title: Adenosine restores the hepatic artery buffer response and improves survival in a porcine model of small-for-size syndrome.
abstract: The aim of the study is to define the role of the HABR in the pathophysiology of the SFS liver graft and to demonstrate that restoration of hepatic artery flow (HAF) has a significant impact on outcome and improves survival. Nine pigs received partial liver allografts of 60% liver volume, Group 1; 8 animals received 20% LV grafts, Group 2; 9 animals received 20% LV grafts with adenosine infusion, Group 3. HAF and portal vein flow (PVF) were recorded at 10 min, 60 min and 90 min post reperfusion, on POD 3 and POD 7 in Group 1, and daily in Group 2 and 3 up to POD 14. Baseline HAF and PVF (ml/100 g/min) were 29 +/- 12 (mean +/- SD) and 74 +/- 8 respectively, with 28% of total liver blood flow (TLBF) from the HA and 72% from the PV. PVF peaked at 10 mins in all groups, increasing by a factor of 3.8 in the 20% group compared to an increase of 1.9 in the 60% group. By POD 7-14 PVF rates approached baseline values in all groups. The HABR was intact immediately following reperfusion in all groups with a reciprocal decrease in HAF corresponding to the peak PVF at 10 min. However in the 20% group HAF decreased to 12 +/- 8 ml/100 g/min at 90 min and remained low out to POD 7-14 despite restoration of normal PVF rates. Histopathology confirmed evidence of HA vasospasm and its consequences, cholestasis, centrilobular necrosis and biliary ischemia in Group 2. HA infusion of adenosine significantly improved HAF (p < .0001), reversed pathological changes and significantly improved survival (p = .05). An impaired HABR is important in the pathophysiology of the SFSS. Reversal of the vasospasm significantly improves outcome.
authors.affiliation: Department of Liver Transplantation and Hepatobiliary Surgery, Cleveland Clinic, Cleveland, OH 44195, USA. kellyd@ccf.org
authors.forename: Dympna M
authors.initials: DM
authors.lastname: Kelly
authors.forename: Xiaocheng
authors.initials: X
authors.lastname: Zhu
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Shiba
authors.forename: Samuel
authors.initials: S
authors.lastname: Irefin
authors.forename: Loris
authors.initials: L
authors.lastname: Trenti
authors.forename: Andrei
authors.initials: A
authors.lastname: Cocieru
authors.forename: Teresa
authors.initials: T
authors.lastname: Diago
authors.forename: Lian Fu
authors.initials: LF
authors.lastname: Wang
authors.forename: Cristiano
authors.initials: C
authors.lastname: Quintini
authors.forename: Zhong
authors.initials: Z
authors.lastname: Chen
authors.forename: Joan
authors.initials: J
authors.lastname: Alster
authors.forename: Shunichi
authors.initials: S
authors.lastname: Nakagawa
authors.forename: Charles
authors.initials: C
authors.lastname: Miller
authors.forename: Anthony
authors.initials: A
authors.lastname: Demetris
authors.forename: John J
authors.initials: JJ
authors.lastname: Fung
mesh_terms: D000241:Adenosine / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002021:Buffers; D004195:Disease Models, Animal; D005260:Female; D006085:Graft Survival / Q000187:drug effects*; D006499:Hepatic Artery; D007511:Ischemia / Q000188:drug therapy / Q000401:mortality / Q000473:pathology; D053208:Kaplan-Meier Estimate; D008102:Liver Circulation / Q000187:drug effects; D016031:Liver Transplantation; D009929:Organ Size; D011183:Postoperative Complications / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D013552:Swine; D014661:Vasoconstriction / Q000187:drug effects
chemical_list: D002021:Buffers; D000241:Adenosine