scholarly journals Effects of Caffeine Treatment on Hepatopulmonary Syndrome in Biliary Cirrhotic Rats

2019 ◽  
Vol 20 (7) ◽  
pp. 1566
Author(s):  
Ching-Chih Chang ◽  
Chiao-Lin Chuang ◽  
Ming-Hung Tsai ◽  
I.-Fang Hsin ◽  
Shao-Jung Hsu ◽  
...  
Keyword(s):  
Mortality Rate ◽  
Liver Fibrosis ◽  
Portal Pressure ◽  
Hepatopulmonary Syndrome ◽  
Gas Analysis ◽  
Common Bile Duct Ligation ◽  
Arterial Blood ◽  
Duct Ligation ◽  
Intrapulmonary Shunting ◽  
Protein Expressions

Hepatopulmonary syndrome (HPS) is a lethal complication of cirrhosis characterized by hypoxia and overt intrapulmonary shunting. In this study, we investigated the effect of caffeine in rats with common bile duct ligation (CBDL)-induced liver cirrhosis and HPS. CBDL rats were randomly allocated to receive caffeine or vehicle for 14 days. On the 28th day after CBDL, mortality rate, hemodynamics, liver, and renal biochemistry parameters and arterial blood gas analysis were evaluated. Lung and liver were dissected for the evaluation of inflammation, angiogenesis and protein expressions. In another series with parallel groups, the intrapulmonary shunting was determined. Caffeine significantly reduced portal pressure (caffeine vs. control: 10.0 ± 3.7 vs. 17.0 ± 8.1 mmHg, p < 0.05) in CBDL rats. The mortality rate, mean arterial pressure, biochemistry data and hypoxia were similar between caffeine-treated and control groups. Caffeine alleviated liver fibrosis and intrahepatic angiogenesis but intrapulmonary inflammation and angiogenesis were not ameliorated. The hepatic VEGF/Rho-A protein expressions were down-regulated but the pulmonary inflammation- and angiogenesis-related protein expressions were not significantly altered by caffeine. Caffeine did not reduce the intrapulmonary shunting, either. Caffeine has been shown to significantly improve liver fibrosis, intrahepatic angiogenesis and portal hypertension in cirrhotic rats, however, it does not ameliorate HPS.

Sorafenib treatment improves hepatopulmonary syndrome in rats with biliary cirrhosis

2012 ◽  
Vol 124 (7) ◽  
pp. 457-466 ◽  
Author(s):  
Ching-Chih Chang ◽  
Chiao-Lin Chuang ◽  
Fa-Yauh Lee ◽  
Sun-Sang Wang ◽  
Han-Chieh Lin ◽  
...  
Keyword(s):  
Hepatopulmonary Syndrome ◽  
Gas Analysis ◽  
Vegf Receptor ◽  
Biliary Cirrhosis ◽  
Water Control ◽  
Vegf Mrna ◽  
Common Bile Duct Ligation ◽  
Sorafenib Treatment ◽  
Duct Ligation ◽  
Intrapulmonary Shunting

HPS (hepatopulmonary syndrome) is characterized by oxygen desaturation in patients with chronic liver disease. The initiation of HPS comes from abnormal pulmonary vasodilatation and/or angiogenesis. In the present study, we evaluated anti-angiogenesis therapy using sorafenib in experimental HPS animals. HPS was induced by CBDL (common bile duct ligation) in rats. A 2-week 10 mg·(kg of body weight)−1·day−1 treatment regimen of sorafenib or distilled water (control) was initiated 2 weeks after the surgical procedure. Haemodynamics, liver biochemistry, plasma VEGF (vascular endothelial growth factor) measurements and blood gas analysis of the CBDL rats were performed. The livers of the CBDL rats were dissected for histopathology examination, and the lungs were examined by immunohistochemical staining, real-time PCR and Western blot analysis. In another two parallel groups, intrapulmonary shunts were determined. The AaPO2 (alveolar–arterial O2 gradient) and plasma VEGF levels were reduced after sorafenib treatment [AaPO2, 7.2±3.4 mmHg in sorafenib-treated rats compared with 15.3±4.2 mmHg in controls (P=0.004); VEGF, 45.3±2.7 pg/ml in sorafenib-treated rats compared with 54.4±7.7 pg/ml in controls (P=0.021)]. Sorafenib attenuated pulmonary VEGF mRNA and VEGF, VEGFR-2 (VEGF receptor 2), phospho-VEGFR-2 and Akt protein expression. In addition, sorafenib significantly attenuated intrapulmonary angiogenesis and decreased the degree of intrapulmonary shunting by 33.7% (11.2±5.7% in sorafenib-treated rats compared with 16.9±5.9% in controls; P=0.003). Our findings suggest that sorafenib attenuates intrapulmonary shunting and decreases the AaPO2 in CBDL rats, implicating the improvement of HPS in this experimental animal model. The beneficial effect may be attributed to the reduction in intrapulmonary angiogenesis through inhibition of the VEGF/VEGFR-2/Akt pathway.

