Intrapulmonary Vascular Dilatation Research Articles

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.

Hepatopulmonary syndrome: Favorable outcomes in the MELD exception era

Hepatopulmonary syndrome (HPS) is a pulmonary vascular disorder occurring as a consequence of advanced liver disease, characterized by hypoxemia due to intrapulmonary vascular dilatations. HPS independently increases mortality, regardless of the cause or severity of liver disease. Liver transplantation (LT) improves survival in HPS. We present the largest consecutive series of HPS patients specifically addressing long-term survival relative to the degree of hypoxemia and the era in which LT was conducted. We evaluated 106 HPS patients at the Mayo Clinic from 1986 through 2010. Survival was assessed using Kaplan-Meier methodology. LT was accomplished in 49 HPS patients. Post-LT survival (1, 3, 5, and 10 years) did not differ between groups based on baseline partial pressure of arterial oxygen (PaO2 ) obtained at the time of HPS diagnosis. Improvements in overall survival at 1, 3, and 5 years post-LT in those HPS patients transplanted after January 1 2002 (n = 28) (92%, 88%, and 88%, respectively) as compared with those transplanted prior to that time (n = 21) (71%, 67%, and 67%, respectively) did not reach statistical significance (5-year P = 0.09). Model for Endstage Liver Disease (MELD) exception to facilitate LT was granted to 21 patients since January 1 2002 with post-LT survival of 19/21 patients and one wait-list death. Long-term outcome after LT in HPS is favorable, with a trend towards improved survival in the MELD exception era since 2002 as compared to earlier HPS transplants. Survival after LT was not associated with PaO2 levels at the time of HPS diagnosis. (HEPATOLOGY 2012).

Pulmonary vascular complications in portal hypertension and liver disease: A concise review

Chronic liver disease and/or portal hypertension may be associated with one of the two pulmonary vascular complications: portopulmonary hypertension and hepatopulmonary syndrome. These pulmonary vascular disorders are notoriously underdiagnosed; however, they have a substantial negative impact on survival and require special attention in order to understand their diagnostic approach and to select the best therapeutic options. Portopulmonary hypertension results from excessive vasoconstriction, vascular remodeling, and proliferative and thrombotic events within the pulmonary circulation that lead to progressive right ventricular failure and ultimately to death. On the other hand, abnormal intrapulmonary vascular dilations, profound hypoxemia, and a wide alveolar-arterial gradient are the hallmarks of the hepatopulmonary syndrome, resulting in difficult-to-treat hypoxemia. The aim of this review is to summarize the latest pathophysiologic concepts, diagnostic approach, therapy, and prognosis of portopulmonary hypertension and hepatopulmonary syndrome, as well as to discuss the role of liver transplantation as a definitive therapy in selected patients with these conditions.

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Case Reports: Hepatopulmonary syndrome (HPS) is defined as a clinical triad of chronic liver disease, abnormal pulmonary gas exchange resulting in arterial hypoxemia, and evidence of intrapulmonary vascular dilations producing a right to left intrapulmonary shunt. The only definitive treatment option is liver transplantation, with an anticipated improvement and subsequent resolution of hypoxemia weeks to months following transplantation. In light of an increasing trend to transplant patients with severe HPS characterized by profound hypoxemia, practical alternatives to high flow nasal cannula (HFNC) need to be considered in order to facilitate post-transplant patient mobilization and early discharge from the hospital while treating severe hypoxemia. To this end, we describe our experience with the application of transtracheal oxygen therapy in the management of post-operative hypoxemia following OLT for severe HPS in three patients. Persistent arterial hypoxemia in the immediate post-operative period required the use of high-flow nasal cannula (HFNC) oxygen. Although allograft function steadily improved, the patients’ hypoxemia did not improve in the immediate post-operative period, and they subsequently underwent placement of a transtracheal oxygen (TTO) catheter to facilitate mobilization and weaning from HFNC. Therapy with oxygen via the TTO catheter led to early patient mobilization and discharge, and rapid weaning and eventual liberation from supplemental oxygen. To our knowledge, this is the first report of such a management technique for this unique group of patients. Our observations highlight the utility of transtracheal oxygen therapy in the management of severe HPS after liver transplantation.

