Sıçan uterin horn modelinde enoksaparin ve rapamisinin adezyon oluşumuna etkilerinin karşılaştırılması
Öz
Aim. Several studies have demonstrated that low molecular weight heparins (LMWHs) decreased postoperative adhesion formation. Also, a few studies have noted that immunosuppressive agent rapamycin decreased postoperative adhesion formation. In this experimental study, we aimed to investigate the effect of enoxaparin and rapamycin alone and in combination on the adhesion formation in a rat uterine horn model. Methods. Our study included 40 Wistar-Albino rats weighing between 200-250 g. Control and three study groups were formed including 10 rats. In sterile condition, we performed 3-cm midline incision of abdominal wall under general anesthesia. On the antimesenteric surface of both uterine horns, 8-10 unipolar electrocauterization were applied. Later these antimesenteric surfaces were sutured to abdominal sidewalls with 4.0 polydioxanone. In the control group, no therapy was applied after surgery and incision was closed according to general surgical rules. In the enoxaparin group, enoxaparin 50 U/kg was applied intraperitoneally for 14 days. In the rapamycin group, rapamycin 0.8 mg/kg was applied orally with feeding tube for 14 days. In the enoxaparin plus rapamycin group, enoxaparin 50 U/kg was applied intraperitoneally and rapamycin 0.8 mg/kg orally with the feeding tube for 14 days. The animals were sacrificed by lethal dose pentobarbital 14 days after surgery and a midline laparatomy was carried out and abdominal cavity was inspected for the presence of adhesion and adhesion samples were obtained for histopathological examination. Results. According to the findings of macroscopic and microscopic evaluation, the scores of adhesion severity were found comparable among the enoxaparin, rapamycin and enoxaparin plus rapamycin groups (p>0.05); however, the scores of adhesion extent and total adhesion scores were significantly lower in the drug groups compared to the control group (p<0.05). There was no significant difference among the three drug groups with regard to all the adhesion scores (p>0.05). Conclusion. Enoxaparine and rapamycin prevent total adhesion similarly, however, this effect is considerable on the extent of adhesion rather than the severity of adhesion. Combination of enoxaparin and rapamycin did not show synergistic effect on adhesion formation.
Anahtar Kelimeler
Low molecular weight heparin enoxaparin rapamycin peritoneal adhesion
Kaynakça
- Liakakos T, Thomakos N, Fine PM, Dervenis C, Young RL. Peritoneal adhesions: etiology, pathophysiology, and clinical significance. Recent advances in prevention and management. Dig Surg 2001; 18: 260-73.
- ASRM collobaration with the Society of Reproductive Surgeons. Pathogenesis, consequens and control of peritoneal adhesions in gynecologic surgery. Fertil Steril 2008; 90: 144-9.
- Coleman MG, McLain AD, Moran BJ. Impact of previous surgery on time taken for incision and division of adhesions during laparotomy. Dis Colon Rectum 2000; 43: 1297-9.
- Metwally M, Watson A, Lilford R, Vandekerckhove P. Fluid and Pharmacological agents for adhesion prevention after gynaecological surgery. Cochrane Database Syst Rev 2006; 19: CD001298.
- Miller G, Boman J, Shrier I, Gordon PH. Etiology of small bowel obstruction. Am J Surg 2000; 180: 33-6.
- Kamel RM. Prevention of postoperative peritoneal adhesions. Eur J Obst Gyn 2010: 150; 111-8.
- Kanko M, Ozbudak E, Ozerdem A, Aksoy A, Kilic M, Berki KT. Effect of sirolimus in the prevention of adhesions around intraabdominal prosthetic graft. World J Surg 2006; 30: 1648.
- Akbaba P. Rapamisin’in ratlarda deneysel olarak oluşturulan intraabdominal adezyonların gelişimi üzerine etkisi. Uzmanlık tezi. 2006.
- Linsky CB, Diamond MP, Cunningham T, Constantine B, DeCherney AH, diZerega GS. Adhesion reduction in the rabbit uterine horn model using an absorbable barrier, TC-7. J Reprod Med 1987; 32: 17-20.
- Rose J, Jayaraman S, Colquhoun P, Taylor B. Minimal abdominal adhesions after Sepramesh repair of a parastomal hernia. Can J Surg 2009; 52: 211-2.
