Fatal Scopulariopsis infection in a lung transplant recipient: lessons of organ procurement.

Seventeen days after double lung transplantation, a 56-year-old patient with idiopathic pulmonary fibrosis developed respiratory distress. Imaging revealed bilateral pulmonary infiltrates with pleural effusions and physical examination demonstrated sternal instability. Broad-spectrum antibacterial and antifungal therapy was initiated and bilateral thoracotomy tubes were placed. Both right and left pleural cultures grew a mold subsequently identified as Scopulariopsis brumptii. The patient underwent pleural irrigation and sternal debridement three times but pleural and wound cultures continued to grow S. brumptii. Despite treatment with five antifungal agents, the patient succumbed to his illness 67 days after transplantation. Autopsy confirmed the presence of markedly invasive fungal disease and pleural rind formation. The patient's organ donor had received bilateral thoracostomy tubes during resuscitation in a wilderness location. There were no visible pleural abnormalities at the time of transplantation. However, the patient's clinical course and the location of the infection, in addition to the lack of similar infection in other organ recipients, strongly suggest that Scopulariopsis was introduced into the pleural space during prehospital placement of thoracostomy tubes. This case of lethal infection transmitted through transplantation highlights the unique risk of using organs from donors who are resuscitated in an outdoor location.

Heterozygous germline mutations in BMPR2, encoding a TGF-beta receptor, cause familial primary pulmonary hypertension.

Primary pulmonary hypertension (PPH), characterized by obstruction of pre-capillary pulmonary arteries, leads to sustained elevation of pulmonary arterial pressure (mean >25 mm Hg at rest or >30 mm Hg during exercise). The aetiology is unknown, but the histological features reveal proliferation of endothelial and smooth muscle cells with vascular remodelling (Fig. 1). More than one affected relative has been identified in at least 6% of cases (familial PPH, MIM 178600). Familial PPH (FPPH) segregates as an autosomal dominant disorder with reduced penetrance and has been mapped to a locus designated PPH1 on 2q33, with no evidence of heterogeneity. We now show that FPPH is caused by mutations in BMPR2, encoding a TGF-beta type II receptor (BMPR-II). Members of the TGF-beta superfamily transduce signals by binding to heteromeric complexes of type I and II receptors, which activates serine/threonine kinases, leading to transcriptional regulation by phosphorylated Smads. By comparison with in vitro studies, identified defects of BMPR-II in FPPH are predicted to disrupt ligand binding, kinase activity and heteromeric dimer formation. Our data demonstrate the molecular basis of FPPH and underscore the importance in vivo of the TGF-beta signalling pathway in the maintenance of blood vessel integrity.

Localization of the gene for familial primary pulmonary hypertension to chromosome 2q31-32.

Primary pulmonary hypertension (PPH), an often fatal disease, is characterized by elevated pulmonary artery pressures in the absence of a secondary cause. Endovascular occlusion in the smallest pulmonary arteries occurs by proliferation of cells and matrix, with thrombus and vasospasm. Diagnosis is often delayed because the initial symptoms of fatigue and dyspnea on exertion are nonspecific and definitive diagnosis requires invasive procedures. The average life expectancy after diagnosis is two to three years with death usually due to progressive right heart failure. The aetiology of the disease is unknown. Although most cases appear to be sporadic, approximately 6% of cases recorded in the NIH Primary Pulmonary Hypertension Registry are inherited in an autosomal dominant manner with reduced penetrance. Following a genome-wide search using a set of highly polymorphic short tandem repeat (STR) markers and 19 affected individuals from six families, initial evidence for linkage was obtained with two chromosome 2q markers. We subsequently genotyped patients and all available family members for 19 additional markers spanning approximately 40 centiMorgans (cM) on the long arm of chromosome 2. We obtained a maximum two-point lod score of 6.97 at theta = 0 with the marker D2S389; multipoint linkage analysis yielded a maximum lod score of 7.86 with the marker D2S311. Haplotype analysis established a minimum candidate interval of approximately 25 cM.

BMPR2 mutation alters the lung macrophage endothelin-1 cascade in a mouse model and patients with heritable pulmonary artery hypertension.

