Pulmonary Vascular Abnormalities Research Articles

CFTR gene therapy, a method to rescue lung hypoplasia in congenital diaphragmatic hernia?

despite progress in neonatal care and despite changing concepts in treatment in the recent years, the mortality rate of infants with congenital diaphragmatic hernia (CDH) remains high ([20][1]). Pulmonary hypoplasia and vascular alterations associated with CDH have tremendous postnatal functional

Pulmonary Neovascularity

We sought to characterize the distinctive pulmonary vascular abnormalities seen on chest radiographs and computed tomography (CT) scans in Eisenmenger syndrome. Thoracic CT scans, chest radiographs, and clinical data were reviewed for 24 Eisenmenger syndrome patients subdivided into those with interatrial (pretricuspid) versus interventricular or great arterial (posttricuspid) communications and in 14 acyanotic patients with pulmonary arterial hypertension (PAH) and no congenital heart disease. CT scans were scored blindly by 2 thoracic radiologists for the presence and severity of small, tortuous, intrapulmonary vessels, termed "neovascularity," lobular ground-glass opacification, and systemic perihilar and intercostal vessels. Histopathologic lung sections from 5 patients with Eisenmenger syndrome and from 3 patients with acyanotic PAH were reviewed. Associations between clinical and imaging features were tested by ANOVA and chi2 tests. Kendall's rank-order coefficient and the Kruskal-Wallis test were used to test for significant differences in imaging features between Eisenmenger syndrome and acyanotic PAH. Neovascularity on chest radiographs was more common in Eisenmenger syndrome than acyanotic PAH, but differences were not significant. On CT, neovascularity, lobular ground-glass opacification, and hilar and intercostal systemic collaterals were more prevalent in Eisenmenger syndrome, with severity greater in posttricuspid communications. Three previously undescribed vascular lesions were identified histologically in Eisenmenger syndrome: malformed, dilated, muscular arteries within alveolar septa; congested capillaries within alveolar walls; and congested capillaries within the walls of medium-size, muscular pulmonary arteries. These lesions may correspond to the distinctive vascular abnormalities observed on chest radiographs and CT scans. Distinctive vascular lesions on chest radiographs and CT scans in Eisenmenger syndrome appear to be correlated histologically with collateral vessels that develop more extensively with posttricuspid communications.

