ࡱ> =?:;<j5@bjbj22 QcXXi6!fffft4:2Lfff|b9d9d9d9d9d9d9$;R>9|9f|!E:-,-,-, 8f|b9-,b9-,-,E,r6T7| }>f(6b9[:0:6>+>77>V8 -,99,PROCJENA PRE}IVLJENJA KO}NIH RE}NJEVA POMOU IR TERMOGRAFIJE Dra~en Shejbal* mr. sc., Petar Drvia* mr. sc., Sreko `vai** prof. dr. sc., Ivanka Boras** doc. dr. sc., Mirela `uaa** dipl. ing., Boris Pegan* prof. dr. sc., Livije Kalogjera* prof. dr. sc. * Klinika za otorinolaringologiju i kirurgiju glave i vrata, KB Sestre milosrdnice, Zagreb ** Fakultet strojarstva i brodogradnje, Zagreb Adresa: Dra~en Shejbal, Klinika za otorinolaringologiju i kirurgiju glave i vrata, KB Sestre milosrdnice, Zagreb 10 000, Vinogradska ulica 29 Telefon: 091 1 515 929, fax 01 3 768 293 Mail:  HYPERLINK "mailto:dr.azen@vip.hr" dr.azen@vip.hr, SA}ETAK Ko~ni re~njevi slu~e kao nadomjestak manjku tkiva u plasti no rekonstruktivnoj kirurgiji. Jedan od klju nih ciljeva rekonstrukcije re~njem je njegovo cjelovito pre~ivljenje, ato sam operativni zahvat ini funkcionalno i estetski uspjeanim. Djelomi no ili potpuno odumiranje re~nja naj eai je uzrok neuspjeha ovakovog zahvata. Postoje pripravci i metode koji poboljaavaju postotak pre~ivljenja re~nja. Cilj rada bio je ispitati utjecaj lijekova na pre~ivljenje nasumi nih ko~nih re~njeva . Nasumi ni ko~ni re~njevi odignuti su na leima atakora, potom aavima vraeni nazad u ishodiano le~iate preko gel foam trake natopljene mitomicinom, kapsaicinom, metilprednizolonom i BPC 157 pentadekapeptidom. }ivotnje su podijeljene u etiri eksperimentalne skupine, a u kontrolnoj, petoj, koriatena je 0,9% fizioloaka otopina. Procjena pre~ivljenja vraena je termokamerom. Statisti ki zna ajno pre~ivljenje (p< 0.05) postignuto je u metilprednizolon i BPC 157 skupini. Metilprednizolon i pentadekakpetid BPC 157 koriateni jednokratno lokalno statisti ki zna ajno poboljaavaju pre~ivljenje nasumi nih ko~nih re~njeva. IR termografija izvrsna je metoda u procijeni vitaliteta ko~nog re~nja. UVOD Upotreba termokamere u klini koj i eksperimentalnoj medicini Upotreba termokamere u medicini do~ivjela je svoj najvei uspon sedemdesetih godina proalog stoljea kada se termografijom slu~ilo u dijagnostici tumorskih bolesti dojke, apscesa mekih tkiva, krvo~ilne insuficijencije okrajina i u nekih reumatskih bolesti [1]. Potom termokamera kao dijagnosti ko sredstvo pada u zaborav. Poboljaanjem razlu ivosti termokamere, uvoenjem dinami ke termografije i usavraavanjem ra unalnih programa termokamera danas ponovno postaje dijagnosti ko sredstvo kod procjene debljine eshare opekotina [2], prohodnosti krvnih ~ila u kardiokirurgiji [3], lociranje perforatornih krvnih ~ila u plasti no rekonstruktivnih re~njeva [4], procijeni vitaliteta desni u stomatologiji [5], sindroma naprezanja u sportskoj medicini [6], procjeni vitaliteta re~njeva u rekonstruktivnoj kirurgiji [7,8] i kao dijagnosti ko sredstvo u nistagmologiji [9,10]. Bitna razlika naspram prvog zlatnog doba je da termokamera danaanjim eksperimentalnim radovima prestaje biti samo jednodimenzionalna