O2 uptake in periportal and pericentral regions of liver lobule in perfused liver

Abstract

O2 uptake by the perfused liver decreased at O2 concentrations considerably higher than levels that caused NADH reduction when the input O2 concentration was varied. The maximal rate of O2 uptake was two- to threefold higher in periportal (137 +/- 8 mumol . g-1 . h-1; O2 concentration = 478 +/- 37 microM) than pericentral regions (59 +/- 5 mumol . g-1 . h-1; O2 concentration = 263 +/- 21 microM); however, the O2 concentration required for half-maximal O2 uptake was similar (approximately 20 microM) in the two areas. The infusion of atractyloside, antimycin A, or KCN inhibited O2 uptake in both zones by 50-85%, indicating that O2 uptake in both regions was largely dependent on mitochondrial electron transport. The content of ATP and ADP and ATP:ADP were similar in microdissected samples from periportal and pericentral areas. In contrast, when livers were perfused in the retrograde direction, O2 uptake was two- to threefold greater in pericentral than in periportal regions. Maximal rates of O2 uptake correlated with the local O2 concentration irrespective of the direction of flow when the electrode was moved across the liver lobule with a micromanipulator. Lower rates of O2 uptake in pericentral areas were not altered appreciably by infusion of agents known to uncouple oxidative phosphorylation (DNP), increase ADP supply (fructose), or increase the NADH redox state (ethanol or octanoate). These data are consistent with the hypothesis that maximal rates of O2 uptake are regulated, in part, in the perfused liver by O2 concentrations far above the Km of cytochrome oxidase for O2.

Oxygen and substrate dependence of hepatic cellular respiration: Sinusoidal oxygen gradient and effects of ethanol in isolated perfused liver and hepatocytes

“…There are also previous observations suggesting that the arithmetic mean of portal and venous 0 2 may not represent the space-average concentration, because the apparent Km for oxygen consumption by this calculation becomes 175 pM (Matsumura et al, 1986). Measured with a microelectrode, the local pericentral O2 concentration for a half-maximal NADH fluorescence increase is 20 p M (Matsumura et al, 19861, but this value is high compared with the present data on the behavior of cytochrome oxidase, probably because of the limited spatial resolution of the microelectrode technique.…”

Evidence that hypoxia markers detect oxygen gradients in liver: pimonidazole and retrograde perfusion of rat liver

“…With respect to the distribution of reducing equivalents, previous studies have shown that the potential for oxygen uptake is similar in periportal and pericentral regions of liver (Matsumura et al, 1986). That is, the high rate of oxygen uptake in periportal regions during perfusion in the normal or anterograde direction is shifted to the pericentral region during perfusion in the retrograde direction.…”

“…That is, the high rate of oxygen uptake in periportal regions during perfusion in the normal or anterograde direction is shifted to the pericentral region during perfusion in the retrograde direction. Importantly, about 85% of oxygen consumption in liver tissue is due to oxygen reduction by electrons from the electron transport chain (Matsumura et al, 1986). These are the same electrons that reduce nitroaromatic compounds in the absence of oxygen so it is not surprising that the potential for nitroimidazole reduction and binding (Figure 3), like oxygen uptake, is similar in pericentral and periportal regions of liver.…”

In Vivo Comparison of Non-Gaseous Metabolite and Oxygen Transport in the Heart

“…In the liver, an organ with a relatively large vascular space and discontinuous capillaries, tissue PO 2 measured with surface electrodes is between arterial and venous values (Matsumura et al, 1986). The earlier measurements of Kessler (1967) using penetrating 50μm electrodes probably were too low because the electrode interfered with local flow in the sponge-like liver.…”