Quintana AB, Rodriguez JV, Scandizzi AL, Guibert EE

Language: English
References: 30
Page: 84-91
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Cold liver preservation in the University of Wisconsin solution (UW) followed by reperfusion alters hepatic parenchyma and extra cellular matrix. In this study we analyzed the benefit of adding either 500 µM Sodium Nitroprusside (NPNa) or 100 µM S-nitrosoglutathione (GSNO) as Nitric Oxide (NO) donors to the UW solution to prevent hepatic injury. Wistar adult rat livers were stored in UW solution (0°C) for 48Hs and reperfused (60 minutes) in the isolated perfused rat liver model (IPRL). Untreated livers were used as normal controls. Livers perfused but not preserved were used as controls of reperfusion. Parenchyma damages were evaluated by Hematoxylin-Eosin stain. Picrosirius Red and Gordon-Sweets stains were used for collagen and reticulin networks, respectively. An inmunohistochemistry assay for albumin was used as functional test. Cold preservation step was followed by swollen hepatocytes with “light empty halos” surrounding the nucleus, conserved hepatocyte cords and many rounded endothelial cells. The addition of NPNa or GSNO into UW solution, avoid these alterations. Livers preserved for 48 Hs and then reperfused showed extended areas of vacuolation around central veins, and many endothelial cells were rounded and located inside sinusoidal lumens. The collagen network was disorganized while the reticulin one was less altered. Albumin was distributed preferentially in pericentral areas. On the contrary, livers preserved in presence of NPNa or GSNO did not show vacuolation and both collagen and reticulin networks were unchanged. Albumin was more homogeneously distributed in both groups. In conclusion, the addition of 500 µM NPNa or 100 µM GSNO as a NO donor, improves UW solution properties to preserve rat livers by maintaining the hepatic morphology and avoiding hepatic injury post-cold preservation/reperfusion.

REFERENCES

1. Lemasters JJ and Thurman RG. Perfused Liver. Hypoxic, Ischaemic and Preservation-Induced Injury. In: Ballet F and Thurman RG, eds. Perfused Liver. Clinical and Basic Applications. London: John Libbey, 1991; 97-120.

2. Koeppel TA, Gebhard MM, Otto G, Post E. Inhibition of Nitric Oxyde Synthesis in Ischaemia/Reperfusion of the Rat Liver is followed by Impairment of Hepatic Microvascular Blood Flow. J Hepatol 1997; 27: 163-169.

3. Clavien PA. Sinusoidal Endothelial Cell Injury during Hepatic Preservation and Reperfusion. Hepatology 1998; 28: 281-285.

4. Müller AR, Platz KP, Heckert C, Häusler M, Guckelberger O, Schuppan D, Lobeck H, et al. The Extracellular Matrix. an early target after small bowel Transplantation. Transplantation 1998; 65: 6 770-776.

5. Li XK, Matin AFM, Suzuki H, Uno T, Yamaguchi T and Harada Y. Effect of Protease Inhibitor on Ischemia/Reperfusion Injury of the Rat Liver. Transplantation 1993; 56: 1331-1336.

6. Upadhya AG, Harvey RPC, Howard TK, Lowell JA, Shenoy S, Strasberg SM. Evidence of a Role for Matrix Metalloproteinases in Cold Preservation Injury of the Liver in Humans and in the Rat. Hepatology 1997; 26: 922-928.

7. Churchill TA, Green CJ, Fuller BJ. Protective Properties of Amino Acids in Liver Preservation: Effects of Glycine and a Combination of Amino Acids on Anaerobic Metabolism and Energetics. J Hepatol 1995; 23: 6 720-726.

8. Stansby G, Fuller B, Jeremy J, Cheetan K, Roller K. Endothelin Release. A Facet of Reperfusion Injury in Clinical Liver Transplantation. Transplantation 1993; 56: 239-240.

9. Ignarro LJ, Lippton H, Edwards JC, Barilos WH, Hyman AL, Kadowitz PJ, Gruetter CA. Mechanism of Vascular Smooth Muscle Relaxation by Organic Nitrates, Nitrites, Nitroprusside Oxide. J Pharmacol Expl Ther 1981; 218: 739-749.

10. Rodney Mathews W and Kerr SW. Biological Activity of S-Nitrosothiols: The Role of Nitric Oxyde. J Pharmacol Exp Ther 1993; 267 3: 1529-1537.

11. Rodriguez J, Guibert E, Quintana A, Scandizzi A, Almada L. The Role of Sodium Nitroprusside in the Improvement of Rat Liver Preservation in University of Wisconsin Solution. A Study in the Isolated Perfused Liver Model. J Surg Res 1999; 87: 201-208.

