Intrapulmonary Vascular Dilatation Research Articles

Hepatopulmonary Syndrome.

Hepatopulmonary syndrome (HPS) is a pulmonary complication observed in patients with chronic liver disease and/or portal hypertension, attributable to an intrapulmonary vascular dilatation that may induce severe hypoxemia. Microvascular dilation and angiogenesis in the lung have been identified as pathologic features that drive gas exchange abnormalities in experimental HPS. Pulse oximetry is a useful screening test for HPS, which can guide subsequent use of arterial blood gases. Contrast-enhanced echocardiography, perfusion lung scanning, and pulmonary arteriography are three currently used diagnostic imaging modalities that identify the presence of intrapulmonary vascular abnormalities. The presence of HPS increases mortality and impairs quality of life, but is reversible with liver transplantation. No medical therapy is established as effective for HPS. At the present time, liver transplantation is the only available treatment for HPS.

Hepatopulmonary syndrome in children-an update

Hepato-pulmonary syndrome (HPS) is an uncommon complication of liver disease. It can be acute or chronic and occur with or without portal hypertension. The reported frequency of HPS in patients with liver disease ranges between 4% and 32%. It occurs as a result of vasodilatation of the pulmonary vasculature which is most likely to be mediated by nitric oxide (NO). Three components are essential to the definition of HPS: 1. liver disease, 2. intra-pulmonary vascular dilatation (IPVD) and 3. impaired oxygenation. .Disease severity is determined by quantifying the degree of oxygenation impairment. Contrast enhanced echocardiography (CE-TTE) and Tc-99 labeled macro-aggregated albumin lung scan with uptake in brain are the gold standard investigations to diagnose HPS and plan management. Clinical features which are characteristic of HPS include orthodeoxia and platypnea in the presence of liver disease. Although there are anecdotal reports on the use of several drugs in the medical management of HPS, none have been shown to result in either sustained improvement in oxygenation or reduce mortality. Liver transplantation is possible and no longer considered to be contraindicated in HPS. However it is important to carefully select and prioritize patients with HPS for liver transplantation for optimum results.

Variability of oxygenation in possible hepatopulmonary syndrome: effects of requiring two abnormal arterial blood gas results for diagnosis.

Hepatopulmonary syndrome (HPS) affects 10-32 % of patients with cirrhosis and is defined by liver abnormalities, intrapulmonary vascular dilatations (IPVDs), and abnormal oxygenation. However, published criteria for abnormal oxygenation are inconsistent. We sought to evaluate variation in oxygenation over time and to compare various diagnostic criteria for validity, based on their diagnostic stability over time and ability to identify patients with clinically relevant findings. We retrospectively analyzed oxygenation and diffusion capacity in patients with liver abnormalities and IPVDs who had ≥ 2 arterial blood gases (ABGs) at the University of Toronto or Universite de Montreal. We compared the performance of nine possible oxygenation criteria for HPS and for each explored whether validity improved when requiring two consecutive abnormal ABGs on different days. Mean PaO2 was 68.4 mmHg and annual within-patient coefficient of variation 6.3 % (58 patients). Applying published criteria, 8.6-15.5 % of patients initially diagnosed with HPS no longer met the criterion for HPS on a subsequent ABG (re-classified). Requiring two consecutive abnormal ABGs on different days: (1) reduced the proportion of re-classified patients (9/9 criteria); (2) identified patients with more rapid progression in hypoxemia and greater difference in rate of progression between HPS and non-HPS (7/9 criteria); and (3) identified patients with lower diffusion and a larger difference in diffusion between HPS and non-HPS (8/9 criteria). Oxygenation is variable in this population, and requiring two abnormal results might reduce misdiagnosis and better differentiate patients with and without HPS according to clinically relevant markers of disease.

The involvement of aquaporin 1 in the hepatopulmonary syndrome rat serum-induced migration of pulmonary arterial smooth muscle cells via the p38-MAPK pathway.

