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Biomedical subjects

K Tanikawa

Publications and source records attributed to K Tanikawa.

At least 37 records · Page 2Linked to original sources
PubMed1999

Different lobular distributions of altered hepatocyte tight junctions in rat models of intrahepatic and extrahepatic cholestasis.

Hepatocyte tight junctions (TJs), the only intercellular barrier between the sinusoidal and the canalicular spaces, play a key role in bile formation. Although hepatocyte TJs are impaired in cholestasis, attempts to localize the precise site of hepatocyte TJ damage by freeze-fracture electron microscopy have produced limited information. Recently, several TJ-associated proteins like ZO-1 and 7H6 have been identified and characterized. Immunolocalization of 7H6 appears to closely correlate with paracellular permeability. We used rat models of intrahepatic cholestasis by ethinyl estradiol (EE) treatment and extrahepatic cholestasis by bile duct ligation (BDL) to precisely determine the site of TJ damage. Alterations in hepatocyte TJs were assessed by double-immunolabeling for 7H6 and ZO-1 using a confocal laser scanning microscope. In control rats, immunostaining for 7H6 and ZO-1 colocalized to outline bile canaliculi in a continuous fashion. In contrast, 7H6 and ZO-1 immunostaining was more discontinuous, outlining the bile canaliculi after BDL. Immunostaining for 7H6, not ZO-1, decreased and predominantly appeared as discrete signals in the submembranous cytoplasm of periportal hepatocytes after BDL. After EE treatment, changes in immunostaining for 7H6 and ZO-1 were similar to those seen in periportal hepatocytes after BDL, but distributed more diffusely throughout the lobule. This study is the first to demonstrate that impairment of hepatocyte TJs occurs heterogenously in the liver lobule after BDL and suggests that BDL and EE treatments produce different lobular distributions of increased paracellular permeability.

Animals↗
PubMed1999

Erythropoietic protoporphyria with fatal liver failure.

A 33-year-old woman with a history of photosensitivity, persistent abdominal pain, and liver dysfunction was admitted to our department because of abdominal pain and progression of liver dysfunction. On admission, levels of protoporphyrin and coproporphyrin within erythrocytes were markedly increased. Autofluorescent erythrocytes were also detected, leading to a diagnosis of erythropoietic protoporphyria. A liver biopsy specimen revealed cirrhosis with dark brown granules filling hepatocytes, bile canaliculi, and bile ductules. Transfusion of washed erythrocytes, hemodialysis, and administration of cholestyramine and beta-carotene transiently improved levels of porphyrins and liver function. The patient died of rupture of esophageal varices followed by multiple organ failure. However, the treatments were believed to have extended survival.

Adult↗
PubMed1999

Increased expression of membrane type 1 matrix metalloproteinase and matrix metalloproteinase-2 with tumor dedifferentiation in hepatocellular carcinomas.

Destruction of the extracellular matrices is required for tumor invasion and metastasis. Matrix metalloproteinase-2 degrades type IV collagen and laminin, major components of the basement membrane. Membrane type 1 matrix metalloproteinase activates the latent form of matrix metalloproteinase-2. We studied changes in membrane type 1 matrix metalloproteinase and matrix metalloproteinase-2 expression in relation to the tumor differentiation of hepatocellular carcinomas. Activity of matrix metalloproteinase-2 was also evaluated in hepatocellular carcinomas and noncancerous tissues. Overall, 37 hepatocellular carcinomas were studied. Expression of membrane type 1 matrix metalloproteinase and matrix metalloproteinase-2 was determined by either immunohistochemistry (n=37) or in situ hybridization (n=6). Changes in membrane type 1 matrix metalloproteinase and matrix metalloproteinase-2 expression were evaluated in relation to tumor differentiation. Gelatinolytic activities were analyzed by gelatin zymography (n=4). Membrane type 1 matrix metalloproteinase and matrix metalloproteinase-2 were detected in hepatoma cells and stromal cells. In addition, these matrix metalloproteinases were detected in the same hepatoma cells. Increased expression of membrane type 1 matrix metalloproteinase and matrix metalloproteinase-2 was associated with tumor dedifferentiation. The active form of matrix metalloproteinase-2 was more strongly expressed by hepatocellular carcinomas than by noncancerous tissues. These findings indicate that increased expression of membrane type 1 matrix metalloproteinase and matrix metalloproteinase-2 was associated with tumor dedifferentiation, suggesting that these matrix metalloproteinases are intimately involved in the invasion of hepatocellular carcinomas.

