Increase In Hepatic Arterial Blood Flow Research Articles

The role of ATP and adenosine in the control of hepatic blood flow in the rabbit liver in vivo

BackgroundThe role of adenosine and ATP in the regulation of hepatic arterial blood flow in the "buffer response" was studied in vitro and in a new in vivo model in the rabbit. The model achieves portal-systemic diversion by insertion of a silicone rubber prosthesis between the portal vein and inferior vena cava and avoids alterations in systemic haemodynamics.ResultsHepatic arterial (HA) blood flow increased in response to reduced portal venous (PV) blood flow, the "buffer response", from 19.4 (3.3) ml min-1 100 g-1 to 25.6 (4.3) ml min-1 100 g-1 (mean (SE), p < 0.05, Student's paired t-test). This represented a buffering capacity of 18.7 (5.2) %. Intra-portal injections of ATP or adenosine (1 micrograms kg-1-0.5 mg kg-1) elicited immediate increases in HA blood flow to give -log ED50 values of 2.0 and 1.7 mg kg-1 for ATP and adenosine respectively. Injection of ATP and adenosine had no measurable effect on PV flow. In vitro, using an isolated dual-perfused rabbit liver preparation, the addition of 8-phenyltheophylline (10 MicroMolar) to the HA and PV perfusate significantly inhibited the HA response to intra-arterial adenosine and to mid-range doses of intra-portal or intra-arterial ATP (p < 0.001).ConclusionsIt is suggested that HA vasodilatation elicited by ATP may be partially mediated through activation of P1-purinoceptors following catabolism of ATP to adenosine.

Increase in Hepatic Arterial Blood Flow after Transjugular Intrahepatic Portosystemic Shunt Creation and its Potential Predictive Value of Postprocedural Encephalopathy and Mortality

To determine (i) whether there is a significant increase in hepatic artery blood flow (HABF) after transjugular intrahepatic portosystemic shunt (TIPS) creation and (ii) whether the extent of incremental increase in HABF is predictive of clinical outcome after TIPS creation. Prospective, nonrandomized, nonblinded duplex Doppler ultrasound (US) examinations were performed on 24 consecutive patients (19 men; Child Class A/B/C: 4/12/8, respectively) with a mean age of 52.8 years who were referred for TIPS creation for variceal bleeding. Peak hepatic artery velocity and vessel dimensions were used to calculate the hepatic arterial blood flow (HABF) before and after TIPS creation. Patients were clinically followed in the gastrohepatology clinic and TIPS US surveillance was performed at 1 and 3 months to assess shunt function. The extent of incremental increase in HABF was analyzed as a predictor of post-TIPS encephalopathy and/or death. The technical success rate of TIPS creation was 100%. The shunt diameters were either 10 mm (n = 11) or 12 mm (n = 13). TIPS resulted in a significant reduction in the portosystemic gradient from 24.3 mm Hg +/- 5.7 to 9.3 mm Hg +/- 2.9 (P <.001). The hepatic artery peak systolic velocity and HABF increased significantly after TIPS creation, from 60.8 cm/sec +/- 26.7 to 121 cm/sec +/- 51.5 (P <.001) and from 254.2 mL/min +/- 142.2 to 507.8 mL/min +/- 261.3 (P <.001), respectively. The average incremental increase in HABF from pre-TIPS to post-TIPS was 253.6 mL/min +/- 174.2 and the average decremental decrease in portosystemic gradient was 15.0 mm Hg +/- 5.3, but there was no significant correlation (r = 0.04; P =.86) between the two. All shunts were patent at 30 and 90 days without sonographic evidence of shunt dysfunction. After TIPS creation, new or worsened encephalopathy developed in five patients at 30 days and in an additional three at 90 days. They were all successfully managed medically. Three patients (12.5%) died within 30 days of the TIPS procedure. The extent of incremental increase in HABF after TIPS was variable and did not correlate with the development of 30-day and 90-day encephalopathy (P =.41 and P =.83, respectively) or 30-day mortality (P =.2). HABF increases significantly after TIPS but is not predictive of clinical outcome. The significance of the incremental increase is yet to be determined.

Effects of hypoxia and isoflurane on liver blood flow: the role of adenosine

We investigated the role of endogenous adenosine in mediating the effects of hypoxia and isoflurane on portal tributary blood flow (PTBF) and hepatic arterial blood flow (HABF) in rats. Liver blood flows were determined using radiolabelled microspheres. Hypoxia resulting from the exposure of rats to an atmosphere containing 15% oxygen for 30 min decreased PTBF (23%) (P<0.05) and cardiac index (15%) (P<0.05), and increased HABF (78%) (P<0.05). Isoflurane (1.4 vol%) increased HABF in both normoxic and hypoxic conditions but did not affect PTBF. The adenosine receptor antagonist 8-phenyltheophylline attenuated the hypoxia-induced increase in HABF but did not affect that resulting from the administration of isoflurane. In conclusion, in contrast to the increase in HABF induced by hypoxia, that induced by isoflurane appears to be independent of endogenous adenosine.

Impact of intrinsic blood flow regulation in cirrhosis: maintenance of hepatic arterial buffer response.

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.

Progressive hepatic arterial flow increase after end-to-side portacaval shunt in normal and cirrhotic rats.

Hepatic blood flow (HBF; ml/min/g of liver) has been measured in Wistar rats with a Xenon 133 washout method. The hepatic arterial blood flow (HABF) which amounts to 23 +/- 3% of the total HBF increases immediately after occlusion of the portal vein to ensure 36 +/- 4% of the control HBF, but continues to increase progressively for the next 4 h to furnish 69 +/- 5% of the control HBF. This represents a 183 +/- 16% increase of the control HABF. Thereafter, the liver starts to atrophy, whereas the total liver blood flow remains constant. Thus, the HBF increases and 30 days later does not differ significantly from the control value. Similar experiments were performed in rats in which cirrhosis was induced by CCl4. The HBF is decreased and the contribution of the hepatic artery raised. After portacaval shunting, the increase of the HABF, although less pronounced, is also progressive and takes 4 h to reach its maximum.

Splanchnic arterial blood flow in rats with portacaval shunts.

With indirect methods, it was shown in rats with portacaval shunts (PCS) that total hepatic blood flow (THBF) remained constant when expressed per gram of liver. These results implied an absolute increase in hepatic arterial blood flow (HABF). The aim of this study was to investigate HABF and splanchnic nonhepatic arterial blood flow (SNHABF) with a direct method (57Co microspheres) in PCS rats. One month after surgery, the following results were obtained in PCS rats compared with pair-fed, sham-operated rats: 1) liver mass atrophy was 42.3 +/- 10.9%, 2) HABF (ml X min-1 X g liver-1) was increased by a factor of 2.7, 3) SNHABF (ml X min-1 X 100 g body wt-1) was higher (9.8 +/- 3.3 vs. 5.6 +/- 2.7) (P less than 0.05) and 4) THBF (ml X min-1 X g liver-1) was decreased (1.36 +/- 0.34 vs. 1.85 +/- 0.86) but not significantly. Increases in HABF and SNHABF were not the direct consequence of an increase in cardiac output as attested by a normal cerebral blood flow (ml X min-1 X g organ-1) in PCS rats. In PCS rats, an increase in HABF may prevent the further spread of liver necrosis. The cause and the reason for an increase in SNHABF remain unknown.