A Case of Unexplained Hypoxemia

We present a patient with acute-onset dyspnea and unexplained severe hypoxemia. No signs of severe cardiopulmonary disease, pulmonary arterial hypertension, or pulmonary embolism were present. The patient was diagnosed with hepatopulmonary syndrome, since liver disease of alcoholic origin was present, markedly increased alveolar-arterial oxygen difference existed, and intrapulmonary vascular dilations were demonstrated. The condition of the patient did not improve and he was referred for liver transplantation, which is the only treatment option with documented efficacy. The case highlights the importance of thinking outside the thorax when evaluating patients with dyspnea.

MicroRNA-101 inhibits proliferation of pulmonary microvascular endothelial cells in a rat model of hepatopulmonary syndrome by targeting the JAK2/STAT3 signaling pathway

Hepatopulmonary syndrome (HPS) is one of the reasons for the mortality of patients with perioperative liver disease. Intrapulmonary vascular dilatation is the most important mechanism underlying HPS, and it primarily occurs due to cell proliferation. Inhibiting the proliferation of pulmonary microvascular endothelial cells (PMVECs) may provide a novel strategy to prevent HPS. MicroRNAs (miRNAs) regulate gene expression and are crucial in cell proliferation. To investigate the mechanism underlying the proliferation of PMVECs in HPS, PMVECs were isolated from rat models of HPS. It was demonstrated that interleukin (IL)‑6 could stimulate the janus kinase 2 (JAK2)/ signal transducer and activator of transcription (STAT3) signaling pathway, which promotes the cell proliferation of PMVECs. JAK2 is a novel target gene of miR-101 and it was shown that miR-101 could inhibit cell proliferation by targeting the IL-6/JAK2/STAT3 signal pathway. In conclusion, the present study demonstrated that miR-101 could inhibit the proliferation of PMVECs by targeting the IL-6/JAK2/STAT3 signaling pathway. This clarifies the role of miR-101 in HPS and provides the theoretical basis of the pathogenesis of HPS.

The clinical significance of intrapulmonary vascular dilations in liver transplant candidates

Intrapulmonary vascular dilations (IPVD) are common in patients with cirrhosis, but the majority do not have hepatopulmonary syndrome (HPS). The clinical significance of IPVD is unknown. Our aim was to determine the clinical impact due to the entire spectrum of IPVD in liver transplant (LT) candidates. A total of 122 evaluees for LT underwent contrast transthoracic echocardiography (cTTE). The degree of shunting was graded 1-3 (severe). HPS was defined as PaO(2) < 70 mmHg in the presence of IPVD and exclusion of other causes of hypoxemia. IPVD were detected in 57/122 (47%), and of these HPS was found in 5. IPVD were associated with higher Alveolar-arterial (A-a) gradients, with the highest occurring in patients with HPS (IPVD vs. no IPVD: p = 0.003; HPS vs. no IPVD: p = 0.004). All patients with HPS had grade 3 shunting, and had significantly widened A-a gradient and lower PaO(2) compared with grade 1 or 2 IPVDs. Presence of IPVD did not affect survival measured from evaluation or after LT. Other clinical outcomes were also similar among patients with and without IPVD. IPVD are common among LT candidates. HPS is unlikely in presence of only mild to moderate shunting. Clinical outcomes are similar among patients with and without IPVD.

Hepatopulmonary syndrome: update on pathogenesis and clinical features.

Hepatopulmonary syndrome (HPS) is a serious vascular complication of liver disease that occurs in 5-32% of patients with cirrhosis. The presence of HPS markedly increases mortality. No effective medical therapies are currently available and liver transplantation is the only established treatment option for HPS. The definition and diagnosis of HPS are established by the presence of a triad of liver disease with intrapulmonary vascular dilation that causes abnormal arterial gas exchange. Experimental biliary cirrhosis induced by common bile duct ligation in the rat reproduces the pulmonary vascular and gas exchange abnormalities of human HPS and serves as a pertinent animal model. Pulmonary microvascular dilation and angiogenesis are two central pathogenic features that drive abnormal pulmonary gas exchange in experimental HPS, and thus might underlie HPS in humans. Defining the mechanisms involved in the microvascular alterations of HPS has the potential to lead to effective medical therapies. This Review focuses on the current understanding of the pathogenesis, clinical features and management of HPS.

