Heper, Gulumser Barcin, Cem; Iyisoy, Atila; Tore, Hasan F.
We report a case with an acquired fistula between the left internal mammary artery and the pulmonary artery following coronary bypass surgery treated with a bovine pericardium covered stent. We also reviewed similar cases reported previously.
Obeso Carillo, Gerardo Andrés; Casais Pampín, Rocío; Legarra Calderón, Juan José; Pradas Montilla, Gonzalo
Primary pulmonary artery sarcoma is an uncommon neoplasm with a grim prognosis. Complete resection is the only treatment that can improve the patient's survival. The role of multimodality treatment is still controversial, although adjuvant chemotherapy possibly could improve outcomes of these patients. Several pulmonary artery reconstructive techniques have been reported in the scientific literature, such as patch reconstruction, end-to-end anastomosis, synthetic prosthesis or biological grafts. In this article, we propose a new surgical option for pulmonary artery reconstruction after radical tumour resection using a self-made stapled bovine pericardial graft conduit in a patient with a mass in the pulmonary trunk and right pulmonary artery. We believe that the use of this technique adds safety and effectiveness, and reduces the surgical time.
Ohlstein, E H; Arleth, A; Ezekiel, M; Horohonich, S; Ator, M A; Caltabiano, M M; Sung, C P
The biosynthesis and modulation of the vasoconstrictor peptide endothelin was studied in the conditioned medium from cultured bovine pulmonary artery endothelial (BPAE) cells. Conditioned medium from cultured BPAE cells produced contraction of isolated rabbit aortic rings. Incubation of BPAE cells with the protease inhibitors TPCK or isatoic anhydride attenuated the extent of conditioned medium-induced contractions. Incubation of BPAE cells with thrombin produced an enhancement of conditioned medium-induced contraction by approximately 25%. Endothelin levels in conditioned medium were measured by RIA and incubation of BPAE cells with TPCK or isatoic anhydride significantly reduced endothelin levels, whereas incubation with thrombin or transforming growth factor beta-1 stimulated the levels of endothelin in the conditioned medium. These data indicate that endothelin may be modulated by certain protease inhibitors and by platelet and immune cell mediators and suggest a potential new mode of vascular tone regulation.
Neary, Joseph M.; Lund, Gretchen K.; Holt, Timothy N.; Garry, Franklyn B.; Mohun, Timothy J.; Breckenridge, Ross A.
Abstract Bovine pulmonary hypertension, brisket disease, causes significant morbidity and mortality at elevations above 2,000 m. Mean pulmonary arterial pressure (mPAP) is moderately heritable, with inheritance estimated to lie within a few major genes. Invasive mPAP measurement is currently the only tool available to identify cattle at risk of hypoxia-induced pulmonary hypertension. A genetic test could allow selection of cattle suitable for high altitude without the need for invasive testing. In this study we evaluated three candidate genes (myosin heavy chain 15 [MYH15], NADH dehydrogenase flavoprotein 2, and FK binding protein 1A) for association with mPAP in 166 yearling Angus bulls grazing at 2,182 m. The T allele (rs29016420) of MYH15 was linked to lower mPAP in a dominant manner (CC 47.2 ± 1.6 mmHg [mean ± standard error of the mean]; CT/TT 42.8 ± 0.7 mmHg; P = 0.02). The proportions of cattle with MYH15 CC, CT, and TT genotypes were 55%, 41%, and 4%, respectively. Given the high frequency of the deleterious allele, it is likely that the relative contribution of MYH15 polymorphisms to pulmonary hypertension is small, supporting previous predictions that the disease is polygenic. We evaluated allelic frequency of MYH15 in the Himalayan yak (Bos grunniens), a closely related species adapted to high altitude, and found 100% prevalence of T allele homozygosity. In summary, we identified a polymorphism in MYH15 significantly associated with mPAP. This finding may aid selection of cattle suitable for high altitude and contribute to understanding human hypoxia-induced pulmonary hypertension. PMID:25621163
The effects of bacterial lipopolysaccharide (endotoxin) on the fibrinolytic activity of bovine pulmonary artery endothelial cells were examined. Endotoxin suppressed the net fibrinolytic activity of cell extracts and conditioned media in a dose-dependent manner. The effects of endotoxin required at least 6 h for expression. Cell extracts and conditioned media contained a 44-kDa urokinase-like plasminogen activator. Media also contained multiple plasminogen activators with molecular masses of 65-75 and 80-100 kDa. Plasminogen activators in extracts and media were unchanged by treatment of cells with endotoxin. Diisopropyl fluorophosphate (DFP)-abolished fibrinolytic activity of extracts and conditioned media. DFP-treated samples from endotoxin-treated but not untreated cells inhibited urokinase and tissue plasminogen activator, but not plasmin. Inhibitory activity was lost by incubation at pH 3 or heating to 56/sup 0/C for 10 min. These treatments did not affect inhibitory activity of fetal bovine serum. Incubation of /sup 125/I-urokinase with DFP-treated medium from endotoxin-treated cells produced an inactive complex with an apparent molecular mass of 80-85 kDa.
Badesch, D B; Lee, P D; Parks, W C; Stenmark, K R
Insulin-like growth factor I stimulates mitogenesis in smooth muscle cells, and upregulates elastin synthesis in embryonic aortic tissue. Increased smooth muscle elastin synthesis may play an important role in vascular remodeling in chronic pulmonary hypertension. Therefore, we studied the effect of IGF-I on elastin and total protein synthesis by pulmonary arterial smooth muscle cells in vitro. Tropoelastin synthesis was measured by enzyme immunoassay, and total protein synthesis was measured by [3H]-leucine incorporation. In addition, the steady-state levels of tropoelastin mRNA were determined by slot blot hybridization. Incubation of confluent cultures with various concentrations of IGF-I resulted in a dose-dependent stimulation of elastin synthesis, with a 2.4-fold increase over control levels at 1000 ng/ml of IGF. The increase in elastin synthesis was reflected by a stimulation of the steady-state levels of tropoelastin mRNA. We conclude that IGF-I has potent elastogenic effects on vascular smooth muscle cells, and speculate that it may contribute to vascular wall remodeling in chronic hypertension.
Bourry, N; Chabrot, P; Jeannin, G; Filaire, M; Charpy, C; Bay, J O; Kemeny, J L; Caillaud, D; Escande, G; Boyer, L
Pulmonary artery sarcoma is a rare tumor. We present a case of intimal sarcoma arising from right pulmonary artery and left lower pulmonary vein observed in a 44-year-old man with a non-productive cough. Computed tomographic scans and magnetic resonance imaging showing filling defect enhancement contributed early, suggesting the diagnosis of primary vascular tumor, hypothesis confirmed by pathologist findings.
Jin, Tao; Zhang, Chong; Feng, Zhiying; Ni, Yiming
Primary pulmonary artery sarcoma is an uncommon tumor. We report a case of a 73-year-old male patient with a two-week history of palpitations and shortness of breath, aggravated for two days and was believed to be pulmonary hypertension. Emergency heart ultrasound after admission presented a massive pulmonary embolism in the pulmonary artery. The patient's condition was successfully managed with urgent pulmonary artery embolectomy. The patient demonstrated improvement in hemodynamics after the operation. Histologic and immunohistochemical assays were performed and a diagnosis was made as primary pulmonary artery sarcoma arising from the left pulmonary artery. Resection of the tumor is recommended for the treatment of this rare malignant tumor. The corresponding chemotherapy, follow-up and prognosis are described as well in this case report.
Nilius, B; Prenen, J; Szücs, G; Wei, L; Tanzi, F; Voets, T; Droogmans, G
1. We characterized Ca(2+)-activated Cl- currents in calf pulmonary artery endothelial (CPAE) cells by using a combined patch clamp and fura-2 microfluorescence technique to simultaneously measure ionic currents and the intracellular Ca2+ concentration, [Ca2+]i. 2. Various procedures that increased [Ca2+]i, such as stimulation with ATP or ionomycin, or loading the cells with Ca2+ via the patch pipette, activated a strongly outwardly rectifying current with a reversal potential close to the Cl- equilibrium potential. Changing the extracellular Cl- concentration shifted this reversal potential as predicted for a Cl- current. Buffering Ca2+ rises with BAPTA prevented ATP from activating the current. 3. Ca(2+)-activated Cl- currents could be distinguished from volume-activated Cl- currents, which were sometimes coactivated in the same cell. The latter showed much less outward rectification, their activation was voltage independent, and they could be inhibited by exposing the cells to hypertonic solutions. 4. The permeability ratio for the Ca(2+)-activated conductance of the anions iodide:chloride: gluconate was 1.71 +/- 0.06:1:0.39 +/- 0.03 (n = 12). 5. This Ca(2+)-activated Cl- current, ICl, Ca, inactivated rapidly at negative potentials and activated slowly at positive potentials. Outward tail currents were slowly decaying, while inward tail currents decayed much faster. 6. 4,4'-Diisothiocyanatostilbene-2,2'-disulphonic-acid (DIDS) and niflumic acid inhibited Icl,Ca in a voltage-dependent manner, i.e. they exerted a more potent block at positive potentials. The block by N-phenylanthracilic acid (NPA), 5-nitro-2-(3-phenylpropylamino)-benzoate (NPPB) and tamoxifen was voltage independent. Niflumic acid and tamoxifen were the most potent blockers. 7. The single-channel conductance was 7.9 +/- 0.7 pS (n = 15) at 300 mM extracellular Cl-. The channel open probability was high at positive potentials, but very small at negative potentials. 8. It is concluded that [Ca2+]i
Shomaf, Maha; Obeidat, Nathir; Najjar, Saleh
Pulmonary artery sarcomas (PAS) are extremely rare sarcomas of uncertain histogenesis that often mimic pulmonary thromboemboli. This is a report of a 60-year-old female patient who presented with recurrent chest pain and cough. The patient was first diagnosed with pulmonary embolism but she did not improve on anticoagulant therapy. Follow-up imaging studies revealed a mass in the left hilar region extending into the pulmonary trunk and branches of the left pulmonary artery. The tru-cut biopsy revealed an undifferentiated sarcoma. The patient died 10 months after her initial presentation. PMID:26425600
Kotwica, Tomasz; Szumarska, Joanna; Staniszewska-Marszalek, Edyta; Mazurek, Walentyna; Kosmala, Wojciech
Pulmonary artery aneurysm (PAA) is an uncommon lesion, which may be associated with different etiologies including congenital cardiovascular diseases, systemic vasculitis, connective tissue diseases, infections, and trauma. Idiopathic PAA is sporadically diagnosed by exclusion of concomitant major pathology. We report a case of a 56-year-old female with an idiopathic pulmonary artery dilatation identified fortuitously by echocardiography and confirmed by contrast-enhanced computed tomography. Neither significant pulmonary valve dysfunction nor pulmonary hypertension and other cardiac abnormalities which might contribute to the PAA development were found. Here, we describe echocardiographic and computed tomography findings and review the literature on PAA management.
Celik, Gökhan; Ciledağ, Aydin; Yüksel, Cabir; Yenigün, Bülent Mustafa; Kutlay, Hakan; Yazicıoğlu, Levent; Perçinel, Sibel; Kaya, Akin
A 30 years old male patient was referred to our hospital with a diagnosis of pulmonary thromboembolism due to thorax-computerized tomography (CT) angiography, revealing a thrombus totally occluding left main pulmonary artery. The lesion was evaluated as tumoural mass. Positron emission tomography (PET)-CT revealed pathologic uptake at pulmonary artery mass. Due to localization of tumour, left pneumonectomy was performed. The pathological diagnosis revealed to be pulmonary artery sarcoma. The patient was presented because pulmonary artery sarcomas are very rare tumors and can mimick pulmonary thromboembolism. The true prevalence is underestimated as many pulmonary artery sarcomas are misdiagnosed as pulmonary thromboembolism. PET-CT may help to make a differential diagnosis.
Farsad, Mohsen; Pernter, Patrizia; Triani, Antonio; Osele, Luzian; Wiedermann, Christian J
Pulmonary artery sarcoma, although rare, must be considered in the differential diagnosis of pulmonary thromboembolism. Clinically and radiologically, it may imitate pulmonary embolism, making diagnosis difficult and delaying treatment. Patients often have no symptom resolution despite therapeutic anticoagulation. Visualization of filling defects within a pulmonary artery on contrast-enhanced CT cannot reliably differentiate between pulmonary thromboembolism and malignant lesions like leiomyosarcoma. FDG PET-CT offers the potential for identification of malignant lesions. The authors report a case with pulmonary artery thromboembolism due to thrombi formed on a pulmonary artery leiomyosarcoma. Integrated FDG PET-CT showed no FDG-uptake along the major part of the filling defect within the right main pulmonary artery suggesting blood clot and increased uptake along the posterior wall of the right main pulmonary artery and the left lower lobar artery suggesting malignancy.
Mejía Chew, C R; Alcolea Batres, S; Ríos Blanco, J J
Pulmonary arterial hypertension is a rare and progressive disease that mainly affects the pulmonary arterioles (precapillary), regardless of the triggering aetiology. The prevalence of pulmonary hypertension and pulmonary arterial hypertension in Spain is estimated at 19.2 and 16 cases per million inhabitants, respectively. The diagnosis of pulmonary arterial hypertension is based on haemodynamic criteria (mean pulmonary artery pressure ≥25mmHg, pulmonary capillary wedge pressure ≤15mmHg and pulmonary vascular resistance >3 Wood units) and therefore requires the implementation of right cardiac catheterisation. Sequential therapy with a single drug has been used in clinical practice. However, recent European guidelines recommend combined initial therapy in some situations. This review conducts a critical update of our knowledge of this disease according to the latest guidelines and recommendations.
Pulmonary arterial hypertension (PAH) is a chronic and progressive disease leading to right heart failure and ultimately death if untreated. The first classification of PH was proposed in 1973. In 2008, the fourth World Symposium on PH held in Dana Point (California, USA) revised previous classifications. Currently, PH is devided into five subgroups. Group 1 includes patients suffering from idiopathic or familial PAH with or without germline mutations. Patients with a diagnosis of PAH should systematically been screened regarding to underlying mutations of BMPR2 gene (bone morphogenetic protein receptor type 2) or more rarely of ACVRL1 (activine receptor-like kinase type 1), ENG (endogline) or Smad8 genes. Pulmonary veno occusive disease and pulmonary capillary hemagiomatosis are individualized and designated as clinical group 1'. Group 2 'Pulmonary hypertension due to left heart diseases' is divided into three sub-groups: systolic dysfonction, diastolic dysfonction and valvular dysfonction. Group 3 'Pulmonary hypertension due to respiratory diseases' includes a heterogenous subgroup of respiratory diseases like PH due to pulmonary fibrosis, COPD, lung emphysema or interstitial lung disease for exemple. Group 4 includes chronic thromboembolic pulmonary hypertension without any distinction of proximal or distal forms. Group 5 regroup PH patients with unclear multifactorial mechanisms. Invasive hemodynamic assessment with right heart catheterization is requested to confirm the definite diagnosis of PH showing a resting mean pulmonary artery pressure (mPAP) of ≥ 25 mmHg and a normal pulmonary capillary wedge pressure (PCWP) of ≤ 15 mmHg. The assessment of PCWP may allow the distinction between pre-capillary and post-capillary PH (PCWP > 15 mmHg). Echocardiography is an important tool in the management of patients with underlying suspicion of PH. The European Society of Cardiology and the European Respiratory Society (ESC-ERS) guidelines specify its role
Montani, David; Günther, Sven; Dorfmüller, Peter; Perros, Frédéric; Girerd, Barbara; Garcia, Gilles; Jaïs, Xavier; Savale, Laurent; Artaud-Macari, Elise; Price, Laura C; Humbert, Marc; Simonneau, Gérald; Sitbon, Olivier
Pulmonary arterial hypertension (PAH) is a chronic and progressive disease leading to right heart failure and ultimately death if untreated. The first classification of PH was proposed in 1973. In 2008, the fourth World Symposium on PH held in Dana Point (California, USA) revised previous classifications. Currently, PH is devided into five subgroups. Group 1 includes patients suffering from idiopathic or familial PAH with or without germline mutations. Patients with a diagnosis of PAH should systematically been screened regarding to underlying mutations of BMPR2 gene (bone morphogenetic protein receptor type 2) or more rarely of ACVRL1 (activine receptor-like kinase type 1), ENG (endogline) or Smad8 genes. Pulmonary veno occusive disease and pulmonary capillary hemagiomatosis are individualized and designated as clinical group 1'. Group 2 'Pulmonary hypertension due to left heart diseases' is divided into three sub-groups: systolic dysfonction, diastolic dysfonction and valvular dysfonction. Group 3 'Pulmonary hypertension due to respiratory diseases' includes a heterogenous subgroup of respiratory diseases like PH due to pulmonary fibrosis, COPD, lung emphysema or interstitial lung disease for exemple. Group 4 includes chronic thromboembolic pulmonary hypertension without any distinction of proximal or distal forms. Group 5 regroup PH patients with unclear multifactorial mechanisms. Invasive hemodynamic assessment with right heart catheterization is requested to confirm the definite diagnosis of PH showing a resting mean pulmonary artery pressure (mPAP) of ≥ 25 mmHg and a normal pulmonary capillary wedge pressure (PCWP) of ≤ 15 mmHg. The assessment of PCWP may allow the distinction between pre-capillary and post-capillary PH (PCWP > 15 mmHg). Echocardiography is an important tool in the management of patients with underlying suspicion of PH. The European Society of Cardiology and the European Respiratory Society (ESC-ERS) guidelines specify its role
Presbitero, P; Bull, C; Haworth, S G; de Leval, M R
Of 12 patients with angiographically absent pulmonary artery, 11 were investigated surgically. The previously occult pulmonary artery was found in 10 patients, in five of whom a vestige of an intrapericardial artery was present and in five the artery was patent only at the hilus, a gap existing between the main pulmonary artery and the hilar vessel, and no artery was found in one. All patients with an intrapericardial artery had right ventricular outflow tract obstruction and a ductus descending vertically from underneath the aortic arch. In those without an intrapericardial vessel the occult artery was on the side opposite the aortic arch, and there was evidence of a ductus coming from the innominate artery on the side of the interruption. The occult pulmonary artery, where identified at operation, was usually joined initially to the systemic circulation. Ultimately, continuity between the hilar and main pulmonary artery may be established surgically. Where no intrapericardial vessel exists, however, a conduit may be required to bridge the gap. It seems advisable to search for the occult artery as early in life as is feasible in the hope that providing a blood supply will ensure development of the vessel and normal lung growth. Images PMID:6743435
Jeong, Nari; Seol, Sang-Hoon; Kim, Il Hwan; Kim, Ji Yeon
Pulmonary artery sarcoma (PAS) is a rare and fatal disease. PAS can often be misdiagnosed as pulmonary thromboembolism. Moreover, the correct diagnosis is frequently delayed due to nonspecific signs and symptoms. The prognosis of patients with PAS is poor. We report a case of a woman with a primary PAS who was initially diagnosed with pulmonary thromboembolism.
Jeong, Nari; Seol, Sang-Hoon; Kim, Il Hwan; Kim, Ji Yeon
Pulmonary artery sarcoma (PAS) is a rare and fatal disease. PAS can often be misdiagnosed as pulmonary thromboembolism. Moreover, the correct diagnosis is frequently delayed due to nonspecific signs and symptoms. The prognosis of patients with PAS is poor. We report a case of a woman with a primary PAS who was initially diagnosed with pulmonary thromboembolism. PMID:27833785
Terra, Ricardo M; Fernandez, Angelo; Bammann, Ricardo H; Junqueira, Jader J M; Capelozzi, Vera L
Pulmonary artery sarcoma is an uncommon neoplasm, and its clinical and radiological presentation usually simulates chronic thromboembolic disease. We present the case of a 77-year-old woman admitted with dyspnea, chest pain, and hemoptysis. A chest computed tomographic scan showed moderate right-sided pleural effusion and a saccular dilatation of the interlobar portion of the right pulmonary artery, which was filled with contrast and surrounded by an irregular soft-tissue attenuation mass, suggesting a ruptured pulmonary artery aneurysm. The patient was operated on. Intraoperatively, a pseudoaneurysm and a solid mass were identified within the oblique fissure around the interlobar artery. Therefore, a right pneumonectomy was performed. Definitive pathologic examination was consistent with pulmonary artery sarcoma. The patient had a good outcome and is free of disease 2 years after surgery.
Das, Mrinalendu; Mahindrakar, Pallavi; Das, Debasis; Behera, Sukanta Kumar; Chowdhury, Saibal Roy; Bandyopadhyay, Biswajit
The usual presentation of anomalous left coronary artery from pulmonary artery is severe left-sided heart failure and mitral valve insufficiency presenting during the first months of life. The manifestations of left heart failure may be masked if pulmonary artery pressure remains high. We believe this is a rarest of rare case of anomalous left coronary artery from pulmonary artery with severe mitral stenosis and pulmonary hypertension in which pulmonary hypertension, along with good collateral circulation helped to preserve left ventricular function.
... What Is Pulmonary Hypertension? To understand pulmonary hypertension (PH) it helps to understand how blood ows throughout ... is too high, it is called pulmonary hypertension (PH). How the pressure in the right side of ...
Shehatha, Jaffar; Saxena, Pankaj; Clarke, Belinda; Dunning, John; Konstantinov, Igor E
Primary pulmonary artery sarcoma is a rare tumor that can be misdiagnosed as acute or chronic pulmonary thromboembolic disease. This article reports a patient with a preoperative diagnosis of pulmonary embolism who was found to have an extensive pulmonary artery tumor. Surgical resection of the primary pulmonary artery sarcoma and reconstruction of the central pulmonary arteries, followed by adjuvant chemoradiotherapy, provided significant improvement in his clinical symptoms.
Sandhu, A; Yates, T J; Kuriakose, P
Sarcomas involving the lung are a rare occurrence, often a result of metastatic disease from primary malignancies involving the skin, liver, breast or heart. Primary pulmonary artery sarcomas are rarer still, with limited cases reported world-wide and consequently data regarding treatment modalities are sparse and largely experimental. These tumors are often mistaken for a pulmonary embolism and seemingly supported by radiological findings. Patients will often present without symptom resolution despite therapeutic anticoagulation. The following case illustrates how a soft tissue sarcoma of the pulmonary artery can mimic a pulmonary embolism, thus, resulting in both a diagnostic and therapeutic dilemma. A positron emission tomography scan was an invaluable tool in this case, showing increased radiotracer uptake and placing neoplasm at the top of the differential diagnosis. This ultimately led to a biopsy that was vimentin positive, cytokeratin negative and CD117 negative, thus consistent with soft tissue sarcoma.
Alsoufi, Bahaaldin; Slater, Matthew; Smith, Pamela P; Karamlou, Tara; Mansoor, Atiya; Ravichandran, Pasala
Intimal sarcomas of the pulmonary artery are rare tumors that are often difficult to distinguish from pulmonary thromboembolic disease, complicating accurate diagnosis and timely therapy. We report the case of a gentleman with a primary pulmonary artery sarcoma who presented with a massive pulmonary embolism and complete right ventricular outflow tract obstruction. The patient's condition was successfully managed with urgent pulmonary artery thromboendarterectomy, pulmonary valve replacement, and tricuspid valve annuloplasty.
El-Sayed Ahmed, Magdy M; Aftab, Muhammad; Al-Najjar, Raed M; de la Cruz, Kim I; Benjamin, Robert S; Hallman, Charles H
Primary sarcomas that arise from major blood vessels are exceedingly rare, and some of the published cases have been autopsy reports. Most patients are adults. We report a case of pulmonary artery sarcoma in a 77-year-old man who presented with acute onset of dyspnea. Magnetic resonance imaging of the chest revealed a large mass within the pulmonary trunk and its main branches. Because massive pulmonary embolism was suspected, both anticoagulant and thrombolytic therapies were initiated. The patient responded poorly to these therapies, which then necessitated resection of both the mass and the pulmonary valve. A bioprosthetic porcine valve replaced the native valve, and we reconstructed the right ventricular outflow tract with a Dacron patch. Histopathologic examination revealed a high-grade sarcoma with focal myogenic and chondrogenic differentiation. The patient tolerated the procedure well and was discharged from the hospital on postoperative day 7. He was subsequently treated with chemotherapy and radiation and continued to show no evidence of disease. The diagnosis of pulmonary artery sarcoma should be suspected in patients who present with manifestations of pulmonary embolism, especially when there is no evidence of deep venous thrombosis and poor response to anticoagulant therapy. Multimodal therapy can provide prolonged survival.
Aftab, Muhammad; Al-Najjar, Raed M.; de la Cruz, Kim I.; Benjamin, Robert S.; Hallman, Charles H.
Primary sarcomas that arise from major blood vessels are exceedingly rare, and some of the published cases have been autopsy reports. Most patients are adults. We report a case of pulmonary artery sarcoma in a 77-year-old man who presented with acute onset of dyspnea. Magnetic resonance imaging of the chest revealed a large mass within the pulmonary trunk and its main branches. Because massive pulmonary embolism was suspected, both anticoagulant and thrombolytic therapies were initiated. The patient responded poorly to these therapies, which then necessitated resection of both the mass and the pulmonary valve. A bioprosthetic porcine valve replaced the native valve, and we reconstructed the right ventricular outflow tract with a Dacron patch. Histopathologic examination revealed a high-grade sarcoma with focal myogenic and chondrogenic differentiation. The patient tolerated the procedure well and was discharged from the hospital on postoperative day 7. He was subsequently treated with chemotherapy and radiation and continued to show no evidence of disease. The diagnosis of pulmonary artery sarcoma should be suspected in patients who present with manifestations of pulmonary embolism, especially when there is no evidence of deep venous thrombosis and poor response to anticoagulant therapy. Multimodal therapy can provide prolonged survival. PMID:25425986
Blackmon, Shanda H; Reardon, Michael J
Primary heart tumors are rare, and malignant primary heart tumors are only a small subset of these. Most primary malignant tumors are sarcomas arising from the cells of the structural elements of the heart such as blood vessels, muscle, connective tissue, fat and even bone. Unlike most malignancies, where cell type often dictates treatment choices and prognosis and is used for classification, the histology in primary cardiac sarcoma plays little role in determining therapeutic options or prognosis. We have found that anatomic location within the heart is the major determining factor in clinical presentation, treatment options and prognosis in cardiac sarcoma. Therefore, we accordingly classify primary cardiac sarcomas into right heart sarcomas, left heart sarcomas and pulmonary artery (PA) sarcomas. Since the first autopsy report of a primary PA sarcoma in 1923, there have been fewer than 250 cases reported in the English literature. Most of these reports have been single autopsy or case reports, and patient prognosis has generally been dismal. Since few institutions and even fewer individual physicians acquire much exposure to this disease, the diagnostic and treatment approaches have remained unresolved. Our cardiac sarcoma group working at the Methodist DeBakey Heart & Vascular Center and the MD Anderson Cancer Center has undertaken a systematic study of this disease, and operated on 9 patients using a radical resection with curative intent and multimodality approach. Based on this work, we have suggested a diagnostic strategy, treatment approach and staging system for primary PA sarcoma. A substantial improvement in patient survival over historical controls has also been demonstrated and will be discussed in this review.
Huwer, Hanno; Ozbek, Cem; Waldmann, Rita; Winning, Johannes; Isringhaus, Helmut; Kalweit, Gerhard
We report on a sarcoma of the central pulmonary arteries. Surgical therapy consisted in replacing both main pulmonary arteries and the pulmonary trunk including the pulmonary valve. Six months later a left-sided pneumonectomy had to be performed due to an intravascular tumor. Fifteen months after first resection treatment, recurrent tumors of the right pulmonary artery and the right ventricle were resected. Two years after the first operation the patient has no detectable tumor.
Coskun, Ugur; Sinan, Umit Yasar; Calpar, Ilknur; Yildizeli, Bedrettin; Yanartas, Mehmet; Filinte, Deniz; Kucukoglu, Mehmet Serdar
We describe the case of a 60-year-old woman who presented with pulmonary artery sarcoma, a very rare tumor of the cardiovascular system. Her tumor was initially misdiagnosed as chronic pulmonary thromboembolism, and she underwent pulmonary endarterectomy. Early diagnosis of primary pulmonary artery sarcoma is crucial. That alternative should always be considered before settling on a diagnosis of pulmonary embolism. Suspicion should be aroused by the failure of anticoagulant treatment to alleviate pulmonary perfusion abnormalities and systemic symptoms. Surgical resection of the tumor-preferably by pulmonary endarterectomy, followed by reconstruction as needed-is currently the most promising treatment for pulmonary artery sarcoma.
Coskun, Ugur; Calpar, Ilknur; Yildizeli, Bedrettin; Yanartas, Mehmet; Filinte, Deniz; Kucukoglu, Mehmet Serdar
We describe the case of a 60-year-old woman who presented with pulmonary artery sarcoma, a very rare tumor of the cardiovascular system. Her tumor was initially misdiagnosed as chronic pulmonary thromboembolism, and she underwent pulmonary endarterectomy. Early diagnosis of primary pulmonary artery sarcoma is crucial. That alternative should always be considered before settling on a diagnosis of pulmonary embolism. Suspicion should be aroused by the failure of anticoagulant treatment to alleviate pulmonary perfusion abnormalities and systemic symptoms. Surgical resection of the tumor—preferably by pulmonary endarterectomy, followed by reconstruction as needed—is currently the most promising treatment for pulmonary artery sarcoma. PMID:25425987
Bhagwat, Krishna; Hallam, Jane; Antippa, Phillip; Larobina, Marco
Primary angiosarcoma of pulmonary artery is a very rare lesion. We present a case of primary angiosarcoma that was initially misdiagnosed as a subacute massive pulmonary thromboembolism in a 30-year-old man. This rare disease is usually indistinguishable from acute or chronic thromboembolic disease of the pulmonary arteries. The clinical and radiological findings of pulmonary artery angiosarcoma are similar to those of pulmonary thromboembolism. Although the incidence of pulmonary artery angiosarcoma is very low, our case demonstrates that this disease entity should be included in the differential diagnosis of pulmonary thromboembolism. Patients with early identification can have curative potential with aggressive surgical intervention.
Arnold, Nadine D.; Chang, William; Watson, Oliver; Swift, Andrew J.; Condliffe, Robin; Elliot, Charlie A.; Kiely, David G.; Suvarna, S. Kim; Gunn, Julian; Lawrie, Allan
Background— Pulmonary arterial hypertension is a devastating disease with high morbidity and mortality and limited treatment options. Recent studies have shown that pulmonary artery denervation improves pulmonary hemodynamics in an experimental model and in an early clinical trial. We aimed to evaluate the nerve distribution around the pulmonary artery, to determine the effect of radiofrequency pulmonary artery denervation on acute pulmonary hypertension induced by vasoconstriction, and to demonstrate denervation of the pulmonary artery at a histological level. Methods and Results— Histological evaluation identified a circumferential distribution of nerves around the proximal pulmonary arteries. Nerves were smaller in diameter, greater in number, and located in closer proximity to the luminal aspect of the pulmonary arterial wall beyond the pulmonary artery bifurcation. To determine the effect of pulmonary arterial denervation acute pulmonary hypertension was induced in 8 pigs by intravenous infusion of thromboxane A2 analogue. Animals were assigned to either pulmonary artery denervation, using a prototype radiofrequency catheter and generator, or a sham procedure. Pulmonary artery denervation resulted in reduced mean pulmonary artery pressure and pulmonary vascular resistance and increased cardiac output. Ablation lesions on the luminal surface of the pulmonary artery were accompanied by histological and biochemical alteration in adventitial nerves and correlated with improved hemodynamic parameters. Conclusions— Pulmonary artery denervation offers the possibility of a new treatment option for patients with pulmonary arterial hypertension. Further work is required to determine the long-term efficacy and safety. PMID:26553697
Kriz, Joseph P; Munfakh, Nabil A; King, Gregory S; Carden, Juan O
Pulmonary artery intimal sarcomas are rare and lethal malignant tumors that typically affect larger vessels: the aorta, inferior vena cava, and pulmonary arteries. Since symptoms and imaging of pulmonary arterial intimal sarcomas mimic pulmonary thromboembolism, the differential diagnosis of a patient presenting with chest pain, dyspnea, and filling defect within the pulmonary arteries should include intimal sarcoma. Often right ventricular failure is observed due to pulmonary hypertension caused by the obstructive effect of the tumor and concomitant chronic thromboembolism. We report the case of a 72-year-old African-American male with arterial intimal sarcoma of the left and right pulmonary artery with extension through the right artery into the bronchus and right lung.
Kriz, Joseph P.; Munfakh, Nabil A.; King, Gregory S.; Carden, Juan O.
Pulmonary artery intimal sarcomas are rare and lethal malignant tumors that typically affect larger vessels: the aorta, inferior vena cava, and pulmonary arteries. Since symptoms and imaging of pulmonary arterial intimal sarcomas mimic pulmonary thromboembolism, the differential diagnosis of a patient presenting with chest pain, dyspnea, and filling defect within the pulmonary arteries should include intimal sarcoma. Often right ventricular failure is observed due to pulmonary hypertension caused by the obstructive effect of the tumor and concomitant chronic thromboembolism. We report the case of a 72-year-old African-American male with arterial intimal sarcoma of the left and right pulmonary artery with extension through the right artery into the bronchus and right lung. PMID:27239183
Robinson, Jeffrey C; Pugliese, Steven C; Fox, Daniel L; Badesch, David B
Pulmonary arterial hypertension (PAH) is characterized by molecular and pathologic alteration to the pulmonary circulation, resulting in increased pulmonary vascular resistance, right ventricular failure, and eventual death. Pharmacologic treatment of PAH consists of use of a multitude of pulmonary vasodilators, sometimes in combination. PAH has been associated with increased thrombosis and disrupted coagulation and fibrinolysis, making anticoagulation an attractive and frequently employed therapeutic modality. Observational studies have provided some insight into the therapeutic potential of anticoagulation in idiopathic PAH, but there is a distinct lack of well-controlled prospective trials. Due to the conflicting evidence, there is a large amount of heterogeneity in the application of therapeutic anticoagulation in PAH and further well-controlled prospective trials are needed to clarify its role in treating PAH.
Koch, Achim; Mechtersheimer, Gunhild; Tochtermann, Ursula; Karck, Matthias
A 64-year-old male developed chest pain while gardening. Aortic dissection and coronary artery disease were excluded but chest computed tomography (CT) scan showed an aneurysmic enlargement of the pulmonary artery and a fluttering structure within. He underwent immediate sternotomy for replacement of the pulmonary artery. Histology showed an intimal sarcoma of both branches of the pulmonary artery. The pulmonary artery was replaced by a T-shaped Gore-Tex-prosthesis.
Kanjanauthai, Somsupha; Kanluen, Tony; Ray, Cynthia
Pulmonary artery sarcoma is a highly malignant tumour. Therefore, making the diagnosis is very important. We describe a case which presented with dyspnea on exertion and was initially diagnosed as saddle pulmonary embolism per CT thorax with contrast. Despite adequate anticoagulation, symptoms still progressed. Follow-up CT thorax showed an extension of the presumed filling defect or clots into the left main pulmonary artery with new lung nodules. This prompted suspicion that this may not be a pulmonary embolism. Biopsy of the lung nodule revealed high grade soft tissue sarcoma with primary source from the pulmonary artery. Our case highlights that pulmonary artery sarcoma should always be included in the differential diagnosis of pulmonary embolism especially, if symptoms still progress while on adequate anticoagulation, or any pulmonary nodules develop on follow-up exam.
Beghetti, Maurice; Tissot, Cecile
Pulmonary hypertension complicates the course of many children and adults with congenital heart diseases (CHDs). The increase in pulmonary pressure associated with CHD is secondary to either increased pulmonary blood flow or increased postcapillary pressures. Pulmonary arterial hypertension is in the vast majority associated with congenital cardiac shunts. Despite major advances in the understanding of the regulation of the pulmonary vascular bed and the pulmonary endothelial lesions leading to pulmonary vascular disease, despite the advances in surgical repair and the discovery of potential therapies in the pre- and postoperative period, pulmonary hypertension still carries a significant mortality and morbidity in patients with CHD. The recent introduction of targeted therapies in other forms of pulmonary arterial hypertension has led to a renewed interest in pulmonary hypertension associated with CHD and this particularly for the most advanced form, the so-called Eisenmenger syndrome (ES). This review summarizes the current knowledge on pulmonary hypertension associated with CHD, focusing on the pathophysiology and treatment of ES.
Siordia, Juan A; Garlish, Amanda; Truong, Huong
Primary pulmonary artery sarcoma is a rare disease that has a poor survival prognosis due to misdiagnosis with pulmonary thromboembolism or metastatic embolisation, detailed image findings and complicated surgical procedures. Surgical procedures established for treatment include pneumonectomy and pulmonary endarterectomy. Survival after surgery still remains at 1 year survival of 50%. The following case report demonstrates a patient's status postpneumonectomy for pulmonary artery sarcoma that presented with no complications after 1.5-year follow-up.
Gan, C.T.; Noordegraaf, A. Vonk; Marques, K.M.J.; Bronzwaer, J.G.F.; Postmus, P.E.; Boonstra, A.
Pulmonary arterial hypertension (PAH) is a disease characterised by an increased pulmonary artery pressure. The precapillary pulmonary arteries show distinct pathobiological changes, i.e. medial hypertrophy, intimal fibrosis, microthrombi and plexiform lesions. Although the pathogenesis is not completely understood, pulmonary vascular proliferation and remodelling, due to a variety of mediators, is believed to play the pathogenetic key role. Genetic research reveals molecular deformities and gene mutations associated with phenotypic PAH. This article covers novel insights into pathobiology, pathogenesis and genes of PAH, which led to a novel classification system and a diagnostic work-up, emanated from the World Health Organisation Symposium on Pulmonary Hypertension in Venice in June 2003. PMID:25696347
Emerson, Lyska L.; Bull, David A.; Hatton, Nathan; Nativi-Nicolai, Jose; Hildebrandt, Gerhard C.; Ryan, John J.
Abstract Amyloidosis involves extravascular deposition of fibrillar proteins within tissues and organs. Primary light chain amyloidosis represents the most common form of systemic amyloidosis involving deposition of monoclonal immunoglobulin light chains. Although pulmonary amyloid deposition is common in primary amyloidosis, clinically significant pulmonary amyloidosis is uncommon, and elevated pulmonary artery pressures are rarely observed in the absence of other underlying etiologies for pulmonary hypertension, such as elevated filling pressures secondary to cardiac amyloid. In this case report, we present a patient with primary light chain amyloidosis and pulmonary arterial hypertension in the setting of pulmonary vascular and right ventricular myocardial amyloid deposition. PMID:27252852
Elliott, C Gregory
Painstaking research led to the discovery of gene mutations responsible for heritable forms of pulmonary arterial hypertension (PAH). Mutations in the gene BMPR2, which codes for a cell surface receptor (BMPRII), cause the approximately 80% of heritable cases of PAH. Less commonly mutations in ALK1, CAV1, ENG, and SMAD9, and newly discovered mutations in KCNK3, may cause heritable PAH. Other family members of many patients diagnosed with idiopathic PAH may be diagnosed with PAH. Genetic counseling and testing should be offered to patients diagnosed with heritable or idiopathic PAH.
Yamamoto, Kei; Nozue, Tsuyoshi; Tsuchida, Masayuki; Iwaki, Taku; Nagamine, Hiroshi; Yasuda, Tamotsu; Kawase, Hiroshi; Matsushita, Kazuhiko; Michishita, Ichiro
We herein report the case of a 39-year-old woman with a pulmonary embolism caused by intimal sarcoma of the pulmonary artery. She presented with shortness of breath and leg edema. Computed tomography showed a low density area that extended from the main pulmonary artery to the bilateral pulmonary arteries. We diagnosed her to have a pulmonary thromboembolism. The thrombosis did not decrease after the administration of anti-coagulant therapy, and she underwent resection of the thrombotic tissue. Histopathologically, the surgical specimen was not found to be thrombotic tissue but rather an intimal sarcoma of the pulmonary artery. After undergoing surgery, she received radiation therapy and chemotherapy; however, she died 31 months after being diagnosed.
Hou, Yulong; Shen, Zhenya; Gao, Wei; Ye, Wenxue
A 72-year-old woman with pulmonary artery intimal sarcoma was successfully treated with surgery. With heightened clinical awareness and technological advancement, more and more cases were diagnosed definitely before operation. Computed tomography of the chest showed a mass in right ventricular extending to pulmonary trunk and the left pulmonary artery. The patient underwent complete surgical resection and repair of the pulmonary artery with no evidence of recurrence during the 12-month follow-up, suggesting that early identification and aggressive surgical intervention would improve survival.
Santos-Ribeiro, Diana; Mendes-Ferreira, Pedro; Maia-Rocha, Carolina; Adão, Rui; Leite-Moreira, Adelino F; Brás-Silva, Carmen
Pulmonary arterial hypertension is a progressive syndrome based on diverse aetiologies, which is characterized by a persistent increase in pulmonary vascular resistance and overload of the right ventricle, leading to heart failure and death. Currently, none of the available treatments is able to cure pulmonary arterial hypertension; additional research is therefore needed to unravel the associated pathophysiological mechanisms. This review summarizes current knowledge related to this disorder, and the several experimental animal models that can mimic pulmonary arterial hypertension and are available for translational research.
Akagi, Satoshi; Nakamura, Kazufumi; Matsubara, Hiromi; Ogawa, Aiko; Sarashina, Toshihiro; Ejiri, Kentaro; Ito, Hiroshi
Pulmonary arterial hypertension (PAH) is characterized by elevation of pulmonary artery pressure caused by pulmonary vasoconstriction and vascular remodeling, which leads to right heart failure and death. Epoprostenol (prostaglandin I2) has a potent short-acting vasodilator property, and intravenous continuous epoprostenol is therefore used for treatment of PAH. Here we review evidence for the usefulness of intravenous continuous epoprostenol therapy in patients with PAH. Epoprostenol therapy is effective in idiopathic PAH patients and in patients with PAH associated with connective tissue disease, portal hypertension or congenital heart diseases, but it is not effective in patients with pulmonary veno-occlusive disease or pulmonary capillary hemangiomatosis. High-dose epoprostenol therapy markedly improved hemodynamics in some patients with PAH, possibly due to reverse remodeling of pulmonary arteries. This therapy has several side effects and complications such as headache, hypotension and catheter-related infections. Intravenous continuous epoprostenol is an effective treatment, but there are still some problems to be resolved.
Roman, Antonio; López-Meseguer, Manuel; Domingo, Enric
Treatment of pulmonary arterial hypertension has achieved significant progress over the past 20 years. Currently, 3 groups of drugs have proven useful for the treatment of this disease: endothelin receptor antagonist, phosphodiesterase inhibitors and prostacyclin and its analogues. It is recommended to initiate treatment with one of these drugs, the choice depending on the initial severity of patient disease and the preferences of the treating physician. When the patient does not have a satisfactory response, new drugs acting at a different pathway are most commonly added. At this time, considering referral for lung transplantation could be an alternative. Most experts recommend grouping maximum experience in what is known as expert centers. Treatment has led to better survival in these patients, but there is still a long way to cure this life-threatening disease.
Leopold, Jane A.; Maron, Bradley A.
Pulmonary arterial hypertension (PAH) is a devastating disease that is precipitated by hypertrophic pulmonary vascular remodeling of distal arterioles to increase pulmonary artery pressure and pulmonary vascular resistance in the absence of left heart, lung parenchymal, or thromboembolic disease. Despite available medical therapy, pulmonary artery remodeling and its attendant hemodynamic consequences result in right ventricular dysfunction, failure, and early death. To limit morbidity and mortality, attention has focused on identifying the cellular and molecular mechanisms underlying aberrant pulmonary artery remodeling to identify pathways for intervention. While there is a well-recognized heritable genetic component to PAH, there is also evidence of other genetic perturbations, including pulmonary vascular cell DNA damage, activation of the DNA damage response, and variations in microRNA expression. These findings likely contribute, in part, to dysregulation of proliferation and apoptosis signaling pathways akin to what is observed in cancer; changes in cellular metabolism, metabolic flux, and mitochondrial function; and endothelial-to-mesenchymal transition as key signaling pathways that promote pulmonary vascular remodeling. This review will highlight recent advances in the field with an emphasis on the aforementioned molecular mechanisms as contributors to the pulmonary vascular disease pathophenotype. PMID:27213345
Lai, Yen-Chun; Potoka, Karin C.; Champion, Hunter C.; Mora, Ana L.; Gladwin, Mark T.
Pulmonary arterial hypertension (PAH) is a progressive disorder in which endothelial dysfunction and vascular remodeling obstruct small pulmonary arteries, resulting in increased pulmonary vascular resistance and pulmonary pressures. This leads to reduced cardiac output, right heart failure, and ultimately death. In this review, we attempt to answer some important questions commonly asked by patients diagnosed with PAH pertaining to the disease, and aim to provide an explanation in terms of classification, diagnosis, pathophysiology, genetic etiologies, demographics, and prognostic factors. Furthermore, important molecular pathways that are central to the pathogenesis of PAH are reviewed, including nitric oxide, prostacyclin, endothelin-1, reactive oxygen species, and endothelial and smooth muscle proliferation. PMID:24951762
Yamasaki, Motohisa; Sumi, Yuki; Sakakibara, Yumi; Tamaoka, Meiyo; Miyazaki, Yasunari; Arai, Hirokumi; Kojima, Katsuo; Itoh, Fusahiko; Amano, Tomonari; Yoshizawa, Yasuyuki; Inase, Naohiko
A 63-year-old female presented with abnormal lung shadows but had, apart from this, few symptoms. Computed tomography (CT) revealed multiple nodules and blockage of the pulmonary artery. She was immediately diagnosed with pulmonary artery sarcoma based on a careful differential diagnosis and underwent surgery. Her tumor was pathologically diagnosed as leiomyosarcoma (i.e. intimal sarcoma). Pulmonary artery sarcoma can be easily confounded with thromboembolism in a clinical setting and some cases are diagnosed post mortem only. In our case, clinical prediction scores (Wells score, Geneva score, and revised Geneva score) for the pulmonary embolism showed low probability. Moreover, chest CT showed uncommon findings for pulmonary thromboembolism, as the nodules were too big for thrombi. Because surgical resection can provide the only hope of long-term survival in cases of pulmonary artery sarcoma, clinicians should consider this possibility in the differential diagnosis of pulmonary embolism. Clinical prediction scores and CT findings might help to reach the correct diagnosis of pulmonary artery sarcoma.
Guzeltas, Alper; Ozturk, Erkut; Tanidir, Ibrahim Cansaran; Kasar, Taner; Haydin, Sertac
Objective This study evaluated clinical and diagnostic findings, treatment methods, and follow-up of cases of anomalous coronary arteries from the pulmonary artery. Methods The study included all cases diagnosed with anomalous coronary arteries from the pulmonary artery between January 2012 and January 2016. Data from patients’ demographic characteristics, electrocardiography, echocardiography, angiographic findings, operation, intensive care unit stay, and follow-up were evaluated. Results The study included 12 patients (8 male, 4 female), 10 with anomalous left coronary artery from the pulmonary artery (ALCAPA) and 2 with anomalous right coronary artery from the pulmonary artery (ARCAPA). Median age at diagnosis was 4 months (range, 1 month - 10 years old) and median weight was 5.5 kg (range, 3-30 kg). The most common complaints were murmur (n=7) and respiratory distress (n=5). In 4 cases, the initial diagnosis was dilated cardiomyopathy. Electrocardiographs were pathologic in all cases. Echocardiographic examination revealed medium to severe mitral valve regurgitation in 4 cases and reduced (< 40%) ejection fraction in 6 patients. Of the 12 patients, 8 underwent direct implantation of the left coronary artery into the aorta, 2 underwent implantation of the right coronary artery into the aorta, and the remaining 2 underwent a Takeuchi procedure. There were no early mortalities. Median hospital stay was 20 days (range, 5-35 days). Median follow-up duration was 18 months (range, 5-36 months), and no cases required further surgery during follow-up. Conclusions Anomalous coronary arteries from the pulmonary artery can be successfully repaired providing there is early diagnosis and effective, appropriate intensive care unit follow-up. Therefore, coronary artery origins should be evaluated carefully, especially in cases with dilated cardiomyopathies.
Shingaki, Masami; Kobayashi, Yutaka
60-year-old female who complained of severe dyspnea was admitted with a diagnosis of massive pulmonary embolism. An emergency operation was undertaken due to right side heart failure. Under extracorporeal circulation with beating heart, large, white and smooth surface mass which was originated from right pulmonary artery was removed. Pathology of the mass showed low differentiated sarcoma. No evidence of other primary lesion by positron emission tomography-computed tomography (PET-CT) suggested primary pulmonary artery sarcoma. We scheduled total resection of the right lung, however postoperative CT showed large mass occupying from right pulmonary artery to main pulmonary trunk. Palliative chemo radiation therapy was introduced. Pulmonary artery sarcoma mimicking pulmonary thromboembolism is so malignant that the diagnosis and treatment should not be delayed.
Enderby, Cher Y; Burger, Charles
Pulmonary arterial hypertension is a chronic, progressive disease of the pulmonary vasculature resulting in poor outcomes if left untreated. The management of group 1 pulmonary arterial hypertension has included the use of prostanoids, phosphodiesterase-5 inhibitors, and endothelin receptor antagonists targeting the prostacyclin, endothelin-1, and nitric oxide pathways. Three new medications have been approved by the US Food and Drug Administration over the past couple of years. Macitentan is the newest endothelin receptor antagonist, riociguat is a soluble guanylate cyclase stimulator, and treprostinil diolamine is the first oral prostanoid. This review will focus on the key trials leading to their approval, special considerations for each medication, and their potential place in therapy. The use of combination therapy as initial therapy in pulmonary arterial hypertension will also be discussed.
Genetic analysis has uncovered that familial and idiopathic pulmonary arterial hypertension (PAH) is linked to germline mutations in BMP type II receptor (BMPRII). PAH is characterized by enhanced remodeling of pulmonary arteries due to arterial smooth muscle cell proliferation. BMPRII mutations contribute to abnormal mitotic responses to BMP ligands in pulmonary artery smooth muscle cells. Unbalanced Smad signaling induced by BMP and TGFbeta is functionally involved in the pathogenesis of PAH. BMPRII mutations also increase the susceptibility of endothelial cell apoptosis. The combination of increased endothelial injury and impaired suppression of smooth muscle cell proliferation is critical for the cellular pathogenesis of PAH. However, the detailed molecular mechanism leading to severe vascular remodeling caused by BMPRII mutations has yet to be elucidated.
Stacher, Elvira; Graham, Brian B.; Hunt, James M.; Gandjeva, Aneta; Groshong, Steve D.; McLaughlin, Vallerie V.; Jessup, Marsha; Grizzle, William E.; Aldred, Michaela A.; Cool, Carlyne D.
Rationale: The impact of modern treatments of pulmonary arterial hypertension (PAH) on pulmonary vascular pathology remains unknown. Objectives: To assess the spectrum of pulmonary vascular remodeling in the modern era of PAH medication. Methods: Assessment of pulmonary vascular remodeling and inflammation in 62 PAH and 28 control explanted lungs systematically sampled. Measurements and Main Results: Intima and intima plus media fractional thicknesses of pulmonary arteries were increased in the PAH group versus the control lungs and correlated with pulmonary hemodynamic measurements. Despite a high variability of morphological measurements within a given PAH lung and among all PAH lungs, distinct pathological subphenotypes were detected in cohorts of PAH lungs. These included a subset of lungs lacking intima or, most prominently, media remodeling, which had similar numbers of profiles of plexiform lesions as those in lungs with more pronounced remodeling. Marked perivascular inflammation was present in a high number of PAH lungs and correlated with intima plus media remodeling. The number of profiles of plexiform lesions was significantly lower in lungs of male patients and those never treated with prostacyclin or its analogs. Conclusions: Our results indicate that multiple features of pulmonary vascular remodeling are present in patients treated with modern PAH therapies. Perivascular inflammation may have an important role in the processes of vascular remodeling, all of which may ultimately lead to increased pulmonary artery pressure. Moreover, our study provides a framework to interpret and design translational studies in PAH. PMID:22679007
Boucherat, Olivier; Chabot, Sophie; Antigny, Fabrice; Perros, Frédéric; Provencher, Steeve; Bonnet, Sébastien
Pulmonary arterial hypertension (PAH) is a devastating cardiopulmonary disorder with various origins. All forms of PAH share a common pulmonary arteriopathy characterised by vasoconstriction, remodelling of the pre-capillary pulmonary vessel wall, and in situ thrombosis. Although the pathogenesis of PAH is recognised as a complex and multifactorial process, there is growing evidence that potassium channels dysfunction in pulmonary artery smooth muscle cells is a hallmark of PAH. Besides regulating many physiological functions, reduced potassium channels expression and/or activity have significant effects on PAH establishment and progression. This review describes the molecular mechanisms and physiological consequences of potassium channel modulation. Special emphasis is placed on KCNA5 (Kv1.5) and KCNK3 (TASK1), which are considered to play a central role in determining pulmonary vascular tone and may represent attractive therapeutic targets in the treatment of PAH.
Nakashima, S; Kuwaki, K; Komatsu, K; Tsukamoto, M; Abe, T
A 63-year-old woman who underwent surgical correction of a recurrent pulmonary artery aneurysm associated with pulmonary stenosis and regurgitation is reported. On April 1986, she underwent commissurotomy of pulmonary valve, reconstruction of right ventricle out flow tract using a Polystan monocusp patch and pulmonary aneurysmorrhaphy for pulmonary artery aneurysm. Pathological examination of the resected pulmonary arterial wall revealed mucoid degeneration of media and fragmentation of elastic fiber. Nine years after the operation, recurrence of pulmonary artery aneurysm, pulmonary stenosis and regurgitation were recognized. On September 1995, she underwent redo operation with graft replacement of pulmonary artery and pulmonary valve replacement using woven Dacron prosthesis containing a Carpentier-Edwards bioprosthetic valve. We should choose as an initial procedure with graft replacement for pulmonary artery aneurysm with fragility of the pulmonary arterial wall. She is now doing very well at one year and 5 months after the redo operation.
Presti, B; Berthrong, M; Sherwin, R M
Chronic massive thrombosis of major pulmonary arteries, usually described in 0.1% of autopsies, was found in 68 of 7,753 autopsies (0.9%) in our hospital. For comparison, 201 of the 7,753 autopsies (2.6%) revealed acute-massive pulmonary emboli. The 68 cases of chronic thromboses by definition had the right, left, or main pulmonary artery occluded or severely stenosed by organized thrombi. The average age was 67; males predominated 3 to 2. Dyspnea and right heart failure were the most common clinical features, though a correct antemortem diagnosis was rare. Severe lung disease was present in 34 cases (50%); one patient (1%) had mitral stenosis. In the remaining patients, clinical thrombophlebitis had been present in 20 cases (29%), and 13 cases (19%) had no recognized related disease. When the lung disease had prominent laterality, thrombi were invariably located on the side of the most serious disease, implying propagation of smaller thrombi in diseased lung retrograde to major arteries. In bilateral lung disease or in patients without lung disease, thromboses were randomly distributed between right or left sides, suggesting an embolic origin. Assessment of the severity of pulmonary arteriosclerosis and distal arterial patency indicated that most patients could have potentially benefited from surgical thromboendarterectomy. The reason for the high incidence of chronic pulmonary artery thrombosis in our autopsy service has not been elucidated. The effects of high altitude may be important in the pathogenesis, although polycythemia was not excessive in our cases.
Badesch, David B; Champion, Hunter C; Sanchez, Miguel Angel Gomez; Hoeper, Marius M; Loyd, James E; Manes, Alessandra; McGoon, Michael; Naeije, Robert; Olschewski, Horst; Oudiz, Ronald J; Torbicki, Adam
The diagnosis and assessment of pulmonary arterial hypertension is a rapidly evolving area, with changes occurring in the definition of the disease, screening and diagnostic techniques, and staging and follow-up assessment. The definition of pulmonary hypertension has been simplified, and is now based on currently available evidence. There has been substantial progress in advancing the imaging techniques and biomarkers used to screen patients for the disease and to follow up their response to therapy. The importance of accurate assessment of right ventricular function in following up the clinical course and response to therapy is more fully appreciated. As new therapies are developed for pulmonary arterial hypertension, screening, prompt diagnosis, and accurate assessment of disease severity become increasingly important. A clear definition of pulmonary hypertension and the development of a rational approach to diagnostic assessment and follow-up using both conventional and new tools will be essential to deriving maximal benefit from our expanding therapeutic armamentarium.
Zhou, Guofei; Chen, Tianji
Pulmonary arterial hypertension (PAH) is a devastating disease without effective treatment. Despite decades of research and the development of novel treatments, PAH remains a fatal disease, suggesting an urgent need for better understanding of the pathogenesis of PAH. Recent studies suggest that microRNAs (miRNAs) are dysregulated in patients with PAH and in experimental pulmonary hypertension. Furthermore, normalization of a few miRNAs is reported to inhibit experimental pulmonary hypertension. We have reviewed the current knowledge about miRNA biogenesis, miRNA expression pattern, and their roles in regulation of pulmonary artery smooth muscle cells, endothelial cells, and fibroblasts. We have also identified emerging trends in our understanding of the role of miRNAs in the pathogenesis of PAH and propose future studies that might lead to novel therapeutic strategies for the treatment of PAH. PMID:25192340
Barker, S; Khan, N Q; Wood, E G; Corder, R
Endothelin-1 (ET-1) is secreted from endothelial and vascular smooth muscle cells (VSMC) after intracellular hydrolysis of big ET-1 by endothelin converting enzyme (ECE). The metallopeptidase called ECE-1 is widely thought to be the physiological ECE, but unequivocal evidence of this role has yet to be provided. Endothelial cells express four isoforms of ECE-1 (ECE-1a, ECE-1b, ECE-1c, and ECE-1d), but the identity of ECE-1 isoforms expressed in VSMC is less clear. Here, we describe the characterization of ECE-1 isoforms in bovine pulmonary artery smooth muscle cells (BPASMC) and the effect on ET-1 synthesis of an antisense oligodeoxynucleotide (ODN) to ECE-1c. Reverse transcriptase-polymerase chain reaction (RT-PCR) evaluation of total RNA from BPASMC showed that ECE-1a and ECE-1d were not expressed. Sequencing of cloned ECE-1 cDNA products and semiquantitative RT-PCR demonstrated that ECE-1b and ECE-1c were expressed in BPASMC, with ECE-1c being the predominant isoform. Basal release of ET-1 from BPASMC was low. Treatment for 24 h with tumor necrosis factor-alpha (TNFalpha) stimulated ET-1 production by up to 10-fold with parallel increases in levels of preproET-1 mRNA. Levels of ECE-1c mRNA were also raised after TNFalpha, whereas amounts of ECE-1b mRNA were decreased significantly. Treatment of BPASMC with a phosphorothioate antisense ODN to ECE-1c caused a marked reduction in ECE-1c mRNA levels and ECE-1 protein levels. However, basal and TNFalpha-stimulated ET-1 release were largely unaffected by the ECE-1c antisense ODN despite the inhibition of ECE-1c synthesis. Hence, an endopeptidase distinct from ECE-1 is mainly responsible big ET-1 processing in BPASMC.
Slavik, Z; Webber, S A; Lamb, R K; Horvath, P; LeBlanc, J G; Keeton, B R; Monro, J L; Tax, P; Tuma, S; Reich, O
Right-sided BSCA provides for satisfactory pulmonary arterial growth in infants and children with complex congenital heart defects, and it could enhance the growth of a small right pulmonary artery. The growth of the left pulmonary artery, particularly in younger patients, needs close attention to confirm the safe role of BSCA in long-term palliation.
Hako, René; Fedačko, Ján; Morochovič, Radoslav; Kristian, Pavol; Pekárová, Tímea; Tuomainen, Petri; Pella, Daniel
Background. Pulmonary arterial dissection with chronic pulmonary arterial hypertension as its major cause is a very rare but life-threatening condition. In most cases the main pulmonary trunk is the affected site usually without involvement of its branches. Segmental or lobar pulmonary artery dissection is extremely rare. Case Presentation. We report a unique case of left lower lobe pulmonary artery dissection in a 70-year-old male, with confirmed chronic pulmonary hypertension. To confirm dissection MDCT pulmonary angiography was used. Multiplanar reformation (MPR) images in sagittal, coronal, oblique sagittal, and curved projections were generated. This case report presents morphologic CT features of rare chronic left lobar pulmonary artery dissection associated with chronic pulmonary hypertension at a place of localised pulmonary artery calcification. CT pulmonary angiography excluded signs of thromboembolism and potential motion or flow artefacts. Conclusion. To the best of our knowledge, no case of lower lobe pulmonary artery dissection with flap calcification has been reported yet. CT imaging of the chest is a key diagnostic tool that is able to detect an intimal flap and a false lumen within the pulmonary arterial tree and is preferred in differential diagnosis of rare complications of sustained pulmonary arterial hypertension. PMID:28154579
Velebit, V.; Christenson, J. T.; Simonet, F.; Maurice, J.; Schmuziger, M.; Hauser, H.; Didier, D.
A pulmonary artery sarcoma was diagnosed preoperatively by magnetic resonance imaging enhanced with gadolinium and confirmed by percutaneous computed tomographic guided needle biopsy. Accurate preoperative diagnosis allowed planned curative surgery with removal of the right ventricular outflow tract and reconstructive surgery using a cryopreserved homograft. Images PMID:8539663
Zajtchuk, Rustik; Resnekov, Leon; Ranniger, Klaus; Gonzalez-Lavin, Lorenzo
A case of chronic aortic to pulmonary artery traumatic fistula is presented and the surgical repair is detailed. Closure through the aorta is recommended; this approach provides a dry operative field and avoids the need for dissection of adhesions around the fistulous tract. Fistulae of this type are not common and the pertinent literature is reviewed. Images PMID:5576540
Khomaziuk, V A
Echocardiographic evaluation was done of left ventricular functional state in 90 patients with primary and secondary pulmonary arterial hypertension with and without intercavitary shunting. Changes in left ventricular function were identified in 86% cases; they reflected disturbances in both ventricles compensatory interaction. The degree of changes depended on the degree of dilatation of the right ventricle and level of interchamber shunting.
SMA with some globular domains, predominantly colocalizing with GFP endothelial lineage-marked cells in the neointima (Figure 4F). Figure 4. VE...whether the neointima arises from a small population of apoptosis- resistant pulmonary artery endothelial cells that proliferate after injury to produce
Prasad, Rajniti; Srivastava, G N; Mishra, O P; Singh, Utpal Kant
We report a two-and-half–year-old boy who presented with recurrent respiratory tract infections. He had cortriatum of right atrium, spina bifida occulta, hemivertebra and dysplastic right thumb. On CT of chest, he had also unilateral pulmonary artery agenesis. The case is being reported because of common manifestations of rare disease and its associated cardiac and skeletal abnormalities. PMID:23784756
Jiang, Xinguo; Tamosiuniene, Rasa; Sung, Yon K.; Shuffle, Eric M.; Tu, Allen B.; Valenzuela, Antonia; Jiang, Shirley; Zamanian, Roham T.; Fiorentino, David F.; Voelkel, Norbert F.; Peters-Golden, Marc; Stenmark, Kurt R.; Chung, Lorinda; Rabinovitch, Marlene; Nicolls, Mark R.
A recent study demonstrated a significant role for leukotriene B4 (LTB4) causing pulmonary vascular remodeling in pulmonary arterial hypertension (PAH). LTB4 was found to directly injure luminal endothelial cells and promote growth of the smooth muscle cell layer of pulmonary arterioles. The purpose of the current study was to determine the effects of LTB4 on the pulmonary adventitial layer, largely composed of fibroblasts. Here, we demonstrate that LTB4 enhanced human pulmonary artery adventitial fibroblast (HPAAF) proliferation, migration and differentiation in a dose-dependent manner through its cognate G-protein coupled receptor, BLT1. LTB4 activated HPAAF by up-regulating p38 MAPK as well as Nox4 signaling pathways. In an autoimmune model of PH, inhibition of these pathways blocked perivascular inflammation, decreased Nox4 expression, reduced reactive oxygen species production, reversed arteriolar adventitial fibroblast activation and attenuated PH development. This study uncovers a novel mechanism by which LTB4 further promotes PAH pathogenesis, beyond its established effects on endothelial and smooth muscle cells, by activating adventitial fibroblasts. PMID:26558820
Perros, Frédéric; Humbert, Marc; Cohen-Kaminsky, Sylvia
It is admitted that autoimmunity results from a combination of risks such as genetic background, environmental triggers, and stochastic events. Pulmonary arterial hypertension (PAH) shares with the so-called prototypic autoimmune diseases, genetic risk factors, female predominance and sex hormone influence, association with other chronic inflammatory and autoimmune diseases, defects in regulatory T cells function, and presence of autoantibodies. Case reports have been published indicating the beneficial effect of some immunosuppressive and anti-inflammatory therapies in PAH, supporting the potential role of immune mechanisms in the pathophysiology of the disease. In this review, we discuss the current knowledge on autoimmune mechanisms operating in PAH, especially mounting a local autoimmune response inside the pulmonary tissue, namely pulmonary lymphoid neogenesis. A better understanding of the role of autoimmunity in pulmonary vascular remodelling may help develop targeted immunomodulatory strategies in PAH.