- Tayyar M, Turan R, Ayata D. The use of amniotic membrane plus heparin to prevent postoperative adhesions in the rabbit. Tokai J Exp Clin Med 1993; 18: 57Tayyar M, Başbuğ M. The effects of intraperitoneal piroxicam and low molecular weight heparin in prevention of adhesion reformation in rat uterine horn. Res Exp Med 1999; 198: 269-75.
- Başbuğ M, Aygen E, Tayyar M, Kaya E, Narin F, Oktem O. Hyaluronic acid plus heparin for improved efficacy in prevention of adhesion formation in rat uterine horn model. Eur J Obstet Gynecol 1998; 78: 109-12.
- Altun Ö, Tayyar AT, Tayyar A, Özgün T, Öztürk F, Tayyar M. Sıçanlarda oluşturulan deneysel uterin horn adezyon modelinde düşük molekül ağırlıklı heparin ile oktreotid’in karşılaştırılması. Cumhuriyet Med J 2012; 34: 307-13.
- Türkçapar AG, Ozarslan C, Erdem E, Bumin C, Erverdi N, Kutlay J. The effectiveness of low molecular weight heparin on adhesion formation in experimental rat model. Int Surg 1995; 80: 92-4.
- Diamond MP, Linsky CB, Cunningham T, Kamp L, Pines E, DeCherney AH, diZerega GS. Adhesion reformation: reduction by the use of Interceed (TC7) plus heparin. J Gynecol Sum 1991; 7: 1.
- Fukasawa M, Girgis W, diZerega GS. Inhibition of postsurgical adhesions in a standardized rabbit model: II. Intraperitoneal treatment with heparin. Int J Fertil 1991; 36: 296-301.
- Reid RL, Hahn PM, Spence JE, Tulandi T, Yuzpe AA, Wiseman DM. A randomized clinical trial of oxidized regenerated cellulose adhesion barrier (Interceed, TC7) alone or in combination with heparin. Fertil Steril 1997; 67: 23. Perju D, Lupaşcu C. Comparative experimental study of the effect of various locally administered pharmacological agents on the appearance of peritoneal adhesions. Rev Med Chir Soc Med Nat Iasi 2006; 110: 116-21. diZerega GS. Biochemical events in peritoneal tissue repair. Eur J Surg Suppl 1997; 577: 10-6.
- Rodgers KE, diZerega GS. Function of peritoneal exudate cells after abdominal surgery. J Invest Surg 1993; 6: 9-23.
- Kaidi AA, Nazzal M, Gurchumelidze T, Ali MA, Dawe EJ, Silva YJ. Preoperative administration of antibodies against tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 (IL-1) and their impact on peritoneal adhesion formation. Am Surg 1995; 61: 569-72.
- Başoğlu M, Kızıltunç A, Akçay F, Keles S, Gündoğdu C, Ören D. D. Tumor necrosis factor-α and interleukin-6 in peritoneal adhesion formation. Tr J Med Sci 1998; 28: 253-8.
- Banaszynski LA, Liu CW, Wandless TJ. Characterization of the FKBP.rapamycin.FRB ternary complex. J Am Chem Soc 2005; 127: 4715-21.
- Liu L, Chen L, Chung J, Huang S. Rapamycin inhibits F-actin reorganization and phosphorylation of focal adhesion proteins. Oncogene 2008; 27: 4998-5010.
- Maciver AH, McCall MD, Edgar RL, Thiesen AL, Bigam DL, Churchill TA, Shapiro AM. Sirolimus drug-eluting, hydrogel-impregnated polypropylene mesh reduces intra-abdominal adhesion formation in a mouse model. Surgery 2011; 150; 907-15.
