Estimation of aqueous distributional spaces in the dual perfused rat liver

1. The aim of this study was to estimate the aqueous distributional spaces of the liver as a function of the route of input: portal vein (PV) versus h epatic artery (HA). 2. Studies were performed in the in situ single (PV) and dual (PV-HA) perfu sed rat liver (n = 6-10) using Krebs bicarbonate buffer at constant PV (12 ml min(-1)) and HA (3 ml min(-1)) flow rates. An impulse input-output respo nse technique was employed, varying the route of input, using non-labelled erythrooytes (intravascular marker), I-125-albumin and [C-14]sucrose (extra cellular markers), and [C-14]urea and (H2O)-H-3 (total water markers) as th e reference indicators. 3. Distributional spaces were estimated using two different methods, namely standard and specific. The standard method was applied to hepatic outflow data obtained from the single PV perfused liver. The specific method was us ed when operating in the dual perfused mode to provide an estimate of the e xcess space perfused solely by the HA input. Specific spaces, interstitial and intracellular volumes, were estimated by difference. 4. The results were evaluated by means of visual inspection of the outflow profiles and comparison of the distributional spaces. Different hepatic eff luent profiles obtained as a function of the route of input indicated that these two inputs did not completely mix within the liver. Estimates of the distributional spaces supported this observation, and further suggested tha t the arterial input perfuses 9-12 % more hepatic tissue than the venous in put. 5. The knowledge obtained from the existence of a specific arterial space c an be extended to help make predictions about the fate of an eliminated com pound following arterial administration. Any difference between the HA and PV in terms of hepatic recovery could be attributed to this excess space an d its enzyme density.