Adult↗
PubMed1999

Histological changes in liver biopsies after one year of lamivudine treatment in patients with chronic hepatitis B infection.

BACKGROUND/AIMS: The aim of this study was to examine the histological changes in liver biopsies induced by 52 weeks of lamivudine therapy in patients with e-antigen positive and e-antigen negative chronic hepatitis B infection. METHODS: Twenty patients were enrolled into this open-label study. All patients had a liver biopsy within the 4 weeks before starting lamivudine therapy. Lamivudine was given orally at a dose of 100 mg OD for 52 weeks. A second liver biopsy was taken for comparison at the end of week 52. Blinded biopsies were evaluated by a histopathologist and scored according to Knodell's histology activity index (HAI). RESULTS: Ninety-five percent (19/20) patients had a reduction of their hepatic necroinflammatory HAI score (components 1 through 3) by > or =2 points at the end of 52 weeks of lamivudine therapy compared to their pretreatment values. Not only were improvements in necroinflammatory activity observed, but 7/20 (35%) of patients had improvement in fibrosis. This histologic improvement was independent of the presence or absence of e-antigen. CONCLUSIONS: Significant improvements in liver histology can be obtained in the majority of patients when they are treated with lamivudine for 1 year.

Adult↗
PubMed1999

Integrin alpha6beta1 plays a significant role in the attachment of hepatoma cells to laminin.

BACKGROUND/AIMS: Tumor invasion and metastasis consist of a series of complex events. During this process, the ability of tumor cells to adhere to laminin, a major component of basement membranes, is required at various steps. The expression of laminin-binding integrins and the extent of tumor metastasis and progression appear to be related. In hepatocellular carcinoma, increased expression of laminin-binding integrins is observed. However, little is known concerning the possible functional interactions between laminin-binding integrins and laminin. Therefore, we investigated the participation of laminin-binding integrins in the attachment of hepatoma cells to laminin. METHODS: Human hepatoma cell lines (KIM-1, KYN-1, 2) were used. We investigated the expression of integrin alpha1, alpha2, alpha3, alpha6, beta1, and beta4 subunits on hepatoma cells by immunocytochemical and flow cytometric analysis. Participation of these integrin subunits in the attachment of hepatoma cells to laminin was evaluated by an inhibition of cell adhesion assay. RESULTS: Integrin alpha1, alpha2, alpha3, alpha6 and beta1 subunits were expressed at the marginal areas of hepatoma cells, while the integrin beta4 subunit was scarcely detected. Laminin promoted the attachment of hepatoma cells in a dose-dependent manner. Although anti-integrin alpha1, alpha2, beta3 and beta4 subunit antibodies did not inhibit cell attachment to laminin, anti-integrin alpha6 and beta1 subunit antibodies inhibited the attachment by 50% or more. CONCLUSIONS: These findings indicate that integrin alpha6beta1 is very important in the attachment of hepatoma cells to laminin, suggesting the participation of this integrin in metastasis and invasion of hepatoma cells.

Carcinoma, Hepatocellular↗
PubMed1999

Detection of hepatitis-C virus and hepatitis-C virus replication in hepatocellular carcinoma by in situ hybridization.

