Hepatic Venous Plasma Research Articles

Binge drinking episode causes acute, specific alterations in systemic and hepatic inflammation-related markers.

Frequent binge drinking is a known contributor to alcohol-related harm, but its impact on systemic and hepatic inflammation is not fully understood. We hypothesize that changes in immune markers play a central role in adverse effects of acute alcohol intake, especially in patients with early liver disease. To investigate the effects of acute alcohol intoxication on inflammation-related markers in hepatic and systemic venous plasma in people with alcohol-related liver disease (ArLD), non-alcoholic fatty liver disease (NAFLD) and healthy controls. Thirty-eight participants (13 with ArLD, 15 with NAFLD and 10 healthy controls) received 2.5 mL of 40% ethanol per kg body weight via a nasogastric tube. Seventy-two inflammation-related markers were quantified in plasma from hepatic and systemic venous blood, at baseline, 60 and 180 min after intervention. Alcohol intervention altered the levels of 31 of 72 and 14 of 72 markers in the systemic and hepatic circulation. All changes observed in the hepatic circulation were also identified in the systemic circulation after 180 min. Only FGF21 and IL6 were increased after alcohol intervention, while the remaining 29 markers decreased. Differences in response to acute alcohol between the groups were observed for 8 markers, and FGF21 response was blunted in individuals with steatosis. Acute alcohol intoxication induced changes in multiple inflammation-related markers, implicated in alcohol metabolism and hepatocellular damage. Differences identified between marker response to binge drinking in ArLD, NAFLD and healthy controls may provide important clues to disease mechanisms and potential targets for treatment. NCT03018990.

Diagnosis and management of hypertension understanding imperative role of various biomarkers

As hypertension, almost 90% of cases of hypertension with an unknown origin called essential hypertension, continue to be one of the most important risk factors for various fatal health conditions, its early diagnosis using trustworthy biomarkers to predict, diagnose, and monitor the therapeutic progress of hypertension is proving to be of utmost importance for the preventive as well as curative purpose of various health hazards. A rise in the activity of biochemical markers of endothelial dysfunction and blood lipids, notablyLow-density lipoprotein (LDL) andverylow-density lipoprotein(VLDL)measurements, and inflammation markers including C-reactive protein(CRP), cytokines, and adhesion molecules are linked to the development of hypertension. Growth and differentiation factor-15, red cell distribution width, uric acid, creatinine, inflammatory markers including interleukin-6, angiopoietins, and microRNAs are prognostic indicators in individuals with pulmonary arterial hypertension (PAH).The most extensively used blood markers for portal hypertension (PH) are the fibrosis-4 index and the improved liver fibrosis test. Likewise, Hepatic venous pressure gradient (HVPG), liver/SSMs and Plasma cyclic guanosine monophosphate (cGMP) being clinically significant tools to assess for PH. Along with Copeptin, serum levels of uric acid, potassium, and sodium may be crucial for the identification and monitoring of hypertension in pediatrics.Similarly, the severity of gestational hypertension correlates with hyperuricemia, elevated CRP, and interleukin-1 serum levels. Here, in this study, literature on biomarkers has been reviewed which are versatile diagnostic tools posing that influence healthcare professionals’ judgment and assist in patient education regarding diagnosis, prognosis, early detection, and treatment intervention.

Lipopolysaccharide-Induced Neutrophil Dysfunction Following Transjugular Intrahepatic Portosystemic Stent Shunt (TIPSS) Insertion is Associated with Organ Failure and Mortality

Systemic lipopolysaccharide (LPS) is implicated in increasing mortality in patients with alcoholic hepatitis but the underlying mechanisms are not well characterised. The objective of this study was to characterise neutrophil function, LPS and cytokine concentrations within the splanchnic circulation of alcoholic cirrhotic patients undergoing TIPSS insertion for variceal haemorrhage and correlate this with outcome. 26 patients with alcoholic cirrhosis and variceal haemorrhage were studied prior to and 1-hour after TIPSS insertion. Neutrophil function, LPS and cytokine concentrations were determined in arterial, hepatic venous (HV) and portal venous blood (PV). Significantly higher LPS concentrations and neutrophil reactive oxidant species (ROS) production were observed in PV vs HV blood. Cross-incubation of HV plasma with PV neutrophils resulted in reduced ROS production. Insertion of TIPSS was associated with a significant increase in arterial LPS concentrations and deterioration in neutrophil phagocytosis. Number of organ failures and arterial IL-6 concentrations at presentation were associated with increased mortality. The portal circulation has a distinct immunological milieu characterised by a pathological neutrophil phenotype and an anti-inflammatory cytokine profile associated with heightened LPS levels. TIPSS insertion renders this neutrophil functional defect systemic, associated with an increase in arterial LPS and a susceptibility to sepsis.