Common bile duct ligation in the rat: a model of intrapulmonary vasodilatation and hepatopulmonary syndrome

1997 ◽  
Vol 272 (4) ◽  
pp. G779-G784 ◽  
Author(s):  
M. B. Fallon ◽  
G. A. Abrams ◽  
J. W. McGrath ◽  
Z. Hou ◽  
B. Luo
Keyword(s):  
Portal Hypertension ◽  
Bile Duct ◽  
Gas Exchange ◽  
Common Bile Duct ◽  
Lung Injury ◽  
Bile Duct Ligation ◽  
Hepatopulmonary Syndrome ◽  
Common Bile Duct Ligation ◽  
Arterial Blood ◽  
Duct Ligation

Hepatopulmonary syndrome (HPS) causes impaired oxygenation due to intrapulmonary vasodilatation in patients with cirrhosis. Chronic common bile duct ligation (CBDL) in the rat results in gas-exchange abnormalities similar to HPS, but intrapulmonary vasodilatation has not been evaluated. We assess intrapulmonary vasodilatation, measured in vivo, after CBDL. Sham, 2- and 5-wk CBDL, and 3-wk partial portal vein ligated (PVL) rats had hepatic and lung injury, portal pressure, and arterial blood gases assessed. The pulmonary microcirculation was evaluated by injecting microspheres (size range 5.5-10 microm) intravenously and measuring the size and number of microspheres bypassing the lungs in arterial blood. CBDL animals developed progressive hepatic injury and portal hypertension accompanied by gas-exchange abnormalities and intrapulmonary vasodilatation. PVL animals, with a similar degree of portal hypertension, did not develop intrapulmonary vasodilatation or abnormal gas exchange. No lung injury was observed. CBDL, but not PVL, causes progressive intrapulmonary vasodilatation, which accompanies worsening arterial gas exchange. These findings validate CBDL as a model to study HPS.

scholarly journals Hepatopulmonary Syndrome. Review

2021 ◽  
Vol 6 (3) ◽  
pp. 45-52
Author(s):  
V. V. Potii ◽  
◽  
V. T. Kiriienko ◽  
E. I. Glukhova ◽  
O. S. Kunickaya ◽  
...  
Keyword(s):  
Liver Transplantation ◽  
Portal Hypertension ◽  
Hepatopulmonary Syndrome ◽  
Gas Analysis ◽  
Arterial Oxygen ◽  
Common Symptom ◽  
Portopulmonary Hypertension ◽  
Oxygen Gradient ◽  
Arterial Blood ◽  
Intrapulmonary Shunting

