Abstract: Aims/Background: 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: 13NH3 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 13N-metabolism was quantified by the coefficient of variation of tissue 13N-radioactivity measured 10 min after tracer infusion. Sinusoidal zonal clearances of 13NH3 into 13N-urea and 13N-glutamine were calculated by kinetic PET modelling.
Results: Liver metabolic heterogeneity was 0.65±0.20 (mean±SD, n=6) following 13NH3-infusion into HA, 0.34±0.17 into PV and 0.10±0.02 into the caval vein. Clearance of 13NH3 to 13N-urea was of similar magnitude following 13NH3 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 13NH3 to 13N-glutamine when 13NH3 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 13NH3 showed metabolic heterogeneity compatible with variation of the HA supply of the acini. Second, results of PET modelling of the sinusoidal zonation metabolism of 13NH3 to 13N-urea and to 13N-glutamine did not indicate metabolically important partial downstream arterial entry into the sinusoids.