Sıçan uterin horn modelinde enoksaparin ve rapamisinin adezyon oluşumuna etkilerinin karşılaştırılması
Öz
Amaç. Birçok çalışmada düşük molekül ağırlıklı heparinlerin (DMAH) postoperatif adezyon gelişimini önlemede etkili olduğu, bazı çalışmalarda da rapamisinin immünosüpresif bir ajan olarak postoperatif adezyon gelişimini azaltabileceği saptanmıştır. Bu deneysel çalışmada bir DMAH olan enoksaparin ile rapamisinin tek tek veya birlikte adezyon oluşumu üzerine etkileri sıçan uterin horn modelinde incelendi. Yöntem. Çalışmada ağırlıkları 200-250 gr arasında olan 40 adet Wistar-Albino dişi sıçan kullanıldı. Sıçanların karın duvarına anestezi altında steril koşullarda 3 cm’lik orta hat kesisi yapıldı. Her iki uterin hornda antimezenterik yüzeye 8-10 adet unipolar koterizasyon uygulandı ve antimezenterik yüzeyler 4/0 polidioksanon ile karın ön duvar peritonuna dikildi. Sıçanlar kontrol, enoksaparin, rapamisin ve enoksaparin ve rapamisin gruplarına (n= 10) ayrıldı. Kontrol grubunda adezyon önleyici tedavi uygulanmadan karın katları usulüne uygun olarak kapatıldı. Enoksaparin grubunda 14 gün süreyle enoksaparin 50 U/kg intraperitoneal olarak uygulandı. Rapamisin grubunda 14 gün süreyle 0,8 mg/kg oral yoldan gavaj tüpüyle rapamisin uygulandı. Enoksaparin ve rapamisin grubunda 14 gün süreyle enoksaparin 50 U/kg intraperitoneal olarak verildi, ayrıca aynı süreyle 0,8 mg/kg oral yoldan gavaj tüpüyle rapamisin ilave olarak uygulandı. Sıçanların tümü 14 gün sonra letal doz pentobarbital ile öldürülerek orta hat kesisi ile laparotomi yapılarak adezyon gelişimi gözle ve histopatolojik olarak değerlendirildi. Bulgular. Makroskopik ve mikroskopik olarak incelendiğinde çalışma gruplarının adezyon şiddetleri benzer bulundu (p>0,05). İlaç uygulanan grupların adezyon yaygınlığı ve total adezyon skorları kontrol grubununkine göre daha düşük bulundu (p<0,05). İlaç uygulanan grupların adezyon yaygınlığı ve total adezyon skorları arasında anlamlı fark bulunmadı (p>0,05). Sonuç. Enoksaparin ve rapamisin benzer düzeylerde total adezyonu önlemekte, bunu yaparken adezyon şiddetinden daha çok adezyon yaygınlığını azaltarak etkili olmaktadır. Birlikte kullanımlarında ise adezyon oluşumu üzerine etkileri sinerjistik değildir.
Anahtar Kelimeler
Düşük molekül ağırlıklı heparin enoksaparin rapamisin peritoneal adezyon
Kaynakça
- Liakakos T, Thomakos N, Fine PM, Dervenis C, Young RL. Peritoneal adhesions: etiology, pathophysiology, and clinical significance. Recent advances in prevention and management. Dig Surg 2001; 18: 260-73.
- ASRM collobaration with the Society of Reproductive Surgeons. Pathogenesis, consequens and control of peritoneal adhesions in gynecologic surgery. Fertil Steril 2008; 90: 144-9.
- Coleman MG, McLain AD, Moran BJ. Impact of previous surgery on time taken for incision and division of adhesions during laparotomy. Dis Colon Rectum 2000; 43: 1297-9.
- Metwally M, Watson A, Lilford R, Vandekerckhove P. Fluid and Pharmacological agents for adhesion prevention after gynaecological surgery. Cochrane Database Syst Rev 2006; 19: CD001298.
- Miller G, Boman J, Shrier I, Gordon PH. Etiology of small bowel obstruction. Am J Surg 2000; 180: 33-6.
- Kamel RM. Prevention of postoperative peritoneal adhesions. Eur J Obst Gyn 2010: 150; 111-8.
- Kanko M, Ozbudak E, Ozerdem A, Aksoy A, Kilic M, Berki KT. Effect of sirolimus in the prevention of adhesions around intraabdominal prosthetic graft. World J Surg 2006; 30: 1648.
- Akbaba P. Rapamisin’in ratlarda deneysel olarak oluşturulan intraabdominal adezyonların gelişimi üzerine etkisi. Uzmanlık tezi. 2006.
- Linsky CB, Diamond MP, Cunningham T, Constantine B, DeCherney AH, diZerega GS. Adhesion reduction in the rabbit uterine horn model using an absorbable barrier, TC-7. J Reprod Med 1987; 32: 17-20.