Macrophage derived-endothelin-1 (ET-1) has been suggested to contribute to a number of chronic lung diseases. Whether the ET-1 cascade from non-vascular sources (inflammatory cells) also contributes to pulmonary artery hypertension (PAH) and in particular to heritable PAH (HPAH) with known bone morphogenetic protein type 2 receptor (BMPR2) mutations is not known. We tested this notion using bone marrow-derived macrophages (BMDM; precursors of tissue macrophages) isolated from ROSA26rtTAXTetO(7)-tet-BMPR2(R899X) mice (model of PAH with universal expression of a mutated BMPR2 gene) with and without activation by LPS and in human lung tissue from HPAH with BMPR2 mutations and idiopathic PAH (IPAH). At baseline ET(A) and ET(B) receptors and endothelin converting enzyme (ECE) gene expression was reduced in BMPR2 mutant BMDM compared with controls. In control BMDM, LPS resulted in increased ppET-1 gene expression and ET-1 in culture media, whereas ET(A) and ET(B) receptor and ECE gene expression was decreased. These findings were more severe in BMPR2 mutant BMDM. Antagonism of the ET(B) receptor resulted in increased ET-1 in the media, suggesting that decreased ET-1 uptake by the ET(B) receptor contributes to the elevation. While ET-1 expression was demonstrated in lung macrophages from controls and IPAH and HPAH patients, ET(A) and ET(B) expression was decreased in the HPAH, but not IPAH, patients compared with controls. We conclude that reduced expression of macrophage ET-1 receptors in HPAH increases lung ET-1 and may contribute to the pathogenesis and maintenance of HPAH. This is the first description of protein expression that distinguishes HPAH from IPAH in patients.

Transcripts from a novel BMPR2 termination mutation escape nonsense mediated decay by downstream translation re-initiation: implications for treating pulmonary hypertension.

Bone morphogenetic protein receptor type 2 (BMPR2) gene mutations are a major risk factor for heritable pulmonary arterial hypertension (HPAH), an autosomal dominant fatal disease. We have previously shown that BMPR2 transcripts that contain premature termination codon (PTC) mutations are rapidly and nearly completely degraded through nonsense mediated decay (NMD). Here we report a unique PTC mutation (W13X) that did not behave in the predicted manner. We found that patient-derived cultured lymphocytes (CLs) contained readily detectable levels of the PTC-containing transcript. Further analysis suggested that this transcript escaped NMD by translational re-initiation at a downstream Kozak sequence, resulting in the omission of 173 amino acids. Treatment of CLs containing the PTC with an aminoglycoside decreased the truncated protein levels, with a reciprocal increase in full-length BMPR2 protein and, importantly, BMPR-II signaling. This is the first demonstration of aminoglycoside-mediated 'repair' of a BMPR2 mutation at the protein level in patient-derived cells and has obvious implications for treatment of HPAH where no disease-specific treatment options are available. Our data also suggest the need for a more thorough characterization of mutations prior to labeling them as haploinsufficient or dominant negative based simply on sequencing data.

Alterations in oestrogen metabolism: implications for higher penetrance of familial pulmonary arterial hypertension in females.

Mutations in bone morphogenetic protein receptor type 2 (BMPR2) cause familial pulmonary arterial hypertension (FPAH), but the penetrance is reduced and females are significantly overrepresented. In addition, gene expression data implicating the oestrogen-metabolising enzyme CYP1B1 suggests a detrimental role of oestrogens or oestrogen metabolites. We examined genetic and metabolic markers of altered oestrogen metabolism in subjects with a BMPR2 mutation. Genotypes for CYP1B1 Asn453Ser (N453S) were determined for 140 BMPR2 mutation carriers (86 females and 54 males). Nested from those subjects, a case-control study of urinary oestrogen metabolite levels (2-hydroxyoestrogen (2-OHE) and 16alpha-hydroxyoestrone (16alpha-OHE(1))) was conducted in females (five affected mutation carriers versus six unaffected mutation carriers). Among females, there was four-fold higher penetrance among subjects homozygous for the wild-type genotype (N/N) than those with N/S or S/S genotypes (p = 0.005). Consistent with this finding, the 2-OHE/16alpha-OHE(1) ratio was 2.3-fold lower in affected mutation carriers compared to unaffected mutation carriers (p = 0.006). Our findings suggest that variations in oestrogens and oestrogen metabolism modify FPAH risk. Further investigation of the role of oestrogens in this disease with profound sex bias may yield new insights and, perhaps, therapeutic interventions.

