Karaciğer transplantasyonunda tiyopental’in soğuk iskemi üzerine etkileri: Deneysel bir çalışma

Year 2019, , 143 - 148, 25.02.2019

Başak Büyük , Ebru Karakoç

https://doi.org/10.28982/josam.460075

Cited By: 1

Abstract

Amaç: Bu çalışmanın amacı; tiyopentalin metabolizma hızını azaltıcı etkisinden faydalanarak, organ nakli öncesi uygulanacak olan dozlar ile, nakledilecek organın bazal metabolizma hızını düşürerek enerji ihtiyacını azaltmak ve bu sayede soğuk iskemi sürecinde meydana gelebilecek doku hasarını en aza indirerek organların viabilitesini artırmaktır.

Yöntemler: Çalışmada kullanılan 20 adet Wistar Albino cinsi sıçan iki gruba ayrılmıştır. Grup 1 (Kontrol=Ketamin-Ksilazin grubu) ve Grup 2 (Tiyopental grubu)’deki sıçanlara, kendi grupları için uygun olan ajanlarla anestezi uygulandıktan sonra karın derisi traşlanıp orta hat insizyonu yapıldı. Portal vene bir kanül ile girilerek +4 °C’deki organ saklama sıvısı enjekte edildi. Böylece karaciğer perfüzyonu sağlandı. Ardından hepatektomi yapılarak karaciğerler, içerisinde +4°C’de organ saklama sıvısı bulunan Falkon tüplere konuldu ve yine +4°C’de saklandı. 12 saat saklama süresinin sonunda histopatolojik ve TUNEL değerlendirmeler için doku örnekleri alınırken, saklama sıvısından da biyokimyasal analizler için numune alındı.

Bulgular: Histopatolojik değerlendirme sonucunda, hidropik dejenerasyon ve sinusoidal dilatasyon ortalamaları grup 1’de Grup 2’ye kıyasla yüksek bulundu ancak sonuçlar istatistiksel olarak anlamlı değildi. Apoptotik indeks (AI) değerleri Grup 1’de Grup 2’ye kıyasla yüksekti ancak ortanca değerlerinde istatistiksel olarak anlamlı bir farklılık bulunmadı(sırasıyla 3.50 (Min:1.00-Max:16.00) vs. 2.50 (Min:1.00-Max:20.00) p=0.974). Biyokimyasal ALT, AST ve ALP ortalama değerleri de Grup 1’de yüksek bulundu.

Sonuç: Sonuç olarak, tiyopentalin, soğuk iskemi sürecinde karaciğer dokusu üzerine koruyucu bir etkisi olduğu ve bu etkiyi histopatolojik, apopitotik ve biyokimyasal değerlendirme sonuçlarının ortalama değerlerini azaltmak yoluyla gerçekleştirdiği görülmüştür, ancak bu bulgular istatistiksel olarak anlamlı bulunamamıştır.

Keywords

Tiyopental, Soğuk iskemi, Karaciğer nakli, TUNEL, Histopatoloji

Effects of thiopental in cold ischemia in liver transplantation: An experimental study

Abstract

Aim: The aim of this study is to use the reducing effect of thiopental on metabolic rate to reduce basal metabolic rate and thus energy requirements in organs with doses administered before organ transplantation and in this way to increase organ viability by reducing to a minimum tissue damage occurring during the cold ischemia process.

Methods: The study was started with 20 Wistar albino rats in 2 groups. In Group 1 (Control=Ketamine-Xylazine group) and Group 2 (Thiopental group), rats had a midline incision made after shaving the abdominal region under anesthesia with appropriate agents. The portal vein was entered with a cannula and organ storage solution at +4 °C was injected to the portal vein to perfuse the liver. Then hepatectomy was performed, the livers were placed in Falcon tubes containing +4°C organ storage solution and stored at +4°C. Tissue samples were taken for histopathologic and TUNEL investigation and storage solution samples were taken for biochemical analysis at 12th hour.

Results: In histopathologic evaluation, the mean for hydropic degeneration and sinusoidal dilatation was higher in Group 1 compared to Group 2, but the results weren’t statistically significant. Apoptotic Index (AI) values in Group 1 were higher than Group 2; however, there was no statistically significant difference between the median values (3.50 (Min:1.00-Max:16.00) vs. 2.50 (Min:1.00-Max:20.00), respectively p=0.974). The mean values for ALT, AST and ALP were appeared to be higher in Group 1.

Conclusion: In conclusion, thiopental has a protective effect on liver tissue during the cold ischemia process via reducing the mean values of histopathological, apoptotic and biochemical assessment results, but these findings weren’t statistically significant.