The role of CX3CL1/CX3CR1 in pulmonary angiogenesis and intravascular monocyte accumulation in rat experimental hepatopulmonary syndrome

Hepatopulmonary syndrome (HPS), classically attributed to intrapulmonary vascular dilatation, occurs in 15-30% of cirrhotics and causes hypoxemia and increases mortality. In experimental HPS after common bile duct ligation (CBDL), monocytes adhere in the lung vasculature and produce vascular endothelial growth factor (VEGF)-A and angiogenesis ensues and contribute to abnormal gas exchange. However, the mechanisms for these events are unknown. The chemokine fractalkine (CX(3)CL1) can directly mediate monocyte adhesion and activate VEGF-A and angiogenesis via its receptor CX(3)CR1 on monocytes and endothelium during inflammatory angiogenesis. We explored whether pulmonary CX(3)CL1/CX(3)CR1 alterations occur after CBDL and influence pulmonary angiogenesis and HPS. Pulmonary CX(3)CL1/CX(3)CR1 expression and localization, CX(3)CL1 signaling pathway activation, monocyte accumulation, and development of angiogenesis and HPS were assessed in 2- and 4-week CBDL animals. The effects of a neutralizing antibody to CX(3)CR1 (anti-CX(3)CR1 Ab) on HPS after CBDL were evaluated. Circulating CX(3)CL1 levels and lung expression of CX(3)CL1 and CX(3)CR1 in intravascular monocytes and microvascular endothelium increased in 2- and 4-week CBDL animals as HPS developed. These events were accompanied by pulmonary angiogenesis, monocyte accumulation, activation of CX(3)CL1 mediated signaling pathways (Akt, ERK) and increased VEGF-A expression and signaling. Anti-CX(3)CR1 Ab treatment reduced monocyte accumulation, decreased lung angiogenesis and improved HPS. These events were accompanied by inhibition of CX(3)CL1 signaling pathways and a reduction in VEGF-A expression and signaling. Circulating CX(3)CL1 levels and pulmonary CX(3)CL1/CX(3)CR1 expression and signaling increase after CBDL and contribute to pulmonary intravascular monocyte accumulation, angiogenesis and development of experimental HPS.

671 HEPATORENAL SYNDROME IN PATIENTS WITH HEPATOPULMONARY SYNDROME

Background and Aims: Hepatopulmonary syndrome (HPS) occurs in 20–30% of patients with cirrhosis. Patients with HPS have >2fold increased mortality. Contributing causes are unknown. There is lack data of concerning impairment of kidney function and hepatorenal syndrome (HRS) in patients with HPS. Methods: 203 patients with liver cirrhosis were screened for presence of HPS and HRS. HPS wsa defined according to consensus guidelines (1.) cirrhosis, 2.) AaDO2 >15mmHg, 3.) intrapulmonary vascular dilatation in contrast enhanced echocardiography). [1] HRS was defined according to established criteria. [2] Liver transplantation and survial was assessed during follow up. A p-value 1.5mg/dL. Underlying causes of renal impairment were HRS in 12 (33%), diabetic nephropathy in 6 (17%), hypovloemia in 8 (22%), glomerulanephritis in 3 (8%) and shock in 7 (19%) patients. HRS was the only cause of renal impairment that was significantly higher in HPS positive patients (7 (54%) versus 5 (22%), p < 0.05). Multivariate regression analysis revealed 2 risk factors for presence of HRS: refractory ascites (OR 33.4, p < 0.001) and presence of HPS (OR 4.9, p < 0.05). Discussion: HPS is an independent riask factor for presence of HRS. Patients with HRS should be screened for presence of HPS for early recognition and oxygen administration in case of severe gas exchange abnormality.