Gan, C.T.; Noordegraaf, A. Vonk; Marques, K.M.J.; Bronzwaer, J.G.F.; Postmus, P.E.; Boonstra, A.
Medical therapy for pulmonary arterial hypertension (PAH) focuses on pulmonary vascular remodelling and smooth muscle cell proliferation. This article covers the drugs which are approved or are in sight and the evidence-based treatment strategies that target the different pathobiological pathways, emanated from the World Health Organisation Symposium on Pulmonary Hypertension in Venice, June 2003. In addition we briefly look at the 'Venice consensus' on surgical treatment. In the past five and a half years more than 360 patients were seen for pulmonary hypertension in the Free University Medical Centre (VUmc). Present-day treatment, research studies and novel treatment strategies in the VUmc will be reviewed. Future treatments will be on the basis of insights into pathobiology, pathogenesis and genes in PAH and should focus on drug combinations, which theoretically target different or similar pathobiological pathways. PMID:25696358
Lee, Ran; Son, Jae Sung; Park, Yong Mean
Aneurysm of the main pulmonary artery is a rare clinical entity that can be congenital or acquired. Most cases occur in association with other congenital malformations, severe pulmonary hypertension, vasculitides, infectious agents, or collagen vascular disorders. We report here a pediatric case of left pulmonary artery aneurysm associated with valvular pulmonary stenosis and a hypoplastic right pulmonary artery, which we confirmed via multidetector computed tomography angiography.
Ryan, John; Dasgupta, Asish; Huston, Jessica; Chen, Kuang-Huieh; Archer, Stephen L.
Pulmonary arterial hypertension (PAH) is an idiopathic cardiopulmonary disease characterized by obstruction of small pulmonary arteries by excessive proliferation and apoptosis-resistance of vascular cells, as well as inflammation, thrombosis and vasoconstriction. Vascular obstruction increases the afterload faced by the right ventricle (RV), leading to RV failure. The proliferative, obstructive vasculopathy of PAH shares several mitochondrial abnormalities with cancer, notably a shift to aerobic glycolysis and mitochondrial fragmentation. Mitochondria in the pulmonary artery smooth muscle cell (PASMC) normally serve as oxygen sensors. In PAH, acquired mitochondrial abnormalities, including epigenetic silencing of superoxide dismutase (SOD2), disrupt oxygen sensing creating a pseudo-hypoxic environment characterized by normoxic activation of Hypoxia-Inducible Factor-1α (HIF-1α). The resulting metabolic shift to aerobic glycolysis (the Warburg phenomenon) reflects inhibition of pyruvate dehydrogenase by pyruvate dehydrogenase kinases. In addition, altered mitochondrial dynamics result in mitochondrial fragmentation. The molecular basis of this structural change includes upregulation and activation of fission mediators, notably dynamin-related protein 1 (DRP-1), and downregulation of fusion mediators, especially mitofusin-2 (MFN2). These pathogenic mitochondrial abnormalities offer new therapeutic targets. Inhibition of mitotic fission or enhancement of fusion in PAH PASMC slows cell proliferation, causes cell cycle arrest, and induces apoptosis. DRP-1 inhibition or MFN2 gene therapy can regress PAH in experimental models of PAH. This review focuses on the etiology of mitochondrial fragmentation in PAH and explores the therapeutic implications of mitochondrial dynamics in the pulmonary vasculature and RV. PMID:25672499
Geyik, Serdar; Yavuz, Kivilcim; Keller, Frederick S.
Connections between the systemic and pulmonary arterial systems are rare conditions that can be due to either congenital or acquired diseases such as anomalous systemic arterial supply to normal lung, pulmonary sequestration, and systemic supply to pulmonary arteriovenous malformations. Herein, a unique case of systemic artery to pulmonary arterial malformation and its endovascular treatment in a patient with no history of the usual etiologies is reported.
Shinkawa, Takeshi; Anagnostopoulos, Petros V.; Johnson, Natalie C.; Watanabe, Naruhito; Sapru, Anil; Azakie, Anthony
Background The purpose of this study is to determine the outcome and performance of bovine pericardial valves in the pulmonary position. Methods This is a retrospective review of all patients with congenital heart disease who had pulmonary valve replacement using a bovine pericardial valve from 2002 to 2009 at a single institution. Results There were 73 consecutive patients, with a median age of 17.3 years (range, 2.1 to 64.4). Their diagnosis was tetralogy of Fallot (n = 47), pulmonary stenosis (n = 11), or other (n = 15). Sixty-nine patients had 91 previous surgical procedures. The mean time from last surgery was 19.9 ± 11.6 years. Forty-three patients had concomitant surgical procedures. There were no perioperative deaths. Clinical follow-up was available in 68 patients (93%). There were no late deaths, and all patients were in New York Heart Association functional class I during a median follow-up period of 2.6 years (range, 0.2 to 8.0). One patient had endocarditis necessitating valve removal 2 years after surgery. Freedom from pulmonary valve reoperation was 100%, 97.7%, and 97.7% at 1, 3, and 5 years, respectively (95% confidence interval: 93.2% to 100%). Mean pulmonary valve gradient at follow-up was 19 ± 14 mm Hg. Degree of pulmonary insufficiency was less than moderate in 62 patients, moderate in 4, and more than moderate in 2. Freedom from moderate-severe or severe pulmonary insufficiency was 97.7%, 89.1%, and 89.1% at 1, 3, and 5 years, respectively (5-year 95% confidence interval: 77.0% to 100%). Conclusions Pulmonary valve replacement using a bovine pericardial valve can be accomplished with low perioperative morbidity and favorable midterm outcomes. Further follow-up is necessary to evaluate the long-term performance of bovine pericardial valves in the pulmonary position. PMID:20868832
Fujio, Hideki; Nakamura, Kazufumi; Matsubara, Hiromi; Kusano, Kengo Fukushima; Miyaji, Katsumasa; Nagase, Satoshi; Ikeda, Tetsuya; Ogawa, Aiko; Ohta-Ogo, Keiko; Miura, Daiji; Miura, Aya; Miyazaki, Masahiro; Date, Hiroshi; Ohe, Tohru
Idiopathic pulmonary arterial hypertension (IPAH) is associated with proliferation of smooth muscle cells (SMCs) in small pulmonary arteries. Inhibition of proliferation of pulmonary artery smooth muscle cells (PASMCs) may be an effective treatment of patients with idiopathic pulmonary arterial hypertension. Recent studies have shown that carvedilol, an alpha- and beta-blocker with antioxidant and calcium channel blocking properties, inhibits the proliferation of cultured normal human pulmonary artery smooth muscle cells. In this study, we tested the hypothesis that carvedilol has antiproliferative effects on pulmonary artery smooth muscle cells of patients with idiopathic pulmonary arterial hypertension. Pulmonary artery smooth muscle cells from six idiopathic pulmonary arterial hypertension patients who had undergone lung transplantation were cultured. To determine cell proliferation, H-thymidine incorporation was measured. Platelet-derived growth factor-induced proliferation of IPAH-PASMCs was significantly greater than that of normal control pulmonary artery smooth muscle cells. Carvedilol (0.1 microM to 10 microM) inhibited the proliferation of idiopathic pulmonary arterial hypertension-pulmonary artery smooth muscle cells in a concentration-dependent manner. Prazosin (an alpha-blocker) and N-acetyl L cysteine (an antioxidant agent) (0.1 microM to 10 microM) did not inhibit their proliferation, but the high concentration of propranolol (a beta-blocker) and nifedipine (a calcium channel blocker) (10 microM) inhibited the proliferation. The combination of propranolol and nifedipine inhibited the proliferation but only at a high concentration (10 microM) combination. Cell cycle analysis revealed that carvedilol (10 microM) significantly decreased the number of cells in S and G2/M phases. These results indicate that carvedilol inhibits the exaggerated proliferation of pulmonary artery smooth muscle cells of patients with idiopathic pulmonary arterial hypertension
Tanaka, Akiko; Shirasaka, Tomonori; Okada, Kenji; Okita, Yutaka
We describe our experience with a patient who had metastasized pulmonary artery sarcoma, but survived 7 years after diagnosis. A 61-year-old man was diagnosed with pulmonary artery intimal sarcoma after resection of metastatic tumours to the bilateral lungs. The primary lesion in the pulmonary artery trunk extending into the bilateral branches was treated by tumour endoarterectomy followed by chemotherapy. He underwent resections of lung metastases two more times before detection of recurrent obstructive pulmonary artery sarcoma 4 years after the tumour endoarterectomy. En bloc resection of the tumour including the pulmonary artery trunk, valve and interventricular septum was performed, and the right ventricular out flow tract was reconstructed with a stentless pulmonary valve and equine pericardium. He died of the disease soon after an operation for metastatic brain tumour 3 years later. Pulmonary artery sarcoma has a dismal prognosis, but aggressively repeated surgical interventions may lengthen survival.
Fukuda, Wakako; Morohashi, Satoko; Fukuda, Ikuo
Pulmonary artery intimal sarcoma is a rare tumour and the diagnosis is often delayed. We report the case of a woman with a primary pulmonary artery intimal sarcoma who presented with massive pulmonary embolism. The definitive diagnosis was elucidated after the patient's death by autopsy specimen. We discuss the diagnosis and lessons learned from this case.
Green, Nicholas J; Rollason, Terence P
Fatal haemopericardium in a 27 year old pregnant woman was caused by rupture of a dissecting aneurysm of the pulmonary artery. She had an uncorrected patent ductus arteriosus and severe pulmonary hypertension. The wall of the pulmonary artery showed atherosclerosis and cystic medionecrosis. PMID:1467058
AOKI, Takuma; SUNAHARA, Hiroshi; SUGIMOTO, Keisuke; ITO, Tetsuro; KANAI, Eiichi; FUJII, Yoko
Case 1 involved a 4-month-old intact male Somali cat in which peripheral pulmonary artery stenosis (PPS) was recognized after a cardiac murmur remained following patent ductus arteriosus ligation. Case 2, which involved a 1-year-old neutered male Norwegian Forest cat, and Case 3, which involved a 6-month-old intact female American Curl cat, were referred, because of cardiac murmurs. Grades III to IV/VI systolic heart murmurs were auscultated at the left heart base in all 3 cats. All cases showed bilateral pulmonary artery stenosis, although there were no associated clinical signs. In Cases 1 and 2, the pressure gradient through the stenosis decreased after treatment with atenolol. PMID:25650057
Khattar, R S; Fox, D J; Alty, J E; Arora, A
Pulmonary arterial dissection is an extremely rare and usually lethal complication of chronic pulmonary hypertension. The condition usually manifests as cardiogenic shock or sudden death and is therefore typically diagnosed at postmortem examination rather than during life. However, recent isolated reports have described pulmonary artery dissection in surviving patients. The first case of pulmonary artery dissection in a surviving patient with cor pulmonale caused by chronic obstructive pulmonary disease is presented. The aetiology, pathophysiology, and clinical presentation of pulmonary artery dissection are reviewed and factors that may aid diagnosis during life are discussed.
Perros, Frédéric; Montani, David; Dorfmüller, Peter; Huertas, Alice; Chaumais, Marie-Camille; Cohen-Kaminsky, Sylvia; Humbert, Marc
Inflammation is important for the initiation and the maintenance of vascular remodeling in the most commun animal models of pulmonary hypertension (PH), and its therapeutical targeting blocks PH development in these models. In human, pulmonary vascular lesions of PH are also the source of an intense chemokine production, linked to inflammatory cell recruitment. However, arteritis is uncommon in PH patients. Of note, current PH treatments have immunomodulatory properties. In addition, some studies have shown a correlation between levels of circulating inflammatory mediators and patients' survival. The study of autoimmunity in the pathophysiology of pulmonary arterial hypertension is becoming an area of intense investigation. New immunopathological approaches to PH should allow the development of innovative treatments for this very severe condition.
Martínez, A C; Novella, S; Raposo, R; Recio, P; Labadía, A; Costa, G; Garcia-Sacristán, A; Benedito, S
The present in vitro study was designed to evaluate the effect of histamine on isolated rings of bovine oviductal artery and to characterize the histamine receptors involved in the histamine-induced response. Endothelial dependence of the response was also investigated. Cumulative addition of histamine and 2-pyridylethylamine (histamine H receptor agonist) induced a concentration-dependent relaxation in intact arterial segments precontracted with noradrenaline. The histamine H1 receptor antagonist mepyramine showed non-competitive antagonism in the histamine-induced concentration-response curve. However, when the response to histamine was evaluated in the presence of mepyramine and histamine H1 and H3 receptors were blocked, Schild analysis yielded a line with a slope of 1.10 and a pA2 value of 8.91, indicating simple competitive antagonism of mepyramine at histamine H1 receptor sites. The histamine H2 receptor agonist, dimaprit, caused marked dilatation only at high doses. Cimetidine, propranolol and mepyramine failed to inhibit this relaxant effect. In precontracted oviductal arteries, cimetidine did not modify the histamine-induced concentration-response curves. Combined treatment with histamine H1 and H2 receptor antagonists did not induce an additional displacement with respect to the isolated effect of mepyramine thus excluding activation of histamine H2 receptors. Histamine and (R)-alpha-methylhistamine, a selective histamine H3 receptor agonist, produced a moderate contractile effect on the resting tone of preparations. Pretreatment with the selective histamine H1 receptor antagonist decreased the (R)-alpha-methylhistamine response but increased the maximal relaxant effect and abolished the contractile effect of histamine, suggesting the presence of a limited population of contractile histamine H3 receptors. Removal of the endothelium or pretreatment with methylene blue produced a significant inhibition of the relaxant response to histamine. Remaining
Weir, E. Kenneth; Archer, Stephen L.; Markowitz, Jeremy; Rose, Lauren; Pritzker, Marc; Madlon-Kay, Richard; Thenappan, Thenappan
Abstract Pulmonary pulse wave transit time (pPTT), defined as the time for the systolic pressure pulse wave to travel from the pulmonary valve to the pulmonary veins, has been reported to be reduced in pulmonary arterial hypertension (PAH); however, the underlying mechanism of reduced pPTT is unknown. Here, we investigate the hypothesis that abbreviated pPTT in PAH results from impaired right ventricular–pulmonary artery (RV-PA) coupling. We quantified pPTT using pulsed-wave Doppler ultrasound from 10 healthy age- and sex-matched controls and 36 patients with PAH. pPTT was reduced in patients with PAH compared with controls. Univariate analysis revealed the following significant predictors of reduced pPTT: age, right ventricular fractional area change (RV FAC), tricuspid annular plane excursion (TAPSE), pulmonary arterial pressures (PAP), diastolic pulmonary gradient, transpulmonary gradient, pulmonary vascular resistance, and RV-PA coupling (defined as RV FAC/mean PAP or TAPSE/mean PAP). Although the correlations between pPTT and invasive markers of pulmonary vascular disease were modest, RV FAC (r = 0.64, P < 0.0001), TAPSE (r = 0.67, P < 0.0001), and RV-PA coupling (RV FAC/mean PAP: r = 0.72, P < 0.0001; TAPSE/mean PAP: r = 0.74, P < 0.0001) had the strongest relationships with pPTT. On multivariable analysis, only RV FAC, TAPSE, and RV-PA coupling were independent predictors of pPTT. We conclude that shortening of pPTT in patients with PAH results from altered RV-PA coupling, probably occurring as a result of reduced pulmonary arterial compliance. Thus, pPTT allows noninvasive determination of the status of both the pulmonary vasculature and the response of the RV in patients with PAH, thereby allowing monitoring of disease progression and regression. PMID:28090301
Sheikh, Abdul Q; Lighthouse, Janet K; Greif, Daniel M
Excess smooth muscle accumulation is a key component of many vascular disorders, including atherosclerosis, restenosis, and pulmonary artery hypertension, but the underlying cell biological processes are not well defined. In pulmonary artery hypertension, reduced pulmonary artery compliance is a strong independent predictor of mortality, and pathological distal arteriole muscularization contributes to this reduced compliance. We recently demonstrated that embryonic pulmonary artery wall morphogenesis consists of discrete developmentally regulated steps. In contrast, poor understanding of distal arteriole muscularization in pulmonary artery hypertension severely limits existing therapies that aim to dilate the pulmonary vasculature but have modest clinical benefit and do not prevent hypermuscularization. Here, we show that most pathological distal arteriole smooth muscle cells, but not alveolar myofibroblasts, derive from pre-existing smooth muscle. Furthermore, the program of distal arteriole muscularization encompasses smooth muscle cell dedifferentiation, distal migration, proliferation, and then redifferentiation, thereby recapitulating many facets of arterial wall development.
Tajima, Hiroyuki Murata, Satoru; Kumazaki, Tatsuo; Abe, Yutaka; Takano, Teruo
A distal pulmonary artery perforation was successfully occluded by percutaneous microcoil embolization via a microcatheter. Microcoil embolization is a reasonable alternative therapeutic approach for this rare complication of pulmonary interventional procedures.
Nadler, Samuel T; Edelman, Jeffrey D
Multiple conditions result in development of pulmonary hypertension. Pulmonary arterial hypertension (PAH) is the subclassification of pulmonary hypertension, in which known or unknown underlying conditions lead to similar intrinsic alterations in the pulmonary vasculature. PAH is a progressive condition characterized by restricted blood flow through the pulmonary circulation leading to poor survival in the absence of effective therapy. Over the last two decades, new therapeutic agents have substantially improved the course and prognosis for PAH patients. Three available classes of drugs, ie, prostacyclins, endothelin receptor antagonists, and phosphodiesterase-5 inhibitors provide multiple options for treatment of PAH. Endothelin receptor antagonists and phosphodiesterase-5 inhibitors are administered orally, whereas prostacyclin therapies are delivered by continuous intravenous or subcutaneous infusion, or as aerosols by nebulization. Because of the risks and inconveniences associated with administration, prostacyclins are typically reserved for patients with more advanced disease or progression despite oral therapy. Inhaled administration may be a safer and easier route for prostacyclin administration. Treprostinil is a prostacyclin analog that has been demonstrated to be effective when administered by continuous subcutaneous or intravenous infusion, and more recently by nebulization. PMID:21191432
Araki, Y; Tajima, K; Yoshikawa, M; Abe, T; Suenaga, Y
We report the pulmonary intimal sarcoma of the pulmonary artery which is encountered infrequently. The patient, a 67-year-old man, was admitted with right heart failure. Diagnosis was not established completely by computed tomography of the thorax, pulmonary angiogram and pulmonary scintigram, therefore chronic pulmonary thromboembolism was suspected. Palliative resection was performed with cardiopulmonary bypass and total circulatory arrest. Pathologic examination of the resected tumor revealed pulmonary intimal sarcoma, which originated from the pulmonary artery. The patient died four months postoperatively. The cause of death was determined by autopsy to be recurrent pulmonary intimal sarcoma invading the left atrium and multiple metastasis of the brain, pancreas, adrenal glands and right lung.
Betkier-Lipińska, Katarzyna; Czarkowski, Sebastian; Hendzel, Piotr; Cwetsch, Andrzej
Idiopathic dilatation of the pulmonary artery (IDPA) is a rare congenital heart disease. It has been described for almost one hundred years, and numerous definitions have been proposed. The IDPA diagnostic criteria have not been updated for years. Secondary to primary disease, pulmonary artery aneurism was recognised as a lethal defect; however, long-term follow-up of patients with IDPA has not been well researched. Thus, indications to medical or surgical treatment are not evidence based. Here, we present a rare case of a 54-year-old patient with IDPA, who remained under observation for 36 years without surgical intervention. PMID:26855651
Dornas, Ana Paula Alves Valle; Campos, Frederico Thadeu Assis Figueiredo; Rezende, Cláudia Juliana; Ribeiro, Carlos Alberto; Amaral, Nilson Figueiredo; Corrêa, Ricardo de Amorim
Intimal sarcoma of the pulmonary artery is a rare and potentially lethal tumor, the diagnosis of which is difficult and therefore frequently delayed. The clinical signs and symptoms are nonspecific, often mimicking chronic pulmonary thromboembolism (CPTE). We report the case of a 45-year-old male under treatment for CPTE associated with pulmonary arterial hypertension and chronic cor pulmonale. There was no response to treatment with anticoagulants and sildenafil. We emphasize the difficulties in diagnosing intimal sarcoma of the pulmonary artery, the need to investigate this neoplasm in the differential diagnosis of CPTE and the systematic use of criteria for the appropriate prescription of new medications for pulmonary artery hypertension.
Gutiérrez, Alejandra; Sauler, Maor; Mitchell, James M; Siegel, Mark D; Trow, Terence K; Bacchetta, Matthew; Fares, Wassim H
Pulmonary artery sarcomas (PAS) are rare tumors with a poor prognosis. They are often misdiagnosed as pulmonary embolism (PE) leading to futile anticoagulation treatment and delay in proper diagnosis. We present a case of a patient who was initially misdiagnosed and anticoagulated for presumed pulmonary embolism. Progressive symptoms and additional imaging led to the diagnosis of intimal pulmonary artery sarcoma for which he underwent surgical resection. This case serves as a reminder to consider pulmonary artery sarcoma in the differential diagnosis of patients with dyspnea and filling defects on CT pulmonary angiogram offering the potential for resection prior to metastasis.
Darwazah, Ahmad K; Alhaddad, Imad A
Unilateral agenesis of the pulmonary artery is a rare congenital anomaly, which commonly involves the right side. Cases are associated with systemic collaterals, that may also rarely arise from the coronary arteries.Two adult patients are presented with a right pulmonary artery agenesis associated with collaterals from the right coronary artery. The implications of such an anomaly on pulmonary artery pressure and lung pathology differs among both cases. The association of coronary collaterals is rare and its implication is variable among various patients.
Min, Daniel; Lee, Ji-Hyun; Jeong, Hye-Cheol; Kim, Jung-Hyun; Shin, Suk-Pyo; Kim, Hong-Min; Han, Kyu Hyun; Jeong, Hye Yun; Kim, Eun-Kyung
Pulmonary artery sarcoma (PAS) is a rare, poorly differentiated malignancy arising from the intimal layer of the pulmonary artery. Contrast-enhanced chest computed tomography (CT) is a good diagnostic modality that shows a low-attenuation filling defect of the pulmonary artery in PAS patients. An 18-year-old man was referred to our hospital for the evaluation and management of cavitary pulmonary lesions that did not respond to treatment. A contrast-enhanced CT of the chest was performed, which showed a filling defect within the right interlobar pulmonary artery. The patient underwent a curative right pneumonectomy after confirmation of PAS. Although lung parenchymal lesions of PAS are generally nonspecific, it can be presented as cavities indicate pulmonary infarcts. Clinicians must consider the possibility of PAS as well as pulmonary thromboembolism in patients with pulmonary infarcts. So, we report the case with PAS that was diagnosed during the evaluation of cavitary pulmonary lesions and reviewed the literatures.
Min, Daniel; Lee, Ji-Hyun; Jeong, Hye-Cheol; Kim, Jung-Hyun; Shin, Suk-Pyo; Kim, Hong-Min; Han, Kyu Hyun; Jeong, Hye Yun
Pulmonary artery sarcoma (PAS) is a rare, poorly differentiated malignancy arising from the intimal layer of the pulmonary artery. Contrast-enhanced chest computed tomography (CT) is a good diagnostic modality that shows a low-attenuation filling defect of the pulmonary artery in PAS patients. An 18-year-old man was referred to our hospital for the evaluation and management of cavitary pulmonary lesions that did not respond to treatment. A contrast-enhanced CT of the chest was performed, which showed a filling defect within the right interlobar pulmonary artery. The patient underwent a curative right pneumonectomy after confirmation of PAS. Although lung parenchymal lesions of PAS are generally nonspecific, it can be presented as cavities indicate pulmonary infarcts. Clinicians must consider the possibility of PAS as well as pulmonary thromboembolism in patients with pulmonary infarcts. So, we report the case with PAS that was diagnosed during the evaluation of cavitary pulmonary lesions and reviewed the literatures. PMID:24734102
Schulze-Neick, I.; Hausdorf, G.; Lange, P. E.
In a patient with pulmonary valve atresia with hypoplastic main pulmonary artery selective angiography showed absence of the central left pulmonary artery and a right pulmonary artery originating from the ascending aorta close to the left coronary artery. This unusual anatomical arrangement complicates interventional and surgical treatment. Images PMID:8297705
Mori, Shohei; Uehara, Hirofumi; Motoi, Noriko; Okumura, Sakae
We report a very rare case of pulmonary artery sarcoma that presented as an isolated lung mass, which we attempted to resect via lobectomy, although this resulted in incomplete resection due to unnoticed latent proximal presentations. A 54-year-old man complained of a dry cough that had persisted for 2 months. Enhanced chest computed tomography revealed a lobular mass in his left lower lobe. Therefore, left lower lobectomy was performed as a radical surgery, and the tumor was ultimately diagnosed as pulmonary artery sarcoma. However, follow-up computed tomography at 16 months revealed proximal presentations in the pulmonary trunk and right pulmonary artery, which we retrospectively discovered were present before the surgery. This case highlights the importance of evaluating the lumen of the pulmonary artery, to accurately determine the required extent of any radical surgery, even in cases of pulmonary artery sarcoma that presents as an isolated lung mass.
Guntheroth, W; Miyaki-Hull, C
The Coanda effect (the tendency of a jet stream to adhere to a boundary wall), and the relevant anatomy, may explain the location of ductal jets within the main pulmonary artery. With the usual insertion of the duct close to the left pulmonary artery, during right ventricular ejection, the ductal jet adheres to the left wall of the main pulmonary artery. When right ventricular ejection is absent in pulmonary atresia, the ductal jet streams down the right wall of the pulmonary artery to the pulmonary valve, reverses, and maintains a parallel column back toward the bifurcation. If the reversed flow is mistaken for ejection from the right ventricle, the diagnosis of pulmonary atresia may be missed.
Rubin, Lewis J; Badesch, David B
Increased pressure in the pulmonary circulation, or pulmonary hypertension, is a common disorder that may complicate various cardiopulmonary conditions, including severe obstructive airways disease and left ventricular dysfunction. An increase in pulmonary arterial pressure that is not due to coexistent cardiopulmonary disease, known as pulmonary arterial hypertension, may occur in the absence of a demonstrable cause (idiopathic or familial); as a complication of systemic conditions, such as connective tissue disease, HIV infection, or chronic liver disease; or as a result of the use of fenfluramine anorexigens, amphetamines, or cocaine. The development of disease-specific therapies for pulmonary arterial hypertension over the past decade underscores the importance of diagnosing pulmonary hypertension early in the course of the condition and implementing a treatment strategy that is based on the condition's cause and severity. In this review, the authors present approaches to the diagnosis and management of pulmonary arterial hypertension, using a hypothetical case to highlight the key management points.
Zhang, Yun; Chen, Weijie; Xu, Yanping; Liu, Hang; Chen, Yunlin; Yang, Hanxuan; Yin, Yuehui
Sympathetic activation plays an important pathophysiological role in the progression of pulmonary artery hypertension. Although adrenergic vasomotor fibers are present in the adventitia of pulmonary arteries, the anatomy of the peri-arterial pulmonary nerves is still poorly understood. The aim of the current study was to determine the sympathetic nerve distribution in canine pulmonary arteries. A total of 2160 sympathetic nerves were identified in six Chinese Kunming canines. Nerve counts were greatest in the proximal segment, with a slight decrease in the distal segment; the middle segment showed the least number of nerves. In the left and right pulmonary arteries, 77.61% and 78.97% of the nerves were located within a 1-3-mm range, respectively. The number of nerves in the posterior region of the bifurcation and pulmonary trunk outnumbered those in the anterior region. Furthermore, 65.33% of the nerves were located in the first 2-mm range of the posterior region of bifurcation, and 89.62% of the nerves were located within the 1-3-mm range of the posterior region of the pulmonary trunk. In conclusion, a great abundance of sympathetic nerves occurred in the proximal and distal segments of the bilateral pulmonary arteries. There is a clear predominance of sympathetic nerve distribution in the posterior region of the bifurcation and pulmonary trunk. This anatomic distribution may have implications for the future development of percutaneous pulmonary artery denervation. PMID:27158332
Ricci, Silvia; Fainardi, Valentina; Spaziani, Gaia; Favilli, Silvia; Chiappa, Enrico
We describe a rare case of right aortic arch (RAA) and nonconfluent pulmonary arteries. RAA and a right-sided arterial duct (AD) were identified on the prenatal scan, but a second left-sided AD and disconnection of the left pulmonary artery were missed. The missed diagnosis in fetal life adversely affected postnatal management. We suggest that fetuses with a prenatal diagnosis of RAA and right-sided AD be delivered in tertiary care centres to rule out an association with bilateral AD and nonconfluent pulmonary arteries after birth. Prompt postnatal diagnosis will enable preservation of flow in the disconnected pulmonary artery through prostaglandin E1 infusion until surgical reconstruction.
Wilkins, Martin R.
Developing new treatments for pulmonary arterial hypertension (PAH) is a challenge. We have enjoyed success with regulatory approvals for three drug classes—prostanoids, endothelin receptor antagonists and phosphodiesterase type 5 inhibitors. But we have also seen some disappointing results, for example, from studies with vasoactive intestinal polypeptide, statins and tergolide. Animal models are an unreliable predictor of efficacy in humans. The best model for the disease is the patient. This review discusses three major issues facing the evaluation of drugs in PAH patients—target validation, choosing the right dose, and early trial design. PMID:23662193
Izzo, Anthony; McSweeney, Julia; Kulik, Thomas; Khatwa, Umakanth; Kothare, Sanjeev V
The usual differential diagnoses of nocturnal events in children include parasomnias, nocturnal seizures, nocturnal reflux (Sandifer syndrome), hypnic jerks, periodic limb movements of sleep, and sleep disordered breathing. We report a previously healthy young girl who presented to the sleep clinic for evaluation of nocturnal events which were diagnosed as medically refractory nocturnal seizures. It was not until a syncopal event occurred in the daytime, which prompted referral for cardiac evaluation, the diagnosis of idiopathic pulmonary arterial hyper-tension (IPAH) was made. Sleep physicians should consider IPAH in the differential diagnosis of nocturnal events in children.
Parshin, V D; Motus, I Ya; Belov, Yu V; Chernyavsky, A M; Neretin, A V; Rusinov, V V
Sarcoma of the pulmonary artery is a rare tumor. At present the literature describes single cases. However the number of publications increases in recent time due to improved diagnostics. There are appeared papers, which provide a series of observations of surgical treatment for this kind of tumor exceeded more than 10 cases. It can be assumed that today the number of these cases in the literature contains several hundreds. Thus despite the rarity of this tumor there is a certain understanding of the clinical picture of this disease and treatment that we tried to do in this paper being studied the available literature and bringing four of our observation.
Akagi, Satoshi; Kusano, Kengo Fukushima
Vascular thrombosis implicates in the pathogenesis of pulmonary arterial hypertension (PAH). Anticoagulation therapy (warfarin) has been recommended by many experts in the treatment of PAH. However, the long-term effectiveness of anticoagulation therapy remains controversial. Because of the various drugs, such as epoprostenol, bosentan, and sildenafil, for the treatment of PAH recently, warfarin alone is not a realistic therapy for PAH. Accordingly we reviewed the previous manuscript regarding anticoagulation therapy for PAH, and looked at the current role of anticoagulation therapy in Japan.
Adeli, Hassan; Nemati, Bardia; Jandaghi, Mahboubeh; Riahi, Mohammad Mahdi; Salarvand, Fatemeh
BACKGROUND Primary pulmonary artery sarcomas are very rare and their histologic type called leiomyosarcoma is even rarer. These tumors are frequently misdiagnosed as pulmonary thromboembolism in clinical settings. Many patients receive anticoagulant therapy without response, and many are diagnosed postmortem only. Most of the tumors reported in the literature have involved the right ventricular outflow tract and the main pulmonary trunk, often extending into the main pulmonary artery (MPA) branches. CASE REPORT A 64-year-old woman presented with weakness, fatigue, malaise, dyspnea, and marked elevation of pulmonary artery pressure was admitted to our hospital. She was initially diagnosed with chronic pulmonary thromboembolism, and chest computed tomography (CT) scan revealed lobulated heterogeneous left hilar mass extended to precarinal and subcarinal space. Magnetic resonance imaging (MRI) demonstrated a polypoid lesion at the trunk with extension to left MPA and its first branch. The patient was operated, and a yellowish-shiny solid mass in pulmonary trunk was seen intra-operation and pulmonary endarterectomy was performed. Her tumor was pathologically diagnosed as pulmonary artery leiomyosarcoma. CONCLUSION Clinicians must consider pulmonary artery sarcoma when making the differential diagnosis for patients with pulmonary artery masses. The clinical prediction scores and the CT and MRI findings can help identifying patients with pulmonary artery sarcoma. PMID:25161682
Samánek, M; Fiser, B; Ruth, C; Tůma, S; Hucín, B
Radioisotope lung scanning was used to investigate the distribution of pulmonary blood flow after banding of the pulmonary artery in children with a left-to-right shunt and pulmonary hypertension. An abnormal distribution of blood flow in the lung on the side of the operation approach was observed in all patients in the first three weeks following surgery. Abnormalities were still observed in 17 of 21 children 10 months to more than 8 years after the banding operation. There was no significant relation between the occurrence of these abnormalities and time after surgery. Diminished flow to the zones of the right lung was observed less frequently. The incidence of abnormalities in flow distribution was also high preoperatively. Respiratory complications in infants with large left-to-right shunts were considered to be responsible for most of the abnormal blood flow distributions observed. Radioactive lung scanning was found to be a valuable diagnostic method in the early and late postoperative period in infants and small children. It was more sensitive than the other techniques used in revealing deviation of blood flow from one lung in those cases with shifting of the applied band. Images PMID:1111558
Jaijee, Shareen K; Ariff, Ben; Howard, Luke; O'Regan, Declan P; Gin-Sing, Wendy; Davies, Rachel; Gibbs, J Simon R
Pulmonary arterial dilatation associated with pulmonary hypertension may result in significant compression of local structures. Left main coronary artery and left recurrent laryngeal nerve compression have been described. Tracheobronchial compression from pulmonary arterial dilatation is rare in adults, and there are no reports in the literature of its occurrence in idiopathic pulmonary arterial hypertension. Compression in infants with congenital heart disease has been well described. We report 2 cases of tracheobronchial compression: first, an adult patient with idiopathic pulmonary arterial hypertension who presents with symptomatic left main bronchus compression, and second, an adult patient with Eisenmenger ventricular septal defect and right-sided aortic arch, with progressive intermedius and right middle lobe bronchi compression in association with enlarged pulmonary arteries.
Wang, Xiaobing; Ren, Weidong; Yang, Jun
Pulmonary artery sarcoma (PAS) is an extremely rare malignancy. It is usually found after it grows large enough to occupy almost the entire lumen of the pulmonary artery and causes serious clinical symptoms. Thus, it is usually difficult to distinguish PAS from pulmonary thromboembolism based on imaging examinations. Few case reports had shown the attachment of PAS to pulmonary artery, a key characteristic for diagnosis, and differential diagnosis of PAS. In this case, we found a PAS, which did not cause local obstruction and some tumor emboli, which obstructed the branches of the pulmonary arteries and caused pulmonary hypertension and clinical symptoms. Transthoracic echocardiography (TTE) revealed a part of the tumor attached to the intima of the main pulmonary artery with a peduncle and had obvious mobility, which was suggestive of PAS and differentiated it from the pulmonary thromboembolism. To our knowledge, this is the first case report of a pedunculated PAS suggested by TTE. Combined with pulmonary artery computed tomography angiography, the diagnosis of PAS is strongly suggested before the operation. This case indicates that TTE could reveal the attachment and mobility of PAS in the main pulmonary and may provide useful information for the diagnosis and differential diagnosis of PAS, especially a pedunculated PAS.
Matsubara, Hiromi; Ogawa, Aiko
Treatment of pulmonary hypertension has progressed by recently developed pulmonary arterial hypertension-targeted drugs. However, long-term survival of the patients with idiopathic/heritable pulmonary arterial hypertension is still suboptimal. To improve the outcomes, treatment goals of pulmonary hypertension were proposed at the 5th World Symposium on Pulmonary Hypertension held at Nice, France in 2013; parameters were obtained from cardiopulmonary exercise test, blood tests, echocardiography, and magnetic resonance imaging. In particular, parameters evaluating right ventricular function have been highlighted because survival of the patients with pulmonary arterial hypertension is closely related to right ventricular function. However, treatment specifically targeted to improve right ventricular function in pulmonary hypertension is not yet established. In this setting, we need to maintain or improve right ventricular function with available vasodilators. In this review, we focus on the following two points: (1) Why can pulmonary arterial hypertension-targeted drugs improve right ventricular function without an apparent decrease in pulmonary artery pressure? (2) Are proposed goals sufficient to improve long-term prognosis of the patients? Further, we will discuss what would be the appropriate goal in treating patients with pulmonary arterial hypertension.
de Carvalho, Adriana Castro; Hovnanian, André Luiz; Fernandes, Caio Julio César dos Santos; Lapa, Mônica; Jardim, Carlos; Souza, Rogério
Phosphodiesterase inhibitors like sildenafil have already been shown to improve functional capacity and hemodynamics in the treatment of pulmonary arterial hypertension. Few studies address the effects of new phosphodiesterase inhibitors as tadalafil. We report a case of a patient with idiopathic pulmonary arterial hypertension in functional class IV (New York Heart Association) with significant response to treatment with tadalafil.
Sunavala, A J; Thacker, H P; Khann, J N
Agenesis or hypoplasia of the right or left pulmonary arteries are among the rarest pulmonary artery anomalies with left sided anomalies being reported even less frequently. Pulmonary artery agenesis should be suspected in asymptomatic patients if a plain chest X-ray shows asymmetric lung fields, lung hypoplasia, or hyperinflation of the contralateral lung. It must be considered as a rare cause of recurrent lower respiratory tract infections in childhood and in subjects with a low threshold for or recurrent "High Altitude Pulmonary Edema".
Vitiello, Renato; Pisanti, Chiara; Pisanti, Antonello; Silberbach, Michael
Pulmonary artery agenesis and hypoplasia of the homolateral lung occasionally occurs as an isolated lesion, but more often has associated congenital cardiac anomalies. We present a case where pulmonary artery agenesis was the sole lesion in an asymptomatic child. Pulmonary artery agenesis should be suspected in asymptomatic patients if a plain chest X-ray shows asymmetric lung fields, lung hypoplasia, or hyperinflation of the contralateral lung. Echocardiography is the best tool to establish the diagnosis. In our opinion, invasive procedures, such as cardiac catheterization, may be postponed if there is no echocardiographic evidence of pulmonary hypertension.
Records from yearling Angus (n = 10,647) cattle from elevation 2,340 m were used in genetic analysis of pulmonary arterial pressure (PAP). Bulls were developed within a grain-supplemented performance test, whereas heifers and steers were grazed. The BovineSNP50 Beadchip was used to genotype a subset...
Naeije, Robert; Manes, Alessandra
Pulmonary arterial hypertension (PAH) is a right heart failure syndrome. In early-stage PAH, the right ventricle tends to remain adapted to afterload with increased contractility and little or no increase in right heart chamber dimensions. However, less than optimal right ventricular (RV)-arterial coupling may already cause a decreased aerobic exercise capacity by limiting maximum cardiac output. In more advanced stages, RV systolic function cannot remain matched to afterload and dilatation of the right heart chamber progressively develops. In addition, diastolic dysfunction occurs due to myocardial fibrosis and sarcomeric stiffening. All these changes lead to limitation of RV flow output, increased right-sided filling pressures and under-filling of the left ventricle, with eventual decrease in systemic blood pressure and altered systolic ventricular interaction. These pathophysiological changes account for exertional dyspnoea and systemic venous congestion typical of PAH. Complete evaluation of RV failure requires echocardiographic or magnetic resonance imaging, and right heart catheterisation measurements. Treatment of RV failure in PAH relies on: decreasing afterload with drugs targeting pulmonary circulation; fluid management to optimise ventricular diastolic interactions; and inotropic interventions to reverse cardiogenic shock. To date, there has been no report of the efficacy of drug treatments that specifically target the right ventricle.
Mikaberidze, Nino; Goldberg, Ythan; Khosraviani, Khashayar; Taub, Cynthia
Unilateral pulmonary artery agenesis (UPAA) with pulmonary hypoplasia is a rare congenital anomaly. We describe a 71-year old male who was incidentally diagnosed with the right UPAA and a hypoplastic right lung supplied by collateralized right coronary.
Resveratrol increases nitric oxide synthase, induces accumulation of p53 and p21(WAF1/CIP1), and suppresses cultured bovine pulmonary artery endothelial cell proliferation by perturbing progression through S and G2.
Hsieh, T C; Juan, G; Darzynkiewicz, Z; Wu, J M
Epidemiological studies have shown that the regular consumption of red wine may in part account for the apparent compatibility of a high fat diet with a low incidence of coronary atherosclerosis. This phenomenon, commonly referred to as the French paradox, may be associated with red wine constituents that exhibit tumor-preventive properties as well as inhibit reactions that increase the risk of coronary heart disease. Here we show that resveratrol, a polyphenol in red wine, induces nitric oxide synthase, the enzyme responsible for the biosynthesis of NO, in cultured pulmonary artery endothelial cells, suggesting that resveratrol could afford cardioprotection by affecting the expression of nitric oxide synthase. We also show that resveratrol inhibits the proliferation of pulmonary artery endothelial cells, which, based on flow cytometric analysis, correlates with the suppression of cell progression through S and G2 phases of the cell cycle. Western blot analysis and immunocytochemical protein detection combined with multiparameter flow cytometry further demonstrate that the perturbed progression through S and G2 phases is accompanied by an increase in the expression of tumor suppressor gene protein p53 and elevation of the level of cyclin-dependent kinase inhibitor p21(WAF1/CIP1). All of the observed effects of resveratrol, including induction of apoptosis at its higher concentration, are also compatible with its putative chemopreventive and/or antitumor activity.
Tsapenko, Mykola V; Tsapenko, Arseniy V; Comfere, Thomas BO; Mour, Girish K; Mankad, Sunil V; Gajic, Ognjen
Pulmonary artery pressure elevation complicates the course of many complex disorders treated in a noncardiac intensive care unit. Acute pulmonary hypertension, however, remains underdiagnosed and its treatment frequently begins only after serious complications have developed. Significant pathophysiologic differences between acute and chronic pulmonary hypertension make current classification and treatment recommendations for chronic pulmonary hypertension barely applicable to acute pulmonary hypertension. In order to clarify the terminology of acute pulmonary hypertension and distinguish it from chronic pulmonary hypertension, we provide a classification of acute pulmonary hypertension according to underlying pathophysiologic mechanisms, clinical features, natural history, and response to treatment. Based on available data, therapy of acute arterial pulmonary hypertension should generally be aimed at acutely relieving right ventricular (RV) pressure overload and preventing RV dysfunction. Cases of severe acute pulmonary hypertension complicated by RV failure and systemic arterial hypotension are real clinical challenges requiring tight hemodynamic monitoring and aggressive treatment including combinations of pulmonary vasodilators, inotropic agents and systemic arterial vasoconstrictors. The choice of vasopressor and inotropes in patients with acute pulmonary hypertension should take into consideration their effects on vascular resistance and cardiac output when used alone or in combinations with other agents, and must be individualized based on patient response. PMID:19183752
Orun, Utku Arman; Yilmaz, Osman; Bilici, Meki; Karademir, Selmin; Uner, Cigdem; Senocak, Filiz; Dogan, Vehbi
Unilateral pulmonary artery agenesis is a rare congenital anomaly caused by a backward displacement of the conical artery of the truncus arteriosus. It is commonly associated with additional cardiovascular abnormalities. A 7-year-old girl was admitted to our clinic with the complaint of shortness of breath upon exertion. Chest radiography revealed a hypoplastic right lung. Absence of the right pulmonary artery with atrial septal defect and pulmonary hypertension was demonstrated by echocardiography, computed tomography, and cardiac catheterization. Bosentan is effectively used to treat pulmonary arterial hypertension.
Ginghina, Carmen; Popescu, Bogdan A; Enache, Roxana; Ungureanu, Catalina; Deleanu, Dan; Platon, Pavel
Dilatation of the pulmonary artery may lead to the compression of adjacent structures. Of those, the extrinsic compression of the left main coronary artery is the most worrisome. We present the case of a 48-year-old woman who was diagnosed with pulmonary artery dilatation due to severe, thromboembolic pulmonary hypertension. She also had angina and coronary angiography revealed a 70% ostial stenosis of the left main coronary artery. The presence of this isolated lesion in a young woman without risk factors for atherosclerosis suggests extrinsic compression of the left main coronary artery by the dilated pulmonary artery as the likely mechanism. The patient underwent direct stenting of the left main coronary stenosis with a good result.
Suzuki, Chihiro; Takahashi, Masafumi . E-mail: firstname.lastname@example.org; Morimoto, Hajime; Izawa, Atsushi; Ise, Hirohiko; Hongo, Minoru; Hoshikawa, Yasushi; Ito, Takayuki; Miyashita, Hiroshi; Kobayashi, Eiji; Shimada, Kazuyuki; Ikeda, Uichi
Pulmonary arterial hypertension (PAH) is characterized by abnormal proliferation of smooth muscle cells (SMCs), leading to occlusion of pulmonary arterioles, right ventricular (RV) hypertrophy, and death. We investigated whether mycophenolate mofetil (MMF), a potent immunosuppresssant, prevents the development of monocrotaline (MCT)-induced PAH in rats. MMF effectively decreased RV systolic pressure and RV hypertrophy, and reduced the medial thickness of pulmonary arteries. MMF significantly inhibited the number of proliferating cell nuclear antigen (PCNA)-positive cells, infiltration of macrophages, and expression of P-selectin and interleukin-6 on the endothelium of pulmonary arteries. The infiltration of T cells and mast cells was not affected by MMF. In vitro experiments revealed that mycophenolic acid (MPA), an active metabolite of MMF, dose-dependently inhibited proliferation of human pulmonary arterial SMCs. MMF attenuated the development of PAH through its anti-inflammatory and anti-proliferative properties. These findings provide new insight into the potential role of immunosuppressants in the treatment of PAH.
Perros, Frédéric; Dorfmüller, Peter; Humbert, Marc
Regardless of the initial trigger, the elevated pulmonary arterial pressure and vascular resistance in patients with pulmonary arterial hypertension are primarily caused by remodeling and thrombosis of small- and medium-sized pulmonary arteries and arterioles, as well as sustained vasoconstriction. The process of pulmonary vascular remodeling involves all layers of the vessel wall and is complicated by cellular heterogeneity within each compartment. Indeed, each cell type (endothelial cells, smooth muscle cells, and fibroblasts), as well as inflammatory cells and platelets, may play significant roles in this condition. Recent studies have emphasized the relevance of several mediators in this condition, including prostaglandin-I (2) (prostacyclin), nitric oxide, endothelin-1, angiopoietin-1, 5-hydroxytryptamine (serotonin), cytokines, chemokines, and members of the transforming growth factor beta (TGF-beta) superfamily. Targeting some of these dysfunctional pathways (prostacyclin, nitric oxide, and endothelin-1) has been beneficial in subjects displaying pulmonary arterial hypertension.
Pérez del Río, M J; Molina Suárez, R; Fresno Forcelledo, M F; Veiga González, M; Madrigal Rubiales, B; González González, M; Herrero Zapatero, A
Pulmonary artery intimal sarcomas tend to be presented with symptoms of pulmonary thromboembolism and grow regionally, with little capacity to metastasize. They probably originate from subendothelial cells, that become myofibroblasts. Knowledge of it is important to establish a presurgery diagnosis, with the possibility of a total resection, the only useful treatment until now. We report a case of a pulmonary artery primary sarcoma, in a 73 year old woman, admitted with hemoptysis and pleuritic chest pain, who died ten days after. Autopsy revealed an intraluminal mass at the pulmonary artery trunk, without regional nor distance involvement. Microscopic study showed a pleomorphic tumor with spindle and epithelioid cells, positive for actin, desmin and vimentin. All these data support the diagnosis of primary intimal sarcoma of the pulmonary artery. We want to emphasize the myogenic differentiation of the tumor, uncommon in previously reported cases.
Chaachoui, Najia; Haik, William; Tournoux, François
A 72-year-old woman with no significant medical history presented to the emergency room for severe dyspnoea. The initial clinical diagnosis was acute pulmonary embolism. Heparin infusion was initiated while awaiting a computed tomographic scan but the patient's condition deteriorated dramatically and stat echocardiogram showed tamponade. Post-evacuation echo showed a dilated right ventricle with pulmonary hypertension and obstruction of the right pulmonary artery by a homogeneous mass attached to the pulmonary artery, suggesting a tumour rather than a thrombus. Computed tomographic scan confirmed the presence of an obstructive mass with almost no perfusion of the right lung. The patient was referred to cardiac surgery and the mass was removed, with anatomo-pathological diagnosis of a typical pulmonary artery sarcoma. Unfortunately, the patient died a few days after surgery. Primary pulmonary artery sarcoma is a rare tumour that arises in the central pulmonary arteries. Clinical presentation is often attributed to other causes of pulmonary hypertension, like pulmonary embolism. Magnetic resonance imaging could help to distinguish a soft tissue mass from a thrombus but definitive diagnosis is almost always made at surgery or autopsy since patients usually present in acute and unstable situations. Prognosis is poor, from several months to a few years, and depends on how early the diagnosis is made, the presence of recurrence or metastasis after surgical resection, and the use of adjuvant therapy like radiation and chemotherapy.
Mouratoglou, Sophia-Anastasia; Giannakoulas, George; Deftereos, Spyridon; Giannopoulos, Georgios; Angelidis, Christos; Cleman, Michael W; Vassilikos, Vassilios P
Pulmonary arterial hypertension (PAH) is a serious life threatening disease that leads to right heart failure and death. Elevated pulmonary vascular resistance (PVR) is the main pathophysiological component that leads to elevated pulmonary arterial pressures and increased right ventricular afterload. Increased PVR is related to different mechanisms that include vasoconstriction, proliferative and obstructive remodeling of the pulmonary vessel wall and in situ thrombosis. Numerous molecular, genetic and humoral abnormalities have been proposed to play an important role in pulmonary vasoconstriction and remodeling. Of those, calcium (Ca(+2)) is a well recognized parameter involved in the pathogenetic mechanisms of PAH, because of its twofold role in both vasoconstriction and pulmonary artery smooth muscle cell (PASMC) proliferation. The aim of this review is to focus on Ca(+2) handling and dysregulation in PASMC of PAH patients.
Among connective tissue diseases, pulmonary arterial hypertension (PAH) is frequently associated with systemic sclerosis and systemic lupus erythematosus. PAH is less common in mixed connective tissue diseases and Sjögren's syndrome, and rare in rheumatoid arthritis. PAH in systemic sclerosis may be either isolated (prevalence about 8%) or associated with interstitial lung disease. Echocardiographic screening for PAH is worthwhile in patients with systemic sclerosis, especially as treatments for idiopathic PAH (endothelin receptor antagonists, phosphodiesterase-5 inhibitors, and prostanoids) are effective in this setting. The prevalence of PAH among patients with systemic lupus erythematosus is poorly known; immunosuppressive treatment is sometimes effective by itself but most patients benefit from PAH treatment. PAH associated with connective tissue diseases has a worse prognosis than idiopathic PAH.
D’Andrilli, Antonio; Venuta, Federico; Rendina, Erino Angelo
Bronchovascular reconstructive procedures employed in order to avoid pneumonectomy (PN) in patients functionally unsuitable have provided, over time, excellent results, similar or even better than those obtained by PN. In recent years, new successful techniques have been developed that pertain in particular the prevention of major complications and the reconstruction of the pulmonary artery (PA). Encouraging data from increasing number of published experiences support the choice of parenchymal sparing procedures for lung cancer also in patients with good functional reserve. This is even more true if considering trials published in the last 10 years, thus indicating that improved outcome can be achieved with increased experience in reconstructive techniques and perioperative management. This article discusses the main technical aspects and results of literature. PMID:26981268
Dhariwal, AK; Bavdekar, SB
Pulmonary arterial hypertension (PAH) is a life-threatening disease of varied etiologies. Although PAH has no curative treatment, a greater understanding of pathophysiology, technological advances resulting in early diagnosis, and the availability of several newer drugs have improved the outlook for patients with PAH. Sildenafil is one of the therapeutic agents used extensively in the treatment of PAH in children, as an off-label drug. In 2012, the United States Food and Drug Administration (USFDA) issued a warning regarding the of use high-dose sildenafil in children with PAH. This has led to a peculiar situation where there is a paucity of approved therapies for the management of PAH in children and the use of the most extensively used drug being discouraged by the regulator. This article provides a review of the use of sildenafil in the treatment of PAH in children. PMID:26119438
Sidorenko, B A; Preobrazhenskiĭ, D V; Batyraliev, T A; Belenkov, Iu N
The review is devoted to different aspects of pulmonary arterial hypertension (PAH); new classification of PAH is published in 2010. There are idiopathic PAH and PAH associated with other diseases. Current guidelines recommend to treat PAH only after the verification of diagnosis with right heart catheterization and acute tests with vasodilators. Patients-reactors should be treated with calcium antagonists. The following drugs related to one of three categories should be used in PAH: (1) prostanoids (epoprostenol, iloprost et al.); (2) blockers of endothelin receptors (bosentan, ambrisentan, sitaxsentan); (3) phosphodiesterase 5 type inhibitors (sildenafil, tadalafil et al.) In majority of cases the combined treatment is used, usually the combination of bosentan and sildenafil is used.
Murphy, Glenn S; Nitsun, Martin; Vender, Jeffery S
In the United States more than 1.5 million pulmonary artery catheters (PACs) are inserted each year. Of these, approximately 55% are placed in high-risk surgical and trauma patients. Most clinicians believe that PAC use is beneficial in guiding therapy and may improve outcome. Despite these beliefs and hundreds of published articles related to PACs, appropriate use and impact on outcome remain unclear. A review of the current literature reveals conflicting data and significant flaws in most study designs. Inadequate sample size, lack of randomization, lack of standardization of therapies to PAC data, and deficiencies in user knowledge all significantly limit interpretation of clinical trials. Despite these deficiencies and the need for better-designed investigations, it is the opinion of the authors that access to hemodynamic data provided by the PAC, coupled with accurate interpretation of the data, may lead to reduced perioperative morbidity and mortality.
Dhariwal, A K; Bavdekar, S B
Pulmonary arterial hypertension (PAH) is a life-threatening disease of varied etiologies. Although PAH has no curative treatment, a greater understanding of pathophysiology, technological advances resulting in early diagnosis, and the availability of several newer drugs have improved the outlook for patients with PAH. Sildenafil is one of the therapeutic agents used extensively in the treatment of PAH in children, as an off-label drug. In 2012, the United States Food and Drug Administration (USFDA) issued a warning regarding the of use high-dose sildenafil in children with PAH. This has led to a peculiar situation where there is a paucity of approved therapies for the management of PAH in children and the use of the most extensively used drug being discouraged by the regulator. This article provides a review of the use of sildenafil in the treatment of PAH in children.
Linguraru, Marius George; Mukherjee, Nisha; Van Uitert, Robert L.; Summers, Ronald M.; Gladwin, Mark T.; Machado, Roberto F.; Wood, Bradford J.
Pulmonary arterial hypertension is a known complication associated with sickle-cell disease; roughly 75% of sickle cell disease-afflicted patients have pulmonary arterial hypertension at the time of death. This prospective study investigates the potential of image analysis to act as a surrogate for presence and extent of disease, and whether the size change of the pulmonary arteries of sickle cell patients could be linked to sickle-cell associated pulmonary hypertension. Pulmonary CT-Angiography scans from sickle-cell patients were obtained and retrospectively analyzed. Randomly selected pulmonary CT-Angiography studies from patients without sickle-cell anemia were used as negative controls. First, images were smoothed using anisotropic diffusion. Then, a combination of fast marching and geodesic active contours level sets were employed to segment the pulmonary artery. An algorithm based on fast marching methods was used to compute the centerline of the segmented arteries. From the centerline, the diameters at the pulmonary trunk and first branch of the pulmonary arteries were measured automatically. Arterial diameters were normalized to the width of the thoracic cavity, patient weight and body surface. Results show that the pulmonary trunk and first right and left pulmonary arterial branches at the pulmonary trunk junction are significantly larger in diameter with increased blood flow in sickle-cell anemia patients as compared to controls (p values of 0.0278 for trunk and 0.0007 for branches). CT with image processing shows great potential as a surrogate indicator of pulmonary hemodynamics or response to therapy, which could be an important tool for drug discovery and noninvasive clinical surveillance.
Gangadharan, Venkat; Sivagnanam, Kamesh; Murtaza, Ghulam; Ponders, Michael; Teixeira, Otto; Paul, Timir
A 36-year-old woman was seen with complaints of exertional chest pain and shortness of breath. Her medical history included atrial fibrillation and diabetes. Physical examination was unremarkable except for an irregular cardiac rhythm. Myocardial perfusion imaging revealed the presence of a large area of infarction involving the entire anterior and apical walls and part of the anteroseptal wall with minimal periinfarct ischemia. Computed tomography coronary angiogram revealed an anomalous left main coronary artery arising from the main pulmonary artery. Right and left heart catheterizations demonstrated moderate pulmonary hypertension with a slight step-up in oxygen saturation between the right ventricle and main pulmonary artery. Coronary angiography showed a large tortuous right coronary artery with collaterals to the left anterior descending artery that drained into the main pulmonary artery. She was referred for surgery. This case demonstrates a rare coronary artery anomaly in an adult where survival is dependent on collateral circulation. PMID:28210637
Mun, Da-Na; Park, Chun Soo; Kim, Young-Hwue; Goo, Hyun Woo
A multistage plan and multidisciplinary approach are the keys to successful repair in patients with pulmonary atresia (PA) with ventricular septal defect (VSD) and major aortopulmonary collateral arteries (MAPCAs). In this article, we present a multidisciplinary approach adopted to treat a patient with PA with VSD and MAPCAs associated with left pulmonary artery interruption. PMID:27733998
Ataya, Ali; Cope, Jessica; Alnuaimat, Hassan
Significant advances in the understanding of the pathophysiology of pulmonary arterial hypertension over the past two decades have led to the development of targeted therapies and improved patient outcomes. Currently, a broad armamentarium of pulmonary arterial hypertension-specific drugs exists to assist in the treatment of this complex disease state. In this manuscript, we provide a comprehensive review of the current Food and Drug Administration (FDA)-approved pulmonary arterial hypertension-specific therapies, and their supporting evidence for adults, targeting the nitric oxide, soluble guanylate cyclase, endothelin, and prostacyclin pathways. PMID:27929408
Ataya, Ali; Cope, Jessica; Alnuaimat, Hassan
Significant advances in the understanding of the pathophysiology of pulmonary arterial hypertension over the past two decades have led to the development of targeted therapies and improved patient outcomes. Currently, a broad armamentarium of pulmonary arterial hypertension-specific drugs exists to assist in the treatment of this complex disease state. In this manuscript, we provide a comprehensive review of the current Food and Drug Administration (FDA)-approved pulmonary arterial hypertension-specific therapies, and their supporting evidence for adults, targeting the nitric oxide, soluble guanylate cyclase, endothelin, and prostacyclin pathways.
Hadinnapola, Charaka; Pepke-Zaba, Joanna
Chronic thromboembolic pulmonary hypertension (CTEPH) is a rare disease characterised by the presence of organised chronic thromboembolic material occluding the proximal pulmonary arteries and a vasculopathy in the distal pulmonary arterial tree. Pulmonary endarterectomy (PEA) is a potential cure for many patients with CTEPH. However, PEA is not suitable for patients with a significant distal distribution of chronic thromboembolic material or with significant comorbidities. Also, a proportion of patients are left with residual CTEPH post PEA. Until recently, pulmonary arterial hypertension-targeted therapies have been used off licence to treat patients with inoperable or residual CTEPH. The CHEST1 study investigated the use of riociguat and was the first randomised controlled trial to show efficacy in inoperable or residual CTEPH. In this review, we explore the pathophysiology of CTEPH and review the current trial evidence for pulmonary arterial hypertension-targeted therapies. We also include a discussion of physiological considerations that require further investigation.
Hiraki, T. Kanazawa, S.; Mimura, H.; Yasui, K.; Okumura, Y.; Dendo, S.; Yoshimura, K.; Takahara, M.; Hiraki, Y.
A 29-year-old woman with primary pulmonary hypertension presented with recurrent hemoptysis. Contrast-enhanced CT of the chest demonstrated the enhanced mass surrounded by consolidation related to parenchymal hemorrhage. Pulmonary angiography suggested that the mass was a pulmonary artery false aneurysm. After a microcatheter was superselectively inserted into the parent artery of the falseaneurysm, the false aneurysm was successfully treated by transcatheterembolization with coils. Her hemoptysis has never recurred.
Contreras-Arias, Catalina; Duarte, Diana; Ramírez, Luis F; Serrano, Carlos D
Unilateral absence of a pulmonary artery is an uncommon congenital heart disease. It can be related to respiratory symptoms such as asthma, an unusual finding in some of these patients. This paper reports the case of a 4-year-old male with recurrent respiratory infections and asthma symptoms, in who further studies found agenesia of right pulmonary artery with pulmonary hypoplasia of the same side.
Yan, Tao; Zhang, Guan-xin; Li, Bai-lin; Zhong, Keng; Xu, Zhi-yun; Han, Lin
We sought to explore the pulmonary haemodynamic changes in rheumatic mitral stenosis patients with secondary pulmonary hypertension. The pulmonary artery resistance and compliance of 35 patients with rheumatic mitral stenosis and 12 controls without cardiopulmonary vascular disease were evaluated by using an improved method, which is based on making calculations with parameters obtained from right heart catheterisation. The results are as follows: (1) pulmonary artery compliance in patients with secondary pulmonary hypertension was significantly lower than that of the control group (P<0.01); (2) linear correlation analyses showed that preoperative mean pulmonary artery pressure (mPAP) closely correlated with zero-pressure compliance in the mitral stenosis group (r=-0.745, P<0.05); (3) PAP and pulmonary vascular resistance decreased significantly in both groups with mitral stenosis after infusing 0.5 μg kg(-1) min(-1) of sodium nitroprusside (P<0.01). The pulmonary zero pressure compliance and mean pressure compliance increased significantly in the group with mild pulmonary hypertension; whereas in the severe group, the mean compliance changed with significance as the mPAP decreased (1.51 ± 0.59 vs 1.81 ± 0.77 ml/mmHg), however no significant change occurred in the pulmonary zero pressure compliance (2.35 ± 1.24 ml/mmHg vs. 2.24 ± 1.53 ml/mmHg, P>0.05) The walls of pulmonary artery vessels in patients with pulmonary hypertension secondary to rheumatic mitral stenosis appeared to be remodelled by varying degrees as indicated by their haemodynamic properties. Structural remodelling may be a factor affecting preoperative pulmonary artery pressure. Mitral stenosis patients with severe pulmonary hypertension have significantly lower responses to sodium nitroprusside possibly due to aggradation and deposition of collagen in the artery walls, decreasing constriction and dilation, or atrophy of smooth muscle cells.
Nielson, Jeffery L. Kang, Preet S.
Fistula formation between a coronary artery bypass graft (CABG)and the pulmonary arterial circulation represents a rare cause of recurrent angina in patients following bypass grafting. Therapy has traditionally involved surgical ligation by open thoracotomy. We describe a case of left internal mammary artery-left upper lobe pulmonary artery fistula presenting as early recurrent angina following CABG. The fistula was embolized using platinum coils, resulting in symptomatic relief and improvement in myocardial perfusion on cardiac perfusion scintigraphy. Coil embolization should be considered a therapeutic option in patients with coronary-pulmonary steal syndrome.
Wang, Kai; Ma, Jianfa; Pang, Yusheng; Lao, Jinquan; Pan, Xuanren; Tang, Qiaoyun; Zhang, Feng; Su, Danyan; Qin, Suyuan; Shrestha, Arnav Prasad
Calcium-activated chloride channels (CaCCs) play a vital role in regulating pulmonary artery tone during pulmonary arterial hypertension (PAH) induced by high blood flow. The role of CaCCs inhibitor niflumic acid (NFA) in vivo during this process requires further investigation. We established the PAH model by abdominal shunt surgery and treated with NFA in vivo. Fifty rats were randomly divided into normal, sham, shunt, NFA group 1 (0.2 mg/kg), and NFA group 2 (0.4 mg/kg). Pathological changes, right ventricle hypertrophy index, arterial wall area/vessel area, and arterial wall thickness/vessel external diameter were analyzed. Then contraction reactions of pulmonary arteries were measured. Finally, the electrophysiological characteristics of pulmonary arterial smooth muscle cells were investigated using patch-clamp technology. After 11 weeks of shunting, PAH developed, accompanied with increased right ventricle hypertrophy index, arterial wall area/vessel area, and arterial wall thickness/vessel external diameter. In the NFA treatment groups, the pressure and pathological changes were alleviated. The pulmonary artery tone in the shunt group increased, whereas it decreased after NFA treatment. The current density of CaCC was higher in the shunt group, and it was decreased in the NFA treatment groups. In conclusion, NFA attenuated pulmonary artery tone and structural remodeling in PAH induced by high pulmonary blood flow in vivo. CaCCs were involved and the augmented current density was alleviated by NFA treatment.