BACKGROUND: Although hepatitis C virus (HCV) is a major causative agent of hepatocellular carcinoma (HCC), the role of this virus in carcinogenesis is not fully understood. METHODS: We studied HCV infection and replication by detecting plus- and minus-strand HCV RNA by in situ hybridization (ISH) in surgically resected HCCs and adjacent non-cancerous tissue obtained from 15 anti-HCV antibody-positive patients with HCC. RESULTS: Plus-strand HCV RNA was found in 9 of 15 HCCs. Both plus- and minus-strand HCV RNA were detected in four of these nine patients. In non-cancerous tissues obtained adjacent to the HCC, plus-strand HCV RNA was found in 10 of 15 patients, whereas both plus- and minus-strand HCV RNA were detected in 7 of these 10 patients. The degree of staining by ISH did not correlate with the differentiation of the HCC, histologic classification of the non-cancerous tissue, serum HCV RNA levels, or serum transaminase levels. CONCLUSIONS: HCV can be found in and replicates in both hepatoma cells and in non-cancerous hepatocytes in anti-HCV antibody-positive patients with HCC. The direct effects of HCV viral gene products on normal hepatocytes in the development of HCC require additional study.

Aged↗
PubMed1999

Helicobacter pylori in the natural environment.

The presence of Helicobacter pylori (H. pylori) in the natural environment has been demonstrated in a number of studies. However, its route of infection into humans is unknown. To study this further, we attempted to detect H. pylori in the natural environment in a region of Japan with a high infection rate. Tap and well water and field soil samples were collected from around the residences of subjects who had participated in an epidemiological survey in 1996. Samples of water from rivers and ponds, and specimens of flies and cow faeces were collected in the region. DNA was extracted from the water, field soil and faecal samples after selective collection of H. pylori by the immunomagnetic-bead separation technique. H. pylori-specific DNA was detected in water, field soil, flies and cow faeces by nested polymerase chain reaction (PCR), and the ureA partial sequences of the PCR products were aligned. The nucleotide sequences of the samples amplified by PCR were highly homologous (96-100%) with the H. pylori sequence in the GenBank database and the H. pylori-specific DNA sequences were highly homologous with each other. These findings suggest the existence of H. pylori in the natural environment and a possible transmission route.

Animals↗
PubMed1999

Intraspousal transmission of GB virus C/hepatitis G virus in an hepatitis C virus hyperendemic area in Japan.

OBJECTIVE: An immunoassay for antibodies against an hepatitis G virus (HGV) protein (anti-E2) was recently developed that might serve as a useful marker for diagnosing recovery from HGV infection. METHODS: We investigated the intraspousal transmission of GB virus C/hepatitis G virus (GBV-C/HGV) using both reverse transcription hemipolymerase chain reaction (RT-hemi-PCR for the 5' untranslated region) and a recently developed anti-E2. RESULTS: Thirty-two GBV-C/HGV-infected index subjects were selected from an hepatitis C virus hyperendemic area in Japan. Of the 32 subjects, seven (6.4%) were GBV-C/HGV RNA-positive, 24 (21.8%) were anti-E2-positive, and one (0.9%) was both GBV-C/HGV RNA- and anti-E2-positive. Among the 32 spouses of these subjects, GBV-C/HGV RNA, anti-E2, and both GBV-C/HGV RNA and anti-E2 positivity were detected in 0, 6, (18.8%), and one (3.1%) spouses, respectively (the total prevalence of GBV-C/HGV was 7 spouses [21.9%]). Thus, the intraspousal transmission of GBV-C/HGV was undeniable in these seven couples. The respective positive rates of 175 sex- and age-matched controls were 7 (4.0%), 26 (14.9%), and 0 (the total prevalence of GBV-C/HGV was 34 [19.4%]). No significant difference in positive rates was observed between the subjects/spouses and the controls. Five spouses among the seven couples who were positive for any of GBV-C/HGV markers had parenteral risk factors such as blood transfusion, acupuncture, and major surgery. CONCLUSION: Based on these observations, we cannot draw a definitive conclusion that intraspousal transmission of GBV-C/HGV had occurred among these seven couples.