Issue Highlights

HomeCirculationVol. 112, No. 18Issue Highlights Free AccessIn BriefPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessIn BriefPDF/EPUBIssue Highlights Originally published1 Nov 2005https://doi.org/10.1161/circ.112.18.2753Circulation. 2005;112:2753PULMONARY NEOVASCULARITY: A DISTINCTIVE RADIOGRAPHIC FINDING IN EISENMENGER SYNDROME, by Sheehan et al.Sheehan and colleagues characterized distinctive pulmonary vascular abnormalities seen on chest radiographs and computed tomography (CT) scans in 24 patients with Eisenmenger syndrome, as compared with 14 patients with acyanotic pulmonary artery hypertension (PAH). Eisenmenger patients had distinctive features on chest radiographs and CT scans more often than did those with acyanotic PAH. On CT, neovascularity, lobular ground glass, and increased systemic collaterals were identified regardless of the etiology of PAH, although they were significantly more common in Eisenmenger syndrome. Neovascularity and ground glass opacification were more prevalent and more severe in post-tricuspid defects in which pulmonary hypertension was present early in life, suggesting that the lesions were influenced by time of onset and duration of pulmonary vascular disease. See p 2778.PIOGLITAZONE REDUCES NEOINTIMA VOLUME AFTER CORONARY STENT IMPLANTATION: A RANDOMIZED, PLACEBO-CONTROLLED, DOUBLE-BLIND TRIAL IN NONDIABETIC PATIENTS, by Marx et al.Thiazolidinediones (TZDs) are a class of compounds commonly used to treat diabetes mellitus. These agents act as agonists for the peroxisome-proliferator-activated receptor-γ (PPAR-γ) nuclear receptor that controls the expression of many genes involved in energy metabolism. Recently, in vitro and animal studies have implicated this class of nuclear receptors in the inflammatory response, although the applicability of these findings to humans remains unclear. In this issue, Marx and colleagues have advanced our knowledge of TZDs on human inflammation. Using restenosis as a model, they investigated the efficacy of TZDs on the response to arterial injury in a nondiabetic population. They provide clear evidence of an antiinflammatory effect that is independent of glucose control. See p 2792.MAGNETIC RESONANCE ASSESSMENT OF THE SUBSTRATE FOR INDUCIBLE VENTRICULAR TACHYCARDIA IN NONISCHEMIC CARDIOMYOPATHY, by Nazarian et al.A vexing issue undergoing intense scrutiny involves optimizing selection of patients with heart failure and left ventricular dysfunction for placement of implantable defibrillators. Markers of risk that would allow for more efficient patient selection would be of great interest and clinical relevance. In this issue of Circulation, Nazarian and colleagues focus on patients with nonischemic dilated cardiomyopathy and hypothesize that a heterogeneous myocardial structural substrate would be associated with a propensity for inducible arrhythmias. Using cardiac magnetic resonance imaging, the authors demonstrate that nontransmural distribution of scar in this patient group was predictive of inducible ventricular tachycardia and remained so in a multivariable model. These biologically plausible data set the stage for further investigations on optimizing implantable cardioverter-defibrillator selection by this method and add to the growing body of literature on the clinical implications of myocardial fibrosis identified by cardiac magnetic resonance imaging in various cardiomyopathies. See p 2821.Visit http://www.circ.ahajournals.org:Cardiology Patient PagePalpitations. See p e299.Images in Cardiovascular MedicineThe Catch: A Graphic Demonstration of the Value of Embolic Protection Devices. See p e302.Novel Magnetic Resonance-Compatible Coronary Stent: The Absorbable Magnesium-Alloy Stent. See p e303.Dehiscence of Mitral Annuloplasty Ring. See p e305. Download figureDownload PowerPointCorrespondenceSee p e306. Previous Back to top Next FiguresReferencesRelatedDetails November 1, 2005Vol 112, Issue 18 Advertisement Article InformationMetrics https://doi.org/10.1161/circ.112.18.2753 Originally publishedNovember 1, 2005 PDF download Advertisement

Simvastatin Inhibits Cigarette Smoking–induced Emphysema and Pulmonary Hypertension in Rat Lungs

In cigarette smoking-induced chronic obstructive pulmonary disease, structural and functional derangements are characterized by parenchymal destruction and pulmonary hypertension. Statins are 3-hydroxy-3-methyl-glutaryl-coenzyme-A reductase inhibitors that have been used as lipid-lowering agents. These drugs also have additional pharmacologic properties, including antiinflammation, scavenging reactive oxygen species, restoring endothelial function, and antithrombogenesis, all of which can counteract the harmful effects of cigarette smoking. We performed assays to determine whether simvastatin could attenuate lung damage induced by chronic cigarette smoking in rats. In Sprague-Dawley rats exposed to cigarette smoke for 16 weeks, morphologic changes in the lungs and pulmonary arterial pressure were examined. Simvastatin inhibited lung parenchymal destruction and development of pulmonary hypertension, and also inhibited peribronchial and perivascular infiltration of inflammatory cells and induction of matrix metalloproteinase-9 activity in lung tissue. Simvastatin additionally prevented pulmonary vascular remodeling and the changes in endothelial nitric oxide synthase expression induced by smoking. In human lung microvascular endothelial cells, simvastatin increased expression of endothelial nitric oxide synthase mRNA. Simvastatin ameliorated the structural and functional derangements of the lungs caused by cigarette smoking, partly by suppressing inflammation and matrix metalloproteinase-9 induction and preventing pulmonary vascular abnormality. These findings indicate that statins may play a role in the treatment of cigarette smoking-induced chronic obstructive pulmonary disease.