Kasikcioglu, Erdem; Akhan, Hulya; Cuhadaroglu, Caglar; Erkan, Feyza
The pulmonary artery is the second most common site of arterial involvement in Behcet's disease. A 32-year-old man presented with bilateral ankle edema, abdominal discomfort, and hemoptysis. He had a history of recurrent oral and genital aphthous ulcerations for 1 year. The diagnosis of Behcet's disease was made on the basis of the criteria published by the International Study Group for Behcet's Disease. His chest X-ray revealed left hilar enlargement. A helical computed tomography (CT) scan showed a pulmonary aneurysm with intramural thrombosis in the left pulmonary artery and enlarged hepatic veins. Treatment with colchicine and cyclophosphamide was given for 24 months, and helical thoracic CT was performed again. Helical CT showed that the pulmonary aneurysm was reduced by treatment. Helical CT could be used in Behcet's disease for the diagnosis and follow-up of pulmonary involvement.
Hoogma, Danny; Meyns, Bart; Van Raemdonck, Dirk; Van de Velde, Marc; Missant, Carlo; Rex, Steffen
We describe a patient who presented with a bilateral pulmonary artery sarcoma, initially treated as pulmonary embolism, that necessitated concomitant pulmonary endarterectomy and pneumonectomy. We reviewed the anesthetic management used for this procedure, which bears many similarities to the management of patients undergoing pulmonary thromboendarterectomy. Right ventricular failure, pulmonary hemorrhage, and cerebral ischemia due to circulatory arrest are life-threatening perioperative complications. The anesthesiologist can play a key role in the prevention (or timely recognition and treatment) of these perioperative complications by establishing adequate hemodynamic, echocardiographic, and neurologic monitoring and by optimizing cardiopulmonary function and coagulation.
Pulmonary arterial hypertension; Sporadic primary pulmonary hypertension; Familial primary pulmonary hypertension; Idiopathic pulmonary arterial hypertension; Primary pulmonary hypertension; PPH; Secondary pulmonary ...
Serino, G; Giacomazzi, F
Pulmonary Hypertension (PH) is definited by a mean pulmonary artery pressure (PAPm) >25 mmHg at rest. The Dana Point 2008 Revised Classification System represents the most recent classification system update with respect of various etiologies of PH. About 10 % of adolescents or adults with uncorrected congenital heart disease (CHD) with left-to-right shunt and high pulmonary blood flow develop Pulmonary Arterial Hypertension (PAH) . Progressive vascular remodeling and increase in pulmonary vascular resistance (PVR) may ultimately lead to reversal of the shunt (pulmonary to systemic) causing cyanosis and determining the so-called Eisenmenger Syndrome (ES). Recent advances in the early diagnosis and medical targeted treatment of adult patients with CHD-PAH and ES can improve PAP, PVR and exercise tolerance, together with NYHA Class and survival, and may potentially reverse the vascular remodeling process in selected patients.
Soubrier, Florent; Chung, Wendy K; Machado, Rajiv; Grünig, Ekkehard; Aldred, Micheala; Geraci, Mark; Loyd, James E; Elliott, C Gregory; Trembath, Richard C; Newman, John H; Humbert, Marc
Major discoveries have been obtained within the last decade in the field of hereditary predisposition to pulmonary arterial hypertension (PAH). Among them, the identification of bone morphogenetic protein receptor type 2 (BMPR2) as the major predisposing gene and activin A receptor type II-like kinase-1 (ACVRL1, also known as ALK1) as the major gene when PAH is associated with hereditary hemorrhagic telangiectasia. The mutation detection rate for the known genes is approximately 75% in familial PAH, but the mutation shortfall remains unexplained even after careful molecular investigation of these genes. To identify additional genetic variants predisposing to PAH, investigators harnessed the power of next-generation sequencing to successfully identify additional genes that will be described in this report. Furthermore, common genetic predisposing factors for PAH can be identified by genome-wide association studies and are detailed in this paper. The careful study of families and routine genetic diagnosis facilitated natural history studies based on large registries of PAH patients to be set up in different countries. These longitudinal or cross-sectional studies permitted the clinical characterization of PAH in mutation carriers to be accurately described. The availability of molecular genetic diagnosis has opened up a new field for patient care, including genetic counseling for a severe disease, taking into account that the major predisposing gene has a highly variable penetrance between families. Molecular information can be drawn from the genomic study of affected tissues in PAH, in particular, pulmonary vascular tissues and cells, to gain insight into the mechanisms leading to the development of the disease. High-throughput genomic techniques, on the basis of next-generation sequencing, now allow the accurate quantification and analysis of ribonucleic acid, species, including micro-ribonucleic acids, and allow for a genome-wide investigation of epigenetic or
Badesch, David B; McLaughlin, Vallerie V; Delcroix, Marion; Vizza, Carmine Dario; Olschewski, Horst; Sitbon, Olivier; Barst, Robyn J
Prostanoids have played a prominent role in the treatment of pulmonary arterial hypertension (PAH). Several compounds and methods of administration have been studied: chronic intravenously infused epoprostenol, chronic subcutaneously infused treprostinil, inhaled iloprost, and oral beraprost. Chronic intravenous epoprostenol therapy has had a substantial impact on the clinical management of patients with severe PAH. It improves exercise capacity, hemodynamics, and survival in patients with idiopathic pulmonary arterial hypertension (IPAH). It also improves exercise capacity and hemodynamics in patients with PAH occurring in association with scleroderma. The complexity of epoprostenol therapy (chronic indwelling catheters, reconstitution of the drug, operation of the infusion pump, and others) has led to attempts to develop other prostanoids with simpler modes of delivery. Treprostinil, a stable prostacyclin analogue with a half-life of 3 h, has been developed for subcutaneous delivery. It has beneficial effects on exercise and hemodynamics, which depend somewhat on the dose achieved. This, in turn, is determined by the patient's ability to tolerate the drug's side effects, including pain and erythema at the infusion site. Inhaled iloprost therapy may provide selectivity of the hemodynamic effects to the lung vasculature, thus avoiding systemic side effects. In a randomized and controlled trial, iloprost resulted in improvement in a combined end point incorporating the New York Heart Association functional class, 6-min walk test, and deterioration or death. Beraprost is the first orally active prostacyclin analogue. In the first of two randomized controlled trials, beraprost increased exercise capacity in patients with IPAH, with no significant changes in subjects with associated conditions. Hemodynamics did not change significantly, and no difference in survival was detected between the two treatment groups. The second study showed that beraprost-treated patients
Kissling, Pascal; Brosi, Philippe; Kull, Christof; Toia, Damien; Maurer, Christoph Andreas
In a patient with a huge endothelial sarcoma of the left pulmonary artery, we report successful implantation of a stent graft in the right pulmonary artery, including the pulmonary arterial trunk. This preoperative measure enabled a safe and radical left-sided pneumonectomy, including the tumor and the central parts of the left pulmonary artery. No major blood loss occurred, and neither use of a heart-lung machine nor cardiopulmonary bypass was necessary.
Badet, J; Soncin, F; Guitton, J D; Lamare, O; Cartwright, T; Barritault, D
Specific binding of angiogenin (ANG) to calf pulmonary artery endothelial cells was demonstrated. Cellular binding at 4 degrees C of 125I-labeled human recombinant ANG was time and concentration dependent, reversible, and saturable in the presence of increasing amounts of the unlabeled molecules. The interaction was shown to be specific since a large excess of unlabeled ANG reduced labeled ANG binding by 80%, whereas similar doses of RNase A, a structurally related protein, had no effect. Scatchard analyses of binding data revealed two apparent components. High-affinity sites with an apparent dissociation constant of 5 x 10(-9) M were shown to represent cell-specific interactions. The second component, comprising low-affinity/high-capacity sites with an apparent dissociation constant of 0.2 x 10(-6) M, was essentially associated with pericellular components. High-affinity ANG binding sites varied with cell density and were found on other endothelial cells from bovine aorta, cornea, and adrenal cortex capillary but not on Chinese hamster lung fibroblasts. Divalent copper, a modulator of angiogenesis, was found to induce a severalfold increase in specific cell-bound radioactivity. Placental ribonuclease inhibitor, a tight-binding inhibitor of both ribonucleolytic and angiogenic activities of ANG, abolished 125I-labeled human recombinant ANG binding only in the absence of copper.
Schäfer, Michal; Myers, Cynthia; Brown, R Dale; Frid, Maria G; Tan, Wei; Hunter, Kendall; Stenmark, Kurt R
Stiffening of the pulmonary arterial bed with the subsequent increased load on the right ventricle is a paramount feature of pulmonary hypertension (PH). The pathophysiology of vascular stiffening is a complex and self-reinforcing function of extracellular matrix remodeling, driven by recruitment of circulating inflammatory cells and their interactions with resident vascular cells, and mechanotransduction of altered hemodynamic forces throughout the ventricular-vascular axis. New approaches to understanding the cell and molecular determinants of the pathophysiology combine novel biopolymer substrates, controlled flow conditions, and defined cell types to recapitulate the biomechanical environment in vitro. Simultaneously, advances are occurring to assess novel parameters of stiffness in vivo. In this comprehensive state-of-art review, we describe clinical hemodynamic markers, together with the newest translational echocardiographic and cardiac magnetic resonance imaging methods, to assess vascular stiffness and ventricular-vascular coupling. Finally, fluid-tissue interactions appear to offer a novel route of investigating the mechanotransduction processes and disease progression.
Sen, Supratim; Rao, Suresh G; Kulkarni, Snehal
We describe the cases of two patients with tetralogy of Fallot, aged 4 years and 8 months, who were incidentally detected to have concomitant anomalous left coronary artery from pulmonary artery and total anomalous pulmonary venous connection, respectively, on preoperative imaging. They underwent surgical correction with good mid-term outcomes. In this study, we discuss the embryological basis, physiological effects, and review the literature of these two unusual associations. Awareness of these rare associations will avoid missed diagnoses and consequent surgical surprises.
Dupuis, J; Hoeper, M M
The endothelin (ET) system, especially ET-1 and the ET(A) and ET(B) receptors, has been implicated in the pathogenesis of pulmonary arterial hypertension (PAH). Together with prostanoids and phosphodiesterase 5 inhibitors, ET receptor antagonists have become mainstays in the current treatment of PAH. Three substances are currently available for the treatment of PAH. One of these substances, bosentan, blocks both ET(A) and ET(B) receptors, whereas the two other compounds, sitaxsentan and ambrisentan, are more selective blockers of the ET(A) receptor. There is ongoing debate as to whether selective or nonselective ET receptor blockade is advantageous in the setting of PAH, although there is no clear evidence that receptor selectivity is relevant with regard to the clinical effects of these drugs. For the time being, other features, such as safety profiles and the potential for pharmacokinetic interactions with other drugs used in the treatment of PAH, may be more important than selectivity or nonselectivity when selecting treatments for individual patients.
Wodniecki, Jan; Jacheć, Wojciech; Poloński, Lech; Tomasik, Andrzej Robert; Wojciechowska, Celina; Foremny, Ala
Primary pulmonary arterial hypertension (PPH) is a rare disease of undetermined origin and fatal prognosis. A better prognosis is associated with at least 20% reduction of either pulmonary artery pressure or pulmonary vascular resistance ("responders") in acute vasodilatory trials. Prostacycline (PGI2) or nitric oxide (NO) administration promises valuable results. NO is one of the most powerful vasodilating agents, endogenously produced by endothelial cells. It migrates from these cells to smooth muscle cells and stimulates production of cGMP, that induces smooth muscle relaxation. cGMP is hydrolyzed by 5-phopshodiesterase (PDE-5). Several papers documenting hypotensive effect in pulmonary circulation of specific PDE5 inhibitor--sildenafil (Viagra--Pfizer) have been published recently. We present a case report of a 26 year old female patient with PPH--"nonresponder" in a trial with NO--and NO responder after sildenafil administration. Initial values were: mean pulmonary artery pressure (mPAP) was 58 mmHg, pulmonary vascular resistance was 10.9 Wood's units. mPAP and PVR during NO inhalation (40 ppm) decrease from 62 to 54 mmHg and from 11.4 to 10.3 Wood's units, respectively. Measurements performed 60 minutes after 50 mg of sildenafil orally disclosed a 19% reduction of mPAP and 21% reduction of PVR. NO inhalation caused further decrease of both parameters: mPAP was decreased for additional 28% and PVR for additional 36% in comparison to initial results. Neither peripheral hypotension nor other side effects were observed. A month-long administration of sildenafil in a dose 2 x 25 mg daily reduced mPAP and PVR to values reported for the acute trial. Physical capability improved also. It was assessed as increased distance in a six-minute-walk test (280 vs. 400 m in the first week of treatment, and 330 m in a fourth week of treatment). Echocardiography showed moderate decrease of right ventricle and right atrium diameters, along with decrease of the degree of relative
Ewert, Ralf; Gläser, Sven; Bollmann, Tom; Schäper, Christoph
Iloprost (Ventavis, Bayer Schering Pharma, Germany) is a synthetic prostacyclin that is used in its inhalative form for the therapy of pulmonary arterial hypertension. Long-term therapy can increase exercise capacity and quality of life. The use of modern nebulizers especially designed for the administration of iloprost guarantees the pulmonary deposition of the required doses and systematically minimizes side effects. Regarding existing data, inhalative iloprost acts in effective and safe combination with other classes of medication; indeed, such combination therapy is frequently necessary in pulmonary arterial hypertension.
Wang, Kai; Chen, Chuansi; Ma, Jianfa; Lao, Jinquan; Pang, Yusheng
The correlation between calcium-activated chloride channel (CaCC) and pulmonary arterial hypertension (PAH) induced by high pulmonary blood flow remains uncertain. In this study, we investigated the possible role and effects of CaCC in this disease. Sixty rats were randomly assigned to normal, sham, and shunt groups. Rats in the shunt group underwent abdominal aorta and inferior vena cava shunt surgery. The pulmonary artery pressure was measured by catheterization. Pathological changes, right ventricle hypertrophy index (RVHI), arterial wall area/vessel area (W/V), and arterial wall thickness/vessel external diameter (T/D) were analyzed by optical microscopy. Electrophysiological characteristics of pulmonary arterial smooth muscle cells (PASMCs) were investigated using patch clamp technology. After 11 weeks of shunting, PAH and pulmonary vascular structural remodeling (PVSR) developed, accompanied by increased pulmonary pressure and pathological interstitial pulmonary changes. Compared with normal and sham groups, pulmonary artery pressure, RVHI, W/V, and T/D of the shunt group rats increased significantly. Electrophysiological results showed primary CaCC characteristics. Compared with normal and sham groups, membrane capacitance and current density of PASMCs in the shunt group increased significantly, which were subsequently attenuated following chloride channel blocker niflumic acid (NFA) treatment. To conclude, CaCC contributed to PAH induced by high pulmonary blood flow and may represent a potential target for treatment of PAH.
Wang, Kai; Chen, Chuansi; Ma, Jianfa; Lao, Jinquan; Pang, Yusheng
The correlation between calcium-activated chloride channel (CaCC) and pulmonary arterial hypertension (PAH) induced by high pulmonary blood flow remains uncertain. In this study, we investigated the possible role and effects of CaCC in this disease. Sixty rats were randomly assigned to normal, sham, and shunt groups. Rats in the shunt group underwent abdominal aorta and inferior vena cava shunt surgery. The pulmonary artery pressure was measured by catheterization. Pathological changes, right ventricle hypertrophy index (RVHI), arterial wall area/vessel area (W/V), and arterial wall thickness/vessel external diameter (T/D) were analyzed by optical microscopy. Electrophysiological characteristics of pulmonary arterial smooth muscle cells (PASMCs) were investigated using patch clamp technology. After 11 weeks of shunting, PAH and pulmonary vascular structural remodeling (PVSR) developed, accompanied by increased pulmonary pressure and pathological interstitial pulmonary changes. Compared with normal and sham groups, pulmonary artery pressure, RVHI, W/V, and T/D of the shunt group rats increased significantly. Electrophysiological results showed primary CaCC characteristics. Compared with normal and sham groups, membrane capacitance and current density of PASMCs in the shunt group increased significantly, which were subsequently attenuated following chloride channel blocker niflumic acid (NFA) treatment. To conclude, CaCC contributed to PAH induced by high pulmonary blood flow and may represent a potential target for treatment of PAH. PMID:25755701
Yu, Lunyin; Hales, Charles A.
Background Hypoxia results in pulmonary hypertension and vascular remodeling due to induction of pulmonary artery cell proliferation. Besides pulmonary artery smooth muscle cells, pulmonary artery endothelial cells (PAECs) are also involved in the development of pulmonary hypertension, but the effect of hypoxia on PAEC proliferation has not been completely understood. Methods We investigated PAEC proliferation in mice and rats with hypoxia-induced pulmonary hypertension and vascular remodeling as well as in human PAECs under hypoxia. Results and Conclusion We did not find significant PAEC proliferation in chronically hypoxic rats or mice. There was a slight decrease in proliferation in mice and rats with pulmonary hypertension and vascular remodeling. We also did not find significant human PAEC proliferation and cell cycle progression under different levels of oxygen (1, 2, 3, 5 and 10%) for one day, although the same conditions of hypoxia induced significant proliferation and cell cycle progression in pulmonary artery smooth muscle cells and pulmonary artery fibroblasts. Exposure to hypoxia for 7 days also did not increase PAEC proliferation. These results demonstrated that hypoxia alone is not a stimulus to PAEC proliferation in vivo and in vitro. The present study provides a novel role for PAECs in hypoxia-induced pulmonary hypertension and vascular remodeling. PMID:21691120
Karau, Kelly L.; Molthen, Robert C.; Johnson, Roger H.; Dhyani, Anita H.; Haworth, Steven T.; Dawson, Christopher A.
Animal models and micro-CT imaging are useful for understanding the functional consequences of, and identifying the genes involved in, the remodeling of vascular structures that accompanies pulmonary vascular disease. Using a micro-CT scanner to image contrast-enhanced arteries in excised lungs from fawn hooded rats (a strain genetically susceptible to hypoxia induced pulmonary hypertension), we found that portions of the pulmonary arterial tree downstream from a given diameter were morphometrically indistinguishable. This 'self-consistency' property provided a means for summarizing the pulmonary arterial tree architecture and mechanical properties using a parameter vector obtained from measurements of the contiguous set of vessel segments comprising the longest (principal) pathway and its branches over a range of vascular pressures. This parameter vector was used to characterize the pulmonary vascular remodeling that occurred in rats exposed to a hypoxic (11.5% oxygen) environment and provided the input to a hemodynamic model relating structure to function. The major effect of the remodeling was a longitudinally (pulmonary artery to arterioles) uniform decrease in vessel distensibility that resulted in a 90% increase in arterial resistance. Despite the almost uniform change in vessel distensibility, over 50% of the resistance increase was attributable to vessels with unstressed diameters less than 125 microns.
Yilmaz, Sema; Cimen, Kadriye Akar
Behçet's disease is the most common cause of pulmonary artery aneurysms. Pulmonary artery aneurysms are rare, but they are life-threatening because of their high tendency to rupture. However, there is also a chance that the aneurysms may completely resolve with immunosuppressive therapy. A 30-year-old man was admitted with chest pain, painful oral and genital ulcers, skin rash, weakness, and intermittent hemoptysis. He had a history of Behçet's disease for 6 years. The chest radiography showed a round opacity superior part of hilus on right. The helical thoracic computed tomography (CT) angiography demonstrated pulmonary aneurysms associated with Behçet's disease. The patient was successfully treated with colchicine, corticosteroids, and cyclophosphamide. A discussion about pulmonary artery aneurysms associated with Behçet's disease is provided in this case.
Mathai, Stephen C.; Hassoun, Paul M.
Purpose of review Systemic sclerosis is commonly complicated by pulmonary arterial hypertension (PAH-SSc) and is a leading cause of death in this population. We will review existing challenges and recent advances in the treatment of this disease. Recent findings Traditionally employed outcome measures in pulmonary arterial hypertension research may not be applicable in PAH-SSc. Importantly, new therapies that target abnormal cellular proliferation in the pulmonary vasculature are currently under investigation and may be particularly relevant to PAH-SSc. Summary Pulmonary arterial hypertension complicating systemic sclerosis occurs commonly and portends a poor prognosis. However, recent advances in our understanding of the disease in the context of systemic sclerosis may lead to novel diagnostic and therapeutic strategies that will ultimately improve quality of life and survival in this population. PMID:19667994
Ahmed, Mostafa; Hamed, Fadi; Prieto, Lourdes R.
Abstract Peripheral pulmonary artery stenosis (PPAS) is an underrecognized condition in the adult population. PPAS can lead to pulmonary hypertension but is likely misdiagnosed as either idiopathic pulmonary arterial hypertension or chronic thromboembolic pulmonary hypertension. We retrospectively identified adult patients with PPAS either in its isolated form or related to other congenital defects from January 1998 to September 2012. We reviewed the patients’ clinical data by using our hospital electronic medical records and/or their paper charts. We identified 6 adult patients with PPAS with an age range of 16–56 years (1 woman and the rest men). Presenting signs and symptoms were thoracic murmurs, progressive dyspnea, and syncope. Three patients had Williams-Beuren syndrome. Pulmonary angiography showed that PPAS was predominantly located in main branches or lobar pulmonary arteries in 5 patients, while in 1 patient the arterial narrowing was at the level of the segmental pulmonary arteries. Right heart catheterization showed a mean pulmonary artery pressure (PAP) ranging from 35 to 60 mmHg. Balloon dilation was performed in all patients, predominantly in the lobar arteries, and it caused a decrease in mean PAP that ranged from 16% to 46% in 5 patients. In 1 patient the mean PAP did not decrease. All but 1 patient had follow-up echocardiograms at 1 year that showed stable echocardiographic findings. Pulmonary hypertension due to PPAS continues to presents a diagnostic challenge. Therefore, a high index of suspicion during the initial evaluation of pulmonary hypertension is essential for its prompt diagnosis and adequate treatment. PMID:25992283
Yang, Ying; Qiao, Jian; Wang, Huiyu; Gao, Mingyu; Ou, Deyuan; Zhang, Jianjun; Sun, Maohong; Yang, Xin; Zhang, Xiaobo; Guo, Yuming
Calcium signaling has been reported to be involved in the pathogenesis of hypertension. Verapamil, one of the calcium antagonists, is used to characterize the role of calcium signaling in the development of pulmonary arterial hypertension syndrome in broilers. The suppression effect of verapamil on pulmonary arterial hypertension and pulmonary vascular remodeling was examined in broilers, from the age of 16 days to 43 days. Our results showed that oral administration of lower dose of verapamil (5 mg/kg body weight every 12 h) prevented the mean pulmonary arterial pressure, the ascites heart index and the erythrocyte packed cell volume of birds at low temperature from increasing, the heart rate from decreasing, and pulmonary arteriole median from thickening, and no pulmonary arteriole remodeling in broilers treated with the two doses of verapamil at low temperature was observed. Our results indicated that calcium signaling was involved in the development of broilers' pulmonary arterial hypertension, which leads to the development of ascites, and we suggest that verapamil may be used as a preventive agent to reduce the occurrence and development of pulmonary arterial hypertension in broilers.
Perros, Frédéric; Humbert, Marc
The combined effects of vasoconstriction, remodelling of the pulmonary vessel walls and in situ thrombosis contribute to the increase in pulmonary vascular resistance during pulmonary arterial hypertension. Vascular remodelling involves all the sheaths of the vessel wall and all the cell types of which it is composed (endothelial cells, smooth muscle cells, fibroblasts, inflammatory cells and platelets). Excessive vasoconstriction has been related to a defect in the function of expression of the potassium channels and endothelial dysfunction. This leads to chronic insufficiency in the production of vasodilators, notably nitrogen monoxide and prostacyclin and the excessive production of vasoconstrictors such as endotheline-1. These defects contribute to the increase in vascular tonus and pulmonary vascular remodelling and represent pertinent pharmacological targets. Certain growth factors, including those of the super-family of transforming growth factor beta, angiopoietine-1 and serotonin, may play a part in the pathogenesis of pulmonary arterial hypertension.
Sanges, Sébastien; Yelnik, Cécile M.; Sitbon, Olivier; Benveniste, Olivier; Mariampillai, Kuberaka; Phillips-Houlbracq, Mathilde; Pison, Christophe; Deligny, Christophe; Inamo, Jocelyn; Cottin, Vincent; Mouthon, Luc; Launay, David; Lambert, Marc; Hatron, Pierre-Yves; Rottat, Laurence; Humbert, Marc; Hachulla, Eric
Abstract Occurrence of pulmonary arterial hypertension (PAH) in idiopathic inflammatory myopathies (IIMs) without extensive interstitial lung disease (ILD) has rarely been described in the medical literature. This study aimed to report all cases with association of PAH and IIM in the French Pulmonary Hypertension (PH) Registry, to identify IIM features associated with the presence of PAH, and to describe treatment modalities of these patients. All cases of IIM-PAH were retrieved from the French PH Registry, which gathers PH patients prospectively enrolled by 27 referral hospital centers across France. Patients were excluded if they had an extensive ILD or overlap syndrome. Characteristics of IIM-PAH patients were compared with a control group of IIM patients without PH. Among the 5223 PH patients in the Registry, 34 had a diagnosis of IIM. Among them, 3 IIM-PAH patients (2 females and 1 male) had no evidence of extensive ILD or overlap syndrome, and were included in this study. In these 3 patients, dermatomyositis (DM) was the only identified IIM. One patient had autoantibodies classically associated with IIM (anti-Ku). PAH had always developed after IIM onset, was severe in all cases, and led to a marked functional impairment. By pooling our cases with 6 patients previously reported in the literature, and comparing them with a control cohort of 35 IIM patients without PH, we identify several IIM characteristics possibly associated with PAH occurrence, including DM subtype (78% vs 46%; P = 0.02), skin involvement (P = 0.04), anti-SSA antibodies (P = 0.05), and peripheral microangiopathy (P = 0.06). Overall, IIM-PAH patients were managed by corticosteroids and/or immunosuppressants, either alone or combined with PAH therapy. Patients did not seem to respond to IIM treatment alone. Our study reports for the first time the rare but possible association of PAH and IIM in a large prospective PH Registry. In that setting, PAH seems associated with DM, skin involvement
Hsieh, Caleb G; Le, Thomas; Fogelfeld, Keren; Kamangar, Nader
Bronchial artery aneurysm (BAA) is a rare vascular phenomenon. This review highlights a case of a BAA that was complicated by the presence of a bronchial artery to pulmonary artery (BA-PA) fistula, consequently presenting a unique challenge to management. BAAs have a strongly reported risk of rupture resulting in life-threatening hemoptysis. Embolization has thus become routine for the management such severe cases. The management of incidentally found anomalies is less obvious, but prophylactic embolization is a generally accepted practice. In this report, we review some of the risks and benefits associated with BAA embolization with specific consideration of the challenges in cases of co-existing BA-PA fistula. PMID:28217405
Kitajima, Takamasa; Marumo, Satoshi; Shoji, Tsuyoshi; Huang, Cheng-Long; Yuba, Yoshiaki; Fukui, Motonari
Chronic pulmonary arterial obstructions are caused mostly by chronic pulmonary artery thromboembolism and rarely by vasculitis or intimal sarcoma of the pulmonary artery. We herein report an unusual case of a 42-year-old woman with a solitary obstruction of the pulmonary artery in the right lower lobe of her lung. Because we could not exclude the possibility of intimal sarcoma, middle and lower lobectomy was performed. The resected specimens revealed large vessel vasculitis (LVV) and an isolated lesion in the right lower lobe pulmonary artery. LVV should therefore be considered in the differential diagnosis for single pulmonary arterial stenosis or obstruction.
Lever, M.J.; Jay, M.T. )
Experiments have been performed both in vivo and in vitro to measure the steady-state uptake of labeled albumin and Cr-ethylenediaminetetraacetate by various blood vessels of the rabbit: the ascending and descending portions of the thoracic aorta, the carotid artery, the pulmonary artery, and the inferior vena cava. The in vitro experiments indicated that the wall tissues of the pulmonary artery and the vena cava have much greater distribution volumes for albumin than do the systemic arteries. This may in part explain the differences in wall tissue concentrations in vivo and, in turn, the differences between vessels in their susceptibility to atherosclerosis.
Talwar, Sachin; Anderson, Robert H; Keshri, Vikas Kumar; Choudhary, Shiv Kumar; Gulati, Gurpreet Singh; Airan, Balram
Surgical correction of patients with tetralogy of Fallot with pulmonary atresia is now one of the routine procedures performed by pediatric cardiac surgeons. In one variant, the pulmonary arterial supply is derived from a fistulous communication from the coronary arteries. This rare and interesting situation poses a diagnostic and therapeutic dilemma, as well as providing specific management challenges to the surgical team. Here, we discuss important aspects of this rare variant, specifically its morphology, presentation, evaluation and management.
Sakamoto, K; Nishioka, M; Fujimoto, K; Ohta, N; Murata, M; Nakada, T; Sekine, Y; Yokota, M
Unilateral pulmonary arterial hypoplasia and/or pulmonary venous obstruction are serious hazards for Fontan candidates. For these patients, we have started new surgical approach "intrapulmonary septation technic". This consists of 3 components; (A) partial right heart bypass to well-grown side, (B) mandatory pulmonary blood flow to low-capacity side, (aorto-pulmonary shunt or others) and (C) a patch between partial right heart bypass and mandatory pulmonary blood flow. Thirteen patients underwent the approach. The source of partial right heart bypass was brought from superior vena cava (11 patients), inferior vena cava (1 patient) and fenestrated Fontan (1 patient). The mandatory pulmonary blood flow was supplied by aorto-pulmonary shunt (11 patients), pulmonary arterial banding (1 patient) and native pulmonary valve stenosis (1 patient). We added pulmonary artery enlargement (9 patients), release of pulmonary venous obstruction (8 patients) and/or atrio-ventricular valve plasty (5 patients), simultaneously. No hospital death. Early post-operative course was uneventful in all cases except 1, as pulmonary blood flow to low-capacity side had increased gradually after this intervention. Eight patients had reached Fontan operation. In this approach, nearly whole pulmonary artery can grow without any affect of volume overload through well-grown side from collateral arteries of low-capacity side. All procedures of "intrapulmonary septation technic" and reconstruction of pulmonary artery in Fontan operation can be easily performed in larger pulmonary artery of well-grown side, eliminating need for extensive dissection.
Bishop, Bryan M; Mauro, Vincent F; Khouri, Samer J
Pulmonary arterial hypertension is a devastating disease. Before the 1990s, when pharmacologic treatment was finally approved, only supportive therapy was available, consisting of anticoagulation, digoxin, diuretics, and supplemental oxygen. Calcium channel blocker therapy was also an option, but only a small percentage of patients respond to it. However, starting with epoprostenol in 1996, the number of drugs approved to treat pulmonary arterial hypertension increased. Three distinct classes of drugs were developed based on the pathophysiology of the disease: the prostanoids, endothelin-1 receptor antagonists, and phosphodiesterase type 5 inhibitors. The prostanoids are administered either parenterally or by inhalation to replace the lack of prostacyclin within the pulmonary arterial vasculature. The endothelin-1 receptor antagonists were the first class of oral drugs to be developed, but drug interactions and adverse effects are prominent with this class. The phosphodiesterase type 5 inhibitors increase the second messenger cyclic guanosine monophosphate (GMP) that is induced by nitric oxide stimulation. All of the drugs within these three classes are distinct in and of themselves, and their clinical use requires in-depth knowledge of pulmonary arterial hypertension and its pathophysiology. Because these drugs have different mechanisms of action, combination therapy has shown promise in patients with severe disease, although data are still lacking. This article should serve as a practical guide for clinicians who encounter patients with pulmonary arterial hypertension and the drugs used for the treatment of this devastating disease.
Murat, Gurbuz; Cellier, François; Leobon, Bertand; Boudou, Nicolas
Anomalous origin of the left coronary artery from the pulmonary artery is a rare congenital disease responsible for a high mortality rate in childhood. Here, we report for the first time the case of an asymptomatic 61-year old patient showing a combination of anomalous origin of the left anterior descending artery from pulmonary artery and atherosclerotic stenosis in both the right coronary artery and the left circumflex artery without anomalous origin.
Al Jabbari, Odeaa; Abu Saleh, Walid K.; Ramchandani, Mahesh; Scheinin, Scott
Unilateral agenesis of the pulmonary artery (UAPA) is a rare congenital anomaly. This report describes a 52-year-old female who gave a long history of chronic, recurrent, left-sided pulmonary infections related to UAPA. For many years, she was managed medically but the infection continued to recur. She eventually underwent left pneumonectomy and made a good recovery. PMID:27127564
Zhao, Zhi-Min; Liu, Su-Xuan; Zhang, Guan-Xin; Yang, Fan; Wang, Yang; Wu, Feng; Zhao, Xian-Xian; Xu, Zhi-Yun
While the molecular chaperone heat shock protein 90 (HSP90) is involved in a multitude of physiological and pathological processes, its role relating to pulmonary arterial hypertension (PAH) remains unclear. In the present study, we investigated the effect in which HSP90 improves pulmonary arteriole remodeling, and explored the therapeutic utility of targeting HSP90 as therapeutic drug for PAH. By Elisa and immunohistochemistry, HSP90 was found to be increased in both plasma and membrane walls of pulmonary arterioles from PAH patients. Moreover, plasma HSP90 levels positively correlated with mean pulmonary arterial pressure and C-reactive protein. In a monocrotaline-induced rat model of PH, we found that 17-AAG, a HSP90-inhibitor, alleviated the progress of PH, demonstrated by lower pulmonary arterial pressure and absence of right ventricular hypertrophy. Immunohistochemical staining demonstrated that 17-AAG improved pulmonary arteriole remodeling on the basis of reduced wall thickness and wall area. The inflammatory response attributed to PH could be attenuated by 17-AAG through reduction of NF-κB signaling. Moreover, 17-AAG was found to suppress PDGF-stimulated proliferation and migration of pulmonary artery smooth muscle cells (PASMCs) through induction of cell cycle arrest in the G1 phase. In conclusion, HSP90 inhibitor 17-AAG could improve pulmonary arteriole remodeling via inhibiting the excessive proliferation of PASMCs, and inhibition of HSP90 may represent a therapeutic avenue for the treatment of PAH. PMID:27472464
Al Jabbari, Odeaa; Abu Saleh, Walid K; Ramchandani, Mahesh; Scheinin, Scott
Unilateral agenesis of the pulmonary artery (UAPA) is a rare congenital anomaly. This report describes a 52-year-old female who gave a long history of chronic, recurrent, left-sided pulmonary infections related to UAPA. For many years, she was managed medically but the infection continued to recur. She eventually underwent left pneumonectomy and made a good recovery.
Kitami, Akihiko; Sano, Fumitoshi; Hayashi, Shoko; Suzuki, Kosuke; Uematsu, Shugo; Suzuki, Takashi; Saeki, Noriyuki
We present a surgical case of bronchial artery aneurysm (BAA) connecting pulmonary artery accompanied with racemose hemangioma. This is a third surgical case report of BAA directly connecting pulmonary artery in the English literature. A 63-year-old female was found a BAA, 2 cm in diameter, connecting right A4 pulmonary artery. The patient underwent two attempts for embolization. However, due to extensive collaterals, there was persistent flow in the aneurysm. Standard lateral thoracotomy was performed. A BAA was located between A4 and A5 PA. A small branch of A4 PA was separated, and the small vessel connecting to the BAA could be ligated. A5 PA was separated similarly, however BAA was ruptured not to identify the other small vessel connecting to the BAA. After a clamp of the BAA, middle lobe lobectomy was performed. We removed the aneurysm with dilated bronchial artery connecting to the aneurysm. The postoperative course was uneventful.
Weir-McCall, Jonathan R.; Struthers, Allan D.; Lipworth, Brian J.; Houston, J. Graeme
COPD is the second most common cause of pulmonary hypertension, and is a common complication of severe COPD with significant implications for both quality of life and mortality. However, the use of a rigid diagnostic threshold of a mean pulmonary arterial pressure (mPAP) of ≥25mHg when considering the impact of the pulmonary vasculature on symptoms and disease is misleading. Even minimal exertion causes oxygen desaturation and elevations in mPAP, with right ventricular hypertrophy and dilatation present in patients with mild to moderate COPD with pressures below the threshold for diagnosis of pulmonary hypertension. This has significant implications, with right ventricular dysfunction associated with poorer exercise capability and increased mortality independent of pulmonary function tests. The compliance of the pulmonary artery (PA) is a key component in decoupling the right ventricle from the pulmonary bed, allowing the right ventricle to work at maximum efficiency and protecting the microcirculation from large pressure gradients. PA stiffness increases with the severity of COPD, and correlates well with the presence of exercise induced pulmonary hypertension. A curvilinear relationship exists between PA distensibility and mPAP and pulmonary vascular resistance (PVR) with marked loss of distensibility before a rapid rise in mPAP and PVR occurs with resultant right ventricular failure. This combination of features suggests PA stiffness as a promising biomarker for early detection of pulmonary vascular disease, and to play a role in right ventricular failure in COPD. Early detection would open this up as a potential therapeutic target before end stage arterial remodelling occurs. PMID:26095859
Qureshi, Athar M; Krasuski, Richard A; Prieto, Lourdes R
Percutaneous pulmonary valve technology has had a great impact on patients with congenital and acquired heart disease. In some patients, implantation of a percutaneous pulmonary valve may not be possible due to the morphology of the existing right ventricular outflow tract. In this report, we describe implantation of a Melody transcatheter pulmonary valve in the left pulmonary artery in a patient with acquired right pulmonary artery occlusion and a large right ventricular outflow tract.
Kagioka, Hitoshi; Ishitoko, Manabu; Itotani, Ryo; Suzuki, Shinko; Aihara, Kensaku; Matsumoto, Masataka; Oguma, Tsuyoshi; Takemura, Masaya; Tokuhisa, Hidetoshi; Fukui, Motonari
A 77-year-old woman presented with hoarseness and hemoptysis. Chest CT scan revealed a mediastinal tumor in the lumen of the left pulmonary artery. A definitive diagnosis could not be made based on mediastinoscopy and thoracotomy. Eight months later, multiple nodular shadows appeared in both lung fields.Video-assisted lung biopsy showed that these nodules were lung metastases of a spindle cell sarcoma. Based on the pathological and radiological findings, a pulmonary artery sarcoma was eventually diagnosed. Interestingly, on immunohistological staining, the tumor cells were diffusely positive for KIT, which is an immunohistochemical marker of gastrointestinal stromal tumors. The patient was treated with imatinib, a KIT tyrosine kinase inhibitor; however, the tumors progressed. The relationship between pulmonary artery sarcoma and KIT requires further study.
Hou, Xiaomeng; Li, Ji; Li, Jing; Cai, Baiqiang
OBJECTIVES: This study described the characteristics of the systemic arterial supply of pulmonary sequestration (PS) in an attempt to better distinguish PS from other acquired lesions. METHODS: We identified 25 patients hospitalized at the Peking Union Medical College Hospital during January 2013 to December 2015 with the assistance of medical catalogers. Twenty-three patients with a definite diagnosis of “pulmonary sequestration” clinically or pathologically were included in the study. The medical records, imaging information, and pathological data were reviewed retrospectively. The general characteristics of the patients and the features of the anomalous arteries were summarized. RESULTS: Aberrant arterial supply of PS was found in all 23 (100%) cases. Among them, twenty patients received surgery, including 14 (70%) with aberrant arterial supply found before surgery, and the other 6 (30%) found during surgery. Nineteen (82.6%) patients had a single systematic arterial supply, with a median diameter of 8 mm. More than one arterial supplies were found in four (17.4%) cases. In 21 (91.3%) cases, the anomalous systemic artery originated from the descending thoracic aorta just adjacent to the sequestrated lung which it supplied, without the presence of accompanying bronchi. In twenty (87.0%) patients who received the surgical intervention, samples of 12 (85.7%) were proved to have elastic vessel walls, out of the 14 samples in which the anomalous systemic arteries were available for analysis. CONCLUSIONS: There are no certain pathology diagnostic criteria for the diagnosis of PS. The detecting of the aberrant systematic artery and distinguishing it from the bronchial arteries corresponded to certain lung abnormalities are the keys to the accurate diagnosis of pulmonary sequestration in adult patients. We propose that the characteristic features of the anomalous arteries include: Originating from aorta and its main branches, adjacent to the sequestrated area
Sanal, Shirin; Aronow, Wilbert S; Ravipati, Gautham; Maguire, George P; Belkin, Robert N; Lehrman, Stuart G
We investigated the accuracy of computed tomographic measurements of main pulmonary artery diameter (MPAD) and of MPAD/ascending aorta diameter (AAD) in predicting moderate or severe pulmonary hypertension in 190 patients with acute pulmonary embolism. A pulmonary artery systolic pressure of > or = 50 mm Hg measured by Doppler echocardiography was considered moderate or severe pulmonary hypertension. A MPAD of > 28.6 mm and a MPAD/AAD ratio of > or = 1.00 measured by computed tomography were considered abnormal. A MPAD of > 28.6 mm had a 75% sensitivity and specificity, a 52% positive predictive value, a 89% negative predictive value, a 3.0 likelihood ratio for a positive test, and a 0.33 likelihood ratio for a negative test in predicting moderate or severe pulmonary hypertension. A MPAD/AAD ratio of > or = 1.00 had a 59% sensitivity, a 82% specificity, a 55% positive predictive value, a 84% negative predictive value, a 3.3 likelihood ratio for a positive test, and a 0.50 likelihood ratio for a negative test.
Wideman, R F; Rhoads, D D; Erf, G F; Anthony, N B
Pulmonary arterial hypertension (PAH) syndrome in broilers (also known as ascites syndrome and pulmonary hypertension syndrome) can be attributed to imbalances between cardiac output and the anatomical capacity of the pulmonary vasculature to accommodate ever-increasing rates of blood flow, as well as to an inappropriately elevated tone (degree of constriction) maintained by the pulmonary arterioles. Comparisons of PAH-susceptible and PAH-resistant broilers do not consistently reveal differences in cardiac output, but PAH-susceptible broilers consistently have higher pulmonary arterial pressures and pulmonary vascular resistances compared with PAH-resistant broilers. Efforts clarify the causes of excessive pulmonary vascular resistance have focused on evaluating the roles of chemical mediators of vasoconstriction and vasodilation, as well as on pathological (structural) changes occurring within the pulmonary arterioles (e.g., vascular remodeling and pathology) during the pathogenesis of PAH. The objectives of this review are to (1) summarize the pathophysiological progression initiated by the onset of pulmonary hypertension and culminating in terminal ascites; (2) review recent information regarding the factors contributing to excessively elevated resistance to blood flow through the lungs; (3) assess the role of the immune system during the pathogenesis of PAH; and (4) present new insights into the genetic basis of PAH. The cumulative evidence attributes the elevated pulmonary vascular resistance in PAH-susceptible broilers to an anatomically inadequate pulmonary vascular capacity, to excessive vascular tone reflecting the dominance of pulmonary vasoconstrictors over vasodilators, and to vascular pathology elicited by excessive hemodynamic stress. Emerging evidence also demonstrates that the pathogenesis of PAH includes characteristics of an inflammatory/autoimmune disease involving multifactorial genetic, environmental, and immune system components. Pulmonary
Dykes, John C; Torres, Marilyn; Alexander, Plato J
This report describes the case of a neonate with d-transposition of the great arteries and severe pulmonary arterial hypertension stabilised in the post-operative period with continuous iloprost nebulisation. To our knowledge, this is the first documented method of treating post-operative severe pulmonary arterial hypertension with continuous inhaled iloprost in a patient with complex CHD. We found this method of delivering the drug very effective in stabilising haemodynamic swings in the setting of severe pulmonary arterial hypertension.
Nhu, Quan M; Knowles, Harry; Pockros, Paul J; Frenette, Catherine T
Transarterial chemoembolization (TACE) is an effective palliative intervention that is widely accepted for the management of hepatocellular carcinoma (HCC). Post-TACE pulmonary complications resulting in acute lung injury (ALI) or acute respiratory distress syndrome (ARDS) are rare events. Pulmonary complications after TACE are thought to be related to chemical injury subsequent to the migration of the infused ethiodized oil or chemotherapeutic agent to the lung vasculature, facilitated by arteriovenous (AV) shunts within the hyper-vascular HCC. We review herein the literature on pulmonary complications related to TACE for HCC. Post-TACE pulmonary complications have included pulmonary oil embolism, interstitial pneumonitis, chemical pneumonitis, ALI, ARDS, lipoid pneumonia, acute eosinophilic and neutrophilic pneumonia, bilious pleuritis, pulmonary abscess, pulmonary tumor embolism, and possibly pulmonary metastasis with HCC. The risk factors associated with post-TACE pulmonary complications identified in the literature include large hyper-vascular HCC with AV shunts, large-volume Lipiodol infusion, and embolization via the right inferior phrenic artery. However, the absence of known risk factors is not a guarantee against serious complications. An astute awareness of the potential post-TACE pulmonary complications should expedite appropriate therapeutic interventions and increase potential for early recovery. PMID:27904836
Morais, Sandra A; Oliveira, Hugo M; de Almeida, José R; Eiras, Eduardo; Silva, Ana Catarina; Gavina, Cristina
The authors report the case of a 74-year-old man, with a history of chronic obstructive pulmonary disease (COPD), GOLD grade 3, stable for the past two decades, who was admitted to our center with severe right heart failure. The chest radiograph showed moderate heart enlargement mainly of the right atrium and pulmonary artery, similar to previous chest radiographs in the previous 20 years. The transthoracic echocardiogram showed a pulmonary artery aneurysm (PAA), dilatation of the right chambers with pulmonary artery systolic pressure of 52 mmHg, and preserved right ventricular systolic function. A thoracic computed tomography scan confirmed the presence of a giant PAA 72 mm in diameter. The patient was started on high-dose diuretics, with significant clinical improvement. After optimization of medical therapy right heart catheterization was carried out with the patient in optimal clinical condition, which revealed mild precapillary pulmonary hypertension with a mean pulmonary artery pressure of 26 mmHg. On the basis of the clinical and imaging findings a stable, giant, high-pressure, PAA was diagnosed secondary to pulmonary hypertension induced by COPD, with a 20-year follow-up without need for surgical repair, which helped in our decision to maintain medical surveillance. The recent onset of heart failure is explained by the unfavorable evolution of COPD. This case may change the attitude expressed in previous studies favoring the choice of an invasive approach to treat giant high-pressure PAAs, instead supporting the maintenance of medical treatment.
Furest, I; Marín, M; Escribano, P; Gómez, M A; Cortinac, J; Blanquer, R
Intimal sarcoma of the pulmonary artery is a rare tumor that is usually diagnosed during surgery or autopsy. Such tumors are characterized by local growth, with only slight ability to metastasize. Diagnosis is difficult and often delayed owing to the nonspecific nature of the symptoms. Since intimal sarcoma of the pulmonary artery is so rare and insidious it is often confused with pulmonary thromboembolism and is therefore treated inappropriately with prolonged anticoagulation or thrombolysis. With a mean survival of 12 months from the onset of symptoms, the prognosis is poor. We present the case of a woman who was preoperatively diagnosed with intimal sarcoma of the pulmonary artery and who underwent surgical resection with no apparent recurrence at long term follow-up. A review of the literature is also included.
McLaughlin, Vallerie V; Badesch, David B; Delcroix, Marion; Fleming, Thomas R; Gaine, Sean P; Galiè, Nazzareno; Gibbs, J Simon R; Kim, Nick H; Oudiz, Ronald J; Peacock, Andrew; Provencher, Steeve; Sitbon, Olivier; Tapson, Victor F; Seeger, Werner
New and emerging therapies might provide benefit in patients with pulmonary arterial hypertension. Their efficacy and safety will be compared with existing combination therapies in randomized clinical trials. Appropriate end points for these trials need to be identified: these will include exercise testing, the composite end point of time to clinical worsening, and hemodynamic markers, including advanced imaging modalities and biomarkers. Quality-of-life questionnaires are useful and important secondary end points; pulmonary arterial hypertension-specific questionnaires are currently being developed. Advantages and disadvantages of various trial designs, including placebo-controlled monotherapy or add-on trials, noninferiority studies, and withdrawal trials are also discussed.
Funatsu, Yohei; Hirayama, Miwa; Shiraishi, Junichi; Asakura, Takanori; Wakaki, Misa; Yamada, Erina; Fujimoto, Kazuyuki; Satomi, Ryosuke; Inaki, Shunsuke; Murata, Yuya; Oyamada, Yoshitaka
Intimal sarcoma is a rare disease with a poor prognosis. We herein report the case of a 71-year-old man with intimal sarcoma of the pulmonary artery treated with pazopanib. The tumor showed regression after 1 month of treatment. Hand-foot syndrome led to cessation of pazopanib, which triggered a disease flare. Pazopanib should be considered in patients with intimal sarcoma of the pulmonary artery that is unresectable or recurrent after surgery or cytotoxic chemotherapy. We must be careful about drug cessation, as it can lead to a disease flare.
Ventetuolo, Corey E; Benza, Raymond L; Peacock, Andrew J; Zamanian, Roham T; Badesch, David B; Kawut, Steven M
Pulmonary arterial hypertension is a rare and often devastating disease, although various effective therapies are now available. Clinical trials have used hemodynamic, cardiac imaging, laboratory, and exercise measurements as surrogate and intermediate end points in pulmonary arterial hypertension. Yet, based on the current literature, it is difficult to surmise which of these (if any) have been definitively validated. In addition, investigators have advocated the use of combined clinical end points in future clinical trials. The dependence of clinical trials and clinical management on such end points warrants a review of their use.
Nair, Kiron K S; Zisman, Lawrence S; Lader, Ellis; Dimova, Aneta; Canver, Charles C
Anomalous origin of the left coronary artery from the pulmonary artery is a congenital coronary artery malformation most commonly present in infancy. A variety of surgical procedures have been described to achieve physiological correction of the coronary flow abnormalities. These techniques are effective as long as there is potential for myocardial recovery. However the sequelae of chronic myocardial ischemia that characterize this entity often irreversibly damage the heart and preclude correction and palliation of the native anomaly. In this type of setting, heart transplantation is a realistic option. Anomalous origin of the left coronary artery from the pulmonary artery (ALCAPA) occasionally presents in adulthood. Anatomic repair with a two coronary artery system may not be optimal in patients presenting with ischemic cardiomyopathy. We report an adult patient with platelet factor 4 (PF4) antibodies who underwent orthotopic heart transplantation (OHT) for ALCAPA.
Ahmad, Nawaid; Srinivasan, Koottalai; Panayi, Jeannette; Moudgil, Harmesh
Lumbo-sacral spinal disease due to bovine tuberculosis (TB) in a patient with concurrent pulmonary disease is rare. We report this unpredicted finding in an immunocompetent patient and discuss the natural history in an area of low prevalence.
Kaderli, Aysel Aydin; Baran, Ibrahim; Sağ, Saim; Biçer, Murat; Aker, Sibel
Primary sarcoma of the pulmonary artery (PSPA) is an extremely rare tumor of the cardiovascular system. The prognosis is very poor. The clinical symptoms and imaging findings imitate those of pulmonary emboli, causing delays in diagnosis. In this case report, we describe a 73-year-old man with PSPA who initially was admitted with exertional shortness of breath. Transthoracic echocardiographic evaluation revealed 2 masses in the pulmonary artery causing pulmonary hypertension. The patient underwent operation, but he could not be weaned off cardiopulmonary bypass at the end of the operation and died. Pathologic examination of the masses revealed pulmonary sarcoma. Although this patient was admitted to our clinic only 2 weeks after the initial symptoms, he already had distal metastases.
Reesink, Herre J.; Henneman, Onno D. F.; Delden, Otto M. van; Biervliet, Jules D.; Kloek, Jaap J.; Reekers, Jim A.; Bresser, Paul
We report a 38-year-old patient who presented with pulmonary hypertension and right ventricular dysfunction due to pulmonary artery stenoses as a manifestation of Williams syndrome, mimicking chronic thromboembolic pulmonary hypertension. The patient was treated with balloon angioplasty and stent implantation. Short-term follow-up showed a good clinical result with excellent patency of the stents but early restenosis of the segments in which only balloon angioplasty was performed. These stenoses were subsequently also treated successfully by stent implantation. Stent patency was observed 3 years after the first procedure.
Nesme, P; Arnouk, H; Perol, M; Bayle, J Y; Bejui-Thivolet, F; Baulieux, J; Guérin, J C
Intimal sarcomas growing from the pulmonary trunk or branches of the pulmonary artery, are rare tumours in which the diagnosis is most often made at autopsy or during a thoracotomy. Usually the clinical pictures is non specific resembling a severe pulmonary embolus which is resistant of all treatment. With the help of new imaging techniques, a pre-operative diagnosis is made in more than half the cases. When there is a tumour which is relatively localised and without endoluminal invasion, as in the observation reported here, the diagnosis rests on the histology from the operative specimen.
Anand, Girija Lewanski, Conrad R.; Cowman, Steven A.; Jackson, James E.
Migration of superior vena cava (SVC) stents is a well-recognised complication of their deployment, and numerous strategies exist for their retrieval. To our knowledge, only three cases of migration of an SVC stent to the pulmonary vasculature have previously been reported. None of these patients developed complications that resulted in death. We report a case of SVC stent migration to the pulmonary vasculature with delayed pulmonary artery thrombosis and death from pulmonary infarction. We conclude that early retrieval of migrated stents should be performed to decrease the risk of serious complications.
Garg, Ashok; Mooney, John; Amado Escañuela, Maximiliano German; Mathur, Alok; Goyal, Vikram; Nanda, Navin C
In this report, we present a case of spindle cell sarcoma of the pulmonary artery diagnosed by transthoracic echocardiography. To the best of our knowledge, this case is the youngest reported case of pulmonary artery sarcoma (PAS) to date. PAS is frequently confused for pulmonary embolism; in this case, echocardiographic findings allowed for differentiation between pulmonary embolism and solid tumor.
De Dominicis, Florence; Leborgne, Laurent; Raymond, Alexandre; Berna, Pascal
Isolated unilateral pulmonary artery agenesis is a rare congenital anomaly that may be complicated with hemoptysis, recurrent pulmonary infections or pulmonary hypertension. To our knowledge the occurrence of a coronary syndrome associated with a coronary-to-bronchial artery saccular aneurysmal collateralization has never been described before. A 44-year-old female presented a congenital right pulmonary artery agenesis associated with a hypotrophic and multicystic right lung complicated with recurrent bronchitis. This patient had a coronary syndrome for which the coronary artery imaging showed a coronary-to-bronchial artery collateralization with an aneurysm at this level. It gives rise to a coronary syndrome by coronary steal. Two bronchial collaterals arising from a diaphragmatic artery and the subclavian artery were also found on the computed tomography (CT)-scan. This last collateral also showed another saccular aneurysm. We first performed an embolization of those two aneurysms in order to decrease the risk of hemorrhage and coronary steal, before performing a right pneumonectomy. In this case, the surgery was indicated because of the pathological lung and the risk of postembolization ischaemia. The postoperative course was uneventful and the patient was doing well six months later.
Sondheimer, H.M.; Oliphant, M.; Schneider, B.; Kavey, R.E.W.; Blackman, M.S.; Parker, F.B. Jr.
To expand the search for central pulmonary arteries in six patients with absence of cardiac-pulmonary continuity, computerized axial tomography (CAT) of the chest was performed. The CAT scans were compared with previous arteriograms and pulmonary vein wedge angiograms. Three patients with type IV truncus arteriosus were studied, and none had a central, right or left pulmonary artery on CAT scan. However, two patients with tetralogy of Fallot with pulmonary atresia and a patent ductus arteriosus to the right lung demonstrated the presence of a left pulmonary artery. In addition, one child with truncus arteriosus with ''absent'' left pulmonary artery demonstrated a left pulmonary artery on the CAT scan. The CAT scan may therefore enhance our ability to search for disconnected pulmonary arteries in children with complex cyanotic congenital heart disease.
Kamimura, R; Suzuki, S; Miura, N; Miyahara, K
The lung produces many vasoactive substances originating from its vascular endothelium and plays an important part in various pathose. The present study was carried out to clarify pulmonary atherosclerosis and pulmonary arterial pressure, and to elucidate a part of the pulmonary pathosis in cholesterol-fed rabbits. Atherosclerosis was induced by feeding the animals a cholesterol-rich diet. When the rabbits were fed the cholesterol-enriched diets for 15 weeks, the grade of the atherosclerosis was severer than in 8W-feeding rabbits. The lesions of 8W-feeding rabbits were mainly composed of foam cells and fibrous components, whereas in 15W-feeding rabbits, the aggregation of foam cells beneath the endothelium of the vessel was infiltrating the media and severe stenose of the lumen was observed. In the entire pulmonary arterial system, the severe obstructive vascular lesions were localized and not diffused. The pulmonary arterial pressures of the rabbits increased slightly with time and the mean pressures were 11.3+/-0.9 (control group), 11.8+/-1.0 (8W group) and 13.7+/-1.5 mmHg (15W group) respectively. A significant difference existed in the mean pressure between the control group and 15W-feeding group, but there were no significant differences in the systolic and diastolic pressures among the three groups. In conclusion, we could induce pulmonary atherosclerosis in rabbits by feeding them a hyper-cholesterol diet but not overt pulmonary hypertension.
Santos-Martínez, Luis Efren; Moreno-Ruiz, Luis Antonio; Jiménez-Santos, Moisés; Olmos-Temois, Sergio Gabriel; Bojorquez-Guerrero, Luis Armando; Baranda-Tovar, Francisco Martín
Inhaled iloprost is a drug from the group of prostacyclins used in the treatment of pulmonary arterial hypertension. Its efficacy and safety have allowed its use as monotherapy and combination therapy. This review describes the product characteristics, amenable to treatment groups, and updated clinical evidence of drug use.
Sandoval-Gutiérrez, José Luis; Santos-Martínez, Luis Efren; Rodríguez-Silverio, Juan; Baranda-Tovar, Francisco Martín; Rivera-Rosales, Rosa María; Flores-Murrieta, Francisco Javier
From the advent of the highly effective antiretroviral treatment, the life expectancy of patients with human immunodeficiency virus has increased significantly. At present, the causes of death are non-infectious complications. Between them, the pulmonary arterial hypertension has a special importance. It is important early detection to establish the therapeutic, with the objective of preventing a fatal outcome to future.
Yamanari, Mauricio Gustavo Ieiri; Mansur, Maria Clara Dias; Kay, Fernando Uliana; Silverio, Paulo Rogerio Barboza; Jayanthi, Shri Krishna; Funari, Marcelo Buarque de Gusmão
The authors report the case of a patient victim of gunshots, with a very rare complication: venous bullet embolism from the left external iliac vein to the lingular segment of the left pulmonary artery. Diagnosis is made with whole-body radiography or computed tomography. Digital angiography is reserved for supplementary diagnosis or to be used as a therapeutic procedure.
Pankey, Edward A; Epps, Matthew; Nossaman, Bobby D; Hyman, Albert L; Kadowitz, Philip J
Pulmonary arterial hypertension (PAH) is a devastating disease with limited therapeutic options. Moreover, when PAH occurs in patients diagnosed with systemic sclerosis, worse outcomes are observed. The purpose of this review is to discuss the etiologies of PAH found in the systemic sclerosis patient, limitations of current medical therapies, and, finally, potential therapies for patients with this combination. PMID:23626904
Leiomyoma of the lung is extremely rare. The entity is not described in WHO blue book. Less than 100 cases of leiomyoma of the lung have been reported in the literature. However, vascular leiomyoma has not been reported in the literature, to the author's best knowledge. Herein reported is the first case of vascular leiomyoma of the lung arising from smooth muscles of the pulmonary artery. A 62-year-old woman (non-smoker) was found to have a small tumor in the upper lobe in the right lung in routine check. Imaging modalities including CT demonstrated no metastatic lesions. Although clinical cytology and biopsy revealed no malignant cell, right upper lobectomy was performed under the clinical diagnosis of lung carcinoma. Grossly, a white tumor of 1 x 0.8 cm was recognized in the lung. Microscopically, the tumor was connected to the pulmonary arteries. The tumor was composed of mature smooth muscles. Small pulmonary arteries are embedded in the tumor. No lymphatics were seen. Immunohistochemically, the tumor cells were poisitive for alpha-smooth muscle actin, vimentin and Ki-67 (labeling 2%). However, they were negative for cytokeratin (CK) AE1/3, CK CAM5.2, desmin, S100 protein, p53, CD34, KIT, HMB45, estrogen receptor, progesterone receptor, and myoglobin. A pathological diagnosis of primary vascular leiomyoma arising from the smooth muscle of pulmonary artery was made. The patient is now free from tumor, and is now alive 10 year after the operation.
... is a heart defect. The left coronary artery (LCA), which carries blood to the heart muscle, begins ... not attach correctly. In the normal heart, the LCA originates from the aorta. It supplies oxygen-rich ...
Aziz, K; Tasneem, H
Blood flow in the pulmonary artery was studied by Doppler colour flow mapping and cardiac catheterisation in 19 patients with a ductus arteriosus and different pulmonary artery pressures. In the four patients with normal pulmonary artery pressures colour Doppler flow mapping showed multicoloured wide and long systolic and diastolic jets in the pulmonary artery. In the 15 patients with raised pulmonary arterial pressure the systolic jets varied from multicoloured to red and were thinner: in patients with considerably raised pulmonary arterial pressure the jets became redder during diastole. The Doppler velocity tracings showed that in patients with normal pulmonary artery pressures the mean peak systolic velocity was higher than the mean end diastolic velocity--so that in all four the ratio of peak systolic velocity to end diastolic velocity was less than 2. The mean peak systolic velocity was much higher than the mean end diastolic velocity in 13 of the 15 patients with raised pulmonary artery pressure; this meant that the ratio of peak systolic velocity to end diastolic velocity was greater than 2 in 10 of 11 patients. The end diastolic velocity was significantly lower in those patients with raised pulmonary artery pressure than in those with normal artery pressure. There was an inverse linear correlation between the mean pulmonary artery pressure and end diastolic ductal jet velocity in 17 of the 19 patients. Colour flow mapping and this quantitative Doppler technique can detect pulmonary artery hypertension in patients with a ductus arteriosus. Images PMID:2278800
Hamoda, Haitham; Tait, P.; Edmonds, D. K.
We report a 44-year-old woman who developed a fatal pulmonary embolus after uterine artery fibroid embolisation (UAE). Bilateral UAE was carried out through a single right-femoral artery puncture. The largest fibroid in the anterior fundal wall measured 4.5 cm, and the largest fibroid in the posterior fundal wall measured 6 cm. The appearances after UAE were satisfactory, and the procedure was apparently uneventful. No immediate complications were noted. The patient developed sudden-onset shortness of breath and went into cardiac arrest 19 h after the procedure. Postmortem autopsy confirmed that the cause of a death was a pulmonary embolism. To our knowledge this is the first reported case in the United Kingdom in which death occurred from a pulmonary embolus after UAE.
Kingman, Martha S; Thompson, Brenda S; Newkirk, Trixie; Torres, Fernando
Pulmonary arterial hypertension complicated by decompensated cor pulmonale is a challenging clinical problem with few effective therapeutic options. B-type natriuretic peptide is a pluripotent hormone that promotes diuresis and natriuresis, vasodilates systemic and pulmonary vessels, and reduces circulating levels of endothelin and aldosterone. It may represent a possible therapeutic strategy for decompensated cor pulmonale in the same manner that it is used to treat decompensated left heart failure. The authors report their experience with B-type natriuretic peptide as adjunctive therapy for pulmonary arterial hypertension complicated by decompensated cor pulmonale. A detailed case report is presented followed by the evaluation of a series of 11 cases occurring in eight patients from December 2002 through April 2004.
Erlij, Daniel; Michalland, Susana; Neira, Óscar; Fernández, Cristina; Wolff, Verónica
Pulmonary artery sarcoma is an uncommon entity with high mortality. Its clinical presentation is usually indistinguishable from pulmonary embolism, which leads to a significant delay in diagnosis. Hughes-Stovin syndrome is characterized by venous thrombosis and aneurysms of the pulmonary or bronchial artery. We report a 59 year-old female with a history of recurrent pulmonary embolism. In the last thromboembolic episode a pulmonary artery aneurysm was found on a CT scan. The patient was operated performing a left inferior lobectomy. The patient died five days after surgery and the pathological examination of the surgical piece revealed a pulmonary artery sarcoma.
