Casts of hepatic blood vessels: a comparison of the microcirculation of the penguin, Pygoscelis adeliae, with some common laboratory animals. (1/997)

Latex casts of the hepatic blood vessels of the penguin, Pygoscelis adeliae, and of some common laboratory animals were compared. There was general similarity between the different species, but the portal venous and hepatic arterial systems of the penguin were simpler than those of other species. Measurements were made of the volume and length of portal veins and it appears that the portal venous system is capable of being a more efficient blood reservoir in the penguin than in other species studied. The peribiliary plexus was especially well formed in the penguin and was drained by long veins which usually joined portal venous branches. Some of the long veins drained directly into the hepatic venous tree: these translobular veins were more prominent than in mammals. Anastomoses between hepatic artery and portal vein were not present in penguins, and the supply to the sinusoids appeared to be separate. The morphology of small hepatic veins of all the species appeared to be similar.  (+info)

Pulsed Doppler ultrasonographic evaluation of portal blood flow in dogs with experimental portal vein branch ligation. (2/997)

Portal blood flow was measured using pulsed Doppler ultrasound in 6 dogs before and after left portal vein branch ligation. Mean portal vein blood flow velocity and mean portal vein blood flow were significantly reduced after ligation and the congestion index was increased (p < 0.01). Pulsed Doppler ultrasound studies provide valuable physiological information which may assist the clinician with the diagnosis of canine hepatic circulatory disorders.  (+info)

Colorectal liver metastasis thymidylate synthase staining correlates with response to hepatic arterial floxuridine. (3/997)

We assessed whether intensity of colorectal liver metastasis staining with the thymidylate synthase (TS) antibody TS106 predicted response to hepatic arterial infusion (HAI) of floxuridine chemotherapy. Liver metastasis biopsies were taken during laparotomy for hepatic arterial cannulation and stained using the TS106 monoclonal antibody. Staining intensity was designated at histological examination by two independent assessors as either "high" or "low." Patients were treated by HAI, and liver metastasis response was assessed by comparison of computed tomography scan tumor volume before and after 4 months of treatment. A significant correlation (Fisher's exact test, P = 0.01) was noted between partial response to HAI and TS106 staining intensity in patients with colorectal liver metastases. Seventy-five percent of patients with evidence of a partial response had low TS staining compared with 29% of nonresponders. There was a significant difference (Fisher's exact test, P = 0.01) in the proportion of low (9 of 16) compared with high (3 of 20) TS staining tumors in which a partial response occurred. There was no significant difference (logrank test, P = 0.4) in survival from hepatic cannulation and HAI treatment of high (median, 322 days; interquartile range, 236-411) compared with low (median, 335 days; interquartile range, 301-547) TS staining patients. This study demonstrates an inverse correlation between TS immunohistochemical staining intensity in colorectal liver metastases and response to HAI. The results suggest that a prospective assessment of TS staining intensity in colorectal liver metastases would be useful to determine whether this method can be used to define patients who will benefit from HAI chemotherapy.  (+info)

A phase I/II study of continuous intra-arterial chemotherapy using an implantable reservoir for the treatment of liver metastases from breast cancer: a Japan Clinical Oncology Group (JCOG) study 9113. JCOG Breast Cancer Study Group. (4/997)