Gene expression patterns in the lungs of patients with primary pulmonary hypertension: a gene microarray analysis.

Primary pulmonary hypertension (PPH) is a disease of unknown etiology characterized by lumen-obliterating endothelial cell proliferation and vascular smooth muscle hypertrophy of the small precapillary pulmonary arteries. Because the vascular lesions are homogeneously distributed throughout the entire lung, we propose that a tissue fragment of the lung is representative of the whole lung. RNA extracted from the fragments is likely to provide meaningful information regarding the changes in gene expression pattern in PPH when compared with structurally normal lung tissue. We hypothesize that the lung tissue gene expression pattern of patients with PPH has a characteristic profile when compared with the gene expression pattern of structurally normal lungs and that this characteristic gene expression profile provides new insights into the pathobiology of PPH. Using oligonucleotide microarray technology, we characterized the expression pattern in the lung tissue obtained from 6 patients with primary pulmonary hypertension (PPH)-including 2 patients with the familial form of PPH (FPPH)-and from 6 patients with histologically normal lungs. For the data analysis, gene clusters were generated and the gene expression pattern differences between PPH and normal lung tissue and between PPH and FPPH lung tissue were compared. All PPH lung tissue samples showed a decreased expression of genes encoding several kinases and phosphatases, whereas several oncogenes and genes coding for ion channel proteins were upregulated in their expression. Importantly, we could distinguish by pattern comparison between sporadic PPH and FPPH, because alterations in the expression of transforming growth factor-beta receptor III, bone morphogenic protein 2, mitogen-activated protein kinase kinase 5, RACK 1, apolipoprotein C-III, and the gene encoding the laminin receptor 1 were only found in the samples from patients with sporadic PPH, but not in FPPH samples. We conclude that the microarray gene expression technique is a new and useful molecular tool that provides novel information pertinent to a better characterization and understanding of the pathobiology of the distinct clinical phenotypes of pulmonary hypertension.

Sporadic primary pulmonary hypertension is associated with germline mutations of the gene encoding BMPR-II, a receptor member of the TGF-beta family.

BACKGROUND: Primary pulmonary hypertension (PPH), resulting from occlusion of small pulmonary arteries, is a devastating condition. Mutations of the bone morphogenetic protein receptor type II gene (BMPR2), a component of the transforming growth factor beta (TGF-beta) family which plays a key role in cell growth, have recently been identified as causing familial PPH. We have searched for BMPR2 gene mutations in sporadic PPH patients to determine whether the same genetic defect underlies the more common form of the disorder. METHODS: We investigated 50 unrelated patients, with a clinical diagnosis of PPH and no identifiable family history of pulmonary hypertension, by direct sequencing of the entire coding region and intron/exon boundaries of the BMPR2 gene. DNA from available parent pairs (n=5) was used to assess the occurrence of spontaneous (de novo) mutations contributing to sporadic PPH. RESULTS: We found a total of 11 different heterozygous germline mutations of the BMPR2 gene in 13 of the 50 PPH patients studied, including missense (n=3), nonsense (n=3), and frameshift (n=5) mutations each predicted to alter the cell signalling response to specific ligands. Parental analysis showed three occurrences of paternal transmission and two of de novo mutation of the BMPR2 gene in sporadic PPH. CONCLUSION: The sporadic form of PPH is associated with germline mutations of the gene encoding the receptor protein BMPR-II in at least 26% of cases. A molecular classification of PPH, based upon the presence or absence of BMPR2 mutations, has important implications for patient management and screening of relatives.

Mediastinal fibrosis complicating histoplasmosis.

Mediastinal fibrosis, the most serious late complication of remote infection by Histoplasma capsulatum, is a thick, dense fibrotic capsule which surrounds a small mediastinal focus of old caseous adenitis. The fibrotic process may accrue over prolonged periods and extend within the lumina of critical mediastinal structures to produce complete occlusion. We summarized clinical and radiographic data for 71 patients with mediastinal fibrosis; the criteria for inclusion were the clinical demonstration of occlusion of major central airways (trachea or mainstem bronchus) or major vessels (pulmonary arteries or veins) and the absence of other disease processes which might cause such obstruction. We selected 65 patients who met these criteria from the medical literature of the last 40 years and report 6 new cases from our experience. The majority of patients were diagnosed between ages 20 and 40. The most common symptoms included hemoptysis, dyspnea, and cough. An accentuated pulmonic component of the second heart sound, wheezing, and localized murmur were among the physical findings reported. Radiographic abnormalities consisted of mass lesions and atelectasis or infiltrates, but were often nonspecific. Chest radiography was deceptively normal in some patients, even in the presence of major central airway or vascular occlusion, especially when the focus was subcarinal. Computed tomography has particular promise to depict the mediastinal abnormalities in this process. Surgery had minimal therapeutic benefit. Because of incomplete followup, the mortality of 30% in this series surely does not represent the true overall mortality of mediastinal fibrosis.

