HYPEROSMOLARITY ASSOCIATED WITH DIABETES-INSIPIDUS ALTERS HEPATOCYTE STRUCTURE AND FUNCTION BUT NOT SURVIVAL AFTER ORTHOTOPIC LIVER-TRANSPLANTATION IN RATS

Background. This study was designed to evaluate the effect of donor hy perosmolarity secondary to diabetes insipidus, an almost universal occ urrence among brain-dead patients, on hepatic function, Methods, In vi tro (isolated liver perfusion) and in vivo (hyaluronic acid and indocy anine green uptake, arterial ketone body ratio, orthotopic liver trans plantation) experiments were conducted using Brattleboro rats, with he reditary hypothalamic diabetes insipidus, and Sprague-Dawley rats, wit h normal pituitary function, ATP content and recovery after cold prese rvation were measured during the perfusion, Results, Cold-preserved li vers from hyperosmolar rats were observed to have elevated hepatic enz yme release and decreased bile production compared with normosmolar co ntrols, Moreover, in these livers, the recovery of ATP after cold pres ervation was completely absent, Transmission electron microscopy of li ver biopsies collected from hyperosmolar rats demonstrated profound ul trastructural changes, particularly in the mitochondria, that were not evident in the biopsies from normosmolar rats. All the experimental g roups demonstrated similar hyaluronic acid uptake, whereas indocyanine green uptake was markedly impaired in the hyperosmolar group, suggest ing that hepatocyte and not sinusoidal endothelial cell function is ad versely affected by hyperosmolarity. The arterial ketone body ratio wa s profoundly compromised by chronic and, to an even greater degree, by acute hyperosmolarity, Survival after transplantation using hyperosmo lar donors was not affected in this study, Conclusions, These results are an important step toward understanding the mechanism whereby brain death, a complicated pathophysiologic phenomenon, adversely affects t he hepatic allograft.