Hepatopulmonary syndrome (HPS) is characterized by arterial oxygenation defects induced by intrapulmonary vascular dilation (IPVD). Pulmonary vascular remodeling (PVR) is an important pathological feature of IPVD; however, the details regarding the underlying mechanisms of this process remain undefined. Recent studies have determined that the abnormal migration of pulmonary arterial smooth muscle cells (PASMCs) plays a role in the pathogenesis of the PVR associated with HPS. Additionally, aquaporin 1 (AQP1) not only functions as a water channel molecule but also promotes cell migration by facilitating water transport in the lamellipodia of migrating cells. Common bile duct ligation (CBDL) rat is a well-accepted HPS model; we determined that the immunoperoxidase labeling of AQP1 was enhanced in the media of the pulmonary vessels in CBDL rats. HPS rat serum mediated the overexpression of AQP1 in PASMCs, and also upregulated PASMC migration. Small interfering RNAs (siRNAs) that targeted rat AQP1 caused significant downregulation of AQP1, which resulted in decreased PASMC migration. Furthermore, the inhibition of the p38-MAPK pathway abolished AQP1-dependent PASMC migration. In conclusion, this study demonstrated that AQP1 enhanced PASMC migration via the p38-MAPK pathway in rat with HPS and may represent a potential therapeutic strategy in the setting of pulmonary vascular remodeling associated with HPS.

English

INTRODUCTION: Pulmonary abnormalities and symptoms are common in patients with chronic liver disease. Hepatopulmonary syndrome is an important cause in a patient with hypoxemia and chronic liver disease. Hepatopulmonary syndrome consists of a triad of hepatic dysfunction and/or portal hypertension, intrapulmonary vascular dilatations and hypoxemia/ widened alveolar- arterial gradient. The present study evaluated the arterial blood gas levels and correlated these with 2D contrast echocardiographic findings in patients of liver cirrhosis. METHODS: 40 patients of liver cirrhosis were included in the study. All patients underwent ultrasonography, LFTs, biochemical tests and upper gastrointestinal endoscopy, chest X-ray, 2-D contrast enhanced transthoracic echocardiogram, viral markers and arterial blood gas analysis. The patients in whom arterial hypoxemia/ widened alveolar-arterial gradient was detected with a positive contrast echocardiogram were considered to have hepatopulmonary syndrome. Patients with intrinsic heart disease like patent foramen ovale, atrial septal defect, ventricular septal defect, haemoglobin less than 7gm% and history of COPD were excluded from the study. RESULTS: 4 patients of liver cirrhosis with hypoxemia had intrapulmonary vascular dilatations were labelled as hepatopulmonary syndrome. 2 additional patients with IPVDs had widened alveolar arterial gradient without hypoxemia and were also labelled as HPS. Dyspnoea (p=0.001), platypnea (p<0.001), clubbing (p=0.002) and cyanosis (p=0.001) were significantly commoner in the six patients of hepatopulmonary syndrome. Patients with cyanosis had poor prognosis. CONCLUSION: Hepatopulmonary syndrome is an important cause of hypoxemia in patients of liver cirrhosis. It is not uncommon in patients of liver cirrhosis. Platypnea is both sensitive as well as specific marker of the disease. Transthoracic contrast enhanced echocardiogram is a safe and accurate bedside tool for the detection of IPVDs.