Butyrylated starch affects colorectal cancer markers beneficially and dose-dependently in genotoxin-treated rats

Population studies suggest that greater dietary fiber intake may lower colorectal cancer (CRC) risk, possibly through the colonic bacterial fermentative production of butyrate. Butyrylated starch delivers butyrate to the colon of humans with potential to reduce CRC risk but high doses may exacerbate risk through promoting epithelial proliferation. Here we report the effects of increasing dietary butyrylated high amylose maize starch (HAMSB) on azoxymethane (AOM) induced distal colonic DNA damage, cell proliferation, mucus layer thickness and apoptosis in rats. Five groups of 15 rats were fed AIN-93G based diets containing 0–40% HAMSB for 4 weeks then injected with (AOM) and killed 6 hours later. Large bowel total SCFA, acetate and butyrate pools and hepatic portal venous plasma total SCFA, acetate and butyrate concentrations were higher with greater HAMSB intake. Distal colonic epithelial apoptotic index and colonic mucus thickness increased, while DNA single strand breaks decreased dose-dependently with greater HAMSB intake. Colonocyte proliferation rates were unaffected by diet. These data suggest that increasing large bowel butyrate may reduce the risk of CRC in a dose dependent manner by enhancing apoptotic surveillance in the colonic epithelium for damaged cells without promoting the risk of tumorigenesis through increased cell proliferation.

TIMP-1 in patients with cirrhosis: relation to liver dysfunction, portal hypertension, and hemodynamic changes

Objective. Cirrhotic portal hypertensive patients often develop hemodynamic complications and the diagnosis is often based on liver biopsy and measurements of the hepatic venous pressure gradient (HVPG). Potential noninvasive biomarkers for the severity of cirrhosis are the matrix metalloproteinase and their specific inhibitors such as tissue inhibitor of metalloproteinases-1 (TIMP-1). The aim of the study was to investigate TIMP-1 levels in cirrhosis in relation to the degree of liver dysfunction, portal hypertension, and hemodynamic changes. Materials and methods. We retrospectively studied 84 patients with cirrhosis and 14 controls without liver disease. All individuals underwent a liver vein catheterization with a hemodynamic assessment. TIMP-1 was determined in arterial and hepatic venous plasma using an MAC-15 TIMP-1 ELISA. Results. Hepatic venous concentrations of TIMP-1 were significantly increased in patients compared to controls: 336 (166) ng/ml versus 145 (100) (median/IQ range) (p < 0.001) with a progressive increase throughout the Child classes (p < 0.001). Circulating TIMP-1 correlated significantly with indocyanine green clearance (r = –0.44, p < 0.0001), Child Turcotte score (r = 0.50, p < 0.0001), HVPG (r = 0.40, p < 0.0001), mean arterial pressure (r = –0.29, p = 0.008), and systemic vascular resistance (r = –0.23, p = 0.03). Receiver operating characteristic curve analysis enabled us to establish cutoff values for TIMP-1 with regard to portal hypertension. Conclusions. TIMP-1 is significantly increased in patients with cirrhosis and correlates with the severity of the disease, degree of portal hypertension, and vasodilatory state. TIMP-1 is therefore a promising new noninvasive marker to predict hemodynamic-related complications in cirrhosis.