Detection of hepatopulmonary syndrome in patients with liver cirrhosis using 3D contrast echocardiography

Background and study aimsHepatopulmonary syndrome (HPS) is characterised by the triad of advanced liver disease, arterial hypoxaemia and intrapulmonary vascular dilatation (IPVD). The present study aimed to evaluate HPS in patients with liver cirrhosis and the role of three-dimensional (3D) contrast echocardiography in the detection of this syndrome. Patients and methodsA total of 78 chronic liver disease patients aged 42±11years fulfilled the criteria for this study and were subjected to clinical examination, laboratory investigations, arterial blood gases measurement, pulmonary function tests, upper gastrointestinal endoscopy, 3D contrast echocardiography and computed tomography (CT) pulmonary angiography. ResultsAccording to 3D contrast echocardiography results, we divided the patients into a positive group (n=26) in which patients showed a delayed appearance of contrast in left heart chambers and a negative group (n=52). Among 26 patients of the positive group, nine had hypoxaemia (partial pressure of oxygen (PaO2) <70mmHg) and were diagnosed as having hepatopulmonary syndrome (HPS), the other 17 who had shown echocardiographic evidence of IPVDs but without hypoxaemia were diagnosed as having sub-clinical HPS. This study showed significant correlation between positive contrast echocardiography findings and duration of liver disease, Child score, cyanosis, clubbing, orthodeoxia, portal vein diameter, spleen size and oesophageal varices grades. No significant correlation was found between 3D contrast echocardiography findings and age, sex, spider naevi and pulmonary function tests. Multivariate logistic regression showed that cyanosis, clubbing, orthodeoxia, Child score and portal vein diameter are independent predictors of HPS. ConclusionCyanosis, clubbing and platypnoea-orthodeoxia are suggestive indicators of HPS, which can be easily detected by 3D contrast echocardiography which can replace the trans-oesophageal echocardiogram (TEE) in cirrhotic patients.

Hepatopulmonary Syndrome

Hepatopulmonary syndrome (HPS) is characterized by an oxygenation defect induced by pulmonary vascular dilatation in the setting of liver cirrhosis or portal hypertension. It is defined by an alveolar-arterial gradient > 15 mm Hg measured at sea level. This syndrome is seen in 15 to 30% of cirrhotic patients and has been associated with worse survival. Most HPS patients are either asymptomatic or develop the insidious onset of dyspnea. The key event in its pathogenesis is the development of intrapulmonary vascular dilatation (IPVD), which has been linked to increased pulmonary levels of nitric oxide. Pulse oximetry is a useful screening test for HPS, which can guide subsequent use of arterial blood gases. Contrast-enhanced transthoracic echocardiography is the most effective test to demonstrate IPVD. Another method for detecting IPVD is the radionuclide lung perfusion scanning, using technetium-labeled macroaggregated albumin particles. Liver transplantation is the only available treatment for HPS, resulting in complete resolution or significant improvement in gas exchange in over 85% of patients.

Hepatopulmonary Syndrome in Children with Cirrhotic and Non-Cirrhotic Portal Hypertension: A Single-Center Experience

Hepatopulmonary syndrome (HPS) is defined as an arterial oxygenation defect induced by intrapulmonary vascular dilatation (IPVD) associated with hepatic disease. The prevalence and clinical characteristics of HPS in portal hypertensive children is not well characterized. The aim of this study was to investigate the prevalence and clinical characteristics of HPS in 40 portal hypertensive children. We studied 40 children (11 girls and 29 boys; mean age, 111 months ± 52 months; range, 24-216 months) with portal hypertension (24 cirrhotic, 16 non-cirrhotic) for the presence of HPS using blood gas analysis, contrast-enhanced echocardiography (CEE), and Tc99m-macroaggregated albumin scintigraphy. Clinical and laboratory characteristics of patients were recorded. HPS was considered to be present in a patient with hypoxemia and/or an elevated alveolar-arterial oxygen gradient (PAaO(2)) ≥ 15 mmHg) and positive CEE and/or scintigraphy. Elevated PAaO(2) was detected in 7 of 24 patients with cirrhosis. Four of them also had IPVD with CEE. An intrapulmonary shunt in Tc99m-MAA with CEE was shown in one patient. A diagnosis of HPS was made in 16.7% of the patients with cirrhosis. Cirrhotic patients without IPVD had significantly better hepatic function and lower pediatric end-stage liver disease scores. Although, 2 of the 16 patients with non-cirrhotic portal hypertension had elevated PAaO(2,) none of them showed IPVD. One normoxemic patient in the non-cirrhotic portal hypertension group showed IPVD with CEE. None of the non-cirrhotic patients fulfilled the diagnostic criteria of HPS. Hepatopulmonary syndrome particularly occurs in cirrhotic portal hypertensive patients with severe hepatic dysfunction.