metoda oslikavanja temperature ljudske ko~e, ve kombinacijom viaesmjernog vektorskog snimanja, dinami ke termografije i slo~ene ra unalne obrade uspjeva slojevno locirati procese u tkivu. Razvija se i metodologija koja kombinira mjerenje otpora tkiva i termografsko snimanje za dijagnostiku tumorskih bolesti dojke [11,12,13]. Termografija je takoer zahvalna metoda u ispitivanju odnosa ~ivog tkiva i ne~ive tvari, ato nalazi svoju upotrebu kod umjetnih usadaka [14]. Danas nema sigurne i standardizirane metode za dijagnostiku vitalnosti plasti no rekonstruktivnih re~njeva. Koristi se fotopletizmografija zelenog svijetla ( mjeri se spektar isijavanja hemoglobina eritrocita), laser Doppler mjerenje protoka kroz krve ~ile, puls oksimetrija, PH metrija i termografija. Sve su metode neetablirane, i prakti ki najupotrebljavanija je iskustvena metoda: ispekcijom, dakle gledanjem [15,16]. Termografija u eksperimentalnoj medicini izvrsna je metoda procjene i kvantificiranja razlu ivosti ~ivog naspram ne~ivog tkiva, ishemijskih promjena, utjecaja implanata i vanjskih energetskih umjetnih izvora na promjene temperature tkiva, te procjene utjecaja toplinskih i laserskih kirurakih instrumenata na tkivo [17, 18]. Pre~ivljenje ko~nih re~njeva u plasti norekonstruktivnoj kirurgiji Re~anj je dio tkiva odstranjen iz svog prirodnog anatomskog okru~ja i preseljen na drugi dio tijela. Pri tom mo~e imati vezu s svojim primarnim anatomskim sijelom, kroz koji dobiva prehranu ili se mo~e sasvim odvojiti te ponovno presaditi u novu anatomsku lokaciju. Ukoliko ostane vezan za anatomsko ishodiate, mo~e se planirano uzeti re~anj s ~ilom hranilicom, ato podrazumjeva dobro poznavanje anatomskih odnosa ili prethodno prepoznavanje toka ~ile hranilice navedenog podru ja. Re~anj se mo~e uzeti i nasumi no, tada ra unamo na prehranu iz hvatiata za anatomsko ishodiate te na prehranu difuzijom i preko naknadno uraslih kapilara u anatomskom le~iatu. Nasumi ni re~anj je dakle manje idealan no lakae dostupan i tehni ki izvodiv, te stoga airoko upotrebljavan u plasti no rekonstruktivnoj kirurgiji. Odumiranje, gubitak vitalnosti re~nja, naj eai je razlog neuspjeha kod kirurakih zahvata s upotrebom re~nja. Danas se istra~uje upotreba viae raznih metoda i lijekova u poboljaanju pre~ivljenja nasumi nog re~nja. Kapsaicin je spoj koji se normalno nalazi u ekstraktu chili paprike i daje mu ljutinu. Ima viaestruk utjecaj na tkivo na koje se primjeni lokalno, uglavnom preko smanjenja koncentracije neuropeptida odgovornih za senzoneuralno provoenje i utjecaj na lokalne faktore rasta. Utjecaj na pre~ivljenje re~njeva je po dosadaanjim studijama kontroverzan, a termokamera nije koriatena u procjeni pre~ivljenja re~nja [18,19,20,21]. Metilprednizolon je kortikosteroid, spada u grupu lijekova airoko koriatenih u medicini u svim pripravnim oblicima. Na tkivo djeluje preko kortikosteroidnih receptora, utjecajem na upalne medijatore i oslobaanje faktora rasta. Za udno je malo eksperimentalnih radova o