The role of the A2a receptor agonist, regadenoson, in modulating hepatic artery flow in the porcine small-for-size liver graft.
BACKGROUND
Hepatic artery vasoconstriction plays a major role in the pathophysiology of the small-for-size (SFS) liver graft injury and is reversed by adenosine. The A2a adenosine receptor (AR) has been suggested to be one of the key receptors that modulate hepatic hemodynamic changes. The aim of the study is to define the effects of the A2a AR agonist, regadenoson, in modulating hepatic artery flow (HAF) in SFS liver grafts of a porcine model.


METHODS
Seven female recipient pigs (66-70 kg) receiving 20% liver grafts were treated with regadenoson, 0.1 ug/kg/min starting on POD1 (n = 7). Results were compared with those with untreated 20% liver grafts (n= 8). The recipients were observed for 14 d. Hepatic artery flow (HAF) and portal vein flow (PVF) were recorded. Liver biopsies and serum samples were also taken at the designed time points through postoperative day (POD)14.


RESULTS
Dose-response curves of regadenoson established 0.1 ug/kg/min as the most effective dose of regadenoson for maintaining an increase in HAF. No adverse effects were seen with regadenoson infusion. HAF immediately increased by up to 2.2-fold after regadenoson infusion. The levels of daily average of HAF and percentage of HAF in total liver blood flow were 34.5% and 41.8%, respectively, higher in the regadenoson group than in the untreated group. Histologic scores of hepatic artery spasm and bile duct necrosis were significantly lower in the regadenoson group than in the untreated group (P = 0.01 and 0.04, respectively). The complication rates of hepatic artery thrombosis and gastrointestinal bleeding were lower in the regadenoson group than in the untreated group (0/7, 0% versus 2/8, 25% and 0/7, 0% versus 2/8 and 25%, respectively). The 14-d survival rates were 4/7 (57.1 %) in regadenoson group compared with 2/8 (25%) in the untreated group.


CONCLUSIONS
Adenosine A2a AR agonist, regadenoson, increases HAF in the recipients of SFS grafts with modest improvements in outcome.
Department of General Surgery, Cleveland Clinic, Cleveland, OH 44195, USA. zhux@ccf.org
Xiaocheng
X
Zhu
Hiroaki
H
Shiba
John J
JJ
Fung
Lian-Fu
LF
Wang
Yusuke
Y
Arakawa
Samuel
S
Irefin
Anthony J
AJ
Demetris
Dympna M
DM
Kelly
D058908:Adenosine A2 Receptor Agonists / Q000494:pharmacology*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D005260:Female; D006499:Hepatic Artery / Q000187:drug effects* / Q000502:physiology; D008099:Liver / Q000473:pathology; D008102:Liver Circulation / Q000187:drug effects*; D016031:Liver Transplantation; D009929:Organ Size; D011182:Postoperative Care; D011687:Purines / Q000494:pharmacology*; D011720:Pyrazoles / Q000494:pharmacology*; D043705:Receptor, Adenosine A2A / Q000502:physiology; D015996:Survival Rate; D013552:Swine
D058908:Adenosine A2 Receptor Agonists; D011687:Purines; D011720:Pyrazoles; D043705:Receptor, Adenosine A2A; C430916:regadenoson