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 hepatic artery (HA). 2. Studies were performed in the situ single (PV) and dual (PV-HA) perfused 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 response technique was employed, varying the route of input, using non-labelled erythrocytes (intravascular marker), 125I-albumin and [14C]sucrose (extracellular markers), and [14C]urea and 3H2O (total water markers) as the 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 used when operating in the dual perfused mode to provide an estimate of the excess 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 effluent 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 that the arterial input perfuses 9-12 % more hepatic tissue than the venous input. 5. The knowledge obtained from the existence of a specific arterial space can be extended to help make predictions about the fate of an eliminated compound following arterial administration. Any difference between the HA and PV in terms of hepatic recovery could be attributed to this excess space and its enzyme density.