking at the different typesof wounds it was found thatposttraumatic tissue necrosis had thelargest wound surface area beforeESWT with a mean size of 12.6cm2

(range: 0.24 – 140cm2, median: 6cm2)followed by decubital ulcers (mean:12.2cm2, range: 0.5 – 120cm2, median:6cm2) and wounds with healingdisturbances (mean: 12.2cm2, range:0.3 – 375cm2, median: 4cm2). Most ofthe wounds were superficial meaningthat they did not exceed beyond thedermis (276 wounds out of 390).Plaster cast pressure ulcers showed in54.6% a wound depth which extendedthe dermis layer and reached thesubcutaneous tissue. In the decubital

ulcers this was the case in 40%, in37.7% in the disturbed healingwounds and in 33.3% in arterialulcers. 33.5% of all included ulcerswere judged as deep ulcers. Woundcavities were present in 60 patients(=15.4%) while in 68.3% the cavitywas smaller than 1cm and in residual31.7% the cavity showed an extensionof or greater than 1cm.

Treatment Outcome:Of the 390 patients treated with

ESWT during August 2004 andDecember 2008, of which 330 patientscould be evaluated, 279 patientsshowed complete healing of theirwounds (=71.5%) while 5.4% werenon-responsive to shock wave therapyand wound size remained unchangedwhen compared to the beginning oftherapy. In total 60 patients (15.4%)missed the follow-up without havinginformation whether wounds werehealed or stayed unchanged. At theend of therapy 3.3% (13 patients) hada greater than 50% healing responsein comparison to baseline wound sizeand 4.4% (17 patients) smaller than50% (for summary of treatmentoutcome see Table 2).

The mean time from the firsttreatment with ESW to completehealing was 44 ± 44 days (mean ± SD;median: 33.5 days, range: 4 – 381days). Wounds with healingdisturbances as well as burn woundsshowed the fastest healing with amedian duration from the firsttreatment to complete healing of 29and 28 days, respectively (range: 4 –134 days and 7 – 62 days,respectively). In the ESWT responsivedecubital ulcers and venous stasisulcers it took longest to heal (median:63 days (range from 14 – 224 days)and median: 61 days (range from 7 –237 days).

Analyzing the influence of thewound etiology and healing rate whendelayed/non-healing burn woundsshow the best efficacy of ESWT with ahealing rate of 94% followed by post-traumatic wound necrosis with atreatment success of 83%. Descendingsuccess has been found in woundhealing disturbances (74%), plastercast pressure ulcers (73%), arterialinsufficiency ulcers (67%), anddecubital ulcers (65%). However, all ofthe mentioned show a better healingrate than 50% following shock wavetherapy. Contrary, the worst resultsshowed the venous stasis ulcers with asuccess rate of only 28%.

A clinical study evaluating ulcersprimarily of the lower extremity

treated with ESWT showed a healingrate of 36% in venous stasis ulcerswhich is comparable to our results. Incontrast, 69% of post-traumatic ulcerswhich were also investigated healedcompletely after shock wave therapy 61.

No differences exist between bothgenders. On the other hand, patients’age is related to wound outcomeindependent of wound etiology. Ingeneral, higher age is associated with ahigher incidence of failure to completehealing after ESWT (Figure 5).

The wound size also influences thehealing rate independently of woundetiology, except for the plaster castpressure ulcer where no correlationbetween wound size and outcomecould be found (Figure 6). However,not surprisingly, larger wound sizecomes along with worser outcome. Inthe study of Schaden et al. in which amultivariant logistic regressionanalysis was performed, patient age,and wound size emerged asindependent predictors of completehealing 26.

The wound depth also plays a rolein the healing tendency in response toESWT although the influence of thisparameter is not as important asprimarily thought. While superficialwounds completely healed in 73% ofthe cases this was only in 67% fordeeper wounds reaching thesubcutaneous layer. If wound cavitiesare pre-existent the healing rate aftershock wave therapy is slightly lower(67%) than in wounds without anycavities (72%). Hereby it is notablythat no differences were found if thecavity is larger or smaller than 1cm.This is in accordance to the analysesof Schaden et al. 26.

In average wounds were treated2.9 times (range from 1 – 15)whereby wounds receiving 14 and 15sessions were performed in only 1case, each, and 11 to 13 treatmentsession were never necessary. Asexpected, venous stasis ulcers had tobe treated more often (mean: 5.2times) with a median of 1700 pulses(range: 150 – 44700 pulses). A hugenumber of patients only needed 1session. The mean total amount ofpulses applied was 1482.7 (range from100 to 44700).

