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Cytochrome P-450 gene expression in the functional units of the fetal liver.

Hepatocytes of the right and left lobes of the fetal liver are surrounded by different microenvironments. The right and left lobes of the fetal liver are perfused by vascular systems carrying different concentrations of oxygen and constitute distinct functional units. The aim of this study was to assess the expression of the phenobarbital-inducible cytochrome P-450 b,e genes in hepatocytes of the right and left fetal liver lobes in mice. Northern-blot analysis using [32P]cDNAs and quantitative dot-blot hybridization were performed to assess the size and levels of these mRNAs in the right and left fetal liver lobes. In fetal mice, the levels of cytochrome P-450, b,e mRNAs were higher in the left than in the right fetal liver lobe. During the last days of gestation and in the immediate postnatal period, the levels of liver cytochrome P-450 b,e mRNAs increased predominantly in the left liver lobe. In contrast, the levels of albumin and alpha-fetoprotein mRNAs (genes studied to assess the specificity of these findings) were similar in each of functional units of the fetal liver. Phenobarbital induction of cytochromes P-450 b,e mRNAs was not observed in either of the fetal liver lobes. Postnatally, phenobarbital induced these cytochromes similarly in the right and left liver lobes. Therefore, the microenvironment surrounding fetal hepatocytes seems to influence the expression of the cytochrome P-450 b,e genes. This lobar heterogeneity of expression disappears as the pattern of adult liver circulation is attained.

Animals↗

Cardiac output and liver blood flow in humans: effect of the volatile anesthetic halothane.

In 40 men with normal circulatory and liver function, from whom 10 were undergoing general anesthesia with halothane for minor orthopedic surgery, the relationship between hemodynamic parameters and total hepatic blood flow (HBF) was investigated. Cardiac output (CO) was measured noninvasively by means of the thoracic electrical bioimpedance method, systemic arterial blood pressure (BPsys, BPdia, mean arterial pressure) by an automated oscillometric device and HBF by indocyanine green clearance. In the subjects without halothane anesthesia no relationship was found between BP and HBF, but a significant correlation could be seen between CO and HBF, whereby the fraction of HBF decreased with increasing CO. In contrast, in the presence of halothane the systemic arterial blood pressure correlated with the HBF, indicating a loss of autoregulation of the liver circulation.

Adult↗

Noninvasive ICG clearance test for estimating hepatic blood flow during halothane and isoflurane anaesthesia.

The purpose of this study was to estimate hepatic blood flow during halothane (HAL) or isoflurane (ISO) anaesthesia with the noninvasive indocyanine green (ICG) clearance test. Twenty-four ASA status I adult patients, scheduled for elective surgery without liver disease, were allocated into four groups. Before surgery, ICG clearance was measured twice in patients before and after 1, 2 MAC HAL-N2O, 1 and 2 MAC ISO-N2O anaesthesia by ICG clearance meter (Sumitomo Electronics, Japan). This method eliminates the blood sampling and delay of the conventional ICG test. The ICG clearance is displayed in two indices: K (ICG disappearance rate) and R15 (ICG retention rate 15 min after 0.5 mg.kg-1 ICG injection). Indirect blood pressure and heart rate were measured simultaneously. Mean arterial pressure (MAP) decreased by 27, 22 and 29% with 2 MAC HAL-N2O, and with 1 and 2 MAC ISO-N2O groups, respectively (P < 0.05). The ICG clearance was less (P < 0.05) in the 2 MAC HAL-N2O group (K, 0.087 min-1) than with either awake (K, 0.131 min-1) or other groups (K, 0.114 and 0.144 min-1, in the 1 MAC HAL and ISO-N2O groups, respectively) in spite of a similar degree of the depletion of MAP in 2 MAC ISO-N2O group (K, 0.124 min-1). We conclude that isoflurane has a more favourable effect on liver circulation than does halothane.

Adult↗

Hepatic blood flow after acute biliary obstruction and drainage in conscious dogs.

BACKGROUND AIMS: Obstructive jaundice is a factor which effects hepatic blood flow and the relative contribution of the hepatic arterial flow and portal venous flow. In this study, and were measured in conscious dogs and the influence of biliary obstruction and drainage was investigated. MATERIAL AND METHODS: Hepatic arterial flow (HAF) and portal venous flow (PVF) after biliary obstruction and subsequent drainage were continuously measured in conscious dogs using implantable transit time ultrasonic flow-meters. RESULTS: After biliary obstruction hepatic arterial flow rapidly increased compared to the pre-obstructed values(p < 0.01), while portal venous flow was significantly decreased (p < 0.01). Total hepatic blood flow was initially increased (p < 0.01) until 2 hours after obstruction. It then decreased gradually. After 2 weeks, it was less than the pre-obstructed values, but this was not significant. Biliary drainage was performed after 2 weeks. Hepatic arterial flow subsequently decreased (p < 0.01) and portal venous flow increased (p < 0.05). Blood flow did not change. CONCLUSION: Biliary obstruction resulted in significant changes in liver circulation. Biliary drainage facilitated recovery from these changes.

