title: Hyperosmolarity associated with diabetes insipidus alters hepatocyte structure and function but not survival after orthotopic liver transplantation in rats.
abstract: BACKGROUND
  This study was designed to evaluate the effect of donor hyperosmolarity secondary to diabetes insipidus, an almost universal occurrence among brain-dead patients, on hepatic function.
  
  
  METHODS
  In vitro (isolated liver perfusion) and in vivo (hyaluronic acid and indocyanine green uptake, arterial ketone body ratio, orthotopic liver transplantation) experiments were conducted using Brattleboro rats, with hereditary hypothalamic diabetes insipidus, and Sprague-Dawley rats, with normal pituitary function. ATP content and recovery after cold preservation were measured during the perfusion.
  
  
  RESULTS
  Cold-preserved livers from hyperosmolar rats were observed to have elevated hepatic enzyme release and decreased bile production compared with normosmolar controls. Moreover, in these livers, the recovery of ATP after cold preservation was completely absent. Transmission electron microscopy of liver biopsies collected from hyperosmolar rats demonstrated profound ultrastructural changes, particularly in the mitochondria, that were not evident in the biopsies from normosmolar rats. All the experimental groups demonstrated similar hyaluronic acid uptake, whereas indocyanine green uptake was markedly impaired in the hyperosmolar group, suggesting that hepatocyte and not sinusoidal endothelial cell function is adversely affected by hyperosmolarity. The arterial ketone body ratio was profoundly compromised by chronic and, to an even greater degree, by acute hyperosmolarity. Survival after transplantation using hyperosmolar 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 the hepatic allograft.
authors.affiliation: Department of Surgery, Mount Sinai School of Medicine, New York, New York 10029, USA.
authors.forename: S S
authors.initials: SS
authors.lastname: Florman
authors.forename: D
authors.initials: D
authors.lastname: Podkameni
authors.forename: L
authors.initials: L
authors.lastname: Wang
authors.forename: R E
authors.initials: RE
authors.lastname: Gordon
authors.forename: S
authors.initials: S
authors.lastname: Curtiss
authors.forename: P
authors.initials: P
authors.lastname: Boros
authors.forename: C M
authors.initials: CM
authors.lastname: Miller
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001647:Bile Acids and Salts / Q000378:metabolism; D001926:Brain Death / Q000473:pathology*; D015925:Cryopreservation; D003919:Diabetes Insipidus / Q000473:pathology*; D006820:Hyaluronic Acid / Q000493:pharmacokinetics; D007208:Indocyanine Green / Q000493:pharmacokinetics; D007657:Ketone Bodies / Q000097:blood; D008099:Liver / Q000201:enzymology / Q000473:pathology*; D016031:Liver Transplantation / Q000473:pathology*; D008297:Male; D008854:Microscopy, Electron; D009926:Organ Preservation; D009994:Osmolar Concentration; D010477:Perfusion; D051381:Rats; D011910:Rats, Brattleboro; D017207:Rats, Sprague-Dawley
chemical_list: D001647:Bile Acids and Salts; D007657:Ketone Bodies; D000255:Adenosine Triphosphate; D006820:Hyaluronic Acid; D007208:Indocyanine Green