Shock wave treatment ischaracterized by number of pulsesapplied, the frequency and energyflux density. Until now, we normallyuse the same energy level as well asfrequency due to empiricalexperimental but also clinical data andto keep the treatment variables low.

15

Only the total number of shock wavepulses differs and is adopted to woundsurface area (approximately 100pulses/cm2). However, changing theother parameters it is likely that alsooutcome is influenced. Therefore,several studies are performed (seeabove – basic research) investigatingthis topic.

Since 2007 we use additional theActiVitor (SwiTech Medical AG,Switzerland) in parallel to theorthowave 180C (MTS Europe GmbH,Konstanz, Germany). In comparing thistwo systems (both use electrohydraulicmode) no differences could beobserved in terms of treatmentefficacy, although these findings onlyreflect the clinical observations and nocomparative study was carried out.

Adverse Events:There were no reported cardiac,

neurological, dermal, thermal orallergic reactions or adverse events.For the few patients that reported painduring unfocused shock wavetreatment appropriate reduction inenergy flux density (0.06-0.08 mJ/mm2)and frequency (2 – 3 pulses persecond) for the first 50 to 100 impulseswith subsequent gradual escalation totarget parameters was well tolerated.However, no patient needed furtherlocal or general anesthesia. Duringtreatments no event of bleeding,petechiae, hematoma or seromaformation was observed. All ESWT wasadministered on an outpatient basis(excluding those patients hospitalizedfor various medical reasons). Noclinically evident wound infectiondeveloped in soft tissue defects treatedwith shock waves, and no patient inthis study experienced anydeterioration of the treated wound.

Conclusions In summary ESWT was found as a

feasible therapeutic tool in preventingexperimental necrosis in ischemicchallenged tissue. The therapeuticeffect was seen independent of time oftreatment. This is of important clinicalrelevance, because it providesclinicians with a certain therapeuticwindow in which ESWT is effective.Tissue subjected to hypoxia/ischemiaafter surgery is suitable for this non-invasive, cost-effective approach andmay help to reduce extensive surgicalrevisions and prolonged wound care.Likewise, patients susceptible towound healing disturbances could betreated prior to necessary surgicalinterventions, thus minimizingpostoperative complications.

The experimental findings supportthe clinical results of ESWT in patientssuffering from delayed/non-healing orchronic wounds. Multiple indications inthe field of soft tissue wound healingare highly responsive to ESWT, exceptvenous stasis ulcers which show limitedsuccess.

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16

therapy ameliorates hindlimb ischemia inrabbits. Tohoku J. Exp. Med. 214, 151-158(2008).

31. Yan, X., Zeng, B., Chai, Y., Luo, C. & Li, X.Improvement of blood flow, expression ofnitric oxide, and vascular endothelialgrowth factor by low-energy shockwavetherapy in random-pattern skin flap model.Ann. Plast. Surg. 61, 646-653 (2008).

32. 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).

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

54. Kuo, Y. R. et al. Extracorporeal shock wavetreatment modulates skin fibroblastrecruitment and leukocyte infiltration forenhancing extended skin-flap survival.Wound. Repair Regen. 17, 80-87 (2009).

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17

Fig. 1

Fig. 2 Fig. 3

Figures:

Fig. 4

18

Patient Characteristics I

Parameter No. of patients Percentage (%)

Total number of study subjects 390 100

Gender

- Female 166 42.6

- Male 224 57.4

Age

- Mean 59.4

- Median (range) 60 (11-102)

Wound site

- Upper extremity 58 14.9

- Lower extremity 311 79.7

- Trunk 18 4.6

- Head 3 0.8

Wound Etiology

- Disturbed wound healing 168 43.1

- Post-traumatic wound necrosis 122 31.3

- Venous stasis ulcer 43 11.0

- Decubitus ulcer 20 5.1

- Plaster cast pressure ulcer 11 2.8

- Arterial insufficiency ulcer 9 2.3

- Burn wound 16 4.1

Table 1.

