title: Somatostatin therapy protects porcine livers in small-for-size liver transplantation.
abstract: Small-for-size (SFS) injury occurs in partial liver transplantation due to several factors, including excessive portal inflow and insufficient intragraft responses. We aim to determine the role somatostatin plays in reducing portal hyperperfusion and preventing the cascade of deleterious events produced in small grafts. A porcine model of 20% liver transplantation is performed. Perioperatively treated recipients receive somatostatin and untreated controls standard intravenous fluids. Recipients are followed for up to 5 days. In vitro studies are also performed to determine direct protective effects of somatostatin on hepatic stellate cells (HSC) and sinusoidal endothelial cells (SEC). At reperfusion, portal vein flow (PVF) per gram of tissue increased fourfold in untreated animals versus approximately threefold among treated recipients (p = 0.033). Postoperatively, markers of hepatocellular, SEC and HSC injury were improved among treated animals. Hepatic regeneration occurred in a slower but more orderly fashion among treated grafts; functional recovery was also significantly better. In vitro studies revealed that somatostatin directly reduces HSC activation, though no direct effect on SEC was found. In SFS transplantation, somatostatin reduces PVF and protects SEC in the critical postreperfusion period. Somatostatin also exerts a direct cytoprotective effect on HSC, independent of changes in PVF.
authors.affiliation: Department of Surgery, Institut de Malalties Digestives I Metabòliques (IMDiM), Hospital Clínic, CIBERehd, IDIBAPS, University of Barcelona, Barcelona, Spain.
authors.forename: A J
authors.initials: AJ
authors.lastname: Hessheimer
authors.forename: B
authors.initials: B
authors.lastname: Escobar
authors.forename: J
authors.initials: J
authors.lastname: Muñoz
authors.forename: E
authors.initials: E
authors.lastname: Flores
authors.forename: J
authors.initials: J
authors.lastname: Gracia-Sancho
authors.forename: P
authors.initials: P
authors.lastname: Taurá
authors.forename: J
authors.initials: J
authors.lastname: Fuster
authors.forename: A
authors.initials: A
authors.lastname: Rimola
authors.forename: J C
authors.initials: JC
authors.lastname: García-Valdecasas
authors.forename: C
authors.initials: C
authors.lastname: Fondevila
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000166:cytology; D006085:Graft Survival; D006439:Hemodynamics; D055166:Hepatic Stellate Cells / Q000166:cytology; D006728:Hormones / Q000627:therapeutic use; D006801:Humans; D008099:Liver / Q000187:drug effects* / Q000473:pathology; D016031:Liver Transplantation; D008297:Male; D009929:Organ Size; D010477:Perfusion; D011169:Portal Vein / Q000473:pathology; D011184:Postoperative Period; D012038:Regeneration; D015424:Reperfusion; D013004:Somatostatin / Q000627:therapeutic use*; D013552:Swine
chemical_list: D006728:Hormones; D013004:Somatostatin
keywords: Hepatic stellate cell; living donor; pig; portal vein flow; split