Influence of the para-aminohippuric acid analysis method on the net hepatic flux of nutrients in lactating cows1

Para-aminohippuric acid (pAH) is a marker frequently used to measure plasma or blood flow. In sheep studies, it is recognized that its determination must include a deacetylation step to counteract the hepatic acetylation of pAH. Such a procedure is not of common usage in cattle studies although a recent suggestion of hepatic pAH acetylation in dairy cows may have important consequences for hepatic nutrient fluxes. The aims of this study were to evaluate pAH analytical methods according to international procedures of metrology and confirm hepatic acetylation of pAH in dairy cows. The effect of the matrix used to prepare the standard curve was tested, and the influence of the pAH analytical method on blood flows and subsequent net hepatic fluxes of nutrients was determined. For the first objective, accuracy profiles were established and bias, indicators of precision, and limits of quantification were reported for 2 analytical methods (without and with a pAH deacetylation step) using 2 different standard matrices (water and plasma). Second, the net hepatic flux of different nutrients was determined including or not the deacetylation step and preparing the standard curves in plasma using samples collected from 5 multicatheterized lactating Jersey cows. The choice of the matrix had a significant impact on plasma pAH concentrations as illustrated by accuracy profiles. Water matrix decreased (P < 0.01) the slope, y-intercept, and the absorbance at concentration 0 mg pAH/L of the standard curve in both methods (without and with the deacetylation), supporting that standards prepared in water should not be used to analyze plasma samples. Samples collected on cows confirmed hepatic acetylation of pAH across the liver. Deacetylation, performed using plasma as the standard matrix, increased (P < 0.05) plasma pAH concentrations from 18.4, 26, and 23.5 to 21.4, 28.9, and 27.3 mg/L in the artery, portal vein, and hepatic vein, respectively. Deacetylation decreased the hepatic venous and arterial plasma and blood flows (P < 0.05) by 9 and 55%, respectively, modifying the net hepatic flux of acetate, total amino acid, and oxygen by more than 19% (P < 0.05). In conclusion, our results highlight the importance of including a deacetylation step in the pAH analysis method in cattle studies and of using plasma as standard matrix.

Human taurine metabolism: fluxes and fractional extraction rates of the gut, liver, and kidneys

Taurine is involved in numerous biological processes. However, taurine plasma level decreases in response to pathological conditions, suggesting an increased need. Knowledge on human taurine metabolism is scarce and only described by arterial-venous differences across a single organ. Here we present taurine organ fluxes using arterial-venous concentration differences combined with blood flow measurements across the 3 major organ systems involved in human taurine metabolism in patients undergoing hepatic surgery. In these patients, we collected blood from an arterial line, portal vein, hepatic vein, and renal vein, and determined blood flow of the hepatic artery, portal vein, and renal vein using Doppler ultrasound. Plasma taurine was determined by high-performance liquid chromatography, and net organ fluxes and fractional extraction rates were calculated. Seventeen patients were studied. No differences were found between taurine concentrations in arterial, portal venous, hepatic venous, and renal venous plasma. The only significant finding was a release of taurine by the portally drained viscera (P = .04). Our data show a net release of taurine by the gut. This probably is explained by the enterohepatic cycle of taurine. Future studies on human taurine metabolism are required to determine whether taurine is an essential aminosulfonic acid during pathological conditions and whether it should therefore be supplemented.

Butyrate delivered by butyrylated starch increases distal colonic epithelial apoptosis in carcinogen-treated rats

Animal studies show that increasing large bowel butyrate concentration through ingestion of butyrylated or resistant starches opposes carcinogen-induced tumorigenesis, which is consistent with population data linking greater fiber consumption with lowered colorectal cancer (CRC) risk. Butyrate has been shown to regulate the apoptotic response to DNA damage. This study examined the impact of increasing large bowel butyrate concentration by dietary butyrylated starch on the colonic epithelium of rats treated with the genotoxic carcinogen azoxymethane (AOM). Four groups of 10 male rats were fed AIN-93G based-diets containing either low amylose maize starch (LAMS), LAMS with 3% tributyrin, 10% high amylose maize starch (HAMS) or 10% butyrylated HAMS (HAMSB). HAMS and HAMSB starches were cooked by heating in water. After 4 weeks, rats were injected once with AOM and killed 6 h later. Rates of apoptosis and proliferation were measured in colonic epithelium. Short-chain fatty acid concentrations in large bowel digesta and hepatic portal venous plasma were higher in HAMSB than all other groups. Apoptotic rates in the distal colon were increased by HAMSB and correlated with luminal butyrate concentrations but cellular proliferation rates were unaffected by diet. The increase in apoptosis was most marked in the base and proliferative zone of the crypt. Regulation of luminal butyrate using HAMSB increases the rates of apoptotic deletion of DNA-damaged colonocytes. We propose this pro-apoptotic function of butyrate plays a major role reducing tumour formation in the AOM-treated rat and that these data support a potential protective role of butyrate in CRC.