Mechanisms of Pulmonary Vascular Complications of Liver Disease

To assess the incidence of oral complementary and alternative medicine (CAM) usage by gastroenterology patients at a single university center and compare against controls. The public awareness and usage of CAM have increased. The use of CAM has been described in patients with functional bowel disorders; however, their role in patients with gastrointestinal disease is less clear. Patients attending luminal gastroenterology clinics and customers at local supermarkets completed a 30-point, structured questionnaire assessing their use of CAM. A total of 1,409 subjects were recruited. The incidence of CAM use was 49.5% for inflammatory bowel disease, 50.9% for irritable bowel syndrome, 20% for general gastrointestinal diseases, and 27% for controls. Pearson's chi(2) tests showed that patients with inflammatory bowel disease (IBD) or irritable bowel syndrome were more likely to use CAM than controls (P < 0.001). Binary logistic regression analysis showed that females were more likely to take CAM than men (P < 0.05). The percentage of CAM users among patients with IBD is similar to those with a functional diagnosis. Increasing numbers of IBD patients are using CAM in addition to conventional therapy. Awareness of this may prevent adverse CAM and conventional drug interactions.

Pulmonary Vasodilator Therapy in Congenital Diaphragmatic Hernia: Acute, Late, and Chronic Pulmonary Hypertension

Pulmonary hypertension complicates the course of many newborns with congenital diaphragmatic hernia. In the most severe cases, the fetal condition of markedly elevated pulmonary vascular resistance persists after birth and is associated with hypoxemic respiratory failure and severe disturbances in cardiac performance. Late pulmonary hypertension (weeks to months after birth) is increasingly recognized in this population, and chronic pulmonary vascular abnormalities (months to years after birth) are now being discovered. In this review, we will discuss the pathophysiology of acute, late, and chronic pulmonary hypertension in patients with congenital diaphragmatic hernia. We will also review the role of currently available pulmonary vasoactive drugs in the management of pulmonary hypertension in this population.

Pulmonary vascular morphology in a fetal rabbit model for congenital diaphragmatic hernia

Background/Purpose Although the pulmonary vascular abnormalities in congenital diaphragmatic hernia (CDH) are described from a morphologic point of view, the treatment of pulmonary hypertension (PH) remains one of the main unsolved problems in clinical daily practice. For this reason, detailed studies in well-validated animal models could still be of significance in our understanding of the pathogenesis of CDH. Methods In does of 23 days’ gestational age (GA), 39 fetuses underwent creation of diaphragmatic hernia (DH) and 15 fetuses a sham thoracotomy (SHAM). Thirty-nine nonoperated littermates served as internal controls (CTR). Fetuses were harvested by cesarean section on days 25, 27, 29, and 30 of gestation. Lung specimens were obtained and formalin fixed for further vascular morphometry studies. Results Lung vessels from DH fetuses started to show significantly smaller internal diameter (ID), external diameter (ED), larger arterial wall thickness (WT), and, in particular, a proportionally higher medial thickness (%MT) and adventitial thickness (%AT) from day 27 onward when compared with control fetuses. SHAM fetuses, which were harvested at term, showed no differences with CTR. Conclusions This is the first report documenting changes over time in the vascular system in a rabbit fetal model of surgically induced DH. These changes mimic pathologic findings observed in human fetuses and are also concordant with earlier observations in the surgical ovine model and the toxic nitrofen rat model.

Contrast echocardiography in the diagnosis of intrapulmonary vascular dilations in candidates for liver transplantation.