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

Common bile duct ligation (CBDL) rats is an accepted experimental model of hepatopulmonary syndrome (HPS), defined as liver disease and intrapulmonary vascular dilatation and hypoxaemia. Pulmonary Akt and ERK activation followed by angiogenesis in the later stages of CBDL, contribute to the pathogenesis of HPS. However, the mechanisms behind Akt and ERK activation remain undefined. Pulmonary injury induced by increased bilirubin, endotoxin and inflammatory mediators occurs in the early stages of CBDL. We assessed the effects of relieving pulmonary injury on Akt and ERK activation and on the development of HPS following CBDL. Pulmonary injury, angiogenesis, arterial oxygenation, cell proliferation and, phospho-Akt and ERK1 were evaluated in CBDL animals with or without caspase-3 inhibition (Z-DEVD-FMK). Pulmonary injury was assessed by histology and quantifying apoptosis and aquaporin-1 (AQP1) levels. Lung angiogenesis was assessed by quantifying AQP1 level, vWF-positive cells and microvessel count. Pulmonary apoptosis and caspase-3 activation were markedly increased in the early stages of CBDL. Caspase-3 inhibition alleviated apoptosis, the reduction in AQP1, phospho-Akt and ERK1 levels and pulmonary injury 1 week after CBDL. Caspase-3 inhibition also reduced AQP1, phospho-Akt and ERK1 levels, vWF-positive cells, cell proliferation, microvessel count, and microvascular dilatation and improved arterial oxygenation 3 weeks following CBDL. Caspase-3 inhibition alleviates pulmonary injury, thereby preventing angiogenesis as well as the development of HPS in CBDL rats. These effects are related to the regulation of the Akt and ERK1 pathways.

Prevalence and predictors of hepatopulmonary syndrome in liver transplant candidates

BackgroundHepatopulmonary syndrome (HPS) is an independent predictor of survival after liver transplantation. Although the prevalence of chronic liver diseases is high in Egypt, the frequency of HPS among liver transplant candidates (LTC) is unknown. AimTo assess the frequency of HPS and factors predictive of diagnosis of HPS in patients with end-stage liver diseases who are LTC. MethodsA cross sectional study of patients with end stage liver diseases who are LTC. Patients were subjected to clinical examination, laboratory investigations, arterial blood gas (ABG) measurement, pulmonary function tests, upper gastrointestinal endoscopy, and transthoracic contrast enhanced echocardiography (TCEE). The severity of liver disease was assessed by Model for end-stage liver disease (MELD) score. The diagnostic criteria for HPS were intrapulmonary vascular dilatation (IPVD) documented by TCEE, and alveolar-arterial oxygen gradient (A-aDO2) ⩾15mmHg. ResultsEighty-four LTC patients were enrolled in the study. Sixteen patients (19%) fulfilled the criteria for diagnosis of HPS. Patients with HPS showed older ages, longer duration of liver diseases which were more severe (MELD score). Dyspnoea, cyanosis, clubbing, platypnoea, spider naevi and features of portal hypertension were significantly more common in the HPS group. In the recumbent position; patients with HPS had a significantly lower PaO2 and larger A-aDO2 compared to those without HPS. Patients with HPS showed a further fall in their PaO2 on sitting up (orthodeoxia). ConclusionsThe prevalence of HPS among the studied group of Egyptian liver transplant candidates is 19%. Cyanosis, clubbing, spider naevi and platypnoea–orthodeoxia are suggestive indicators of HPS.

Intrapulmonary vascular dilatation evaluated by 99mTc-MAA scintigraphy and its association with portal hypertension in schistosomiasis.

BackgroundPortal hypertension is responsible for various complications in patients with schistosomiasis, among them intrapulmonary vascular dilations (IPVD). In cirrhotic patients the presence of IPVD is a sign of poor prognosis, but in patients with hepatosplenic schistosomiasis (HSS) there are no studies assessing the significance of this change. The aim of this study was to evaluate the occurrence of IPVD through 99mTc-MAA scintigraphy in patients with HSS and its relationship with clinical, laboratory, endoscopic and ultrasound parameters.MethodsCross-sectional study evaluating 51 patients with HSS. Patients were diagnosed with IPVD when the brain uptake of 99mTc-MAA was higher than 6%. Subsequently, they were divided according to presence (G1) or absence (G2) of IPVD and variables were compared between groups.ResultsOverall, 51 patients with mean age of 56±12 years were assessed. IPVD was observed in 31 patients (60%). There was no statistically significant differences between groups when clinical, laboratory and endoscopic parameters were compared. Regarding ultrasound parameters, the splenic vein diameter was smaller in G1 (0.9±0.3 cm) compared to G2 (1.2±0.4 cm), p = 0.029.ConclusionIn patients with HSS, the occurrence of IPVD by 99mTc-MAA scintigraphy was high and was associated with lower splenic vein diameter, which can be a mechanism of vascular protection against portal hypertension. However, more studies are needed to determine the clinical significance of the early diagnosis and natural evolution of IPVD in this population.