BACKGROUND: Liver metastasis from breast cancer has a poor prognosis. While there are some reports of good response rates of hepatic metastasis from breast cancer by hepatic intra-arterial infusion chemotherapy, no phase I study including pharmacokinetic analysis has been reported. We performed a phase I/II study of intra-arterial infusion chemotherapy using adriamycin and 5-fluorouracil to find the maximum tolerated dose and response rate in patients with advanced or recurrent breast cancer. METHODS: A hepatic arterial catheter with an access port was inserted into the proper hepatic artery. Patients received 30 mg/m2 adriamycin on days 1 and 8 and 100 mg/m2 5-fluorouracil at level 1, 200 mg/m2 at level 2,300 mg/m2 at level 3 and 400 mg/m2 at level 4 continuously from day 1 through day 14 every 28 days. At least two cycles were required before evaluation. Twenty-eight patients were entered into this study and 26 patients were evaluable. Seventeen patients had hepatic metastasis only, although nine patients had additional metastasis to other sites. RESULTS: Dose-limiting toxicity of thrombocytopenia and neurotoxicity occurred at level 4. Leukocytopenia (ECOG grade 3-4) was observed in five (19%), thrombocytopenia in three (12%) and anemia in two (8%) patients. There were 11 catheter-related complications which were not dose dependent. Seven out of 13 evaluable patients (54%) responded at level 3. The median duration of response was 5.8 months (range, 1-23+) and median survival was 25.3 months (range, 6.2-54.7+). CONCLUSION: Hepatic arterial infusion therapy appears to be safe and effective but catheter-related complications must be overcome before starting a phase III trial.  (+info)

Preserved arterial flow secures hepatic oxygenation during haemorrhage in the pig. (5/997)

1. This study examined the extent of liver perfusion and its oxygenation during progressive haemorrhage. We examined hepatic arterial flow and hepatic oxygenation following the reduced portal flow during haemorrhage in 18 pigs. The hepatic surface oxygenation was assessed by near-infrared spectroscopy and the hepatic metabolism of oxygen, lactate and catecholamines determined the adequacy of the hepatic flow. 2. Stepwise haemorrhage until circulatory collapse resulted in proportional reductions in cardiac output and in arterial, central venous and pulmonary wedge pressures. While heart rate increased, pulmonary arterial pressure remained stable. In addition, renal blood flow decreased, renal vascular resistance increased and there was elevated noradrenaline spill-over. Further, renal surface oxygenation was lowered from the onset of haemorrhage. 3. Similarly, the portal blood flow was reduced in response to haemorrhage, and, as for the renal flow, the reduced splanchnic blood flow was associated with an elevated noradrenaline spill-over. In contrast, hepatic arterial blood flow was only slightly reduced by haemorrhage, and surface oxygenation did not change. The hepatic oxygen uptake was maintained until the blood loss represented more than 30 % of the estimated blood volume. At 30 % reduced blood volume, hepatic catecholamine uptake was reduced, and the lactate uptake approached zero. 4. Subsequent reduction of cardiac output and portal blood flow elicited a selective dilatation of the hepatic arterial vascular bed. Due to this dilatation liver blood flow and hepatic cell oxygenation and metabolism were preserved prior to circulatory collapse.  (+info)

Hepatosplanchnic haemodynamics and renal blood flow and function in rats with liver failure. (6/997)

BACKGROUND: Massive liver necrosis, characteristic of acute liver failure, may affect hepatosplanchnic haemodynamics, and contribute to the alterations in renal haemodynamics and function. AIMS: To investigate the relation between hepatosplanchnic haemodynamics, including portal systemic shunting, and renal blood flow and function in rats with acute liver failure. METHODS: Liver failure was induced in male Wistar rats by intraperitoneal injection of 1.1 g/kg of D(+)-galactosamine hydrochloride. The parameters assessed included; systemic, hepatosplanchnic, and renal blood flow (57Co microsphere method); portal-systemic shunting and intrarenal shunting (consecutive intrasplenic, intraportal, or renal arterial injections of 99mTc methylene diphosphonate and 99mTc albumin microspheres); arterial blood pressure and portal pressure; renal function; and liver function (liver function tests and 14C aminopyrine breath test). RESULTS: Progressive liver dysfunction was accompanied by the development of a hyperdynamic circulation, a highly significant decrease in renal blood flow and function, and an increase in intrarenal shunting 36, 42, and 48 hours after administration of D-galactosamine. The alterations in renal blood flow and function were accompanied by significant increases in portal pressure, portal venous inflow, and intrahepatic portal systemic shunting in galactosamine treated rats compared with controls. There was a significant correlation between changes in renal blood flow and changes in portal pressure, intrahepatic portal systemic shunting, and deterioration in liver function (r = 0.8, p < 0.0001). CONCLUSIONS: The results of this study suggest that both increased intrahepatic portal systemic shunting and hepatocyte impairment may contribute to alterations in renal haemodynamics and function.  (+info)