To determine the importance of contrast echocardiography in the diagnosis of intrapulmonary vascular dilations in patients with severe liver disease, who are candidates for liver transplantation. The study comprised 76 patients with chronic liver disease and no evidence of intrinsic pulmonary disease, heart failure, or congenital heart disease with intracardiac communications, who underwent transthoracic echocardiography with second harmonic imaging. Thirty-two of them underwent consecutive transesophageal study. The result of contrast echocardiography was considered positive when the presence of contrast was detected in the left cardiac chambers with a delay of 4 to 6 cardiac cycles after initial opacification of the right cardiac chambers. The prevalence of intrapulmonary vascular dilations was 53.9% (41/76 patients). The sensitivity, specificity, positive and negative predictive values, and accuracy of transthoracic echocardiography as compared with those of transesophageal echocardiography for confirming pulmonary vascular abnormalities in patients with liver disease were, respectively, 75%, 100%, 100%, 80%, and 87.5%. The degree of arterial oxygenation showed no correlation with the occurrence of a positive echocardiographic study. Arterial hypoxemia (PaO2 < 70 mm Hg) was observed in 9 (15.9%) of the 76 patients. The echocardiographic study was positive in 37 (55.2%) of the 67 nonhypoxemic patients and in 4 (44.4%) of the 9 hypoxemic ones. Contrast echocardiography proved to be effective, easy, and safe to use in candidates for liver transplantation. Transthoracic echocardiography may be used in the diagnostic routine of intrapulmonary vascular dilations, the transesophageal study being reserved for inconclusive cases with clinical suspicion.

Relationship between vasoactive intestinal peptide and intrapulmonary vascular dilatation in children with various liver diseases

Aim: To evaluate the potential of vasoactive intestinal peptide (VIP) as a pathogenic factor of intrapulmonary vascular dilatation (IVD) in hepatopulmonary syndrome (HPS). Background: HPS comprises a triad comprising liver dysfunction, IVD and hypoxaemia. Although the pathogenesis of the process has not been elucidated, many vasodilating substances, such as VIP, have been implicated in the development of pulmonary vascular abnormalities. IVD can be detected by contrast‐enhanced echocardiography (CEE) before the development of abnormal gas exchange. Methods: Forty‐two children (20M, 22F; mean age 4.39 ±4.17 y) with various liver diseases who attended the paediatric liver clinic of King Chulalongkorn Memorial Hospital between March 2000 and February 2001 were recruited to the study. Each patient was tested for transcutaneous O2 saturation, CEE (applying the agitated normal saline technique), liver function test and serum VIP level. Results: Fourteen of the 42 patients (33%) were CEE positive. Only one of the 14 patients had associated hypoxia and clinical cyanosis. The serum VIP levels of children with liver disease were significantly higher than those of the controls (60.21 ± 35.04 pg/ml vs 43.71 ± 34.61 pg/ml, p= 0.03). CEE‐positive children tended to have higher serum VIP levels than CEE‐negative children (72.65 ± 40.31 vs 53.99 ±31 pg/ml, p= 0.3). The serum VIP levels of biliary atresia (BA) patients with favourable outcomes (serum bilirubin ±34μmol/L) were not significantly different from those with unfavourable outcomes (serum bilirubin &gt;34μmol/L) (42.95 ± 14.53 pg/ml vs 66.07 ± 32.17 pg/ml, p= 0.5).Conclusions: CEE is a non‐invasive test for early detection of IVD in children with liver disease. VIP is not solely responsible for the pathogenesis of IVD in HPS. Further studies are required to determine which substances cause the development of IVD.

Relationship between vasoactive intestinal peptide and intrapulmonary vascular dilatation in children with various liver diseases.

To evaluate the potential of vasoactive intestinal peptide (VIP) as a pathogenic factor of intrapulmonary vascular dilatation (IVD) in hepatopulmonary syndrome (HPS). HPS comprises a triad comprising liver dysfunction, IVD and hypoxaemia. Although the pathogenesis of the process has not been elucidated, many vasodilating substances, such as VIP, have been implicated in the development of pulmonary vascular abnormalities. IVD can be detected by contrast-enhanced echocardiography (CEE) before the development of abnormal gas exchange. Forty-two children (20M, 22F; mean age 4.39 +/- 4.17 y) with various liver diseases who attended the paediatric liver clinic of King Chulalongkorn Memorial Hospital between March 2000 and February 2001 were recruited to the study. Each patient was tested for transcutaneous O2 saturation, CEE (applying the agitated normal saline technique), liver function test and serum VIP level. Fourteen of the 42 patients (33%) were CEE positive. Only one of the 14 patients had associated hypoxia and clinical cyanosis. The serum VIP levels of children with liver disease were significantly higher than those of the controls (60.21 +/- 35.04 pg/ml vs 43.71 +/- 34.61 pg/ml, p = 0.03). CEE-positive children tended to have higher serum VIP levels than CEE-negative children (72.65 +/- 40.31 vs 53.99 +/- 31 pg/ml, p = 0.3). The serum VIP levels of biliary atresia (BA) patients with favourable outcomes (serum bilirubin < or = 34 micromol/L) were not significantly different from those with unfavourable outcomes (serum bilirubin > 34 micromol/L) (42.95 +/- 14.53 pg/ml vs 66.07 +/- 32.17 pg/ml, p = 0.5). CEE is a non-invasive test for early detection of IVD in children with liver disease. VIP is not solely responsible for the pathogenesis of IVD in HPS. Further studies are required to determine which substances cause the development of IVD.