Animals↗

[Abdominal Doppler sonography in childhood].

With the help of pulsed Doppler sonography and colour coded Doppler sonography noninvasive measurements of blood flow within the abdominal vessels are possible. Cystic and tubular abdominal masses and vascular structures can be differentiated. Laminar and turbulent flow as well as arterial and venous flow can be distinguished. The direction of blood flow can be shown. Regarding liver circulation Doppler sonography of portal hypertension, portal vein thrombosis, veno-occlusive-disease, Budd-Chiari-Syndrome and transplant rejection or other vascular complications after liver transplantation can be shown. The circulation of the spleen should be examined if aneurysms, thrombosis or portal hypertension are suspected. Mesenterial circulation should be investigated in suspected vascular occlusion, arterial stenosis and necrotizing enterocolitis. Renal Doppler sonography is helpful for the diagnosis of renal artery stenosis, arterio-venous fistulas, renal vein thrombosis and acute transplant rejection.

Abdomen↗

Splanchnic vascular responses to the infusion of prostaglandins A1, A2 and B1.

The effects of PGA1, PGA2 and PGB1 on the vasculature of the liver and small intestine were studied in 73 dogs. Infusions were made into a branch of the superior mesenteric artery, the hepatic artery, portal vein or femoral vein. They decreased systemic arterial pressure and dilated the hepatic arterial and prehepatic splanchnic (small intestinal) vascular beds, PGA being most active. Dilator response was not decreased by beta-adrenergic blockade. Compounds appear to be inactivated by liver and decreased systemic pressure less when infused directly into liver circulation. Dilator response was transient, particulary in small intestine, and abated or even converted to constriction when infusion was continued for a period of time. Intrahepatic portal venous vasculature appeared to be constricted by PGA.

Animals↗

The effect of enteral oxygen administration on the hepatic circulation during halothane anaesthesia: experimental investigations.

An investigation of the hepatic microcirculation and oxygen tension in 20 white rats showed that halothane anaesthesia was associated with a reduction in the diameter of the terminal portal venous branches, sinusoids and central veins, and with a decrease in the hepatic oxygen tension from 28.8+/-4.8 to 22.4+/-3.9 mmHg (mean +/-SEM). Enteral oxygen administration was followed by an increased blood flow in all the observed vessels, by an increase in the number of simultaneously filled sinusoids and also by an increase in the hepatic oxygen tension to 35.2+/-10.1 mm Hg. Subsequently, changes in blood flow in the hepatic artery and portal vein were investigated in 10 cats by cineangiography. During inhalation of halothane the hepatic artery blood flow was observed to increase by 30%, while portal vein blood flow was found to decrease by 57% of the initial value. Thus total hepatic blood flow was reduced by 40%, with the ratio of hepatic artery blood flow to total hepatic blood flow increasing from 19% to 43%. When enteral oxygen was administered, the total hepatic blood flow was restored to 92% of the value before anaesthesia. This resulted from an increase in the portal blood flow fraction only. It is concluded that disturbances in the liver circulation in cats and rats produced by halothane anaesthesia can be modified by the simultaneous administration of enteral oxygen.

Anesthesia, Inhalation↗

[Liver-specific lipoprotein component level in circulating immune complexes in liver diseases].

The examinations have involved 177 subjects (80 of these were regularly examined for a year), 148 of them suffering from acute or chronic diseases of the liver and 29 normal subjects. Circulating immune complexes (CIC) containing specific liver lipoprotein (SLL) were detected by the enzyme-binding immunosorption complement-fixation test. SLL CICs are most frequently detectable in the patients with acute hepatitis B (in 19 of 48), with chronic active autoimmune hepatitis (in 8 of 9), and with primary biliary cirrhosis of the liver (in 18 of 20 patients).

Adult↗

Hemodynamic changes after ligation of a major branch of the portal vein in rats: comparison with rats with portal vein constriction.