Genetics and immunogenetic aspects of primary pulmonary hypertension.

Primary pulmonary hypertension (PPH), also referred to as unexplained or idiopathic pulmonary hypertension, is the clinical term used to describe a condition in patients for which we can find no underlying cause. Patients with PPH not uncommonly also have evidence of immune dysregulation: autoimmune disorders, drug therapy, or HIV infections. We will review these associations and possible relevant abnormalities in immune regulation with regard to how they may play a role in the pathogenesis of PPH. Autoantibody-HLA correlations have been observed in several subsets of PPH patients. In addition, a familial form of PPH has been described and characterized with linkage to chromosome 2q31-q32. The identification of a specific gene for PPH and the subsequent understanding of its effects will help us identify the basic cause of PPH. Furthering our understanding regarding the role(s) and significance of immunogenetic as well as genetic aspects of the pathogenesis and pathophysiology of PPH should also lead to improved therapeutic modalities for PPH.

Respiratory bronchiolitis associated with severe dyspnea, exertional hypoxemia, and clubbing.

Respiratory bronchiolitis-associated interstitial lung disease (RBILD) is a distinct clinicopathologic disease described almost exclusively in cigarette smokers.(1) (2) The disease usually presents with mild symptoms and is associated with a good prognosis. (2) Severe lung dysfunction has not been reported with RBILD, which is often confused clinically and radiographically with desquamative interstitial lung disease or idiopathic pulmonary fibrosis (IPF). Two patients with RBILD who developed severe dyspnea, hypoxemia, and clubbing are described. Initially, IPF was diagnosed in both patients. The severity of symptoms was such that the first patient's room air saturation was 85% and the second patient had severe impairment of lung function, with FEV(1) of 39% and FVC of 40%. Advanced lung disease required supplemental home oxygen therapy in the first patient and referral for lung transplant evaluation in the second patient. After a detailed review of histology revealed a diagnosis of RBILD, both patients were encouraged to stop smoking; smoking cessation led to considerable improvement in symptoms and lung function tests. We conclude that advanced lung dysfunction occurs in some patients with RBILD and should not dissuade that diagnosis.

A survey of diagnostic practices and the use of epoprostenol in patients with primary pulmonary hypertension.

STUDY OBJECTIVE: To obtain information about the diagnosis and management of primary pulmonary hypertension (PPH), especially about the use of epoprostenol (Glaxo-Wellcome; Research Triangle Park, NC) in this patient population. BACKGROUND: Long-term IV epoprostenol therapy was approved recently for use in patients with PPH who are unresponsive to conventional therapy. Although epoprostenol represents a major advance in the treatment of PPH, there is no published consensus regarding the optimal use of this therapy. METHODS: A five-page survey was mailed to 23 investigators at medical centers treating five or more patients with PPH with long-term epoprostenol therapy. RESULTS: Nineteen of 23 investigators responded to the survey. During the initial hemodynamic evaluation, 11 investigators used changes in pulmonary vascular resistance (PVR), pulmonary artery pressure (PAP), and cardiac output, 5 investigators considered PVR and PAP only, and 2 investigators analyzed PVR alone to define a short-term vasodilator response. During long-term therapy, two thirds of the investigators increased the dose at scheduled intervals, while all investigators increased the dose in response to worsening symptoms. Epoprostenol doses were reported to range from 0.5 to 270 ng/kg/min. Nine investigators routinely repeated right heart catheterization an average of 7.5+/-3.8 months after starting epoprostenol, and the mean decrease in pulmonary artery pressure was between 15 and 25%. CONCLUSION: This survey indicates that there is wide variation in the evaluation of patients with PPH and in the use of epoprostenol therapy. The lack of consensus suggests the need for multicenter collaborative studies in order to optimize the use of epoprostenol therapy for PPH.