Peripheral vasodilatory dysfunction in adult patients with congenital heart disease and severely elevated pulmonary vascular resistance.

Several studies have demonstrated that pulmonary vascular abnormalities precede alterations in aortic circulation downstream in animal models of heart failure. The relationship between increased pulmonary vascular resistance (PVR) and agonist-induced limb vasodilatory response remains unknown in patients with congenital cardiovascular shunt lesions (CSL). The authors hypothesized that patients with CSL and severely elevated PVR will show a defective vasomotor response in the peripheral vascular bed. To examine this hypothesis we measured forearm blood flow (FBF) responses to the endothelium-dependent vasodilator acetylcholine and the endothelium-independent vasodilator sodium nitroprusside. The values for these FBF responses were compared with PVR in adult patients with CSL (n=20) and healthy age- and sex-matched controls (n = 15). When patients with CSL were divided into 2 subgroups by median value of PVR, in the lower PVR subgroup, acetylcholine-induced FBF changes were selectively and significantly lower than in the healthy control group (p <0.05). In the higher PVR subgroup, FBF responses to both acetylcholine and sodium nitroprusside were significantly blunted compared to healthy controls (both p < 0.01). In addition, when FBF changes above baseline for each dose of acetylcholine and sodium nitroprusside were cumulated and used as acetylcholine response and sodium nitroprusside response, the sensitivity and specificity for identifying patients with Eisenmenger's type of CSL was 100% and 80% by acetylcholine response, and 67% and 80% by sodium nitroprusside response, respectively. In conclusion, adult CSL patients with elevated PVR and severe pulmonary arterial hypertension showed generalized vasodilator dysfunction in the forearm vasculature. This result suggests that upper limb resistance vessel dysfunction may be an indicator for advanced stage of adult patients with CSL.

Delayed rectifier potassium channels contribute to the depressed pulmonary artery contractility in pneumonia.

We investigated the role of K(+) channels in the attenuated pulmonary artery (PA) contractility characteristic of acute Pseudomonas pneumonia. Contractility of PA rings from the lungs of control or pneumonia rats was assessed in vitro by obtaining cumulative concentration-response curves to the contractile agonists KCl, phenylephrine, or PGF(2 alpha) on PA rings before and after treatment with K(+) channel blockers. In rings from pneumonia rats, paxilline (10 microM), tetraethylammonium (2 mM) (blockers of large-conductance Ca(2+)-activated K(+) channels), and glybenclamide (ATP-sensitive K(+) channel blocker, 80 microM) had no significant effect on the attenuated contractile responses to KCl, phenylephrine, and PGF(2 alpha). However, 4-aminopyridine (2 mM), a blocker of voltage-gated K(+) channels (delayed rectifier K(+) channel) reversed this depressed contractility. Therefore, large-conductance Ca(2+)-activated K(+) and ATP-sensitive K(+) channels do not contribute to the attenuated PA contractility observed in this model of acute pneumonia. In contrast, 4-aminopyridine enhances contraction in PA rings from pneumonia lungs, consistent with involvement of a voltage-gated K(+) channel in the depressed PA contractility in acute pneumonia. Unraveling the precise mechanism of attenuated contractility in pneumonia could lead to innovative therapies for the pulmonary vascular abnormalities associated with this disease.