Immediate noninvasive ventilation may improve mortality in patients with hepatopulmonary syndrome after liver transplantation

Hepatopulmonary syndrome (HPS) is defined as hypoxemia induced by intrapulmonary vascular dilations associated with liver disease. Although liver transplantation (LT) is the only effective therapy established for severe HPS, patients with a partial pressure of arterial oxygen (PaO(2) ) less than 60 mm Hg have a poor prognosis. We treated a 4-year-old boy with HPS whose preoperative PaO(2) level was 48.8 mm Hg. After LT, he had persistent severe hypoxemia, although he was receiving high-flow oxygen. Noninvasive ventilation (NIV) was introduced, and his respiratory insufficiency promptly improved. Therefore, NIV therapy immediately after extubation following transplantation was administered to the next 4 consecutive HPS patients whose preoperative PaO(2) was less than 60 mm Hg. The NIV treatment of these 5 patients could have been responsible for preventing severe postoperative complications as well as reintubation and hospital death. NIV therapy for both pediatric and adult patients with severe HPS immediately after extubation might protect them from severe hypoxemia after transplantation and from complications necessitating reintubation and might improve their prognosis.

Hepatopulmonary syndrome in children - is conventional liver transplantation always needed?

Hepatopulmonary syndrome (HPS) is the association of liver disease, hypoxemia, and intrapulmonary vascular dilatations. There are little data on the management of HPS in children other than conventional orthotopic liver transplantation (OLT). To describe the patient characteristics, mode of diagnosis, treatment, and outcomes of children with HPS at our center. Retrospective review of patients diagnosed with HPS between 1997 and 2007 after IRB approval. There were 10 patients, six females; median age at diagnosis of HPS was 12 yr. Six with cirrhosis underwent OLT and had subsequent resolution of HPS and are stable at last follow-up. Of the remaining four, two had cirrhosis. HPS resolved without conventional OLT in the following four patients: hepatitis C after antiviral treatment, biliary atresia with portal hypertension after transjugular intrahepatic portosystemic shunting, Abernethy syndrome after auxiliary partial OLT, and in a child with splenic vein thrombosis after splenectomy. Our series shows resolution of HPS in all patients and 100% survival after conventional OLT. Four children had resolution of HPS after surgical or medical treatments other than conventional OLT. Careful review of clinical status and underlying pathophysiology and anatomy at diagnosis of HPS should inform treatment decisions.

Role of Contrast‐Enhanced Transesophageal Echocardiography for Detection of and Scoring Intrapulmonary Vascular Dilatation

Intrapulmonary vascular dilatations (IVD) are microvascular pulmonary changes mediated by nitric oxide that cause right-to-left shunt and hypoxemia. Contrast-enhanced transthoracic echocardiography (cTTE) is the gold standard diagnostic test for IVD. To evaluate contrast-enhanced transesophageal echocardiography (cTEE) in the diagnosis and grading of IVD. A study group (SG) of 63 cirrhotic patients were compared to 20 shunt-free control subjects (CG). Both groups underwent cTEE and cTTE using intravenous injections of agitated saline solution for contrast tests. Patients with patent foramen ovale, when detected, were excluded. Late appearance of microbubbles in the left atrium was diagnostic of pulmonary shunt (positive contrast test) and was graded as trivial, mild, moderate or severe by cTEE. Contrast tests were negative in 7 patients (35%) and trivial in the remaining 13 (65%) in CG, so only contrast grades ≥ mild were considered to be positive IVD tests in the SG. Gasometric change was expressed as the alveolar-arterial oxygen tension difference (A-aO₂D) and was considered abnormally high at values >20 mmHg. SG: positive IVD tests were present in 23 patients (36%) by cTTE and 47 (75%) by cTEE (P < 0.001). These patients showed A-aO₂D values significantly higher than those with negative IVD tests (P < 0.02) and were directly proportional to the contrast grade. cTEE allowed the diagnosis of IVD in three additional patients with high A-aO₂D that were not detected by cTTE. cTEE enabled diagnosis of IVD in a greater number of patients with gasometric changes compared to cTTE. The contrast effect grade by cTEE seems to be proportional to IVD magnitude.