The hepatopulmonary syndrome.

IntroductionThe hepatopulmonary syndrome has been acknowledged as an important vascular complication in lungs developing systemic hypoxemia in patients with cirrhosis and portal hypertension. Is formed by arterial oxygenation abnormalities induced from intrapulmonary vascular dilatations with liver disease. It is present in 4-32% of patients with cirrhosis. It increases mortality in the setting of cirrhosis and may influence the frequency and severity. Initially the hypoxemia responds to low-flow supplemental oxygen, but over time, the need for oxygen supplementation is necessary. The liver transplantation is the only effective therapeutic option for its resolution.AimTo update clinical manifestation, diagnosis and treatment of this entity.MethodA literature review was performed on management of hepatopulmonary syndrome. The electronic search was held of the Medline-PubMed, in English crossing the headings "hepatopulmonary syndrome", "liver transplantation" and "surgery". The search was completed in September 2013.ResultsHepatopulmonary syndrome is classically defined by a widened alveolar-arterial oxygen gradient (AaPO2) on room air (>15 mmHg, or >20 mmHg in patients >64 years of age) with or without hypoxemia resulting from intrapulmonary vasodilatation in the presence of hepatic dysfunction or portal hypertension. Clinical manifestation, diagnosis, classification, treatments and outcomes are varied.ConclusionThe severity of hepatopulmonary syndrome is an important survival predictor and determine the improvement, the time and risks for liver transplantation. The liver transplantation still remains the only effective therapeutic.

Role of angiogenic factors/cell adhesion markers in serum of cirrhotic patients with hepatopulmonary syndrome

Hepatopulmonary syndrome is a complication of chronic liver disease resulting in increased morbidity and mortality. It is caused by intrapulmonary vascular dilations and arteriovenous connections with devastating influence on gas exchange. The pathogenesis is not completely understood but evidence mounts for angiogenesis. Aims of this study were to identify angiogenic factors in serum of patients with hepatopulmonary syndrome and to study the possibility to predict its presence by these factors. Multiplex assays were used to measure the concentration of angiogenic factors in patients with (n=30) and without hepatopulmonary syndrome (n=30). Diagnosis was based on the presence of gas exchange abnormality and intrapulmonary vasodilations according to published guidelines. Patients with and without hepatopulmonary syndrome had similar MELD scores (median: 11.2 vs. 11.6; P=0.7), Child-Pugh score (P=0.7) and PaCO2 values (median: 35 vs. 37; P=0.06). PaO2 and P(A-a) O2 gradient were significantly different (respectively median of 80 vs. 86, P=0.02; and 24 vs. 16, P=0.004). Based on area under the curve (AUC) data and P-values, the best predictors were vascular cell adhesion molecule 1 (VCAM1) (AUC=0.932; P<0.001) and intercellular adhesion molecule 3 (ICAM3) (AUC=0.741; P=0.003). Combining these factors results in an AUC of 0.99 (after cross-validation still 0.99). VCAM1 and ICAM3 might be promising biomarkers for predicting hepatopulmonary syndrome. Combining these factors results in an AUC of 0.99 and a negative predictive value of 100%. Determining the concentration of these biomarkers might be a screening method to detect hepatopulmonary syndrome. The use of these biomarkers should be validated in larger groups of patients.

Diagnostic evaluation of hepatopulmonary syndrome in Egyptian children with chronic liver disease.