The influence of a restrictive atrial septal defect on pulmonary vascular morphology in patients with hypoplastic left heart syndrome.

Hypoplastic left heart syndrome (HLHS) with a restrictive atrial septal defect (ASD) is a form of congenital heart disease with considerable morbidity and mortality. This morphologic analysis assesses the pulmonary vasculature in this patient population. Pulmonary arteries, the persistence of high-resistance fetal arterioles, pulmonary veins, and lymphatics from multiple lung sections from each of five patients with HLHS and a restrictive ASD were compared to those of five patients with HLHS and nonrestrictive ASD. Lung sections from each patient were qualitatively graded in severity of pathology from 0 to 3 for each of the structures described previously, with the pathologist blinded to the status of the ASD. Patients with a restrictive ASD exhibited more significant pulmonary venous thickening and lymphatic dilatation (p = 0.02), with a tendency toward persistence of high-resistance fetal vessels (p = 0.2), compared to patients with a nonrestrictive ASD. These findings imply that patients with HLHS and a restrictive ASD possess pulmonary vascular abnormalities that place them at higher risk for the current surgical interventions available compared to patients with a nonrestrictive ASD.

Helical CT of pulmonary vascular abnormalities.

ultidetector helical CT is revolutionizing imaging of the thoracic vasculature. Multidetector helical CT allows high-resolution, noninvasive, volumetric imaging that can be acquired during a single breath-hold, making it the imaging study of choice over conventional catheter angiography. In addition, volumetric helical imaging allows three-dimensional reconstruction of data, which is useful in lesion detection, characterization, and surgical planning. With multidetector helical CT, radiologists can definitively characterize pulmonary vascular lesions. Understanding the anatomy, physiology, and imaging appearance of pulmonary vascular lesions is es

Plasma endothelin-1 level as a marker reflecting the severity of portal hypertension in biliary atresia

Background/Purpose: The aim of this study was to examine if the plasma endothelin-1 (ET-1), a potent vasoconstrictor, level may reflect the severity of portal hypertension associated with liver cirrhosis in biliary atresia (BA). Methods: Forty-eight postoperative BA patients aged 6 months to 20 years were studied. Plasma ET-1 was measured by a sandwich method of enzyme immunoassay. ET-1 was compared with Child's score and laboratory data. ET-1 levels were compared among groups of patients with various degrees of histologic fibrosis and portal hypertension. Results: Plasma ET-1 was 5.3 ± 3.5 pg/mL in BA, higher than in controls (3.1 ± 0.8, n = 27; P < .05). ET-1 correlated with Child's score, serum total bilirubin, direct bilirubin, aspartate aminotransferase, albumin, prothrombin time, hepaplastin test, fibrinogen, cholinesterase, total cholesterol, Fischer's molar ratio, prealubumin, and hyaluronic acid, respectively (P < .05). ET-1 also correlated with the severity of histologic fibrosis, gastroesophageal varices, the presence of splenomegaly, ascites, venous dilatation on the abdominal wall, or pulmonary vascular abnormalities. In 4 patients undergoing liver transplantation (LTx), ET-1 after LTx was lower than that before LTx (P < .05). Conclusion: Plasma ET-1 level may be a useful index reflecting the severity of cirrhosis and portal hypertension in BA. J Pediatr Surg 36:1609-1612. Copyright © 2001 by W.B. Saunders Company.

Assessment of survey radiography as a method for diagnosis of congenital cardiac disease in dogs