Keywords

Thiopental, Cold ischemia, Liver transplantation, TUNEL, Histopathology

References

• 1. Li JH, Jia JJ, Shen W, Chen SS, Jiang L, Xie HY, et al. Optimized postconditioning algorithm protects liver graft after liver transplantation in rats. Hepatobiliary Pancreat Dis Int. 2018;17(1):32-8.
• 2. Jia JJ, Li JH, Jiang L, Lin BY, Wang L, Su R, et al. Liver protection strategies in liver transplantation. Hepatobiliary Pancreat Dis Int. 2015;14(1):34-42.
• 3. Vajdová K, Graf R, Clavien PA. ATP‐supplies in the cold‐preserved liver: A long‐neglected factor of organ viability. Hepatology. 2002;36(6):1543-52.
• 4. Lanir A, Clouse ME, Lee RG. Liver preservation for transplant: Evaluation of hepatic energy metabolism by 31P NMR 1. Transplantation. 1987;43(6):786-90.
• 5. Haddad P, Cabrillac JC, Piche D, Musallam L, Huet PM. Changes in intracellular calcium induced by acute hypothermia in parenchymal, endothelial, and Kupffer cells of the rat liver. Cryobiology. 1999;39(1):69-79.
• 6. Yokoyama Y, Beckman J, Beckman T, Wheat J, Cash T, Freeman B, et al. Circulating xanthine oxidase: potential mediator of ischemic injury. Am J Physiol Gastrointest Liver Physiol. 1990;258(4):G564-G70.
• 7. Belzer FO, Southard JH. Principles of solid-organ preservation by cold storage. Transplantation. 1988;45(4):673-6.
• 8. Szilágyi ÁL, Mátrai P, Hegyi P, Tuboly E, Pécz D, Garami A, et al. Compared efficacy of preservation solutions on the outcome of liver transplantation: Meta-analysis. World J Gastroenterol. 2018;24(16):1812.
• 9. Demmy TL, Biddle JS, Bennett LE, Walls JT, Schmaltz RA, Curtis JJ. Organ preservation solution in heart transplantation patern of useage and related survival. Transplantation. 1997;63(2):262–9.
• 10. Akbulut S, Sevmis S, Karakayali H, Bayraktar N, Unlukaplan M, Oksuz E, et al. Amifostine enhances the antioxidant and hepatoprotective effects of UW and HTK preservation solutions. World J Gastroenterol. 2014;20(34):12292.
• 11. Hosseini F, Naseri MG, Badavi M, Ghaffari MA, Shahbazian H, Rashidi I. Effect of beta carotene on lipid peroxidation and antioxidant status following renal ischemia/reperfusion injury in rat. Scand J Clin Lab Invest. 2010;70(4):259-63.
• 12. Sanches SC, Ramalho LNZ, Mendes-Braz M, Terra VA, Cecchini R, Augusto MJ, et al. Riboflavin (vitamin B-2) reduces hepatocellular injury following liver ischaemia and reperfusion in mice. Food Chem Toxicol. 2014;67:65-71.
• 13. Liu A, Dong W, Peng J, Dirsch O, Dahmen U, Fang H, et al. Growth differentiation factor 11 worsens hepatocellular injury and liver regeneration after liver ischemia reperfusion injury. FASEB J. 2018;fj-201800195R.
• 14. Wang X, Xu M, Jia J, Zhang Z, Gaut JP, Upadhya GA, et al. CD 47 blockade reduces ischemia/reperfusion injury in donation after cardiac death rat kidney transplantation. Am J Transplant. 2018;18(4):843-54.
• 15. Zhan X, Zhang Z, Huang H, Zhang Y, Zeng Z. Effect of heme oxygenase-1 on the protection of ischemia reperfusion injury of bile duct in rats after liver transplantation. Clin Res Hepatol Gastroenterol. 2018;42:245-54.
• 16. Rossetti A, Togliatto G, Rolo AP, Teodoro JS, Granata R, Ghigo E, et al. Unacylated ghrelin prevents mitochondrial dysfunction in a model of ischemia/reperfusion liver injury. Cell Death Dis. 2017;3:17077.
• 17. Zhang W, Li F, Ye Y, Liu Y, Yu S, Cen C, et al. Isoglycyrrhizinate Magnesium Enhances Hepatoprotective Effect of FK506 on Ischemia-Reperfusion Injury Through HMGB1 Inhibition in a Rat Model of Liver Transplantation. Transplantation. 2017;101(12):2862-72.
