SEMRA KARŞIDAĞ, Soner TATLIDEDE, Uğur TOSUN, KEMALETTİN YILDIZ, FEVZİYE KABUKCUOĞLU, Arzu AKÇAL

Diyabetik sıçanlarda vinblastinin mikrovasküler anastomoz iyileşmesi üzerine etkileri

Amaç: Diabetes mellitus ve kemoterapi mikrovasküler cerrahinin başarısını etkileyen faktörlerin başında gelir. Bu iki faktörün tek başına etkilerini inceleyen birçok çalışma olmasına rağmen, ikisinin birlikte olduğu durumlardaki etkilerini araştıran çalışmaya rastlamadık. Çalışmamızda vinka alkaloidi olan vinblastinin diyabetik ve diyabetik olmayan sıçanlarda mikrovasküler anastomoz iyileşmesi üzerine etkilerini araştırdık. Çalışma planı: Bu çalışmada 144 Sprague Dawley cinsi sıçan kullanıldı. Deney ve kontrol grupları rastgele ve eşit sayıda oluşturuldu. Deney grubuna (72 sıçan) alloksan verilerek diyabet oluşumu sağlandı. Alloksan enjeksiyonundan 3 gün sonra sıçanlarda glukozüri (>%2) ve artmış plazma glukoz seviyeleri (>300 mg/100 ml) sağlandı. Tek doz vinblastin intraperitoneal olarak uygulandı. Medikasyonların tamamlanmasından sonra iki ana grup üç alt guba ayrıldı. Her bir grupta femoral artere, sırasıyla 7., 14. ve 21. günlerde uç-uca anastomoz uygulandı. Daha sonra, her alt grup geçirgenlik testi amacıyla üç küçük gruba ayrıldı ve sırasıyla 7., 14. ve 21. günlerde biyopsileri alındı. Histopatolojik incelemeler yapıldı. Bulgular: Anostomozun geçirgenlik testlerinde ve patolojik incelemede guplar arasında istatistiksel olarak anlamlı bir fark saptanmadı. Çıkarımlar: Diyabetin negatif etkileri ve birlikte vinblastin verilmesi mikrovasküler anastomoz iyileşmesini belirgin olarak etkilememektedir.

Effects of vinblastine on microvascular anastomosis healing in diabetic rats

Objective: Diabetes mellitus and chemotherapy use are well-known factors that can affect success after microvascular repair. Although many studies have investigated each factor individually, no study exists on their combined effect. The aim of our study was to investigate the effects of preoperative vinblastine, a vinca alkaloid, on the healing of microvascular anastomosis in diabetic and non-diabetic rats. Methods: In this study, 144 Sprague Dawley rats were assigned randomly and equally into experimental or control groups. The experimental group consisted of 72 rats which were made diabetic by alloxan injections. Diabetes was confirmed by glycosuria (>2%) and elevated plasma glucose (>300 mg/100 ml) after three days of alloxan injections. The experimental group then received a single dose of intraperitoneal vinblastine. After applying the medication, the two main groups were divided into three subgroups. For each group, we performed end-to-end femoral artery anastomosis on Day 7, 14, and 21, respectively. We further divided each subgroup equally into three smaller groups to test patency and took biopsies at Day 7, 14 and 21, respectively. Histopathologic evaluation was carried out. Results: The comparison of patency tests and pathologic examination indicated that there was no statistically significant difference between the two groups. Conclusion: The negative effects of diabetes and the administration of vinblastine did not significantly influence anastomosis healing.

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1. Krizek TJ, Tani T, Desprez JD, Kiehn CL. Experimental transplantation of composite grafts by microsurgical vascular anastomosis. Plast Reconstr Surg 1965;36:538-46.
2. Robertson WB, Strong JP. Atherosclerosis in persons with hypertension and diabetes mellitus. Laboratory Invest 1968;18:538-51.
3. Cwikiel M, Zhang B, Eskilsson J, Wieslander JB, Albertsson M. The influence of 5-fluorouracil on the endothelium in small arteries: an electron microscopy study in rabbits. Scanning Microsc 1995;9:561-76.
4. Colen LB, Stevenson A, Siderov V, et al. Microvascular anastomotic thrombosis in experimental diabetes mellitus. Plast Reconstr Surg 1997;99:156-62.
5. Park SJ, Shin SH, Junk IK. Histopathologic study on the microvascular anastomosis of streptozotocin induced diabetic rats. [Article in Korean] Journal of Korean Association of Maxillofacial Plastic and Reconstructive Surgeons 2000;22:133-41.
6. Nahabedian MY, Momen B, Manson PN. Factors associated with anastomotic failure after microvascular reconstruction of the breast. Plast Reconstr Surg 2004;114:74-82.
7. Nahabedian MY, Singh N, Deune EG, Silverman R, Tufaro AP. Recipient vessel analysis for microvascular reconstruction of the head and neck. Ann Plast Surg 2004;52:148-55.
8. Peter FW, Schuschke DA, Barker JH, Fleischer-Peter B, Hussmann J, Steinau HU. Leukocyte behavior in a freeflap model following chemotherapy and application of granulocyte colony-stimulating factor (GCSF). Microsurgery 1998;18:290-7.
9. Tatlidede S, Karsidag SH, Tosun U, Kabukcuoglu F, Gul M, Kuran I. Effects of vinblastine on healing in microvascular anastomosis. Microsurgery 2003;23:354-8.
10. Heimberg M, Meng HC, Park CR. Effect of sex, fasting and alloxan diabetes on the uptake of neutral fat by isolated perfused rat liver. Am J Physiol 1958;195:673-7.
11. Golfman L, Dixon I, Takeda N, Lukas A, Dakshinamurti K, Dhalla NS. Cardiac sarcolemmal Na+-Ca2+ exchange and Na+-K+ ATPase activities and gene expression in alloxan-induced diabetes in rats. Mol Cell Biochem 1998;188:91-101.
12. Alberdas JL, Shibahara T, Noma H. Histopathologic damage to vessels in head and neck microsurgery. J Oral Maxillofac Surg 2003;61:191-6.
13. McDonald DJ, Capanna R, Gherlinzoni F, et al. Influence of chemotherapy on perioperative complications in limb salvage surgery for bone tumors. Cancer 1990;65:1509- 16.
14. Barr LC, Joyce AD. Microvascular anastomoses in diabetes: An experimental study. Br J Plast Surg 1989;42:50- 3.
15. Shibahara T, Schmelzeisen R, Alberdas JL, Noma H. Microvascular anastomosis in oral reconstructive study of recipient vessels between Japanese and German patients. Int J Oral Maxillofacial Surg 1999;28:387-92.
16. Brade W. Critical review of pharmacology, toxicology, pharmacokinetics of vincristine, vindesine, vinblastine. In: Brade W, Nagel GA, Seeber S, editors. Proceedings of the International Vinca Alcaloid Symposium: Vindesine. Basel: Karger; 1980. p. 95.
17. Thomson SR, Gregory MA, Mars M, Natasen J, Naicker T, Baker LW. Morphological aspects of microarterial anastomoses: a comparison of nylon with polydioxanone. Br J Plast Surg 1995;48:165-71.
18. Guelinckx PJ, Boeckx WD, Fossion E, Gruwez JA. Scanning electron microscope of irradiated recipient blood vessels in head and neck free flaps. Plast Reconstr Surg 1984;74:217.