Aged↗
PubMed1999

[Population pharmacokinetic analysis of theophylline: relationship between serum concentrations and clinical effects in therapeutic drug monitoring].

Therapeutic drug monitoring (TDM) of theophylline is essential duties at hospital pharmacy in Japan. The relationship between serum concentrations and clinical effects of theophylline has been investigated. The pharmacokinetics of theophylline was determined from the concentration of theophylline in the serum which were calculated on the basis of TDM for patients administered theophylline. The one-compartment model as a pharmacokinetic model was assumed. The relationship between clinical effects of theophylline and the predicted concentrations calculated using population parameters was evaluated. The obtained parameters are ka(h-1) = 0.223, ke(h-1) = 0.047 (1-0.0025.age(y) (p.o.) and 0.076(1-0.0025.age(y)) (d.i.v.), Vd(1/kg) = 0.733 (p.o.) and 0.830 (d.i.v.). The bioavailability is 0.732, and theophylline/aminophylline is 0.846. The model including no serum creatinine as a variational factor was considered to be best. The following three groups were used as a clinical evaluation; effective as theophylline therapy was 43%, no change of the clinical status after administration of theophylline was 42%, and aggravation after administration of theophylline was 15%. There is no relationship between the predicted concentration using parameters of the final model and these three groups. These results suggest that TDM of theophylline should be assessed in terms of clinical effects and also suggests that in should be kept monitoring from the viewpoint of the prevention of toxic effects in the theophylline therapy.

Administration, Oral↗
PubMed1999

OK-432 treatment increases matrix metalloproteinase-9 production and improves dimethylnitrosamine-induced liver cirrhosis in rats.

Kupffer cells are major matrix metalloproteinase-producing cells in the liver. The production of metalloproteinases in Kupffer cells may contribute to the improvement of liver fibrosis inducing liver cirrhosis. In this study, we examined the effect of the OK-432 (a biological response modifier) on the dimethylnitrosamine-induced liver cirrhosis in rats. Dimethylnitrosamine (10 microg/ml) was injected intraperitoneally into 20 male Wistar rats 3x/week for 4 weeks. For the subsequent 4 weeks, the animals were injected with saline (1 ml, 1x/week) (Group I, n=10) or OK-432 (1 Klinishe Einheit, 1x/week) (Group II, n=10). The control rats were injected with 1 ml saline for the initial 4 weeks and subsequent 4 weeks (Group III, n=10). The degree of hepatic fibrosis, the immunolocalization of type IV collagen, hyaluronic acid, and alpha-smooth muscle actin, and the mRNA expression by Northern blotting and the activity by gelatin zymography of metalloproteinase-9 were evaluated. Serum aminotransferase, hyaluronic acid, interleukin-1beta and tumor necrosis factor-alpha levels were measured. The deposition of á-smooth muscle actin and extracellular matrix containing type IV collagen and hyaluronic acid was markedly suppressed by OK-432. The mRNA expression and the activity of metalloproteinase-9 were markedly increased by OK-432. The serum aminotransferase and hyaluronic acid levels were decreased by OK-432. The serum interleukin-1 and tumor necrosis factor-alpha values were lower than the detectable limit in all samples from all three groups. These results indicate that OK-432 increased the production of metalloproteinase-9 and improved the rat dimethylnitrosamine-induced liver cirrhosis. OK-432 is suggested to be useful for the treatment of liver cirrhosis.

Actins↗
PubMed1998

Inhibitory effect of OPC-15161, a component of fungus Thielavia minor, on proliferation and extracellular matrix production of rat cultured hepatic stellate cells.