Effect of abomasal glucose infusion on plasma concentrations of gut peptides in periparturient dairy cows

Six Holstein cows fitted with ruminal cannulas and permanent indwelling catheters in the portal vein, hepatic vein, mesenteric vein, and an artery were used to study the effects of abomasal glucose infusion on splanchnic plasma concentrations of gut peptides. The experimental design was a randomized block design with repeated measurements. Cows were assigned to one of 2 treatments: control or infusion of 1,500g of glucose/d into the abomasum from the day of parturition to 29 d in milk. Cows were sampled 12±6 d prepartum and at 4, 15, and 29 d in milk. Concentrations of glucose-dependent insulinotropic polypeptide, glucagon-like peptide 1(7–36) amide, and oxyntomodulin were measured in pooled samples within cow and sampling day, whereas active ghrelin was measured in samples obtained 30min before and after feeding at 0800h. Postpartum, dry matter intake increased at a lower rate with infusion compared with the control. Arterial, portal venous, and hepatic venous plasma concentrations of the measured gut peptides were unaffected by abomasal glucose infusion. The arterial, portal venous, and hepatic venous plasma concentrations of glucose-dependent insulinotropic polypeptide and glucagon-like peptide 1(7–36) amide increased linearly from 12 d prepartum to 29 d postpartum. Plasma concentrations of oxyntomodulin were unaffected by day relative to parturition. Arterial and portal venous plasma concentrations of ghrelin were lower postfeeding compared with prefeeding concentrations. Arterial plasma concentrations of ghrelin were greatest prepartum and lowest at 4 d postpartum, giving a quadratic pattern of change over the transition period. Positive portal venous-arterial and hepatic venous–arterial concentration differences were observed for glucagon-like peptide 1(7–36) amide. A negative portal venous–arterial concentration difference was observed for ghrelin pre-feeding. The remaining portal venous–arterial and hepatic venous–arterial concentration differences of gut peptides did not differ from zero. In conclusion, increased postruminal glucose supply to postpartum transition dairy cows reduced feed intake relative to control cows, but did not affect arterial, portal venous, or hepatic venous plasma concentrations of gut peptide hormones. Instead, gut peptide plasma concentrations increased as lactation progressed. Thus, the lower feed intake of postpartum dairy cows receiving abomasal glucose infusion was not attributable to changes in gut peptide concentrations.

Splanchnic Balance of Free Fatty Acids, Endocannabinoids, and Lipids in Subjects With Nonalcoholic Fatty Liver Disease

Animal studies suggest that endocannabinoids could contribute to the development of nonalcoholic fatty liver disease (NAFLD). In addition, NAFLD has been shown to be associated with multiple changes in lipid concentrations in liver biopsies. There are no data on splanchnic free fatty acid (FFA), glycerol, ketone body, endocannabinoid, and lipid fluxes in vivo in subjects with NAFLD. We performed hepatic venous catheterization studies in combination with [(2)H(2)]palmitate infusion in the fasting state and during a low-dose insulin infusion in 9 subjects with various degrees of hepatic steatosis as determined using liver biopsy. Splanchnic balance of endocannabinoids and individual lipids was determined using ultra performance liquid chromatography coupled to mass spectrometry. Concentrations of the endocannabinoid 2-arachidonoylglycerol were higher in arterialized (91 ± 33 μg/L basally) than in hepatic venous (51 ± 19 μg/L; P < .05) plasma. Fasting arterial (r = 0.72; P = .031) and hepatic venous (r = 0.70; P = .037) concentrations of 2-arachidonoylglycerol were related positively to liver fat content. Analysis of fluxes of 85 different triglycerides showed that the fatty liver overproduces saturated triglycerides. In the plasma FFA fraction in the basal state, the relative amounts of palmitoleate and linoleate were lower and those of stearate and oleate were higher in the hepatic vein than in the artery. Absolute concentrations of all nontriglyceride lipids were comparable in arterialized venous plasma and the hepatic vein both in the basal and insulin-stimulated states. The human fatty liver takes up 2-arachidonoylglycerol and overproduces triacylglycerols containing saturated fatty acids, which might reflect increased de novo lipogenesis.

