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Delivery of the Bioactive Gas Hydrogen Sulfide During Cold Preservation of Rat Liver: Effects on Hepatic Function in an Ex vivo Model
Author(s) -
Balaban Cecilia L.,
Rodriguez Joaquín V.,
Guibert Edgardo E.
Publication year - 2011
Publication title -
artificial organs
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.684
H-Index - 76
eISSN - 1525-1594
pISSN - 0160-564X
DOI - 10.1111/j.1525-1594.2011.01256.x
Subject(s) - viaspan , chemistry , ex vivo , cold storage , lactate dehydrogenase , liver transplantation , reperfusion injury , transplantation , nitric oxide , liver function , andrology , medicine , biochemistry , ischemia , biology , in vitro , organic chemistry , horticulture , enzyme
The insults sustained by transplanted livers (hepatectomy, hypothermic preservation, and normothermic reperfusion) could compromise hepatic function. Hydrogen sulfide (H 2 S) is a physiologic gaseous signaling molecule, like nitric oxide (NO) and carbon monoxide (CO). We examined the effect of diallyl disulfide as a H 2 S donor during hypothermic preservation and reperfusion on intrahepatic resistance (IVR), lactate dehydrogenase (LDH) release, bile production, oxygen consumption, bromosulfophthalein (BSP) depuration and histology in an isolated perfused rat liver model (IPRL), after 48 h of hypothermic storage (4°C) in University of Wisconsin solution (UW, Viaspan). Livers were retrieved from male Wistar rats. Three experimental groups were analyzed: Control group (CON): IPRL was performed after surgery; UW: IPRL was performed in livers preserved (48 h—4°C) in UW; and UWS: IPRL was performed in livers preserved (48 h—4°C) in UW in the presence of 3.4 mM diallyl disulfide. Hypothermic preservation injuries were manifested at reperfusion by a slight increment in IHR and LDH release compared with the control group. Also, bile production for the control group (1.32 µL/min/g of liver) seemed to be diminished after preservation by 73% in UW and 69% in UW H 2 S group at the end of normothermic reperfusion. Liver samples analyzed by hematoxylin/eosin clearly showed the deleterious effect of cold storage process, partially reversed (dilated sinusoids and vacuolization attenuation) by the addition of a H 2 S delivery compound to the preservation solution. Hepatic clearance (HC) of BSP was affected by cold storage of livers, but there were no noticeable differences between livers preserved with or without diallyl disulfide. Meanwhile, livers preserved in the presence of H 2 S donor showed an enhanced capacity for BSP uptake (k A CON = 0.29 min −1 ; k A UW = 0.29 min −1 ; k A UWS = 0.36 min −1 ). In summary, our animal model suggests that hepatic hypothermic preservation for transplantation affects liver function and hepatic depuration of BSP, and implies that the inclusion of an H 2 S donor during hypothermic preservation could improve standard methods of preparing livers for transplant.