There are few data on prevalence of hepatopulmonary syndrome (HPS) in children with chronic liver disease (CLD). This prospective study evaluated the prevalence and diagnostic procedures of HPS in Egyptian children with CLD. One hundred twenty (120) children with CLD were subjected to room-air pulse oximetry in supine and upright position, contrast enhanced echocardiography (CEE) and technetium-99m-labeled macroaggregated albumin (99mTc-MAA) perfusion lung scan. Arterial blood gas (ABG) analysis in upright position was performed for all children with identified intrapulmonary vascular dilatation (IPVD). Clinical, laboratory, imaging and endoscopic data were recorded and analyzed. Hypoxemia was found in 14 cases (11.7%) of the total cohort all of them had IPVD, whereas 6 cases (5%) of the patients had IPVD without hypoxemia. Therefore, HPS and subclinical HPS were diagnosed in 11.7% and 5% of CLD patients, respectively. Only 10 HPS patients had a pathological arterial oxygen saturation (SaO2) in the supine position (< or = 97%) but all showed a pathological SaO2 decrease (> or = 4%) after changing from supine to upright position. 99mTc-MAA perfusion lung scan revealed IPVD in 16.7% whereas CEE detected IPVD in 10% only of enrolled patients. There were strong correlations between shunt index estimated by lung scintiscan and oxygenation parameters in HPS patients. The characteristics of HPS patients were similar to that of non-HPS patients except for clubbing, dyspnea, cyanosis, orthodoexia and bleeding varices that were more associated with HPS patients as well as well as the Child-Pugh grades, which tended toward higher scores in HPS patients.

Pulmonary complications in chronic liver disease.

The association of chronic liver disease with respiratory symptoms and hypoxia is well recognized. Over the last century, three pulmonary complications specific to chronic liver disease have been characterized: hepatopulmonary syndrome (HPS), portopulmonary hypertension (POPH), and hepatic hydrothorax (HH). The development of portal hypertension is fundamental in the pathogenesis of each of these disorders. HPS is the most common condition, found in 5%-30% of cirrhosis patients, manifested by abnormal oxygenation due to the development of intrapulmonary vascular dilatations. The presence of HPS increases mortality and impairs quality of life, but is reversible with liver transplantation (LT). POPH is characterized by development of pulmonary arterial hypertension in the setting of portal hypertension, and is present in 5%-10% of cirrhosis patients evaluated for LT. Screening for POPH in cirrhosis patients eligible for LT is critical since severe POPH is a relative contraindication for LT. Patients with moderate POPH, who respond adequately to medical therapy, may benefit from LT, although sufficient controlled data are lacking. HH is a transudative pleural effusion seen in 5%-10% of cirrhosis patients, in the absence of cardiopulmonary disease. Diagnosis of HH should prompt consideration for LT, which is the ultimate treatment for HH. Conservative management includes salt restriction and diuretics, with thoracentesis and transjugular intrahepatic portosystemic shunt (TIPS) as second-line therapeutic options.

Cirrhosis and hepatopulmonary syndrome

Hepatopulmonary syndrome (HPS) is characterized as a triad: liver disease, intrapulmonary vascular dilatation and arterial hypoxemia. HPS is reported to be present in 4% to 32% of adult patients with end-stage liver disease and in 9%-20% of children. The pathogenesis of HPS has not been clearly identified. Portal hypertension causes impairment in the perfusion of the bowel and increases the enteral translocation of Gram (-) bacteria and endotoxins. This stimulates the release of vasoactive mediators, such as tumor necrosis factor-alpha, heme oxygenase-derived carbon monoxide and nitric oxide. Genetic alterations have not been associated with this syndrome yet; however, cytokines and chemokines have been suggested to play a role. Recently, it was reported that cumulated monocytes lead to the activation of vascular endothelial growth factor-dependent signaling pathways and pulmonary angiogenesis, which plays an important role in HPS pathogenesis. At present, the most effective and only radical treatment is a liver transplant (LT). Cirrhotic patients who are on the waiting list for an LT have a shorter survival period if they develop HPS. Therefore, it is suggested that all cirrhotic cases should be followed closely for HPS and they should have priority in the waiting list.