11C]palmitate kinetics across the splanchnic bed in arterial, portal and hepatic venous plasma during fasting and euglycemic hyperinsulinemia

The liver is fundamental in regulating lipid metabolism, and it supplies fatty acids (FA) to the rest of the body in the form of triglycerides (TG); the time-related relevance of this process is incompletely defined. The aim of the study was to investigate the appearance of labeled TG in the hepatic vascular bed after [11C]palmitate injection during fasting and insulin stimulation. Plasma [11C]palmitate kinetics in arterial, portal and hepatic venous lipid fractions was studied in eight anesthetized pigs during fasting or euglycemic hyperinsulinemia. Plasma analyses were conducted at 10 and 40 min after tracer injection. Corresponding liver positron emission tomography (PET) images were acquired for the semiquantitative determination of hepatic FA uptake. At 10 min, plasma levels of unchanged [11C]palmitate were lower in hyperinsulinemic than in fasting experiments in the artery and in the portal vein (P< or=.03), suggesting faster clearance. Levels of unmetabolized [11C]palmitate did not differ between portal and arterial plasma. In the fasting state, a tendency to a positive arterial and portal vs. hepatic venous gradient was observed, indicative of net hepatic [11C]palmitate extraction. Labeled TG were already detectable at 10 min (fasting vs. hyperinsulinemia, ns) and were higher in fasting than in hyperinsulinemic animals at 40 min (92+/-1% and 82+/-6% of arterial plasma radioactivity). Higher proportions of labeled TG were recovered in portal vein plasma, suggesting release by the gut. The portal and the arterial-portal vs. hepatic venous TG gradient tended to be positive. Accordingly, hepatic FA uptake was higher, but declined more rapidly during fasting than during hyperinsulinemia. The study indicates that the redistribution of [11C]palmitate between different lipid pools occurs within the short time interval of most PET experiments and is strongly influenced by insulin. Labeled TG constitute an additional [11C]palmitate source in the modeling of PET data.

Correlation between Hcy level in hepatic venous blood and plasma levels of folacin and vitamin B12 in patients with Budd-Chiari syndrome

目的 探讨Budd-Chiari综合征肝静脉血Hcy浓度与其血浆叶酸、维生素B12水平的相关性.方法应用高效液相色谱分析法测定46例Budd-Chiari综合征病人的肝静脉血及肘静脉血Hcy的含量,化学发光法测定其肘静脉血的叶酸、维生素B12的含量.25例健康志愿者作正常对照,22例缩窄性心包炎病人作类比对照,SPSS 6.0版本统计软件对其数据进行统计学处理.结果 (1)Budd-Chiari综合征病人肝静脉血Hcy浓度明显高于其自身肘静脉血(P＜0.01)和对照组(P＜0.005),血清叶酸、维生素B12浓度均明显低于对照组(P＜0.05);(2)Budd-Chiari综合征病人血浆Hcy水平与叶酸、维生素B12平呈负相关(r值分别为-0.6254和-0.3963);(3)肝静脉血Hcy的水平与其狭窄程度呈正相关.结论局部高Hcy血症是Budd-Chiari综合征发病的独立危险因素之一。

Increased Protein Glycation in Cirrhosis and Therapeutic Strategies to Prevent It