Singla Long, Svati; Johnson, Pamela T; Hruban, Ralph H; Fishman, Elliot K
Pulmonary artery sarcoma is an uncommon and highly malignant neoplasm that presents a diagnostic challenge to radiologists due to its tendency to mimic the more common condition of pulmonary thromboembolism. Presented in this case report is a patient with pulmonary artery sarcoma who was initially diagnosed with saddle pulmonary embolism based upon computed tomography (CT) findings. The case emphasizes the importance of including pulmonary artery sarcoma in the differential diagnosis of a large filling defect in the pulmonary arteries when specific CT findings are identified in the appropriate clinical setting.
Hao, Mingwen; Li, Miaomiao; Li, Wenjun
Galectin-3 (Gal-3) is a β-galactoside-binding lectin, which is important in inflammation, fibrosis and heart failure. The present study aimed to investigate the role and mechanism of Gal-3 in hypoxia-induced pulmonary arterial hypertension (PAH). Male C57BL/6J and Gal-3−/− mice were exposed to hypoxia, then the right ventricular systolic pressure (RVSP) and Fulton's index were measured, and Gal-3 mRNA and protein expression in the pulmonary arteries was analyzed by reverse transcription-quantitative polymerase chain reaction and western blotting. Compared with the control, hypoxia increased the mRNA and protein expression levels of Gal-3 in wild type murine pulmonary arteries. Gal-3 deletion reduced the hypoxia-induced upregulation of RVSP and Fulton's index. Furthermore, human pulmonary arterial endothelial cells (HPAECs) and human pulmonary arterial smooth muscle cells (HPASMCs) were stimulated by hypoxia in vitro, and Gal-3 expression was inhibited by small interfering RNA. The inflammatory response of HPAECs, and the proliferation and cell cycle distribution of HPASMCs was also analyzed. Gal-3 inhibition alleviated the hypoxia-induced inflammatory response in HPAECs, including tumor necrosis factor-α and interleukin-1 secretion, expression of intercellular adhesion molecule-1 and adhesion of THP-1 monocytes. Gal-3 inhibition also reduced hypoxia-induced proliferation of HPASMCs, partially by reducing cyclin D1 expression and increasing p27 expression. Furthermore, Gal-3 inhibition suppressed HPASMC switching from a ‘contractile’ to a ‘synthetic’ phenotype. In conclusion, Gal-3 serves a fundamental role in hypoxia-induced PAH, and inhibition of Gal-3 may represent a novel therapeutic target for the treatment of hypoxia-induced PAH. PMID:27959409
Kim, Young Il; Kang, Hyo Cheol; Lee, Ho Sung; Choi, Jae Sung; Seo, Ki Hyun; Kim, Yong Hoon; Na, Juock
Pulmonary mucormycosis is a rare opportunistic invasive fungal infection involving the pulmonary vasculature in immunocompromised patients. Pseudoaneurysm of pulmonary artery in mucormycosis is a rare fatal complication after invasion and rupture of a pulmonary artery. We report a patient with diabetes mellitus and incidental lung cancer who developed massive hemoptysis because of a huge pseudoaneurysm of the left pulmonary artery by mucormycosis. Although the patient had been managed by amphotericin B followed by left pneumonectomy for persistent hemoptysis, he died from septic shock and multiorgan failure after surgery. Histologic analysis of a surgical specimen revealed concomitant squamous cell lung cancer.
Iwazawa, Jin; Nakamura, Kenji; Hamuro, Masao; Nango, Mineyoshi; Sakai, Yukimasa; Nishida, Norifumi
We present the case of a 60-year-old woman with symptomatic mitral regurgitation caused by a left-to-right shunt via anastomoses consisting of microfistulae, most likely of inflammatory origin, between the right subclavian artery and the right pulmonary artery. The three arteries responsible for fistulous formation, including the internal mammary, thyrocervical, and lateral thoracic arteries, were successfully occluded by transcatheter embolization using superabsorbent polymer microsphere (SAP-MS) particles combined with metallic coils. No complications have been identified following treatment with SAP-MS particles. This approach significantly reduced the patient's mitral regurgitation and she has remained asymptomatic for more than 4 years.
Mittal, Kartik; Dey, Amit K; Gadewar, Rohit; Sharma, Rajaram; Pandit, Nilesh; Rajput, Priya; Hira, Priya
The incidence of congenital heart disease (CHD) is 2.4-3.8/1000 live births. Up to 70.7 % of all cases of CHD are reported to be benign; complex heart anomalies are extremely rare. Our case is extremely rare, as we report three very rare findings-truncus arteriosus, anomalous origin of the right coronary artery from the pulmonary artery (ARCAPA), and unilateral left pulmonary artery agenesis-in a single patient. Congenital complex cardiac abnormalities are very rare, and two-dimensional echocardiography screening should be supported by cardiac computed tomography (CT). We report a case of truncus arteriosus associated with ARCAPA and left pulmonary artery agenesis diagnosed by cardiac computed tomography; we believe that such an unusual case with all three of these entities has never been reported before.
Meloche, Jolyane; Le Guen, Marie; Potus, François; Vinck, Jérôme; Ranchoux, Benoit; Johnson, Ian; Antigny, Fabrice; Tremblay, Eve; Breuils-Bonnet, Sandra; Perros, Frederic; Provencher, Steeve; Bonnet, Sébastien
Pulmonary arterial hypertension (PAH) is a devastating disease affecting lung vasculature. The pulmonary arteries become occluded due to increased proliferation and suppressed apoptosis of the pulmonary artery smooth muscle cells (PASMCs) within the vascular wall. It was recently shown that DNA damage could trigger this phenotype by upregulating poly(ADP-ribose)polymerase 1 (PARP-1) expression, although the exact mechanism remains unclear. In silico analyses and studies in cancer demonstrated that microRNA miR-223 targets PARP-1. We thus hypothesized that miR-223 downregulation triggers PARP-1 overexpression, as well as the proliferation/apoptosis imbalance observed in PAH. We provide evidence that miR-223 is downregulated in human PAH lungs, distal PAs, and isolated PASMCs. Furthermore, using a gain and loss of function approach, we showed that increased hypoxia-inducible factor 1α, which is observed in PAH, triggers this decrease in miR-223 expression and subsequent overexpression of PARP-1 allowing PAH-PASMC proliferation and resistance to apoptosis. Finally, we demonstrated that restoring the expression of miR-223 in lungs of rats with monocrotaline-induced PAH reversed established PAH and provided beneficial effects on vascular remodeling, pulmonary resistance, right ventricle hypertrophy, and survival. We provide evidence that miR-223 downregulation in PAH plays an important role in numerous pathways implicated in the disease and restoring its expression is able to reverse PAH.
Tanabe, Yoshiyuki; Saito-Tanji, Maki; Morikawa, Yuki; Kamataki, Akihisa; Sawai, Takashi; Nakayama, Koichi
Excessive stretching of the vascular wall in accordance with pulmonary arterial hypertension (PAH) induces a variety of pathogenic cellular events in the pulmonary arteries. We previously reported that indoxam, a selective inhibitor for secretory phospholipase A(2) (sPLA(2)), blocked the stretch-induced contraction of rabbit pulmonary arteries by inhibition of untransformed prostaglandin H(2) (PGH(2)) production. The present study was undertaken to investigate involvement of sPLA(2) and untransformed PGH(2) in the enhanced contractility of pulmonary arteries of experimental PAH in rats. Among all the known isoforms of sPLA(2), sPLA(2)-X transcript was most significantly augmented in the pulmonary arteries of rats with monocrotaline-induced pulmonary hypertension (MCT-PHR). The pulmonary arteries of MCT-PHR frequently showed two types of spontaneous contraction in response to stretch; 27% showed rhythmic contraction, which was sensitive to indoxam and SC-560 (selective COX-1 inhibitor), but less sensitive to NS-398 (selective COX-2 inhibitor); and 47% showed sustained incremental tension (tonic contraction), which was insensitive to indoxam and SC-560, but sensitive to NS-398 and was attenuated to 45% of the control. Only the rhythmically contracting pulmonary arteries of MCT-PHR produced a substantial amount of untransformed PGH(2), which was abolished by indoxam. These results suggest that sPLA(2)-mediated PGH(2) synthesis plays an important role in the rhythmic contraction of pulmonary arteries of MCT-PHR.
Jain, Pritesh P; Leber, Regina; Nagaraj, Chandran; Leitinger, Gerd; Lehofer, Bernhard; Olschewski, Horst; Olschewski, Andrea; Prassl, Ruth; Marsh, Leigh M
Prostacyclin analogues are standard therapeutic options for vasoconstrictive diseases, including pulmonary hypertension and Raynaud’s phenomenon. Although effective, these treatment strategies are expensive and have several side effects. To improve drug efficiency, we tested liposomal nanoparticles as carrier systems. In this study, we synthesized liposomal nanoparticles tailored for the prostacyclin analogue iloprost and evaluated their pharmacologic efficacy on mouse intrapulmonary arteries, using a wire myograph. The use of cationic lipids, stearylamine, or 1,2-di-(9Z-octadecenoyl)-3-trimethylammonium-propane (DOTAP) in liposomes promoted iloprost encapsulation to at least 50%. The addition of cholesterol modestly reduced iloprost encapsulation. The liposomal nanoparticle formulations were tested for toxicity and pharmacologic efficacy in vivo and ex vivo, respectively. The liposomes did not affect the viability of human pulmonary artery smooth muscle cells. Compared with an equivalent concentration of free iloprost, four out of the six polymer-coated liposomal formulations exhibited significantly enhanced vasodilation of mouse pulmonary arteries. Iloprost that was encapsulated in liposomes containing the polymer polyethylene glycol exhibited concentration-dependent relaxation of arteries. Strikingly, half the concentration of iloprost in liposomes elicited similar pharmacologic efficacy as nonencapsulated iloprost. Cationic liposomes can encapsulate iloprost with high efficacy and can serve as potential iloprost carriers to improve its therapeutic efficacy. PMID:25045260
Jain, Pritesh P; Leber, Regina; Nagaraj, Chandran; Leitinger, Gerd; Lehofer, Bernhard; Olschewski, Horst; Olschewski, Andrea; Prassl, Ruth; Marsh, Leigh M
Prostacyclin analogues are standard therapeutic options for vasoconstrictive diseases, including pulmonary hypertension and Raynaud's phenomenon. Although effective, these treatment strategies are expensive and have several side effects. To improve drug efficiency, we tested liposomal nanoparticles as carrier systems. In this study, we synthesized liposomal nanoparticles tailored for the prostacyclin analogue iloprost and evaluated their pharmacologic efficacy on mouse intrapulmonary arteries, using a wire myograph. The use of cationic lipids, stearylamine, or 1,2-di-(9Z-octadecenoyl)-3-trimethylammonium-propane (DOTAP) in liposomes promoted iloprost encapsulation to at least 50%. The addition of cholesterol modestly reduced iloprost encapsulation. The liposomal nanoparticle formulations were tested for toxicity and pharmacologic efficacy in vivo and ex vivo, respectively. The liposomes did not affect the viability of human pulmonary artery smooth muscle cells. Compared with an equivalent concentration of free iloprost, four out of the six polymer-coated liposomal formulations exhibited significantly enhanced vasodilation of mouse pulmonary arteries. Iloprost that was encapsulated in liposomes containing the polymer polyethylene glycol exhibited concentration-dependent relaxation of arteries. Strikingly, half the concentration of iloprost in liposomes elicited similar pharmacologic efficacy as nonencapsulated iloprost. Cationic liposomes can encapsulate iloprost with high efficacy and can serve as potential iloprost carriers to improve its therapeutic efficacy.
Chen, Gui-Lan; Jiang, Hongni; Zou, Fangdong
Background Septic shock is a pathologic condition caused by endotoxin-producing bacteria, and often associated with severe pulmonary hypertension. Inflammation is a major systemic response to endotoxin; however, it is unknown whether endotoxin has a direct impact on pulmonary arteries that contributes to pathogenesis of pulmonary hypertension. Material/Methods Rat pulmonary arteries and primary pulmonary arterial smooth muscle cells (PASMCs) were cultured in vitro and treated with lipopolysaccharide (LPS) and blockers of transient receptor potential canonical (TRPC) channels. Neointimal growth and arterial stenosis were observed on cryosections of cultured pulmonary arteries. Proliferation of PASMCs was examined by a WST-1 (water-soluble tetrazolium salt) assay. Expression of TRPC genes in pulmonary arteries and PASMCs were detected and quantified by real-time polymerase chain reaction and Western blotting. Results LPS significantly induced neointimal growth and stenosis of pulmonary arteries and promoted proliferation of PASMCs. TRPC channel blockers 2-aminoethoxydiphenyl borate and SKF-96365 inhibited LPS-induced remodeling of pulmonary arteries and PASMC proliferation. Expression of TRPC1/3/4/6 was detected in pulmonary arteries and PASMCs. LPS treatment dramatically increased the expression of TRPC3 and TRPC4 at both messenger RNA and protein levels. Conclusions LPS stimulates stenosis of pulmonary arteries through enhancement of TRPC-mediated Ca2+ entry into PASMCs, which is caused by upregulation of TRPC3 and TRPC4 channels. PMID:27471122
Ruffenach, Grégoire; Umar, Soban; Motayagheni, Negar; Reddy, Srinivasa T.; Eghbali, Mansoureh
Abstract Pulmonary arterial hypertension (PAH) is a multifactorial disease characterized by interplay of many cellular, molecular, and genetic events that lead to excessive proliferation of pulmonary cells, including smooth muscle and endothelial cells; inflammation; and extracellular matrix remodeling. Abnormal vascular changes and structural remodeling associated with PAH culminate in vasoconstriction and obstruction of pulmonary arteries, contributing to increased pulmonary vascular resistance, pulmonary hypertension, and right ventricular failure. The complex molecular mechanisms involved in the pathobiology of PAH are the limiting factors in the development of potential therapeutic interventions for PAH. Over the years, our group and others have demonstrated the critical implication of lipids in the pathogenesis of PAH. This review specifically focuses on the current understanding of the role of oxidized lipids, lipid metabolism, peroxidation, and oxidative stress in the progression of PAH. This review also discusses the relevance of apolipoprotein A-I mimetic peptides and microRNA-193, which are known to regulate the levels of oxidized lipids, as potential therapeutics in PAH. PMID:27683603
Chu, YanBiao; XiangLi, XiaoYing; Niu, Hu; Wang, HongChao; Jia, PingDong; Gong, WenBin; Wu, DaWei; Qin, WeiDong; Xing, ChunYan
Hypoxia-induced pulmonary arterial hypertension (HPAH) is a refractory disease characterized by increased proliferation of pulmonary vascular smooth cells and progressive pulmonary vascular remodeling. The level of nitric oxide (NO), a potential therapeutic vasodilator, is low in PAH patients. L-arginine can be converted to either beneficial NO by nitric oxide synthases or to harmful urea by arginase. In the present study, we aimed to investigate whether an arginase inhibitor, S-(2-boronoethyl)-L-cysteine ameliorates HPAH in vivo and vitro. In a HPAH mouse model, we assessed right ventricle systolic pressure (RVSP) by an invasive method, and found that RSVP was elevated under hypoxia, but was attenuated upon arginase inhibition. Human pulmonary artery smooth muscle cells (HPASMCs) were cultured under hypoxic conditions, and their proliferative capacity was determined by cell counting and flow cytometry. The levels of cyclin D1, p27, p-Akt, and p-ERK were detected by RT-PCR or Western blot analysis. Compared to hypoxia group, arginase inhibitor inhibited HPASMCs proliferation and reduced the levels of cyclin D1, p-Akt, p-ERK, while increasing p27 level. Moreover, in mouse models, compared to control group, hypoxia increased cyclin D1 expression but reduced p27 expression, while arginase inhibitor reversed the effects of hypoxia. Taken together, these results suggest that arginase plays an important role in increased proliferation of HPASMCs induced by hypoxia and it is a potential therapeutic target for the treatment of pulmonary hypertensive disorders.
Fraisse, A; Habib, G
Treatment strategies for pulmonary hypertension in children have dramatically evolved. Traditional therapy with calcium channel blockers and pulmonary transplantation is only indicated in selected patients and does not reduce mortality very significantly. New pulmonary vasodilators are emerging from recent trials in the adult population. Their indications are based on the patient's NYHA classification. The epoprostenol (prostacyclin, Flolan) has shown reduction in mortality and improvement in functional symptoms in pediatric patients. The frequent side effects and continuous intravenous infusion limit the indication of prostacyclin in NYHA class IV children. The endothelin receptor blocker bosentan (Tracleer) is an orally given agent. It improves functional symptoms in adults and hemodynamic measures in children. It can be started in children with moderate functional symptoms (NYHA class II and III). The type V phosphodiesterase inhibitor sildenafil (Viagra) is being evaluated and may represent a promising therapy in the future. Invasive strategies like catheter-based atrial septostomy may be useful in particular cases. Randomized-controlled studies are urgently needed to evaluate the safety and efficacy of these new therapies.
Hirano, Y; Kitagawa, H; Sasaki, Y
To examine effects of thromboemboli due to dead worms on pulmonary arterial pressure (PAP), 20 to 50 dead heartworms were inserted into the pulmonary arteries of 4 heartworm uninfected dogs (uninfected group) and 11 dogs infected with heartworms (infected group). In the uninfected group, the mean PAP rose 1 week after worm insertion (10.9 to 166. mmHg), but it recovered by the 4th week. Clinical signs, hemodynamics and blood gas findings also deteriorated at the 1st week, but recovered at the 4th week. Angiographic and pathological findings indicated that blood flow recovered through the spaces between thromboemboli and vessel walls at the 4th week. The infected dogs were divided into three groups. In the infected-I group (5 dogs), the intimal lesions of the pulmonary arteries were slight, and clinical and laboratory findings showed changes similar to those of the uninfected group. In the infected-II group (4 dogs), the pulmonary arterial lesions were severe and the mean PAP was higher (25.7 mmHg) than in the uninfected group before worm insertion. An increase in PAP (34.1 mmHg) and worsening of clinical and laboratory findings were noticed till the 4th week. Thromboemboli adhered extensively to the vessel walls. Two dogs in the infected-III group died of severe dyspnea on the 9th and 10th day, and the mean PAP rose remarkably at the 1st week (from 19.4 to 28.2 mmHg). Severe pulmonary parenchymal lesions with edema or perforation were observed. From the above results, it was clarified that effects of dead worms on PAP and clinical signs depended on the severity of pulmonary arterial lesions before worm insertion.(ABSTRACT TRUNCATED AT 250 WORDS)
Cock, Dries De; Meuris, Bart; Benett, Johan; Desmet, Walter
Carotid artery dissections are commonly associated with trauma or various connective tissue disorders. Dissection of the cerebrovascular arteries can result in ischemic stroke and is a frequent stroke etiology in younger patients. Anatomical variants of aortic arch branching, such as the 'bovine' aortic arch, are assumed to have little or no physiological consequence. To the best of our knowledge, we present for the first time a case of spontaneous dissection of the common origin of the innominate and left common carotid artery in a bovine aortic arch, resulting in bilateral dissection of the carotid arteries.
Ammari, Chady; Campisi, Alessio; D’Andrea, Rocco
Peripheral vein catheterization is generally considered a harmless procedure. Venous catheter rupture associated with pulmonary embolism is an unlikely but potentially serious complication. We report a case of a peripheral venous catheter (PVC) fracture with pulmonary artery embolization in the left lower lobe treated successfully by a surgical approach. The positioning of a PVC is not always a harmless procedure. Every time there are difficulties in positioning or in removal of a catheter device, it should be carefully inspected to verify integrity. The advisability of removal of these small foreign bodies is debated; percutaneous retrieval is preferred, while surgery should be discussed case by case. PMID:28149586
Pulmonary arterial hypertension (PAH) is characterized by vasoconstriction and cell proliferation in the pulmonary vasculature. Guideline-driven interventions with infused prostacyclin treatment are the mainstay for patients with advanced symptoms. Infused prostacyclin therapy is complex. It is critical to manage prostacyclin therapy with precision because boluses or interruptions can be fatal. Education of patients and inpatient staff nurses is necessary to prevent negative outcomes. Nurses are an essential part of the multidisciplinary team caring for patients with PAH. The diagnostic evaluation and treatment of PAH are reviewed here, and challenges associated with the care of patients on prostacyclin therapy are discussed.
Hassoun, Paul M
Pulmonary arterial hypertension (PAH), a common complication of systemic sclerosis, carries a very severe prognosis and is one of the leading causes of death in patients who suffer from it. Indeed, response to modern medical therapy has been disappointing in scleroderma-related PAH compared with other forms of PAH from the WHO group 1 classification of diseases, despite similar histological changes involving the pulmonary vasculature. This review discusses specific features of scleroderma-related PAH, currently available and US FDA-approved therapy for this syndrome, as well as potential future therapeutic developments based on newly acquired knowledge of this disorder. PMID:19885388
Lai, Ying-Rong; Hong, Jun-Mou; Liu, Zhen-Guo; Deng, Zhen-Sheng; Yeung, Sai-Ching J; Cheng, Chao
Massive hemoptysis in Behçet disease (BD) is rare but often fatal. This report presents a 28-year-old man with recurrent massive hemoptysis. He was diagnosed with bilateral multiple pulmonary artery aneurysms (PAAs), coronary artery aneurysm, and ventricular pseudoaneurysm from BD. The patient underwent emergency right lower lobectomy with no obvious complications. No hemoptysis recurred during an 18-month follow-up. This report also reviews the occurrence of PAAs in BD, with an emphasis on the treatment approaches.
Nomori, Hiroaki; Cong, Yue; Sugimura, Hiroshi
It is often difficult to expose the pulmonary artery buried in a scar tissue, especially in lung cancer patients that responded well to neoadjuvant chemoradiotherapy. Difficulty to access pulmonary artery branches may lead to potentially unnecessary pneumonectomy. To complete lobectomy in such cases, a technique with preceding bronchial cutting for exposure of the pulmonary artery is presented. After dissecting the pulmonary vein, the lobar bronchus is cut from the opposite side of the pulmonary artery with scissors. The back wall of the lobar bronchus is cut using a surgical knife from the luminal face, which can expose the pulmonary artery behind the bronchial stump and then complete lobectomy. Fourteen patients have been treated using the present technique, enabling complete resection by lobectomy (including sleeve lobectomy in 3 patients) without major bleeding. The present procedure can expose pulmonary artery buried in scar tissue, resulting in making the lobectomy safer.
Talavera, María L; Diez, Mirta; Cáneva, Jorge O; Boughen, Roberto P; Valdivieso, León; Mendiz, Oscar
Chest pain is a frequent symptom in patients with pulmonary hypertension of any etiology. Its pathophysiology has not been clearly established, the proposed causes are ischemia due to increased right ventricle wall stress, transient increased pulmonary hypertension resulting in acute pulmonary artery dilatation and external compression of the left main coronary artery (LMCA) by a dilated pulmonary artery. We report and discuss here three cases where the association between chest pain and compression of the LMCA by a dilated pulmonary artery could be shown, and they were treated with coronary stenting.
Ooi, Masaya; Omoto, T; Ishikawa, N; Mouri, M; Okayama, T; Fukusumi, M; Ono, M; Tedoriya, T
Primary sarcoma of the pulmonary artery is rare. Diagnosis is difficult and often delayed; pulmonary embolism is part of the differential diagnosis. We treated a 46-year-old woman with progressive dyspnea. Computed tomography showed a lesion occupying the main pulmonary artery and peripheral branches on both sides. The pulmonary artery tumor, resected under cardiopulmonary bypass, was diagnosed pathologically as intimal sarcoma. Two weeks after the operation, the patient was feeling well and discharged from our hospital. Although the prognosis of pulmonary artery sarcoma is poor, early diagnosis and resection may prolong survival.
Kao, Philip H; Lammers, Steve; Tian, Lian; Hunter, Kendall; Stenmark, Kurt R.; Shandas, Robin; Qi, H. Jerry
A new constitutive model for elastic, proximal pulmonary artery tissue is presented here, called the Total Crimped Fiber Model. This model is based on the material and micro-structural properties of the two main, passive, load-bearing components of the artery wall, elastin and collagen. Elastin matrix proteins are modeled with an orthotropic neo-Hookean material. High stretch behavior is governed by an orthotropic crimped fiber material, modeled as a planar sinusoidal linear elastic beam, which represents collagen fiber deformations. Collagen-dependent artery orthotropy is defined by a structure tensor representing the effective orientation distribution of collagen fiber bundles. Therefore, every parameter of the total crimped fiber model is correlated with either a physiologic structure or geometry or is a mechanically-measured material property of the composite tissue. Further, by incorporating elastin orthotropy, this model better represents the mechanics of arterial tissue deformation. These advancements result in a micro-structural total crimped fiber model of pulmonary artery tissue mechanics which demonstrates good quality of fit and flexibility for modeling varied mechanical behaviors encountered in disease states. PMID:21599093
Santhosh, M C B; Pai, R B; Rao, R P
Arterial tourniquets are used as one of the methods for reducing blood loss and for allowing blood free surgical field. A 20-year-old, 45 kg healthy female with a sphere shaped pendunculated hemangioma in the popliteal fossa of her left lower limb was applied with arterial tourniquet after exsanguination. The procedure was performed under general anesthesia. Soon after exsanguination and tourniquet inflation, the patient developed pulmonary edema which subsided after deflating the tourniquet. The clinical evolution, treatment and pathophysiology of this complication are described.
Meyrick, B.; Perkett, E.A.; Harris, T.R.; Brigham, K.L.
Changes in vascular permeability are associated with structural damage to endothelial cells. These functional and structural changes can be produced experimentally and examined by using intimal explants from bovine pulmonary artery. Correlation of functional with structural changes allows the authors to dissect the mechanisms responsible for endothelial damage. They have shown that incubation of intimal explants with histamine causes transient formation of interendothelial dilations and an increased rate of equilibration of tritiated water and (/sup 14/C)sucrose across the intimal explant. Exposure to endotoxin also causes interendothial dilations but the endothelial damage is more severe than that with histamine, and in vivo experiments show a more prolonged increase in pulmonary vascular permeability. Leukocyte migration has also been suggested to result in a decreased barrier function of the endothelial layer. Experiments with the endothelial layer of intimal explants and separated bovine leukocytes suggest that transendothelial migration may depend on the chemotactic stimulus. Migration toward lymphocyte-conditioned medium does result in increased equilibration of (/sup 14/C)sucrose. Finally, a theoretical model has been used to examine the permeability changes seen for the intimal explants exposed to histamine. The model consists of two compartments with radioactive tracers diffusing across a filter of known permeability. Such a model gives good agreement with data obtained in intact sheep, indicating that mathematical models allow quantitative estimates of barrier function in intimal explants that compare favorably with in vivo data.
Schiebler, Mark L.; Bhalla, Sanjeev; Runo, James; Jarjour, Nizar; Roldan, Alejandro; Chesler, Naomi; François, Christopher J.
The current Dana Point classification system (2009) divides elevation of pulmonary artery pressure into Pulmonary Arterial Hypertension (PAH) and Pulmonary Hypertension (PH). Fortunately, pulmonary arterial hypertension (PAH) is not a common disease. However, with the aging of the first world’s population, heart failure is now an important cause of pulmonary hypertension with up to 9% of the population involved. PAH is usually asymptomatic until late in the disease process. While there are indirect features of PAH found on noninvasive imaging studies, the diagnosis and management still requires right heart catheterization. Imaging features of PAH include: 1. Enlargement of the pulmonary trunk and main pulmonary arteries, 2. Decreased pulmonary arterial compliance, 3. Tapering of the peripheral pulmonary arteries, 4. Enlargement of the inferior vena cava, and 5. Increased mean transit time. The chronic requirement to generate high pulmonary arterial pressures measurably affects the right heart and main pulmonary artery. This change in physiology causes the following structural and functional alterations that have been shown to have prognostic significance: Relative area change of the pulmonary trunk, RVSVindex, RVSV, RVEDVindex, LVEDVindex, and baseline RVEF <35%. All of these variables can be quantified non-invasively and followed longitudinally in each patient using MRI to modify the treatment regimen. Untreated PAH frequently results in a rapid clinical decline and death within 3 years of diagnosis. Unfortunately, even with treatment, less than 1/2 of these patients are alive at four years. PMID:23612440
Agarwal, Richa; Gomberg-Maitland, Mardi
Pulmonary arterial hypertension (PAH) develops from an abnormal interaction between the endothelium and smooth muscle cells in the pulmonary vasculature and is characterized by a progressive rise in pulmonary vascular resistance resulting from vascular remodeling, vasoconstriction, and cellular proliferation. Currently, 3 classes of drugs are approved for the treatment of PAH based on results from small short-term clinical trials-prostacyclin analogues, endothelin receptor antagonists, and phosphodiesterase type 5 inhibitors. The pharmacologic management of PAH is rapidly evolving as newer therapeutic targets that stabilize or reverse pulmonary vascular disease and target right ventricular function are being sought and as clinical practice patterns shift in favor of earlier diagnosis and aggressive treatment. This manuscript will review the practical management aspects of currently approved PAH treatments and briefly discuss combination therapy and novel pharmacologic targets. In addition, the treatment of acute right ventricular failure and evidence (or lack thereof) for therapies in non-PAH pulmonary hypertension, such as pulmonary hypertension from left side of the heart disease, are addressed.
Neves, Paulo; Guerra, Miguel; Mâncio, Jennifer; Ponce, Paulo; Vouga, Luís
Pulmonary artery sarcomas (PAS) are extremely rare and the prognosis of patients seems to be very poor. Their clinical appearance is highly nonspecific and variable, rendering the diagnosis difficult. Surgery remains the mainstay of treatment for PAS since early radical resection could offer the only chance of a potential cure. We describe the case of a 88-year old man who was admitted in the emergency department with syncope. The diagnostic study revealed a mass in the main pulmonary artery, extending into the right and left branches and occupying almost the whole of its size. The patient was successfully submitted to complete surgical excision of the mass, which revealed to be a malignant sarcoma.
Kholdani, Cyrus A; Fares, Wassim H; Trow, Terence K
Macitentan is the most recently approved dual endothelin-receptor antagonist (ERA) for the treatment of symptomatic pulmonary arterial hypertension. Compared to other available ERAs, it demonstrates superior receptor-binding properties, with consequently improved tissue penetration, and a longer duration of action allowing for once-daily dosing. It has a favorable adverse-effect profile, with notably no demonstrable increase in the risk of hepatotoxicity or peripheral edema, but like other ERAs, it is potentially limited by significant anemia. Phase I data have demonstrated a favorable drug–drug interaction profile and no need for dose adjustment with hepatic and renal impairment. In the pivotal SERAPHIN study, treatment of symptomatic pulmonary arterial hypertension patients with macitentan led to statistically significant improvements in functional class, exercise tolerance, and hemodynamic parameters, in addition to a reduction in morbidity in an event-driven long-term trial. PMID:25473292
Kim, Kyu Seon; Jo, Eun Young; Yu, Jae Hyeon
Isolated anomalous right coronary artery originating from the pulmonary artery (ARCAPA) is a rare congenital coronary anomaly that is asymptomatic and discovered incidentally in most cases. ARCAPA is generally not considered a fatal defect in infancy or childhood, although cases of sudden death have been reported. Here, we report a 2-month-old female infant who presented with a prolonged fever that was determined to be caused by rhinovirus infection. Myocardial ischemia of the left ventricular posterior wall was already seen on echocardiography, and ARCAPA was discovered incidentally. The patient underwent successful surgical reimplantation of the right coronary artery to the aortic root to re-establish dual ostial circulation. PMID:28018453
Meyer, F J; Lossnitzer, D; Kristen, A V; Schoene, A M; Kübler, W; Katus, H A; Borst, M M
Idiopathic pulmonary arterial hypertension (IPAH) is a pulmonary vasculopathy of unknown aetiology. Dyspnoea, peripheral airway obstruction and inefficient ventilation are common in IPAH. Data on respiratory muscle function are lacking. This prospective single-centre study included 26 female and 11 male patients with IPAH in World Health Organization functional classes II-IV. Mean+/-SD pulmonary artery pressure was 48.6+/-16.9 in females and 53.1+/-22.9 mmHg in males; cardiac output was 3.7+/-1.3 and 4.2+/-1.7 L x min(-1). Maximal inspiratory pressure (PI,max) was lower in the female patients than in 20 controls (5.3+/-2.0 versus 8.2+/-2.0 kPa). In the male patients, PI,max was lower than in 25 controls (6.8+/-2.2 versus 10.5+/-3.7 kPa). Maximal expiratory pressure (PE,max) was lower in the female patients than in controls (6.2+/-2.6 versus 9.5+/-2.1 kPa), and in male patients as compared to controls (7.1+/-1.6 versus 10.3+/-3.9 kPa). There was no correlation between PI,max or PE,max and parameters of pulmonary haemodynamics or exercise testing. The ratio of mouth occlusion pressure within the first 0.1 s of inspiration and PI,max was higher in IPAH than in controls (females 0.067+/-0.066 versus 0.021+/-0.008; males 0.047+/-0.061 versus 0.023+/-0.016). In conclusion, this study provides the first evidence of inspiratory and expiratory muscle weakness in idiopathic pulmonary arterial hypertension. The pathomechanisms and the prognostic significance should be further investigated.
Ghatnekar, Angela; Chrobak, Izabela; Reese, Charlie; Stawski, Lukasz; Seta, Francesca; Wirrig, Elaine; Paez-Cortez, Jesus; Markiewicz, Margaret; Asano, Yoshihide; Harley, Russell; Silver, Richard; Feghali-Bostwick, Carol; Trojanowska, Maria
Pulmonary arterial hypertension (PAH) is a chronic and progressive disease characterized by pulmonary vasculopathy with elevation of pulmonary artery pressure, often culminating in right ventricular failure. GATA-6, a member of the GATA family of zinc-finger transcription factors, is highly expressed in quiescent vasculature and is frequently lost during vascular injury. We hypothesized that endothelial GATA-6 may play a critical role in the molecular mechanisms underlying endothelial cell (EC) dysfunction in PAH. Here we report that GATA-6 is markedly reduced in pulmonary ECs lining both occluded and nonoccluded vessels in patients with idiopathic and systemic sclerosis-associated PAH. GATA-6 transcripts are also rapidly decreased in rodent PAH models. Endothelial GATA-6 is a direct transcriptional regulator of genes controlling vascular tone [endothelin-1, endothelin-1 receptor type A, and endothelial nitric oxide synthase (eNOS)], pro-inflammatory genes, CX3CL1 (fractalkine), 5-lipoxygenease-activating protein, and markers of vascular remodeling, including PAI-1 and RhoB. Mice with the genetic deletion of GATA-6 in ECs (Gata6-KO) spontaneously develop elevated pulmonary artery pressure and increased vessel muscularization, and these features are further exacerbated in response to hypoxia. Furthermore, innate immune cells including macrophages (CD11b(+)/F4/80(+)), granulocytes (Ly6G(+)/CD45(+)), and dendritic cells (CD11b(+)/CD11c(+)) are significantly increased in normoxic Gata6-KO mice. Together, our findings suggest a critical role of endothelial GATA-6 deficiency in development and disease progression in PAH.
Chan, Christina K.; Eriksson, Inger; Johnson, Pamela Y.; Cao, Xiaofang; Westöö, Christian; Norvik, Christian; Andersson-Sjöland, Annika; Westergren-Thorsson, Gunilla; Johansson, Staffan; Hedin, Ulf; Kjellén, Lena; Wight, Thomas N.; Tran-Lundmark, Karin
Abstract Pulmonary arterial hypertension (PAH) is a lethal condition for which there is no effective curative pharmacotherapy. PAH is characterized by vasoconstriction, wall thickening of pulmonary arteries, and increased vascular resistance. Versican is a chondroitin sulfate proteoglycan in the vascular extracellular matrix that accumulates following vascular injury and promotes smooth-muscle cell proliferation in systemic arteries. Here, we investigated whether versican may play a similar role in PAH. Paraffin-embedded lung sections from patients who underwent lung transplantation to treat PAH were used for immunohistochemistry. The etiologies of PAH in the subjects involved in this study were idiopathic PAH, scleroderma, and congenital heart disease (atrial septal defect) with left-to-right shunt. Independent of the underlying etiology, increased versican immunostaining was observed in areas of medial thickening, in neointima, and in plexiform lesions. Western blot of lung tissue lysates confirmed accumulation of versican in patients with PAH. Double staining for versican and CD45 showed only occasional colocalization in neointima of high-grade lesions and plexiform lesions. In vitro, metabolic labeling with [35S]sulfate showed that human pulmonary artery smooth-muscle cells (hPASMCs) produce mainly chondroitin sulfate glycosaminoglycans. In addition, hypoxia, but not cyclic stretch, was demonstrated to increase both versican messenger RNA expression and protein synthesis by hPASMCs. Versican accumulates in vascular lesions of PAH, and the amount of versican correlates more with lesion severity than with underlying etiology or inflammation. Hypoxia is a possible regulator of versican accumulation, which may promote proliferation of pulmonary smooth-muscle cells and vascular remodeling in PAH. PMID:27683612
Kaya, Seyda Ors; Samancilar, Ozgur; Ceylan, Kenan Can
A 73-year-old man underwent left pneumonectomy for squamous cell lung carcinoma 3 years ago. The postoperative and follow-up periods were uneventful. A thrombus was detected in the left pulmonary artery stump during the last chest computed tomography (CT) scan. Anticoagulant treatment was applied: intravenous heparin for 3 days followed by oral warfarin. The follow-up chest CT examination revealed regression in the size of the thrombus. PMID:27785144
Liu, Min; Luo, Chunhai; Wang, Ying; Guo, Xiaojuan; Ma, Zhanhong; Yang, Yuanhua; Zhang, Tianjing
PURPOSE We aimed to define multiparametric magnetic resonance imaging (MRI) findings to differentiate between pulmonary artery sarcoma (PAS) and pulmonary thromboembolism (PTE). METHODS Eleven patients with suspected PTE were prospectively included to undergo pulmonary MRI before surgery or biopsy. MRI protocol included an unenhanced sequence, diffusion-weighted imaging (DWI, b=800 s/mm2) and a dynamic contrast-enhanced sequence. Morphologic characteristics including distribution, filling defect, and intensity were observed on T1-, T2-, and fat-suppressed T2-weighted imaging, DWI, and contrast-enhanced MRI. Apparent diffusion coefficient (ADC) values were calculated. RESULTS Six patients were pathologically diagnosed as PAS and the other five as chronic PTE. There were no significant differences in age, gender, presenting symptoms, D-dimer, and N-terminal pro-brain natriuretic peptide between the two groups (P > 0.05). Among MRI findings that were tested for their ability to diagnose PAS, area under the curve (AUC) was significantly higher than 0.5 for main pulmonary artery involvement (AUC, 0.83±0.13; P = 0.011), hyperintensity on fat-suppressed T2-weighted imaging (AUC, 0.82±0.14; P = 0.025), hyperintensity on DWI (AUC, 0.88±0.12; P = 0.002), contrast enhancement (AUC, 0.92±0.10; P < 0.001) and pleural effusion (AUC, 0.82±0.14; P = 0.025). Moreover, grape-like appearance in distal pulmonary artery and cardiac invasion had 100% specificity for diagnosis of PAS. However, ADC value of PAS was not significantly different than that of chronic PTE (U, 12.00; P = 0.584). CONCLUSION Hyperintense filling defect in main pulmonary artery on fat-suppressed T2-weighted imaging and DWI and contrast enhancement may help to discriminate PAS from PTE. PMID:27919861
Simsek, Pelin Ozlem; Ozcelik, Ugur; Celiker, Alpay; Yalcin, Ebru; Cobanoglu, Nazan; Pekcan, Sevgi; Alehan, Dursun; Ucar, Canan; Dogru, Deniz; Kiper, Nural
Congenital unilateral absence of a pulmonary artery is a rare anomaly most frequently accompanied by other cardiovascular anomalies. We report a 10-year-old girl presenting with fatigue and recurrent hemoptysis who was initially misdiagnosed with idiopathic pulmonary hemosiderosis. Her symptoms did not resolve despite treatment so she was referred to our center for further evaluation. We carried out an angiography which revealed the absence of the right pulmonary artery and multiple collaterals originating from the right subclavian and right internal mammary arteries supplying the right lung. During the follow-up the patient developed a severe episode of pulmonary infection and pulmonary hypertension which responded well to medical treatment. Physicians should be aware of the congenital absence of the right pulmonary artery especially in patients presenting with recurrent respiratory symptoms. Although this condition is generally considered to have a good prognosis, close observation is mandatory in order to prevent further complications and comorbidities.
El Chami, Hala; Hassoun, Paul M.
Altered immunity and inflammation are increasingly recognized features of pulmonary arterial hypertension (PAH). This is suggested by infiltration of various inflammatory cells (e.g., macrophages, T and B lymphocytes), increased cytokine and growth factor (e.g., VEGF and PDGF) expression in remodeled pulmonary vessels, and the presence of circulating chemokines and cytokines. In certain diseases associated with PAH, increased expression of growth and transcriptional (e.g., Nuclear Factor of Activated T cells or NFAT) factors, and viral protein components (e.g., HIV-1 Nef), appear to contribute directly to recruitment of inflammatory cells in remodeled vessels, and may potentially serve as specific therapeutic targets. This section provides an overview of inflammatory pathways highlighting their potential role in pulmonary vascular remodeling in PAH and the possibility of future targeted therapy. PMID:23009917
Timofeev, Julia; Ruiz, George; Fries, Melissa; Driggers, Rita W.
Background Pulmonary arterial hypertension carries a high risk of mortality in pregnancy. Recent advances in treatment may improve disease course and allow for successful management of the pregnancy. Case Report We present the case of a 20-year-old gravida 1, para 0 with diagnosis of severe primary pulmonary hypertension. The patient was managed with epoprostenol (prostacyclin) infusion via an indwelling catheter, which was initiated at 23 weeks' gestation. The dose was adjusted to the patient's symptoms and a successful vaginal delivery was achieved at 36 weeks' gestation. Although maternal postpartum course was uncomplicated, unexplained neonatal demise occurred at 11 days of life. Conclusion Successful management of pulmonary hypertension in pregnancy can be accomplished with a multidisciplinary approach and intensive therapy. Long-term effects of epoprostenol on fetal or neonatal well-being are unknown. PMID:24147238
Timofeev, Julia; Ruiz, George; Fries, Melissa; Driggers, Rita W
Background Pulmonary arterial hypertension carries a high risk of mortality in pregnancy. Recent advances in treatment may improve disease course and allow for successful management of the pregnancy. Case Report We present the case of a 20-year-old gravida 1, para 0 with diagnosis of severe primary pulmonary hypertension. The patient was managed with epoprostenol (prostacyclin) infusion via an indwelling catheter, which was initiated at 23 weeks' gestation. The dose was adjusted to the patient's symptoms and a successful vaginal delivery was achieved at 36 weeks' gestation. Although maternal postpartum course was uncomplicated, unexplained neonatal demise occurred at 11 days of life. Conclusion Successful management of pulmonary hypertension in pregnancy can be accomplished with a multidisciplinary approach and intensive therapy. Long-term effects of epoprostenol on fetal or neonatal well-being are unknown.
Ugalde P, Héctor; Rozas A, Sebastián; Sanhueza F, María Ignacia; Yubini L, María Cecilia; García B, Sebastián
Anomalies of the origin of coronary arteries are detected in 0.5-1.5% of all angiographies. Anomalous origin of the left main trunk is the most uncommon and its origin from pulmonary artery in adults is exceptional, usually because it is associated with a short survival. We report a 49-year-old female, presenting with a two months history of angina. The exercise electrocardiogram suggested ischemia. A coronary angiography was performed, showing the absence of the left main trunk in the left coronary sinus, a dilated right coronary artery, with no lesions and extensive collateral circulation to the anterior descending and circumflex arteries, with inverted flow and the left main trunk draining to the pulmonary artery. The left ventricle was mildly dilated with middle and apical anterior hypokinesia. Global systolic function was conserved. A surgical correction was decided, occluding the left main anomalous origin and performing a coronary artery bypass grafting from the left internal thoracic artery. The patient was discharged with no complications. At two years of follow-up she is symptom free and has a normal physical capacity.
Fisher, M R; Criner, G J; Fishman, A P; Hassoun, P M; Minai, O A; Scharf, S M; Fessler, H E
In patients with emphysema being evaluated for lung volume reduction surgery, Doppler echocardiography has been used to screen for pulmonary hypertension as an indicator of increased peri-operative risk. To determine the accuracy of this test, the present authors compared the results of right heart catheterisations and Doppler echocardiograms in 163 patients participating in the cardiovascular substudy of the National Emphysema Treatment Trial. Substudy patients had both catheterisation and Doppler echocardiography performed before and after randomisation. In 74 paired catheterisations and echocardiograms carried out on 63 patients, the mean values of invasively measured pulmonary artery systolic pressures and the estimated right ventricular systolic pressures were similar. However, using the World Health Organization's definitions of pulmonary hypertension, echocardiography had a sensitivity of 60%, specificity of 74%, positive predictive value of 68% and a negative predictive value of 67% compared with the invasive measurement. Bland-Altman analysis revealed a bias of 0.37 kPa with 95% limits of agreement from -2.5-3.2 kPa. In patients with severe emphysema, echocardiographic estimates of pulmonary artery pressures correlate very weakly with right heart catheterisations, and the test characteristics (e.g. sensitivity, specificity, etc.) of echocardiographic assessments are poor.
Alvarez-Díaz, F.; Brito, J. M.; Cordovilla, G.; De León, J. Pérez; Sanchez, P. A.; Bordiú, C. M.
The results of 180 cases of congenital heart disease with diminished pulmonary flow operated upon with Waterston's technique are presented. It is considered that Waterston's operation is to be preferred in children under 2 years of age and in older children who have had a previous thrombotic or insufficient Blalock operation and in whom total correction is not indicated. The problem of pseudotruncus with hypoplastic pulmonary arteries is discussed. The convenience of the Waterston operation in these cases, and the importance of creating an anastomosis at the pulmonary bifurcation and as far back as possible in the aorta, is emphasized. The need to perform this technique in the correct way is stressed. This will avoid the kinking and pulling of the right pulmonary artery, which are causes of preferential blood flow to the right lung, as we have demonstrated experimentally. The possible complications caused by such a technical failure are discussed. The necessity for previous angiocardiographic study, in order properly to repair the defect during total correction, is also considered. Images PMID:4731106
Kawata, Hiroaki; Kishimoto, H; Iwai, S; Ishimaru, K; Saito, T; Kayatani, F; Inamura, N; Hamamichi, Y; Kawada, Y; Nasuno, S; Maekawa, S
We assessed the effect of reconstructing the pulmonary artery during arterial switch surgery for transposition of the great arteries on late pulmonary stenosis. Sixty-five patients who underwent Lecompte procedure between September 1991 and December 2006 were divided, by the procedure used chronologically to reconstruct the pulmonary artery, into group XP (single pantaloon patch with equine pericardium, n = 11), group P (direct reconstruction, n = 47), and group AP (single pantaloon patch with fresh autopericardium, n = 7). Outcome and pulmonary stenosis on the most recent ultrasound cardiography (UCG) were compared in the 3 groups. The median follow-up was 13, 7.5, and 1.3 years, respectively. Both early and late mortalities were 1.5% (1/65). Although percutaneous trans-pulmonary angioplasty was necessary in 1, 13, and 3 patients, there was 1, 1, and 0 reoperation for pulmonary stenosis in the 3 groups, respectively. Pulmonary stenosis (pulmonary arterial maximum flow velocity > 3 m/sec on UCG) was present in 4 (40%). 14 (30%). and 3 patients (43%). Although there was no significant difference among the 3 procedures in preventing pulmonary stenosis 10 years after arterial switch surgery, direct reconstruction of the pulmonary artery may show a superior outcome, in particular, over 10 years after arterial switch surgery.
Su, Junjing; Hilberg, Ole; Howard, Luke; Simonsen, Ulf; Hughes, Alun D
Mean pulmonary arterial pressure and pulmonary vascular resistance remain the most common hemodynamic measures to evaluate the severity and prognosis of pulmonary hypertension. However, pulmonary vascular resistance only captures the non-oscillatory component of the right ventricular hydraulic load and neglects the dynamic compliance of the pulmonary arteries and the contribution of wave transmission. Wave intensity analysis offers an alternative way to assess the pulmonary vasculature in health and disease. Wave speed is a measure of arterial stiffness and the magnitude and timing of wave reflection provide information on the degree of impedance mismatch between the proximal and distal circulation. Studies in the pulmonary artery have demonstrated distinct differences in arterial wave propagation between individuals with and without pulmonary vascular disease. Notably, greater wave speed and greater wave reflection are observed in patients with pulmonary hypertension and in animal models exposed to hypoxia. Studying wave propagation makes a valuable contribution to the assessment of the arterial system in pulmonary hypertension and here, we briefly review the current state of knowledge of the methods used to evaluate arterial waves in the pulmonary artery. PMID:27636734
Hunter, Kendall S.; Feinstein, Jeffrey A.; Ivy, D. Dunbar; Shandas, Robin
The hemodynamic state of the pulmonary arteries is challenging to routinely measure in children due to the vascular circuit's position in the lungs. The resulting relative scarcity of quantitative clinical diagnostic and prognostic information impairs management of diseases such as pulmonary hypertension, or high blood pressure of the pulmonary circuit, and invites new techniques of measurement. Here we examine recent applications of macro-scale computational mechanics methods for fluids and solids – traditionally used by engineers in the design and virtual testing of complex metal and composite structures – applied to study the pulmonary vasculature, both in healthy and diseased states. In four subject areas, we briefly outline advances in computational methodology and provide examples of clinical relevance. PMID:21499523
Han, Ying; Cho, Young-Eun; Ayon, Ramon; Guo, Rui; Youssef, Katia D.; Pan, Minglin; Dai, Anzhi; Yuan, Jason X.-J.
Inhibitors of sodium-glucose cotransporter (SGLT)2 are a new class of oral drugs for type 2 diabetic patients that reduce plasma glucose levels by inhibiting renal glucose reabsorption. There is increasing evidence showing the beneficial effect of SGLT2 inhibitors on glucose control; however, less information is available regarding the impact of SGLT2 inhibitors on cardiovascular outcomes. The present study was designed to determine whether SGLT inhibitors regulate vascular relaxation in mouse pulmonary and coronary arteries. Phlorizin (a nonspecific SGLT inhibitor) and canagliflozin (a SGLT2-specific inhibitor) relaxed pulmonary arteries in a dose-dependent manner, but they had little or no effect on coronary arteries. Pretreatment with phlorizin or canagliflozin significantly inhibited sodium nitroprusside (SNP; a nitric oxide donor)-induced vascular relaxation in pulmonary arteries but not in coronary arteries. Phlorizin had no effect on cGMP-dependent relaxation in pulmonary arteries. SNP induced membrane hyperpolarization in human pulmonary artery smooth muscle cells, and pretreatment of cells with phlorizin and canagliflozin attenuated SNP-induced membrane hyperpolarization by decreasing K+ activities induced by SNP. Contrary to the result observed in ex vivo experiments with SGLT inhibitors, SNP-dependent relaxation in pulmonary arteries was not altered by chronic administration of canagliflozin. On the other hand, canagliflozin administration significantly enhanced SNP-dependent relaxation in coronary arteries in diabetic mice. These data suggest that SGLT inhibitors differentially regulate vascular relaxation depending on the type of arteries, duration of the treatment, and health condition, such as diabetes. PMID:26361875
Hirose, Takashi; Ishikawa, Noboru; Hamada, Kenji; Inagaki, Tomoko; Kusumoto, Sojiro; Shirai, Takao; Okuda, Kentaro; Ohnishi, Tsukasa; Kadokura, Mitsutaka; Adachi, Mitsuru
We report on a 45-year-old woman with intimal sarcoma of the pulmonary artery. She presented with a chief complaint of shortness of breath. Computed tomography (CT) of the chest showed an intraluminal hypoattenuated area extending from the main pulmonary artery into the right main pulmonary artery and bilateral lobar pulmonary arteries. She underwent resection of the lobulated mass from the pulmonary artery. The tumor was diagnosed as an intimal sarcoma. Although she received chemotherapy with amrubicin and carboplatin when the tumor recurred, the tumor enlarged. After radiotherapy was performed, CT of the chest showed shrinkage of the tumor and the regression of consolidation and ground-glass opacity. Radiotherapy and chemotherapy are treatment option for patients with pulmonary artery sarcoma.
Han, Daehee; Lee, Kyung Soo; Franquet, Tomas; Müller, Nestor L; Kim, Tae Sung; Kim, Hojoong; Kwon, O Jung; Byun, Hong Sik
Along with clinical examination and laboratory tests, imaging plays a key role in the diagnosis of pulmonary embolism. Multi-detector row helical computed tomography (CT) is particularly helpful in the diagnosis of acute pulmonary thromboembolism (PTE) owing to its capacity to directly show emboli as intravascular filling defects. Although parenchymal abnormalities at CT are nonspecific for acute PTE, they may contribute to a correct diagnosis of chronic PTE, the characteristic helical CT features of which are similar to its angiographic features and include webs or bands, intimal irregularities, abrupt narrowing or complete obstruction of the pulmonary arteries, and "pouching defect." Nonthrombotic pulmonary embolism is an uncommon condition but is sometimes associated with specific imaging findings, including discrete nodules with cavitation (septic embolism), widespread homogeneous and heterogeneous areas of increased opacity or attenuation that typically appear 12-24 hours after trauma (fat embolism), and fine miliary nodules that subsequently coalesce into large areas of increased opacity or attenuation (talcosis). Knowledge of appropriate imaging methods and familiarity with the specific imaging features of pulmonary embolism should facilitate prompt, effective diagnosis.
Patel, Dhara; Kandhi, Sharath; Kelly, Melissa; Neo, Boon Hwa
The activity of glucose-6-phosphate dehydrogenase (G6PD) controls a vascular smooth muscle relaxing mechanism promoted by the oxidation of cytosolic NADPH, which has been associated with activation of the 1α form of protein kinase G (PKG-1α) by a thiol oxidation-elicited subunit dimerization. This PKG-1α-activation mechanism appears to contribute to responses of isolated endothelium-removed bovine pulmonary arteries (BPA) elicited by peroxide, cytosolic NADPH oxidation resulting from G6PD inhibition, and hypoxia. Dehydroepiandrosterone (DHEA) is a steroid hormone with pulmonary vasodilator activity, which has beneficial effects in treating pulmonary hypertension. Because multiple mechanisms have been suggested for the vascular effects of DHEA and one of the known actions of DHEA is inhibiting G6PD, we investigated whether it promoted relaxation associated with NADPH oxidation, PKG-1α dimerization, and PKG activation detected by increased vasodilator-stimulated phosphoprotein (VASP) phosphorylation. Relaxation of BPA to DHEA under aerobic or hypoxic conditions was associated with NADPH oxidation, PKG-1α dimerization, and increased VASP phosphorylation. The vasodilator activity of DHEA was markedly attenuated in pulmonary arteries and aorta from a PKG knockin mouse containing a serine in place of a cysteine involved in PKG dimerization. DHEA promoted increased PKG dimerization in lungs from wild-type mice, which was not detected in the PKG knockin mouse model. Thus PKG-1α dimerization is a major contributing factor to the vasodilator actions of DHEA and perhaps its beneficial effects in treating pulmonary hypertension. PMID:24375799
Timmers, Liesbeth; Bové, Thierry; De Pauw, Michel
Intimal sarcoma of the pulmonary artery (PAS) is a rare but potentially lethal tumour, frequently misdiagnosed as chronic thrombo-embolic pulmonary artery disease. Despite the availability of advanced imaging technologies, its preoperative diagnosis remains difficult. We report on two patients with clinical features mimicking chronic pulmonary thrombo-embolism. Further discussion will focus on the differential diagnosis with more classical causes of obstructive pulmonary vascular disease.
Bornak, Arash; Baqai, Atif; Li, Xiaoyi; Rey, Jorge; Tashiro, Jun; Velazquez, Omaida C
Enlarging aneurysms in the thoracic aorta frequently remain asymptomatic. Fistulization of thoracic aortic aneurysms (TAA) to adjacent structures or the presence of a patent ductus arteriosus and TAA may lead to irreversible cardiopulmonary sequelae. This article reports on a large aneurysm of the thoracic aorta with communication to the pulmonary artery causing pulmonary edema and cardiorespiratory failure. The communication was ultimately closed after thoracic endovascular aortic aneurysm repair allowing rapid symptom resolution. Early diagnosis and closure of such communication in the presence of TAA are critical for prevention of permanent cardiopulmonary damage.
Ludwig, J.W.; Verhoeven, L.A.J.; Kersbergen, J.J.; Overtoom, T.T.C.
A comparative study of radionuclide scanning (perfusion studies in all 18 patients and ventilation studies in 9) and digital subtraction angiography (DSA) was performed in 18 patients with suspected pulmonary thromboembolism. In 17 patients good visualization of the arteries was obtained with DSA; 10 of these patients had no pre-existing lung disease, and 7 had chronic obstructive pulmonary disease (COPD). The information provided by DSA in this small group was equal to or better than that of scintigraphy, especially in patients with COPD, and the reliability of DSA was superior to that of the radionuclide scintigraphy. Methods for preventing motion artifacts with DSA are also described.
Ramjee, Vimal; Lewis, Melinda M; Clements, Stephen D
Pulmonary artery sarcomas are exceptionally rare, and they are often misdiagnosed as chronic pulmonary thromboemboli. Early and accurate diagnosis is crucial to the prognosis of patients who have pulmonary artery sarcomas.Herein, we describe the case of a 74-year-old man who presented with dyspnea and was initially thought to have a pulmonary embolus. Anticoagulation with unfractionated heparin was ineffective. Rare angiographic findings during routine cardiac catheterization led to the diagnosis of a high-grade, nonmyogenic, primary pulmonary artery sarcoma. This case illustrates the usefulness of angiographic findings as an adjunct to conventional diagnostic methods in correctly identifying this rare, aggressive malignancy.
Introduction Disconnected pulmonary arteries are unusual and may result in pulmonary hypertension with acute right heart failure. Case presentation We report a case of a three-month-old Asian girl who presented with heart failure and severe pulmonary hypertension due to a disconnected right pulmonary artery. An epoprostenol (prostacyclin) infusion was instrumental in lowering pulmonary artery pressures and stabilizing the child prior to surgery. Conclusions This is, to the best of our knowledge, the first report of successful prostacyclin usage in such a situation. PMID:20525186
Kheyfets, Vitaly O.; Schroeder, Joyce D.; Dunning, Jamie; Shandas, Robin; Buckner, J. Kern; Browning, James; Hertzberg, Jean; Hunter, Kendall S.; Fenster, Brett E.
Abstract Pulmonary hypertension (PH) is associated with proximal pulmonary arterial remodeling characterized by increased vessel diameter, wall thickening, and stiffness. In vivo assessment of wall shear stress (WSS) may provide insights into the relationships between pulmonary hemodynamics and vascular remodeling. We investigated the relationship between main pulmonary artery (MPA) WSS and pulmonary hemodynamics as well as markers of stiffness. As part of a prospective study, 17 PH patients and 5 controls underwent same-day four-dimensional flow cardiac magnetic resonance imaging (4-D CMR) and right heart catheterization. Streamwise velocity profiles were generated in the cross-sectional MPA in 45° increments from velocity vector fields determined by 4-D CMR. WSS was calculated as the product of hematocrit-dependent viscosity and shear rate generated from the spatial gradient of the velocity profiles. In-plane average MPA WSS was significantly decreased in the PH cohort compared with that in controls (0.18 ± 0.07 vs. 0.32 ± 0.08 N/m2; P = 0.01). In-plane MPA WSS showed strong inverse correlations with multiple hemodynamic indices, including pulmonary resistance (ρ = −0.74, P < 0.001), mean pulmonary pressure (ρ = −0.64, P = 0.006), and elastance (ρ = −0.70, P < 0.001). In addition, MPA WSS had significant associations with markers of stiffness, including capacitance (ρ = 0.67, P < 0.001), distensibility (ρ = 0.52, P = 0.013), and elastic modulus (ρ = −0.54, P = 0.01). In conclusion, MPA WSS is decreased in PH and is significantly associated with invasive hemodynamic indices and markers of stiffness. 4-D CMR–based assessment of WSS may represent a novel methodology to study blood-vessel wall interactions in PH. PMID:27076906
Tahara, Masahiro; Shimozono, Saiko; Nitta, Tetsuya; Yamaki, Shigeo
Congestive heart failure is a major cause of early death in patients with trisomy 13 or 18 and congenital heart disease (CHD). Pulmonary artery banding for these patients early in life is preferred to protect the lungs from high pulmonary flow rates and improve survival. We performed open lung biopsies in 11 patients with trisomy 13 or 18 accompanied by CHD and severe pulmonary artery hypertension (PAH) between 2009 and 2011. Two (18.2%) of these 11 patients had medial defects of the small pulmonary arteries. One patient with trisomy 13 and an atrial septal defect developed lung hemorrhage and lung edema at the age of 9 months and died at the age of 13 months. The lumens of the small pulmonary arteries of the other patient with trisomy 18 and a ventricular septal defect became occluded due to the intimal proliferation of fibrous tissues at the age of 2 months. This patient died at the age of 27 months. The deaths of both patients were associated with heart-related factors. Patients with medial defects are vulnerable to intimal proliferation in the small pulmonary arteries. More patients with trisomy 13 or 18 and CHD might have similar pulmonary vascular changes. The small pulmonary arteries of patients with trisomy 13 and 18 should be further analyzed.
Pousada, Guillermo; Baloira, Adolfo; Valverde, Diana
Pulmonary Arterial Hypertension (PAH) is a rare and progressive disease with low incidence and prevalence, and elevated mortality. PAH is characterized by increased mean pulmonary artery pressure. The aim of this study was to analyse patients with combined mutations in BMPR2, ACVRL1, ENG and KCNA5 genes and to establish a genotype-phenotype correlation. Major genes were analysed by polymerase chain reaction (PCR) and direct sequencing. Genotype-phenotype correlation was performed. Fifty-seven (28 idiopathic PAH, 29 associated PAH group I) were included. Several mutations in different genes, classified as pathogenic by in silico analysis, were present in 26% of PAH patients. The most commonly involved gene was BMPR2 (12 patients) followed by ENG gene (9 patients). ACVRL1 and KCNA5 genes showed very low incidence of mutations (5 and 1 patients, respectively). Genotype-phenotype correlation showed statistically significant differences for gender (p = 0.045), age at diagnosis (p = 0.035), pulmonary vascular resistance (p = 0.030), cardiac index (p = 0.035) and absence of response to treatment (p = 0.011). PAH is consequence of a heterogeneous constellation of genetic arrangements. Patients with several pathogenic mutations seem to display a more severe phenotype. PMID:27630060
Fernandez-Bonetti, P; Lupi-Herrera, E; Martinez-Guerra, M L; Barrios, R; Seoane, M; Sandoval, J
The mechanical properties of the lung were studied in ten nonsmokers with idiopathic pulmonary artery hypertension (IPAH) (mean pulmonary artery pressure 65.7 +/- 30 mm Hg). In the routine lung test, residual volume was found to be abnormal (greater than 120 percent of the predicted) in seven patients, and measured airway resistance was normal in eight out of the ten patients. A decreased FEF 75-85 percent, abnormal values for the helium-air flow ratios and increased closing capacities were documented in eight of ten patients in whom lung elastic recoil was normal (six of ten) or increased (four of ten). These features suggest peripheral airways obstruction (PAO) which was also supported by histopathologic findings in three cases (one biopsy and two necropsies). The observed changes in lung compliance could be related to the behavior of the coupling of the air-space and vascular compartments. The etiology of PAO in IPAH patients is not known, but our results indicate that both the peripheral airways and the pulmonary circulation are affected. The knowledge of PAO in IPAH patients could help to better understand the observed V/Q inequality in this entity.
Takatsuki, Shinichi; Calderbank, Michelle; Ivy, David Dunbar
This study aimed to investigate the safety, tolerability, and effects of tadalafil on children with pulmonary arterial hypertension (PAH) after transition from sildenafil or after tadalafil received as initial therapy. A total of 33 pediatric patients with PAH were retrospectively evaluated. Of the 33 patients, 29 were switched from sildenafil to tadalafil. The main reason for the change from sildenafil was once-daily dosing. The average dose of sildenafil was 3.4 ± 1.1 mg/kg/day, and that of tadalafil was 1.0 ± 0.4 mg/kg/day. For 14 of the 29 patients undergoing repeat catheterization, statistically significant improvements were observed after transition from sildenafil to tadalafil in terms of mean pulmonary arterial pressure (53.2 ± 18.3 vs. 47.4 ± 13.7 mmHg; p < 0.05) and pulmonary vascular resistance index (12.2 ± 7.0 vs 10.6 ± 7.2 Units/m(2); p < 0.05). Clinical improvement was noted for four patients treated with tadalafil as initial therapy. The side effect profiles were similar for the patients who had transitioned from sildenafil to tadalafil including headache, nausea, myalgia, nasal congestion, flushing, and allergic reaction. Two patients discontinued tadalafil due to migraine or allergic reaction. One patient receiving sildenafil had no breakthrough syncope after transition to tadalafil. Tadalafil can be safely used for pediatric patients with PAH and may prevent disease progression.
