title: Discriminant quantitation of posttransplant hepatic reticuloendothelial function. The impact of ischemic preservation.
abstract: This study focuses upon two discrete components of posttransplant hepatic reticuloendothelial system (RES) function-phagocytosis and killing of bacteria-under various conditions of ischemic preservation. We had previously reported that, following intravenous injection of rats with 51Cr and 125I double-labeled Escherichia coli, hepatic 51Cr levels can be used to reliably quantify hepatic phagocytic clearance of the bacteria from the blood (HPC), while the subsequent release of 125I from the liver accurately parallels hepatic bacterial killing. Here, Wistar rats were transplanted with syngeneic livers perfused with either normal saline (NS) or University of Wisconsin solution (UW) and stored at 4 degrees C for 1, 2, or 3 hr prior to implantation. Control rats underwent laparotomy and hepatic artery ligation. Using the double-labeled E coli assay, HPC was decreased in all transplanted animals when compared with controls, reaching a nadir on the third postoperative day (P < 0.05). In rats transplanted with livers preserved in NS, the fraction of phagocytosed organisms that were subsequently killed (hepatic killing efficiency=HKE) was increased to 142%, 129%, or 112% of normal following 1, 2, or 3 hr of cold ischemia, respectively; P < 0.05). Conversely, preservation of donor allografts in UW was associated with marked depression of HKE. Moreover, rats receiving NS- or UW-preserved livers tolerated an intravenous challenge with Streptococcus pneumoniae poorly (50% mortality) compared with hepatic artery ligated controls (12% mortality) at 7 days. Ischemic preservation of rat livers in NS resulted in a dose (of ischemia)-dependent reduction of hepatic phagocytosis coupled with a potentiation of HKE. Preservation in UW, however, produced a striking suppression of both components of hepatic RES function. Following a septic challenge survival was reduced in both groups of transplanted rats.
authors.affiliation: The Department of Surgery, The Johns Hopkins University School of Medicine, Baltimore, MD 21287-8611, USA.
authors.forename: A S
authors.initials: AS
authors.lastname: Klein
authors.forename: M
authors.initials: M
authors.lastname: Zhadkevich
authors.forename: D
authors.initials: D
authors.lastname: Wang
authors.forename: J B
authors.initials: JB
authors.lastname: Margolick
authors.forename: J A
authors.initials: JA
authors.lastname: Winkelstein
authors.forename: G B
authors.initials: GB
authors.lastname: Bulkley
mesh_terms: D000241:Adenosine; D000493:Allopurinol; D000818:Animals; D004926:Escherichia coli; D004927:Escherichia coli Infections / Q000503:physiopathology; D005978:Glutathione; D007328:Insulin; D007728:Kupffer Cells / Q000382:microbiology / Q000502:physiology*; D008099:Liver / Q000382:microbiology* / Q000473:pathology; D016031:Liver Transplantation; D008297:Male; D019188:Organ Preservation Solutions; D010587:Phagocytosis; D011887:Raffinose; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000382:microbiology* / Q000503:physiopathology; D014021:Tissue Preservation
chemical_list: D007328:Insulin; D019188:Organ Preservation Solutions; C055206:University of Wisconsin-lactobionate solution; D000493:Allopurinol; D005978:Glutathione; D000241:Adenosine; D011887:Raffinose