Glycation of liver proteins by reactive aldehydes formed from the metabolism of ethanol and lipid peroxidation has been implicated in the development of both alcoholic and nonalcoholic liver cirrhosis. Modified proteins are targeted to the proteasome for proteolysis. Release of glycation-free adducts into the circulation may provide a diagnostic "signature" of hepatic protein damage. We quantitatively screened protein glycation, oxidation, and nitrosation adduct residues and free adducts in portal, hepatic, and peripheral venous blood plasma of cirrhotic patients; we also screened the hepatic and peripheral venous blood plasma of control subjects by liquid chromatography-mass spectrometry. There was a remarkable 14-16-fold increase of glyoxal-derived, hydroimidazolone-free adduct in portal and hepatic venous plasma of cirrhotic patients with respect to normal controls. There was only a twofold increase of glycation adduct residues in plasma proteins in cirrhotic patients, which was attributed mainly to decreased albumin turnover. Therapeutic strategies to decrease dicarbonyl compounds may be beneficial, such as dicarbonyl scavengers, glutathione repleting agents, and high-dose thiamine therapy.

Effects of ruminally protected betaine and choline on net flux of nutrients across the portal-drained viscera and liver of meat goat wethers consuming diets differing in protein concentration

Six Boer × Spanish goat wethers (43 ± 5.1 kg BW) were used in an experiment with a 2 × 3 factorial arrangement of treatments to investigate effects of dietary CP level (9% and 15% DM) and supplementation with ruminally protected betaine or choline (0.9% DM) on plasma concentrations and net fluxes of oxygen, ammonia N, non-esterified fatty acids (NEFA), triacylglycerols (TG) and cholesterol across the portal-drained viscera (PDV) and liver. Neither betaine nor choline affected blood flow, packed cell volume, hemoglobin concentration or oxygen consumption. Blood flow and oxygen consumption were greater ( P < 0.05) for 15% versus 9% dietary CP. Arterial plasma ammonia N concentration was greater ( P < 0.05) for 9% versus 15% CP. Compared with Control, choline supplementation decreased ( P < 0.05) PDV release and hepatic uptake of ammonia N with the 15% CP diet, whereas betaine decreased ( P < 0.05) PDV release and hepatic uptake of ammonia N with 9% dietary CP. With 9% dietary CP, the concentration of NEFA in arterial, hepatic venous and portal venous plasma ranked ( P < 0.05) choline < Control < betaine; with 15% CP, NEFA concentration also was greater ( P < 0.05) for betaine versus Control, although the magnitude of difference was smaller than with 9% CP. The only treatment effect on NEFA net fluxes was greater ( P < 0.05) hepatic uptake with 9% CP than with 15%. Plasma TG concentrations also were increased ( P < 0.05) by betaine with 9% dietary CP, whereas choline did not have any influence with either dietary CP level. Concentrations and net fluxes of cholesterol were similar among treatments. In conclusion, these data indicate that potential effects of ruminally protected betaine on performance of ruminants might involve changes in lipid metabolism, with the magnitude of alteration varying with dietary CP level.

Processing of protein glycation, oxidation and nitrosation adducts in the liver and the effect of cirrhosis

Plasma proteins are modified non-enzymatically in vivo by glycation, oxidation and nitrosation processes. Hepatic extraction of albumin glycated in vitro was reported but it is not clear if plasma proteins glycated in vivo also undergo hepatic extraction. We investigated the hepatic extraction of glycated, oxidised and nitrosated proteins in vivo. Protein glycation, oxidation and nitrosation marker residues and free adducts were determined in portal, hepatic and peripheral venous blood plasma of cirrhotic patients and hepatic and peripheral venous blood plasma (as a surrogate of portal venous blood) of control subjects by liquid chromatography-mass spectrometry. There was no evidence for extraction of glycated, oxidised or nitrosated proteins or related free adducts by the liver in control subjects. There was limited extraction of methylglyoxal-modified proteins in cirrhotic patients and twofold increases in the concentrations of fructosyl-lysine and advanced glycation endproduct residues of plasma protein, with respect to controls. Remarkably, glyoxal-derived hydroimidazolone free adduct was increased 14-16-fold probably as a consequence of hepatic lipid peroxidation. We found no evidence for hepatic extraction of glycated, oxidised and nitrosated proteins or related free adducts in subjects with normal liver function and limited extraction of methylglyoxal-modified protein in cirrhotic subjects.