LeVarge, Barbara L
Prostacyclin is an endogenous eicosanoid produced by endothelial cells; through actions on vascular smooth-muscle cells, it promotes vasodilation. Pulmonary arterial hypertension (PAH) is characterized by elevated mean pulmonary artery pressure due to a high pulmonary vascular resistance state. A relative decrease in prostacyclin presence has been associated with PAH; this pathway has thus become a therapeutic target. Epoprostenol, the synthetic equivalent of prostacyclin, was first utilized as short-term or bridging therapy in the 1980s. Further refinement of its long-term use via continuous intravenous infusion followed. A randomized controlled trial by Barst et al in 1996 demonstrated functional, hemodynamic, and mortality benefits of epoprostenol use. This work was a groundbreaking achievement in the management of PAH and initiated a wave of research that markedly altered the dismal prognosis previously associated with PAH. Analogs of prostacyclin, including iloprost and treprostinil, exhibit increased stability and allow for an extended array of parenteral and non-parenteral (inhaled and oral) therapeutic options. This review further examines the pharmacology and clinical use of epoprostenol and its analogs in PAH. PMID:25848300
Hu, Bangchuan; Gong, Shijin; Yu, Yihua; Dai, Haiwen
Arterial stiffness contributes to heart failure and is decreased by angiotensin receptor blockers (ARBs). This cross-sectional study aimed to assess associations of lung function and ARB with arterial stiffness in patients with chronic heart failure. 354 outpatients (168 males; 186 females; 68.2 ± 7.2 years old) with chronic heart failure were evaluated. Lung function parameters, including forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), and FEV1 to FVC ratio (FEV1/FVC), were assessed. The cardio-ankle vascular index (CAVI) was used to estimate arterial stiffness. Unadjusted correlation analyses revealed a positive association of CAVI with ARB but not ACEI, and a negative correlation with FEV1 (r = −0.2987, p < 0.0001). Multiple stepwise regression analyses showed that ARB and FEV1 (p < 0.0001) were independent predicting factors for CAVI. These findings suggest that reduced pulmonary function is associated with increased CAVI. Pulmonary function protection could be used to improve the prognosis in heart failure, but additional studies are necessary. PMID:28097138
Causes of pulmonary arterial hypertension (PAH) are similar in adults and children. The main difference is that PAH secondary to congenital heart diseases, is the predominant cause in pediatric patients. Persistent pulmonary hypertension of the newborn shows completely different clinical course and pathophysiological mechanisms. It is usually seen in full term babies with a high morbidity and mortality rate. Improved prognosis has been reported with inhaled nitric oxide (NO) and extracorporeal membrane oxygenation therapy in babies hospitalized in well equipped and experienced newborn centers. Primary pulmonary hypertension and familial pulmonary hypertension are rare in pediatric age group because the diagnosis is initially made in adolescence. The incidence of PAH secondary to congenital heart disease is estimated as 1.6 - 12.5 case/million/year. Eisenmenger syndrome is diagnosed in 1% of patients with PAH. Patients with left to right shunts are the main group who develop pulmonary vascular disease if not treated in the early infancy. Some cyanotic congenital heart diseases are also the causes of PAH. The best treatment of patients at risk for the development of pulmonary vascular disease is prevention by early surgical elimination of defects or repairing the anatomy. Treatment options with vasodilating agents like NO, prostaglandin analogs, phosphodiesterase -5 inhibitors and endothelin receptor antagonists are used to improve survival and quality of life. Heart lung or bilateral lung transplantation is the only surgical option for many of these patients. Results of national and international registries will bring valuable epidemiological and prognostic perspectives to pediatric PAH.
Szenczi, Orsolya; Karlócai, Kristóf; Bucsek, László; Rigó, János
Idiopathic pulmonary arterial hypertension is characterized by progressive increase in pulmonary arterial pressure and pulmonary vascular resistance which lead to right ventricular failure and death. Pregnancy in patients with idiopathic pulmonary arterial hypertension is contraindicated because of the high maternal and fetal mortality. The authors present a case of successful pregnancy and delivery of a patient with idiopathic pulmonary arterial hypertension in Hungary for the first time. The aim of the report was to demonstrate that management and treatment of idiopathic pulmonary arterial hypertension in a pregnant woman is a complex and multidisciplinary task that should involve obstetrician, cardiologist and anesthesiologist. Those patients who become pregnant and do not wish to terminate the pregnancy must be referred to obstetric centers where a multidiciplinary approach is taken.
Choi, Eui-Young; Yoon, Young-Won; Kwon, Hyuck Moon; Kim, Dongsoo; Park, Byung-Eun; Hong, Yoo-Sun; Koo, Ja-Seung; Kim, Tae-Hoon; Kim, Hyun-Seung
Pulmonary artery intimal sarcoma is a rare highly lethal disease, with additional retrograde extension to pulmonic valve and right ventricle being an extremely rare condition. It is frequently mistaken for pulmonary thromboembolism. We report a case of 64-year-old woman with progressive dyspnea initially suspected and treated for pulmonary thromboembolism. Her helical chest CT scan with 3 dimensional (3D) reconstruction combined with echocardiography revealed a compacting main pulmonary artery mass extending to the right ventricular outflow tract and the right pulmonary artery. After excision of the mass, the patient's condition improved dramatically, and the pathologic findings revealed pulmonary intimal sarcoma. This report emphasizes that helical chest CT with 3D reconstruction can be an important tool to differentiate the characteristics of pulmonary artery lesions, such as intimal sarcoma and thromboembolism.
Schuuring, Mark J.; Bonta, Peter I.; van Vugt, Michele; Smithuis, Frank; van Delden, Otto M.; Annema, Jouke T.; Stijnis, Kees
A 44-year-old woman with a history of pulmonary embolism and abdominal echinococcosis complained of sudden thoracic pain and shortness of breath. A D-dimer of 77.5 mg/l (reference ≤0.5 mg/l) was found. Chest CT scan revealed obstruction of the right lower and middle lobe pulmonary artery (PA). Anticoagulation therapy was initiated for the presumed diagnosis of recurrent pulmonary embolism. However, due to persistent symptoms of dyspnea, follow-up CT angiography of the chest was performed 3 months later. A persistent PA obstruction was found and the presumed diagnosis of embolism was questioned. Subsequently, endobronchial ultrasound (EBUS) imaging was performed to support an alternative diagnosis. EBUS imaging showed an inhomogeneous, sharply demarcated, intravascular lesion with round hypoechoic areas compatible with cysts. The diagnosis of embolism was rejected and treatment with albendazole was initiated for pulmonary echinococcosis. Echinococcosis is a parasitic disease and cystic spread in the PA is exceptional. The patient has remained stable for more than 4 years. In case of disease progression, including progressive PA obstruction or life-threatening hemoptysis, surgical resection will be considered. PMID:27760423
Kim, Hae Jin
Pulmonary arterial hypertension (PAH) is a progressive disease characterized by vascular remodeling of pulmonary arteries (PAs) and increased vascular resistance in the lung. Monocrotaline (MCT), a toxic alkaloid, is widely used for developing rat models of PAH caused by injury to pulmonary endothelial cells; however, characteristics of vascular functions in MCT-induced PAH vary and are not fully understood. Here, we investigated hypoxic pulmonary vasoconstriction (HPV) responses and effects of various vasoconstrictors with isolated/perfused lungs of MCT-induced PAH (PAH-MCT) rats. Using hematoxylin and eosin staining, we confirmed vascular remodeling (i.e., medial thickening of PA) and right ventricle hypertrophy in PAH-MCT rats. The basal pulmonary arterial pressure (PAP) and PAP increase by a raised flow rate (40 mL/min) were higher in the PAH-MCT than in the control rats. In addition, both high K+ (40 mM KCl)- and angiotensin II-induced PAP increases were higher in the PAH-MCT than in the control rats. Surprisingly, application of a nitric oxide synthase inhibitor, L-NG-Nitroarginine methyl ester (L-NAME), induced a marked PAP increase in the PAH-MCT rats, suggesting that endothelial functions were recovered in the three-week PAH-MCT rats. In addition, the medial thickening of the PA was similar to that in chronic hypoxia-induced PAH (PAH-CH) rats. However, the HPV response (i.e., PAP increased by acute hypoxia) was not affected in the MCT rats, whereas HPV disappeared in the PAH-CH rats. These results showed that vascular contractility and HPV remain robust in the MCT-induced PAH rat model with vascular remodeling. PMID:27847441
Al-Dairy, Alwaleed; Rezaei, Yousef; Pouraliakbar, Hamidreza; Mahdavi, Mohammad; Bayati, Parvin
Anomalous origin of the right coronary artery from the pulmonary artery (ARCAPA) is a very rare congenital heart defect. Herein, we describe three cases of ARCAPA in an 8 months old, 18 months old, and 4 year old child. Two cases were incidentally diagnosed using a computed tomographic angiograph, and the other was incidentally diagnosed using a coronary angiograph. These cases underwent a reimplantation technique on diagnosis and resulting in positive clinical outcomes during the follow-up period which was a mean of 1.5 years. PMID:28154604
Silverman, Norman H
In the 1970s, diagnosing anomalous origin of the left coronary artery from the pulmonary artery (ALCAPA) was often uncertain using imaging alone; however, with the advances in high-frequency transducers, advanced image processing, and other ultrasound modalities such as Doppler colour flow imaging, tissue Doppler imaging, and speckle tracking to asses regional wall motion abnormalities, modern echocardiography now permits accurate diagnosis of ALCAPA with greater certainty. Although many consider ultrasound to be the only imaging test necessary if there is a question as to the diagnosis, other imaging modalities such as MRI, CT, and cardiac catheterisation with angiography remain valuable complementary tests, especially in older patients.
Pugh, Meredith E; Hemnes, Anna R
Pulmonary arterial hypertension (PAH) is a progressive disease of the pulmonary vasculature, ultimately resulting in right heart failure and death. This disease is strongly predominant in females, although little is known regarding how sex influences disease development. Recent developments highlighting the importance of estrogen metabolites in both animal models and human disease have substantially increased our understanding of PAH in women. This review will focus on general knowledge of PAH, translational and basic science data regarding sex hormones in the pulmonary vasculature and on clinical issues that are particular to women with PAH. Future directions for study include the influence of sex hormones on right ventricular responses, improving the understanding of the influence of estrogen exposure in human disease and the study of dehydroepiandrosterone in basic science and human disease. PMID:20187732
Sugimoto, Koichi; Yoshihisa, Akiomi; Nakazato, Kazuhiko; Jin, Yuichiro; Suzuki, Satoshi; Yokokawa, Tetsuro; Misaka, Tomofumi; Yamaki, Takayoshi; Kunii, Hiroyuki; Suzuki, Hitoshi; Saitoh, Shu-ichi; Takeishi, Yasuchika
Background Although pulmonary hypertension due to left heart disease (LHD-PH) accounts for the largest proportion of pulmonary hypertension, few reports on the epidemiological analysis of LHD-PH exist. Recently, pulmonary arterial capacitance (PAC) has attracted attention as a possible factor of right ventricular afterload along with pulmonary vascular resistance. We therefore investigated the clinical significance of PAC in LHD-PH. Methods The subject consisted of 252 LHD-PH patients (145 men, mean age 63.4 ± 14.7 years) diagnosed by right heart catheterization. PAC was estimated by the ratio between stroke volume and pulmonary arterial pulse pressure. Patients were classified into four groups according to the PAC (1st quartile was 0.74 to 1.76 ml/mmHg, the 2nd quartile 1.77 to 2.53 ml/mmHg, the 3rd quartile 2.54 to 3.59 ml/mmHg, and the 4th quartile 3.61 to 12.14 ml/mmHg). The end-points were defined as rehospitalization due to worsening heart failure and/or cardiac death. The Cox proportional hazard regression model was used to determine what variables were associated with cardiac events. Results The patients in the 1st quartile had the lowest cardiac index and stroke volume index, and the highest mean pulmonary arterial pressure, mean pulmonary capillary wedge pressure, and pulmonary vascular resistance compared with the 2nd, 3rd, and 4th quartiles. Fifty-four patients experienced cardiac events during the follow-up period (median 943 days). The event-free rate of the 1st quartile was significantly lower than that of the 3rd and 4th quartiles (66.7% vs 82.5% [3rd quartile], P = 0.008; and 92.1% [4th quartile], P < 0.001). The Cox hazard analysis revealed that PAC was significantly associated with cardiac events (HR 0.556, 95% CI 0.424–0.730, P < 0.001). Conclusion PAC is useful in the prediction of cardiac event risk in LHD-PH patients. PMID:27875533
Hussain, Azar; Bennett, Robert T; Chaudhry, Mubarak A; Qadri, Syed S; Cowen, Mike; Morice, Alyn H; Loubani, Mahmoud
AIM To determine the optimum resting tension (ORT) for in vitro human pulmonary artery (PA) ring preparations. METHODS Pulmonary arteries were dissected from disease free sections of the resected lung in the operating theatre and tissue samples were directly sent to the laboratory in Krebs-Henseleit solution (Krebs). The pulmonary arteries were then cut into 2 mm long rings. PA rings were mounted in 25 mL organ baths or 8 mL myograph chambers containing Krebs compound (37 °C, bubbled with 21% O2: 5% CO2) to measure changes in isometric tension. The resting tension was set at 1-gram force (gf) with vessels being left static to equilibrate for duration of one hour. Baseline contractile reactions to 40 mmol/L KCl were obtained from a resting tension of 1 gf. Contractile reactions to 40 mmol/L KCl were then obtained from stepwise increases in resting tension (1.2, 1.4, 1.6, 1.8 and 2.0 gf). RESULTS Twenty PA rings of internal diameter between 2-4 mm were prepared from 4 patients. In human PA rings incrementing the tension during rest stance by 0.6 gf, up to 1.6 gf significantly augmented the 40 mmol/L KCl stimulated tension. Further enhancement of active tension by 0.4 gf, up to 2.0 gf mitigate the 40 mmol/L KCl stimulated reaction. Both Myograph and the organ bath demonstrated identical conclusions, supporting that the radial optimal resting tension for human PA ring was 1.61 g. CONCLUSION The radial optimal resting tension in our experiment is 1.61 gf (15.78 mN) for human PA rings. PMID:27721938
Zhang, Yun-yun; Xu, Fan; Chu, Ming; Bi, Li-qing
Objective: To assess the incidence, possible risk factors and prognosis of pulmonary arterial hypertension (PAH) in critically ill elderly patients. Methods: We selected 122 cases admitted to the ICU, ages 60–93 years old. An echocardiography examination was performed within four days after admission to the ICU. PAH is usually suspected if the patient’s pulmonary artery systolic pressure ≥ 40 mmHg. We collected echocardiography data, relevant clinical data and routine laboratory data; we then used a statistical method to analyze the risk factors for PAH in critically ill elderly patients and examined its impact on the prognosis. Results: Total 51 patients were diagnosed with PAH. The prevalence of critically ill elderly patients with PAH was 41.8%. The ANOVA analysis showed that if patients had COPD (P = 0.031) and/or respiratory failure (P = 0.021), they were more prone to PAH. An enlarged left atrium (P = 0.038) and/or right ventricle (P = 0.029), a declining left ventricle fractional shortening rate (P = 0.038), and an elevated amount of the brain natriuretic peptides (P = 0.046) were all associated with the occurrence of PAH. Multivariate regression analysis showed that the left atrial diameter (P = 0.045) was the risk factor in critically ill elderly patients with PAH. The 30-day mortality rate was 33.3% for elderly patients with PAH, which is statistically significant (P = 0.035) when compared with the mortality rate of patients with normal pulmonary artery pressure. Our multivariate regression analysis also showed that, for critically ill elderly patients admitted in the ICU, PAH (P = 0.039) is risk factor for increased mortality. Conclusions: A higher incidence of PAH occurs in critically ill elderly patients. PAH is more likely to occur in patients with an enlarged left atrium, and these problems adversely impact the prognosis. PMID:28367167
Gupta, Nilesh; Ibrahim, Hany M; Ahsan, Fakhrul
This study investigates the respirability and efficacy of peptide-micelle hybrid nanoparticles as carriers for inhalational therapy of pulmonary arterial hypertension (PAH). CARSKNKDC (CAR), a cell-penetrating and lung-homing peptide, conjugated polyethylene glycol-distearoyl-phosphoethanolamine micelles containing fasudil, an investigational anti-PAH drug, were prepared by solvent evaporation method and characterized for various physicochemical properties. The pharmacokinetics and pharmacological efficacy of hybrid particles containing fasudil were evaluated in healthy rats and monocrotaline-induced PAH rats. CAR micelles containing fasudil had an entrapment efficiency of approximately 58%, showed controlled release of the drug, and were monodispersed with an average size of approximately 14 nm. Nuclear magnetic resonance scan confirmed the drug's presence in the core of peptide-micelle hybrid particles. Compared with plain micelles, CAR peptide increased the cellular uptake by approximately 1.7-fold and extended the drug half-life by approximately fivefold. The formulations were more prone to accumulate in the pulmonary vasculature than in the peripheral blood, which is evident from the ratio of the extent of reduction of pulmonary and systemic arterial pressures. On the whole, this study demonstrates that peptide-polymer hybrid micelles can serve as inhalational carriers for PAH therapy.
Armstrong, Anderson C.; Bandeira, Ângela M. P.; Correia, Luis C. L.; Melo, Humberto C. O.; Silveira, Carlos A. M.; Albuquerque, Eugênio; Moraes, Jeová C.; Silva, Antônio M. L.; Lima, João A. C.; Sobral, Dário C.
Background Schistosomiasis-associated pulmonary arterial hypertension (SPAH) is a major concern worldwide. However, the role of gender specific contributing factors in SPAH is unknown. Objective We investigated how systolic pulmonary artery pressure (SPAP) values and the presence of severe SPAP relate to gender, menopausal status, and pregnancy history in SPAH patients. Methods Seventy-nine patients diagnosed with SPAH from 2000 to 2009 were assessed and 66 were enrolled in the study. Information about age, menopausal status, pregnancy, echocardiography-derived SPAP, and invasive mean pulmonary artery pressure (mPAP) was collected from medical records. The relation between values of SPAP and mPAP and their agreement for severe disease were assessed. Regression models assessed the association of gender, menopausal status, and pregnancy history with SPAP values and the presence of severe SPAP. Results Moderate correlation and good agreement for severe disease were found between mPAP and SPAP. Mean SPAP values were similar for men and women. A trend toward higher values of SPAP was found for non-menopausal women compared to men. Higher SPAP values were found for menopausal compared to non-menopausal women; the values were non-significant after adjustment for age. Pregnancy history had no association with SPAP. Menopause and positive pregnancy had no association with severe SPAP. Conclusion In SPAH patients, neither gender, nor menopausal status, nor pregnancy history showed independent correlation with SPAP values assessed by echocardiography. PMID:23821406
Pellett, A A; Johnson, R W; Morrison, G G; Champagne, M S; deBoisblanc, B P; Levitzky, M G
Using the arterial occlusion method, we compared five literature-based estimates of pulmonary capillary pressure (Ppc) with the corresponding double occlusion pressures (Pdo) in anesthetized dogs whose chests had been closed after sternotomy for instrumentation. Arterial occlusions were performed with a balloon-tipped pulmonary artery catheter that housed pressure transducers immediately proximal and distal to the balloon. Separation of the proximal and distal pressure waveforms during balloon inflation allowed us to precisely define the moment of occlusion. We fit a monoexponential curve to pressure data beginning 200 ms after the onset of occlusion and a biexponential curve to data beginning at the instant of occlusion, with data obtained over a range of vascular states (control, serotonin infusion, histamine infusion). In addition, we investigated the use of sampling of the raw data to estimate capillary pressure. Three of the five literature-based estimates of Ppc yielded values similar to Pdo. The optimal (least average difference from Pdo) interpolation/extrapolation time points of the curve fits varied, depending on the type of curve fitting and the state of the pulmonary vasculature. We also determined that a close approximation of Pdo may be derived from the raw data, as an alternative to exponential curve fitting.
Xiao, Qingyang; Guo, Xiaoquan; Zhuang, Yu; Zhang, Caiying; Wang, Tiancheng; Lin, Huayuan; Song, Yalu; Hu, Guoliang; Liu, Ping
Background Pulmonary arterial hypertension, also known as Ascites syndrome (AS), remains a clinically challenging disease with a large impact on both humans and broiler chickens. Pulmonary arterial remodeling presents a key step in the development of AS. The precise molecular mechanism of pulmonary artery remodeling regulating AS progression remains unclear. Methodology/Principal Findings We obtained pulmonary arteries from two positive AS and two normal broilers for RNA sequencing (RNA-seq) analysis and pathological observation. RNA-seq analysis revealed a total of 895 significantly differentially expressed genes (DEGs) with 437 up-regulated and 458 down-regulated genes, which were significantly enriched to 12 GO (Gene Ontology) terms and 4 KEGG (Kyoto Encyclopedia of Genes and Genomes) pathways (Padj<0.05) regulating pulmonary artery remodeling and consequently occurrence of AS. These GO terms and pathways include ribosome, Jak-STAT and NOD-like receptor signaling pathways which regulate pulmonary artery remodeling through vascular smooth cell proliferation, inflammation and vascular smooth cell proliferation together. Some notable DEGs within these pathways included downregulation of genes like RPL 5, 7, 8, 9, 14; upregulation of genes such as IL-6, K60, STAT3, STAT5 Pim1 and SOCS3; IKKα, IkB, P38, five cytokines IL-6, IL8, IL-1β, IL-18, and MIP-1β. Six important regulators of pulmonary artery vascular remodeling and construction like CYP1B1, ALDH7A1, MYLK, CAMK4, BMP7 and INOS were upregulated in the pulmonary artery of AS broilers. The pathology results showed that the pulmonary artery had remodeled and become thicker in the disease group. Conclusions/Significance Our present data suggested some specific components of the complex molecular circuitry regulating pulmonary arterial remodeling underlying AS progression in broilers. We revealed some valuable candidate genes and pathways that involved in pulmonary artery remodeling further contributing to the AS
Huang, Jianfei; Zhou, Xiaoyu; Xie, Hao; Zhu, Qilin; Huang, Minjie
Acute pulmonary thromboembolism (PTE) refers to the obstruction of thrombus in pulmonary artery or its branches. Recent studies have suggested that PTE-induced endothelium injury is the major physiological consequence of PTE. And it is reasonal to use PTE-induced endothelium injury to stratify disease severity. According to the massive morphologic and histologic findings, rabbit models could be applied to closely mimic the human PE. Genomewide gene expression profiling has not been attempted in PTE. In this study, we determined the accuracy of rabbit autologous thrombus PTE model for human PTE disease, then we applied gene expression array to identify gene expression changes in pulmonary arteries under PTE to identify potential molecular biomarkers and signaling pathways for PTE. We detected 1343 genes were upregulated and 923 genes were downregulated in PTE rabbits. The expression of several genes (IL-8, TNF-α, and CXCL5) with functional importance were further confirmed in transcript and protein levels. The most significantly differentially regulated genes were related to inflammation, immune disease, pulmonary disease, and cardiovascular diseases. Totally 87 genes were up-regulated in the inflammatory genes. We conclude that gene expression profiling in rabbit PTE model could extend the understanding of PTE pathogenesis at the molecular level. Our study provides the fundamental framework for future clinical research on human PTE, including identification of potential biomarkers for prognosis or therapeutic targets for PTE. PMID:27798647
Tang, Zhiyuan; Wang, Xudong; Huang, Jianfei; Zhou, Xiaoyu; Xie, Hao; Zhu, Qilin; Huang, Minjie; Ni, Songshi
Acute pulmonary thromboembolism (PTE) refers to the obstruction of thrombus in pulmonary artery or its branches. Recent studies have suggested that PTE-induced endothelium injury is the major physiological consequence of PTE. And it is reasonal to use PTE-induced endothelium injury to stratify disease severity. According to the massive morphologic and histologic findings, rabbit models could be applied to closely mimic the human PE. Genomewide gene expression profiling has not been attempted in PTE. In this study, we determined the accuracy of rabbit autologous thrombus PTE model for human PTE disease, then we applied gene expression array to identify gene expression changes in pulmonary arteries under PTE to identify potential molecular biomarkers and signaling pathways for PTE. We detected 1343 genes were upregulated and 923 genes were downregulated in PTE rabbits. The expression of several genes (IL-8, TNF-α, and CXCL5) with functional importance were further confirmed in transcript and protein levels. The most significantly differentially regulated genes were related to inflammation, immune disease, pulmonary disease, and cardiovascular diseases. Totally 87 genes were up-regulated in the inflammatory genes. We conclude that gene expression profiling in rabbit PTE model could extend the understanding of PTE pathogenesis at the molecular level. Our study provides the fundamental framework for future clinical research on human PTE, including identification of potential biomarkers for prognosis or therapeutic targets for PTE.
Nair, Krishna Kumar Mohanan; Pillai, Harikrishnan Sivadasan; Titus, Thomas; Varaparambil, Ajitkumar; Sivasankaran, Sivasubramonian; Krishnamoorthy, Kavassery Mahadevan; Namboodiri, Narayanan; Sasidharan, Bijulal; Thajudeen, Anees; Ganapathy, Sanjay; Tharakan, Jaganmohan
Pulmonary artery pressure (PAP) is known to regress after successful balloon mitral valvotomy (BMV). Data of persistent pulmonary artery hypertension (PPAH) following BMV is scarce. We analyzed the clinical, echocardiographic, and hemodynamic data of 701 consecutive patients who have undergone successful BMV in our institute from 1997 to 2003. Data of 287 patients who had PPAH (defined by pulmonary artery systolic pressure [PASP] of ≥ 40 mmHg at one year following BMV) were compared to the data of 414 patients who did not have PPAH. Patients who had PPAH were older (39.9 ± 9.9 years vs. 29.4 ± 10.1; P < 0.001). They had higher prevalence of atrial fibrillation (AF; 21.9 vs. 12.1%, P < 0.05), moderate or severe pulmonary artery hypertension (PAH) defined as PASP more than 50 mmHg (43.5 vs. 33.8%, P = 0.00), anatomically advanced mitral valve disease as assessed by Wilkin's echocardiographic score > 8 (33.7 vs. 23.2%, P < 0.001), and coexistent aortic valve disease (45.6 vs. 37.9%, P < 0.001) at the baseline. Those patients with PPAH had comparatively lower immediate postprocedural mitral valve area (MVA). On follow-up of more than five years, the occurrence of restenosis (39.3 vs. 10.1%, P = 0.000), new onset heart failure (14% vs. 4%, P < 0.05) and need for reinterventions (9.5% vs. 2.8%, P < 0.05) were higher in the PPAH group. Patients with PPAH were older, sicker, and had advanced rheumatic mitral valve disease. They had higher incidence of restenosis, new onset heart failure, and need for reinterventions on long term follow-up. PPAH represents an advanced stage of rheumatic valve disease and indicates chronicity of the disease, which may be the reason for the poorer prognosis of these patients. Patients with PPAH requires intense and more frequent follow-up. PMID:24015345
Geraci, Mark W.; Bull, Todd M.; Tuder, Rubin M.
Synopsis Pulmonary arterial hypertension remains a vexing clinical disease with no cure. Despite advances and the discovery of a gene (BMPR2) associated with many of the hereditary forms of the disease, and some cases not previously known to be inherited, the reasons for mutations in this gene as a cause remain somewhat elusive. Clearly, a complex interplay exists between genetic alterations, environmental exposures (including infections) and disease development. This article addresses the advances in the genetics of PAH, including the identification of genetic etiologies and modulators, and the role of genetics in predicting disease progression and targeting therapeutics. PMID:19945066
Rubin, Lewis J; Simonneau, Gerald; Badesch, David; Galiè, Nazzareno; Humbert, Marc; Keogh, Anne; Massaro, Joseph; Matucci Cerinic, Marco; Sitbon, Olivier; Kymes, Steven
A growing body of published evidence exists on the risk factors for disease progression in pulmonary arterial hypertension (PAH). The Scientific Steering Committee for the Study of Risk in PAH was established to bring together leading clinical and statistical experts in PAH and risk modelling, for the purpose of advancing the understanding of the risk of development and progression of PAH. Herein, we discuss the impact of this information on three key areas: 1) clinical decision-making; 2) policy and reimbursement; and 3) future trials and research.
Murtaza, Ghulam; Mermer, Petra; Goldenberg, Anna; Pfeil, Uwe; Paddenberg, Renate; Weissmann, Nobert; Lochnit, Guenter; Kummer, Wolfgang
The two-pore domain potassium channel KCNK3 (TASK-1) is expressed in rat and human pulmonary artery smooth muscle cells. There, it is associated with hypoxia-induced signalling, and its dysfunction is linked to pathogenesis of human pulmonary hypertension. We here aimed to determine its role in hypoxic pulmonary vasoconstriction (HPV) in the mouse, and hence the suitability of this model for further mechanistic investigations, using appropriate inhibitors and TASK-1 knockout (KO) mice. RT-PCR revealed expression of TASK-1 mRNA in murine lungs and pre-acinar pulmonary arteries. Protein localization by immunohistochemistry and western blot was unreliable since all antibodies produced labelling also in TASK-1 KO organs/tissues. HPV was investigated by videomorphometric analysis of intra- (inner diameter: 25–40 μm) and pre-acinar pulmonary arteries (inner diameter: 41–60 μm). HPV persisted in TASK-1 KO intra-acinar arteries. Pre-acinar arteries developed initial HPV, but the response faded earlier (after 30 min) in KO vessels. This HPV pattern was grossly mimicked by the TASK-1 inhibitor anandamide in wild-type vessels. Hypoxia-provoked rise in pulmonary arterial pressure (PAP) in isolated ventilated lungs was affected neither by TASK-1 gene deficiency nor by the TASK-1 inhibitor A293. TASK-1 is dispensable for initiating HPV of murine intra-pulmonary arteries, but participates in sustained HPV specifically in pre-acinar arteries. This does not translate into abnormal rise in PAP. While there is compelling evidence that TASK-1 is involved in the pathogenesis of pulmonary arterial hypertension in humans, the mouse does not appear to serve as a suitable model to study the underlying molecular mechanisms. PMID:28301582
Manes, Alessandra; Palazzini, Massimiliano; Dardi, Fabio; D'Adamo, Antonio; Rinaldi, Andrea; Galiè, Nazzareno
Pulmonary arterial hypertension (PAH) is a severe clinical condition defined as mean pulmonary artery pressure ≥25 mmHg and normal pulmonary capillary wedge pressure (≤15 mmHg). In PAH the increase in pulmonary pressure is due to an intrinsic disease of the small pulmonary arteries (resistance vessels) characterized by vascular proliferation and remodeling. The increase in pulmonary vascular resistance with subsequent elevation of the right ventricular afterload leads to right ventricular failure after variable periods of time. Although targeted disease therapies have been developed over the last decade that resulted in improved quality of life and outcome for PAH patients, the prognosis is still severe and there remains no cure for this disease. From a clinical standpoint, PAH includes a group of heterogeneous pathological conditions: in idiopathic, heritable and drug- and toxin-induced PAH, since there are no predisposing clinical conditions, the structural changes in pulmonary circulation are "isolated"; on the other hand, PAH may be associated with some predisposing diseases such as connective tissue disease, HIV infection, portal hypertension, congenital heart disease, schistosomiasis, and chronic hemolytic anemia. PAH can affect individuals of all age groups, and mean age at diagnosis is around 50 years. Epidemiological data show a great preponderance of females in PAH; the high prevalence of females is particularly evident in the so-called "isolated" PAH forms, whereas in PAH associated with other diseases the female:male ratio is strongly influenced by the epidemiological features of the specific predisposing condition. The reason for the higher female prevalence in PAH has never been clarified: some hypotheses involve the role of sexual hormones (estrogens), autoimmunity, or an X-linked locus in disease predisposition. Female gender is not associated with a different clinical presentation. However, the age of onset tends to be earlier in females than
Panfeng, Xu; Zheying, Zhang; Jie, Wang; Jianying, Zhou; Xiaodong, Teng
Pulmonary artery sarcoma is a rare tumor of the cardiovascular system. We reported a case of primary pulmonary artery sarcoma. In this case, the patient was misdiagnosed with tuberculosis for nearly 1 year and diagnosed by contrast-enhanced computed tomography and histopathologic examination at last.
Al Amri, Salem Mohammad; Banjar, Ahmad Hassan; Cheema, Ahsan Iqbal
We report a case of an acute episode of massive hemoptysis in a diagnosed patient of Behcet's disease, managed conservatively, using angio-guided vascular plug and coils for occluding the multiple bilateral pulmonary artery aneurysms with thoracic surgery backup. The episode of massive hemoptysis was caused by ruptured Pulmonary Artery Aneurysms (PAA).
Ozbek, Cengiz; Emrecan, Bilgin; Calli, Aylin Orgen; Gurbuz, Ali
We describe the case of a 42-year-old man who presented with dyspnea on exertion and a history of anticoagulation therapy for what was thought to be pulmonary arterial thromboembolism. He underwent surgery for obstruction of the right ventricular outflow tract. This is a very rare case of an intimal sarcoma of the pulmonary artery, which we confirmed by pathologic studies.
Kuo, H.-Cg; Ko, Sheung-Fat; Wu, Yu-Tsun; Huang, Chien-Fu; Chien, Shao-Ju; Tiao, Mao-Meng; Liang, Chi-Di
We report an unusual case of simultaneous obstruction of the left pulmonary artery and descending thoracic aorta after Gianturco coil occlusion in a 15-month-old boy. The diagnosis was made by echocardiography and cardiac angiography. At surgery, thrombi coating on the protruded parts of the Gianturco coil in the pulmonary artery and aorta were found.
Kherbeck, Nada; Tamby, Mathieu C; Bussone, Guillaume; Dib, Hanadi; Perros, Frederic; Humbert, Marc; Mouthon, Luc
Pulmonary arterial hypertension is characterized by a remodeling of pulmonary arteries with endothelial cell, fibroblast, and vascular smooth muscle cell activation and proliferation. Since pulmonary arterial hypertension occurs frequently in autoimmune conditions such as systemic sclerosis, inflammation and autoimmunity have been suspected to play a critical role in both idiopathic pulmonary arterial hypertension and systemic sclerosis-associated pulmonary arterial hypertension. High levels of pro-inflammatory cytokines such as interleukin-1 and interleukin-6, platelet-derived growth factor, or macrophage inflammatory protein 1 have been found in lung samples of patients with pulmonary arterial hypertension, along with inflammatory cell infiltrates mainly composed of macrophages and dendritic cells, T and B lymphocytes. In addition, circulating autoantibodies are found in the peripheral blood of patients. Thus, autoimmunity and inflammation probably play a role in the development of pulmonary arterial hypertension. In this setting, it would be important to set-up new experimental models of pulmonary arterial hypertension, in order to define novel therapeutics that specifically target immune disturbances in this devastating condition.
Kluess, H A; Stafford, J; Evanson, K W; Stone, A J; Worley, J; Wideman, R F
This study examined factors contributing to increased vascular resistance and plexiform lesion formation in broiler chickens susceptible to idiopathic pulmonary arterial hypertension (IPAH). A diet supplemented with excess tryptophan (high-Trp diet), the precursor for serotonin, was used to accelerate the development of IPAH. Broilers fed the high-Trp diet had higher pulmonary arterial pressures than broilers fed the control diet, and plexiform lesion incidences tended to be higher (P = 0.11) in the high-Trp group than in the control group at 30 d of age. The intrapulmonary arteries were assessed for vasoconstriction in response to serotonin and adenosine triphosphate (ATP) and for activities of key metabolic enzymes for serotonin and ATP. The pulmonary artery (defined as the first major branch of the pulmonary artery inside the lung) and the primary pulmonary arterial rami (defined as the second major branch of the pulmonary artery inside the lung) both exhibited vasoconstriction in response to serotonin and ATP. This is the first study to demonstrate purinergic-mediated vasoconstriction in intrapulmonary arteries from broilers. Arteriole responsiveness did not differ between broilers fed the control diet or the high-Trp diet. Therefore, the high-Trp diet enhanced the development of IPAH but did not affect the artery's sensitivity to serotonin or ATP. Monoamine oxidase activity, responsible for the breakdown of serotonin, was severely impaired in pulmonary arteries from broilers in the high-Trp group. Accordingly, serotonin may persist longer and elicit an amplified response in broilers fed the high-Trp diet.
Lee, Jason E.; Patel, Kirit; Almodóvar, Sharilyn; Tuder, Rubin M.; Flores, Sonia C.
Although reduced bioavailability of nitric oxide (NO) has been implicated in the pathogenesis of pulmonary arterial hypertension (PAH), its consequences on organellar structure and function within vascular cells is largely unexplored. We investigated the effect of reduced NO on the structure of the Golgi apparatus as assayed by giantin or GM130 immunofluorescence in human pulmonary arterial endothelial (HPAECs) and smooth muscle (HPASMCs) cells, bovine PAECs, and human EA.hy926 endothelial cells. Golgi structure was also investigated in cells in tissue sections of pulmonary vascular lesions in idiopathic PAH (IPAH) and in macaques infected with a chimeric simian immunodeficiency virus containing the human immunodeficiency virus (HIV)-nef gene (SHIV-nef) with subcellular three-dimensional (3D) immunoimaging. Compounds with NO scavenging activity including 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (c-PTIO), methylene blue, N-acetylcysteine, and hemoglobin markedly fragmented the Golgi in all cell types evaluated as did monocrotaline pyrrole, while LY-83583, sildenafil, fasudil, Y-27632, Tiron, Tempol, or H2O2 did not. Golgi fragmentation by NO scavengers was inhibited by diethylamine NONOate, was evident in HPAECs after selective knockdown of endothelial nitric oxide synthase using small interfering RNA (siRNA), was independent of microtubule organization, required the GTPase dynamin 2, and was accompanied by depletion of α-soluble N-ethylmaleimide-sensitive factor (NSF) acceptor protein (α-SNAP) from Golgi membranes and codispersal of the SNAP receptor (SNARE) Vti1a with giantin. Golgi fragmentation was confirmed in endothelial and smooth muscle cells in pulmonary arterial lesions in IPAH and the SHIV-nef-infected macaque with subcellular 3D immunoimaging. In SHIV-nef-infected macaques Golgi fragmentation was observed in cells containing HIV-nef-bearing endosomes. The observed Golgi fragmentation suggests that NO plays a significant role in
Li, Juan; Zhao, Qian; He, Lirong; Zhuang, Xiaoqing; Li, Fang
A 59-year-old man presented cough, chest pain, and shortness of breath for 2 weeks and fever for 4 days. A contrast chest CT revealed a large right pulmonary artery filling defect, suggestive of pulmonary embolism that failed to respond to anticoagulation therapy. FDG PET/CT was performed to evaluate possible malignancy, which revealed intense activity in the right main pulmonary artery without any extrathoracic abnormality. The ratio of the SUVmax of this lesion to the liver was significantly increased in the delayed PET images. The pathological examination demonstrated primary pulmonary artery sarcoma.
Gaumann, A; Petrow, P; Mentzel, T; Mayer, E; Dahm, M; Otto, M; Kirkpatrick, C J; Kriegsmann, J
Primary tumors of the great vessels (aorta, pulmonal artery, and inferior vena cava) are rare and represent in most cases vascular leiomyosarcomas. Furthermore, there also exists a group of sarcomas arising from the intima, known as intimal sarcomas, associated with early metastasis and a very poor prognosis. Osteopontin (OPN) is an extracellular matrix protein that binds to alphav integrins, thereby promoting cell attachment, chemotaxis, and signal transduction. The reported association of OPN with malignancy and metastasis prompted us to examine the expression of this protein in seven sarcomas of the pulmonary artery. Strong OPN-specific staining could be detected in tumor cells and the adjacent extracellular matrix. Using a double labeling procedure, proliferating cells showed a strong positive reaction with antibodies against OPN. In addition, this protein could be demonstrated in the cytoplasm of macrophages. CD44, a putative receptor of OPN, was expressed on the cellular surface of tumor-associated lymphocytes. The expression of OPN in macrophages and tumor cells indicates that this molecule could possibly mediate cellular adhesion of both cell types in pulmonary sarcomas. The detection in the extracellular matrix shows that OPN is actively secreted and may interact with the corresponding receptor, CD44, on the surface of lymphocytes. Although the function of OPN is not yet fully understood, our data indicate that strong expression of this molecule in poorly differentiated sarcomas could play a role in the progression of malignancy and metastasis as described previously for carcinomas.
Hassine, Elyès; Bousnina, Sophia; Marniche, Kamel; Fennira, Hammouda; Ben Khelil, Jalila; Ben Mustapha, Mohamed Ali; Megdiche, Mohamed Lamine; Chabbou, Abdellatif
Pulmonary involvement in Behçet's disease is an uncommon condition (12%). Thromboembolism of the superior vena cava and/or other mediastinal veins, aneurysms of the aorta and pulmonary arteries are the main vascular manifestations in addition to pulmonary infarct and intrathoracic hemorrhage. Despite their scarcity, respiratory symptoms may be life-threatening. The aim of this study was to assess the contribution of thoracic imaging for one of the most serious aspects of the disease: pulmonary artery aneurysm. We report five patients with pulmonary artery aneurysms (mean age: 39.5 years). Hemoptysia revealed Behçet's disease in three. Initially explored by conventional radiography, computed tomography and angiography, pulmonary artery aneurysms are currently investigated well with helicoidal computed tomography, digital angiography, magnetic resonance imaging (MRI) and angio-MRI. These imaging techniques provide helpful information for the diagnosis of Behçet's disease.
Portillo-Sanchez, José; Hessein-Abdou, Yasser; Puga-Alcalde, Eugenio; Perez-Martinez, Maria Angeles; Del Carmen Jimenez-Meneses, Maria; Camacho-Pedrero, Agustín; Valdepeñas-Herrero, Luís Ruíz
Primary pulmonary artery sarcoma is a rare tumor that is highly fatal. It can be misdiagnosed as acute or chronic pulmonary thromboembolic disease. Herein, we report the case of a 22-year-old woman with a preoperative diagnosis of pulmonary embolism and superior vena caval thrombosis. Intraoperatively, an extensive sarcoma was seen to extend retrograde from the pulmonary artery, past the right ventricle and right atrium, and into the superior vena cava. Surgical resection of the tumor and reconstruction of the central pulmonary arteries, followed by adjuvant chemotherapy, relieved the clinical symptoms. The patient remained free of cancer at 14 months postoperatively. We believe that this is the 1st report of a primary pulmonary artery sarcoma that extended retrograde into the superior vena cava.
Becker, Eva Maria; Stasch, Johannes-Peter; Bechem, Martin; Keldenich, Jörg; Klipp, Alexandra; Schaefer, Katja; Ulbrich, Hannes-Friedrich; Truebel, Hubert
Background Approved therapies for pulmonary arterial hypertension can induce oxygen desaturation when administered to patients with secondary forms of pulmonary hypertension (PH), probably due to an increase in ventilation/perfusion mismatch. Thus, so far these treatments have largely failed in secondary forms of PH. Methods We established an animal model of heterogeneous lung ventilation to evaluate the desaturation potential of mechanistically distinct vasoactive drugs launched or currently in clinical development for the treatment of PH. Single-lung ventilation was induced in five groups (N = 6) of anesthetized minipigs (7 weeks, 4 to 5 kg BW), and their hemodynamic parameters were monitored before and after intravenous injection of control (vehicle only), endothelin antagonist (bosentan; 0.3, 1, 3, 10 mg/kg), phosphodiesterase type 5 inhibitor (sildenafil; 3, 10, 30, 100 µg/kg), and soluble guanylate cyclase stimulators (BAY 41–8543 and riociguat; 1, 3, 10, 30 µg/kg). Cumulative doses were administered before successive unilateral ventilation cycles. The doses were chosen to achieve equal effect on blood pressure by the different pharmacologic principles. Results Single-lung ventilation resulted in transient increases in mean pulmonary artery pressure (mPAP) and desaturation. In contrast to control, all drugs dose-dependently decreased hypoxic mPAP (a positive treatment effect) and increased area under the arterial hemoglobin saturation curve (unwanted desaturation effect). Riociguat and bosentan reduced hypoxic mPAP to the greatest extent, while the soluble guanylate cyclase stimulators riociguat and BAY 41–8543 lowered arterial oxygen saturation of hemoglobin the least. Conclusions Future investigations will be required to confirm these findings in clinical settings. PMID:24015306
Ishimaru, Kazuhiko; Araki, Kanta; Nakamura, Tsuneyuki; Sawa, Yoshiki
A 2-month-old patient with anomalous origin of the left coronary artery from the pulmonary artery (ALCAPA) underwent an alternative repair involving coronary transfer with the bay window technique because of the very short left main coronary trunk. This procedure is a clinically relevant and feasible technique for ALCAPA with such a delicate coronary artery anomaly. PMID:27656197
Feng, Shasha; Chen, Siyao; Yu, Wen; Zhang, Da; Zhang, Chunyu; Tang, Chaoshu; Du, Junbao; Jin, Hongfang
This study aimed to determine whether hydrogen sulfide (H2S) inhibits pulmonary arterial endothelial inflammation in rats with monocrotaline (MCT)-induced pulmonary hypertension and its possible mechanisms. Twenty-four male Wistar rats were divided randomly into control, MCT, and MCT+H2S treatment groups. Human pulmonary arterial endothelial cells (HPAEC) were cultured and divided into four groups: control, MCT, MCT+H2S, and H2S. Pulmonary artery pressure was determined using a right cardiac catheterization procedure 3 weeks after MCT administration. Pulmonary vascular morphological changes and inflammatory infiltration were measured. Endogenous H2S levels, cystathionine-γ-lyase (CSE) expression, and inflammatory cytokines were determined both in vivo and in vitro. In addition, phosphorylation of NF-κB p65 and IκBα was detected by western blotting, and NF-κB p65 nuclear translocation, as well as its DNA-binding activity, was determined. Pulmonary hypertension and vascular remolding developed 3 wks after MCT administration, with elevated lung tissue inflammatory infiltration and cytokine level associated with activation of the NF-κB pathway, both in vivo and in vitro. However, the endogenous H2S/CSE pathway was downregulated in MCT rats. By contrast, an H2S donor markedly reduced pulmonary artery pressure, pulmonary vascular structural remolding, and increased lung inflammatory infiltration and cytokine levels of MCT-treated rats. Meanwhile, H2S reversed the activation of the NF-κB pathway successfully. The downregulated pulmonary arterial endothelial H2S/CSE pathway is involved in the pulmonary inflammatory response in MCT-treated pulmonary hypertensive rats. H2S attenuated endothelial inflammation by inhibiting the NF-κB pathway.
Marrone, Chiara; Santoro, Giuseppe; Palladino, Maria Teresa; Caianiello, Giuseppe; Russo, Maria Giovanna; Calabrò, Raffaele
A 2 month-old infant with severe congestive heart failure due to unrestrictive ventricular septal defect and absence of the left pulmonary artery was submitted to a hybrid transcatheter-surgical palliation consisting in percutaneous re-canalization of the occluded arterial duct-left pulmonary artery complex and surgical banding of the right pulmonary artery. The post-operative course was uneventful and the baby was discharged in a few days under mild anti-congestive therapy. This hybrid approach was highly effective in stabilizing this critical infant in view of a later and safer surgical repair.
Rol, Nina; Timmer, Esther M; Faes, Theo J C; Noordegraaf, Anton Vonk; Grünberg, Katrien; Bogaard, Harm-Jan; Westerhof, Nico
In idiopathic pulmonary arterial hypertension (PAH), increased pulmonary vascular resistance is associated with structural narrowing of small (resistance) vessels and increased vascular tone. Current information on pulmonary vascular remodeling is mostly limited to averaged increases in wall thickness, but information on number of vessels affected and internal diameter decreases for vessels of different sizes is limited. Our aim was to quantify numbers of affected vessels and their internal diameter decrease for differently sized vessels in PAH in comparison with non-PAH patients. Internal and external diameters of transversally cut vessels were measured in five control subjects and six PAH patients. Resistance vessels were classified in Strahler orders, internal diameters 13 μm (order 1) to 500 μm (order 8). The number fraction, that is, percentage of affected vessels, and the internal diameter fraction, that is, percentage diameter of normal diameter, were calculated. In PAH, not all resistance vessels are affected. The number fraction is about 30%, that is, 70% of vessels have diameters not different from vessels of control subjects. Within each order, the decrease in diameter of affected vessels is variable with an averaged diameter fraction of 50-70%. Narrowing of resistance vessels is heterogeneous: not all vessels are narrowed, and the decrease in internal diameters, even within a single order, vary largely. This heterogeneous narrowing alone cannot explain the large resistance increase in PAH We suggest that rarefaction could be an important contributor to the hemodynamic changes.
Ventetuolo, Corey E.; Gabler, Nicole B.; Fritz, Jason S.; Smith, K. Akaya; Palevsky, Harold I.; Klinger, James R.; Halpern, Scott D.; Kawut, Steven M.
Background While frequently assessed in trials and clinical practice, hemodynamic response to therapy has never been validated as a surrogate endpoint for clinical events in pulmonary arterial hypertension (PAH). Methods and Results We performed a patient-level pooled analysis of four randomized placebo-controlled trials to determine if treatment-induced changes in hemodynamic values at 12 weeks accounted for the relationship between treatment assignment and the probability of early clinical events (death, lung transplantation, atrial septostomy, PAH hospitalization, withdrawal for clinical worsening, escalation in PAH therapy). We included 1119 subjects with PAH. The median (interquartile range) age was 48 (37 – 59), and 23% were men. 656 (59%) received active therapy (101 [15%] iloprost, 118 [18%] sitaxsentan, 204 [31%] sildenafil, and 233 [36%] subcutaneous treprostinil). Active treatment significantly lowered right atrial pressure (RAP), mean pulmonary artery pressure (mPAP), and pulmonary vascular resistance and increased cardiac output and index (p < 0.01 for all). Changes in hemodynamic values (except for RAP and mPAP) were significantly associated with the risk of a clinical event (p ≤ 0.01 for all). While active treatment approximately halved the odds of a clinical event compared to placebo (p < 0.001), changes in hemodynamics accounted for only 1.2 – 13.9% of the overall treatment effect. Conclusions Treatment-induced changes in hemodynamics at 12 weeks only partially explain the impact of therapy on the probability of early clinical events in PAH. These findings suggest that resting hemodynamics are not valid surrogate endpoints for short-term events in PAH clinical trials. PMID:24951771
Al-Naamani, Nadine; Palevsky, Harold I.; Lederer, David J.; Horn, Evelyn M.; Mathai, Stephen C.; Roberts, Kari E.; Tracy, Russell P.; Hassoun, Paul M.; Girgis, Reda E.; Shimbo, Daichi; Post, Wendy S.
Rationale: Pulmonary arterial hypertension (PAH) is a rare progressive disease of the pulmonary vasculature that is characterized by endothelial dysfunction, inflammation, and right ventricular dysfunction. Objectives: The main objective was to determine whether endothelial, inflammatory, and cardiac biomarkers would be associated with the World Health Organization functional assessment and survival in patients with PAH. Methods: We performed a retrospective cohort study of patients with PAH enrolled in the Randomized Clinical Trial of Aspirin and Simvastatin for Pulmonary Arterial Hypertension (ASA-STAT). Biomarkers (N-terminal fragment of pro-BNP [NT-pro-BNP], von Willebrand factor [vWF], soluble P selectin, C-reactive protein, total and high-density lipoprotein cholesterol, triglycerides, tumor necrosis factor, IL-6, β-thromboglobulin, and thromboxane B2) were measured at baseline. Patients from the study were followed until lung transplantation, death, or August 1, 2013. Ordinal logistic regression and Cox regression analyses were performed. Measurements and Main Results: Sixty-five patients with PAH were enrolled. The mean age was 51 years, and 86% were women. Higher vWF activity, lower high-density lipoprotein cholesterol, and higher thromboxane B2 levels were associated with worse World Health Organization functional class after adjustment for age, sex, and etiology of PAH. Higher NT-pro-BNP levels, lower vWF activity, and lower total cholesterol were associated with an increased risk of death or lung transplant after adjustment for age, sex, etiology of PAH, and 6-minute-walk distance. Conclusions: In patients with PAH, lower vWF activity and cholesterol levels and higher NT-pro-BNP levels at baseline were associated with an increased risk of death or transplantation. Clinical trial registered with www.clinicaltrials.gov (NCT00384865). PMID:26501464
Miranda, Carlos D; Kenny, Damien
We report our experience with stenting a right ductus arteriosus in a neonate with ductal origin of the right pulmonary artery (PA), who subsequently developed severe pulmonary hypertension in the left PA requiring decompression of the right ventricle with stenting of the left ductus. © 2015 Wiley Periodicals, Inc.
Flores, Saul; Daily, Joshua; Pratap, Jayant Nick; Cash, Michelle C; Hirsch, Russel
We describe the course and management of a 12-year-old girl with severe pulmonary arterial hypertension who initially presented with severe systemic hypertension. Successful therapy included pulmonary vasodilators and an atrial septostomy, while ensuring adequate maintenance of her systemic vascular resistance to maintain cardiac output. Clear understanding of the physiology and judicious medical management in patients with severe pulmonary arterial hypertension using extreme compensatory mechanisms is vitally important.
Waters, Kendall R.; Mukdadi, Osama M.
Secondary pediatric pulmonary hypertension is a disease that could benefit from improved ultrasonic diagnostic techniques. We perform high-frequency in vitro ultrasound measurements (25 MHz to 100 MHz) on fresh and fixed pulmonary arterial walls excised from normoxic and hypoxic Long-Evans rat models. Estimates of the elastic stiffness coefficients are determined from measurements of the speed of sound. Preliminary results indicate that hypoxia leads to up to increase of 20 % in stiffening of the pulmonary arterial wall.
Lin, Chien-Heng; Li, Tsai-Chung; Tsai, Po-Pang; Lin, Wei-Ching
The improvement of the resolution of rapid scanning in multidetector computed tomography (CT) has an increased accuracy that allows for the demonstration of the relationship of the pulmonary arteries and lung lesions, even in the peripheral lung. The purpose of this study is to evaluate the relationship between the pulmonary arteries and lung lesions by CT, and to use this relationship to distinguish between benign and malignant lung lesions. The relationships of the lung lesions and the adjacent pulmonary artery were recorded as encasement, displacement, penetration, in the margin, and disconnection. Statistical analyses were then performed to evaluate the relationship of the pulmonary arteries to each lesion with a focus toward the possibility of malignancy and the degree of pulmonary arterial encasement in the lesion. The relationship between the pulmonary arteries and lung lesions had a statistically significant difference between benignancy and malignancy (P < 0.001). Inter-observer agreement was substantial (κ = 0.639; 95% CI: 0.518-0.719). The average degrees of pulmonary arterial encasement in benign and malignant lesions were 52.1% ± 27.3% and 71.8% ± 18.8%, respectively (P = 0.011). The ROC curve showed that the degree of pulmonary arterial encasement had a moderate discriminating ability in diagnosing lung carcinoma, and the area under the curve was 0.738. The best cutoff value was 44.4%. The relationships of the pulmonary arteries to lung lesions and the degree of pulmonary arterial encasement could be used in differentiating benignancy from malignancy not only for central lung lesions but also peripheral lung lesions.
Papathanasiou, Athanasios; Nakos, George
Pulmonary hypertension (PH) is a condition characterized by the elevation of the mean pulmonary artery pressure above 25 mmHg and the pulmonary vascular resistance above 3 wood units. Pulmonary arterial hypertension (PAH) is an uncommon condition with severe morbidity and mortality, needing early recognition and appropriate and specific treatment. PH is frequently associated with hypoxemia, mainly chronic obstructive pulmonary disease and DPLD and/or left heart diseases (LHD), mainly heart failure with reduced or preserved ejection fraction. Although in the majority of patients with PH the cause is not PAH, a significant number of published studies are still in regard to group I PH, leading to a logical assumption that PH due to other causes is not such an important issue. So, is there a reason to discuss PH other than PAH? Chronic lung diseases, mainly chronic obstructive lung disease and DPLD, are associated with a high incidence of PH which is linked to exercise limitations and a worse prognosis. Although pathophysiological studies suggest that specific PAH therapy may benefit such patients, the results presented from small studies in regard to the safety and effectiveness of the specific PAH therapy are discouraging. PH is a common complication of left heart disease and is related to disease severity, especially in patients with reduced ejection fraction. There are two types of PH related to LHD based on diastolic pressure difference (DPD, deﬁned as diastolic pulmonary artery pressure - mean PAWP): Isolated post-capillary PH, defined as PAWP > 15 mmHg and DPD < 7 mmHg, and combined post-capillary PH and pre-capillary PH, defined as PAWP > 15 mmHg and DPD ≥ 7 mmHg. The potential use of PAH therapies in patients with PH related to left heart disease is based on a logical pathobiological rationale. In patients with heart failure, endothelial dysfunction has been proposed as a cause of PH and hence as a target for treatment, supported by the presence of
Karimi, Mohsen; Kirshbom, Paul M
Anomalous origins of coronary arteries from the pulmonary artery are rare malformations in which the coronary arteries originate from pulmonary artery sinuses or branches. The consequences are variable although, in most cases, these anomalies lead to severe coronary hypoperfusion and ventricular dysfunction. Surgical correction is indicated once the diagnosis is established due to high early mortality associated with the disease. In nearly all cases, the anomalous artery can be excised from its pulmonary origin, mobilized, and reimplanted directly into the ascending aorta using different surgical techniques. In rare circumstances, technical modifications must be used to restore a normal dual coronary perfusion. The emphasis of this article is to provide a collective review of surgical options published in the literature.
Bogaard, Harm J; Mizuno, Shiro; Guignabert, Christophe; Al Hussaini, Aysar A; Farkas, Daniela; Ruiter, Gerrina; Kraskauskas, Donatas; Fadel, Elie; Allegood, Jeremy C; Humbert, Marc; Vonk Noordegraaf, Anton; Spiegel, Sarah; Farkas, Laszlo; Voelkel, Norbert F
Obliteration of the vascular lumen by endothelial cell growth is a hallmark of many forms of severe pulmonary arterial hypertension. Copper plays a significant role in the control of endothelial cell proliferation in cancer and wound-healing. We sought to determine whether angioproliferation in rats with experimental pulmonary arterial hypertension and pulmonary microvascular endothelial cell proliferation in humans depend on the proangiogenic action of copper. A copper-depleted diet prevented, and copper chelation with tetrathiomolybdate reversed, the development of severe experimental pulmonary arterial hypertension. The copper chelation-induced reopening of obliterated vessels was caused by caspase-independent apoptosis, reduced vessel wall cell proliferation, and a normalization of vessel wall structure. No evidence was found for a role of super oxide-1 inhibition or lysyl-oxidase-1 inhibition in the reversal of angioproliferation. Tetrathiomolybdate inhibited the proliferation of human pulmonary microvascular endothelial cells, isolated from explanted lungs from control subjects and patients with pulmonary arterial hypertension. These data suggest that the inhibition of endothelial cell proliferation by a copper-restricting strategy could be explored as a new therapeutic approach in pulmonary arterial hypertension. It remains to be determined, however, whether potential toxicity to the right ventricle is offset by the beneficial pulmonary vascular effects of antiangiogenic treatment in patients with pulmonary arterial hypertension.
Gavilanes, Francisca; Jr, José Leonidas Alves; Fernandes, Caio; Prada, Luis Felipe Lopes; Jardim, Carlos Viana Poyares; Morinaga, Luciana Tamie Kato; Dias, Bruno Arantes; Hoette, Susana; Souza, Rogerio
OBJECTIVE: To evaluate the role of right heart catheterization in the diagnosis of pulmonary arterial hypertension (PAH). METHODS: We evaluated clinical, functional, and hemodynamic data from all patients who underwent right heart catheterization because of diagnostic suspicion of PAH-in the absence of severe left ventricular dysfunction (LVD), significant changes in pulmonary function tests, and ventilation/perfusion lung scintigraphy findings consistent with chronic pulmonary thromboembolism-between 2008 and 2013 at our facility. RESULTS: During the study period, 384 patients underwent diagnostic cardiac catheterization at our facility. Pulmonary hypertension (PH) was confirmed in 302 patients (78.6%). The mean age of those patients was 48.7 years. The patients without PH showed better hemodynamic profiles and lower levels of B-type natriuretic peptide. Nevertheless, 13.8% of the patients without PH were categorized as New York Heart Association functional class III or IV. Of the 218 patients who met the inclusion criteria, 40 (18.3%) and 178 (81.7%) were diagnosed with PH associated with LVD (PH-LVD) and with PAH, respectively. The patients in the HP-LVD group were significantly older than were those in the PAH group (p < 0.0001). CONCLUSIONS: The proportional difference between the PAH and PH-LVD groups was quite significant, considering the absence of echocardiographic signs suggestive of severe LVD during the pre-catheterization investigation. Our results highlight the fundamental role of cardiac catheterization in the diagnosis of PAH, especially in older patients, in whom the prevalence of LVD that has gone undiagnosed by non-invasive tests is particularly relevant. PMID:25610501
Henderson, A Cortney; Prisk, G Kim; Levin, David L; Hopkins, Susan R; Buxton, Richard B
The arterial spin labeling (ASL) method provides images in which, ideally, the signal intensity of each image voxel is proportional to the local perfusion. For studies of pulmonary perfusion, the relative dispersion (RD, standard deviation/mean) of the ASL signal across a lung section is used as a reliable measure of flow heterogeneity. However, the RD of the ASL signals within the lung may systematically differ from the true RD of perfusion because the ASL image also includes signals from larger vessels, which can reflect the blood volume rather than blood flow if the vessels are filled with tagged blood during the imaging time. Theoretical studies suggest that the pulmonary vasculature exhibits a lognormal distribution for blood flow and thus an appropriate measure of heterogeneity is the geometric standard deviation (GSD). To test whether the ASL signal exhibits a lognormal distribution for pulmonary blood flow, determine whether larger vessels play an important role in the distribution, and extract physiologically relevant measures of heterogeneity from the ASL signal, we quantified the ASL signal before and after an intervention (head-down tilt) in six subjects. The distribution of ASL signal was better characterized by a lognormal distribution than a normal distribution, reducing the mean squared error by 72% (p < 0.005). Head-down tilt significantly reduced the lognormal scale parameter (p = 0.01) but not the shape parameter or GSD. The RD increased post-tilt and remained significantly elevated (by 17%, p < 0.05). Test case results and mathematical simulations suggest that RD is more sensitive than the GSD to ASL signal from tagged blood in larger vessels, a probable explanation of the change in RD without a statistically significant change in GSD. This suggests that the GSD is a useful measure of pulmonary blood flow heterogeneity with the advantage of being less affected by the ASL signal from tagged blood in larger vessels.
Ibarrola, Patricia; German, Alexander J; Stell, Anneliese J; Fox, Richard; Summerfield, Nuala J; Blackwood, Laura
A 13-year-old neutered male Persian cat and an 11-year-old neutered female Persian cat were examined because of an acute onset of lameness. In both cats, conscious proprioception and reflexes were diminished in the affected limb. In 1 cat, no blood flow was detected in the left brachial artery with a Doppler ultrasonic flow detector, whereas blood flow in the right brachial artery was easily documented. In the other cat, the right femoral pulse was not palpable. Neither cat had any echocardiographic evidence of cardiac disease. In both cats, treatment was primarily supportive. One cat died, and the other was euthanatized. At necropsy, lung lobe consolidation was seen. Microscopically, there was multifocal infiltration of the lung parenchyma with cuboidal to columnar neoplastic epithelial cells. Neoplastic epithelial cells of similar morphology were identified in nodular masses in sections of muscle, and intravascular tumor emboli were identified obliterating small and large arterioles. Immunohistochemical staining of pulmonary and muscular tissue for pan-cytokeratin antigen revealed intense cytoplasmic staining of neoplastic cells. Staining for factor VIII-related antigen confirmed that clusters of neoplastic cells represented intravascular emboli. Clinical signs in the cats were attributed to arterial occlusion by tumor emboli.