Liver cirrhosis is often accompanied by complications from the pulmonary system. These include hydrothorax, portopulmonary hypertension and hepatopulmonary syndrome. Hepatic hydrothorax affects about 6-10% of patients with end-stage disease, which results in the passage of ascetic fluid into the pleural space through diaphragm defects. The common cause of the hepatopulmonary syndrome and portopulmonary hypertension is portal hypertension and portosystemic shunting, indicating that vasoactive and angiogenetic factors originating from the liver normally control the pulmonary circulation. Portopulmonary hypertension is like pulmonary arterial hypertension, which develops against the background of portal hypertension as a result of chronic liver disease or without other causes of increased pressure in the pulmonary vessels. The prevalence of portopulmonary hypertension ranges from 2% to 8.5% among patients with portal hypertension and is associated with a poor prognosis. Hepatopulmonary syndrome is characterized by intrapulmonary dilatation of microvessels, which causes intrapulmonary shunting and leads to impaired gas exchange in liver diseases, and is associated with a decrease in the quality and duration of life in patients with cirrhosis. Nitric oxide overproduction and angiogenesis seem to be the hallmarks of a complicated pathogenetic mechanism, leading to intrapulmonary shunting and ventilation-perfusion mismatch. A classification of hepatopulmonary syndrome according to the severity of hypoxemia has been suggested. Hepatopulmonary syndrome includes a triad: hepatic dysfunction and / or portal hypertension, dilatation of intrapulmonary vessels, and increased alveolar-arterial oxygen gradient. The prevalence of hepatopulmonary syndrome varies depending on the study groups from 5% to 30%. The most common symptom of the complication is shortness of breath, but in most cases, hepatopulmonary syndrome is asymptomatic. A decrease in oxygen saturation less than 96% corresponds to a decrease in PaO2<70 mm Hg and testifies to the possible development of hepatopulmonary syndrome. In the case of a positive screening, the patient should undergo arterial blood gas analysis, which helps to determine PaO2 and alveolar to arterial oxygen gradient. Conclusion. Contrast-enhanced echocardiography with agitated saline is the gold standard in the diagnosis of intrapulmonary dilatation. The only effective treatment for hepatopulmonary syndrome is liver transplantation. Complete recovery of hepatopulmonary syndrome after liver transplantation is observed within a year in most patients with cirrhosis and hepatopulmonary syndrome

scholarly journals Correlation analysis of gas and acid-base indices of arterial blood in the pathogenesis of experimental hepatopulmonary syndrome

2017 ◽  
Author(s):  
I. Ya. Krynytska
Keyword(s):  
Correlation Analysis ◽  
Bile Duct Ligation ◽  
Hepatopulmonary Syndrome ◽  
Moderate Correlation ◽  
Plasma Osmolarity ◽  
Acid Base ◽  
Common Bile Duct Ligation ◽  
Strong Negative Correlation ◽  
Arterial Blood ◽  
Duct Ligation

The correlation analysis of indices of gas and acid-base composition of arterial blood in the pathogenesis of experimental hepatopulmonary syndrome was studied in the article. It was established a strong negative correlation between partial pressure of oxygen and AaDO2, positive moderate correlation between the plasma osmolarity and AaDO2 in animals of both experimental groups, the positive moderate correlation between the concentration of lactic acid and AaDO2 in animals with carbon tetrachloride-induced cirrhosis and strong correlation interaction between these parameters in rats the on 31st day after common bile duct ligation.

Caspase-3 inhibition prevents the development of hepatopulmonary syndrome in common bile duct ligation rats by alleviating pulmonary injury

2014 ◽  
Vol 35 (4) ◽  
pp. 1373-1382 ◽  
Author(s):  
Bing Chen ◽  
Jiao L. Ning ◽  
Jian T. Gu ◽  
Jian Cui ◽  
Yong Yang ◽  
...  
Keyword(s):  
Bile Duct ◽  
Common Bile Duct ◽  
Caspase 3 ◽  
Bile Duct Ligation ◽  
Hepatopulmonary Syndrome ◽  
Pulmonary Injury ◽  
Common Bile Duct Ligation ◽  
Duct Ligation

scholarly journals MicroRNA-199a-5p Regulates the Proliferation of Pulmonary Microvascular Endothelial Cells in Hepatopulmonary Syndrome

2015 ◽  
Vol 37 (4) ◽  
pp. 1289-1300 ◽  
Author(s):  
Jing Zeng ◽  
Lin Chen ◽  
Bing Chen ◽  
Kaizhi Lu ◽  
Karine Belguise ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Hepatopulmonary Syndrome ◽  
Stress Fibers ◽  
Microvascular Endothelial Cell ◽  
Common Bile Duct Ligation ◽  
Down Regulation ◽  
Rat Serum ◽  
Rac1 Activity ◽  
Duct Ligation ◽  
Microvascular Endothelial