Tables:

Fig. 5

Fig. 6

Parameters No. % No. % No. % No. % No. % No. % No. % No. %

Wound Location

Head 2 1 0 0 0 0 1 5 0 0 0 0 0 0 3 0.8

Trunk 7 4 1 1 0 0 8 40 0 0 0 0 2 12 18 4.6

Upper Extremity 28 17 17 14 0 0 1 5 4 36 0 0 8 50 58 14.9

Lower Extremity 132 78 104 85 43 100 10 50 7 64 9 1 6 38 311 79.7

Wound Size (median, range)

< 10 cm2 125 74 80 66 31 72 16 80 9 82 8 89 9 56 278 71.3

> 10 cm2 44 26 42 34 12 28 4 20 2 18 1 11 7 44 112 28.7

median (range), cm2

Superficial Wounds 107 63 96 79 33 77 12 60 5 45 6 67 16 100 275 70.5

Deep Wounds 62 37 26 21 10 23 8 40 6 55 3 33 0 0 115 29.5

Wound Cavitation

None 137 81 108 89 37 86 14 70 10 91 8 89 16 100 330 84.6

< 1 cm 22 13 9 7 6 14 3 15 1 1 0 0 0 0 41 10.5

> 1 cm 10 6 5 4 0 0 3 15 0 0 1 11 0 0 19 4.9

Complete Healing 124 73 101 83 12 28 13 65 8 73 6 67 15 94 279 71.5

No. ESWT Tm. *

No. ESWT Pulses *

Time of Healing, d *

* median (range) in completely healed wounds; Tm ... Treatments

% refers to percent od column total

2 (1 - 4)

800 (150 - 3000)

28 (7 - 237) 34 (4 - 381)

700 (100 - 7300)

2 (1 - 14)2 (1 - 3)

500 (200 - 1460)

30 (7 - 105)

2 (2 - 6)

1300 (800 - 2100)

41 (13 - 126)

4 (1 - 14)

925 (300 - 5500)

61 (7 - 237)

2 (1 - 10)

600 (200 - 6350)

63 (14 - 224)

2 (1 - 8)

700 (100 - 7300)

29 (4 - 134)

2 (1 - 9)

700 (100 - 6000)

31 (6 - 381)

2 (0.5 - 18) 4 (1 - 45) 9,5 (1 - 36) 5 (0.2 - 375)4 (0.3 - 375) 6 (0.2 - 141) 4 (1 - 50) 6 (0.5 - 120)

Total

patients

necrosis

n = 122

Patient Characteristics II

ulcer

n = 20

stasis ulcer

n = 43 n = 16

insufficiency

ulcer

pressure

ulcer

n = 11 n = 9

Arterial Burn

wound

Post-traumatic Venous Decubitus Plaster castDisturbed

wound

healing

n = 169

Table 2.

Newsletter of ExtracorporealShockwave Therapy is an international,peer-reviewed journal produced byInternational Society for MusculoskeletalShockwave Therapy(ISMST) and is issuedthree times a year

Newsletter of ExtracorporealShockwave Therapy offers the opportunityto publish original research, clinical studies,review articles, case reports, clinicallessons, abstracts, book reviews,conference reports and communicationsregarding the scientific or medical aspectsshockwave therapy.

Manuscript SubmissionAll manuscripts should be sent to the

Editor: By e-mail: prds@uol.com.brOn disk and mail to:Dr Paulo Roberto Dias dos SantosRua Nathanael Tito Salmon, 233Osasco - São Paulo - BrazilCEP 06016-075 We encourage authors to submit

manuscripts via e-mail. When submitting bye-mail, print mail address and telephoneand fax numbers also should be included.

Manuscript Categories All articles should be well-written in

plain English, whereby jargon, acronyms,abbreviations and complicated data shouldbe avoided. Scientific research:

Theoretical or experimental (basic orapplied) scientific research or the practicalapplication of this research. The articleshould consist of an abstract, key words,introduction, methods, results, discussion,and conclusion.

Length: The manuscript should be nolonger than 2,500 words, including title page,abstract, references, legends and tables.Review articles:

Review articles on topics of generalinterest are welcomed. Reviews shouldinclude the specific question or issue thatis addressed and its importance for theshockwave therapy community, andprovide an evidence-based, balancedreview on this topic. The article shouldinclude a description of how the relevantevidence was identified, assessed forquality, and selected for inclusion;synthesis of the available evidence suchthat the best-quality evidence shouldreceive the greatest emphasis; anddiscussion of controversial aspects andunresolved issues. Meta-analyses also willbe considered as reviews. Authorsinterested in submitting a review manuscriptshould contact the editorial office prior tomanuscript preparation and submission.

Length: Approximately 2,000 to 2,500words and no more than 40 references. Case reports

Authors are encouraged to submitarticles with interesting case reports withrelevant information regarding diagnosisand therapy, unique for shockwavetherapy. The articles should be short,accurate and easy to understand, andshould consist of the following:

- A summary with the clinical relevance;

- An introduction explaining the clinicalproblem;

- A short report of the cases, consistingof history, physical examination, furtherinvestigation, treatment and follow-up.