Atkins, C E; Keene, B W; McGuirk, S M; Sato, T
In an effort to better understand the role of vasodilators in the management of pulmonary hypertension associated with chronic heartworm disease (HWD), pulmonary hemodynamic measurements were obtained from 7 experimentally infected, anesthetized dogs before and after hydralazine administration (mean dose, 1.96 mg/kg of body weight). Five dogs were maintained on room air, while 2 were maintained on 100% oxygen during the hydralazine study. The hemodynamic effect of hydralazine in dogs with HWD was evaluated, using heart rate, cardiac index, mean pulmonary artery pressure, mean arterial pressure, total pulmonary resistance, total systemic resistance, total systemic resistance/total pulmonary resistance, left ventricular dP/dtmax, left ventricular end diastolic pressure, and left and right ventricular double products ([mean arterial pressure x heart rate] and [mean pulmonary artery pressure x heart rate], respectively). Responders were defined as those in which total pulmonary resistance decreased > or = 20% without an increase in mean pulmonary arterial pressure and in which heart rate increase was < or = 10%. Comparison was also made between maximal hemodynamic effect of hydralazine with that after 100% oxygen administration for 15 minutes to previously normoxemic dogs (n = 5). Significance was determined if P < 0.05, using the paired t-test. Hydralazine induced significant reductions in mean pulmonary and systemic arterial pressures and total pulmonary resistance, with no significant change in heart rate, cardiac index, total systemic resistance, left ventricular dP/dtmax, left ventricular end diastolic pressure, or right and left ventricular double products. Four (57%) of the 7 dogs studied were considered responders. Pretreatment cardiac index, mean pulmonary artery pressure, and total pulmonary resistance did not allow differentiation of responders from nonresponders.(ABSTRACT TRUNCATED AT 250 WORDS)
Guo, Haipeng; Zhang, Xin; Cui, Yuqian; Deng, Wei; Xu, Dachun; Han, Hui; Wang, Hao; Chen, Yuguo; Li, Yu; Wu, Dawei
Highlights: • We focus on PASMCs proliferation in the pathogenesis of PAH. • Isorhynchophylline inhibited PASMCs proliferation and alleviated PAH. • IRN blocked PDGF-Rβ phosphorylation and its downstream signal transduction. • IRN regulated cyclins and CDKs to arrest cell cycle in the G0/G1 phase. • We reported IRN has the potential to be a candidate for PAH treatment. - Abstract: Increased pulmonary arterial smooth muscle cells (PASMCs) proliferation is a key pathophysiological component of pulmonary vascular remodeling in pulmonary arterial hypertension (PAH). Isorhynchophylline (IRN) is a tetracyclic oxindole alkaloid isolated from the Chinese herbal medicine Uncaria rhynchophylla. It has long been used clinically for treatment of cardiovascular and cerebrovascular diseases. However, very little is known about whether IRN can influence the development of PAH. Here we examined the effect of IRN on monocrotaline (MCT) induced PAH in rats. Our data demonstrated that IRN prevented MCT induced PAH in rats, as assessed by right ventricular (RV) pressure, the weight ratio of RV to (left ventricular + septum) and RV hypertrophy. IRN significantly attenuated the percentage of fully muscularized small arterioles, the medial wall thickness, and the expression of smooth muscle α-actin (α-SMA) and proliferating cell nuclear antigen (PCNA). In vitro studies, IRN concentration-dependently inhibited the platelet-derived growth factor (PDGF)-BB-induced proliferation of PASMCs. Fluorescence-activated cell-sorting analysis showed that IRN caused G0/G1 phase cell cycle arrest. IRN-induced growth inhibition was associated with downregulation of Cyclin D1 and CDK6 as well as an increase in p27Kip1 levels in PDGF-BB-stimulated PASMCs. Moreover, IRN negatively modulated PDGF-BB-induced phosphorylation of PDGF-Rβ, ERK1/2, Akt/GSK3β, and signal transducers and activators of transcription 3 (STAT3). These results demonstrate that IRN could inhibit PASMCs proliferation and
Jeon, Chang-Seok; Shim, Man-shik; Yang, Ji-Hyuk; Jun, Tae-Gook
We report the case of a newborn with a rare anatomic variation: a right aortic arch with a retroesophageal left subclavian artery and an anomalous origin of the pulmonary artery from the aorta. This variation was diagnosed using echocardiography and computed tomography, and we treated the condition surgically. PMID:28180103
Xie, Yiting; Liang, Mingzhu; Yankelevitz, David F.; Henschke, Claudia I.; Reeves, Anthony P.
A new measurement of the pulmonary artery diameter is obtained where the artery may be robustly segmented between the heart and the artery bifurcation. An automated algorithm is presented that can make this pulmonary artery measurement in low-dose non-contrast chest CT images. The algorithm uses a cylinder matching method following geometric constraints obtained from other adjacent organs that have been previously segmented. This new measurement and the related ratio of pulmonary artery to aortic artery measurement are compared to traditional manual approaches for pulmonary artery characterization. The algorithm was qualitatively evaluated on 124 low-dose and 223 standard-dose non-contrast chest CT scans from two public datasets; 324 out of the 347 cases had good segmentations and in the other 23 cases there was significant boundary inaccuracy. For quantitative evaluation, the comparison was to manually marked pulmonary artery boundary in an axial slice in 45 cases; the resulting average Dice Similarity Coefficient was 0.88 (max 0.95, min 0.74). For the 45 cases with manual markings, the correlation between the automated pulmonary artery to ascending aorta diameter ratio and manual ratio at pulmonary artery bifurcation level was 0.81. Using Bland-Altman analysis, the mean difference of the two ratios was 0.03 and the limits of agreement was (-0.12, 0.18). This automated measurement may have utility as an alternative to the conventional manual measurement of pulmonary artery diameter at the bifurcation level especially in the context of noisy low-dose CT images.
Stieger-Vanegas, Susanne M; Bottorff, Bryan; Sisson, David; Löhr, Christiane V
Intravascular pulmonary artery sarcomas in combination with myocardial metastasis are rare in dogs. We describe the radiographic, echocardiographic, and electrocardiographic-gated (ECG-gated) computed tomographic angiography (CTA) findings in a dog with pulmonary artery sarcoma. All imaging studies demonstrated severe main pulmonary artery enlargement. Echocardiography and ECG-gated CTA revealed a mass occluding the lumen of the right pulmonary artery. In addition, CTA revealed focal left ventricular myocardial contrast enhancement and parenchymal lung changes. Postmortem examination confirmed the presence of a large thrombus associated with arteriosclerosis and an intravascular sarcoma in the right pulmonary artery with metastases to the myocardium, lungs and brain.
Kage, Hidenori; Goto, Yasushi; Amano, Yosuke; Makita, Kosuke; Isago, Hideaki; Kobayashi, Kouichi; Narumoto, Osamu; Okudaira, Reiko; Tanaka, Goh; Takami, Kazutaka; Ohishi, Nobuya; Nagase, Takahide
We herein describe a patient with Behçet's disease in whom we followed the development and resolution of pulmonary artery aneurysms. He presented with intermittent hemoptysis, pulmonary thromboembolism was initially diagnosed, and anticoagulant therapy was started. Over the next several months, the expansion of pulmonary arteries was noted. Five months after his initial admission, he was readmitted for massive hemoptysis, and further examinations revealed that he had Behçet's disease. Corticosteroids and intravenous cyclophosphamide were started. Over the next five months, the pulmonary artery aneurysms and thrombosis resolved. The development of pulmonary artery aneurysms led to the diagnosis of Behçet's disease, and they resolved after immunosuppressive therapy. PMID:27853079
Chowdhury, Ujjwal Kumar; Kapoor, Poonam Malhotra; Rao, Keerthi; Gharde, Parag; Kumawat, Mukesh; Jagia, Priya
We report a rare complication of massive aneurysm of the proximal ligated end of the main pulmonary artery which occurred in the setting of a patient with a functionally univentricular heart and increased pulmonary blood flow undergoing superior cavopulmonary connection. Awareness of this possibility may guide others to electively transect the pulmonary artery in such a clinical setting. PMID:27397472
Soliman, D; Bolliger, D; Skarvan, K; Kaufmann, B A; Lurati Buse, G; Seeberger, M D
The clinical value of the estimation of systolic pulmonary artery pressure, based on Doppler assessment of peak tricuspid regurgitant velocity using transoesophageal echocardiography, is unclear. We studied 109 patients to evaluate the feasibility of obtaining adequate Doppler recordings, and compared Doppler estimates with values measured using a pulmonary artery catheter in a subset of 33 patients. Tricuspid regurgitation was evaluated at the mid-oesophageal level at 0-120° using Doppler echocardiography. A Doppler signal was defined as adequate if there was a ≤ 20° alignment and a full envelope. Doppler estimates of systolic pulmonary artery pressure within 10 mmHg and 15% of the value recorded with the pulmonary artery catheter were considered to be in sufficient agreement. Adequate Doppler signals were obtained in 64/109 (59%) patients before and 54/103 (52%) after surgery. Doppler estimates by transoesophageal echocardiography were within 10 mmHg and 15% of values recorded with the pulmonary artery catheter in 28/33 (75%) patients and 22/31 (55%) patients, respectively. In 7 (21%) patients, the echocardiographic Doppler measurement exceeded the measured systolic pulmonary artery pressure by more than 30%. Our study indicates that estimation of the systolic pulmonary artery pressure using transoesophageal Doppler echocardiography is not a reliable and clinically useful method in anaesthetised patients undergoing mechanical ventilation.
Delcroix, M; Naeije, R
Pulmonary arterial hypertension (PAH) is a rare and potentially fatal disease whose management is usually restricted to a few specialised centres. As patients do not necessarily live in the neighbourhood of these centres, daily care and emergencies have to be delegated to first and second lines. Treatment guidelines do not usually provide recommendations for acute emergency situations as evidence is scarce. This short review provides a description of our therapeutic protocols based on available data. A model of transmural organisation of care for PAH patients, currently applied in Belgium, is described. Thereafter, based on an analysis of the reasons of death in the PAH population, a review of the main emergencies is provided. Cardiac arrest and resuscitation, decompensated right heart failure, respiratory failure, arrhythmia, pericardial effusion, haemoptysis, surgery and drug-related adverse events will be discussed successively. Case reports showing the precariousness of PAH patients will enforce our thesis of the need for optimal patient management organisation.
Chester, Adrian H.; Yacoub, Magdi H.
Pulmonary arterial hypertension (PAH) is a rare but debilitating disease, which if left untreated rapidly progresses to right ventricular failure and eventually death. In the quest to understand the pathogenesis of this disease differences in the profile, expression and action of vasoactive substances released by the endothelium have been identified in patients with PAH. Of these, endothelin-1 (ET-1) is of particular interest since it is known to be an extremely powerful vasoconstrictor and also involved in vascular remodelling. Identification of ET-1 as a target for pharmacological intervention has lead to the discovery of a number of compounds that can block the receptors via which ET-1 mediates its effects. This review sets out the evidence in support of a role for ET-1 in the onset and progression of the disease and reviews the data from the various clinical trials of ET-1 receptor antagonists for the treatment of PAH. PMID:25405182
Austin, Bethany A; Griffin, Brian P
Primary pulmonary artery intimal sarcomas are often diagnosed only at the time of surgery or autopsy as a result of few specific findings both clinically and on imaging studies. We report two cases of this rare and lethal malignancy, both of which were initially thought to be manifestations of thromboembolic disease. In the case of one man, the diagnosis was delayed several months, at which point attempted surgical resection was not feasible. In the second case the echocardiographic and computed tomographic results generated further evaluation. This led to a more prompt diagnosis and treatment extending the patient's survival. In addition, we describe the echocardiographic findings that lent support to the need for surgical intervention and histologic diagnosis.
Bonnet, Sebastien; Provencher, Steeve; Guignabert, Christophe; Perros, Frédéric; Boucherat, Olivier; Schermuly, Ralph Theo; Hassoun, Paul M; Rabinovitch, Marlene; Nicolls, Mark R; Humbert, Marc
Despite important advances in its therapeutic management, pulmonary arterial hypertension (PAH) remains an incurable disease. Although numerous drugs exhibited beneficial effects in preclinical settings, only few have reached clinical trial phases, highlighting the challenges of translating preclinical investigations into clinical trials. Potential reasons for delayed PAH drug development may include the inherent limitations of the currently available animal and in vitro models, potential lack of appropriate standardization of the experimental design, regulatory agencies requirements, competing clinical trials and insufficient funding. Although this is not unique to PAH, there is urgency for reducing the number of false positive signals in preclinical studies and optimizing the development of innovative therapeutic targets through performance of clinical trials based on more robust experimental data. The current review discusses the challenges and opportunities in preclinical research to foster drug development in PAH.
García Hernández, Francisco José; Castillo Palma, María Jesús; González León, Rocío; Garrido Rasco, Rocío; Ocaña Medina, Celia; Sánchez Román, Julio
Despite advances in the treatment of patients with pulmonary arterial hypertension (PAH), survival has not improved greatly (is still very affected). Imatinib, an antagonist of platelet-derived growth factor with antiproliferative activity, has been effective in experimental models and clinically in several published reports. We report the results of imatinib therapy in 4 patients with PAH (functional class IV) who were refractory to treatment with drug combinations for this condition. The final outcome was favorable in only 1 of the 4 cases. In this case, the patient was in functional class III and his hemodynamic parameters had improved significantly within 5 months after starting therapy. However, the patient died as a result of severe toxic hepatitis in which imatinib may have played a role. The present report adds to the few already in the literature (4 cases) and suggests that care should continue to be shown when using imatinib to treat PAH.
Tefera, Endale; Teodori, Michael
Congenital or acquired aneurysm of the pulmonary artery (PA) is rare. Although aneurysms are described following surgical treatment of patent ductus arteriosus (PDA), occurrence of this lesion in association with PDA without previous surgery is extremely uncommon. An eight-year-old patient with PDA and aneurysm of the main PA is described in this report. Clinical diagnosis of PDA was made upon presentation. Diagnosis of PA aneurysm was suspected on chest x-ray and was confirmed on transthoracic echocardiography. Successful surgical resection of the aneurysm and division of the duct were performed under cardiopulmonary bypass. The patient did well on follow-up both from clinical and echocardiographic point of view.
Abolmaali, Nasreddin D; Hietschold, Volker; Appold, Steffen; Ebert, Wolfgang; Vogl, Thomas J
The goal of this study was visualisation and quality assessment of the pulmonary arteries in pigs with modified navigator-echo magnetic resonance angiography using an intravascular contrast agent. Five sedated pigs were examined in a clinical 1.5-T system with modified three-dimensional navigator-echo magnetic resonance angiography (slice thickness 3 mm, pixel size 2.4x1.8 mm2) to evaluate the pulmonary arteries. Using a phased-array four-element thorax coil the entire thorax was scanned before and after intravenous infusion of a gadolinium-based intravascular contrast agent. Assessment of image quality, enhancement-related contrast-to-noise ratio (CNR) measurements and improvement of visibility of peripheral pulmonary vessels was performed. Improvement of quality using Gadomer-17 was found for smaller vessels; pulmonary trunks and the main pulmonary arteries were sufficiently imaged without enhancement. Mean rise of CNR measured in the pulmonary trunks was 28.64% ( P=0.0002), mean rise of CNR in the main pulmonary arteries and the segmental arteries were 79.6% and 148.2%, respectively. Mean distance between the visible peripheral end of 60 sub-segmental arteries and the inner thoracic wall was 12.2 +/- 0.4 mm, and was significantly ( P=0.00002) reduced after contrast infusion to 8.0 +/- 0.4 mm. The combination of inherent flow sensitivity of navigator-echo angiography and Gadomer-17 proved effective for imaging of the pulmonary arteries. In contrast to standard contrast-enhanced pulmonary MRA studies, breath holding is not required. Further studies and the evaluation of findings of patients suffering from pulmonary embolism are needed to evaluate the possible benefits of a higher spatial resolution which is achievable using navigator-echo techniques in contrast to the higher temporal resolution of ultra-fast pulmonary MRA.
Chida, Ayako; Shintani, Masaki; Matsushita, Yoshihisa; Sato, Hiroki; Eitoku, Takahiro; Nakayama, Tomotaka; Furutani, Yoshiyuki; Hayama, Emiko; Kawamura, Yoichi; Inai, Kei; Ohtsuki, Shinichi; Saji, Tsutomu; Nonoyama, Shigeaki; Nakanishi, Toshio
Mutations of BMPR2 and other TGF-β superfamily genes have been reported in pulmonary arterial hypertension (PAH). However, 60–90% of idiopathic PAH cases have no mutations in these genes. Recently, the expression of NOTCH3 was shown to be increased in the pulmonary artery smooth muscle cells of PAH patients. We sought to investigate NOTCH3 and its target genes in PAH patients and clarify the role of NOTCH3 signaling. We screened for mutations in NOTCH3, HES1, and HES5 in 41 PAH patients who had no mutations in BMPR2, ALK1, endoglin, SMAD1/4/8, BMPR1B, or Caveolin-1. Two novel missense mutations (c.2519 G>A p.G840E, c.2698 A>C p.T900P) in NOTCH3 were identified in two PAH patients. We performed functional analysis using stable cell lines expressing either wild-type or mutant NOTCH3. The protein-folding chaperone GRP78/BiP was colocalized with wild-type NOTCH3 in the endoplasmic reticulum, whereas the majority of GRP78/BiP was translocated into the nuclei of cells expressing mutant NOTCH3. Cell proliferation and viability were higher for cells expressing mutant NOTCH3 than for those expressing wild-type NOTCH3. We identified novel NOTCH3 mutations in PAH patients and revealed that these mutations were involved in cell proliferation and viability. NOTCH3 mutants induced an impairment in NOTCH3-HES5 signaling. The results may contribute to the elucidation of PAH pathogenesis. PMID:24936512
Lee, Pilhwa; Carlson, Brian E; Chesler, Naomi; Olufsen, Mette S; Qureshi, M Umar; Smith, Nicolas P; Sochi, Taha; Beard, Daniel A
Individualized modeling and simulation of blood flow mechanics find applications in both animal research and patient care. Individual animal or patient models for blood vessel mechanics are based on combining measured vascular geometry with a fluid structure model coupling formulations describing dynamics of the fluid and mechanics of the wall. For example, one-dimensional fluid flow modeling requires a constitutive law relating vessel cross-sectional deformation to pressure in the lumen. To investigate means of identifying appropriate constitutive relationships, an automated segmentation algorithm was applied to micro-computerized tomography images from a mouse lung obtained at four different static pressures to identify the static pressure-radius relationship for four generations of vessels in the pulmonary arterial network. A shape-fitting function was parameterized for each vessel in the network to characterize the nonlinear and heterogeneous nature of vessel distensibility in the pulmonary arteries. These data on morphometric and mechanical properties were used to simulate pressure and flow velocity propagation in the network using one-dimensional representations of fluid and vessel wall mechanics. Moreover, wave intensity analysis was used to study effects of wall mechanics on generation and propagation of pressure wave reflections. Simulations were conducted to investigate the role of linear versus nonlinear formulations of wall elasticity and homogeneous versus heterogeneous treatments of vessel wall properties. Accounting for heterogeneity, by parameterizing the pressure/distention equation of state individually for each vessel segment, was found to have little effect on the predicted pressure profiles and wave propagation compared to a homogeneous parameterization based on average behavior. However, substantially different results were obtained using a linear elastic thin-shell model than were obtained using a nonlinear model that has a more
Chung, Wook-Jin; Park, Yong Bum; Jeon, Chan Hong; Jung, Jo Won; Ko, Kwang-Phil; Choi, Sung Jae; Seo, Hye Sun; Lee, Jae Seung; Jung, Hae Ok
Despite recent advances in understanding of the pathobiology and targeted treatments of pulmonary arterial hypertension (PAH), epidemiologic data from large populations have been limited to western countries. The aim of the Korean Registry of Pulmonary Arterial Hypertension (KORPAH) was to examine the epidemiology and prognosis of Korean patients with PAH. KORPAH was designed as a nationwide, multicenter, prospective data collection using an internet webserver from September 2008 to December 2011. A total of 625 patients were enrolled. The patients' mean age was 47.6 ± 15.7 yr, and 503 (80.5%) were women. The diagnostic methods included right heart catheterization (n = 249, 39.8%) and Doppler echocardiography (n = 376, 60.2%). The etiologies, in order of frequency, were connective tissue disease (CTD), congenital heart disease, and idiopathic PAH (IPAH) (49.8%, 25.4%, and 23.2%, respectively). Patients with WHO functional class III or IV at diagnosis were 43.4%. In total, 380 (60.8%) patients received a single PAH-specific treatment at the time of enrollment, but only 72 (18.9%) patients received combination therapy. Incident cases during the registry represented 297 patients; therefore, the incidence rate of PAH was 1.9 patients/yr/million people. The 1st-, 2nd-, and 3rd-yr estimated survival rates were 90.8%, 87.8%, and 84.4%, respectively. Although Korean PAH patients exhibited similar age, gender, and survival rate compared with western registries, they showed relatively more CTD-PAH in the etiology and also systemic lupus erythematosus among CTD-PAH. The data suggest that earlier diagnosis and more specialized therapies should be needed to improve the survival of PAH patients.
Lee, Jin Hwa; Cho, Michael H.; Hersh, Craig P.; McDonald, Merry-Lynn N.; Wells, J. Michael; Dransfield, Mark T.; Bowler, Russell P.; Lynch, David A.; Lomas, David A.; Crapo, James D.
Pulmonary hypertension is associated with advanced chronic obstructive pulmonary disease (COPD), although pulmonary vascular changes occur early in the course of the disease. Pulmonary artery (PA) enlargement (PAE) measured by computed tomography correlates with pulmonary hypertension and COPD exacerbation frequency. Genome-wide association studies of PAE in subjects with COPD have not been reported. To investigate whether genetic variants are associated with PAE within subjects with COPD, we investigated data from current and former smokers from the COPDGene Study and the Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints study. The ratio of the diameter of the PA to the diameter of the aorta (A) was measured using computed tomography. PAE was defined as PA/A greater than 1. A genome-wide association study for COPD with PAE was performed using subjects with COPD without PAE (PA/A ≤ 1) as a control group. A secondary analysis used smokers with normal spirometry as a control group. Genotyping was performed on Illumina platforms. The results were summarized using fixed-effect meta-analysis. Both meta-analyses revealed a genome-wide significant locus on chromosome 15q25.1 in IREB2 (COPD with versus without PAE, rs7181486; odds ratio [OR] = 1.32; P = 2.10 × 10−8; versus smoking control subjects, rs2009746; OR = 1.42; P = 1.32 × 10−9). PAE was also associated with a region on 14q31.3 near the GALC gene (rs7140285; OR = 1.55; P = 3.75 × 10−8). Genetic variants near IREB2 and GALC likely contribute to genetic susceptibility to PAE associated with COPD. This study provides evidence for genetic heterogeneity associated with a clinically important COPD vascular subtype. PMID:25101718
Lee, Jin Hwa; Cho, Michael H; Hersh, Craig P; McDonald, Merry-Lynn N; Wells, J Michael; Dransfield, Mark T; Bowler, Russell P; Lynch, David A; Lomas, David A; Crapo, James D; Silverman, Edwin K
Pulmonary hypertension is associated with advanced chronic obstructive pulmonary disease (COPD), although pulmonary vascular changes occur early in the course of the disease. Pulmonary artery (PA) enlargement (PAE) measured by computed tomography correlates with pulmonary hypertension and COPD exacerbation frequency. Genome-wide association studies of PAE in subjects with COPD have not been reported. To investigate whether genetic variants are associated with PAE within subjects with COPD, we investigated data from current and former smokers from the COPDGene Study and the Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints study. The ratio of the diameter of the PA to the diameter of the aorta (A) was measured using computed tomography. PAE was defined as PA/A greater than 1. A genome-wide association study for COPD with PAE was performed using subjects with COPD without PAE (PA/A ≤ 1) as a control group. A secondary analysis used smokers with normal spirometry as a control group. Genotyping was performed on Illumina platforms. The results were summarized using fixed-effect meta-analysis. Both meta-analyses revealed a genome-wide significant locus on chromosome 15q25.1 in IREB2 (COPD with versus without PAE, rs7181486; odds ratio [OR] = 1.32; P = 2.10 × 10(-8); versus smoking control subjects, rs2009746; OR = 1.42; P = 1.32 × 10(-9)). PAE was also associated with a region on 14q31.3 near the GALC gene (rs7140285; OR = 1.55; P = 3.75 × 10(-8)). Genetic variants near IREB2 and GALC likely contribute to genetic susceptibility to PAE associated with COPD. This study provides evidence for genetic heterogeneity associated with a clinically important COPD vascular subtype.
Shimohama, S.; Tsukahara, T.; Taniguchi, T.; Fujiwara, M.
Cholinergic receptor sites in bovine cerebral arteries were analyzed using radioligand binding techniques with the cholinergic agonist, /sup 3/H-acetylcholine (ACh), as the ligand. Specific binding of /sup 3/H-ACh to membrane preparations of bovine cerebral arteries was saturable, of two binding sites, with dissociation constant (K/sub D/) values of 0.32 and 23.7 nM, and maximum binding capacity (Bmax) values of 67 and 252 fmol/mg protein, respectively. Specific binding of /sup 3/H-ACh was displaced effectively by muscarinic cholinergic agents and less effectively by nicotinic cholinergic agents. IC/sub 50/ values of cholinergic drugs for /sup 3/H-ACh binding were as follows: atropine, 38.5 nM; ACh, 59.8 nM; oxotremorine, 293 nM; scopolamine 474 nM; carbamylcholine, 990 nM. IC/sub 50/ values of nicotinic cholinergic agents such as nicotine, cytisine and ..cap alpha..-bungarotoxin exceeded 50 ..mu..M. Choline acetyltransferase activity was 1.09 nmol/mg protein/hour in the cerebral arteries. These findings suggest that the cholinergic nerves innervate the bovine cerebral arteries and that there are at least two classes of ACh binding sites of different affinities on muscarinic reporters in these arteries. 18 references, 2 figures, 2 tables.
Coche, Emmanuel; Pawlak, Sebastien; Dechambre, Stéphane; Maldague, Baudouin
Our objective was to analyze the peripheral pulmonary arteries using thin-collimation multi-slice spiral CT. Twenty consecutive patients underwent enhanced-spiral multi-slice CT using 1-mm collimation. Two observers analyzed the pulmonary arteries by consensus on a workstation. Each artery was identified on axial and 3D shaded-surface display reconstruction images. Each subsegmental artery was measured at a mediastinal window setting and compared with anatomical classifications. The location and branching of every subsegmental artery was recorded. The number of well-visualized sub-subsegmental arteries at a mediastinal window setting was compared with those visualized at a lung window setting. Of 800 subsegmental arteries, 769 (96%) were correctly visualized and 123 accessory subsegmental arteries were identified using the mediastinal window setting. One thousand ninety-two of 2019 sub-subsegmental arteries (54%) identified using the lung window setting were correctly visualized using the mediastinal window setting. Enhanced multi-slice spiral CT with thin collimation can be used to analyze precisely the subsegmental pulmonary arteries and may identify even more distal pulmonary arteries.
Beltrán-Gámez, Miguel E; Sandoval-Zárate, Julio; Pulido, Tomás
In experimental and clinical cardiology, phosphodiesterase type 5 (PDE-5) inhibitors have brought scientific interest as a therapeutic tool in pulmonary arterial hypertension (PAH) management in recent years. Phosphodiesterases are a superfamily of enzymes that inactivate cyclic adenosine monophosphate and cyclic guanosine monophosphate, the second messengers of prostacyclin and nitric oxide. The rationale for the use of PDE-5 inhibitors in PAH is based on their capacity to overexpresss the nitric oxide pathway pursued inhibition of cyclic guanosine monophosphate hydrolysis. By increasing cyclic guanosine monophosphate levels it promotes vasodilation, antiproliferative and pro-apoptotic effects that may reverse pulmonary vascular remodeling. There is also evidence that these drugs may directly enhance right ventricular contractility through an increase in cyclic adenosine monophosphate mediated by the inhibition of the cyclic guanosine monophosphate -sensitive PDE-3. Sildenafil, tadalafil and vardenafil are 3 specific PDE-5 inhibitors in current clinical use, which share similar mechanisms of action but present some significant differences regarding potency, selectivity for PDE-5 and pharmacokinetic properties. Sildenafil received approval in 2005 by the Food and Drug Administration and the European Medicines Agency and tadalafil in 2009 by the Food and Drug Administration and the European Medicines Agency for the treatment of PAH in patients classified as NYHA/WHO functional class II and III. In Mexico, sildenafil and tadalafil were approved by Comisión Federal de Protección contra Riesgos Sanitarios for this indication in 2010 and 2011, respectively.
de Jesus Perez, Vinicio
Over the past 20 years, there has been an explosion in the development of therapeutics to treat pulmonary arterial hypertension (PAH), a rare but life-threatening disorder associated with progressive elevation of pulmonary pressures and severe right heart failure. Recently, the field has seen the introduction of riociguat, a soluble guanylate cyclase stimulator, a new endothelin receptor antagonist (macitentan), and oral prostanoids (treprostinil and selexipag). Besides new drugs, there have been significant advances in defining the role of upfront combination therapy in treatment-naïve patients as well as proposed methods to deliver systemic prostanoids by use of implantable pumps. In this review, we will touch upon the most important developments in PAH therapeutics over the last three years and how these have changed the guidelines for the treatment of PAH. These exciting developments herald a new era in the treatment of PAH which will be punctuated by the use of more clinically relevant endpoints in clinical research trials and a novel treatment paradigm that may involve upfront double- or triple-combination therapy. We anticipate that the future will make use of these strategies to test the efficacy of upcoming new drugs that aspire to reduce disease progression and improve survival in patients afflicted with this devastating disease. PMID:27990270
Hinzmann, Barbara; Heinz, Sabina; Gall, Henning; Jenkins, David; Kim, Nick H.; Lang, Irene
Abstract We conducted an international study to evaluate practices in the diagnosis and management of pulmonary arterial hypertension (PAH) globally across different geographic regions. Between July and October 2012, PAH-treating physicians completed a 15-minute online questionnaire and provided patient record data for their 3 or 5 most recent patients with PAH. Overall, 560 physicians (Europe: 278; United States: 160; Argentina: 53; Japan: 69) completed the questionnaire and provided data for 2,618 patients. The proportion of physicians who described themselves as working in or affiliated with a specialized pulmonary hypertension center ranged from 13% in Argentina to 74% in the United States. At the time of diagnosis, patients’ New York Heart Association functional class differed significantly between regions. At the time of last assessment, functional class had improved overall, and differences between regions had largely disappeared. A large proportion of patients did not undergo right heart catheterization for the diagnosis of PAH (Europe: 7%–21%; United States: 21%; Japan: 19%; Argentina: 51%). Variations in management included greater use of phosphodiesterase 5 inhibitors in the United States than in Europe and Japan and greater use of triple or greater combination therapy in Japan than in other regions. Results from this study, which includes a global aspect of PAH care, demonstrate that there are significant differences in PAH management between regions and low adherence to guidelines recommending right heart catheterization for the diagnosis of PAH. PMID:27683611
Gabbay, Eli; Fraser, John; McNeil, Keith
The dual endothelin receptor antagonist, bosentan, is an orally active therapy, which is effective in the treatment of pulmonary arterial hypertension (PAH). This review critically appraises the evidence for the efficacy of bosentan in idiopathic and familial PAH, in PAH associated with connective tissue disease and in PAH which may develop in association with other conditions. Data from the pivotal placebo controlled studies and their open labeled extensions as well as long term survival and quality of life data is presented. Data is also presented on the potential benefit of bosentan in patients with inoperable chronic thromboembolic pulmonary hypertension. The safety and tolerability of bosentan as well as drug interactions are discussed. Dosage recommendations in adults and pediatrics are presented. An algorithm is provided to guide the reader in monitoring potential increases in alanine and aspartate transaminase levels that may occur with bosentan use and the dose adjustments that are recommended as a result of any increase in the levels of these enzymes are shown. Finally, the role of bosentan as part of combination therapy in PAH is examined. PMID:18200808
Dias-Neto, Marina; Luísa-Neves, Ana; Pinho, Sónia; Gonçalves, Nádia; Mendes, Maria; Eloy, Catarina; Lopes, José M; Gonçalves, Daniel; Ferreira-Pinto, Manuel; Leite-Moreira, Adelino F; Henriques-Coelho, Tiago
Pediatric pulmonary arterial hypertension (PAH) presents certain specific features. In this specific age group, experimental models to study the pathophysiology of PAH are lacking. To characterize hemodynamic, morphometric, and histological progression as well as the expression of neurohumoral factors and regulators of cardiac transcription in an infantile model of PAH induced by monocrotaline (MCT), eight-day-old Wistar rats were randomly injected with MCT (30 mg/kg, sc, n = 95) or equal volume of saline solution (n = 92). Animals were instrumented for biventricular hemodynamic recording 7, 14, and 21 days after MCT, whereas samples were collected at 1, 3, 7, 14, and 21 days after MCT. Different time point postinjections were defined for further analysis. Hearts and lungs were collected for morphometric characterization, assessment of right- and left-ventricle (RV and LV) cardiomyocyte diameter and collagen type-I and type-III ratio, RV collagen volume fraction, and pulmonary vessels wall thickness. mRNA quantification was undertaken for brain natriuretic peptide (BNP), endothelin-1 (ET-1), and for cardiac transcription regulators (HOP and Islet1). Animals treated with MCT at the 8th day of life presented RV hypertrophy since day 14 after MCT injection. There were no differences on the RV collagen volume fraction or collagen type-I and type-III ratio. Pulmonary vascular remodelling and PAH were present on day 21, which were accompanied by an increased expression of BNP, ET-1, HOP, and Islet1. The infantile model of MCT-induced PAH can be useful for the study of its pathophysiology and to test new therapeutic targets in pediatric age group.
Gomberg-Maitland, Mardi; Demarco, Teresa; Frost, Adaani E.; Torbicki, Adam; Langleben, David; Pulido, Tomas; Correa-Jaque, Priscilla; Passineau, Michael J.; Wiener, Howard W.; Tamari, Mayumi; Hirota, Tomomitsu; Kubo, Michiaki; Tiwari, Hemant K.
Rationale: Pulmonary arterial hypertension (PAH) is a progressive fatal disease. Variable response and tolerability to PAH therapeutics suggests that genetic differences may influence outcomes. The endothelin pathway is central to pulmonary vascular function, and several polymorphisms and/or mutations in the genes coding for endothelin (ET)-1 and its receptors correlate with the clinical manifestations of other diseases. Objectives: To examine the interaction of ET-1 pathway polymorphisms and treatment responses of patients with PAH treated with ET receptor antagonists (ERAs). Methods: A total of 1,198 patients with PAH were prospectively enrolled from 45 U.S. and Canadian pulmonary hypertension centers or retrospectively from global sites participating in the STRIDE (Sitaxsentan To Relieve Impaired Exercise) trials. Comprehensive objective measures including a 6-minute-walk test, Borg dyspnea score, functional class, and laboratory studies were completed at baseline, before the initiation of ERAs, and repeated serially. Single-nucleotide polymorphisms from ET-1 pathway candidate genes were selected from a completed genome-wide association study performed on the study cohort. Measurements and Main Results: Patient efficacy outcomes were analyzed for a relationship between ET-1 pathway polymorphisms and clinical efficacy using predefined, composite positive and negative outcome measures in 715 European descent samples. A single-nucleotide polymorphism (rs11157866) in the G-protein alpha and gamma subunits gene was significantly associated, accounting for multiple testing, with a combined improvement in functional class and 6-minute-walk distance at 12 and 18 months and marginally significant at 24 months. Conclusions: ET-1 pathway associated polymorphisms may influence the clinical efficacy of ERA therapy for PAH. Further prospective studies are needed. PMID:26252367
Hardin, Elizabeth Ashley; Chin, Kelly M
Pulmonary arterial hypertension is characterized by abnormalities in the small pulmonary arteries including increased vasoconstriction, vascular remodeling, proliferation of smooth muscle cells, and in situ thrombosis. Selexipag, a novel, oral prostacyclin receptor agonist, has been shown to improve hemodynamics in a phase II clinical trial and reduce clinical worsening in a large phase III clinical trial involving patients with pulmonary arterial hypertension. In this paper, we describe the prostacyclin signaling pathway, currently available oral prostanoid medications, and the development and clinical use of selexipag. PMID:27895464
Gottwalles, Yannick; Wunschel-Joseph, Marie-Eve; Hanssen, Michel
Rupture of the pulmonary artery or one of its branches during Swan-Ganz catheterization is a complication that is rare but remains fatal in almost 50% of cases. The risk factors and mechanisms involved in the pathogenesis of this accident have been widely reported. Management is twofold: resuscitation procedures and specific medical or even surgical treatment. We report a case of pulmonary artery rupture occurring during Swan-Ganz catheterization that was treated by coil embolization. This technique, which is quick and simple to use, would appear to be very promising. This is the first case of successful emergency treatment of pulmonary artery rupture using an endovascular technique.
Shingyoji, Masato; Ikebe, Dai; Itakura, Meiji; Nakajima, Takahiro; Itami, Makiko; Kimura, Hideki; Iizasa, Toshihiko
Pulmonary artery sarcoma (PAS) is a rare tumor that is often detected at an advanced stage, when disease is so widespread that a radical surgical procedure is no longer indicated. Therefore, less invasive biopsy techniques are required to establish a definitive preoperative diagnosis. Endobronchial ultrasound (EBUS) is useful for producing real-time images of both lymph nodes and the interior of pulmonary arteries adjacent to the bronchi. We report a case with masslike lesions in the pulmonary artery that were observed by EBUS and from which tissue was obtained by endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) to establish a diagnosis of PAS.
Chen, Xiaoxia; Ren, Shengxiang; Li, Aiwu; Zhou, Caicun
The incidence rate of pulmonary artery sarcoma is very low, but its prognosis is extremely poor. In this case report, after various initial diagnoses at the early stage, pulmonary artery sarcoma was confirmed by surgery. 1 year later, the tumor recurred. After chemotherapy, the patient showed improvement of the subjective complaint of tightness in the chest, and radiological lesion decreased in size. The survival time was extended by 2.5 years. This is the first case report of pulmonary artery sarcoma with such chemo-sensitivity.
Hardin, Elizabeth Ashley; Chin, Kelly M
Pulmonary arterial hypertension is characterized by abnormalities in the small pulmonary arteries including increased vasoconstriction, vascular remodeling, proliferation of smooth muscle cells, and in situ thrombosis. Selexipag, a novel, oral prostacyclin receptor agonist, has been shown to improve hemodynamics in a phase II clinical trial and reduce clinical worsening in a large phase III clinical trial involving patients with pulmonary arterial hypertension. In this paper, we describe the prostacyclin signaling pathway, currently available oral prostanoid medications, and the development and clinical use of selexipag.
Taçoy, Gülten; Ekim, Numan Nadir; Cengel, Atiye
Idiopathic pulmonary arterial hypertension (IPAH) is characterized by a progressive increase in pulmonary vascular resistance, which may lead to right ventricular failure and death. Major cardiovascular and pulmonary alterations occur during pregnancy and therefore worsen or increase the complications of pulmonary arterial hypertension (PAH). A patient diagnosed with IPAH after a successful full-term pregnancy and cesarean section with epidural anesthesia is presented. The postoperative course was complicated by progressive dyspnea, and lower limb edema. The outcome of treatment with sildenafil during puerperium was favorable in this patient. The clinical course was complicated by an unexpected spontaneous pregnancy after primary infertility.
Guo, Yuehong; Wang, Tie; Yang, Minfu
A 32-year-old woman, who presented with "sharp pain" in the right chest for more than 1 month and worsening dyspnea and fever for 10 days, was initially thought to have a pulmonary embolism. Cardiac ultrasound showed an ill-defined echogenic mass within the pulmonary trunk. F-FDG PET/CT was performed for further evaluation. PET/CT showed an intense hypermetabolism in the main, bilateral proximal, and the right main pulmonary arteries, suggesting the presence of a malignant lesion. Biopsy confirmed the lesion as a primary pulmonary artery sarcoma.
Rahimtoola, S H; Ongley, P A; Swan, H J
Introduction of a cardiac catheter into the pulmonary artery from the right heart is not possible in a substantial proportion of patients with transposition of the great vessels. It is necessary to obtain the pulmonary artery pressure and oxygen saturation value to evaluate the degree of pulmonary stenosis and the pulmonary vascular resistance. Twenty-three patients are described in whom this was accomplished by percutaneous suprasternal puncture. There was no mortality and there were no significant complications. The technique appears to be safe and reliable.
Hirata, Naoyuki; Kanaya, Noriaki; Yamazaki, Yutaka; Sonoda, Hajime; Namiki, Akiyoshi
We report a rare case of pulmonary embolism (PE) caused by a carbon dioxide (CO2) blower during off-pump coronary artery bypass grafting (OPCAB). When the anastomosis of the right internal thoracic artery to left anterior descending artery was performed, the operator tore the right ventricle outflow track (RVOT) that was adjacent to the left anterior descending artery. Immediately after the anastomosis and repair of the torn RVOT with CO2 blower, the systolic pulmonary artery pressure (PAP) increased from 28 to 64 mmHg, and end-tidal CO2 decreased from 32 to 12 mmHg. Because transesophageal echocardiograph (TEE) showed numerous gas bubbles in the main pulmonary artery, we diagnosed PE caused by invasion of CO2 gas bubbles via the torn RVOT. Although a CO2 blower is useful to enhance visualization of the anastomosis during OPCAB, it should not be used for the venous system because it may cause CO2 embolism.
Munoz, J.J. Garcia, J.A.; Bentabol, M.; Padin, M.I.; Serrano, F.
We report the case of a 29-year-old man with hemoptysis. The patient came to the emergency department, where a laboratory test and chest radiograph were reported as normal. The following day the patient again had hemoptysis, though less than previously. He reported no chest pain, dyspnea, fever, catarrh, changes in urine or feces, contact with patients with bacillus disease or constitutional symptoms. Doppler ultrasound of the chest showed right basal parenchymatous condensation containing a vessel with arterial flow (in the opposite direction to the aortic flow) compatible with an aberrant vessel, possibly a sequestration, leaving the aorta above the celiac trunk. Because of the findings of the chest echogram and magnetic resonance study, thoracoabdominal computed tomography angiography was undertaken; this showed right basal condensation and an anomalous vessel originating 1 cm above the celiac trunk, supplying the right lower lobe. An aortic and pulmonary arteriogram via an arterial and right femoral vein approach confirmed the findings. The patient was treated successfully with percutaneous embolization with coils. The relevant literature is reviewed.
Tagawa, Miki; Iwai, Hidetaka; Fukatsu, Ken; Shimada, Mami; Hirabayashi, Yoshihiro
We report a case of negative-pressure pulmonary edema occurring by tracheal obstruction caused by the brachiocephalic artery. The patient had deformed thorax with cerebral palsy, which deformed thorax placing the brachiocephalic artery high over the trachea, resulting in close and tight contact between the artery and trachea. Additional deformity of the thorax associated with myotonic attacks after general anesthesia might shorten the distance between the sternal notch and the vertebral body, resulting in the tracheal obstruction by the artery.
Shi, Zhaoling; Wu, Huajie; Luo, Jianfeng; Sun, Xin
STARS (STriated muscle Activator of Rho Signaling) is a sarcomeric protein, which expressed early in cardiac development and involved in pathological remodeling. Abundant evidence indicated that STARS could regulate cell proliferation, but it's exact function remains unclear. In this study, we aimed to investigate the role of STARS in the proliferation of pulmonary arterial smooth muscle cells (PASMC) and the potential effect on the progression of pulmonary arterial hypertension (PAH). In this study, we established a PAH mouse model through chronic hypoxia exposure as reflected by the increased RVSP and RVHI. Western blot and RT-qPCR detected the increased STARS protein and mRNA levels in PAH mice. Next, we cultured the primary PASMC from PAH mice. After STARS overexpression in PASMC, STARS, SRF and Egr-1 were up-regulated significantly. The MTT assay revealed an increase in cell proliferation. Flow cytometry showed a marked inhibition of cell apoptosis. However, STARS silence in PASMC exerted opposite effects with STARS overexpression. SRF siRNA transfection blocked the effects of STARS overexpression in PASMC. In order to further confirm the role of STARS in PAH mice in vivo, we exposed STARS knockout mice to hypoxia and found lower RVSP and RVHI in knockout mice as compared with controls. Our results not only suggest that STARS plays a crucial role in the development of PAH by increasing the proliferation of PASMC through activation of the SRF/Egr-1 pathway, but also provides a new mechanism for hypoxia-induced PAH. In addition, STARS may represent a potential treatment target.
Xing, Ai-ping; Hu, Xiao-yun; Shi, Yi-wei; Du, Yong-cheng
Pulmonary artery hypertension (PAH) is a severe disease characterized with progressive increase of pulmonary vascular resistance that finally causes right ventricular failure and premature death. Cigarette smoke (CS) is a major factor of Chronic Obstructive Pulmonary Disease (COPD) that can lead to PAH. However, the mechanism of CS-induced PAH is poorly understood. Mounting evidence supports that pulmonary vascular remodeling play an important role in the development of PAH. PDGF signaling has been demonstrated to be a major mediator of vascular remodeling implicated in PAH. However, the association of PDGF signaling with CS-induced PAH has not been documented. In this study, we investigated CS-induced PAH in rats and the expression of platelet derived growth factor (PDGF) and PDGF receptor (PDGFR) in pulmonary artery. Forty male rats were randomly divided into control group and three experimental groups that were exposed to CS for 1, 2, and 3 months, respectively. CS significantly increased right ventricular systolic pressure (RVSP) and right ventricular hypertrophy index (RVHI). Histology staining demonstrated that CS significantly increased the thickness of pulmonary artery wall and collagen deposition. The expression of PDGF isoform B (PDGF-B) and PDGF receptor beta (PDGFRβ) were significantly increased at both protein and mRNA levels in pulmonary artery of rats with CS exposure. Furthermore, Cigarette smoke extract (CSE) significantly increased rat pulmonary artery smooth muscle cell (PASMC) proliferation, which was inhibited by PDGFR inhibitor Imatinib. Thus, our data suggest PDGF signaling is implicated in CS-induced PAH.
McMahon, Colin J; Oslizlok, Paul; Walsh, Kevin P
Traditionally, the implantation of stents in young children with small blood vessels has been avoided as the presence of a metallic or fixed stent structure limits the ability to further dilate the stent with vessel growth. Pulmonary atresia with ventricular septal defect and hypoplastic pulmonary arteries represents one such cohort where the placement of fixed nondegradable stents has been difficult. We report a 2-month-old girl with pulmonary atresia, VSD, and multiple aorto-pulmonary collaterals with severely hypoplastic pulmonary arteries who underwent placement of a biodegradable magnesium stent within a stenotic aorto-pulmonary collateral. Although there was an initial significant increase in vessel diameter, significant restenosis occurred 4 months after stent placement. This to our knowledge represents the first case of the use of biodegradable stents in a child with severely hypoplastic pulmonary arteries. Although further refinements in stent technology are required, this development will hopefully usher in a new era of potential intervention in children previously deemed unsuitable for stent placement.
Vida, Vladimiro L; Biffanti, Roberta; Stellin, Giovanni; Milanesi, Ornella
We describe the natural history of an adolescent patient who developed an aortopulmonary fistula (APF) after transcatheter stent placement for left pulmonary artery stenosis after neonatal repair of d-transposition of the great arteries. Due to its rarity, the APF was not initially diagnosed and treated until 4 months later. The APF was occluded with a covered stent. Because this is not an isolated report in the literature, we believe it should be considered as a potential complication in all patients after balloon dilation of stenotic pulmonary artery branches after arterial switch surgery.
Buggeskov, Katrine B; Sundskard, Martin M; Jonassen, Thomas; Andersen, Lars W; Secher, Niels H; Ravn, Hanne B; Steinbrüchel, Daniel A; Jakobsen, Janus C; Wetterslev, Jørn
Introduction Absence of pulmonary perfusion during cardiopulmonary bypass (CPB) may be associated with reduced postoperative oxygenation. Effects of active pulmonary artery perfusion were explored in patients with chronic obstructive pulmonary disease (COPD) undergoing cardiac surgery. Methods 90 patients were randomised to receive pulmonary artery perfusion during CPB with either oxygenated blood (n=30) or histidine-tryptophan-ketoglutarate (HTK) solution (n=29) compared with no pulmonary perfusion (n=31). The coprimary outcomes were the inverse oxygenation index compared at 21 hours after starting CPB and longitudinally in a mixed-effects model (MEM). Secondary outcomes were tracheal intubation time, serious adverse events, mortality, days alive outside the intensive care unit (ICU) and outside the hospital. Results 21 hours after starting CPB patients receiving pulmonary artery perfusion with normothermic oxygenated blood had a higher oxygenation index compared with no pulmonary perfusion (mean difference (MD) 0.94; 95% CI 0.05 to 1.83; p=0.04). The blood group had also a higher oxygenation index both longitudinally (MEM, p=0.009) and at 21 hours (MD 0.99; CI 0.29 to 1.69; p=0.007) compared with the HTK group. The latest result corresponds to a difference in the arterial partial pressure of oxygen of 23 mm Hg with a median fraction of inspired oxygen of 0.32. Yet the blood or HTK groups did not demonstrate a longitudinally higher oxygenation index compared with no pulmonary perfusion (MEM, p=0.57 and 0.17). Similarly, at 21 hours there was no difference in the oxygenation index between the HTK group and those no pulmonary perfusion (MD 0.06; 95% CI −0.73 to 0.86; p=0.87). There were no statistical significant differences between the groups for the secondary outcomes. Discussion Pulmonary artery perfusion with normothermic oxygenated blood during cardiopulmonary bypass appears to improve postoperative oxygenation in patients with COPD undergoing
Sosnowski, Cyndi; Matella, Thomas; Fogg, Louis; Ilbawi, Michel; Nagaraj, Hosakote; Kavinsky, Clifford; Wolf, Andrew R; Diab, Karim; Caputo, Massimo; Kenny, Damien
Objective/Background Historically, the sole option for patients with a dysfunctional native right ventricular outflow tract (RVOT) requiring re-establishment of pulmonary competence has been surgical PVR. We sought to compare early outcomes of hybrid pulmonary valve replacement (PVR) combining surgical plication of the main pulmonary artery followed by transcatheter PVR, with a contemporary cohort of surgical PVR patients. Methods Retrospective chart analysis of all patients with a dilated native RVOT eligible for surgical PVR over 36 months was performed. The cohorts included patients with previous tetralogy of Fallot repair (n = 14), and previous intervention for congenital abnormality of the pulmonary valve (n = 7). Results Twenty-one patients with a dysfunctional native RVOT met criteria for PVR; 8 using the hybrid procedure (group 1: age, 31.5 +/- 17.4 years) and 13 with cardiopulmonary bypass (CPB) (group 2: age, 31 +/- 18.4 years). Valve delivery was successful in all patients with no procedural mortality. Group 1 had a lesser requirement for blood products (P =< 0.001) and a trend toward shorter hospital stay and higher post-operative hemoglobin. No patients in group 1 received inotropic support post-operatively compared to 54% of patients in group 2. Mean follow-up was 3.4 months for group 1 and 13.6 months for group 2 with the average peak gradient across the RVOT of 20.1 and 15.1 mm Hg respectively (P = 0.12), all with no more than mild PI. Conclusions Transcatheter hybrid PVR following RVOT plication provides a reasonable alternative to surgical PVR particularly in higher risk cohorts, reducing possible longer-term consequences of repeated runs of CPB. © 2016 Wiley Periodicals, Inc.
Howard, Luke S.; Tzoulaki, Ioanna; Gin-Sing, Wendy; Grapsa, Julia; Wilkins, Martin R.; Davies, Rachel J.; Nihoyannopoulos, Petros; Connolly, Susan B.; Gibbs, J. Simon R.
Abstract The age at diagnosis of pulmonary arterial hypertension (PAH) and the prevalence of cardiovascular (CV) risk factors are increasing. We sought to determine whether the response to drug therapy was influenced by CV risk factors in PAH patients. We studied consecutive incident PAH patients (n = 146) between January 1, 2008, and July 15, 2011. Patients were divided into two groups: the PAH–No CV group included patients with no CV risk factors (obesity, systemic hypertension, type 2 diabetes mellitus, permanent atrial fibrillation, mitral and/or aortic valve disease, and coronary artery disease), and the PAH-CV group included patients with at least one. The response to PAH treatment was analyzed in all the patients who received PAH drug therapy. The PAH–No CV group included 43 patients, and the PAH-CV group included 69 patients. Patients in the PAH–No CV group were younger than those in the PAH-CV group (P < 0.0001). In the PAH–No CV group, 16 patients (37%) improved on treatment and 27 (63%) did not improve, compared with 11 (16%) and 58 (84%) in the PAH-CV group, respectively (P = 0.027 after adjustment for age). There was no difference in survival at 30 months (P = 0.218). In conclusion, in addition to older age, CV risk factors may predict a reduced response to PAH drug therapy in patients with PAH. PMID:25610602
Charalampopoulos, Athanasios; Howard, Luke S; Tzoulaki, Ioanna; Gin-Sing, Wendy; Grapsa, Julia; Wilkins, Martin R; Davies, Rachel J; Nihoyannopoulos, Petros; Connolly, Susan B; Gibbs, J Simon R
The age at diagnosis of pulmonary arterial hypertension (PAH) and the prevalence of cardiovascular (CV) risk factors are increasing. We sought to determine whether the response to drug therapy was influenced by CV risk factors in PAH patients. We studied consecutive incident PAH patients (n = 146) between January 1, 2008, and July 15, 2011. Patients were divided into two groups: the PAH-No CV group included patients with no CV risk factors (obesity, systemic hypertension, type 2 diabetes mellitus, permanent atrial fibrillation, mitral and/or aortic valve disease, and coronary artery disease), and the PAH-CV group included patients with at least one. The response to PAH treatment was analyzed in all the patients who received PAH drug therapy. The PAH-No CV group included 43 patients, and the PAH-CV group included 69 patients. Patients in the PAH-No CV group were younger than those in the PAH-CV group (P < 0.0001). In the PAH-No CV group, 16 patients (37%) improved on treatment and 27 (63%) did not improve, compared with 11 (16%) and 58 (84%) in the PAH-CV group, respectively (P = 0.027 after adjustment for age). There was no difference in survival at 30 months (P = 0.218). In conclusion, in addition to older age, CV risk factors may predict a reduced response to PAH drug therapy in patients with PAH.
Senturk, Aysegul; Er, Mukremin; Karalezli, Aysegul; Yakut, Zeynep Ilerisoy; Soyturk, Ayse Nur; Cetin, Huseyin; Canan Hasanoglu, Hatice
Hydatid cyst (HC) is a parasitic disease that may involve many organs, especially the lung and the liver. Pulmonary artery location of the hydatid cyst is extremely rare, but it may cause life-threatening complications. We report a case of a hydatid cyst that completely filled the left main pulmonary artery and its distal part without cardiac involvement. Thoracic computed tomography showed filling defects in the pulmonary arteries. Endobronchial ultrasound was performed for differential diagnosis and it showed a cystic lesion. Hydatid cyst-specific IgE and hem agglutination test results were positive. In the literature, cases like this in which the diagnosis of pulmonary hydatid cyst is made by endobronchial ultrasound are not usually seen. Although many imaging modalities such as plain chest radiography, cross-sectional imaging (MDCT and MRI), echocardiography and conventional pulmonary angiography have been used in the diagnostic approach, we recommend endobronchial ultrasound for the differential diagnosis of cases with cystic formation. PMID:25793087
Beyer, J; Brunner, L; Klinner, W
Among 843 patients with Tetralogy of Fallot, 10 showed unilateral absence of a pulmonary artery. In 7 cases the cause was congenital aplasia, whereas thrombosis of one of the pulmonary arteries following systemic-pulmonary anastomosis was the cause in the remaining 3 patients. According to the reports of other authors and to our own experiences, this rare malformation is treated best with palliative operations, the technique depending on the patient's age and on the individual anatomical condition. Only in very few cases with an acceptable pathologic anatomy there will be a reasonable chance for successful repair with reconstruction of the continuity from the right ventricle to the affected lung. However, if complete repair is performed, reconstruction of the absent pulmonary artery usually will be necessary for avoidance of pulmonary hypertension of the contralateral lung.
Jing, Ran; Tang, Hao; Shen, Kangjun; Luo, Junming; Zhou, Xinmin
Primary myofibroblastic sarcomas of the pulmonary artery are very uncommon, but early detection is critical. Common clinical symptoms include shortness of breath, chest discomfort, and syncope. Patients diagnosed with a pulmonary tumor have a high risk of fatal pulmonary embolism. In this case study, we identified and diagnosed pulmonary artery myofibroblastic sarcoma in a young man by its imaging and pathologic characters. Surgery to excise the tumor was successfully performed and the operation was considered to have improved his prognosis. Postoperative examinations did not show any evidence of residual tumor, recurrence, or metastasis in the lungs or cardiac tissue. Based on the results of this case study, we concluded that the imaging and pathologic features of primary pulmonary artery myofibroblastic sarcoma can assist physicians in making a prompt diagnosis and an immediate surgical and treatment plan to greatly improve prognosis.
Bohn, Olga L; de León, Eric Acosta-Ponce; Lezama, Oscar; Rios-Luna, Nina P; Sánchez-Sosa, Sergio; Llombart-Bosch, Antonio
Primary sarcomas of the major blood vessels can be classified based on location in relationship to the wall or by histologic type. Angiosarcomas are malignant neoplasms that arise from the endothelial lining of the blood vessels; those arising in the intimal compartment of pulmonary artery are rare. We report a case of pulmonary artery angiosarcoma in a 36-year old female with pulmonary masses. The patient had no other primary malignant neoplasm, thus excluding a metastatic lesion. Gross examination revealed a thickened right pulmonary artery and a necrotic and hemorrhagic tumor, filling and occluding the vascular lumen. The mass extended distally, within the pulmonary vasculature of the right lung. Microscopically, an intravascular undifferentiated tumor was identified. The tumor cells showed expression for vascular markers VEGFR, VEGFR3, PDGFRa, FGF, Ulex europaeus, FVIII, FLI-1, CD31 and CD34; p53 was overexpressed and Ki67 proliferative rate was increased. Intravascular angiosarcomas are aggressive neoplasms, often associated with poor outcome.
Khan, Asaad Akbar; McFadden, Eugene Patrick
Flash pulmonary edema is characteristically sudden in onset with rapid resolution once appropriate therapy has been instituted (Messerli et al., 2011). Acute increase of left ventricular (LV) end diastolic pressure is the usual cause of sudden decompensated cardiac failure in this patient population. Presence of bilateral renal artery stenosis or unilateral stenosis in combination with a single functional kidney in the susceptible cohort is usually blamed for this condition. We describe a patient who presented with flash pulmonary edema in the setting of normal coronary arteries. Our case is distinct as our patient developed flash pulmonary edema secondary to unilateral renal artery stenosis in the presence of bilateral functioning kidneys. Percutaneous stent implantation in the affected renal artery resulted in rapid resolution of pulmonary edema. PMID:25793128
Tripathi, Mukesh; Kumar, Naresh; Singh, Prabhat K
In a young adult patient having situs solitus with dextrocardia the attempted pulmonary artery catheter placement for emergency mitral valve replacement required an unduly long length (50cm) of catheter insertion to get into right ventricle and then into pulmonary artery. Although catheter coiling was suspected initially, chest x-ray taken after successfully placement revealed an uncommon congenital anomalous venous connection i.e. right internal jugular opening into left sided superior vena cava then into inferior vena cava after running all along the left border of the heart. With the result, it required to pass 50cm of PA catheter to get into right ventricle in our patient. This emphasizes the need to look for abnormal venous connections during echocardiography and x-ray screening in congenital heart disease. Fluoroscopy is recommended when an unusual length of pulmonary artery catheter insertion is required to enter the pulmonary artery.
Divakaran, Vijay; Caldera, Angel; Stephens, Jack; Gonzalez, Rafael
Pulmonary artery catheter entrapment is a reported complication after cardiac surgery from inadvertent suturing of the catheter to the vena-caval wall during surgery. This article reports a simple percutaneous technique to retrieve the trapped catheter.
Gnanappa, Ganesh Kumar; Laohachai, Karina; Orr, Yishay; Ayer, Julian
Anomalous origin of a branch pulmonary artery from the aorta is a rare malformation, accounting for 0.12% of all congenital heart defects. Anomalous origin of the left pulmonary artery from the aorta (ALPA) constitutes a small proportion of these cases. ALPA has been reported to arise from the ascending aorta with various embryologic postulates. We report a case of isolated ALPA arising from the descending aorta in association with a patent ductus arteriosus, to emphasize its embryologic ambiguity.
Vaideeswar, Pradeep; Pillai, Raji
Most of the pulmonary arterial sarcomas arise from multi-potential mesenchymal intimal cells and are designated as intimal sarcomas. These tumors grow in the direction of blood flow into peripheral arteries producing clinical features mimicking pulmonary thromboembolism. Retrograde extension is rare. We report one such case of intimal sarcoma that had a retrograde extension into the right ventricular outflow tract, and review such a presentation in the last ten years.
Brochériou, I; Quillard, A; Gatecel, C; Wassef, M
Primary sarcomas of great vessels are rare and involve the aorta, pulmonary artery and inferior vena cava. The pathologic classification of these tumors can be made on the location of the sarcoma in relation to the vessel wall, luminal or mural. Luminal sarcomas are usually intimal sarcoma and mural sarcoma are most frequently leiomyosarcoma. The myofibroblastic or endothelial differentiation of these tumors is still debated. We report a case of intimal sarcoma of the pulmonary artery.
Akdeniz, Bahri; Ozpelit, Ebru
In recent times, the prevalence of pulmonary arterial hypertension (PAH) is more commonly seen among elderly populations. The increased prevalence of hypertension, diabetes, obesity, arterial stiffness, as well as diastolic dysfunction, may cause endothelial dysfunction and affect pulmonary vasculature. Furthermore, older patients have certain differences in clinical characteristics and outcomes. In this article, the special characteristics of aging in PAH patients have been reviewed, while the risk predictors of elderly patients are also discussed. PMID:28270839
Kaya, Akin; Ertan, Cağatay; Gürkan, Ozlem Ural; Fitöz, Suat; Atasoy, Cetin; Kiliçkap, Mustafa; Numanoğlu, Numan
Behçet's disease is currently recognized as a multisystemic disease that may present with vascular, cutaneous, pulmonary, neurologic, rheumatologic, gastrointestinal, and genitourinary manifestations. Despite this multiplicity, cardiac involvement and also the coexistence of bilateral pulmonary arterial aneurysms are rare. An interesting case is presented here with intracardiac thrombi and bilateral pulmonary arterial aneurysms that showed clinical regression with immunosuppressive therapy.
Chappell, Tresa; Creech, C Buddy; Parra, David; Strauss, Arnold; Scholl, Frank; Whitney, Gina
Intimal sarcoma of the pulmonary artery is rare in the adult population. It is usually diagnosed postmortem in patients thought to have pulmonary emboli. We present a case of intimal sarcoma of the pulmonary artery in an infant with a history of neonatal pulmonic stenosis.
Johnson, Roger H.; Karau, Kelly L.; Molthen, Robert C.; Dawson, Christopher A.
Stiffening, or loss of distensibility, of arterial vessel walls is among the manifestations of a number of vascular diseases including pulmonary arterial hypertension. We are attempting to quantify the mechanical properties of vessel walls of the pulmonary arterial tree using parameters derived from high-resolution volumetric x-ray CT images of rat lungs. The pulmonary arterial trees of the excised lungs are filled with a contrast agent. The lungs are imaged with arterial pressures spanning the physiological range. Vessel segment diameters are measured from the inlet to the periphery, and distensibilities calculated from diameters as a function of pressure. The method shows promise as an adjunct to other morphometric techniques such as histology and corrosion casting. It possesses the advantages of being nondestructive, characterizing the vascular structures while the lungs are imaged rapidly and in a near-physiological state, and providing the ability to associate mechanical properties with vessel location in the intact tree hierarchy.
Xu, Hongfei; Li, Weidong; Teng, Peng; Ni, Yiming
Cardiac haemangioma and coronary-pulmonary artery fistula are both rare entities. We present the case of a 45-year-old symptomatic male patient with a rare cardiac cavernous haemangioma. During assessment, coronary-pulmonary artery fistula was diagnosed by computed tomographic angiography (CTA) of the coronary artery. As far as we know, this is the first case in which cardiac haemangioma has been found to co-exist with coronary-pulmonary artery fistula. Surgery remains the most effective form of therapy. Meanwhile, in patients with heart issues, CTA of the coronary artery has its particularly advantages that can reduce the risk of a second operation and missed diagnosis. We also performed an electronic search of the published literature in English on cases of cardiac haemangioma.
Ngo, My-Linh D; Aggarwal, Avichal; Knudson, Jarrod D
Peripheral pulmonary artery stenosis is a common congenital heart lesion associated with several genetic syndromes. We have reviewed the genetics of the lesion and present an unusual case of peripheral pulmonary stenosis involving a newly reported genetic deletion on chromosome 16. Further studies will be needed to confirm association of this genotype and phenotype.