A component of fungus Thielavia minor, OPC-15161, has been shown to inhibit the proliferation and extracellular matrix production of extracellular matrix-producing mesangial cells in the kidney in vivo. In this study, we examined the effects of OPC-15161 on the proliferation and extracellular matrix production of rat cultured hepatic stellate cells (HSCs). To determine the effect of OPC-15161 on proliferation of HSCs, the cell number and the uptake of [3H]thymidine were investigated in the presence and absence of interleukin-1beta (IL-1beta). IL-1beta significantly increased the uptake of [3H]thymidine in the HSCs, and the addition of OPC-15161 inhibited the uptake in a dose-dependent manner. The cell number of HSCs was also increased by IL-1beta, which was inhibited by OPC-15161. Production of extracellular matrix by OPC-15161 was studied by the production of [3H]-hydroxyproline in the presence and absence of transforming growth factor-beta1 (TGF-beta1). TGF-beta1 significantly increased the production of [3H]-hydroxyproline in the cells, whereas the addition of OPC-15161 inhibited this effect dose dependently. We also investigated the effects of OPC-15161 on Ca2+ mobilization and measured D-myo-inositol 1,4,5-triphosphate (IP3) in the HSCs. IL-1beta induced the increase of intracellular Ca2+ and IP3 concentrations in the HSCs, which were decreased by OPC-15161. Based on these results, we conclude that OPC-1 5161 inhibited the proliferation and production of hydroxyproline in cultured rat HSCs, and thus, it may have a role in prevention of liver fibrosis in vivo.

Animals↗
PubMed1998

Role of extravariceal collateral channels in the development of portal-hypertensive gastropathy before and after sclerotherapy.

We investigated whether extravariceal collateral pattern contributed to the development of portal-hypertensive gastropathy (PHG) before and after sclerotherapy. Ninety-nine patients with cirrhosis and large esophageal varices were examined in this retrospective study. They were divided into four groups according to transhepatic portographic findings: group A (with neither paraesophageal veins nor gastrorenal shunt; n = 46), group B (with paraesophageal veins; n = 27), group C (with gastrorenal shunt; n = 14), and group D (with paraesophageal veins and gastrorenal shunt; n = 12). To assess PHG, endoscopic examinations were carried out before and 1 week and 1 month after sclerotherapy. The severity of PHG was classified according to a modified McCormack's classification and scored as: absence, 0; mild, 1; severe, 2. There were no significant differences in age, sex, cause of cirrhosis, severity of liver dysfunction, and extent of esophageal varices in the four groups. The PHG score before sclerotherapy was significantly higher in group A than in either group C (P < 0.05) or group D patients (P < 0.05). The calculated, integrated incremental change in PHG score after sclerotherapy was significantly higher in group A than in group C (P < 0.01) and group D patients (P < 0.01). Although the integrated change in PHG score was lower in group B than in group A patients, the difference was not significant (P = 0.68). These results suggest that gastrorenal shunt, but not paraesophageal veins, may play a protective role in the development of PHG before and after sclerotherapy.

Collateral Circulation↗
PubMed1998

Sero-epidemiologic study of hepatitis C virus infection in Fukuoka, Japan.

We conducted an epidemiological study of 509 residents of H town, Fukuoka, Japan, to investigate the high mortality rate from liver disease. Antibodies to hepatitis C virus (HCV) (anti-HCV) were detected in 120 residents (23.6%); HCV RNA in 91 (17.9%), and hepatitis B surface antigen (HBsAg) in 13 (2.6%). Multivariate logistic regression analyses showed that presence of anti-HCV, male gender, and history of liver disease were associated with the presence of liver dysfunction, and that age of more than 40 years and a particular district were associated with the presence of anti-HCV. HCV RNA was more frequently detected in anti-HCV-positive men than women (41, or 85.4% versus 50, or 69.4%) (P < 0.05). The incidence of liver dysfunction was significantly higher in HCV RNA-positive men than women (32, or 66.7% versus 22, or 30.6%) (P < 0.05). These findings suggest that: (1) HCV was correlated with the high mortality rate from liver diseases, (2) there were district-related differences in the incidence of HCV, and (3) the lower frequency of elimination of HCV from men may explain why they showed a high mortality from liver disease.