In chronic portal-hypertensive rat models, such as portal vein constriction or cirrhosis, the portal blood flow that effectively perfuses the hepatocytes is substantially reduced because of anatomical or functional shunts. It is possible therefore that a feedback mechanism from the liver to the splanchnic bed is responsible for the splanchnic hyperemia observed in chronic portal hypertension. To investigate the possible role of such a feedback mechanism, we examined the chronological changes in both portal and systemic hemodynamics in rats after ligation of a major branch of the portal vein that supplies about 80% of the liver circulation. Rats submitted to sham surgery and portal vein-constricted rats were also studied. Blood flow and portal-systemic shunting were measured by radioactive microsphere techniques. For 7 days after portal-branch ligation, transient portal hypertension resulted from an elevated portal resistance. However, no significant changes in portal venous inflow or splanchnic arteriolar resistance were found in the portal branch-ligated rats, whereas in the portal vein-constricted rats significant hyperdynamic changes in these parameters were noted. On the other hand, transient hyperdynamic changes occurred in the systemic circulation during the period from the fourth to the sixth day after portal-branch ligation, similar to those observed in the portal vein-constricted rats. The lack of hyperdynamic changes in the portal territory of the portal branch-ligated rats suggests that the splanchnic hyperemia found in chronic portal-hypertensive states is unlikely to be caused by a feedback mechanism from the ischemic hepatic parenchyma.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Combined evaluation of total and functional liver plasma flows and intrahepatic shunting.

A diagnostic protocol was studied, designed to evaluate the main parameters of liver circulation in man. A water solution of D-sorbitol (S) and indocyanine green (ICG) was infused intravenously in six controls and nine cirrhotics. Steady-state renal and hepatic S clearances as well as hepatic ICG clearance were calculated. In controls the values (mean +/- SD) of the independent measurements of S and ICG hepatic clearance were 978 +/- 107 and 519 +/- 142 ml/min, respectively, while in cirrhotic patients they were 554 +/- 238 and 231 +/- 90 ml/min. Owing to the kinetic properties of S, its hepatic clearance may be regarded as a measure of functional liver plasma flow (FLPF). The total liver plasma flow (TLPF) values (mean +/- SD), calculated according to Fick's principle, were 1091 +/- 157 ml/min (S method) and 1033 +/- 153 ml/min (ICG method) in controls, and 1251 +/- 554 and 1284 +/- 677 ml/min in cirrhotics. In controls, FLPF was found to be very close to TLPF. In cirrhotic patients the difference between TLPF and FLPF (ranging from 169 to 2093 ml/min when measured by S method) was considered as an approximate estimate of intrahepatic shunting. The procedure is safe and simple and may add a new dimension to the investigation of hepatic circulation.

Adult↗

Nitroprusside prevents adverse hemodynamic effects of vasopressin.

The influence of vasopressin and sodium nitroprusside on liver circulation was investigated in 18 dogs. Cardiac output was determined by the thermal dilution technique using a Swan-Ganz catheter. Hepatic artery and portal vein flows were measured with electromagnetic flowmeters. The infusion of vasopressin (0.01 unit/kg/min) caused a 13% increase in mean arterial pressure, a 38% decrease in cardiac output, a 57% decrease in portal blood flow, and a 35% decrease in portal pressure. Hepatic artery blood flow initially decreased, then increased, and eventually exceeded the baseline value by 25%. The addition of sodium nitroprusside infusion (10 microgram/kg/min) returned the mean arterial pressure to baseline value and increased cardiac output to 83% of baseline value. Portal blood flow remained unchanged, even though an additional decrease in portal pressure of 11% and a further increase in hepatic artery blood flow of 45% were observed. Nitroprusside minimizes the undesirable effects of vasopressin and augments the desirable ones in normal dogs. The combination of these drugs may be more beneficial to patients with esophageal and gastrointestinal bleeding than vasopressin alone.

Animals↗

Circulating neutrophils and liver injury in rat models of experimental alcoholic liver disease.

The present study examined the relationship between circulating neutrophils and liver injury in two widely used rat models of chronic ethanol administration. Hematological alterations, liver histopathology, and biochemical indices of liver injury were assessed in rats receiving chronic ethanol by oral liquid diet feeding (Lieber-DeCarli method) or by continuous intragastric infusion (Tsukamoto-French method). Oral administration of ethanol did not affect circulating neutrophil counts, but resulted in minimal liver injury characterized by elevated serum alanine aminotransferase (79%), increased liver mass (15%), and moderate steatosis. In contrast, rats receiving ethanol by continuous intragastric infusion showed an approximately 2-fold increase in circulating neutrophils, and a moderate degree of liver injury, indicated by a 169% elevation of serum alanine aminotransferase and a 2-fold increase in liver mass. Liver biopsies from these rats showed severe steatosis and scattered necrotic hepatocytes, and some neutrophil infiltrates. To determine whether an increase in the number of circulating neutrophils could potentiate liver injury induced by oral ethanol feeding, rats were treated with human recombinant granulocyte colony-stimulating factor at a dose of 100 microg/kg/day (s.c.) for 4 days. Treatment with granulocyte colony-stimulating factor resulted in a 6- to 9-fold increase in circulating neutrophil counts. Nevertheless, this change did not enhance the minor degree of ethanol-induced liver injury in this model. Our results indicate that, whereas neutrophil leukocytosis accompanies more severe manifestations of ethanol hepatotoxicity in rats, this condition per se does not directly induce or exacerbate ethanol-induced liver injury.

Animals↗