Bissacco, Daniele; Domanin, Maurizio; Schinco, Giuseppina; Gabrielli, Livio
Anatomical variations of carotid arteries may be related to their development (agenesis, aplasia, hypoplasia) or course (coiling, kinking, tortuosity). Partial or total aberrancies in carotid vessel anatomy rarely occur. We describe the case of a 95-year-old woman presented with sudden onset of confusion and disorientation together with upper limb clonus. Computed tomography (CT)-scan revealed a left frontal brain injury with a not conclusive carotid doppler ultrasound. CT angiography reported a bovine aortic arch with bilateral retroesophageal course of both common carotid arteries and left severe (>70%) internal carotid artery stenosis. The knowledge of anatomical variations of the course of carotid arteries is relevant for possible surgical or endovascular repair or in case of otolaryngology or intubation procedures. PMID:27699162
Huber, Adrian; Ott, Daniel; Christe, Andreas
We present a rare case of pulmonary intimal sarcoma mimicking pulmonary embolism in a 40-year-old woman. Although extremely rare, these tumors must be considered in patients who present inappropriate imaging findings that suggest embolism. Chest computed tomography is the modality of choice to determine the extent of the tumor. We present a female patient with suspected embolism that was in fact found to be an endothelial sarcoma of the pulmonary arteries. PMID:24778802
Ebner, Lukas; Huber, Adrian; Ott, Daniel; Christe, Andreas
We present a rare case of pulmonary intimal sarcoma mimicking pulmonary embolism in a 40-year-old woman. Although extremely rare, these tumors must be considered in patients who present inappropriate imaging findings that suggest embolism. Chest computed tomography is the modality of choice to determine the extent of the tumor. We present a female patient with suspected embolism that was in fact found to be an endothelial sarcoma of the pulmonary arteries.
Evison, Matthew; Crosbie, Philip; Chaturvedi, Anshuman; Shah, Rajesh; Booton, Richard
This case illustrates a rare but important differential diagnosis of pulmonary emboli in the field of thoracic oncology, that of pulmonary artery sarcoma. It describes particular clinical features that may raise suspicion of this tumor in cases of suspected pulmonary emboli, and highlights novel radiological modalities and tissue sampling techniques in such cases. Surgical resection, as part of multi-modality therapy, is the cornerstone of treatment that has seen survival dramatically improve in recent years for patients with this rare cancer.
Kervancioglu, Selim Andic, Cagatay; Bayram, Nazan; Telli, Cumali; Sarica, Akif; Sirikci, Akif
Pulmonary parenchymal endometriosis is extremely rare and usually manifests itself with a recurrent hemoptysis associated with the menstrual cycle. The therapies proposed for women with endometriosis consist of medical treatments and surgery. Bronchial artery embolization has become a well-established and minimally invasive treatment modality for hemoptysis, and to the best of our knowledge, it has not been reported in pulmonary endometriosis. We report a case of pulmonary parenchymal endometriosis treated with embolotheraphy for hemoptysis.
Ziganshina, Anna P; Ziganshin, Bulat A; Ziganshin, Ayrat U
Although the presence of purinoreceptors has been shown in many human and animal arteries, there is few data yet about their role in the arteries of the eye. The purpose of the present study was to evaluate the effects of several agonists of purinoreceptors on isolated arteries of the bovine eye. Responses of isolated preparations of bovine ophthalmic (OA) and posterior ciliary arteries (PCA) to agonists of purinoreceptors (ATP, α,β-methylene-ATP-α,β-meATP, 2-methylthioATP-2meSATP, uridine-5'-triphosphate-UTP) as well as agonists of adreno-, cholino-, adenosine and histamine receptors were recorded by a standard organ bath method. ATP induced contractions of the intact vessels but caused relaxation of α,β-meATP-pretreated arteries. Contractile responses of PCA to high concentrations of ATP and α,β-meATP were significantly stronger than responses of OA, as well as relaxative responses to ATP and adenosine were significantly stronger in PCA than in OA. We suggest that there are several subtypes of functionally active purinoreceptors in both OA and PCA, although the potency of agonists of purinoreceptors to produce mechanical responses is higher in PCA than in OA. Purinoreceptors can be potential targets for new drugs, treating vascular pathology of the eye.
Brenner, Laura; Chung, Wendy K
Pulmonary arterial hypertension (PAH) is a rare disorder that may be hereditary (HPAH), idiopathic (IPAH), or associated with either drug-toxin exposures or other medical conditions. Familial cases have long been recognised and are usually due to mutations in the bone morphogenetic protein receptor type 2 gene (BMPR2), or, much less commonly, two other members of the transforming growth factor-β superfamily, activin-like kinase-type 1 (ALK1), and endoglin (ENG), which are associated with hereditary hemorrhagic telangiectasia. In addition, approximately 20% of patients with IPAH carry mutations in BMPR2. Clinical testing for BMPR2 mutations is available and may be offered to HPAH and IPAH patients but should be preceded by genetic counselling, since lifetime penetrance is only 10% to 20%, and there are currently no known effective preventative measures. Identification of a familial mutation can be valuable in reproductive planning and identifying family members who are not mutation carriers and thus will not require lifelong surveillance. With advances in genomic technology and with international collaborative efforts, genome-wide association studies will be conducted to identify additional genes for HPAH, genetic modifiers for BMPR2 penetrance, and genetic susceptibility to IPAH. In addition, collaborative studies of BMPR2 mutation carriers should enable identification of environmental modifiers, biomarkers for disease development and progression, and surrogate markers for efficacy end points in clinical drug development, thereby providing an invaluable resource for trials of PAH prevention.
Humbert, Marc; Ghofrani, Hossein-Ardeschir
Until recently, three classes of medical therapy were available for the treatment of pulmonary arterial hypertension (PAH)—prostanoids, endothelin receptor antagonists and phosphodiesterase type 5 (PDE5) inhibitors. With the approval of the soluble guanylate cyclase stimulator riociguat, an additional drug class has become available targeting a distinct molecular target in the same pathway as PDE5 inhibitors. Treatment recommendations currently include the use of all four drug classes to treat PAH, but there is a lack of comparative data for these therapies. Therefore, an understanding of the mechanistic differences between these agents is critical when making treatment decisions. Combination therapy is often used to treat PAH and it is therefore important that physicians understand how the modes of action of these drugs may interact to work as complementary partners, or potentially with unwanted consequences. Furthermore, different patient phenotypes mean that patients respond differently to treatment; while a certain monotherapy may be adequate for some patients, for others it will be important to consider alternating or combining compounds with different molecular targets. This review describes how the four currently approved drug classes target the complex pathobiology of PAH and will consider the distinct target molecules of each drug class, their modes of action, and review the pivotal clinical trial data supporting their use. It will also discuss the rationale for combining drugs (or not) from the different classes, and review the clinical data from studies on combination therapy. PMID:26219978
Yandrapalli, Srikanth; Raza, Anoshia; Tariq, Sohaib; Aronow, Wilbert S
Heart failure (HF) is an emerging epidemic associate with significant morbidity, mortality, and health care expenditure. Although there were major advances in pharmacologic and device based therapies for the management of HF, mortality of this condition remains high. Accurate monitoring of HF patients for exacerbations is very important to reduce recurrent hospitalizations and its associated complications. With the failure of clinical signs, tele-monitoring, and laboratory bio-markers to function as early markers of HF exacerbations, more sophisticated techniques were sought to accurately predict the circulatory status in HF patients in order to execute timely pharmacological intervention to reduce frequent hospitalizations. CardioMEMSTM (St. Jude Medical, Inc., Saint Paul, Minnesota) is an implantable, wireless pulmonary arterial pressure (PAP) monitoring system which transmits the patient’s continuous PAPs to the treating health care provider in the ambulatory setting. PAP-guided medical therapy modification has been shown to significantly reduce HF-related hospitalization and overall mortality. In advanced stages of HF, wireless access to hemodynamic information correlated with earlier left ventricular assist device implantation and shorter time to heart transplantation. PMID:28163833
Barst, Robyn J
Pulmonary arterial hypertension (PAH) is a rare fatal disease. Current disease-specific therapeutic interventions in PAH target 1 of 3 established pathways in disease pathobiology: prostacyclin, nitric oxide, and endothelin-1. Endothelin receptor antagonists (ERAs) act on the endothelin pathway by blocking binding of endothelin-1 to its receptors (endothelin type-A [ETA] and/or type-B [ETB]) on the surface of endothelial and smooth muscle cells. Ambrisentan is an oral, once-daily, ETA-selective ERA in development for the treatment of PAH. In Phase 3 clinical trials in patients with PAH, ambrisentan (2.5–10 mg orally once-daily) improved exercise capacity, Borg dyspnea index, time to clinical worsening, WHO functional class, and quality of life compared with placebo. Ambrisentan provided durable (at least 2 years) improvement in exercise capacity in a Phase 2 long-term extension study. Ambrisentan was well tolerated with a lower incidence and severity of liver function test abnormalities compared with the ETA/ETB ERA, bosentan, and the ETA-selective ERA, sitaxsentan. Ambrisentan does not induce or inhibit P450 enzymes; therefore, ambrisentan is unlikely to affect the pharmacokinetics of P450-metabolized drugs. The demonstration of clinical efficacy, low incidence of acute hepatic toxicity, and low risk of drug–drug interactions support the role of ambrisentan for the treatment of PAH. PMID:17583171
Taichman, Darren B.; Chung, Lorinda; Klinger, James R.; Lewis, Sandra; Mandel, Jess; Palevsky, Harold I.; Rich, Stuart; Sood, Namita; Rosenzweig, Erika B.; Trow, Terence K.; Yung, Rex; Elliott, C. Gregory; Badesch, David B.
OBJECTIVE: Choices of pharmacologic therapies for pulmonary arterial hypertension (PAH) are ideally guided by high-level evidence. The objective of this guideline is to provide clinicians advice regarding pharmacologic therapy for adult patients with PAH as informed by available evidence. METHODS: This guideline was based on systematic reviews of English language evidence published between 1990 and November 2013, identified using the MEDLINE and Cochrane Library databases. The strength of available evidence was graded using the Grades of Recommendations, Assessment, Development, and Evaluation methodology. Guideline recommendations, or consensus statements when available evidence was insufficient to support recommendations, were developed using a modified Delphi technique to achieve consensus. RESULTS: Available evidence is limited in its ability to support high-level recommendations. Therefore, we drafted consensus statements to address many clinical questions regarding pharmacotherapy for patients with PAH. A total of 79 recommendations or consensus statements were adopted and graded. CONCLUSIONS: Clinical decisions regarding pharmacotherapy for PAH should be guided by high-level recommendations when sufficient evidence is available. Absent higher level evidence, consensus statements based upon available information must be used. Further studies are needed to address the gaps in available knowledge regarding optimal pharmacotherapy for PAH. PMID:24937180
Vaid, Haris M.; Camacho, Ximena; Granton, John T.; Mamdani, Muhammad M.; Yao, Zhan; Singh, Samantha; Juurlink, David N.; Gomes, Tara
Background. There are no Canadian prevalence studies on pulmonary arterial hypertension (PAH) to date. We described the characteristics of treated PAH patients and the healthcare utilization and costs associated with PAH in a population of public drug plan beneficiaries in Ontario, Canada. Methods. A retrospective cross-sectional analysis was conducted between April 2010 and March 2011 to identify treated PAH patients using population-based health administrative databases. We investigated demographic and clinical characteristics of treated PAH patients and conducted a cohort study to determine treatment patterns, healthcare utilization, and associated costs, over a one-year follow-up period (March 2012). Results. We identified 326 treated PAH cases in Ontario's publicly funded drug plan. Overall mean age was 59.4 years (±20.3 years) and over 77% of cases were women (n = 251). Combination therapy was used to treat 22.9% (n = 69) of cases, costing an average of $4,569 (SD $1,544) per month. Median monthly healthcare costs were $264 (IQR $96–$747) for those who survived and $2,021 (IQR $993–$6,399) for those who died over a one-year period, respectively (p < 0.01). Conclusions. PAH care in Ontario is complex and has high healthcare costs. This data may help guide towards improved patient management. PMID:27445555
Saito, Yukihiro; Nakamura, Kazufumi; Akagi, Satoshi; Sarashina, Toshihiro; Ejiri, Kentaro; Miura, Aya; Ogawa, Aiko; Matsubara, Hiromi; Ito, Hiroshi
The release of endogenous prostacyclin (PGI2) is depressed in patients with pulmonary arterial hypertension (PAH). PGI2 replacement therapy by epoprostenol infusion is one of the best treatments available for PAH. Here, we provide an overview of the current clinical data for epoprostenol. Epoprostenol treatment improves symptoms, exercise capacity, and hemodynamics, and is the only treatment that has been shown to reduce mortality in patients with idiopathic PAH (IPAH) in randomized clinical trials. We have reported that high-dose epoprostenol therapy (>40 ng/kg/min) also results in marked hemodynamic improvement in some patients with IPAH. High-dose epoprostenol has a pro-apoptotic effect on PAH-PASMCs via the IP receptor and upregulation of Fas ligand (FasL) in vitro. However, long-term intravenous administration of epoprostenol is sometimes associated with catheter-related infections and leads to considerable inconvenience for the patient. In the future, the development of new routes of administration or the development of powerful PGI2 analogs, IP-receptor agonists, and gene and cell-based therapy enhancing PGI2 production with new routes of administration is required.
Saito, Yukihiro; Nakamura, Kazufumi; Akagi, Satoshi; Sarashina, Toshihiro; Ejiri, Kentaro; Miura, Aya; Ogawa, Aiko; Matsubara, Hiromi; Ito, Hiroshi
The release of endogenous prostacyclin (PGI2) is depressed in patients with pulmonary arterial hypertension (PAH). PGI2 replacement therapy by epoprostenol infusion is one of the best treatments available for PAH. Here, we provide an overview of the current clinical data for epoprostenol. Epoprostenol treatment improves symptoms, exercise capacity, and hemodynamics, and is the only treatment that has been shown to reduce mortality in patients with idiopathic PAH (IPAH) in randomized clinical trials. We have reported that high-dose epoprostenol therapy (>40 ng/kg/min) also results in marked hemodynamic improvement in some patients with IPAH. High-dose epoprostenol has a pro-apoptotic effect on PAH-PASMCs via the IP receptor and upregulation of Fas ligand (FasL) in vitro. However, long-term intravenous administration of epoprostenol is sometimes associated with catheter-related infections and leads to considerable inconvenience for the patient. In the future, the development of new routes of administration or the development of powerful PGI2 analogs, IP-receptor agonists, and gene and cell-based therapy enhancing PGI2 production with new routes of administration is required. PMID:25999730
Tcherakian, Colas; Couderc, Louis-Jean; Humbert, Marc; Godot, Véronique; Sitbon, Olivier; Devillier, Philippe
Pulmonary arterial hypertension (PAH) is a severe complication of human immunodeficiency virus (HIV) infection and a leading major cause of death when present. HIV-PAH could be the consequence of multiple hits including the direct effects of HIV proteins, use of illicit drugs, and chronic inflammation. Indeed, HIV infection has long been identified as an immunosuppressive disease but, since the advent of highly active antiretroviral treatments (HAART), HIV infection is considered as an inflammatory disease in which vascular complications have become a major cause of morbidity and death. Conversely to immunosuppression, which correlates with blood CD4 + T cell level, inflammation in HIV infection is due to the lack of gut CD4 + T cell restoration. Such gut T cell depletion favors lipopolysaccharide translocation and, in turn, chronic systemic interleukin-6 overproduction. Conversely to blood CD4 + T cells, gut CD4 + T cells are only partially restored with HAART, usually slowly after several months or years, with a large heterogeneity from one patient to another. These characteristics may cause chronic inflammation, and we hypothesize that PAH may occur because of this inflammatory component despite HAART, even with apparently good response to therapy (i.e., blood CD4 + T cell normalization and undetectable HIV load). Inflammation theory in HIV-PAH (as in other forms of PAH) could open new treatment options.
Kooli, C; Salem, M; Hamzaoui, A; Fredj, M; Kaouache, Z; Khalfallah, N; Chabbou, A; Haddad, A
Behçet's disease, frequent in our region, can have many clinical presentations. Arterial lesions generally lead to poor prognosis. We report two cases of pulmonary artery aneurysm in two young adults whose Behçet's disease was revealed by hemoptysia.
Tartavoulle, Todd M
Pulmonary arterial hypertension is a lethal condition, and the management of sepsis in patients with pulmonary arterial hypertension is challenging. As the disease progresses, the right ventricle is susceptible to failure due to a high pulmonary vascular resistance. The limited ability of the right ventricle to increase cardiac output in septic shock makes it difficult to deliver oxygen to the organ and tissues. Intravascular volume replacement and vasoactive drugs should only be considered after a thorough assessment. Priorities of care include improving cardiac output and oxygen delivery by optimizing preload, reducing afterload, and improving contractility.
Pan, Jun-Yen; Lin, Chu-Chuan; Chang, Jen-Ping
Assessment of the pulmonary circulation status including pressure, resistance, size, and absence of anatomical distortion, is crucial to the successful Fontan operation. Most patients are found to have acceptable pulmonary arteries after previous palliation, although some degree of distortion is not uncommon. However, in rare instances, some patients have only one functioning lung with another pulmonary artery seriously hypoplastic or atretic. For theses patients, completion of a Fontan operation will be challenging. We reported a 17-year-old girl with a single ventricle and heterotaxy syndrome and only her left lung functioning, who underwent one-lung Fontan operation with a satisfactory result. PMID:27713611
Corson, Neal; Armato, Samuel G.; Labby, Zacariah E.; Straus, Christopher; Starkey, Adam; Gomberg-Maitland, Mardi
Rationale and Objectives Pulmonary hypertension (PH) is a complex and fatal disease that is difficult to diagnose non-invasively. This study evaluated previously published CT-based vessel measurement criteria and investigated the predictive power and diagnostic ability of the main pulmonary artery diameter (MPAD) and the ratio of MPAD to aorta diameter (rPA). Materials and Methods The database for this study consisted of 175 PH patients (for whom mean pulmonary artery pressure (mPAP) was known), 16 patients without PH but with known mPAP (non-PH patients), and 114 “normal” patients without known mPAP. The performance of previously published criteria, MPAD > 29 mm and rPA > 1, was determined. The relationship between vessel measurements and mPAP was evaluated through correlation and linear regression analysis. The ability of these measurements to discriminate between patients with and without PH was determined by receiver operating characteristic analysis. Results For discriminating between PH and “normal” patients, the sensitivity and specificity of the criterion MPAD>29mm were 0.89 (0.84-0.93) and 0.83 (0.76-0.90), respectively, and the sensitivity and specificity of the criterion rPA>1 were 0.89 (0.85-0.94) and 0.82 (0.74-0.89), respectively. At a specificity of 0.95 in the task of separating PH and “normal” patients, the sensitivity of MPAD was 0.81 (0.72-0.90) and the sensitivity of rPA was 0.76 (0.66-0.85), but the specificity for both decreased when non-PH patients were included. For the combined PH and non-PH patient groups, the correlation between the vessel measurements and mPAP was significant but low, and the ability of the vessel measurements to predict mPAP was limited. Conclusion This study found that the sensitivity of previously published vessel criteria for identifying PH patients is high but the specificity may not be high enough for routine use in a clinical patient population. PMID:24594422
Schwaiger, Johannes P.; Loder, Christopher D.; Dobarro, David; Kaier, Thomas; Reddecliffe, Sally; Schreiber, Benjamin E.; Handler, Clive; Denton, Christopher P.; Coghlan, John G.
Our current understanding of the pathophysiology of pulmonary vascular disease is incomplete, since information about alterations of the pulmonary vasculature in pulmonary arterial hypertension (PAH) is primarily provided by autopsy or tissue specimens. The aim of this study was to compare the distal pulmonary vasculature of <2 mm in diameter in Systemic Sclerosis (SSc) patients with (n = 17) and without (n = 5) associated PAH using Optical Coherence Tomography during Right Heart catheterization. SSc-PAH patients showed significant thickening of Intima Media Thickening Area compared to patients without PAH (27 +/− 5.8% vs. 21 +/− 1.4%, p = 0.024). A good haemodynamic response to previous targeted PAH treatment was associated with a significantly greater number of small pulmonary artery side branches <300 μm per cm vessel (3.8 +/− 1.1 vs. 1.8 +/− 1.1; p = 0.010) and not associated with Intima Media thickening Area (26 +/− 5.4% vs. 28 +/− 6.7%; p = 0.6). Unexpected evidence of pulmonary artery thrombus formation was found in 19% of SSc-PAH patients. This is the first in-vivo study demonstrating a direct link between a structural abnormality of pulmonary arteries and a response to targeted treatment in PAH. Intravascular imaging may identify subgroups that may benefit from anticoagulation. PMID:28233825
Molthen, Robert C.; Heinrich, Amy E.; Haworth, Steven T.; Dawson, Christopher A.
To explore and quantify pulmonary arterial remodeling we used various methods including micro-CT, high-resolution 3-dimensional x-ray imaging, to examine the structure and function of intact pulmonary vessels in isolated rat lungs. The rat is commonly used as an animal model for studies of pulmonary hypertension (PH) and the accompanying vascular remodeling, where vascular remodeling has been defined primarily by changes in the vessel wall composition in response to hypertension inducing stimuli such as chronic hypoxic exposure (CHE) or monocrotaline (MCT) injection. Little information has been provided as to how such changes affect the vessel wall mechanical properties or the lumenal architecture of the pulmonary arterial system that actually account for the hemodynamic consequences of the remodeling. In addition, although the link between primary forms of pulmonary hypertension and inherited genetics is well established, the role that genetic coding plays in hemodynamics and vascular remodeling is not. Therefore, we are utilizing Fawn-Hooded (FH), Sprague-Dawley (SD) and Brown Norway (BN)rat strains along with unique imaging methods to parameterize both vessel distensibility and lumenal morphometry using a principal pulmonary arterial pathway analysis based on self-consistency. We have found for the hypoxia model, in addition to decreased body weight, increased hematocrit, increased right ventricular hypertrophy, the distensibility of the pulmonary arteries is shown to decrease significantly in the presence of remodeling.
Lee, Dong-Hyup; Jung, Tae-Eun; Lee, Jang-Hoon; Shin, Dong-Gu; Park, Won-Jong; Choi, Jun-Hyuk
Intimal sarcoma of the pulmonary artery is a rare malignant tumor that may be misdiagnosed as chronic pulmonary thromboembolism, even if various imaging techniques are used. We report a case of a 58-year-old man with pulmonary artery intimal sarcoma.18F-fleuorodeoxyglucose (FDG) uptake was poor in the mass of the pulmonary artery, and no other hypermetabolic lesions were noted elsewhere. Our presumptive diagnosis was a massive mural thrombus and a concomitant chronic thromboembolism. Intravenous heparin and recombinant human tissue-type plasminogen activator was subsequently administered. However, the patient needed an emergency operation for sudden aggravation of the vital signs, and the tissue diagnosis was intimal sarcoma with poor clinical outcomes.
Yotsukura, Masaya; Kohno, Mitsutomo; Asakura, Keisuke; Kamiyama, Ikuo; Ohtsuka, Takashi; Hayashi, Yuichiro; Kurihara, Isao; Nakatsuka, Seishi; Asamura, Hisao
We present the case of a 50-year-old man with Cushing syndrome caused by an ectopic adrenocorticotropic hormone (ACTH)-secreting tumor. A small nodule was located in close association with the lateral segmental branch of the pulmonary artery in the left upper lobe. Blood samples were obtained from various branches of the pulmonary artery by balloon-occluded retrograde sampling for the measurement of location-specific serum ACTH levels. After confirmation that the pulmonary nodule was responsible for the increased ACTH secretion, lobectomy was performed. This report demonstrates the usefulness of balloon-occluded retrograde pulmonary arterial sampling for the preoperative diagnosis of an ACTH-producing tumor whose diagnosis is difficult to confirm.
Espinosa, L; Agarwal, P
The combination of right lung agenesis and left pulmonary artery (LPA) sling is a rare entity that has been described only in the pediatric population. Cross-sectional imaging modalities such as magnetic resonance imaging (MRI) and computed tomography (CT) have an advantage over echocardiography and pulmonary angiography in demonstrating the anomalous left pulmonary artery, particularly in the presence of coexisting lung agenesis, as exemplified in this case. We report the first case of this rare entity in an adult. It is important to be aware that this abnormality, though rare, can present even in adulthood, and therefore close attention should be paid to the course of the pulmonary artery to ensure detection of a sling in association with lung agenesis.
Golovenko, O S; Prokopovych, L M; Moshkivska, L V; Truba, Ya P; Lazoryshynets, V V
Right ventricle insufficiency due to pulmonary hypertensive crysis or persisting pulmonary arterial hypertension (PAH) in patients after the interventricle septum defect (IVSD) closure with the heightened resistance of pulmonary arteries (RPA) constitutes an actual problem and associates with a high risk for a life-threatening complications and high lethality. Experience of the IVSD plasty conduction in a patient with high PAH, using a patch with a valve for right ventricle decompression while pulmonary hypertensive crysis in early postoperative period and nonreversible PAH in the remote period of observation, was presented. In the clinic 38 children were operated on for big IVSD, complicated by high PAH and heightened RPA, using a patch with a valve in 1996 - 2014 yrs. Hospital lethality have constituted 2.6%. Postoperatively a pressure in pulmonary artery (PA) have lowered trustworthy from (93.4 ? 14.9) to (49.2 ? 22.9) mm Hg. In a remote period of observation all the patients were alive. In 6 (16.2%) patients in terms from 4 mo to 18 yrs postoperatively a PAH have occurred, a pressure in PA was by 50% higher, than a systemic one. The IVSD plasty in patients with high PAH and heightened RPA may appear successful if a patch with a valve are applied.
Gibbs, J L; Rothman, M T; Rees, M R; Parsons, J M; Blackburn, M E; Ruiz, C E
OBJECTIVE--To assess the possibility of maintaining ductal patency in neonates with complex pulmonary atresia by percutaneous implantation of balloon expandable stents. PATIENTS--Two duct-dependent neonates with long segment pulmonary atresia, right sided aortic arch, and left sided arterial duct. RESULTS--Stents with final diameter of 3.5 or 4 mm and initial length of 7 or 15 mm were successfully positioned in the arterial duct. Two stents were required in one child and four in the other in order to stent the entire length of the duct. After the procedures the ducts remained widely patent and arterial oxygen saturations remained above 80%. Complications of the procedures included perforation of a peripheral pulmonary artery and cardiac perforation, both caused by guide wire manipulation. Both babies died suddenly, one at five weeks, and the other at nine days after successful stenting of the duct. Both ducts were patent at necropsy; the exact cause of one death was not clearly defined, but the second seemed to be caused by pneumococcal septicaemia. CONCLUSIONS--Stenting of the arterial duct is technically feasible. It provides adequate palliation for neonates with pulmonary atresia at least in the short term and it seems to result in balanced, central perfusion of both pulmonary arteries. This preliminary report suggests that this previously untried technique may prove to be a promising and attractive alternative to neonatal aortopulmonary shunt operation. Images PMID:1372815
Drexler, E. S; Bischoff, J. E; Slifka, A. J; McCowan, C. N; Quinn, T. P; Shandas, R; Ivy, D. D; Stenmark, K. R
Changes in the compliance properties of large blood vessels are critical determinants of ventricular afterload and ultimately dysfunction. Little is known of the mechanical properties of large vessels exhibiting pulmonary hypertension, particularly the trunk and right main artery. We initiated a study to investigate the influence of chronic hypoxic pulmonary hypertension on the mechanical properties of the extrapulmonary arteries of rats. One group of animals was housed at the equivalent of 5000 m elevation for three weeks and the other held at ambient conditions of ~1600 m. The two groups were matched in age and gender. The animals exposed to hypobaric hypoxia exhibited signs of pulmonary hypertension, as evidenced by an increase in the RV/(LV+S) heart weight ratio. The extrapulmonary arteries of the hypoxic animals were also thicker than those of the control population. Histological examination revealed increased thickness of the media and additional deposits of collagen in the adventitia. The mechanical properties of the trunk, and the right and left main pulmonary arteries were assessed; at a representative pressure (7 kPa), the two populations exhibited different quantities of stretch for each section. At higher pressures we noted less deformation among the arteries from hypoxic animals as compared with controls. A four-parameter constitutive model was employed to fit and analyze the data. We conclude that chronic hypoxic pulmonary hypertension is associated with a stiffening of all the extrapulmonary arteries. PMID:27096124
Moscoso, G; Mieli-Vergani, G; Mowat, A P; Portmann, B
A case of extrahepatic biliary atresia presenting with an acute respiratory episode and rapid deterioration, 10 years after a successful portoenterostomy and a very active life, was the setting of unsuspected severe pulmonary arterial hypertension leading to sudden death. The pulmonary arteries showed widespread plexiform lesions, thickening of the muscular media, and subendothelial proliferation. Occasionally, eccentric arterial obstructive lesions and fibrinous thrombi were observed. There was marked reduction of preacinar arterioles with a consequent increase in the alveolar/arterial ratio. The pulmonary veins showed arterialization of their walls. There was marked hypertrophy of myocardial fibres in the right ventricle together with foci of myocardial degeneration and fibrosis. Areas of endocardial thickening were observed in both ventricles. The absence of clinical indicators of pulmonary arterial hypertension at any but the terminal stages of the disease precluded any form of conservative management. Lung-heart and presumably liver transplantation might have been the only option. Prospective assessment of pulmonary function and haemodynamic studies should be considered in cirrhotic patients with portal hypertension.
Benito, F; Oliver, J M
Stents have been previously used to resolve stenoses of branch pulmonary arteries in children. We report 3 patients, with mean age of 22.7 +/- 4.7 years and pulmonary artery stenosis after palliative surgery in whom we implanted seven stents in four procedures. Six P308 Palmaz, overlapped two by two, were implanted by venous femoral approach in two patients, receiving four in the first case and the other two in the third case. In the second case, a NIR type stent was implanted through femoral artery in the right pulmonary artery. Stenosis diameter enlarged from 5.3 +/- 2.3 to 14.4 +/- 4.2 mm and the pressure gradient through stenosis fell from 40.6 +/- 15.3 to 6. 5 +/- 5 mmHg. All stents are well deployed and there are two patients waiting for total correction (previously not feasible) during a follow-up of 30.6 +/- 6.1 months.
Zhang, Qianlong; Fan, Kai; Wang, Peng; Yu, Juan; Liu, Ruxia; Qi, Hanping; Sun, Hongli; Cao, Yonggang
The abnormal apoptosis of pulmonary artery smooth muscle cells (PASMCs) is an important pathophysiological process in pulmonary vascular remodeling and pulmonary arterial hypertension (PAH). Carvacrol, an essential oil compound from oregano and thyme, has displayed antimicrobial, antitumor, and antioxidant properties. Although carvacrol has pro-apoptosis properties in tumor cells, the underlying mechanisms of carvacrol in PASMC apoptosis remain unclear. Thus, in this study, we aim to investigate the role of carvacrol in pulmonary vascular remodeling and PASMC apoptosis in hypoxia. Right Ventricular Hypertrophy Measurements and pulmonary pathomorphology data show that the ratio of the heart weight/tibia length (HW/TL), the right ventricle/left ventricle plus septum (RV/LV+S) and the medial width of the pulmonary artery increased in chronic hypoxia and were reversed by carvacrol treatment under hypoxia. Additionally, carvacrol inhibited PASMC viability, attenuated oxidative stress, induced mitochondria membrane depolarization, increased the percentage of apoptotic cells, suppressed Bcl-2 expression, decreased procaspase-3 expression, promoted caspase-3 activation, and inhibited the ERK1/2 and PI3K/Akt pathway. Taken together, these findings suggest that carvacrol attenuates the pulmonary vascular remodeling and promotes PASMC apoptosis by acting on, at least in part, the intrinsic apoptotic pathway. This process might provide us new insight into the development of hypoxic pulmonary hypertension.
Zhu, Guangfa; Pu, Xin; Guo, Hongjuang; Huang, Xiaoyong; Chen, Dong; Gan, Huili
Pulmonary artery sarcoma (PAS) is a rare and highly malignant tumor of pulmonary artery origin. Since 1923, when the first case was reported, <300 cases have been reported worldwide. PAS has a poor prognosis, and early diagnosis with radical surgical resection offers patients with PAS the only chance of survival. However, due to its rarity and the non-specificity of its clinical manifestations and imaging presentation, PAS is frequently misdiagnosed as a pulmonary thromboembolic disease, including pulmonary thromboembolism (PTE) and chronic thromboembolic pulmonary hypertension (CTEPH). The present study reports three cases of PAS that were initially misdiagnosed as PTE or CTEPH, and were later shown to be PAS following surgery. In addition, the clinical features of these patients are examined in order to improve the differential diagnosis of PAS during the early stages of the disease, when the prognosis of patients with PAS is at its optimum.
Zhu, Guangfa; Pu, Xin; Guo, Hongjuang; Huang, Xiaoyong; Chen, Dong; Gan, Huili
Pulmonary artery sarcoma (PAS) is a rare and highly malignant tumor of pulmonary artery origin. Since 1923, when the first case was reported, <300 cases have been reported worldwide. PAS has a poor prognosis, and early diagnosis with radical surgical resection offers patients with PAS the only chance of survival. However, due to its rarity and the non-specificity of its clinical manifestations and imaging presentation, PAS is frequently misdiagnosed as a pulmonary thromboembolic disease, including pulmonary thromboembolism (PTE) and chronic thromboembolic pulmonary hypertension (CTEPH). The present study reports three cases of PAS that were initially misdiagnosed as PTE or CTEPH, and were later shown to be PAS following surgery. In addition, the clinical features of these patients are examined in order to improve the differential diagnosis of PAS during the early stages of the disease, when the prognosis of patients with PAS is at its optimum. PMID:27446344
Wen, Shusheng; Cen, Jianzheng; Chen, Jimei; Xu, Gang; He, Biaochuan; Teng, Yun
Background In the patients with longer-segment aortic arch hypoplasia or interruption with ventricular septal defect, surgery with homograft vessel or autologous pericardial patch to augment descending aortic arch will not result in adverse reactions caused by end-to-end anastomosis. In this study, we retrospectively analyzed primary experience of surgical correction of complicated aortic arch anomaly with autologous main pulmonary artery. Methods From July 2010 to March 2016, the twenty-one cases of aortic arch complex anomalies were reconstructed with autologous main pulmonary artery. There were 5 patients with interrupted aortic arch and 16 patients with coarctation of aorta. In patients with interrupted aortic arch, anterior wall of main pulmonary artery was excised to form a conduit whose diameter varied according to the area of patient’s body surface. Both ends of the conduit were anastomosed to aortic arch and descending aorta, respectively. In other patients with coarctation of aorta, aortic arch was augmented with tailored pulmonary artery patch in oval shape. The defect of main pulmonary artery was repaired with autologous pericardial patch. Results There was only one patient died of multiple organ failure postoperatively. The other twenty patients survived without any neurologic complications. Differences of blood pressure between upper and lower limbs were not significant in all cases. During follow-up period, the echocardiography for all patients in the third, sixth, twelfth, and twenty-fourth months showed that blood flow in the descending aortic arch was fluent and there was no obvious blood pressure gradient. Conclusions Autologous main pulmonary artery can be used to repair complicated aortic arch anomalies completely without any anastomotic tension or bronchial obstruction postoperatively. This procedure is feasible and possesses predominant early and mid-term effects, and autologous main pulmonary artery can retain growth capacity during follow
Ote, Enrique Leonardo P; Oriuchi, Noboru; Miyashita, Go; Paudyal, Bishnuhari; Ishikita, Tomohiro; Arisaka, Yukiko; Higuchi, Tetsuya; Hirato, Junko; Endo, Keigo
We report the case of 58-year-old man with pulmonary artery intimal sarcoma. He initially presented with cough, right-sided chest pain, and shortness of breath. Although the diagnosis of pulmonary embolism had been considered, chest radiograph and pulmonary perfusion scintigraphy showed a mass in the right hilum and no perfusion in the right lung. (18)F-fluorodeoxyglucose positron emission computed tomography (FDGPET) showed increased FDG uptake in the mass obstructing the right pulmonary artery. Fine-needle biopsy revealed a pathological diagnosis of pulmonary artery intimal sarcoma. The patient was successfully treated with radiotherapy and adjuvant chemotherapy. FDG-PET was used for monitoring the response to therapy.
Afolabi-Brown, Olayinka; Witzke, Christian; Moldovan, Raul; Pressman, Gregg
Anomalous right coronary artery from the pulmonary artery (ARCAPA) is a rare congenital coronary anomaly that has an incidence of 0.002%. We report a case of a previously healthy female who presented to our hospital with pneumonia and was incidentally discovered to have ARCAPA. This was initially diagnosed on echocardiography by the unusual echocardiographic finding of multiple color flow Doppler signals around the right ventricular free wall and apex which were subsequently confirmed by angiography to be due to extensive collateral circulation between the left and right coronary arteries. This represents an unusual echocardiographic manifestation of this very rare condition.
Cantasdemir, Murat; Kantarci, Fatih; Mihmanli, Ismail; Akman, Canan; Numan, Furuzan; Islak, Civan; Bozkurt, A. Kursat
his report describes two patients with a known history of Behcet's disease in whom massive hemoptysis developed from rupture of pulmonary artery aneurysms. The high recurrence rate of complications related to pulmonary artery aneurysms and even the aneurysms themselves due to inadequacy of medical therapy and the disadvantages of surgical treatment make these aneurysms candidates for endovascular management.The pulmonary artery aneurysms reported here were successfully treated with endovascular embolization using n-butylcyanoacrylate. Pulmonary artery aneurysm embolization in Behcet's disease has been reviewed in the light of relevant literature.
Xu, Xiaoling; Zhang, Ruifeng; Hu, Huihui; Ye, Wu; Wang, Jin; Chen, Liying; Qiu, Lijun; Ying, Kejing
Pulmonary artery intimal sarcoma (PAIS) is a rare malignant tumor that presents with nonspecific symptoms and may be misdiagnosed as thromboembolic disease. We report a case of a 40-year-old female who presented with diarrhea as the initial symptom, was misdiagnosed and received thrombolytic therapy for presumed pulmonary embolism. Progressive symptoms and subsequent surgery led to the diagnosis of PAIS, and early relapse after pulmonary endarterectomy. Her survival time was 17 months after pulmonary endarterectomy. To our knowledge, diarrhea as initial manifestation of PAIS has not been described.
Xu, Xiaoling; Zhang, Ruifeng; Hu, Huihui; Ye, Wu; Wang, Jin; Chen, Liying; Qiu, Lijun; Ying, Kejing
Pulmonary artery intimal sarcoma (PAIS) is a rare malignant tumor that presents with nonspecific symptoms and may be misdiagnosed as thromboembolic disease. We report a case of a 40-year-old female who presented with diarrhea as the initial symptom, was misdiagnosed and received thrombolytic therapy for presumed pulmonary embolism. Progressive symptoms and subsequent surgery led to the diagnosis of PAIS, and early relapse after pulmonary endarterectomy. Her survival time was 17 months after pulmonary endarterectomy. To our knowledge, diarrhea as initial manifestation of PAIS has not been described. PMID:26425101
Tan, Xun; Chai, Juan; Bi, Shi-Cheng; Li, Jun-Jun; Li, Wen-Wen; Zhou, Ji-Yong
Medial hypertrophy of pulmonary arterioles during pulmonary arterial hypertension (PAH) in humans is associated with enhanced proliferation of smooth muscle cells (SMCs). Elevated matrix metalloproteinase (MMP)-2 has been found in pulmonary artery SMCs (PA-SMCs) in humans with idiopathic PAH, leading to the hypothesis that MMP-2 contributes to the proliferation and migration of vascular SMCs in the pathogenesis of PAH. Rapidly growing meat-type (broiler) chickens provide a model of spontaneous PAH. The present study was conducted to determine whether MMP-2 is involved in the medial hypertrophy of pulmonary arterioles in this model. Cultured PA-SMCs from normal birds were used to evaluate the effect of MMPs on cell proliferation. Gelatin zymography showed that endothelin (ET)-1-induced proliferation of PA-SMCs was concomitant with increased pro- and active MMP-2 production. Reverse transcription PCR demonstrated upregulation of MMP-2 mRNA. However, PA-SMC proliferation was inhibited by the MMP inhibitors doxycycline and cis-9-octadecenoyl-N-hydroxylamide. In vivo experiments revealed a significant increase of MMP-2 expression in hypertrophied pulmonary arterioles of PAH broiler chickens, which was positively correlated with wall thickness and medial hypertrophy. MMP-2 may contribute to medial hypertrophy in pulmonary arterioles during PAH in broiler chickens by enhancing the proliferation of vascular SMCs.
Lorenzoni, A G; Anthony, N B; Wideman, R F
Previous hemodynamic evaluations demonstrated that pulmonary arterial pressure (PAP) is higher in broilers that are susceptible to pulmonary hypertension syndrome (PHS, ascites) than in broilers that are resistant to PHS. We compared key pulmonary hemodynamic parameters in broilers from PHS-susceptible and PHS-resistant lines (selected for 12 generations under hypobaric hypoxia) and in broilers from a relaxed (control) line. In experiment 1 the PAP was measured in male broilers in which a flow probe positioned on one pulmonary artery permitted the determination of cardiac output and pulmonary vascular resistance (PVR). The PAP and relative PVR were higher in susceptible broilers than in relaxed and resistant broilers, whereas absolute and relative cardiac output did not differ between lines. In experiment 2 male and female broilers from the 3 lines were catheterized to measure pressures in the wing vein, right atrium, right ventricle, pulmonary artery, and pulmonary veins (WP, wedge pressure). The transpulmonary pressure gradient (TPG) was calculated as (PAP-WP), with PAP quantifying precapillary pressure and WP approximating postcapillary pulmonary venous pressure. When compared with resistant and relaxed broilers, PAP values in susceptible broilers were > or =10 mmHg higher, TPG values were > or =8 mmHg higher, and WP values were < or =2 mmHg higher, regardless of sex. The combined hemodynamic criteria (elevated PAP and PVR combined with a proportionally elevated TPG) demonstrate that susceptibility to PHS can be attributed primarily to pulmonary arterial hypertension associated with increased precapillary (arteriole) resistance rather than to pulmonary venous hypertension caused by elevated postcapillary (venous and left atrial) resistance.
Arian, Anahita; Moghadam, Sayyed Gholamreza Mortazavi; Kazemi, Toba; Hajihosseini, Morteza
Objective: Pulmonary hypertension is a serious complication in patients suffering from chronic obstructive pulmonary disease (COPD). The aim of this study is to investigate the effects of atorvastatin in reducing pulmonary arterial pressure in COPD patients. Methods: This double-blind, randomized trial was conducted on 42 known cases of COPD with systolic pulmonary arterial pressure of more than 25 mmHg. The patients were randomly assigned into two groups, 21 patients with atorvastatin treatment (40 mg/daily for 6 months) and 21 patients without receiving atorvastatin. All the patients participated voluntarily and provided written informed consent. The trial was registered in the Iranian Registry of Clinical Trials. Pulmonary pressure was also anticipated by Doppler echocardiography with peak pressure gradient of tricuspid regurgitation. Both groups were tested with echocardiography to measure systolic pulmonary pressure at baseline and posttreatment. Statistical analysis includes Chi-square, Student's t-test, and Wilcoxon test. P < 0.05 was considered statistically significant. Findings: The mean age was 65.8 ± 11.5 years for atorvastatin group and 63.7 ± 7.6 years for control group (P = 0.45). Baseline and posttreatment mean systolic pulmonary artery pressure (PAP) levels in the atorvastatin group were 48.9 ± 3.3 and 38.4 ± 1.9 mmHg, respectively (P = 0.007). In the control group, mean systolic PAP levels at baseline and 6 months later were 45.6 ± 3.1 and 38.9 ± 2.4 mmHg, respectively (P = 0.073). The patients treated with atorvastatin showed significant decrease in total cholesterol (P = 0.001) and low-density lipoprotein cholesterol (P = 0.008). Conclusion: A 40 mg dose of atorvastatin daily for 6 months may have beneficial effects in reducing PAP in patients with COPD. Further studies are necessary to find long-term effects of statins in COPD patients.
Schroer, Alison K.; Chen, Peter; Ryzhova, Larisa M.; Gladson, Santhi; Shay, Sheila; Hutcheson, Joshua D.; Merryman, W. David
Serotonergic anorexigens are the primary pharmacologic risk factor associated with pulmonary arterial hypertension (PAH), and the resulting PAH is clinically indistinguishable from the heritable form of disease, associated with BMPR2 mutations. Both BMPR2 mutation and agonists to the serotonin receptor HTR2B have been shown to cause activation of SRC tyrosine kinase; conversely, antagonists to HTR2B inhibit SRC trafficking and downstream function. To test the hypothesis that a HTR2B antagonist can prevent BMRP2 mutation induced PAH by restricting aberrant SRC trafficking and downstream activity, we exposed BMPR2 mutant mice, which spontaneously develop PAH, to a HTR2B antagonist, SB204741, to block the SRC activation caused by BMPR2 mutation. SB204741 prevented the development of PAH in BMPR2 mutant mice, reduced recruitment of inflammatory cells to their lungs, and reduced muscularization of their blood vessels. By atomic force microscopy, we determined that BMPR2 mutant mice normally had a doubling of vessel stiffness, which was substantially normalized by HTR2B inhibition. SB204741 reduced SRC phosphorylation and downstream activity in BMPR2 mutant mice. Gene expression arrays indicate that the primary changes were in cytoskeletal and muscle contractility genes. These results were confirmed by gel contraction assays showing that HTR2B inhibition nearly normalizes the 400% increase in gel contraction normally seen in BMPR2 mutant smooth muscle cells. Heritable PAH results from increased SRC activation, cellular contraction, and vascular resistance, but antagonism of HTR2B prevents SRC phosphorylation, downstream activity, and PAH in BMPR2 mutant mice. PMID:26863209
Kim, Young-su; Lee, Mina; Cho, Yang Hyun; Yang, Ji-Hyuk; Jun, Tae-Gook
Background For the surgical management of anomalous origin of the left coronary artery from the pulmonary artery (ALCAPA), there have been various techniques that reduce the tension and kinking of the coronary artery during reimplantation to the aorta. The aim of this study is to describe the results of our modified technique of coronary reimplantation for the treatment of ALCAPA. Methods Between October 2003 and February 2011, seven patients underwent coronary reimplantation with the modified technique (tubing formation with the sinus wall of the pulmonary artery and trapdoor formation at the site of implantation in the aorta). The median follow-up duration was 52 months (range, 4 to 72 months). Clinical outcomes and serial echocardiographic data were reviewed. Results There was no mortality. One patient had a small amount of cerebral hemorrhage postoperatively and improved without any sequelae. Another patient had left diaphragm palsy and underwent diaphragm plication. Follow-up echocardiogram showed that all patients had normal ventricular function without chamber enlargement. Conclusion Our modified technique (tubing formation with the sinus wall of the pulmonary artery and trapdoor formation at the site of implantation in the aorta) demonstrated successful clinical outcomes. We conclude that this surgical technique can be a potential alternative for the treatment of ALCAPA. PMID:25207218
Bockeria, Leo A.; Podzolkov, Vladimir P.; Makhachev, Osman A.; Alekyan, Bagrat G.; Khiriev, Titalav Kh.; Zelenikin, Mikhail A.; Shatalov, Konstantin V.; Zaets, Sergey B.
OBJECTIVES Experience with the palliative treatment of congenital heart defects (CHDs) associated with unilateral absence of the pulmonary artery (UAPA) is limited. There is a description of 32 interventions in the available literature. The aim of this retrospective study was to present our experience with palliative interventions in patients with cyanotic CHDs associated with UAPA and to suggest a rational surgical strategy. METHODS Twenty-nine patients were subjected to palliative interventions. All of them had the following cyanotic CHDs with agenesis of the left pulmonary artery: tetralogy of Fallot (n = 26) or double outlet right ventricle (n = 3). Twenty patients were subjected to a single and 9 to multiple staged palliative operations. Patients were grouped according to the type of initial palliation to assess the clinical and haemodynamic results of each surgical intervention: Group 1: systemic-to-pulmonary shunts (n = 13); Group 2: transluminal balloon pulmonary valvuloplasty (n = 5); Group 3: palliative reconstruction of the right ventricular outflow tract (n = 11). The median age of patients at the initial palliative intervention was 2.6 years. Twenty-three of 27 discharged patients were followed up for a median period of 3 years. RESULTS Hospital mortality in our series reached 7% (2 of 29 patients). Both lethal outcomes occurred after palliative reconstruction of the right ventricular outflow tract was performed as a sole intervention. The assessment of angiographic parameters has shown that palliative reconstruction of the right ventricular outflow tract provided more significant and uniform enlargement of the pulmonary artery than systemic-to-pulmonary shunts or transluminal balloon pulmonary valvuloplasty. Fifty-nine percent of patients (17 of 29 patients) were subjected to complete repair of CHDs during the follow-up. CONCLUSIONS Palliative surgical treatment of CHDs associated with UAPA can be performed with a relatively low risk. Systemic-to-pulmonary
Panchabhai, Tanmay S.; Bajaj, Navkaranbir S.; Patil, Pradnya D.; Bunte, Matthew C.
Background Primary pulmonary artery sarcoma (PPAS) is a rare tumor that mimics pulmonary thromboembolism (PE). Similarities to PE can delay the diagnosis and misguide the treatment of PPAS. This study aimed to evaluate tumor characteristics and outcome predictors among those diagnosed with PPAS and misdiagnosed as PE. Methods From 1991–2010, 10 PPAS cases were available from the Cleveland Clinic (CC) institutional database and another 381 cases were reported in the literature. Patient characteristics, tumor subtypes, diagnostic testing & timing, interventions and clinical outcomes were analyzed. We also noted effects of misdiagnosis as PE and clinical outcome as a result of inappropriate intervention. Results Among 391 confirmed cases of PPAS, the mean age at diagnosis was 52±14 years; 55% were male. The median duration of symptoms prior to diagnosis was 100 [interquartile range (IQR), 30–210] days. Nearly half (47%) of PPAS were originally misdiagnosed as PE including 39% that received thrombolytic and/or anticoagulation therapy. For every doubling of time from symptom onset to diagnosis, the odds of death increased by 46% (OR: 1.46, 95% CI: 1.21–1.82; P<0.001). The odds of death (OR: 2.66, 95% CI: 1.58–4.54; P=0.0003) and occurrence of distant metastasis (OR: 2.30, 95% CI: 1.30–4.15; P=0.049) were increased among those who did not receive chemotherapy but chemotherapy did not impact local recurrence. Those with complete resection had a better survival. Conclusions PPAS has a radiological appearance similar to PE, which makes accurate and timely diagnosis challenging. More rapid diagnosis may lead to earlier, appropriate surgical treatment and improved outcomes, when combined with adjuvant treatment. PMID:27747013
Lee, Keng Jin; Berkelhamer, Sara K; Kim, Gina A; Taylor, Joann M; O'Shea, Kelly M; Steinhorn, Robin H; Farrow, Kathryn N
Pulmonary hypertension (PH) occurs in 25 to 35% of premature infants with significant bronchopulmonary dysplasia (BPD). Neonatal mice exposed to 14 days of hyperoxia develop BPD-like lung injury and PH. To determinne the impact of hyperoxia on pulmonary artery (PA) cyclic guanosine monophosphate (cGMP) signaling in a murine model of lung injury and PH, neonatal C57BL/6 mice were placed in room air, 75% O2 for 14 days (chronic hyperoxia [CH]) or 75% O2 for 24 hours, followed by 13 days of room air (acute hyperoxia with recovery [AHR]) with or without sildenafil. At 14 days, mean alveolar area, PA medial wall thickness (MWT), right ventricular hypertrophy (RVH), and vessel density were assessed. PA protein was analyzed for cGMP, soluble guanylate cyclase, and PDE5 activity. CH and AHR mice had RVH, but only CH mice had increased alveolar area and MWT and decreased vessel density. In CH and AHR PAs, soluble guanylate cyclase activity was decreased, and PDE5 activity was increased. In CH mice, sildenafil attenuated MWT and RVH but did not improve mean alveolar area or vessel density. In CH and AHR PAs, sildenafil decreased PDE5 activity and increased cGMP. Our results indicate that prolonged hyperoxia leads to lung injury, PH, RVH, and disrupted PA cGMP signaling. Furthermore, 24 hours of hyperoxia causes RVH and disrupted PA cGMP signaling that persists for 13 days. Sildenafil reduced RVH and restored vascular cGMP signaling but did not attenuate lung injury. Thus, hyperoxia can rapidly disrupt PA cGMP signaling in vivo with sustained effects, and concurrent sildenafil therapy can be protective.
Kumagai, Hozumi; Nio, Kenta; Okumura, Yuta; Komoda, Masato; Shirakawa, Tsuyoshi; Kusaba, Hitoshi; Yasuda, Shioto; Odashiro, Keita; Arita, Shuji; Ariyama, Hiroshi; Yamada, Yuichi; Yamamoto, Hidetaka; Oda, Yoshinao; Nakamura, Katsumasa; Akashi, Koichi; Baba, Eishi
Undifferentiated malignant neoplasms, which occur primarily in the pulmonary artery, are extremely rare and associated with poor outcomes as there is no effective therapy. A 67-year-old woman visited our hospital with complaints of dry cough and dyspnea on exertion. A contrast-enhanced chest computed tomography revealed an intravascular tumor obstructing the left pulmonary artery and a pedunculated lesion extending to the main and right pulmonary artery. Multiple metastases in the lung, bones and bilateral adrenal glands were identified by fluorodeoxyglucose-positron emission tomography. A small sample was obtained by catheter aspiration biopsy of the intravascular tumor, and examination revealed undifferentiated small atypical cells. The tumor was diagnosed as an undifferentiated neoplasm arising from the pulmonary artery based on immunohistochemical findings, including the absence of expressions of organ-specific markers. Systemic chemotherapy (paclitaxel and carboplatin) and concurrent radiation were performed as treatment for the primary tumor. Marked shrinkage of the intravascular tumor was achieved, and no serious adverse events were observed during therapy. Chemotherapy was continued for 5 months, but the patient died because of tumor progression 9 months after the initial diagnosis. Chemoradiotherapy has efficacy against undifferentiated neoplasm of the pulmonary artery. PMID:25202263
Dardi, Fabio; Manes, Alessandra; Palazzini, Massimiliano; Bachetti, Cristina; Mazzanti, Gaia; Rinaldi, Andrea; Albini, Alessandra; Gotti, Enrico; Monti, Enrico; Bacchi Reggiani, Maria Letizia; Galiè, Nazzareno
Pulmonary arterial hypertension is a severe disease with a complex pathogenesis, for which combination therapy is an attractive option.This study aimed to assess the impact of sequential combination therapy on both short-term responses and long-term outcomes in a real-world setting.Patients with idiopathic/heritable pulmonary arterial hypertension, or pulmonary arterial hypertension associated with congenital heart disease or connective tissue disease and who were not meeting treatment goals on either first-line bosentan or sildenafil monotherapy, were given additional sildenafil or bosentan and assessed after 3-4 months. Double combination therapy significantly improved clinical and haemodynamic parameters, independent of aetiology or the order of drug administration. Significant improvements in functional class were observed in patients with idiopathic/heritable pulmonary arterial hypertension. The 1-, 3- and 5-year overall survival estimates were 91%, 69% and 59%, respectively. Patients with pulmonary arterial hypertension associated with connective tissue disease had significantly poorer survival rates compared to other aetiologies (p<0.003).The favourable short-term haemodynamic results and good survival rates, observed in patients receiving both bosentan and sildenafil, supports the use of sequential combination therapy in patients failing on monotherapy in a real-world setting.
Behringer, Arnica; Trappiel, Manuela; Berghausen, Eva Maria; Ten Freyhaus, Henrik; Wellnhofer, Ernst; Odenthal, Margarete; Blaschke, Florian; Er, Fikret; Gassanov, Natig; Rosenkranz, Stephan; Baldus, Stephan; Kappert, Kai; Caglayan, Evren
Pulmonary arterial hypertension (PAH) is a fatal disease with limited therapeutic options. Pathophysiological changes comprise obliterative vascular remodelling of small pulmonary arteries, elevated mean pulmonary arterial systolic pressure (PASP) due to elevated resistance of pulmonary vasculature, adverse right ventricular remodelling, and heart failure. Recent findings also indicate a role of increased inflammation and insulin resistance underlying the development of PAH. We hypothesized that treatment of this condition with the peroxisome proliferator-activated receptor-γ (PPARγ) activator pioglitazone, known to regulate the expression of different genes addressing insulin resistance, inflammatory changes, and vascular remodelling, could be a beneficial approach. PAH was induced in adult rats by a single subcutaneous injection of monocrotaline (MCT). Pioglitazone was administered for 2 weeks starting 3 weeks after MCT-injection. At day 35, hemodynamics, organ weights, and -indices were measured. We performed morphological and molecular characterization of the pulmonary vasculature, including analysis of the degree of muscularization, proliferation rates, and medial wall thickness of the small pulmonary arteries. Furthermore, markers of cardiac injury, collagen content, and cardiomyocyte size were analyzed. Survival rates were monitored throughout the experimental period. Pioglitazone treatment improved survival, reduced PASP, muscularization of small pulmonary arteries, and medial wall thickness. Further, MCT-induced right ventricular hypertrophy and fibrosis were attenuated. This was accompanied with reduced cardiac expression of brain natriuretic peptide, as well as decreased cardiomyocyte size. Finally, pulmonary macrophage content and osteopontin gene expression were attenuated. Based on the beneficial impact of pioglitazone, activation of PPARγ might be a promising treatment option in PAH.
Saha, Punam K.; Gao, Zhiyun; Alford, Sara; Sonka, Milan; Hoffman, Eric
Distinguishing arterial and venous trees in pulmonary multiple-detector X-ray computed tomography (MDCT) images (contrast-enhanced or unenhanced) is a critical first step in the quantification of vascular geometry for purposes of determining, for instance, pulmonary hypertension, using vascular dimensions as a comparator for assessment of airway size, detection of pulmonary emboli and more. Here, a novel method is reported for separating arteries and veins in MDCT pulmonary images. Arteries and veins are modeled as two iso-intensity objects closely entwined with each other at different locations at various scales. The method starts with two sets of seeds -- one for arteries and another for veins. Initialized with seeds, arteries and veins grow iteratively while maintaining their spatial separation and eventually forming two disjoint objects at convergence. The method combines fuzzy distance transform, a morphologic feature, with a topologic connectivity property to iteratively separate finer and finer details starting at a large scale and progressing towards smaller scales. The method has been validated in mathematically generated tubular objects with different levels of fuzziness, scale and noise. Also, it has been successfully applied to clinical CT pulmonary data. The accuracy of the method has been quantitatively evaluated by comparing its results with manual outlining. For arteries, the method has yielded correctness of 81.7% at the cost of 6.7% false positives and 11.6% false negatives. Our method is very promising for automated separation of arteries and veins in MDCT pulmonary images even when there is no mark of intensity variation at conjoining locations.
Molina, J. Ernesto
A consecutive series of 12 patients between the ages of 6½ and 37 years underwent implantation of venous ventricle-pulmonary artery conduits. GORE-TEX material without prosthetic valves was used. Four patients had L-transposition of the great vessels with ventricular septal defect (VSD) and pulmonary stenosis; four had tetralogy of Fallot with pulmonary atresia; and one had double outlet right ventricle, pulmonary stenosis, and a complete form of A-V canal. Two patients had D-transposition of the great arteries, VSD, and pulmonary stenosis; and one patient had L-transposition of the great arteries and isolated pulmonary stenosis. All patients had low pulmonary resistance and pressures. The technique for implanting this noncrimped type of prosthesis is described in detail. Follow-up ranged from 2 months to 5½ years. GORE-TEX offers a good choice of material for the construction of this type of conduit to prevent pseudointima formation and obstruction, which is often observed in woven Dacron grafts. PMID:15226844
De Man, Frances; Tu, Ly; Handoko, Louis; Rain, Silvia; Ruiter, Gerrina; François, Charlène; Schalij, Ingrid; Dorfmüller, Peter; Simonneau, Gérald; Fadel, Elie; Perros, Frederic; Boonstra, Anco; Postmus, Piet; Van Der Velden, Jolanda; Vonk-Noordegraaf, Anton; Humbert, Marc; Eddahibi, Saadia; Guignabert, Christophe
Rationale Patients with idiopathic pulmonary arterial hypertension (iPAH) often have a low cardiac output. To compensate, neurohormonal systems like renin-angiotensin-aldosterone system (RAAS) and sympathetic nervous system are upregulated but this may have long-term negative effects on the progression of iPAH. Objectives Assess systemic and pulmonary RAAS-activity in iPAH-patients and determine the efficacy of chronic RAAS-inhibition in experimental PAH. Measurements and Main Results We collected 79 blood samples from 58 iPAH-patients in the VU University Medical Center Amsterdam (between 2004–2010), to determine systemic RAAS-activity. We observed increased levels of renin, angiotensin (Ang) I and AngII, which was associated with disease progression (p<0.05) and mortality (p<0.05). To determine pulmonary RAAS-activity, lung specimens were obtained from iPAH-patients (during lung transplantation, n=13) and controls (during lobectomy or pneumonectomy for cancer, n=14). Local RAAS-activity in pulmonary arteries of iPAH-patients was increased, demonstrated by elevated ACE-activity in pulmonary endothelial cells and increased AngII type 1 (AT1) receptor expression and signaling. In addition, local RAAS- upregulation was associated with increased pulmonary artery smooth muscle cell proliferation via enhanced AT1-receptor signaling in iPAH-patients compared to controls. Finally, to determine the therapeutic potential of RAAS-activity, we assessed the chronic effects of an AT1-receptor antagonist (losartan) in the monocrotaline PAH-rat model (60 mg/kg). Losartan delayed disease progression, decreased RV afterload and pulmonary vascular remodeling and restored right ventricular-arterial coupling in PAH-rats. Conclusions Systemic and pulmonary RAAS-activities are increased in iPAH-patients and associated with increased pulmonary vascular remodeling. Chronic inhibition of RAAS by losartan is beneficial in experimental PAH. PMID:22859525
Flick, M R; Moody, L E; Block, A J
Twenty patients with mild to severe chronic obstructive pulmonary disease received ultrasonic nebulization to assess the danger of short-term changes in blood gas levels during this therapy. The status of arterial oxygenation was monitored during 20 minutes of therapy and for 20 minutes following therapy. In nine patients with periodic studies of arterial blood, the mean change in arterial oxygen pressure from base line was a decrease of 0.8 mm Hg at ten minutes into therapy, 2.8 mm Hg at the conclusion of therapy, and 2.9 mm Hg 20 minutes after therapy. In all 20 patients, ear oximetric studies showed only a small mean change at ten minutes into therapy, at the end of therapy, and at 20 minutes after therapy. Changes in the status of arterial oxygenation during and after therapy with ultrasonic nebulization in a group of patients with chronic obstructive pulmonary disease are generally small and of no statistical and limited clinical significance; however, alarming falls in arterial oxygenation can occur and cannot be predicted by base-line testing of pulmonary function or studies of arterial blood. It would be prudent to monitor patients with chronic obstructive pulmonary disease during therapy with ultrasonic nebulization or to withhold therapy altogether.
Nagai, T; Mukai, T; Takahashi, S; Takada, A; Saito, K; Harada, K; Mori, S; Abe, N
Anomalous origin of the right coronary artery from the pulmonary artery (ARCAPA) is a rare anomaly. It may contribute to myocardial ischemia or sudden death, although the lesion is usually asymptomatic. We report a sudden death case of a 58-year-old man with ARCAPA coexisting with severe atherosclerotic coronary artery disease. He had been healthy until he complained of chest pain, several days before death, despite the discovery of heart murmur in childhood and suspicion of valvular heart disease. The autopsy revealed not only typical findings of the right coronary anomaly with well-developed collateral circulations but also severe atherosclerotic lesions of the left coronary artery, and ischemic change of the myocardium in the left and right coronary arterial perfusion territory. In addition to the "coronary steal" phenomenon primarily caused by ARCAPA, the reduced flow of both coronary arteries and further increase of "coronary steal" due to atherosclerotic obstructive coronary disease might have contributed to the patient's death.
Katayama, Y.; Higenbottam, T. W.; d Diaz; Cremona, G.; Akamine, S.; Barbera, J. A.; Rodriguez-Roisin, R.