Mediastinal fibrosis is associated with human leukocyte antigen-A2.

OBJECTIVE: To determine the association between mediastinal fibrosis and human leukocyte antigen (HLA) genes. DESIGN: Case-control study. SETTING: Vanderbilt University Medical Center. SUBJECTS: Nineteen consecutive patients with mediastinal fibrosis who presented to the pulmonary clinic at Vanderbilt University Medical Center from 1987 to 1996. The control subjects were 21,086 whites who were cadaveric kidney donors from October 1987 through December 1993. MEASUREMENTS: HLA testing was performed on blood samples from all 19 cases. Information on HLA typing for the control subjects was obtained from the United Network for Organ Sharing. Frequency of HLA class I and II antigens found in the cases was compared with the frequency in the control subjects. RESULTS: The relative risk of mediastinal fibrosis among subjects with the HLA-A2 antigen was 3.32 times that of those who lacked this antigen (95% confidence interval, 1.19 to 9. 2). CONCLUSION: HLA-A2 was strongly associated with mediastinal fibrosis, suggesting that an abnormal immune response is important in the pathogenesis of this disease. Key words: Histoplasma capsulatum; human leukocyte antigen-A2; mediastinal fibrosis

Pulmonary veno-occlusive disease: a case series and new observations.

STUDY OBJECTIVES: The aim of this study was to describe our experience at one institution with pulmonary veno-occlusive disease (PVOD) during the past 10 years, with particular reference to new findings and long-term outcome. SETTING: Tertiary care, academic medical center. PATIENTS AND METHODS: Eleven patients who were evaluated and treated for PVOD at our institution were retrospectively studied. Included were all available clinical, radiographic, hemodynamic, and pathologic data. RESULTS: All 11 patients in our series had at least one symptom or clinical finding that, in conjunction with known pulmonary hypertension, suggested the diagnosis of PVOD. Digital clubbing, not previously reported in PVOD, was found in 5 patients, rales in 6, and increased interstitial markings on chest radiograph in 10. Half of the 10 patients who underwent acute vasodilator testing exhibited a decrease in pulmonary artery pressure of > 20%, although one patient died shortly after receiving IV calcium-channel blockers. Three patients have demonstrated sustained clinical improvement with therapy, which includes calcium-channel blockers, epoprostenol, and lung transplantation in one patient each. However, outcome was generally poor, with a 72% mortality within 1 year of diagnosis. CONCLUSION: The diagnosis of PVOD requires a high clinical suspicion. However, both physical examination findings and radiographic studies often provide clues to the diagnosis, which may obviate the need for lung biopsy in the majority of cases. Although there may be patients who respond to medical therapy, the use of vasoactive medications in patients with PVOD should be undertaken with great caution. Long-term survival is poor, and lung transplantation remains the only proven therapy.

Extrapulmonary thoracic disease caused by Blastomyces dermatitidis.

A case of blastomycosis is reported involving the mediastinum and compromising the plexus brachialis. The pathology, pathophysiology, and treatment of this patient and of a previously reported patient are discussed and compared with the characteristics of extrapulmonary thoracic disease caused by histoplasmosis. Because of the favorable response of these patients to prolonged antifungal therapy, blastomycosis should be considered in the differential diagnosis of invasive extrapulmonary thoracic disease.

Iatrogenic paradoxical air embolism in pulmonary hypertension.

Paradoxical systemic air embolism (PAE) occurring as a complication of right-to-left intracardiac shunting during evaluation and treatment of pulmonary hypertension (PH) has not been previously reported. We report four cases of PH-associated PAE recently encountered at our center. Two patients with PH experienced transient neurologic deficits during agitated-saline contrast echocardiography (ASCE), and a patent foramen ovale was subsequently diagnosed in both patients. Two patients with Eisenmenger's syndrome (ES), while receiving epoprostenol via multilumen catheters, experienced transient neurologic deficits while flushing the unused port of the catheter. No patient experienced permanent neurologic deficits. We conclude that ASCE poses a risk for PAE in patients with PH and clinically silent, previously undetected, right-to-left intracardiac shunts, and that multilumen catheters used for long-term epoprostenol therapy in ES carry a risk of PAE.

Epoprostenol for treatment of pulmonary hypertension in patients with systemic lupus erythematosus.