• 18. Pizarro MAD, Rodríguez JNV, Mamprin MAE, Fuller BJ, Mann BE, Motterlini R, et al. Protective effects of a carbon monoxide-releasing molecule (CORM-3) during hepatic cold preservation. Cryobiology. 2009;58(3):248-55.
• 19. Tüfek A, Tokgöz O, Aliosmanoglu İ, Alabalik U, Evliyaoglu O, Çiftçi T, et al. The protective effects of dexmedetomidine on the liver and remote organs against hepatic ischemia reperfusion injury in rats. Int J Surg. 2013;11(1):96-100.
• 20. Kayhan Z. Lokal / Bolgesel Anestezi Yontemleri, Klinik Anestezi. 2.Baskı. İstanbul: Logos Yayıncılık; 1997. pp.452-98.
• 21. Morgan GE, Mikhail MS, Muray MS, Larson CP. Regional Anesthesia & Pain Management, Clinical Anesthesiology. 3rd Edition. Los Angeles :The Mc Graw - Hill Companies; 2002. pp. 253-344.
• 22. Baugman VL, Brain protection during neurosurgery. Anesthesiol Clin North Am. 2002;20:315–27.
• 23. Morgan GE, Mikhail MS, Murray MJ, Clinical Anesthesiology, third edition, Lange Medical Boks/McGraw-Hill Companies; 2002. pp. 151–177.
• 24. Yagmurdur H, Ayyildiz A, Karaguzel E, Ogus E, Surer H, Caydere M, et al. The preventive effects of thiopental and propofol on testicular ischemia‐reperfusion injury. Acta Anaesthesiol Scand. 2006;50(10):1238-43.
• 25. Almaas R, Saugstad OD, Pleasure D, Rootwelt T. Effect of barbiturates on hydroxyl radicals, lipid peroxidation, and hypoxic cell death in human NT2-N neurons. Anesthesiology. 2000;92(3):764-74.
• 26. Hirotani T, Kameda T, Kumamoto T, Shirota S, Yamano M. Protective effect of thiopental against cerebral ischemia during circulatory arrest. Thorac Cardiovasc Surg. 1999;47(04):223-8.
• 27. Dogan Z, Yuzbasioglu MF, Kurutas EB, Yildiz H, Coskuner I, Senoglu N, et al. Thiopental improves renal ischemia–reperfusion injury. Renal failure. 2010;32(3):391-5.
• 28. Yuzer H, Yuzbasioglu MF, Ciralik H, Kurutas EB, Ozkan OV, Bulbuloglu E,et al. Effects of intravenous anesthetics on renal ischemia/reperfusion injury. Renal failure. 2009;31(4):290-6.
• 29. Mofrad P, Contos MJ, Haque M, Sargeant C, Fisher RA, Luketic VA, et al. Clinical and histologic spectrum of nonalcoholic fatty liver disease associated with normal ALT values. Hepatology. 2003;37(6):1286-92.
• 30. Giannini EG, Testa R, Savarino V. Liver enzyme alteration: a guide for clinicians. CMAJ. 2005;172(3):367-79.
• 31. Lala V, Minter DA. Liver Function Tests. [Updated 2018 Jan 12]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2018 Jan. PMID: 29494096
• 32. Anis NA, Berry SC, Burton NR, Lodge D. The dissociative anaesthetics, ketamine and phencyclidine, selectively reduce excitation of central mammalian neurones by N‐methyl‐aspartate. Br J Pharmacol. 1983;79(2):565-75.
• 33. Ergün Y, Öksüz H, Atli Y, Kılınç M, Darendeli S. Ischemia-reperfusion injury in skeletal muscle: comparison of the effects of subanesthetic doses of ketamine, propofol, and etomidate. J Surg Res. 2010;159(1):e1-e10.
• 34. Hoffman WE, Pelligrino D, Werner C, Kochs E, Albrecht RF. Ketamine decreases plasma catecholamines and improves outcome from incomplete cerebral ischemia in rats. Anesthesiology. 1992;76(5):755-62.
• 35. Yagmurdur H, Ayyildiz A, Karaguzel E, Akgul T, Ustun H, Germiyanoglu C. Propofol reduces nitric oxide‐induced apoptosis in testicular ischemia–reperfusion injury by downregulating the expression of inducible nitric oxide synthase. Acta Anaesthesiol Scand. 2008;52(3):350-7.
• 36. Yagmurdur H, Ayyildiz A, Karaguzel E, Ogus E, Surer H, Caydere M, et al. The preventive effects of thiopental and propofol on testicular ischemia‐reperfusion injury. Acta Anaesthesiol Scand. 2006;50(10):1238-43.