The hepatic arterial buffer response (HABR) effectively controls total blood perfusion in normal livers, but little is known about blood flow regulation in cirrhosis. We therefore studied the impact of HABR on blood perfusion of cirrhotic livers in vivo. After 8-wk CCl(4) treatment to induce cirrhosis, 18 anesthetized rats (and 18 noncirrhotic controls) were used to simultaneously assess portal venous and hepatic arterial inflow with miniaturized ultrasonic flow probes. Stepwise hepatic arterial blood flow (HAF) or portal venous blood flow (PVF) reduction was performed. Cirrhotic livers revealed a significantly reduced total hepatic blood flow (12.3 +/- 0.9 ml/min) due to markedly diminished PVF (7.3 +/- 0.8 ml/min) but slightly increased HAF (5.0 +/- 0.6 ml/min) compared with noncirrhotic controls (19.0 +/- 1.6, 15.2 +/- 1.3, and 3.8 +/- 0.4 ml/min). PVF reduction caused a significant HABR, i.e., increase of HAF, in both normal and cirrhotic livers; however, buffer capacity of cirrhotic livers exceeded that of normal livers (P < 0.05) by 1. 7- to 4.5-fold (PVF 80% and 20% of baseline). Persistent PVF reduction for 1, 2, and 6 h demonstrated constant HABR in both groups. Furthermore, HABR could be repetitively provoked, as analyzed by intermittent PVF reduction. HAF reduction did not induce changes of portal flow in either group. Because PVF is reduced in cirrhosis, the maintenance of HAF and the preserved HABR must be considered as a protective effect on overall hepatic circulation, counteracting impaired nutritive blood supply via the portal vein.

To elucidate the hepatic microvascular response upon the hepatic arterial buffer response (HABR), we analysed blood flow (ultrasonic flowprobes) of the hepatic artery (HA) and portal vein (PV), microcirculation (intravital microscopy), and tissue oxygenation (polarography) in anaesthetized Sprague‐Dawley rats and re‐evaluated the role of adenosine in mediating the HABR by using 8‐phenyltheophylline as a competitive antagonist. Upon restriction of PV blood flow to 11 ± 3 % of baseline values, HA blood flow increased by a factor of 1.77 (P < 0.05), thus confirming HABR. Strikingly, red blood cell velocity and volumetric blood flow in terminal hepatic arterioles (THAs) did not increase but were even found to be slightly decreased, by 8 and 13 %, respectively. In contrast, red blood cell velocity and volumetric blood flow in terminal portal venules (TPVs) decreased to only 66 % (P < 0.05), indicating upstream hepatic arteriolo‐portal venular shunting. As a consequence, red blood cell velocity and volumetric blood flow in sinusoids were found to be reduced to only 66‐68 % compared with baseline (P < 0.05). Diameters of neither of those microvessels changed, thus excluding THA‐, TPV‐, and sinusoid‐associated mechanisms of vasomotor control in HABR. Tissue PO2 and hepatocellular NADH fluorescence remained unchanged, indicating HABR‐mediated maintenance of adequate oxygen delivery, despite the marked reduction of total liver blood flow. Further, hepatic arteriolo‐portal venular shunting guaranteed homogeneity of nutritive blood flow upon HABR, as given by an unchanged intra‐acinar coefficient of variance of sinusoidal perfusion. Pretreatment of animals with the adenosine antagonist 8‐phenyltheophylline completely blocked the hepatic arterial buffer response with the consequence of decreased tissue oxygenation and increased heterogeneity of sinusoidal perfusion. In conclusion, hepatic microhaemodynamics, in particular unchanged diameters of THAs, TPVs and sinusoids, during HABR indicate that reduction in resistance to HA flow is located upstream and functions via hepatic arteriolo‐portal venular shunts resulting in equal distribution of microvascular blood flow and oxygen delivery under conditions of restricted PV blood supply.

We investigated sinusoidal blood flow and hepatic tissue oxygenation during portal vein occlusion in cirrhotic rat livers to examine the effect of cirrhosis on the properties of hepatic microvascular blood flow regulation. After 8 weeks of CCl4/phenobarbital sodium treatment to induce cirrhosis Sprague-Dawley rats were prepared surgically to allow assessment of portal venous and hepatic arterial inflow using miniaturized flow probes with simultaneous analysis of hepatic microcirculation and tissue oxygenation by fluorescence microscopy and polarographic oxymetry. Age-matched noncirrhotic animals served as controls. Upon portal vein occlusion in cirrhotic livers (flow reduction to < 20%), hepatic arterial blood flow increased 1.5-fold (61 +/- 8 ml/min per 100 g liver) of baseline (40 +/- 7 ml/min per 100 g liver), reflecting an appropriate hepatic arterial buffer response (HABR), similarly as seen in control livers. The net result was a reduction in total liver inflow from 90 +/- 12 to 72 +/- 11 ml/min per 100 g liver, which was associated with a significant decrease in both sinusoidal red blood cell velocity and volumetric blood flow to approx. 71% and 76% of baseline values. However, portal vein occlusion did not cause a deterioration in hepatic tissue pO2 (11 +/- 3 vs. 10 +/- 3 mmHg at baseline). Sinusoidal diameters were found unchanged, disproving a major role of the sinusoidal tone in the regulation of HABR. Microvascular response of cirrhotic livers did not generally differ from that in noncirrhotic livers upon portal inflow restriction. We conclude that HABR in cirrhotic livers operates sufficiently to meet the liver tissue oxygen demand, most probably by an increased relative contribution of arterial perfusion of hepatic sinusoids.

Although ONSF does not apparently injure the optic nerve axons, loss and shrinkage of RGCs is a caution when considering ONSF as a treatment.

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