Hypoxia among patients on the liver-transplant waiting list

BackgroundHepatopulmonary syndrome is formed by a triad of liver disease, intrapulmonary vascular dilatation and changes in blood gases. This condition is present in 4-32% of patients with cirrhosis.AimTo analyze the blood gas changes data of patients in liver-transplant waiting list.MethodClinical data of 279 patients in liver transplantation waiting list in May 2013 were studied. Overall patient was analyzed by the demographic aspects, laboratorial and image findings on exams that determine lung disease (hypoxemia) in these cirrhotic patients. The mean values and standard deviations were used to examine normally distributed variables.ResultsThere was a high prevalence of male patients (68%); the mean age was 51(±5,89) years, and the predominant reason for listing was hepatitis C cirrhosis. The MELD score mean was 16±5,89, without prioritization or special situation. The most common blood type was O in 129 cases (46%) and the mean of body max index was 25,94±4,58. Regarding arterial blood gas tests was observed 214 patients with PaO2 <90 mmHg, 80 with PaO2 <80 mmHg and 39 with PaO2 <50 mmHg. In relation to O2 saturation, 50 patients had <90%, 33 <80% and 10 <50%.ConclusionWas observed a high rate of hypoxemia in patients on waiting list liver transplant. Due to the high severity and morbidity, is suggested better monitoring and therapeutic support to hypoxemic patients on liver transplant waiting list.

MiR-206 Controls the Phenotypic Modulation of Pulmonary Arterial Smooth Muscle Cells Induced by Serum from Rats with Hepatopulmonary Syndrome by Regulating the Target Gene, Annexin A2

Background: Hepatopulmonary syndrome (HPS) is a serious complication of advanced liver disease that is characterised by intrapulmonary vascular dilatation (IPVD) and arterial hypoxemia. Pulmonary vascular remodelling (PVR) is an important pathological feature of HPS, but the potential mechanisms underlying PVR remain undefined. Recent findings have established the essential role of changes in Annexin A2 (ANXA2) in controlling the phenotypic modulation of pulmonary artery smooth muscle cells (PASMCs) in PVR associated with HPS. However, the mechanism by which upstream signalling regulates ANXA2 is unclear. Methods: In the present study, computational analysis was used to predict which miRNA might target the 3´-untranslated region (3´-UTR) of the ANXA2 mRNA. Real-time PCR and western blotting were performed to study the level of correlation between ANXA2 and the differentiation marker with the predicted miRNAs in PASMCs stimulated with serum from normal rats or those with HPS. Functional analysis of the miRNA and a luciferase reporter assay were performed to demonstrate that the predicted miRNA suppressed ANXA2 expression by directly targeting the predicted 3´-UTR site of the ANXA2 mRNA. Results: Computational analysis predicted that miR-206 would target the 3´-UTR of ANXA2 mRNA. In HPS rat serum-stimulated PASMCs, the expression of miR-206 displayed an inverse correlation with ANXA2, while a positive correlation was observed with the phenotypic marker smooth muscle α-actin (SM α-actin). The miRNA functional analysis and luciferase reporter assay demonstrated that miR-206 effectively downregulated the expression of ANXA2 by binding to the 3´-UTR of the ANXA2 mRNA. Consistently, miR-206 effectively inhibited the HPS rat serum-induced phenotypic modulation and proliferation, while these effects were reversed in ANXA2-overexpressing PASMCs. Conclusion: This study demonstrates that miR-206 inhibits the HPS rat serum-induced phenotypic modulation and proliferation in PASMCs by down-regulating ANXA2 gene expression.