utjecaju kortikosteroida na pre~ivljenje re~njeva [22]. Mitomicin je je spoj koji ima antifibroti ko djelovanje, spre ava prekomjerno o~iljavanje tkiva, a pentadekapetid BPC-157 novije je izoliran spoj iz sluznice ~eluca s viaestrukim djelovanjem na poboljaano cijeljenje tkiva. Eksperimenti s ta dva spoja i pre~ivljenjem re~njeva nisu raeni [23,24,25]. METODE Po dozvoli eti kog komiteta 50 ~enki Wistar atakora te~ine 200 do 250 g svrstano je u pet skupina, 4 eksperimentalne i jednu kontrolnu. Svim atakorima obrijana su lea, gdje se odignuo ko~ni re~anj, du~ine 10 cm a airine pripoja baze 2 cm ( Ilustracija 1).  SHAPE \* MERGEFORMAT  SHAPE \* MERGEFORMAT  Ilustracija 1. iscrtavanje i odizanje ko~nog nasumi nog re~nja atakora Izmeu ko~e re~nja i miaija lea umetnula se gelatinozna traka ( Gel foam) natopljena s 0,9 % fizioloakom otopinom u kontrolnoj skupini, a s metilprednizolonom (30 mg/kg), kapsaicinom (2%), mitomicinom (0,2 mg/ml) i pentadekapeptidom BPC 157 (0,2 mcg) u eksperimentalnim skupinama. Re~anj je potom saaiven na prvotnu anatomsku poziciju. Mjerila se du~ina pre~ivljenog re~nja 7 dana po odizanju. Procjena pre~ivljenja re~nja vraena je pomou ThermaCAM SC2000 ( Ilustracija 2, 3. ).  SHAPE \* MERGEFORMAz|  & . 2 > J L ~   $ h  ( h jl>b~X&Į̤̠̇㠜ۜ㤜h6 /hSxhbNhF]kh+^U5hvAh? 0Jjh? Ujh? Uh+^Uhw; hQhQhOhQhh? hQCJaJhF]khQ5CJaJ=z|   0   JLVXX"%0(2(gd*gdr 7$8$H$gdSx 7$8$H$gd+^U 7$8$H$gd? $7$8$H$a$gdQ҆&(DrxHJLVXFdfThLNPRT*JLNPRĹ䭢䭢䖋䖋䖋hCJaJh.hCJaJhh^}CJaJh.h^}CJaJh^}h<CJaJh.h<CJaJh<haGhG=hh5hhhr5hrhQhSxhhOh6 /hbN3$&(.0(T " $ & 4 X ` !"!$!4!6!:!R!^! "H"J"L"P"R"V"X"~"""""%ƻƻ픐큷h*h.hrDCJaJhEhrDh}~CJaJh.hBCJaJhBh.Lh6 /haGh.h(CJaJh(CJaJhCJaJhn1+CJaJh.hn1+CJaJhn1+hrhh.hCJaJ2%%%%%%R&l&$'(("(&(*(,(2((()///R/T/// 00(0333444<4|4z5566º͝~v~rrrh{[h$SNCJaJh.h$SNCJaJh$SNhZ1hLKh$hx?h*hx?CJaJhtCJaJh5CJaJhCJaJh.hmKCJaJhmKCJaJhCJaJhbNCJaJhG=CJaJh}~CJaJh.h*CJaJ(2(((/468888;;;;z;|; < <??RRRRRRJSLS$a$gdXMgdVgdrgd*666677N88888888849:9f99L:N:::::::;;; ;8;:;<;>;B;p;r;t;v;x;|;; < <=="=b===~>>¾ƺƲƲƲƾƺhKjhRhjhVjOh2nUjh2nUjh2nUmHnHujh2nUh"hMh$h2nh5LhMh5L5 h*h_),hdCJaJh{[h$SNh{[CJaJh.h{[CJaJ4>>>>\?^?n??????@RRRR R RR&RLRRRRRRJSLSSSTrUUUUUUUUUWWnXXXXXXXX옔쌈hzh<h$hS!hfhjhM5h"hXMB*phhVB*phjohU(FhXMB*UphjhVUjhVUmHnHuUjhVUhXMhMhRhKjhbNhV2T  Ilustracija 2. mjerenje du~ine vitalnosti re~nja. Vidi se vitalni ( bli~e repu) i odmrli ( oko 2/3) dio re~nja  Ilustracija 3. termografska slika re~nja Kompjuterska analiza vitalne povraine vraena je s ThermaCAM Researcher 2002, histogramom a kog se is itavao pad temperature re~nja, a ukoliko je granica vitalnosti i nekroze bila nepravilna histogram se o itavao na pet paralelnih linija, potom je iz njih izra unat prosjek. Statisti ka analiza vraena je pomou Mann Whitney testa. REZULTATI Re~njevi s lokalno apliciranim metilprednizolonom i BPC-157 pentadekapeptidom imali su statisti ki zna ajno vee pre~ivljenje od kontrolne grupe tretirane s fizioloakom otopinom s p vrijednoau manjom od 0.05. Lokalna aplikacija kapsaicina i mitomicina nije u pre~ivljenju re~nja imala statisti ki zna ajne razlike naspram kontrolne skupine ( Ilustracija 4.)  