Hepatic arterial perfusion decreases intrahepatic shunting and maintains glucose uptake in the rat liver

Abstract

Intrahepatic shunts have an important function in the regulation of portal venous pressure in the normal rat liver. The present study determined their location, the region of confluence between the hepatic arterial and portal venous vasculatures, regions within the liver that are bypassed and the effects of hepatic arterial perfusion upon the intrahepatic redistribution of portal venous flow. Livers of male Sprague-Dawley rats were excised and perfused in vitro. Hepatic bromosulphthalein (BSP) and glucose uptake were measured in hepatic venous samples. Diversion of the hepatic arterial supply into the portal venous vasculature opened the portal venous intrahepatic shunts and resulted in a 50% reduction in portal venous glucose uptake from 29.6+/-1.6% to 14.9+/-0.9% ( P<0.0001 Student's paired t-test). Portal venous injection of 15-microm-diameter microspheres also opened the intrahepatic shunts and reduced portal venous glucose uptake to 10% from 29.0+/-1.6% to 7.8+/-0.9% ( P<0.0001 Student's paired t-test). No significant reductions in portal venous BSP uptake (43.0+/-6.9 to 48.0+/-4.8%) or hepatic arterial glucose uptake, from an average value of 94.0%, occurred. Therefore, cessation of hepatic arterial perfusion or portal venous injection of microspheres reduced portal venous glucose uptake without affecting BSP uptake. It is concluded that intrahepatic shunts divert perfusate away from the perivenous, sinusoidal (zone III) regions and into the hepatic venous vasculature, distal to zone III. The microsphere data indicate that confluence between the hepatic arterial and portal venous vasculatures occurs mainly in sinusoidal zone II.

Location and function of intrahepatic shunts in anaesthetised rats

“…This indicates that the main site of confluence of the hepatic artery with the portal vein is intrasinusoidal, in zone II, thus substantiating earlier work. 13 If this were presinusoidal, microspheres should reduce hepatic arterial sorbitol uptake to the same extent as portal venous sorbitol uptake and this did not happen. Haemodynamic observations showed a limited reduction in hepatic arterial blood flow after microsphere injection, possibly secondary to the decreased mean arterial pressure.…”

“…This indicates that the main site of confluence of the hepatic artery with the portal vein is intrasinusoidal, in zone II, thus substantiating earlier work. 13 If this Figure 7 Illustration of the relationship between intrahepatic shunts, hepatic sorbitol uptake, and microsphere induced presinusoidal occlusion in the normal rat liver. (A) Under normal conditions, portal blood flows through the sinusoids with extremely low resistance.…”

“…7 We have demonstrated the existence of intrahepatic shunts, with diameters of up to 80-90 µm, in the normal rat liver using conventional physiological indices 8 9 and have confirmed their existence in the dual perfused normal rat liver using glucose uptake measurements where intrahepatic portal blockade by microspheres significantly increased intrahepatic shunting, as indicated by the reduced portal venous uptake of glucose but retained bromosulphthalein (BSP) uptake. [10][11][12][13] Further in vivo studies of intrahepatic shunting have been hindered by the lack of a reliable technique to measure functional hepatic blood flow and intrahepatic shunt flow. Radioactive microsphere techniques measure the shunt fraction by recording pulmonary recovery of microspheres usually injected intraportally.…”

Chronic hepatic artery ligation does not prevent liver from differentiating portal vs. peripheral glucose delivery

“…No studies have been done with gradients as large as Ϫ163 mg/dl, however, so a bell-shaped response remains possible. A second likely explanation for the blunting of the response to the portal signal in the HAL po dogs may lie in the importance of the hepatic artery in regulation of hepatic circulation (4,5). It has been proposed that the architecture of the liver allows shunting of portal vein blood away from the areas of hepatic glucose uptake (zone III), and the presence of hepatic artery flow decreases intrahepatic shunting and thus stimulates glucose uptake (5).…”

“…A second likely explanation for the blunting of the response to the portal signal in the HAL po dogs may lie in the importance of the hepatic artery in regulation of hepatic circulation (4,5). It has been proposed that the architecture of the liver allows shunting of portal vein blood away from the areas of hepatic glucose uptake (zone III), and the presence of hepatic artery flow decreases intrahepatic shunting and thus stimulates glucose uptake (5). Nevertheless, the fact that the HAL dogs responded qualitatively, even if not completely quantitatively, to both peripheral and portal glucose infusion implies that redundant sensing sites are normally operational or that chronic adaptation to the loss of the hepatic artery allowed other sensing sites to become evident, even though the redundant site or sites may not be as effective as the intrahepatic site.…”