Effect of a selective rise in hepatic artery insulin on hepatic glucose production in the conscious dog. (7/997)

In the present study we compared the hepatic effects of a selective increase in hepatic sinusoidal insulin brought about by insulin infusion into the hepatic artery with those resulting from insulin infusion into the portal vein. A pancreatic clamp was used to control the endocrine pancreas in conscious overnight-fasted dogs. In the control period, insulin was infused via peripheral vein and the portal vein. After the 40-min basal period, there was a 180-min test period during which the peripheral insulin infusion was stopped and an additional 1.2 pmol. kg-1. min-1 of insulin was infused into the hepatic artery (HART, n = 5) or the portal vein (PORT, n = 5, data published previously). In the HART group, the calculated hepatic sinusoidal insulin level increased from 99 +/- 20 (basal) to 165 +/- 21 pmol/l (last 30 min). The calculated hepatic artery insulin concentration rose from 50 +/- 8 (basal) to 289 +/- 19 pmol/l (last 30 min). However, the overall arterial (50 +/- 8 pmol/l) and portal vein insulin levels (118 +/- 24 pmol/l) did not change over the course of the experiment. In the PORT group, the calculated hepatic sinusoidal insulin level increased from 94 +/- 30 (basal) to 156 +/- 33 pmol/l (last 30 min). The portal insulin rose from 108 +/- 42 (basal) to 192 +/- 42 pmol/l (last 30 min), whereas the overall arterial insulin (54 +/- 6 pmol/l) was unaltered during the study. In both groups hepatic sinusoidal glucagon levels remained unchanged, and euglycemia was maintained by peripheral glucose infusion. In the HART group, net hepatic glucose output (NHGO) was suppressed from 9.6 +/- 2.1 micromol. kg-1. min-1 (basal) to 4.6 +/- 1.0 micromol. kg-1. min-1 (15 min) and eventually fell to 3.5 +/- 0.8 micromol. kg-1. min-1 (last 30 min, P < 0.05). In the PORT group, NHGO dropped quickly (P < 0.05) from 10.0 +/- 0.9 (basal) to 7.8 +/- 1.6 (15 min) and eventually reached 3.1 +/- 1.1 micromol. kg-1. min-1 (last 30 min). Thus NHGO decreases in response to a selective increase in hepatic sinusoidal insulin, regardless of whether it comes about because of hyperinsulinemia in the hepatic artery or portal vein.  (+info)

Total and functional hepatic blood flow decrease in parallel with ageing. (8/997)

OBJECTIVES: To study changes in hepatic blood flow with age. DESIGN: Functional hepatic flow (FHF) and total hepatic flow (THF) were determined by non-invasive methods in 40 normal subjects in four age groups (<45, 45-60, 61-75 and >75 years). All subjects had normal routine liver function tests and no history of liver disease. RESULTS: THF was measured by pulsed echo-Doppler, as the sum of portal and hepatic artery blood flow; FHF was measured by the hepatic clearance of D-sorbitol. THF significantly decreased with age, particularly in subjects over 75 (from 1445+/-220 ml/min to 1020+/-148; P<0.001), and a similar reduction was observed in FHF (from 1514+/-250 ml/min to 1015+/-163; P<0.001). THF and FHF were strictly correlated in the whole population (r = 0.871; P<0.001) and both correlated with age (r = -0.510 and r = -0.596; P<0.005). CONCLUSION: With ageing there is a reduction of hepatic blood flow without any additional intrahepatic shunting.  (+info)