Ilustracija 4. pre~ivljenje re~njeva po grupama, u milimetrima. MP: metilprednizolon, BPC: pentadekapeptid BPC-157, CONT: kontrola, CAPS: kapsaicin, MIT: mitomicin, cont: kontrolna skupina, exp: eksperimentalne skupine RASPRAVA Upotreba ko~nih re~njeva u plasti no rekonstruktivnoj kirurgiji zbog poveanih estetskih i funkcionalnih kriterija raste, no nema etabliranih smjernica upotrebe farmakoteraijskih metoda koje bi poboljaavalo njihovo pre~ivljenje. Ovim eksperimentom pokazano je plauzabilno djelovanje metilprednizolona i BPC-157 na pre~ivljenje nasumi nog ko~nog re~nja, ato bi uz daljnju ekperimentalnu doradu otvorilo terapijske opcije i za klini ku primjenu. Termografski model koji je ovdje upotrebljen takoer pru~a smjernice za dalji rad o upotrebi kamere u ocjeni vitaliteta re~nja. Mogua klini ka implikacija bila bi procjena ugro~enosti re~nja nekrozom, u slu aju kada se re~anj mo~e spasiti dodatnim terapijskim opcijama, a osobito ako bi njegovo propadanje bitno ugrozilo ishod operativnog postupka. ZAKLJU AK Lokalno aplicirani metilprednizolon i pentadekapeptid BPC-157 statisti ki zna ajno poboljaavaju pre~ivljenje nasumi nog ko~nog re~nja lea atakora. Kapsaicin i mitomicin ne poboljaavaju pre~ivljenje re~nja. Termografski prikaz uz dodatnu ra unalnu obradu uspjeaan je na in prikaza vitaliteta ko~nog re~nja. BIBLIOGRAFIJA 1. Heine B., Die Tele-Thermographie in der medizinischer diagnostic. Labor med, 3:217, 1978. 2. Kaczmarek M, Nowakowski A, Renkielska A ., Rating burn wounds by dinamic thermography, Quantitative infrared thermography international conference, Reims, 2000, str. 376-379 3. Mohr FW, Falk V, Philippi A, autscbach R, Kreiger H, Diegeler A, Dalichau H., Intraoperative assesment of internal mammmary artery bypass graft patency by thermal coronary angiography, Cardiovasc surg. 2(6):703-710, 1994. 4. Chijiwa T, Arai K, Miyazaki N, Igota S, Yamamoto N., Making of a facial perforator map by thermography. Ann Plast Surg; 44:596-600, 2000. 5. Barnett ML, Gilman RM., Computer based thermal imaging of human gingiva, J. Periodontol 60:628-633, 1989. 6. Koprowski R, Wrobel Z, Konik H, Olex D., Diagnosis of the effectiveness of streching exercises by means of the analysis of termovisual images, Quantitative infrared thermography international conference, Zagreb, 2002, str. 141-142 7. Bradford CR., Flap monitoring, Facial pastic surgery, 1(12): 19-21, 1996. 8. Bulstrode NW, Wilson GR, Inglis MS., No-touch free-flap temperature monitoring, Br J Plast Surg., 55(2):174, 2002. 9. Kitamura K, Ishida T, Kaminaga C, Haga M, Miyata M, Nomoto Y, Suzuki T., Infrared/video ENG recording of positional nystagmus in subjects with peripheral vestibular disease, Acta Otolaryngol Suppl, 520 (2):430-3, 1995. 10. Ichijo H, Ichinohe M, Usami S, Shinkawa H., Observation of positional nystagmus with infrared CCD camera, Acta Otolaryngol Suppl.520 (2):366-8, 1995. 