- Rose J, Jayaraman S, Colquhoun P, Taylor B. Minimal abdominal adhesions after Sepramesh repair of a parastomal hernia. Can J Surg 2009; 52: 211-2.
- Tayyar M, Turan R, Ayata D. The use of amniotic membrane plus heparin to prevent postoperative adhesions in the rabbit. Tokai J Exp Clin Med 1993; 18: 57Tayyar M, Başbuğ M. The effects of intraperitoneal piroxicam and low molecular weight heparin in prevention of adhesion reformation in rat uterine horn. Res Exp Med 1999; 198: 269-75.
- Başbuğ M, Aygen E, Tayyar M, Kaya E, Narin F, Oktem O. Hyaluronic acid plus heparin for improved efficacy in prevention of adhesion formation in rat uterine horn model. Eur J Obstet Gynecol 1998; 78: 109-12.
- Altun Ö, Tayyar AT, Tayyar A, Özgün T, Öztürk F, Tayyar M. Sıçanlarda oluşturulan deneysel uterin horn adezyon modelinde düşük molekül ağırlıklı heparin ile oktreotid’in karşılaştırılması. Cumhuriyet Med J 2012; 34: 307-13.
- Türkçapar AG, Ozarslan C, Erdem E, Bumin C, Erverdi N, Kutlay J. The effectiveness of low molecular weight heparin on adhesion formation in experimental rat model. Int Surg 1995; 80: 92-4.
- Diamond MP, Linsky CB, Cunningham T, Kamp L, Pines E, DeCherney AH, diZerega GS. Adhesion reformation: reduction by the use of Interceed (TC7) plus heparin. J Gynecol Sum 1991; 7: 1.
- Fukasawa M, Girgis W, diZerega GS. Inhibition of postsurgical adhesions in a standardized rabbit model: II. Intraperitoneal treatment with heparin. Int J Fertil 1991; 36: 296-301.
- Reid RL, Hahn PM, Spence JE, Tulandi T, Yuzpe AA, Wiseman DM. A randomized clinical trial of oxidized regenerated cellulose adhesion barrier (Interceed, TC7) alone or in combination with heparin. Fertil Steril 1997; 67: 23. Perju D, Lupaşcu C. Comparative experimental study of the effect of various locally administered pharmacological agents on the appearance of peritoneal adhesions. Rev Med Chir Soc Med Nat Iasi 2006; 110: 116-21. diZerega GS. Biochemical events in peritoneal tissue repair. Eur J Surg Suppl 1997; 577: 10-6.
- Rodgers KE, diZerega GS. Function of peritoneal exudate cells after abdominal surgery. J Invest Surg 1993; 6: 9-23.
- Kaidi AA, Nazzal M, Gurchumelidze T, Ali MA, Dawe EJ, Silva YJ. Preoperative administration of antibodies against tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 (IL-1) and their impact on peritoneal adhesion formation. Am Surg 1995; 61: 569-72.
- Başoğlu M, Kızıltunç A, Akçay F, Keles S, Gündoğdu C, Ören D. D. Tumor necrosis factor-α and interleukin-6 in peritoneal adhesion formation. Tr J Med Sci 1998; 28: 253-8.
- Banaszynski LA, Liu CW, Wandless TJ. Characterization of the FKBP.rapamycin.FRB ternary complex. J Am Chem Soc 2005; 127: 4715-21.
- Liu L, Chen L, Chung J, Huang S. Rapamycin inhibits F-actin reorganization and phosphorylation of focal adhesion proteins. Oncogene 2008; 27: 4998-5010.
- Maciver AH, McCall MD, Edgar RL, Thiesen AL, Bigam DL, Churchill TA, Shapiro AM. Sirolimus drug-eluting, hydrogel-impregnated polypropylene mesh reduces intra-abdominal adhesion formation in a mouse model. Surgery 2011; 150; 907-15.
Ayrıntılar
| Birincil Dil | İngilizce |
|---|---|
| Bölüm | Cerrahi Tıp Bilimleri Araştırma Yazıları |
| Yazarlar | |
| Yayımlanma Tarihi | 16 Ocak 2013 |
| Yayımlandığı Sayı | Yıl 2013Cilt: 35 Sayı: 4 |