Defining and characterizing severe hypoxemia after liver transplantation in hepatopulmonary syndrome

Hepatopulmonary syndrome is defined as a triad of liver disease, intrapulmonary vascular dilatations, and abnormal gas exchange, and it carries a poor prognosis. Liver transplantation is the only known cure for this syndrome. Severe hypoxemia in the early postoperative period has been reported to be a major complication and often leads to death in this population, but it has been poorly characterized. We sought to propose an objective definition for this complication and to describe its risk factors, incidence, and outcomes. We performed a systematic literature search and reviewed our single-center experience to characterize this complication. On the basis of the most commonly applied definition in 27 identified studies, we objectively defined severe postoperative hypoxemia as hypoxemia requiring a 100% fraction of inhaled oxygen to maintain a saturation ≥ 85% and out of proportion to any concurrent lung process. Nineteen of the 27 reports (70%) fulfilled this definition, as did 4 of the 21 patients (19%) at our center. We determined the prevalence and mortality of this complication from reports including 10 or more consecutive patients and providing sufficient postoperative details to determine whether this complication had occurred. In these reports, the prevalence of this complication was 12% (25/209). For the 11 cases with reported outcomes, the posttransplant mortality rate was 45% (5/11). There was a trend toward an increased risk of developing this complication in patients with very severe preoperative hypoxemia, defined as a partial pressure of arterial oxygen ≤ 50 mm Hg (8/41 with very severe hypoxemia versus 3/49 without severe hypoxemia, P = 0.053), and there was a significantly increased risk for patients with anatomic shunting ≥ 20% (7/25 with anatomic shunting ≥ 20% versus 1/25 without anatomic shunting ≥ 20%, P = 0.049). In conclusion, increased preoperative vigilance for this common complication is required among high-risk patients, and further research is required to identify the best management strategies.

Atividade da mieloperoxidase está aumentada na síndrome hepatopulmonar em ratos

Hepatopulmonary syndrome is formed by a triad of liver disease, intrapulmonary vascular dilatation and changes in blood gases. Its pathogenesis is not well defined, but it is speculated that a combination of factors, such as the imbalance of endothelin receptor responses, pulmonary microvascular remodeling, and genetic predisposition, leads to bacterial translocation and intrapulmonary vascular dilatation. To evaluate the myeloperoxidase activity in hepatopulmonary syndrome in rat model. Twenty-nine rats were divided into control, sham and experimental hepatopulmonary syndrome groups. Was evaluated the myeloperoxidase activity and the experimental model used to induce hepatopulmonary syndrome was common bile duct ligation. The myeloperoxidase activity levels were significantly increased in the common bile duct ligation group as compared with the other groups. Myeloperoxidase activity was higher in the common bile duct ligation group than control group (p<0.05) and than sham group (p<0.05). The myeloperoxidase activity is increased in experimental hepatopulmonary syndrome in rats.

Hepatopulmonary syndrome

Hepatopulmonary syndrome (HPS) is a pulmonary complication observed in patients with chronic liver disease and/or portal hypertension, attributable to an intrapulmonary vascular dilatation that induces severe hypoxaemia. Considering the favourable long-term survival of HPS patients as well as the reversal of the syndrome with a functional liver graft, HPS is now an indication for orthotopic liver transplantation (OLT). Consequently, blood gas analysis and imaging techniques should be performed when cirrhotic patients present with shortness of breath as well as when OLT candidates are placed on the transplant waiting list. If the arterial partial pressure of oxygen (PaO2) is more than 10.7 kPa when breathing room air, HPS can be excluded and no other investigation is needed. When the PaO2 when breathing room air is 10.7 kPa or less, contrast-enhanced echocardiography should be performed to exclude pulmonary vascular dilatation. Lung function tests may also help detect additional pulmonary diseases that can contribute to impaired oxygenation. When contrast-enhanced echocardiography is negative, HPS is excluded and no follow-up is needed. When contrast-enhanced echocardiography is positive and PaO2 less than 8 kPa, patients should obtain a severity score that provides them with a reasonable probability of being transplanted within 3 months. In mild-to-moderate HPS (PaO2 8 to 10.6 kPa), periodic follow-up is recommended every 3 months to detect any further deterioration in PaO2. Although no intraoperative deaths have been directly attributed to HPS, oxygenation may worsen immediately following OLT due to volume overload and postoperative infections. Mechanical ventilation is often prolonged with an extended stay in the ICU. A high postoperative mortality (mostly within 6 months) is observed in this group of patients in comparison to non-HPS patients. However, the recovery of an adequate PaO2 within 12 months after OLT explains the similar outcome of HPS and non-HPS patients following OLT over a longer time period.