OBJECTIVE: Pulmonary hypertension with pathological changes similar to those observed in primary pulmonary hypertension occurs in patients with systemic lupus erythematosus (SLE). The efficacy of chronic epoprostenol therapy in SLE has not been well described. The objective of this paper is to describe our experience with long-term epoprostenol therapy in patients with pulmonary hypertension associated with SLE. DESIGN: Case series of six patients with SLE and associated pulmonary hypertension receiving chronic treatment with epoprostenol. RESULTS: All 6 patients had severe pulmonary hypertension. Mean pulmonary artery pressure (mPAP) was 57 +/- 9 mm Hg (mean +/- SD), and pulmonary vascular resistance was 14 +/- 7 units before beginning therapy with epoprostenol. In 4 patients who underwent repeat hemodynamic evaluation (9 to 16 months after starting epoprostenol), mean pulmonary artery pressure decreased by 38 +/- 21% and pulmonary vascular resistance by 58 +/- 12%. Clinically, all patients improved from New York Heart Association class III or IV to class I or II. Doses of epoprostenol ranged from 4 to 46 ng/kg/min, and the longest duration of therapy has been 2.5 years. Side effects from epoprostenol have not differed from those seen in patients with primary pulmonary hypertension, and except for one patient, there has been no exacerbation of SLE. CONCLUSION: Epoprostenol was effective for the treatment of pulmonary hypertension in this small group of patients with SLE. Further evaluation of epoprostenol therapy for patients with SLE and other diseases associated with pulmonary hypertension is warranted.

MR imaging parameters in the study of lung water. A preliminary study.

The use of magnetic resonance (MR) to evaluate lung water is made difficult by several factors: paucity of proton signal from normal lung, respiratory and cardiac motion, and long relaxation times of lung fluids. To optimize scanning parameters for this use, and to test MR's ability to detect and quantitate regional and temporal variations in signal intensity in hydrostatic pulmonary edema, in vivo experiments were performed with a 0.5 tesla whole body MR imaging device. Human volunteers were studied in prone and supine positions using spin echo technique (TE = 30 msec) with varying TR, and with respiratory and cardiac gating. In addition, sedated, intubated, chronically prepared sheep were paralyzed to control extraneous motion and allow the use of a high frequency ventilator, thereby eliminating respiratory gating. Elevated pulmonary hydrostatic pressure was induced in these sheep by inflation of a left atrial balloon. Relative signal intensity from the lung rises with lengthening TR. Cardiac gating diminishes motion artifact, but masks extravascular water by enhancing signal from slowly flowing blood by an average of 44%. A gravity-dependent gradient of signal intensity predictably shifts in supine and prone positions. The use of longer TRs, respiratory gating, and cardiac gating all proportionally prolong data acquisition times to an objectionable degree. Without the use of gating, a gradual rise in relative signal intensity is seen in the sheep lung following the establishment of elevated hydrostatic pressure in the pulmonary circuit, and is most pronounced in the dependent portion of the lung.(ABSTRACT TRUNCATED AT 250 WORDS)

Inexpensive, air-driven ventricular assist or replacement device for use in MR research.

A simple, inexpensive, non-magnetizable, pulsatile air-driven pump has been devised for use in magnetic resonance environments. The pump has a variable stroke volume and stroke rate, is easily cleaned and sterilized, requires relatively small priming volumes and causes no observable hemolysis when blood is used as the perfusate. This device is usable for phantoms, isolated organs or in situ preparations.

Hydrostatic pulmonary edema in sheep. Effects of bronchial artery embolization on the plain chest radiograph.

RATIONALE AND OBJECTIVES: The bronchial circulation may influence pulmonary edema. This study evaluates possible effects of bronchoesophageal artery embolization on the plain film manifestations of hydrostatic pulmonary edema in sheep. METHODS: Anteroposterior and lateral chest radiographs were obtained during the induction of pulmonary edema both before and after embolization of the bronchoesophageal artery in six adult sheep. Interstitial lines and perivascular, segmental bronchial, proximal bronchial, carinal, tracheal, and parenchymal edema were evaluated. RESULTS: Only parenchymal edema was graded consistently. Though edema increased with left atrial pressure before embolization (P < .001), there was no similar change afterward. The embolized animals tended to be more edematous by the first film. CONCLUSION: Rather than any protective effect, bronchoesophageal artery embolization may increase edema. This model may be inappropriate for further investigation of the bronchial circulation in the development of human pulmonary edema.