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Effect of S-nitrosoglutathione (GSNO) added to the University of Wisconsin solution (UW): II) functional response to cold preservation/reperfusion of rat liver

Alejandra B Quintana, Henrique L. Lenzi, Luciana L. Almada, Angel L. Scandizzi, Graciela Furno, Joaquín V. Rodríguez, Edgardo E. Guibert

Abstract

Livers cold preserved in University of Wisconsin (UW) solution followed by reperfusion suffer ischemia/reperfusion injuries. Microcirculation is the primary target of damage, characterized by sinusoidal perfusion failure due, mainly, to morphological changes of sinusoidal endothelial cells. Here, we demonstrated that the addition of S-nitrosoglutathione (GSNO) to the UW solution before cold storage, as a nitric oxide (NO) donor, attenuated hepatic injuries. Wistar adult rat livers were stored in UW solution (0ºC – 48 hs) and then reperfused during 60 minutes using the Isolated Perfused Rat Model (IPRL). We assayed four GSNO concentration (50, 100, 250 and 500 μM). NO concentration was estimated calculating the amount of nitrite (NO2 -) generated in the UW solution. Injuries during cold preservation were established measuring lactate dehydrogenase (LDH) released to the UW solution. Meanwhile, intrahepatic resistance (IR), LDH released to the perfusate, the effluent/perfusate ratio for K+, bile flow, liver glycogen content and sinusoidal endothelial cell morphology were studied after 1 hour of reperfusion in the IPRL system. In cold preserved livers without GSNO, glycogen content was dramatically reduced, IR increased markedly, LDH released was high, bile flow diminished and sinusoidal endothelial cells appeared rounded and detached from perisinusoidal matrix after reperfusion. The presence of 100 μM GSNO prevented the IR rise and LDH release, improved bile production and partially reduced endothelial cells damages. In conclusion, the addition of 100 μM GSNO to UW solution improved hemodynamic and function capacity of cold preserved/reperfused livers.

Key words. Cold preservation, UW solution, nitric oxide, isolated perfused rat liver, ischemia - reperfusion injury

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The Official Journal of the Mexican Association of Hepatology, the Latin-American Association for the Study of the Liver and the Canadian Association for the Study of the Liver

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