Hepatic ischemia-reperfusion syndrome after partial liver resection (LR): Hepatic venous oxygen saturation, enzyme pattern, reduced and oxidized glutathione, procalcitonin and interleukin-6

The hepatic ischemia-reperfusion syndrome was investigated in 28 patients undergoing elective partial liver resection with intraoperative occlusion of hepatic inflow (Pringle maneuver) using the technique of liver vein catheterization. Hepatic venous oxygen saturation (ShvO2) was monitored continuously up to 24 hours after surgery. Aspartate aminotransferase, glutamate dehydrogenase, gamma-glutamyl transpeptidase, pseudocholinesterase, alpha-glutathione S-transferase, reduced and oxidized glutathione, procalcitonine, and interleukin-6 were serially measured both before and after Pringle maneuver during the resection and postoperatively in arterial and/or hepatic venous blood. ShvO2 measurement demonstrated that peri- and postoperative management was suitable to maintain an optimal hepatic oxygen supply. As expected, we were able to demonstrate a typical enzyme pattern of postischemic liver injury. There was a distinct decrease of reduced glutathione levels both in arterial and hepatic venous plasma after LR accompanied by a strong increase in oxidized glutathione concentration during the phase of reperfusion. We observed increases in procalcitonin and interleukin-6 levels both in arterial and hepatic venous blood after declamping. Our data support the view that liver resection in man under conditions of inflow occlusion resulted in ischemic lesion of the liver (loss of glutathione synthesizing capacity with disturbance of protection against oxidative stress) and an additional impairment during reperfusion (liberation of reactive oxygen species, local and systemic inflammation reaction with cytokine production). Additionally, we found some evidence for the assumption that the liver has an export function for reduced glutathione into plasma in man.

N-acetylcysteine induces shedding of selectins from liver and intestine during orthotopic liver transplantation.

In orthotopic liver transplantation (OLT), N-acetylcysteine (NAC) reduces ischaemia/reperfusion (I/R) injury, improves liver synthesis function and prevents primary nonfunction of the graft. To further elucidate the mechanisms of these beneficial effects of NAC, we investigated influence of high-dose NAC therapy on the pattern of adhesion molecule release from liver and intestine during OLT. Nine patients receiving allograft OLT were treated with 150 mg NAC/kg during the first hour after reperfusion; 10 patients received the carrier only. One hour after reperfusion, samples of arterial, portal venous and hepatic venous plasma were taken and blood flow in the hepatic artery and the portal vein was measured. Absolute concentrations of sICAM-1, sVCAM-1, sP-selectin and sE-selectin were not markedly different. However, balance calculations showed release of selectins from NAC-treated livers as opposed to net uptake in controls (P < or = 0.02 for sP-selectin). This shedding of selectins might be a contributing factor to the decrease in leucocyte adherence and improved haemodynamics found experimentally with NAC-treatment.

Disturbances in hepatocellular function during cardiopulmonary bypass using propofol anaesthesia

Background and objective Serum hyaluronate is thought to be an indicator of derangement in hepatocellular integrity, and the change in serum hyaluronate is a useful indicator in various liver disorders. We assessed the changes in serum hyaluronate in patients undergoing coronary artery bypass graft surgery. Methods Eleven patients scheduled for elective coronary artery bypass graft surgery were studied. An oximetry oxygen saturation catheter was inserted into the right hepatic vein to permit monitoring of hepatic venous oxygen saturation. Perioperative measurements included: haemodynamic variables; systemic oxygen delivery and uptake; arterial, mixed venous and hepatic venous oxygen saturation; arterial and hepatic venous plasma concentrations of lactate, arterial ketone body ratio (ratio of acetoacetate to 3-hydroxybutyrate); and arterial and hepatic venous hyaluronate were measured. Results Arterial and hepatic venous hyaluronate increased during cardiopulmonary bypass compared with the prebypass period. These increases returned to prebypass values after the cessation of bypass (hepatic venous hyaluronate value at the prebypass period: 26 ± 13 ng mL–1, during bypass: 77 ± 40 ng mL–1; 1 h after bypass: 57 ± 42 ng mL–1; 6 h after bypass: 32 ± 15 ng L–1, 24 h after bypass; 62 ± 21 ng mL–1; mean ± SD, P < 0.05). The arterial and hepatic venous hyaluronate during cardiopulmonary bypass was correlated with total bilirubin and hepatic venous lactate concentrations 6 h after bypass (arterial hyaluronate at cardiopulmonary bypass period vs. total bilirubin at 6 h after bypass;r =0.793, P =0.0036, hepatic venous hyaluronate during bypass vs. that at 6 h after bypass;r =0.795, P =0.0035). Conclusions Hepatocellular integrity might be disturbed during cardiopulmonary bypass when propofol anaesthesia is used.