Other causes of pulmonary arterial hypertension: pulmonary veno-occlusive disease, pulmonary capillary hemangiomatosis, porto-pulmonary hypertension, HIV- associated pulmonary arterial hypertension

Idiopathic pulmonary arterial hypertension (PAH) is included in Group 1 of PAH classification, while pulmonary veno-occlusive disease (PVOD), pulmonary capillary hemangiomatosis (PCH), portopulmonary hypertension (PoPH) and HIV-associated PAH constitute the subgroups of Group I PAH disorders. PVOD has similar clinical presentation, hemodynamic characteristics and genetic background with PAH although main pathology is in venules and definite diagnosis is done by biopsy although not recommended due to high risk of bleeding. PCH, a rare idiopathic lung disorder, causes PAH in young adults and mostly is diagnosed after death by autopsy. PoPH is defined as PAH due to primary chronic liver disease associated with intrapulmonary vascular dilatations and hypoxia. HIV associated PAH is a rare complication of HIV-infection, and it is seen especially in HIV-infected patients with intravenous drug abuse.

Ocorrência de síndrome hepatopulmonar em pacientes cirróticos candidatos a transplante de fígado

To determine the occurrence of hepatopulmonary syndrome (HPS) in patients with cirrhosis who are candidates for liver transplantation; to compare demographic, clinical, laboratory, and spirometric characteristics, as well as echocardiography results, arterial blood gas analysis, and severity of liver disease between the groups of patients with and without HPS; and to describe the occurrence of HPS in the subgroup of patients with cirrhosis and schistosomiasis mansoni (mixed liver disease). Between January and November of 2007, we evaluated 44 patients under treatment at the Liver Transplant Outpatient Clinic of the Federal University of Pernambuco Hospital das Clínicas, in the city of Recife, Brazil. The diagnostic criteria for HPS were intrapulmonary vascular dilatation, identified by transthoracic echocardiography, and an alveolar-arterial oxygen tension difference >or= 15 mmHg or a PaO2 < 80 mmHg. The mean age of the patients was 52 years, and 31 patients (70%) were male. The most common cause of cirrhosis was alcohol use. Schistosomiasis was present in 28 patients (64%). Of the 44 patients, 20 (45.5%) were diagnosed with HPS. No significant differences were found between those patients and the patients without HPS in terms of any of the characteristics studied. Of the 28 patients with cirrhosis and schistosomiasis, 10 (35.7%) were diagnosed with HPS. In the population studied, HPS was highly prevalent and did not correlate with any of the variables analyzed.

Effect of chronic methylene blue administration on hypoxemia in rats with common bile duct ligation

Acute administration of methylene blue (MB) can reverse hypoxemia in patients with hepatopulmonary syndrome (HPS). We evaluated the effect of chronic MB administration in common bile duct-ligated rats, which develop HPS by 5 weeks after surgery. A total of 96 Sprague-Dawley rats were used, including 63 rats with common bile duct ligation (CBDL), 22 sham-operated rats and 11 normal control rats. MB (6 mg/kg) was injected s.c. once a day for 4 weeks. Evaluation of hemodynamics and intrapulmonary vascular dilatation (IPVD), as well as blood sampling for arterial blood gas analysis, were done under conscious and unrestrained conditions. Hemodynamics were assessed by the reference sample method using (141)Ce-microspheres (15 microm in diameter), and IPVD was also determined by i.v. injection of these microspheres. Histological examination of the lungs was done with hematoxylin-eosin staining and immunohistochemical staining for von Willebrand factor or vascular endothelial growth factor. Both the arterial oxygen tension and alveolar-arterial oxygen difference were significantly improved in MB-treated CBDL rats. The hyperdynamic circulation and splanchnic hyperemia seen in untreated CBDL rats were also alleviated by MB treatment. However, IPVD was not affected by MB. Histological examination of the lungs indicated that MB treatment reduced the proliferation of alveolar capillary vessels and angiogenesis, leading to improvement of arterial dysoxygenation. Hepatic synthetic and detoxification functions, as well as renal function, were not altered by MB treatment. Methylene blue may be a candidate treatment for HPS that does not cause deterioration of hepatic or renal function.