In order to assess the diagnostic accuracy of survey radiography for canine congenital cardiac anomalies, thoracic radiographs of 57 dogs with congenital cardiac anomalies, 31 normal dogs and 27 dogs with acquired cardiac disease were mixed, and reviewed by two independent observers, who were blinded to any patient information. The congenital anomalies were aortic stenosis (n=25), pulmonic stenosis (n=10), patent ductus arteriosus (n=9), ventricular septal defect (n=8), tricuspid dysplasia (n=3) and mitral dysplasia (n=2). Both observers were moderately accurate at identifying dogs with cardiac disease. Their ability to distinguish dogs with congenital versus acquired cardiac disease was poorer and this assessment was probably influenced by the recognition of patients that were skeletally immature, which biased observers towards a diagnosis of congenital cardiac anomaly. The diagnosis rate for specific congenital anomalies was also poor (the differential list included a correct diagnosis in only 40 and 37 per cent of cases). Radiographic signs of specific cardiac chamber enlargement or pulmonary vascular abnormalities were recognised by both observers in only 20 per cent of instances in which they might be expected. They were, however, recognised more frequently in dogs with anomalies that imposed a volume load on the heart than in dogs with anomalies that induced a pressure load on the organ. It is concluded that survey radiography is an inaccurate method for diagnosis of canine congenital cardiac anomalies because of the difficulty of recognising radiographic signs, which are not present in many cases.

Pulmonary vascular imaging

This article is a pictorial review of the major abnormalities of the pulmonary vessels in children. Vascular, including lymphatic malformations have been covered in previous issues of this journal and so will not be described in detail. Many pulmonary vascular abnormalities are associated with complex intracardiac disorders. This article, however, focuses on extra cardiac abnormalities, particularly those causing pulmonary parenchymal problems.

The hepatopulmonary syndrome

The hepatopulmonary syndrome is a triad of liver disease, increased alveolar–arterial oxygen gradient and intrapulmonary vascular dilatations. Manifestations include orthodeoxia, platypnoea and hyperdynamic circulation. Intrapulmonary vascular abnormalities, perhaps mediated by nitric oxide, cause hypoxaemia by shunting, a perfusion–diffusion defect, and ventilation–perfusion mismatching. Contrast-enhanced echocardiography is the method of choice for demonstrating pulmonary vascular abnormalities, although perfusion lung scanning is a more specific and sensitive test. Angiography is best reserved for patients with poor response to 100% oxygen and defines whether vascular dilatations are of the diffuse ‘spongy’ type or, less commonly, discrete arteriovenous communications amenable to embolization. About 80% of patients with the hepatopulmonary syndrome eventually have improved oxygenation after liver transplantation, thereby making worsening hypoxaemia the primary indication for transplantation in many instances. Nevertheless, severe hypoxaemia carries a peri-operative mortality of 30% and reliable predictors of successful outcome after transplantation remain to be determined.

Mechanisms of exercise limitation in HIV+ individuals.

Cardiopulmonary exercise testing (CPX) is an important diagnostic tool for both clinical and research purposes in HIV positive (HIV+) individuals. Important information can be obtained from the gas exchange responses that can elucidate heart, lung, peripheral vascular, pulmonary vascular, and muscle abnormalities in this population. A large percentage of these patients are deconditioned, respond well to exercise training, and have no intrinsic limitation to exercise. Results of a progressively increasing CPX can be used to: 1) design an exercise prescription for aerobic training in HIV+ individuals; 2) identify and refer patients with subtle abnormalities of gas exchange for further diagnostic studies to exclude early infectious complications: and 3) evaluate the improvements in maximal oxygen uptake, lactic acidosis threshold, and gas exchange kinetics as result from an aerobic exercise training program. Gas exchange kinetic analysis of constant work rate tests can provide similar information in a nonmaximal, reproducible, readily obtainable format. Both progressively increasing and constant work rate CPX tests provide important information on the changes in oxygen flow from the environment to the exercising muscle that occur with aerobic exercise training. Finally, a case study involving the exercise prescription for HIV+ individuals is reviewed as well as the risk of transmission of HIV during competitive sports competition events.

PII: S0003-4975(99)01221-7

The majority of cases of congenital pulmonary venous obstruction present in infancy and undergo surgery successfully. Pulmonary vascular disease is usually limited to an increase in muscularity of both intrapulmonary arteries and veins. Susceptibility to pulmonary hypertensive crises is acknowledged, and crises can be anticipated and treated when they occur. The paper by Dr Endo and coworkers is particularly interesting in showing how the more advanced pulmonary vascular abnormalities seen in older patients of six years or more do not contraindicate surgical repair, even at 16 years of age.