Adenosine nucleotide metabolism in rat liver ex vivo
Palombo, John D.
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Despite the recent advances in liver transplantation nearly 15% of all allograft livers fail to function or function poorly in the early posttransplant period. Although the etiology of this dysfunction is multifunctional, recent clinical reports indicated that success of transplant outcome was directly correlated with the adenine nucleotide content of donor liver following preservation. The objectives of this dissertation were to identify and characterize specific nutritional and biochemical factors which 1) would reduce the loss of adenine nucleotides in rat liver during preservation ex vivo, and 2) would enhance nucleotide recovery following extended preservation using a liver perfusion model. In study 1, liver capacity to support adenine nucleotides by glycolysis during preservation was assessed. Livers obtained from fasted or dextrose-infused rats were stored and sampled over eight hours in preservation solutions rich or devoid in glucose. For a given dietary pretreatment, adenine nucleotide losses and lactate production were similar regardless of the preservation solution. Donor pretreatment with dextrose resulted in significantly higher liver ATP, adenylate energy charge, and lactate concentrations irrespective of the preservation solution. Thus, glycolytic support of adenine nucleotides in liver ex vivo was independent of exogenous glucose during preservation but dependent on the donor's nutritional status. In Study 2, rats which were infused with glucose were pretreated with adenosine i.v. or i.p. in an attempt to augment liver adenine nucleotides. Liver adenine nucleotides in vivo were unchanged by adenosine pretreatment. Nucleotide losses during preservation ex vivo were similar to those in Study 1. Significantly higher quantities of salvageable precursors of adenine nucleotides were present in livers of rats which received higher doses of adenine. In Study 3, nucleotide recovery in liver subjected to extended preservation and sunsequently reperfused was assessed. Independent variables included the donor’s nutritional status and adenine supplementation during perfusion. Restoration of adenine nucleotides to normal levels was achieved within thirty minutes in livers perfused with adenosine (1mM) present in the perfusate. In contrast, adenine nucleotide concentrations of livers perfused without adenosine were 40% lower than those perfused with adenosine. Neither the donor's prior nutritional status nor oxygen delivery were factors in the enhanced recover observed.
PLEASE NOTE: This work is protected by copyright. Downloading is restricted to the BU community: please click Download and log in with a valid BU account to access. If you are the author of this work and would like to make it publicly available, please contact email@example.com.Thesis (D.Sc.D.)--Boston University, Henry M. Goldman School of Graduate Dentistry, 1990 (Nutritional Sciences)Bibliographic references : leaves 134-147.
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