Annexin A1 protein regulates the expression of PMVEC cytoskeletal proteins in CBDL rat serum-induced pulmonary microvascular remodeling

BackgroundHepatopulmonary syndrome (HPS) is characterized by advanced liver disease, hypoxemia and intrapulmonary vascular dilatation (IPVD). The pathogenesis of HPS is not completely understood. Recent findings have established the role of proliferation and phenotype differentiation of pulmonary microvascular endothelial cells (PMVECs) in IPVD of HPS; the change in cytoskeletal proteins and their molecular mechanism play an essential role in the proliferation, phenotype modulation and differentiation of PMVECs. However, little is known about the relevance of cytoskeletal protein expression and its molecular mechanism in IPVD of HPS. In addition, ANX A1 protein has been identified as a key regulator in some important signaling pathways, which influences cytoskeletal remodeling in many diseases, such as lung cancer, liver cancer, etc.MethodsPMVECs were cultured from the normal rats and then divided into three groups(Ad-ANXA1-transfected group, a non-transfected group, and an adenovirus empty vector group) and incubated by nomal rat serum or hepatopulmonary syndrome rat serum respectively. mRNA level was evaluated by real time reverse transcription polymerase chain reaction, and protein expression was detected by western blot. Cell proliferation was determined by the MTT and thymidine incorporation assay.ResultsIn this study, we found that the serum from a common bile duct ligation(CBDL) Rat model decreased the expression levels of the ANX A1 mRNA and protein by at least two-fold in human PMVECs. We also found the expression of cytoskeletal proteins (Destrin, a1-actin, and a1-tubulin) in PMVECs significantly increased. After stimulating ANX A1 over-expression in PMVECs by adenovirus-mediated ANX A1 (Ad-ANXA1) transfection, we found the expression levels of cytoskeletal proteins were significantly suppressed in PMVECs at all time points. Additionally, we report here that serum from a CBDL Rat model increases the proliferation of PMVECs by nearly two-fold and that over-expression of Ad-ANXA1 significantly inhibits HPS-rat-serum-induced PMVEC proliferation (p <0.05). These findings suggest that the ANX A1 down-regulation of PMVEC proliferation in the presence of HPS-rat-serum may be the major cause of aberrant dysregulation of cytoskeletal proteins (Destrin, a1-actin, and a1-tubulin) and may, therefore, play a fundamental role in the proliferation and phenotype differentiation of PMVECs in the PVD of HPS.ConclusionFinally, the fact that transfection with Ad-ANXA1 results in inhibition of the aberrant dysregulation of cytoskeletal proteins and proliferation of PMVECs suggests a potential therapeutic effect on PVD of HPS.

Use of airway pressure release ventilation in a child with refractory hepatopulmonary syndrome after liver transplantation

HPS is a life-threatening condition in patients with end-stage liver disease, in which intrapulmonary vascular dilatations result in intrapulmonary shunts and hypoxemia. The only successful treatment is liver transplantation. Hypoxemia may be severe prior to transplantation; however, it can worsen or become refractory after liver transplantation and result in increased post-operative mortality. Here, we present the case of a 10-month-old female infant with progressive end-stage liver disease and severe HPS, who developed refractory hypoxemia after a successful liver transplantation. After 19days of unsuccessful attempts to reverse the hypoxemia using conventional mechanical ventilation and HFOV, the patient responded dramatically to APRV, with rapid improvement in her PaO2 and sharp decline in her OI. She was able to begin weaning from APRV twodays later and was extubated within sevendays. APRV was successful in treating refractory hypoxemia in this patient with severe HPS after liver transplantation, possibly by modifying distribution of pulmonary blood flow. Although we cannot rule out coincidental natural resolution of the HPS, APRV could be a useful rescue therapy in patients with HPS and refractory hypoxemia.