Deneysel kolon anastomozu modelinde, oluşturulan iskemi-reperfüzyon hasarı üzerine N-asetilsisteinin etkileri
The effect of N-asetilsistein on occured injury of ischmia-reperfüsione in experimental colonic anastomosis model
Yazar: BARIŞ KABALI
Danışman: Y.DOÇ.DR. SADULLAH GİRGİN
Dicle Üniversitesi / Tıp Fakültesi / Genel Cerrahi Ana Bilim Dalı
Derece: Tıpta Uzmanlık, 2006
Konu: Genel Cerrahi = General Surgery

Özet:
ÖZETKolon anastomozlar sonras görülen kaçak oran , gastrointestinal sistemin di erlokalizasyonlar na göre daha yüksektir. skemi, sonras nda o bölgedeki kanak m n n yeniden sa lanmas ve hücre içine moleküler oksijenin yenidensunulmas ile birlikte serbest oksijen radikalleri h zla olu maktad r. Reperfüzyonsonras barsakta aç a ç kan serbest oksijen radikalleri, iskemi-reperfüzyonhasar nda olu an zararl etkilerden neden olur. skemi-reperfüzyon hasar daanastomoz kaçaklar n n önemli nedenlerindendir. N-asetil sistein, serbest oksijenradikalleri taraf ndan olu turulan doku hasar n önledi i bilinmektedir. skemi-reperfüzyon hasar sonras nda yap lan kolon anastomozu üzerine, iskemi-reperfüzyon hasar n n olumsuz etkilerini önlemek için N-asetil sistein kullan m n netkinli ini belirlemeyi amaçlad k.Bu amaçla 40 adet Spraque-Dawley cinsi s çan kullan ld . S çanlar 4 grubaayr ld (n=10).Grup 1: Kolonda 0.5 cm lik rezeksiyon uyguland , takiben 5/0 ipekle end toend kolokolik anastomoz yap ld .Grup 2: skemi-reperfüzyon hasar olu turulup, kolonda 0.5 cm lik rezeksiyonuyguland , takiben 5/0 ipekle end to end kolokolik anastomoz yap ld .Grup 3: skemi-reperfüzyon hasar öncesinde intraperitoneal 300 mg/kg N-asetil sistein uyguland ktan sonra, kolonda 0.5 cm lik rezeksiyon uyguland ,takiben 5/0 ipekle end to end kolokolik anastomoz yap ld .Grup 4: skemi-reperfüzyon hasar öncesinde oral 300 mg/kg N-asetil sisteinuyguland ktan sonra kolonda 0.5 cm lik rezeksiyon uyguland , takiben 5/0 ipekleend to end kolokolik anastomoz yap ld .Post operatif 7. gün s çanlar tekrar opere edildi. Anastomozun, 2 cm proksimalve distalinden kolon rezeksiyonu yap ld . Anastomoz iyile mesi saptamak içinpatlama bas nçlar ölçüldü ve anastomoz bölgesinin histopatolojik incelemeleriyap ld .29En yüksek patlama bas nçlar , N-asetil sistein gruplar nda bulundu. Gruplararas ndaki anastomoz patlama bas nçlar istatistiksel olarak anlaml yd . Gruplar nhistopatolojik olarak incelenmesinde; yap lan istatistiksel analizlere göre vaskülerolu um, inflamatuvar infiltrasyon ve fibroblast proliferasyonu aç s ndan anlamlfark saptanmad . Kollajen birikimi aç s ndan ise; tüm gruplarda kontrol grubunagöre istatistiksel olarak anlaml fark vard . skemi-reperfüzyon hasar nda N-asetilsistein verilen s çanlarda anastomoz dayan kl l n n artt istatistiksel aç danincelendi inde; histopatolojik ve biyomekanik olarak anlaml oldu u saptand .Sonuç olarak klinik çal malarla desteklendi inde, kolon anastomozlar ndaiskemi-reperfüzyon hasar sonras nda N-asetil sistein verilmesi ile anastomozgüvenli inin artaca n ve postoperatif morbidite ile mortalitenin azalaca ndü ünmekteyiz.30

Abstract:
SUMMARYLeakage ratio following colon anastomosis is higher than that of any other partof the gastrointestinal system. Free oxygen radicals are rapidly generated with thereperfusion of the area after ischemia and influx of moleculer oxygen into the cell.Free oxygen radicals generated by ischemia-reperfusion damage are the mainreasons of the noxious effects to the cells. And ischemia-reperfusion damage isone of the most important causative agent for anastomosis leakage. It has beenalready known that N-acetly-cysteine( NAC) can prevent the damage of freeoxygen radicals. We tried to evaluate the efficacy of NAC use in preventingeffects of ischemia-reperfusion damage.For that reason we got 40 Spraque-Dawley type rats and put them into fourgroups(n=10):Group 1: 0,5 cm resection had been performed on colon, then end-to-endcolonic anastomosis with 5/0 silk had been done.Group 2: Ischemia-reperfusion damage had been performed, then weintroduced 0,5 cm resection on colon, and then end-to-end colonic anastomosiswith 5/0 silk sutures had been done.Group 3: We performed 0.5 cm colonic resection after the 300mg /kgintraperitoneal NAC introduction just before the ischemia-reperfusion damage,and end to end colonic anastomosis with 5/0 silk sutures.Group 4: We performed 0.5 cm colonic resection after the 300 mg/kg oralNAC introduction just before the ischemia-reperfusion damage, and end to endcolonic anastomosis with 5/0 silk sutures.The rats were reoperated on postoperative 7th day. Colonic resection had beenperformed on 2 cm distally and proximally to the colon. Rupture pressures hadbeen calculated to evaluate the anstomosis repair function and histopathologicexamination of the anastomis site had been carried out.The most highest rupture pressures were seen in N-acelyl-cysteine groups. Thedifferences of anastomosis rupture pressures between groups were statisticalyimportant. In histopathologic examination of the grous, there was no statistically31important difference between vascular formation, inflammatuary infiltration andfibroblast proliferation according to statistical analyses. On the other hand, inrespect of collagen accumulation, there were statisticaly important difference inall groups compored to the control groups. When we statisticaly investigate theanostomosis streght was increased by the induction of N-acelyl cysteine inischemia-reperfucion damage- there was histopathologly and biomechanicalyimportant difference.As a result, when it is supported with clinical studies, we suggest thatanastomosis streghth will increase and postoperative morbidity and mortality willdecrease by the introduction of N-acetyl-cysteine in colon anastomoses afterischemia-reperfusion damage.32