Adult↗
PubMed1998

Increased expression of vascular endothelial growth factor is associated with tumor progression in hepatocellular carcinoma.

Vascular endothelial growth factor is a potent direct-acting angiogenic factor. Early in hepatocarcinogenesis, hepatocellular carcinomas do not show hypervascularity; at later stages, they require abundant arterial blood flow. We investigated the role of vascular endothelial growth factor in hepatocellular carcinoma arterialization. We studied 51 patients with hepatocellular carcinoma. All patients had undergone hepatic arteriography. Vascular endothelial growth factor expression was investigated by immunohistochemistry (n = 51) and in situ hybridization (n = 13), and the changes in vascular endothelial growth factor expression were evaluated in relation to tumor differentiation and changes in tumor vascularity. The expression of vascular endothelial growth factor isoforms in hepatocellular carcinomas was also analyzed by reverse transcriptase-polymerase chain reaction (n = 10). Vascular endothelial growth factor expression was detected in hepatoma cells and hepatic stellate cells, and increased vascular endothelial growth factor expression was associated with tumor dedifferentiation. Vascular endothelial growth factor expression in hypervascular hepatocellular carcinomas was greater than in those not showing hypervascularity. The major vascular endothelial growth factor isoforms expressed in hepatocellular carcinoma were 121 and 165. These findings indicate that vascular endothelial growth factors 121 and 165 play a critical role in the process of angiogenesis in hepatocellular carcinomas.

Aged↗
PubMed1998

Abnormal accumulation of endotoxin in biliary epithelial cells in primary biliary cirrhosis and primary sclerosing cholangitis.

BACKGROUNDS/AIMS: Previous studies have revealed the involvement of Kupffer cells and hepatocytes in the metabolism of endotoxin in the liver. The aim of this study was to investigate the in vivo localization of endotoxin in liver cells, including Kupffer cells, hepatocytes, and biliary epithelial cells, in primary biliary cirrhosis and primary sclerosing cholangitis. We also examined the effect of ursodeoxycholic acid on the intrahepatic distribution of endotoxin in primary biliary cirrhosis. METHODS: The immunohistochemical localization of endotoxin was examined in liver specimens from 30 cases of primary biliary cirrhosis and seven of primary sclerosing cholangitis using a monoclonal antibody against lipid A. Controls were seven cases of obstructive jaundice, ten of hepatitis C virus-related liver cirrhosis, 14 of chronic hepatitis C, and five histologically normal liver cases. Semi-quantitative analysis of endotoxin accumulation was performed to measure the intensity of fluorescence for endotoxin. Nine of the 30 patients with primary biliary cirrhosis underwent a second liver biopsy for evaluation of the ursodeoxycholic acid treatment. RESULTS: In primary biliary cirrhosis and primary sclerosing cholangitis, biliary epithelial cells showed strong immunostaining for endotoxin as well as hepatocytes and Kupffer cells. Biliary epithelial cells of primary biliary cirrhosis and primary sclerosing cholangitis showed more intense immunoreactivity than those of other controls. In primary biliary cirrhosis, ursodeoxycholic acid reduced the immunoreactivity to endotoxin in biliary epithelial cells, and increased the immunoreactivity to endotoxin in Kupffer cells, but did not affect that in hepatocytes. CONCLUSIONS: Our results revealed that in primary biliary cirrhosis and primary sclerosing cholangitis, endotoxin accumulates abnormally in biliary epithelial cells. In addition, we found that ursodeoxycholic acid treatment in primary biliary cirrhosis may provide a beneficial effect on the intrahepatic metabolism of endotoxin.

Adult↗
PubMed1998

Noninvasive hemodynamic measurements of superior mesenteric artery in the prediction of portal pressure response to propranolol.

