Hepatic microcirculation assessed by positron emission tomography of first-pass ammonia metabolism in porcine liver.
OBJECTIVE
Intrahepatic branching of the hepatic artery (HA) to liver microcirculatory units, the acini, is more heterogeneous than that of the portal vein (PV). Furthermore, part of HA blood enters the sinusoid partially downstream between the in- and outlets. We examined the effects of these vascular variations on porcine hepatic first-pass ammonia metabolism, which is characterised by high uptake and separate periportal urea and perivenous glutamine formations.


METHODS
(13)NH(3) was given via the PV, HA or caval vein, followed by 22 min dynamic liver positron emission tomography (PET) recordings in six pigs. Heterogeneity of liver (13)N-metabolism was quantified by the coefficient of variation of tissue (13)N-radioactivity measured 10 min after tracer infusion. Sinusoidal zonal clearances of (13)NH(3) into (13)N-urea and (13)N-glutamine were calculated by kinetic PET modelling.


RESULTS
Liver metabolic heterogeneity was 0.65+/-0.20 (mean+/-SD, n=6) following (13)NH(3)-infusion into HA, 0.34+/-0.17 into PV and 0.10+/-0.02 into the caval vein. Clearance of (13)NH(3) to (13)N-urea was of similar magnitude following (13)NH(3) administration into HA and PV: 0.27+/-0.11 ml/min/g (mean+/-SD) and 0.29+/-0.09 ml/min/g, respectively. Clearances of (13)NH(3) to (13)N-glutamine when (13)NH(3) was given into HA and PV were also similar: 0.47+/-0.18 and 0.50+/-0.13 ml/min/g, respectively.


CONCLUSIONS
The present measurements of the hepatic metabolism of (13)NH(3) showed metabolic heterogeneity compatible with variation of the HA supply of the acini. Second, results of PET modelling of the sinusoidal zonation metabolism of (13)NH(3) to (13)N-urea and to (13)N-glutamine did not indicate metabolically important partial downstream arterial entry into the sinusoids.
Keiding
Susanne
S
Department of Medicine V (Hepatology and Gastroenterology), Aarhus University Hospital, DK 8000 Aarhus, Denmark. susanne@pet.auh.dk
Munk
Ole Lajord
OL
Vilstrup
Hendrik
H
Nielsen
Dennis Tønner
DT
Roelsgaard
Klaus
K
Bass
Ludvik
L
D000641:Ammonia / Q000493:pharmacokinetics*; D000818:Animals; D005260:Female; D005973:Glutamine / Q000378:metabolism; D008099:Liver / Q000098:blood supply* / Q000000981:diagnostic imaging / Q000378:metabolism; D008833:Microcirculation / Q000000981:diagnostic imaging / Q000502:physiology; D008954:Models, Biological; D009590:Nitrogen Radioisotopes; D049268:Positron-Emission Tomography / Q000379:methods / Q000662:veterinary*; D013552:Swine / Q000502:physiology*; D014508:Urea / Q000378:metabolism
D009590:Nitrogen Radioisotopes; D005973:Glutamine; D000641:Ammonia; D014508:Urea