HYPEROSMOLARITY ASSOCIATED WITH DIABETES-INSIPIDUS ALTERS HEPATOCYTE STRUCTURE AND FUNCTION BUT NOT SURVIVAL AFTER ORTHOTOPIC LIVER-TRANSPLANTATION IN RATS
Ss. Florman et al., HYPEROSMOLARITY ASSOCIATED WITH DIABETES-INSIPIDUS ALTERS HEPATOCYTE STRUCTURE AND FUNCTION BUT NOT SURVIVAL AFTER ORTHOTOPIC LIVER-TRANSPLANTATION IN RATS, Transplantation, 65(1), 1998, pp. 36-41
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.