Background/Aims: Pulmonary microvascular endothelial cell (PMVEC) proliferation and angiogenesis contribute to the development of hepatopulmonary syndrome (HPS). MicroRNA-199a-5p (miR-199a-5p) has emerged as a potent regulator of angiogenesis, and its expression levels significantly decrease in the serum of patients with hepatopathy. However, it has not been reported about whether miR-199a-5p might control PMVEC proliferation. Here, we described the miR-199a-5p governing PMVEC proliferation in HPS. Methods: PMVECs were treated with rat serum from common bile duct ligation (CBDL) or sham. MiR-199a-5p mimic or inhibitor was used to change the miR-199a-5p expression. Knockdown of caveolin-1 (Cav-1) was performed using siRNA. NSC-23766 was used to inhibit Rac1 activity. Gene and protein expressions were quantified by qRT-PCR and western blot. Cell proliferation was analyzed by 3H-TdR incorporation and CCK-8 assays. Stress fibers were detected by immunofluorescence. Results: CBDL rat serum induced the down-regulation of miR-199a-5p. Delivery of miR-199a-5p suppressed the CBDL rat serum-induced PMVEC proliferation whereas knockdown of miR-199a-5p promoted PMVEC proliferation. This was accompanied by a decrease and an increase in Cav-1 expression, respectively. Cav-1 siRNA abolished the enhancement of PMVEC proliferation induced by the miR-199a-5p inhibition. Although stress fibers were disrupted in Cav-1 deficient cells, NSC-23766 increased stress fibers and contributed to cell proliferation. Conclusions: CBDL rat serum induced down-regulation of miR-199a-5p in PMVECs, which led to an increase of Cav-1 gene expression. Increased Cav-1 expression, by inhibiting Rac1 activity, led to the formation of stress fibers, which contribute to PMVEC proliferation and thus the pathogenesis of HPS.

scholarly journals Cholangiocyte-Derived Exosomal Long Noncoding RNA PICALM-AU1 Promotes Pulmonary Endothelial Cell EndMT in Hepatopulmonary Syndrome

2021 ◽  
Author(s):  
Congwen Yang ◽  
Yihui Yang ◽  
Yang Chen ◽  
Jian Huang ◽  
Caiyi Li ◽  
...  
Keyword(s):  
Noncoding Rna ◽  
Critical Role ◽  
Cell Communication ◽  
Hepatopulmonary Syndrome ◽  
Clinical Problem ◽  
Luciferase Reporter ◽  
Target Cells ◽  
Common Bile Duct Ligation ◽  
Mesenchymal Transition ◽  
Duct Ligation

Abstract Background: Hepatopulmonary syndrome (HPS) is an important clinical problem with limited understanding of disease pathologies. Exosome mediated cell-cell communication can modulate various cellular functions by transferring a variety of intracellular components to target cells. A new lncRNA PICALM-AU1 was found and upregulated in the liver of subjects with HPS. However, the expression and biological functions of the lncRNA PICALM-AU1 are still unknown. Methods: HPS rat model was constructed by common bile duct ligation (CBDL). RNA macroarray was used to analyze the expression differential lncRNAs in HPS rat liver. PICALM-AU1 expression in the serum exosome was measured in 56 HPS patients and in 73 patients with liver cirrhosis but not HPS. qPCR, Fluorescence in situ hybridization were used to analyze PICALM-AU1 expression and location. Virus derived PICALM-AU1 upregulation and down regulation were applied in rats and PMVECs cells. The effects of PICALM-AU1 on PMVECs was determined via CCK8 assay and transwell assay. PICALM-AU1 and miR144-3p relationship was analysis by Dual-luciferase reporter assay.Results: In this study, we found lncRNA PICALM-AU1 expressed in the cholangiocyte of liver, secreted as exosome into the serum. PICALM-AU1 carrying serum exosomes induced endothelial-mesenchymal transition (EndMT) of PMVECs and promoted lung injury. Furthermore, overexpression of PICALM-AU1 significantly suppressed miR144-3p and subsequently induced ZEB1 expression.Conclusions: Taken together, our findings present a road map of targeting the newly identified cholangiocyte-derived exosomal lncRNA PICALM-AU1 plays a critical role in the pathologic angiogenesis of HPS by promoting EndMT and represents a potential therapeutic target for HPS.

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