- A discussion, whereby the clinicalconsequences are described and the mostinteresting aspects of the case report.

Length: Approximately 750 to 1,200words and a maximum of 15 references. Clinical lesson

Authors are invited to give a descriptionand background information ofdevelopments in the field of furtherdiagnostics and clinical tests and methodsthat are relevant to all aspects ofshockwave therapy, training andrehabilitation. It is not necessary toinclude examples of patients, as in casereports. The articles should be up-to-date,short, accurate, and easy to understandand should contain the following:

- A summary with the clinicalrelevance (max. 150 words)

- And introduction with the theme ofthe article

- A description of the used test methodor diagnostic

- A conclusion with the practicalrelevance and practical tips.

Length: Approximately 750 to 1,200words and a maximum of 5 references.National organisationcommunications

National organisations are invited todescribe any aspect of medical care orscience in their country, e.g. the functionof their medical committee, medical careof their players, research that is beingconducted etc.

Approximately 300 to 500 wordsLetters to the editor:

Letters discussing an article that hasbeen published in Journal ofExtracorporeal Shockwave Therapy havethe greatest chance of acceptance if theyare sent in with 2 months of publication.Letters that are approved will be forwardedto the author, who will have 6 weeks torespond. The original letter and the replywill be published simultaneously.

Length: Such letters should not exceed400 words of text and 5 references.Research Letters reporting originalresearch also are welcome and should notexceed 600 words of text and 6 referencesand may include a table or figure.Review of the Literature

Authors are invited to submitsummaries of published article of particularinterest for the shockwave therapycommunity. The opinion of the authorshould be stated following each summary.

Length: Such a review should beapproximately 500 to 700 words. A reviewof three articles simultaneously should beno longer than 1,000 words. Conference reports and Abstracts

Authors are invited to submit reportsof conferences they have attended, and toinclude one to three photographs taken atthe meetings. Please include the namesand highest titles of the persons that canbe identified in the photographs.Summaries of work presented at theconference may be submitted forpublication as well.

Length: 300 to 500 words per report orabstract.

Manuscript PreparationManuscripts should be prepared in

accordance with the Uniform Requirementsfor Manuscripts Submitted to BiomedicalJournals (Vancouver Style).http://www.nlm.nih.gov/bsd/uniform_requirements.html

• If submitting by e-mail, text, tables,and figures should be included in the samefile. Do not submit duplicate copies by mailor fax.

• Articles should be in Microsoft Wordformat.

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• Please use Times New Roman, size 12.• On the title page include the full

names, highest academic degrees, andaffiliations of all authors. If an author'saffiliation has changed since the work wasdone, list the new affiliation as well.

• Figures, summary tables and diagramsshould be numbered consecutivelythroughout the paper. Photographs shouldbe clearly labelled.

• References. Number references in theorder they appear in the text; do notalphabetise. In text, tables, and legends,identify references with superscript Arabicnumerals. When listing references, followAMA style and abbreviate names ofjournals according to Index Medicus. Listall authors and/or editors up to 6; if morethan 6, list the first 3 followed by et al.

– Journal: Kibler WB. The role of thescapula in athletic shoulder function. Am JSports Med. 1998;26(2):325-337.

– Book: Perry J. Biomechanics of theshoulder. In: Rowe CR, ed. The shoulder.London: Churchill Livingstone, 1988:1-15.

• Footnotes should be avoided.

Review processContributions will be reviewed by the

editorial board for scientific research,review papers, case reports, clinicallessons, and abstracts. Manuscripts shouldmeet the following criteria: material isoriginal; writing is clear; study methods areappropriate; the data are valid; conclusionsare reasonable and supported by the data;information is important; and topic hasgeneral shockwave therapy interest.

Manuscripts with insufficient priorityor quality for publication are rejectedpromptly. Other manuscripts are sent toexpert consultants for peer review. Peerreviewer identities are kept confidential,but author identities are known byreviewers. The existence of a manuscriptunder review is not revealed to anyoneother than peer reviewers and editorial staff.

Intellectual property• The article must be your own original

work. • If the article contains any photographs,

figures, diagrams, summary tables, graphsor other non-textual elements that are notyour own original work, you must ensurethat you have obtained written permissionfrom the copyright owner to include theirwork in your article for publication inJournal of Extracorporeal ShockwaveTherapy. Permission letters must besubmitted with your article.

Instructions for Authors