11. Zavisek M, Drastich A, Sandera J:, Quantitative Thermography in Breast Cancer Detection, Quantitative infrared thermography international conference, Von Karman institute for fluid dynamics, Bruxelles, 2004. 12. Nowakowski A., Comparison of thermal and electrical tomography in medicine, Quantitative infrared thermography international conference, Von Karman institute for fluid dynamics, Bruxelles, 2004. 13. Parisky YR, Sardi A, Hamm R, Hughes K, Esserman L, Rust S, Callahan K., Efficacy of computerized infrared imaging analysis to evaluate mammographically suspicious lesions, AJR Am J Roentgenol.180:263-9, 2003. 14. Pau HW, Sievert U, Wild W., Thermography of the skin covering a cochlear implant - temperature as an indicator for blood circulation, Laryngorhinootologie, 82(9):615-9, 2003. 15. Cho BC, Shin DP, Byun JS, Park JW, Baik BS., Monitoring flap for buried free tissue transfer: its importance and reliability, Plast. Reconstr. Surg. 110:1249-1250, 2002. 16. Futran ND, Stack BC, Hollenbeak C, Scharf JE., Green light photopletismography monitoring of free flaps, Arch otolaryngol head neck surg, 126:659-662, 2000. 17. Koteles GJ, Benko I, Nemeth G., Use of termography in diagnosis of local radiation injuries. Health Physics, 74:264-265., 1998. 18. Eisenbeis W, Marotz J, Schrade JP. Reflection-optical multispectral imaging method for objective determination of burn depth., Burns, 25:697-704, 1999. 18. IinumaT,SawadaY. Topical application of capsaicin and flap survival., Br J Plast Surg 49:319-20, 1996. 19. Miawaki T, Jackson IT, Bier UC, Andrus L, Williams F, Bradford M., The effect of capsaicin ointment on skin for the survival of a cutaneous flap. Eur J Plast Surg, 24:28-30, 2001. 20. Chang CC, Maruyama Y, Inomata K. Increased flap survival after sensory denervation with capsaicin accompanied by delay., J Reconstr Microsurg, 6(1):29-33, 1990. 21. Westin M, Heden P. Sensory denervation with capsaicin does not influence the critical ischemia time in rat island flaps. Scand J Plast Reconstr Surg Hand Surg, 23:173-6, 1989. 22. Saray A, Can B, Sevin K., Effects of methylprednisolone on the viability of experimental flow-through venous flaps, J Reconstr Microsurg, 18:615-22, 2002. 23. Demir T, Turgut B, Akyol N, Ozercan I, Ulas F, Celiker U., Effects of amniotic membrane transplantation and mitomycin C on wound healing in experimental glaucoma surgery, Ophthalmologica, 216:438-42, 2002. 24. Rahbar R, Jones DT, Nuss RC, Robertson DW, Kenna MA, McGill TJ, Healy GB. The role of Mitomycin in the prevention and treatment of scar formation in the pediatric aerodigestive tract, Arch Otolaryngol Head Neck Surg., 128: 401-406, 2002. 25. Sikiric P, Seiwerth S, Mise M, Staresinic M, Bedekovic V, Zarkovic N, Borovic S, Gjurasin M, Boban-Blagaic A, Blagaic L, Rucman N, Anic T., Corticosteroid-impairment of healing and gastric pentadecapeptide BPC-157 cream in burned mice, Burns, 29: 323-334, 2003.  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