12. Feelisch M, Noack E. Correlation between nitric oxide formation during degeneration of organic nitrate and activation of guanylate cyclase. Eur J Pharmacol 1987; l39(1): 19-30.

13. Fullerton DV, Mitchell MV, Mc Intyre RC. Cold ischemia and reperfusion each produce pulmonary vasomotor dysfunction in the transplanted lung. J Thorac Cardiovasc Surg 1993; 106: 1213–1217.

14. Quintana A, Rodriguez J, Scandizzi A, Guibert E. Effect of S-nitrosoglutathione (GSNO) Added to the University of Wisconsin Solution (UW): I) Morphological Alteration During Cold Preservation/Reperfusion of Rat Liver. I. Journal of Surgical Investigation 2001; 2: 401-411.

15. Belzer FO and Southard JH. Principles of Solid Organ Preservation by Cold Storage. Transplantation 1988; 45: 673-676.

16. Mamprin ME, Rodriguez JV, Guibert EE. The Importance of pH in Resuspension Media on Viability of Hepatocytes Preserved in University of Wisconsin Solution. Cell Transplant 1995; 4(3): 269-274.

17. Chazouillieres O, Calmus Y, Vaubordolle M, Ballet F. Preservation-Induced Liver Injury. Clinical Aspects, Mechanism and Therapeutic Approaches. J Hepatol 1993; 18: 123-134.

18. Miller LL. Thechnique of Isolated Rat Liver Perfusion. In: I. Bartosek, A. Guatain, LL. Miller, eds. Isolated Liver Perfusion and Its Applications. New York: Raven Press, 1973: 11-52.

19. Hart TW. Some Observation Concerning S-nitroso and S-phenylsufonyl Derivatives of L-cysteina and glutathione. Tetrahedron Lett 1985; 26: 2013-2016.

20. Alexander B, Aslarn M, Benjamin IS. Hepatic Function During Prolonged Isolated Rat Liver Perfusion Using a New Miniaturized Perfusion Circuit. J Pharmacol Toxicol Methods 1995; 34(4): 203-210.

21. Almada LL, Scandizzi AL, Guibert EE, Furno G, Rodriguez JV. Biliary Inorganic Phosphate as a Tool for Assessing Cold Preservation-Reperfusion Injury: A Study in the Isolated Perfused Rat Liver Model. Liver Transplantation 2003; 9(2):160-169.

22. Quintana AB, Lenzi HL, Almada LL, Scandizzi AL, Furno G, Rodríguez JV, Guibert EE. Effect of S-Nitrosoglutathione (GSNO) added to the University of Wisconsin Solution (UW): II) Functional Response to Cold Preservation/Reperfusion of Rat Liver. Ann Hepatol 2002; 1(4): 183-191.

23. Junqueira LCU, Bignolas G and Bretani R. Picrosirius Staining plus Polarization Microscopy, a Specific Method for Collagen Detection in Tissue Section. Histochem J 1979; 11: 447-455.

24. Lynch MJ, Raphael SS, Mellor LD, Spare PD, Inwood MJH. Medical Laboratory Technology and Clinical Pathology. Philadelphia: W. B. Saunders Company. 1969: 1113-1114.

25. Urata K, Nguyen B, Brault A, Lavoie J, Rocheleau B, Huet PM. Decreased survival in rat liver transplantation with extended cold preservation: Rol of portal vein clamping time. Hepatology 1998; 28: 366-373.

26. Huet PM, Kassissia I, Semret M. Haemodynamics. In: Ballet F, Thurman RG, eds. Perfused Liver. Clinical and Basic Applications. London: John Libbey 1991: 33-42.

27. Weiss RH and Riley DP. Uses of Inorganic Chemistry in Medicine in: Farrell NP, ed. Therapeutic Aspects of Manganese (II)-based Superoxide Dismutase Mimics. Royal Society of Chemistry. Perfusion Circuit. J Pharmacol Toxicol Met 1999; 34: 203 -210.

28. Shapiro SD. Matrix metalloproteinase degradation of extracellular matrix: biological consequences. Current Opinion in Cell Biology 1998; 10: 602-608.

29. Turpaev KT. Nitric Oxide in Intercellular Communication. Mol Biol 1998; 32 (4): 475-484.

30. Ignarro LJ. Endothelium-derived nitric oxide: pharmacology and relationship to the actions of organic nitrate esters. Pharm Res 1989; 6(8): 651-659.