BACKGROUND/AIMS: The portal pressure response to propranolol administration is heterogeneous in patients with cirrhosis. The aim of this study was to examine the diagnostic accuracy of noninvasive hemodynamic parameters of superior mesenteric artery (SMA) and femoral artery (FA) in the prediction of portal pressure response to propranolol. METHODS: Twenty-six patients with cirrhosis were studied. Portal pressure was assessed by measurements of hepatic venous pressure gradient. Mean arterial pressure and heart rate were also recorded. Cardiac index, and flow velocity of SMA and FA, and pulsatility index of SMA and FA were then measured by means of Doppler ultrasonography. After intravenous propranolol administration (0.10 mg/kg), the above measurements were repeated. RESULTS: Propranolol significantly reduced cardiac index, heart rate, SMA flow velocity, and FA flow velocity and increased SMA pulsatility index and FA pulsatility index. Although propranolol significantly decreased hepatic venous pressure gradient, a reduction of > or =20% was seen in only 10 patients (good responders); the remaining 16 patients exhibited <20% reduction (poor responders). No significant differences in clinical and baseline hemodynamic data were found in the two groups. There were no also significant differences in changes in heart rate and cardiac index. However, reductions in SMA and FA flow velocity were significantly greater in good responders than in poor responders. Although there was no the increase in FA pulsatility index, the increase in SMA pulsatility index was significantly greater in good responders than in poor responders. When appropriate cut-off points were determined for these variables, overall predictive values of SMA flow velocity (-20%) and SMA pulsatility index (+15%) were 91% and 83%, whereas the overall predictive value of FA flow velocity (-25%) was only 69%. CONCLUSIONS: These results suggest that SMA flow velocity and SMA pulsatility index, but not FA flow velocity and FA pulsatility index, are useful noninvasive parameters in the prediction of portal pressure response to propranolol administration.

Adult↗
PubMed1998

Upright posture decreases esophageal varices flow velocity in patients with cirrhosis.

BACKGROUND/AIMS: Patients with cirrhosis tend to have esophageal variceal bleeding episodes at night, rather than during the day time. Since human beings carry on ordinary activities in the upright posture in the day time and are recumbent at night, we hypothesized that posture may be a factor related to a circadian variation of variceal bleeding. The aim of this study was to examine the effect of upright posture on esophageal varices hemodynamics in patients with cirrhosis. METHODS: Nine patients with cirrhosis and esophageal varices were included in a crossover study performed on 2 separate days. On the non-endoscopic day, cardiac output, portal vein flow velocity, and superior mesenteric artery flow velocity were measured with percutaneous Doppler ultrasonography. Plasma renin activity and plasma norepinephrine concentrations were also determined. On the endoscopic day, in addition to the above measurements, esophageal varices flow velocity was measured using transesophageal Doppler ultrasonography. These measurements were performed in the supine position and 20 min after the assumption of the upright position. RESULTS: On the non-endoscopic day, the upright posture significantly decreased cardiac output, portal vein flow velocity, and superior mesenteric artery flow velocity. Plasma renin activity and plasma norepinephrine concentration were significantly increased after assumption of the upright position. On the endoscopic day, similar hemodynamic and hormonal changes were observed. In addition, the upright posture significantly decreased esophageal varices flow velocity. Furthermore, the magnitude of the reduction in esophageal varices flow velocity (-42%) was significantly greater than that in portal vein flow velocity (-22%, p<0.01) and that in superior mesenteric artery flow velocity (-25%, p<0.01). Although the change in esophageal varices flow velocity was not significantly correlated with that in plasma renin activity (r=-0.28) and that in plasma norepinephrine concentration (r=-0.10), it was significantly correlated with the change in superior mesenteric artery flow velocity (r=0.73, p<0.05). CONCLUSIONS: The upright posture decreases esophageal varices flow velocity mainly because of the reduction in splanchnic blood flow. This effect may contribute to a low prevalence of esophageal variceal bleeding in the day time in patients with cirrhosis.

Aged↗