Disturbances in hepatocellular function during cardiopulmonary bypass using propofol anaesthesia.

Serum hyaluronate is thought to be an indicator of derangement in hepatocellular integrity, and the change in serum hyaluronate is a useful indicator in various liver disorders. We assessed the changes in serum hyaluronate in patients undergoing coronary artery bypass graft surgery. Eleven patients scheduled for elective coronary artery bypass graft surgery were studied. An oximetry oxygen saturation catheter was inserted into the right hepatic vein to permit monitoring of hepatic venous oxygen saturation. Perioperative measurements included: haemodynamic variables; systemic oxygen delivery and uptake; arterial, mixed venous and hepatic venous oxygen saturation; arterial and hepatic venous plasma concentrations of lactate, arterial ketone body ratio (ratio of acetoacetate to 3-hydroxybutyrate); and arterial and hepatic venous hyaluronate were measured. Arterial and hepatic venous hyaluronate increased during cardiopulmonary bypass compared with the prebypass period. These increases returned to prebypass values after the cessation of bypass (hepatic venous hyaluronate value at the prebypass period: 26 +/- 13 ng mL(-1), during bypass: 77 +/- 40 ng mL(-1); 1 h after bypass: 57 +/- 42 ng mL(-1); 6 h after bypass: 32 +/- 15 ng L(-1), 24 h after bypass; 62 +/- 21 ng mL(-1); mean +/- SD, P < 0.05). The arterial and hepatic venous hyaluronate during cardiopulmonary bypass was correlated with total bilirubin and hepatic venous lactate concentrations 6 h after bypass (arterial hyaluronate at cardiopulmonary bypass period vs. total bilirubin at 6 h after bypass; r=0.793, P=0.0036, hepatic venous hyaluronate during bypass vs. that at 6 h after bypass; r=0.795, P=0.0035). Hepatocellular integrity might be disturbed during cardiopulmonary bypass when propofol anaesthesia is used.

Hemodynamic effects of the angiotensin II receptor antagonist irbesartan in patients with cirrhosis and portal hypertension

Background & Aims: Angiotensin II receptor antagonists have been proposed as new drugs for portal hypertension.This randomized, placebo-controlled, double-blind study aimed to assess the effect of the angiotensin II receptor antagonist irbesartan on portal and systemic hemodynamics and renal function in patients with cirrhosis.Methods: Thirty-six patients with cirrhosis and portal hypertension received 150 mg/d irbesartan or placebo for 1 week.Systemic hemodynamics, kidney and liver function parameters were recorded regularly; hepatic venous pressure gradient and plasma renin were assessed on days 0 and 7.Results: Irbesartan reduced the hepatic venous pressure gradient by 12.2% ± 6.6% (P < 0.05) and mean arterial pressure by 5.3% ± 4.0% in 13 of 18 verum patients.In 4 (22%) verum patients, arterial hypotension, accompanied by significant renal impairment, required withdrawal of irbesartan.In these patients, baseline plasma renin (P < 0.002) and cystatin C (P < 0.001) levels were higher, and creatinine clearance (P < 0.02), serum sodium (P < 0.01), and albumin (P < 0.05) were lower than in patients who tolerated irbesartan.Four of five patients with baseline renin >900 μU/mL developed treatment-limiting hypotension.Conclusions: The angiotensin II receptor antagonist irbesartan is not advisable in patients with advanced cirrhosis and high plasma renin because it may induce arterial hypotension and only moderately reduces portal pressure.GASTROENTEROLOGY 2001;121:389-395