BACKGROUND: Inhaled nitric oxide (NO) is a selective pulmonary vasodilator which can improve gas exchange in acute lung injury. However, it is uncertain that this effect on arterial oxygenation can be generalised to all lung diseases. METHODS: The effects of inhaled NO on gas exchange were studied in nine patients with chronic obstructive pulmonary disease (COPD), 11 patients with severe pulmonary hypertension, and 14 healthy volunteers. A randomized sequence of 40 ppm of NO or air was inhaled for 20 minutes through an orofacial mask. RESULTS: Inhaled NO reduced mean (SE) transcutaneous arterial oxygen tension (TcPO2) from 9.6 (0.3) to 8.9 (0.4) kPa in healthy volunteers and from 7.4 (0.6) to 7.0 (0.5) kPa in patients with COPD. There was no change in TcPO2 in patients with severe pulmonary hypertension. During inhalation of NO and air no change occurred in transcutaneous arterial carbon dioxide tension (TcPCO2), arterial oxygen saturation (SaO2) measured by pulse oximeter, or cardiac output determined by the transthoracic impedance method. CONCLUSIONS: Inhaled NO does not improve TcPO2 nor increase cardiac output in normal subjects and patients with COPD, suggesting that inhaled NO worsens gas exchange. This could represent inhaled NO overriding hypoxic pulmonary vasoconstriction in COPD. The finding that TcPO2 also fell when normal subjects inhaled NO suggests that a similar mechanism normally contributes to optimal gas exchange. Whilst inhaled NO can improve oxygenation, this effect should not be considered to be a general response but is dependent on the type of lung disease. PMID:9059470
MALIK, ABDUL RAUOOF
Atherosclerosis predominantly affects systemic arteries as compared to pulmonary arteries; however, the reasons for this differential predilection are not clear. Oxidative damage caused by free radicals is a key initiating event in atherogenesis and the lungs are able to produce large quantities of free radicals even under physiological conditions. The present study investigated whether pulmonary venous blood reaching the aorta contained greater quantities of lipid peroxides, a marker of oxidative stress, compared to the pulmonary artery. Aortic and pulmonary artery blood samples were collected at the time of cardiac catheterization from 45 consecutive patients (38% female) without acute coronary event and free of other medical disorders, who were scheduled to undergo coronary angiography for anginal chest pain. Lipid peroxides were measured in terms of malondialdehyde (MDA). MDA levels were significantly higher in the aorta compared to the pulmonary artery (4.93±1.97 vs. 3.36±1.14 nmol/ml; P<0.001); the difference was significant in patients with angiographic coronary artery disease (CAD) (P<0.001) compared to the patients without CAD (P=0.071). Higher aortic MDA levels were associated with the presence of CAD even following adjustment for major risk factors. The results of the present study demonstrate that aortic blood contains significantly greater levels of lipid peroxides compared to pulmonary artery. This differential oxidative stress between systemic and pulmonary arteries could provide a mechanistic explanation for their difference in the propensity to develop atherosclerosis. PMID:27073637
Ghorishi, Zahra; Milstein, Jay M; Poulain, Francis R; Moon-Grady, Anita; Tacy, Theresa; Bennett, Stephen H; Fineman, Jeffery R; Eldridge, Marlowe W
Congenital heart disease with increased blood flow commonly leads to the development of increased pulmonary vascular reactivity and pulmonary arterial hypertension by mechanisms that remain unclear. We hypothesized a shear stress paradigm of hemodynamic reactivity and network remodeling via the persistence and/or exacerbation of a fetal diameter bifurcation phenotype [parent diameter d(0) and daughters d(1) >or= d(2) with alpha < 2 in (d(1)/d(0))(alpha) + (d(2)/d(0))(alpha) and area ratio beta < 1 in beta = (d(1)(2)+ d(2)(2))/ d(0)(2)] that mechanically acts as a high resistance magnifier/shear stress amplifier to blood flow. Evidence of a hemodynamic influence on network remodeling was assessed with a lamb model of high-flow-induced secondary pulmonary hypertension in which an aortopulmonary graft was surgically placed in one twin in utero (Shunt twin) but not in the other (Control twin). Eight weeks after birth arterial casts were made of the left pulmonary arterial circulation. Bifurcation diameter measurements down to 0.010 mm in the Shunt and Control twins were then compared with those of an unoperated fetal cast. Network organization, cumulative resistance, and pressure/shear stress distributions were evaluated via a fractal model whose dimension D(0) approximately alpha delineates hemodynamic reactivity. Fetus and Control twin D(0) differed: fetus D(0)=1.72, a high-resistance/shear stress amplifying condition; control twin D(0) = 2.02, an area-preserving transport configuration. The Shunt twin (D(0)=1.72) maintained a fetal design but paradoxically remodeled diameter geometry to decrease cumulative resistance relative to the Control twin. Our results indicate that fetal/neonatal pulmonary hemodynamic reactivity remodels in response to shear stress, but the response to elevated blood flow and pulmonary hypertension involves the persistence and exacerbation of a fetal diameter bifurcation phenotype that facilitates endothelial dysfunction/injury.
Soydan, Lydia C.; Kellihan, Heidi B.; Bates, Melissa L.; Stepien, Rebecca L.; Consigny, Daniel W.; Bellofiore, Alessandro; Francois, Christopher J.; Chesler, Naomi C.
Objectives To compare noninvasive estimates of pulmonary artery pressure (PAP) obtained via echocardiography (ECHO) to invasive measurements of PAP obtained during right heart catheterization (RHC) across a wide range of PAP, to examine the accuracy of estimating right atrial pressure via ECHO (RAPECHO) compared to RAP measured by catheterization (RAPRHC), and to determine if adding RAPECHO improves the accuracy of noninvasive PAP estimations. Animals Fourteen healthy female beagle dogs. Methods ECHO and RHC performed at various data collection points, both at normal PAP and increased PAP (generated by microbead embolization). Results Noninvasive estimates of PAP were moderately but significantly correlated with invasive measurements of PAP. A high degree of variance was noted for all estimations, with increased variance at higher PAP. The addition of RAPECHO improved correlation and bias in all cases. RAPRHC was significantly correlated with RAPECHO and with subjectively assessed right atrial size (RA sizesubj). Conclusions Spectral Doppler assessments of tricuspid and pulmonic regurgitation are imperfect methods for predicting PAP as measured by catheterization despite an overall moderate correlation between invasive and noninvasive values. Noninvasive measurements may be better utilized as part of a comprehensive assessment of PAP in canine patients. RAPRHC appears best estimated based on subjective assessment of RA size. Including estimated RAPECHO in estimates of PAP improves the correlation and relatedness between noninvasive and invasive measures of PAP, but notable variability in accuracy of estimations persists. PMID:25601540
It is believed that simultaneous targeting of two or more of the three pathogenic pathways of pulmonary arterial hypertension (the endothelin, nitric oxide, and prostacyclin pathways) is associated with additive or synergistic effects with subsequent increasing efficacy and improving outcomes. However, there is lack of evidence to guide the use of combination strategy among pulmonary arterial hypertension patients and many questions remain to be answered. One of these vital questions is whether the strategy of upfront initiation of combination therapy could improve patients outcomes compared to the strategy of initial monotherapy. The recently published AMBITION trial represents an important forward step towards answering this question by comparing a strategy of first-line combination therapy (ambrisentan and tadalafil) versus first-line monotherapy (ambrisentan or tadalafil) in patients with pulmonary arterial hypertension.
Bridges, Elizabeth J
The integration of data from a pulmonary artery catheter when used as part of a goal-directed plan of care may benefit certain groups of critically ill patients. Integral to the successful use of the pulmonary artery catheter is to accurately obtain and interpret invasive pressure monitoring data. This article addresses commonly asked clinical questions and considerations for decision making under complex care conditions, such as obtaining hemodynamic measurements when the patient is prone or has marked respiratory pressure variations or increased intraabdominal pressure. Recommendations to optimize the invasive pressure monitoring system are presented. Finally, functional hemodynamic indices, which are more sensitive and specific indices than static indices (pulmonary artery and right artrial pressure) of the ability to respond to a fluid bolus, will be introduced.
van Soldt, Benjamin J; Danielsen, Carl Christian; Wang, Tobias
Pythons are unique amongst snakes in having different pressures in the aortas and pulmonary arteries because of intraventricular pressure separation. In this study, we investigate whether this correlates with different blood vessel strength in the ball python Python regius. We excised segments from the left, right, and dorsal aortas, and from the two pulmonary arteries. These were subjected to tensile testing. We show that the aortic vessel wall is significantly stronger than the pulmonary artery wall in P. regius. Gross morphological characteristics (vessel wall thickness and correlated absolute amount of collagen content) are likely the most influential factors. Collagen fiber thickness and orientation are likely to have an effect, though the effect of collagen fiber type and cross-links between fibers will need further study.
Lee, Sun Hyang; Kwon, Bo Sang; Bae, Eun Jung; Noh, Chung Il; Kim, Woong Han
Management of severely dilated pulmonary artery (PA) associated with severe pulmonary hypertension from congenital heart disease remains controversial, primarily due to its rare nature and concern for perioperative unpredictable complications. Herein, we report a 25 year-old female with a severely dilated PA (up to 73 mm), who was successfully treated by a PA graft replacement by creating a Y-shaped conduit using a 28 mm hemashield tube in the main PA and a 20 mm hemashield tube in both proximal parts of the branch PA. PMID:28154602
Adams, Dustin S; Marolf, Angela J; Valdés-Martínez, Alejandro; Randall, Elissa K; Bachand, Annette M
Doppler echocardiography is a noninvasive method for estimating and grading pulmonary arterial hypertension. No current literature associates significance of radiographic findings with severity of pulmonary arterial hypertension. We hypothesized that the number and conspicuity of radiographic findings suggestive of pulmonary arterial hypertension would be greater based on the severity of pulmonary arterial hypertension. Dogs with pulmonary arterial hypertension and normal control dogs were included in this retrospective, case control study. Three radiologists blinded to echocardiographic results scored thoracic radiographs for right ventricular and main pulmonary artery enlargement and pulmonary lobar artery enlargement, tortuosity, and blunting by multiple methods. Presence or absence of each finding was scored in an additive fashion and averaged for each grade of pulmonary arterial hypertension severity. Seventy-one dogs (60 dogs with pulmonary arterial hypertension and 11 control dogs) of which some had multiple studies were included: 20 mild, 21 moderate, 25 severe, and 11 absent pulmonary arterial hypertension. The following radiographic findings were significantly associated with increasing pulmonary arterial hypertension severity: right ventricular enlargement by "reverse D" and "3/5-2/5 cardiac ratio" methods, main pulmonary artery enlargement, and caudal lobar artery enlargement by the "3rd rib" method. Mean scores for severe pulmonary arterial hypertension and normal dogs were significantly different (P-value < 0.0001). Mean scores between different pulmonary arterial hypertension grades increased with severity but were not statistically significant. Individually and in combination, radiographic findings performed poorly in differentiating severity of pulmonary arterial hypertension. Findings indicated that thoracic radiographs should be utilized in conjunction with Doppler echocardiography in a complete diagnostic work-up for dogs with suspected
Ziesche, Rolf; Petkov, Venzeslav; Williams, John; Zakeri, Schaker M.; Mosgoller, Wilhelm; Knofler, Martin; Block, Lutz H.
The combined effects of hypoxia and interleukin 1, lipopolysaccharide, or tumor necrosis factor α on the expression of genes encoding endothelial constitutive and inducible nitric oxide synthases, endothelin 1, interleukin 6, and interleukin 8 were investigated in human primary pulmonary endothelial cells and whole pulmonary artery organoid cultures. Hypoxia decreased the expression of constitutive endothelial nitric oxide synthase (NOS-3) mRNA and NOS-3 protein as compared with normoxic conditions. The inhibition of expression of NOS-3 corresponded with a reduced production of NO. A combination of hypoxia with bacterial lipopolysaccharide, interleukin 1β , or tumor necrosis factor α augmented both effects. In contrast, the combination of hypoxia and the inflammatory mediators superinduced the expression of endothelin 1, interleukin 6, and interleukin 8. Here, we have shown that inflammatory mediators aggravate the effect of hypoxia on the down-regulation of NOS-3 and increase the expression of proinflammatory cytokines in human pulmonary endothelial cells and whole pulmonary artery organoid cultures.
Seyahi, Emire; Melikoglu, Melike; Akman, Canan; Hamuryudan, Vedat; Ozer, Harun; Hatemi, Gulen; Yurdakul, Sebahattin; Tuzun, Hasan; Oz, Buge; Yazici, Hasan
Pulmonary artery aneurysms (PAAs) are well known causes of mortality and morbidity in Behçet disease (BD). However, pulmonary artery involvement in BD is not limited to PAA; the other main type of pulmonary artery involvement is pulmonary artery thrombus (PAT), with or without associated PAA. In addition, other types of lung disease like nodules and cavities in the lung parenchyma are frequently associated with pulmonary artery involvement, and can be misinterpreted as being due to infection. We surveyed the clinical, radiologic, and laboratory characteristics and outcome of 47 BD patients with pulmonary artery involvement and the associated findings, all seen and followed at a single dedicated tertiary care center.We identified 47 (41 male, 6 female) patients in whom pulmonary artery involvement was diagnosed, who were registered in the multidisciplinary clinic at Cerrahpasa Medical Faculty between January 2000 and December 2007. Mean age at diagnosis was 29 ± 8 years, and mean disease duration to the onset of pulmonary artery involvement was 3.6 ± 4.8 years. Hemoptysis was the most common presenting symptom (79%) followed by cough, fever, dyspnea, and pleuritic chest pain. Thirty-four of 47 patients (72%) presented with PAA, including 8 with associated PAT. The remaining 13 patients (28%) had isolated PAT. Patients with isolated PAT in general have clinical features similar to patients with PAA. However, hemoptysis was less frequent and voluminous in patients with isolated PAT. Most (91%) of the patients had active disease outside the lungs when they presented with pulmonary artery involvement.Forty (85%) patients had nodules and 6 (13%) had cavities when first seen. Peripheral venous thrombosis was present in 36 of 47 (77%) patients, and intracardiac thrombi in 12 of the 36 (33%) patients. Nodules, cavities, and intracardiac thrombi were mainly present in the acute stages of pulmonary artery involvement.Pulmonary artery involvement is usually multiple, and
Korosoglou, Grigorios; Ringwald, Gerd; Giannitsis, Evangelos; Katus, Hugo A
Here we report for the first time on the diagnostic potential of cardiovascular magnetic resonance (CMR) to delineate the proximal course of an anomalous left circumflex coronary artery (LCX) originating from the right pulmonary artery in an adult patient with no other form of congenital heart disease. The patient was referred to our institution due to exertional chest discomfort. X-Ray coronary angiography showed a normal left anterior descending coronary artery (LAD) and right coronary artery (RCA), while the LCX was filled retrograde by collateral flow through the LAD and the RCA. The origin of the LCX was postulated to be the pulmonary artery, but the exact origin of the anomalous artery could not be depicted on conventional angiograms. CMR provided the unambiguous depiction of the origin of the anomalous LCX from the right pulmonary artery and the delineation of its proximal course in this case of a very rare coronary anomaly in adults.
Allen, Roblee P; Schelegle, Edward S; Bennett, Stephen H
Pulmonary hypertension (PH) is associated with progressive changes in arterial network complexity. An allometric model is derived that integrates diameter branching complexity between pulmonary arterioles of generation n and the main pulmonary artery (MPA) via a power-law exponent (X) in dn = dMPA2(-n/X) and the arterial area ratio β = 2(1-2/X). Our hypothesis is that diverse forms of PH demonstrate early decrements in X independent of etiology and pathogenesis, which alters the arteriolar shear stress load from a low-shear stress (X > 2, β > 1) to a high-shear stress phenotype (X < 2, β < 1). Model assessment was accomplished by comparing theoretical predictions to retrospective morphometric and hemodynamic measurements made available from a total of 221 PH-free and PH subjects diagnosed with diverse forms (World Health Organization; WHO groups I-IV) of PH: mitral stenosis, congenital heart disease, chronic obstructive pulmonary lung disease, chronic thromboembolism, idiopathic pulmonary arterial hypertension (IPAH), familial (FPAH), collagen vascular disease, and methamphetamine exposure. X was calculated from pulmonary artery pressure (PPA), cardiac output (Q) and body weight (M), utilizing an allometric power-law prediction of X relative to a PH-free state. Comparisons of X between PAH-free and PAH subjects indicates a characteristic reduction in area that elevates arteriolar shear stress, which may contribute to mechanisms of endothelial dysfunction and injury before clinically defined thresholds of pulmonary vascular resistance and PH. We conclude that the evaluation of X may be of use in identifying reversible and irreversible phases of PH in the early course of the disease process.
Pfister, Sandra L.
Pulmonary arterial hypertension is characterized by elevated pulmonary artery pressure and vascular resistance. In women the incidence is 4 fold greater than that in men. Studies suggest sustained vasoconstriction is a factor in increased vascular resistance. Possible vasoconstrictor mediators include arachidonic acid-derived lipoxygenase metabolites. Our studies in rabbits showed enhanced endothelium-dependent contractions to arachidonic acid in pulmonary arteries from females compared to males. Because treatment with a non-specific lipoxygenase inhibitor reduced contractions in females but not males, the present study identified which lipoxygenase isoform contributes to sex-specific pulmonary artery vasoconstriction. 15- and 5- but not 12-lipoxygenase protein expression was greater in females. Basal and A23187-stimulated release of 15-, 5- and 12-hydroxyeicosatetraenoic acid from females and males was measured by liquid chromatography/mass spectrometry. Only 15-hydroxyeicosatetraenoic acid synthesis was greater in females compared to males under both basal and stimulated conditions. Vascular contractions to 15-hydroxyeicosatetraenoic acid were enhanced in females compared to males (maximal contraction; 44 ± 6% vs 25 ± 3%). The specific 15-lipoxygenase inhibitor PD146176 (12 μmol/L) decreased arachidonic acid-induced contractions in females (maximal contraction; 93 ± 4% vs 57 ± 10%). If male pulmonary arteries were incubated with estrogen (1 μmol/L, 18 hrs), protein expression of 15-lipoxygenase, and 15-hydroxyeicosatetraenoic acid production increased. Mechanisms to explain the increased incidence of pulmonary hypertension in women are not known. Results suggest the 15-lipoxygenase pathway is different between females and males and is regulated by estrogen. Understanding this novel sex-specific mechanism may provide insight into the increased incidence of pulmonary hypertension in females. PMID:21300669
Taichman, Darren B; Shin, Jennifer; Hud, Laryssa; Archer-Chicko, Christine; Kaplan, Sandra; Sager, Jeffery S; Gallop, Robert; Christie, Jason; Hansen-Flaschen, John; Palevsky, Harold
Background Improved outcomes with expanding treatment options for patients with pulmonary arterial hypertension present the opportunity to consider additional end-points in approaching therapy, including factors that influence health-related quality of life. However, comparatively little is known about health-related quality of life and its determinants in patients with pulmonary arterial hypertension. Methods Health-related quality of life was evaluated in a cross sectional study of 155 outpatients with pulmonary arterial hypertension using generic and respiratory-disease specific measurement tools. Most patients had either World Health Organization functional Class II or III symptoms. Demographic, hemodynamic and treatment variables were assessed for association with health-related quality of life scores. Results Patients with pulmonary arterial hypertension suffered severe impairments in both physical and emotional domains of health-related quality of life. Patients with idiopathic ("primary") pulmonary arterial hypertension had the best, and those with systemic sclerosis the worst health-related quality of life. Greater six-minute walk distance correlated with better health-related quality of life scores, as did functional Class II versus Class III symptoms. Hemodynamic measurements, however, did not correlate with health-related quality of life scores. No differences in health-related quality of life were found between patients who were being treated with calcium channel antagonists, bosentan or continuously infused epoprostenol at the time of quality of life assessment. Conclusion Health-related quality of life is severely impaired in patients with pulmonary arterial hypertension and is associated with measures of functional status. Specific associations with impaired health-related quality of life suggest potential areas for targeted intervention. PMID:16092961
Shi, Xiaoqing; Wang, Xiaoqin; Wang, Chuan; Zhou, Kaiyu; Li, Yifei; Hua, Yimin
Pulmonary artery dissection (PAD) is a rare condition with high mortality and has not been reported in patient with infective endocarditis (IE). Here, we report the first case of such patient who experienced PDA and survived after surgical intervention.A 10-year-old female child was diagnosed as IE with a patent ductus arteriosis (PDA) and a vegetation on the left side of pulmonary artery trunk (10 × 5 mm). Following 3-week antibacterial treatment, the body temperature of patient returned to normal, and the size of vegetation reduced (7 × 3 mm). However, the patient had a sudden attack of sustained and crushing right chest pain, orthopnea with increasing respiratory rate (> 60/min), and acute high fever. Echocardiography revealed the detachment of vegetation on the first day and dissection of pulmonary artery on the next day. The patient received immediate surgical intervention. It was found that aneurysm had a size of 28 × 20 mm and its orifice (the dissecting site) located on the opposite side of the PDA opening (right side of the pulmonary artery trunk). The dissected left wall of pulmonary artery trunk was reconstructed followed by the closure of PDA with suture. The patient recovered uneventfully.From this case, we learned that the surgical intervention should be considered at an early time for IE patients who have a vegetation in pulmonary artery and PDA. After the infection is under control, the earlier surgery may prevent severe complications.
Srivastava, Mukta C; Ramani, Gautam V; Garcia, Jose P; Griffith, Bartley P; Uber, Patricia A; Park, Myung H
We report the case of a treatment-naive patient with pulmonary arterial hypertension who presented with decompensated right ventricular failure and cardiogenic shock. Unstable hemodynamics, hypoxia and end-organ hypoperfusion limited up-titration of pharmacotherapy. Mechanical circulatory support with veno-venous extracorporeal membrane oxygenation (VV-ECMO) was initiated to permit dose titration of pulmonary vasodilator therapy. VV-ECMO was weaned after 10 days of support, with successful transition to intravenous epoprostenol and oral sildenafil.
Ozge, C; Calikoğlu, M; Yildiz, A; Türsen, U; Tamer, L
Behçet's disease is a chronic inflammatory disorder of unknown aetiology, characterized by recurrent attacks. Pulmonary artery aneurysm is a rare but serious complication of Behçet's disease. We describe a patient with Behçet's disease and protein C and S deficiency who developed bilateral pulmonary artery aneurysms.
Drożdż, Jarosław; Warchoł, Ewa; Fijuth, Jacek; Filipiak, Krzysztof; Spych, Michał; Maciejewski, Marek; Piestrzeniewicz, Katarzyna; Ludomir, Stafańczyk; Janaszek-Sitkowska, Hanna; Januszewicz, Andrzej; Zembala, Marian
Intimal sarcoma of the heart and pulmonary artery is a very rare, malignant, primary tumour. The prognosis in patients with primary sarcoma of the pulmonary artery, including intimal sarcoma, is poor. We present the case and 3-years follow-up of 36-year-old woman who was successfully treated with surgical, partial resection of the tumour followed by radiotherapy.
Beker-Acay, Mehtap; Ozkececi, Gulay; Unlu, Ebru; Hocaoglu, Elif; Kacar, Emre; Onrat, Ersel
Unilateral absence of a pulmonary artery a very rare congenital disorder. We here present a case of a 22-year-old female patient with agenesis of the right pulmonary artery accompanying patent ductus arteriosus and Eisenmenger syndrome, diagnosed by chest X-ray and multidetector computed tomography 5 days after giving birth.
Stoecker, Christina; Moltz, Jan H.; Lassen, Bianca; Kuhnigk, Jan-Martin; Krass, Stefan; Welter, Stefan; Peitgen, Heinz-Otto
Purpose: Computed tomography (CT) imaging is the modality of choice for lung cancer diagnostics. With the increasing number of lung interventions on sublobar level in recent years, determining and visualizing pulmonary segments in CT images and, in oncological cases, reliable segment-related information about the location of tumors has become increasingly desirable. Computer-assisted identification of lung segments in CT images is subject of this work.Methods: The authors present a new interactive approach for the segmentation of lung segments that uses the Euclidean distance of each point in the lung to the segmental branches of the pulmonary artery. The aim is to analyze the potential of the method. Detailed manual pulmonary artery segmentations are used to achieve the best possible segment approximation results. A detailed description of the method and its evaluation on 11 CT scans from clinical routine are given.Results: An accuracy of 2–3 mm is measured for the segment boundaries computed by the pulmonary artery-based method. On average, maximum deviations of 8 mm are observed. 135 intersegmental pulmonary veins detected in the 11 test CT scans serve as reference data. Furthermore, a comparison of the presented pulmonary artery-based approach to a similar approach that uses the Euclidean distance to the segmental branches of the bronchial tree is presented. It shows a significantly higher accuracy for the pulmonary artery-based approach in lung regions at least 30 mm distal to the lung hilum.Conclusions: A pulmonary artery-based determination of lung segments in CT images is promising. In the tests, the pulmonary artery-based determination has been shown to be superior to the bronchial tree-based determination. The suitability of the segment approximation method for application in the planning of segment resections in clinical practice has already been verified in experimental cases. However, automation of the method accompanied by an evaluation on a larger
Qureshi, M. Umar; Vaughan, Gareth D.A.; Sainsbury, Christopher; Johnson, Martin; Peskin, Charles S.; Olufsen, Mette S.; Hill, N.A.
A novel multiscale mathematical and computational model of the pulmonary circulation is presented and used to analyse both arterial and venous pressure and flow. This work is a major advance over previous studies by Olufsen and coworkers (Ottesen et al., 2003; Olufsen et al., 2012) which only considered the arterial circulation. For the first three generations of vessels within the pulmonary circulation, geometry is specified from patient-specific measurements obtained using magnetic resonance imaging (MRI). Blood flow and pressure in the larger arteries and veins are predicted using a nonlinear, cross-sectional-area-averaged system of equations for a Newtonian fluid in an elastic tube. Inflow into the main pulmonary artery is obtained from MRI measurements, while pressure entering the left atrium from the main pulmonary vein is kept constant at the normal mean value of 2 mmHg. Each terminal vessel in the network of ‘large’ arteries is connected to its corresponding terminal vein via a network of vessels representing the vascular bed of smaller arteries and veins. We develop and implement an algorithm to calculate the admittance of each vascular bed, using bifurcating structured trees and recursion. The structured-tree models take into account the geometry and material properties of the ‘smaller’ arteries and veins of radii ≥ 50µm. We study the effects on flow and pressure associated with three classes of pulmonary hypertension expressed via stiffening of larger and smaller vessels, and vascular rarefaction. The results of simulating these pathological conditions are in agreement with clinical observations, showing that the model has potential for assisting with diagnosis and treatment of circulatory diseases within the lung. PMID:24610385
Bezgin, Tahir; Demircan, Hacer C; Kaymaz, Cihangir
Aneurysms involving the main pulmonary artery and its branches are rare. Clinical experience is limited, and their management is not well established. We present the case of a 35-year-old male patient with dyspnea and hemoptysis in whom subsequent imaging studies revealed a giant pulmonary artery aneurysm associated with an uncorrected patent ductus arteriosus and Eisenmenger’s syndrome. We chose to treat the patient conservatively with medical management due to the development of Eisenmenger’s physiology while waiting for heart-lung transplantation. PMID:25545802
Gamroth, A H; Schad, L R; Wacker, C M; Gehling, U; Knopp, M V; Betsch, B; Clorius, J H; van Kaick, G
MR blood velocity measurements were performed by the RACE technique in a plane perpendicular to the flow of the pulmonary arteries. MR findings were correlated with those of perfusion scintigraphy, Doppler US and right heart catheter (thermodilution). The ratio of MR blood flow measurements of right and left pulmonary arteries correlated well with the results of perfusion scintigraphy (RPA to LPA) and Doppler. Poor correlation was found when comparing MR blood flow measurements with right heart catheter since absolute flow measurements can be superimposed by neighboring blood vessels in complex anatomic situations.
Dias, Olívia Meira; Lombardi, Elisa Maria Siqueira; Canzian, Mauro; Soares Júnior, José; Vieira, Lucas de Oliveira; Terra Filho, Mário
Pulmonary artery sarcomas are rare, difficult-to-diagnose tumors that frequently mimic chronic pulmonary thromboembolism. We report the cases of two female patients with clinical signs of dyspnea and lung masses associated with pulmonary artery filling defects on chest CT angiography. We performed 18F-fluorodeoxyglucose positron emission tomography, which revealed increased radiotracer uptake in those lesions. Pulmonary artery sarcoma was subsequently confirmed by anatomopathological examination. We emphasize the importance of this type of tomography as a noninvasive method for the diagnosis of these tumors.
Rasmussen, Jason T; Thenappan, Thenappan; Benditt, David G; Weir, E Kenneth; Pritzker, Marc R
Pulmonary arterial hypertension is a manifestation of a group of disorders leading to pulmonary vascular remodeling and increased pulmonary pressures. The right ventricular (RV) response to chronic pressure overload consists of myocardial remodeling, which is in many ways similar to that seen in left ventricular (LV) failure. Maladaptive myocardial remodeling often leads to intraventricular and interventricular dyssychrony, an observation that has led to cardiac resynchronization therapy (CRT) for LV failure. CRT has proven to be an effective treatment strategy in subsets of patients with LV failure resulting in improvement in LV function, heart failure symptoms, and survival. Current therapy for pulmonary arterial hypertension is based on decreasing pulmonary vascular resistance, and there is currently no effective therapy targeting the right ventricle or maladaptive ventricular remodeling in these patients. This review focuses on the RV response to chronic pressure overload, its effect on electromechanical coupling and synchrony, and how lessons learned from left ventricular cardiac resynchronization might be applied as therapy for RV dysfunction in the context of pulmonary arterial hypertension.
Pulmonary arterial hypertension (PAH) is defined as an intractable disease characterized by a progressive elevation of pulmonary vascular resistance (PVR) and pulmonary arterial pressure (PAP), leading to right heart failure and premature death. The five-year survival rate after diagnosis is approximately 57%. Although extensive research has identified some factors associated with the cause of PAH, the etiology and pathogenesis remain unclear. In addition to Ca(2+) channel blockers (nifedipine, diltiazem), three categories of drug have been developed for the treatment of PAH based on the pathological mechanisms: prostacyclin and its analogues (epoprostenol, treprostinil, iloprost), endothelin receptor antagonists (bosentan, ambrisentan), and phosphodiesterase type 5 inhibitors (sildenafil, tadalafil). However, screening of novel types of drug acting on the signal pathway associated with the pathological mechanism underlying PAH is ongoing. We recently found that the extracellular Ca(2+)-sensing receptor (CaSR), which belongs to family C of the G protein-coupled receptor (GPCR) superfamily, is upregulated in pulmonary arterial smooth muscle cells (PASMCs) from patients with idiopathic PAH (IPAH). The upregulated CaSR is necessary for the enhanced Ca(2+) signaling and the augmented cell proliferation in PASMCs from IPAH patients. Most importantly, blockage of CaSR with an antagonist, NPS2143, prevents the development of pulmonary hypertension and right ventricular hypertrophy in animal models of pulmonary hypertension. The use of calcilytics, antagonists of CaSR, may be a novel therapeutic approach for PAH patients.
Spiegelenberg, S R; Hutter, P A; van de Wal, H J; Hitchcock, J F; Meijboom, E J; Harinck, E
Seventy-six patients were studied after arterial switch operation (ASO) between May 1977 and February 1992. Pulmonary artery reconstruction was initially performed by: conduit interposition in 5 patients, direct main pulmonary artery anastomosis and button patches in 60 patients, and pantaloon-like patch repair in 11 patients. Pulmonary stenosis developed in 17 patients (22%), requiring a total of 26 late re-interventions. Re-intervention was required in four out of five patients operated with pulmonary artery conduits, 11 out of 60 with a button patch repair and 2 out of 11 following pantaloon-type repair. In this series pulmonary artery stenosis (PS) involving the pulmonary valve occurred in 9/17 patients. Involvement of the pulmonary valve was related to the technique of pulmonary artery reconstruction. In these patients surgery is necessary. Balloon angioplasty can be a valuable tool when the stenosis is more distal. The incidence of PS was not influenced by the type of reconstruction or the use of Lecompte's maneuver.
Minareci, Edibe; Sadan, Gulay
Objective: Vardenafil was reported to relax rat pulmonary artery through endothelium-dependent mechanisms. The aim of this in vitro study was to investigate other related mechanisms for this effect. Materials and Methods: Endothelium-intact and denuded artery rings were suspended in order to record isometric tension. In the rings with or without endothelium, the concentration-response curves for vardenafil were generated. In the rings without endothelium the contractile response induced by phenylephrine (Phe) or KCl was assessed in the presence or absence of vardenafil. In the last set of experiments, pulmonary artery rings were exposed to calcium-free isotonic depolarizing solution and the contractile response induced by the addition of calcium was evaluated in the presence or absence of vardenafil, nifedipine, verapamil or 1H-[1,2,4] oxadiazolo[4,3-a] quinoxalin-1-one (ODQ). Results: Vardenafil attenuated pulmonary artery contraction induced by phenylephrine in the presence and absence of endothelium. In addition, vardenafil attenuated both Phe or KCl-induced contraction but, it's effect on the KCl dose-response curve was more significant. Vardenafil also inhibited the contractile response induced by calcium in a dose-dependent manner. Addition of nifedipine or verapamil did not significantly alter this effect while ODQ incubation significantly inhibited vardenafil-induced relaxation. Conclusion: From these findings, it was proposed that vardenafil relaxed rat pulmonary artery through inhibiting calcium influx. PMID:24741191
Fal'kovskiĭ, G E; Aleksi-Meskhishvili, V V; Berishvili, I I
Operation was performed on 8 patients whose left coronary artery arose from the pulmonary artery; one of the patients was operated on twice. Three patients had been operated on twice before 1972, the operation in all of them consisted in talcum suspension insufflation into the pericardium. The results of these operations were poor. Operation for ligation of the orifice of the left coronary artery was conducted on 6 patients (including one with the ineffective talcum suspension insufflation into the pericardium). All patients who were operated on at the age of over one year survived. In children of the first year of life with a low ejection fraction and absence of expulsion on the level of the pulmonary artery the results of surgery were poor.
Ernam, Dilek; Atalay, Figen; Alp, Aysun; Hasanoğlu, H Canan
Intracardiac thrombus and pulmonary embolism is a very rare manifestation of Behçet's disease. A twenty-years-old man was admitted to hospital due to dyspnea, haemoptysis, fever and partially loss of vision. On dynamic thorax computed tomography (CT), there was aneurysmatic dilatation and thrombus in bilateral pulmonary artery segments and also findings of pulmonary thromboembolism. A diagnosis of Behçet's disease was made based on his clinical course and radiological findings. During treatment, the patient was admitted two times to the hospital because of recurrent pulmonary thromboembolism. At the 10th months of follow up, partially dissolution of the thrombi and pulmonary defects were observed and right ventricular thrombus was revealed by dynamic thorax CT. On a follow up period of 16 months the patient is still under treatment and doing well. We present this case because Behçet's disease is a rarely considered cause of recurrent pulmonary embolism and intracardiac thrombus which is seen under treatment.
Evison, Matthew; Crosbie, Philip; Chaturvedi, Anshuman; Shah, Rajesh; Booton, Richard
This case illustrates a rare but important differential diagnosis of pulmonary emboli in the field of thoracic oncology, that of pulmonary artery sarcoma. It describes particular clinical features that may raise suspicion of this tumor in cases of suspected pulmonary emboli, and highlights novel radiological modalities and tissue sampling techniques in such cases. Surgical resection, as part of multi-modality therapy, is the cornerstone of treatment that has seen survival dramatically improve in recent years for patients with this rare cancer. PMID:26557921
Okiwelu, Ngozichukwuka; Finn, Chris; Vanden Driesen, Rohan; Sanders, Lucas; Joshi, Pragnesh
Pulmonary artery involvement has been reported in various degrees of complicated dissection of the ascending aorta. The prognosis remains poor without high-risk surgical intervention, but conservative management can be considered in high-risk cases. We report a case of nonoperative management of an octogenarian who presented with a contained rupture of his proximal ascending aorta, likely from a penetrating atherosclerotic ulcer. It was complicated by extrinsic compression of the pulmonary trunk and transient pulmonary hypertension without features of acute right heart failure. He remained alive at the one-year follow-up.
Juscinski, Jacek; Haponiuk, Ireneusz; Chojnicki, Maciej; Steffens, Mariusz; Szofer-Sendrowska, Aneta; Kwasniak, Ewelina; Żelechowski, Pawel
Anomalies in development of the pulmonary valve, pulmonary trunk and peripheral pulmonary arteries are typical accompanying pathologies in patients with tetralogy of Fallot (ToF). Demanding for diagnostics and borderline for treatment is a condition colloquially called “discontinuous pulmonary arteries”, while the main branches are supplied with systemic blood from the ascending aorta, aortic arch or descending thoracic aorta. We present a case of a one-year-old girl with ToF and anomalous origin of the left pulmonary artery (LPA) from Kommerell's diverticulum who underwent two-stage surgical therapy with the support of interventional cardiology. We conclude that early diagnosis of discontinuous pulmonary artery is crucial for choosing the optimal operative strategy. In our opinion, simultaneous anatomic intracardiac correction with direct pulmonary reconstruction seems reasonable and effective, particularly when the result is achieved after joint efforts of cardiac surgery and interventional cardiology. PMID:26336445
Munro, Hamish M; Sorbello, Andrea M C; Nykanen, David G
A baby presented at term with respiratory distress was managed with extracorporeal membrane oxygenation. Bronchoscopy revealed tracheal hypoplasia, complete tracheal rings, and agenesis of the right main bronchus. Echocardiography showed a left pulmonary arterial sling arising from the proximal part of the right pulmonary artery. Cardiac catheterization demonstrated abnormal pulmonary vasculature in the left lung which would have prevented survival, even after surgical repair. Diagnostic catheterization was important in delineating the anatomy, and aided in the decision not to proceed with surgical repair.
Yang, Y; Zhang, B K; Liu, D; Nie, W; Yuan, J M; Wang, Z; Guo, Y M
1. The aim of the study was to determine if H(2)S is involved in the development of hypoxia-induced pulmonary hypertension in broilers, a condition frequently observed in a variety of cardiac and pulmonary diseases. 2. Two-week-old broilers were reared under normoxic conditions or exposed to normobaric hypoxia (6 h/day) with tissue levels of H(2)S adjusted by administering sodium hydrosulfide (NaHS, 10 µmol/kg body weight/day). Mean pulmonary arterial pressure, right ventricular mass, plasma and tissue H(2)S levels, the expression of cystathionine-β-synthase (CSE) and vascular remodeling were determined at 35 d of age. 3. Exposure to hypoxia-induced pulmonary arterial hypertension was characterized by elevated pulmonary pressure, right ventricular hypertrophy and vascular remodeling. This was accompanied by decreased expression of CSE and decreased concentrations of plasma and tissue H(2)S. 4. Hypoxia-induced pulmonary hypertension was significantly reduced by administration of NaHS but this protective effect was largely abolished by D, L-propargylglycerine, an inhibitor of CSE. 5. The results indicate that H(2)S is involved in the development of hypoxia-induced pulmonary hypertension. Supplementing NaHS or H(2)S could be a strategy for reducing hypoxia-induced hypertension in broilers.
Chou Meichun; Liang Hueilung Pan Huayban; Yang Chienfang
Ruptured mycotic pulmonary pseudoaneurysm is a lethal complication. Emergent surgical repair is usually recommended, but still associated with a high mortality rate. We present a patient in whom mycotic pulmonary pseudoaneurysm was a complication after surgical lobectomy 2 weeks earlier. This patient had suffered from repeated massive hemoptysis. After emergent surgical repair of the ruptured pulmonary artery stump, another episode of massive hemorrhage occurred. The pulmonary arteriogram revealed a segmental stenosis and a large, wide-necked, lobulated pseudoaneurysm at the left proximal pulmonary artery. We deployed a balloon-expandable stent-graft (48 mm in length mounted on a 12 mm x 40 mm angioplasty balloon) across the stenotic segment and the neck of the pulmonary pseudoaneurysm. Hemostasis was achieved immediately and, under a 4-week antibiotic treatment, patient was transferred to a local hospital for medical care. This case report demonstrates the benefit of minimally invasive endovascular therapy in a critically ill patient. A literature review of the etiology and management of mycotic pulmonary pseudoaneurysm is included.
Lee, Youngjae; Choi, Wooshin; Lee, Donghoon; Chang, Jinhwa; Kang, Ji-Houn; Choi, Jihye
Caudal pulmonary artery diameter (CPAD) to body surface area (BSA) ratios were measured in ventrodorsal thoracic radiographs to assess the correlation between CPAD to BSA ratios and systolic pulmonary arterial pressure (PAP) in dogs. Thoracic radiographs of 44 dogs with systolic pulmonary arterial hypertension (PAH) and 55 normal dogs were evaluated. Systolic PAP was estimated by Doppler echocardiography. CPADs were measured at their largest point at the level of tracheal bifurcation on ventrodorsal radiographs. Both right and left CPAD to BSA ratios were significantly higher in the PAH group than in the normal group (p < 0.0001). Linear regression analysis showed positive associations between PAP and right and left CPAD to BSA ratio (right, p = 0.0230; left, p = 0.0012). The receiver operating characteristic curve analysis revealed that the CPAD to BSA ratio had moderate diagnostic accuracy for detecting PAH. The operating point, sensitivity, specificity, and area under the curve were 28.35, 81.40%, 81.82%, and 0.870; respectively, for the right side and 26.92, 80.00%, 66.67%, and 0.822, respectively, for the left. The significant correlation of CPAD to BSA ratio with echocardiography-estimated systolic PAP supports its use in identifying PAH on survey thoracic radiographs in dogs. PMID:26645336
Lindenmaier, Tamas J.; Sheikh, Khadija; Bluemke, Emma; Gyacskov, Igor; Mura, Marco; Licskai, Christopher; Mielniczuk, Lisa; Fenster, Aaron; Cunningham, Ian A.; Parraga, Grace
Chronic obstructive pulmonary disease (COPD), is a major contributor to hospitalization and healthcare costs in North America. While the hallmark of COPD is airflow limitation, it is also associated with abnormalities of the cardiovascular system. Enlargement of the pulmonary artery (PA) is a morphological marker of pulmonary hypertension, and was previously shown to predict acute exacerbations using a one-dimensional diameter measurement of the main PA. We hypothesized that a three-dimensional (3D) quantification of PA size would be more sensitive than 1D methods and encompass morphological changes along the entire central pulmonary artery. Hence, we developed a 3D measurement of the main (MPA), left (LPA) and right (RPA) pulmonary arteries as well as total PA volume (TPAV) from thoracic CT images. This approach incorporates segmentation of pulmonary vessels in cross-section for the MPA, LPA and RPA to provide an estimate of their volumes. Three observers performed five repeated measurements for 15 ex-smokers with ≥10 pack-years, and randomly identified from a larger dataset of 199 patients. There was a strong agreement (r2=0.76) for PA volume and PA diameter measurements, which was used as a gold standard. Observer measurements were strongly correlated and coefficients of variation for observer 1 (MPA:2%, LPA:3%, RPA:2%, TPA:2%) were not significantly different from observer 2 and 3 results. In conclusion, we generated manual 3D pulmonary artery volume measurements from thoracic CT images that can be performed with high reproducibility. Future work will involve automation for implementation in clinical workflows.
Wang, J; Qiao, J; Zhao, L H; Li, K; Wang, H; Xu, T; Tian, Y; Gao, M; Wang, X
Pulmonary vascular remodelling, mainly characterized by arterial medial thickening, is an important pathological feature of broiler ascites syndrome (AS). Since vascular smooth muscle cells (VSMC) form the major cellular component of arterial medial layer, we speculate that VSMC proliferation is one of the causes of pulmonary arterial medial thickening in ascitic broilers. Hence, the present study was designed to investigate the role of VSMC proliferation in pulmonary vascular remodelling in development of AS induced by low ambient temperature. Broilers in control group (22 +/- 1.5 degrees C) and low temperature group (11 +/- 2 degrees C) were sampled every week at 15-50 days of age. Proliferative indexes of VSMC in pulmonary arteries were assessed with proliferating cell nuclear antigen, and the relative medial thickness (RMT) and relative wall area (RWA), as indexes of pulmonary vascular remodelling, were examined by computer-image analysing system. The results showed that the high incidence (18.75%) of AS was induced by low temperature, and a significantly increased VSMC proliferation was observed in pulmonary arteries in the low temperature group at 22-50 days of age (P < 0.05). In addition, RMT and RWA in pulmonary arteries were significantly elevated in the low temperature group from 36 days of age (P < 0.05), indicating that pulmonary vascular remodelling occurred following VSMC proliferation in AS. Our data suggest that proliferation of VSMC may facilitate pulmonary vascular remodelling and have a pivotal role in AS induced by low ambient temperature.
LIU, PANPAN; YAN, SHUANGQUAN; CHEN, MAYUN; CHEN, ALI; YAO, DAN; XU, XIAOMEI; CAI, XUEDING; WANG, LIANGXING; HUANG, XIAOYING
The synthesis and accumulation of collagen play an important role in the formation and progression of hypoxic pulmonary hypertension. Baicalin has been reported to prevent bleomycin-induced pulmonary fibrosis. However, the role of baicalin in the treatment of pulmonary hypertension remains unknown. A disintegrin and metalloprotease with thrombospondin type-1 motif (ADAMTS-1) is a secreted enzyme that acts on a wide variety of extracellular matrix (ECM) substrates associated with vascular diseases. In this study, we aimed to investigate the effects of baicalin on the synthesis of collagen I in rats with pulmonary hypertension induced by hypoxia and the changes in ADAMTS-1 expression. A total of 24 Sprague Dawley rats were randomly assigned to 3 groups as follows: the control group (C), the hypoxia group (H) and the hypoxia + baicalin group (B). The rats in groups H and B were kept in a normobaric hypoxic chamber for 4 weeks, and the rats in group C were exposed to room air. We measured the hemodynamic indexes, including mean pulmonary artery pressure (mPAP), mean systemic (carotid) artery pressure (mSAP), and then calculated the mass ratio of right ventricle to left ventricle plus septum [RV/(LV + S)] to reflect the extent of right ventricular hypertrophy. We measured the mRNA and protein expression levels of type I collagen, type III collagen and ADAMTS-1 by hybridization in situ, and immunohistochemistry and western blot analysis, respectively. The results revealed that treatment with baicalin significantly reduced pulmonary artery pressure and attenuated the remodeling of the pulmonary artery under hypoxic conditions by increasing the expression of ADAMTS-1, so that the synthesis of type I collagen and its mRNA expression were inhibited. In conclusion, baicalin effectively inhibits the synthesis of collagen I in pulmonary arteries and this is associated with an increase in the expression of ADAMTS-1. Thus, treatment with baicalin may be an effective method for
Liu, Panpan; Yan, Shuangquan; Chen, Mayun; Chen, Ali; Yao, Dan; Xu, Xiaomei; Cai, Xueding; Wang, Liangxing; Huang, Xiaoying
The synthesis and accumulation of collagen play an important role in the formation and progression of hypoxic pulmonary hypertension. Baicalin has been reported to prevent bleomycin-induced pulmonary fibrosis. However, the role of baicalin in the treatment of pulmonary hypertension remains unknown. A disintegrin and metalloprotease with thrombospondin type-1 motif (ADAMTS-1) is a secreted enzyme that acts on a wide variety of extracellular matrix (ECM) substrates associated with vascular diseases. In this study, we aimed to investigate the effects of baicalin on the synthesis of collagen I in rats with pulmonary hypertension induced by hypoxia and the changes in ADAMTS-1 expression. A total of 24 Sprague Dawley rats were randomly assigned to 3 groups as follows: the control group (C), the hypoxia group (H) and the hypoxia + baicalin group (B). The rats in groups H and B were kept in a normobaric hypoxic chamber for 4 weeks, and the rats in group C were exposed to room air. We measured the hemodynamic indexes, including mean pulmonary artery pressure (mPAP), mean systemic (carotid) artery pressure (mSAP), and then calculated the mass ratio of right ventricle to left ventricle plus septum [RV/(LV + S)] to reflect the extent of right ventricular hypertrophy. We measured the mRNA and protein expression levels of type I collagen, type III collagen and ADAMTS-1 by hybridization in situ, and immunohistochemistry and western blot analysis, respectively. The results revealed that treatment with baicalin significantly reduced pulmonary artery pressure and attenuated the remodeling of the pulmonary artery under hypoxic conditions by increasing the expression of ADAMTS-1, so that the synthesis of type I collagen and its mRNA expression were inhibited. In conclusion, baicalin effectively inhibits the synthesis of collagen I in pulmonary arteries and this is associated with an increase in the expression of ADAMTS-1. Thus, treatment with baicalin may be an effective method for
Wright, Stephen P.; Granton, John T.; Esfandiari, Sam; Goodman, Jack M.
Key points A consistent inverse hyperbolic relationship has been observed between pulmonary vascular resistance and compliance, although changes in pulmonary artery wedge pressure (PAWP) may modify this relationship.This relationship predicts that pulmonary artery systolic, diastolic and mean pressure maintain a consistent relationship relative to the PAWP.We show that, in healthy exercising human adults, both pulmonary vascular resistance and compliance decrease in relation to exercise‐associated increases in PAWP.Pulmonary artery systolic, diastolic and mean pressures maintain a consistent relationship with one another, increasing linearly with increasing PAWP.Increases in PAWP in the setting of exercise are directly related to a decrease in pulmonary vascular compliance, despite small decreases in pulmonary vascular resistance, thereby increasing the pulsatile afterload to the right ventricle. Abstract The resistive and pulsatile components of right ventricular afterload (pulmonary vascular resistance, Rp; compliance, Cp) are related by an inverse hyperbolic function, expressed as their product known as RpCp‐time. The RpCp‐time exhibits a narrow range, although it may be altered by the pulmonary artery wedge pressure (PAWP). Identifying the determinants of RpCp‐time should improve our understanding of the physiological behaviour of pulmonary arterial systolic (PASP), diastolic (PADP) and mean (mPAP) pressures in response to perturbations. We examined the effect of exercise in 28 healthy non‐athletic adults (55 ± 6 years) who underwent right heart catheterization to assess haemodynamics and calculate Rp and Cp. Measurements were made at rest and during two consecutive 8–10 min stages of cycle ergometry, at targeted heart‐rates of 100 beats min–1 (Light) and 120 beats min–1 (Moderate). Cardiac output increased progressively during exercise. PASP, PADP, mPAP and PAWP increased for Light exercise, without any further rise for Moderate
Domingo, Enric; Aguilar, Rio; López-Meseguer, Manuel; Teixidó, Gisela; Vazquez, Manuel; Roman, Antonio
Pulmonary arterial hypertension (PAH) is a rare fatal disease defined as a sustained elevation of pulmonary arterial pressure to more than 25 mmHg at rest, with a mean pulmonary-capillary wedge pressure and left ventricular enddiastolic pressure of less than 15 mmHg at rest. Histopathology of PAH is founded on structural modifications on the vascular wall of small pulmonary arteries characterized by thickening of all its layers. These changes, named as vascular remodelling, include vascular proliferation, fibrosis, and vessel obstruction. In clinical practice the diagnosis of PAH relies on measurements of pulmonary vascular pressure and cardiac output, and calculation of pulmonary vascular resistances. Direct evaluation of pulmonary vascular structure is not routinely performed in pulmonary hypertension since current imaging techniques are limited and since little is known about the relationship between structural changes and functional characteristics of the pulmonary vasculature. Intravascular ultrasound studies in patients with pulmonary hypertension have shown a thicker middle layer, increased wall-thickness ratio and diminished pulsatility than in control patients. Optical Coherence Tomography, a new high resolution imaging modality that has proven its superiority over intravascular ultrasound (IVUS) for the detection and characterization of coronary atherosclerotic plaque composition, may potentially be a useful technique for the in vivo study of the pulmonary arterial wall. In addition current progress in Echo Doppler technique will quantify right ventricular function with parameters independent of loading conditions and not requiring volumetric approximations of the complex geometry of the right ventricle. This would allow the in vivo study of right ventricular and pulmonary artery remodelling in PAH. PMID:19452037
Sasi, Viktor; Forster, Tamás; Ungi, Imre
We report a 71-year-old man who presented with atypical chest pain. Coronary angiography did not reveal left main or proximal left anterior descending coronary artery stenosis, but a fistulous communication with a stronger tube-like fistula was present originating from the proximal left anterior descending coronary artery and emptying into the main pulmonary artery. Fractional flow reserve and coronary flow reserve measurements were performed to gain more data on the potential functional aspects of this fistula. With the present case, the importance of functional evaluation of these fistulas is demonstrated. PMID:25061466
Xu, Fei; Wang, Qian; Zhang, Heng; Chen, Sipeng; Ao, Hushan
Background Pulmonary artery catheters (PAC) are used widely to monitor hemodynamics in patients undergoing coronary bypass graft (CABG) surgery. However, recent studies have raised concerns regarding both the effectiveness and safety of PAC. Therefore, our aim was to determine the effects of the use of PAC on the short- and long-term health and economic outcomes of patients undergoing CABG. Methods 1361 Chinese patients who consecutively underwent isolated, primary CABG at the Cardiovascular Institute of Fuwai Hospital from June 1, 2012 to December 31, 2012 were included in this study. Of all the patients, 453 received PAC during operation (PAC group) and 908 received no PAC therapy (control group). Short-term and long-term mortality and major complications were analyzed with multivariate regression analysis and propensity score matched-pair analysis was used to yield two well-matched groups for further comparison. Results The patients who were managed with PAC more often received intraoperative vasoactive drugs dopamine (70.9% vs. 45.5%; P<0.001) and epinephrine (7.7% vs. 2.6%; P<0.001). In addition, costs for initial hospitalization were higher for PAC patients ($14,535 vs. $13,873, respectively, p = 0.004). PAC use was neither associated with the perioperative mortality or major complications, nor was it associated with long-term mortality and major adverse cardiac and cerebrovascular events. In addition, comparison between two well-matched groups showed no significant differences either in baseline characteristics or in short-term and long-term outcomes. Conclusions There is no clear indication of any benefit or harm in managing CABG patients with PAC. However, use of PAC in CABG is more expensive. That is, PAC use increased costs without benefit and thus appears unjustified for routine use in CABG surgery. PMID:25689312
Abstract Primary sarcomas of the major blood vessels can be classified based on location in relationship to the wall or by histologic type. Angiosarcomas are malignant neoplasms that arise from the endothelial lining of the blood vessels; those arising in the intimal compartment of pulmonary artery are rare. We report a case of pulmonary artery angiosarcoma in a 36-year old female with pulmonary masses. The patient had no other primary malignant neoplasm, thus excluding a metastatic lesion. Gross examination revealed a thickened right pulmonary artery and a necrotic and hemorrhagic tumor, filling and occluding the vascular lumen. The mass extended distally, within the pulmonary vasculature of the right lung. Microscopically, an intravascular undifferentiated tumor was identified. The tumor cells showed expression for vascular markers VEGFR, VEGFR3, PDGFRa, FGF, Ulex europaeus, FVIII, FLI-1, CD31 and CD34; p53 was overexpressed and Ki67 proliferative rate was increased. Intravascular angiosarcomas are aggressive neoplasms, often associated with poor outcome. Virtual slide The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/2315906377648045. PMID:23134683
Badlam, Jessica B.; Bull, Todd M.
Pulmonary arterial hypertension (PAH) is a chronic disease that results in narrowing of the small pre-capillary pulmonary arteries leading to elevation of pulmonary artery pressure and pulmonary vascular resistance, subsequent right ventricular failure, and if unchecked, death. Advances in the treatment of PAH over the last two decades have markedly improved survival. These improvements reflect a combination of changes in treatments, improved patient care strategies, and varying disease phenotypes in the PAH population. Currently approved therapies for PAH are directed at the recognized abnormalities within the pulmonary vasculature and include endothelin receptor antagonists, phosphodiesterase-5 inhibitors, soluble guanylate cyclase stimulators, and prostacyclin pathway agents. Most of these drugs have been approved on the basis of short-term trials that mainly demonstrated improvements in exercise capacity. More recently, long-term, event-driven trials of novel drugs have been performed, demonstrating new efficacy parameters. There have also been exciting advances in the understanding of right heart failure pathophysiology in PAH that have the potential to inspire the development of right ventricular targeted therapy and continued discoveries in the heterogeneity of disease and response to treatment has great potential for developing more ‘personalized’ therapeutic options. In this article, we review the current available data regarding the management of PAH, with an emphasis on the pharmacologic therapies and discussion of novel therapeutic directions for the treatment of this fatal disease. PMID:28348727
Valenzuela-Garcia, Luis Felipe Almendro-Delia, Manuel; Gonzalez-Valdayo, Miguel; Munoz-Campos, Juan; Dorado-Garcia, Jose C.; Gomez-Rosa, Francisco; Vazquez-Garcia, Rafael; Calderon-Leal, Jose M.
To illustrate a successful approach to resolving a pulmonary artery catheter knot in the pacing leads of a cardiac resynchronization device. When planning invasive monitoring for patients having right chamber electrodes, fluoroscopic-guided catheter insertion and extraction is advisable. In the event of coiling or knotting, an interventional radiologist should be contacted as soon as possible to avoid serious complications.
Davie, Neil J.; Gerasimovskaya, Evgenia V.; Hofmeister, Stephen E.; Richman, Aaron P.; Jones, Peter L.; Reeves, John T.; Stenmark, Kurt R.
The precise cellular and molecular mechanisms regulating adventitial vasa vasorum neovascularization, which occurs in the pulmonary arterial circulation in response to hypoxia, remain unknown. Here, using a technique to isolate and culture adventitial fibroblasts (AdvFBs) and vasa vasorum endothelial cells (VVECs) from the adventitia of pulmonary arteries, we report that hypoxia-activated pulmonary artery AdvFBs exhibited pro-angiogenic properties and influenced the angiogenic phenotype of VVEC, in a process of cell-cell communication involving endothelin-1 (ET-1). We demonstrated that AdvFBs, either via co-culture or conditioned media, stimulated VVEC proliferation and augmented the self-assembly and integrity of cord-like networks that formed when VVECs where cultured on Matrigel. In addition, hypoxia-activated AdvFBs produced ET-1, suggesting a paracrine role for this pro-angiogenic molecule in these processes. When co-cultured on Matrigel, AdvFBs and VVECs self-assembled into heterotypic cord-like networks, a process augmented by hypoxia but attenuated by either selective endothelin receptor antagonists or oligonucleotides targeting prepro-ET-1 mRNA. From these observations, we propose that hypoxia-activated AdvFBs exhibit pro-angiogenic properties and, as such, communicate with VVECs, in a process involving ET-1, to regulate vasa vasorum neovascularization occurring in the adventitia of pulmonary arteries in response to chronic hypoxia. PMID:16723696
Lv, Tian-shi Wang, Chao Song, Li Lv, Yong-xing Zou, Ying-hua
We report for the first time an extremely rare anomalous origin of the superior left pulmonary artery in a 60 year-old man. Although it was occult in clinical indications, such a malformation still ought to be considered, especially during endovascular procedures.
Oktay, A Afşin; Dibs, Samer R; Silver, Jeffrey M; Akbar, M Sikander
The Riata family of defibrillator leads (St. Jude Medical, Sylmar, CA) has been recalled because of externalisation of conductor cables and increased electrical failure. We describe the case of a man with an incidental finding of extreme externalisation of a conductor from the right ventricular defibrillator lead (Riata family) with prolapse into the left pulmonary artery.
Calderon, Eduardo G; Khawar, Sarwat; Cunningham, Jennifer A; Russell, Lori D; Alpert, Martin A
HELLP syndrome (hemolysis, elevation of liver enzymes, and low platelet count) occurs during pregnancy. Intrahepatic hemorrhage and subcapsular liver hematoma with or without rupture are reported complications of this syndrome. The patient described in this report developed HELLP syndrome associated with a subcapsular liver hematoma and pulmonary artery thrombus, complications that created a therapeutic conundrum.
Gosalbez, F; Gudin, C; Miralles, M; Naya, J; Valle, J M
A rare case of intimal sarcoma of the left pulmonary artery, diagnosed by fine needle aspiration biopsy and treated by pneumonectomy, is presented. Survival was nearly 4 years and the patient died as the result of attempted resection of a local recurrence. The literature is reviewed.
Sass, D. J.; Ritman, E. L.; Caskey, P. E.; Banchero, N.; Wood, E. H.
Dependent pulmonary atelectasis, arterial-venous shunting, and downward displacement of the heart caused by the gravitational-inertial force environment were prevented in dogs breathing oxygenated liquid fluorocarbon in a whole-body water-immersion respirator. Partial closure of the major airways during part of the expiratory phase of liquid respiration was a significant problem initially but was minimized in subsequent studies.
Tsuneyama, Koichi; Kawaguchi, Makoto; Fukuoka, Junya; Kudo, Fujimi; Nakae, Susumu; Arita, Makoto; Nagai, Yoshinori; Takaki, Satoshi; Takatsu, Kiyoshi
IL-33 is one of the critical cytokines that activates group 2 innate lymphoid cells (ILC2s) and mediates allergic reactions. Accumulating evidence suggests that IL-33 is also involved in the pathogenesis of several chronic inflammatory diseases. Previously, we generated an IL-5 reporter mouse and revealed that lung IL-5–producing ILC2s played essential roles in regulating eosinophil biology. In this study, we evaluated the consequences of IL-33 administration over a long period, and we observed significant expansion of ILC2s and eosinophils surrounding pulmonary arteries. Unexpectedly, pulmonary arteries showed severe occlusive hypertrophy that was ameliorated in IL-5– or eosinophil-deficient mice, but not in Rag2-deficient mice. This indicates that IL-5–producing ILC2s and eosinophils play pivotal roles in pulmonary arterial hypertrophy. Administration of a clinically used vasodilator was effective in reducing IL-33–induced hypertrophy and repressed the expansion of ILC2s and eosinophils. Taken together, these observations demonstrate a previously unrecognized mechanism in the development of pulmonary arterial hypertrophy and the causative roles of ILC2 in the process.
Courand, Pierre-Yves; Pina Jomir, Géraldine; Khouatra, Chahéra; Scheiber, Christian; Turquier, Ségolène; Glérant, Jean-Charles; Mastroianni, Bénédicte; Gentil, Béatrice; Blanchet-Legens, Anne-Sophie; Dib, Alfred; Derumeaux, Geneviève; Humbert, Marc; Mornex, Jean-François; Cordier, Jean-François; Cottin, Vincent
Right ventricle ejection fraction (RVEF) evaluated with magnetic resonance imaging is a strong determinant of patient outcomes in pulmonary arterial hypertension. We evaluated the prognostic value of RVEF assessed with conventional planar equilibrium radionuclide angiography at baseline and change 3-6 months after initiating pulmonary arterial hypertension-specific therapy. In a prospective cohort of newly diagnosed patients with idiopathic, heritable or anorexigen-associated pulmonary arterial hypertension, RVEF was measured at baseline (n=100) and 3-6 months after initiation of therapy (n=78). After a median follow-up of 4.1 years, 41 deaths occurred, including 35 from cardiovascular causes. Patients with a (median) baseline RVEF >25% had better survival than those with a RVEF <25% using Kaplan-Meier analysis (p=0.010). RVEF at baseline was an independent predictor of all-cause and cardiovascular mortality in adjusted Cox regression model (p=0.002 and p=0.007, respectively; HR 0.93 for both). Patients with stable or increased RVEF at 3-6 months had a trend for improved all-cause survival (HR 2.43, p=0.086) and had less cardiovascular mortality (HR 3.25, p=0.034) than those in whom RVEF decreased despite therapy. RVEF assessed with conventional planar equilibrium radionuclide angiography at baseline and change in RVEF 3-6 months after therapy initiation independently predict outcomes in patients with pulmonary arterial hypertension.
Bronte, Enrico; Coppola, Giuseppe; Di Miceli, Riccardo; Sucato, Vincenzo; Russo, Antonio; Novo, Salvatore
The idiopathic pulmonary arterial hypertension is a complex disease that mainly affects pulmonary arterial circulation. This undergoes a remodeling with subsequent reduction of flow in the small pulmonary arteries. Because of this damage an increased vascular resistance gradually develops, and over time it carries out in heart failure. The inflammatory process is a key element in this condition, mediated by various cytokines. The inflammatory signal induces activation of NF-κB, and prompts TGF-β-related signaling pathway. Clinical evolution leads to progressive debilitation, greatly affecting the patient quality of life. The actual therapeutic approaches, are few and expensive, and include systemic drugs such as prostanoids, phosphodiesterase inhibitors and antagonists of endothelin-1 (ERBs). Some researchers have long investigated the anti-inflammatory effects of curcumin. It shows a role for inactivation of NF-κB-mediated inflammation. On the basis of these findings we propose a potential role of curcumin and its pharmacologically fit derivatives for treatment of idiopathic pulmonary arterial hypertension.
Nara, Akina; Nagai, Hisashi; Shintani-Ishida, Kaori; Ogura, Sayoko; Shimosawa, Tatsuo; Kuwahira, Ichiro; Shirai, Mikiyasu; Yoshida, Ken-ichi
Pulmonary arterial hypertension (PAH) is prevalent in patients with obstructive sleep apnea syndrome (OSAS). Aging induces arginase activation and reduces nitric oxide (NO) production in the arteries. Intermittent hypoxia (IH), conferred by cycles of brief hypoxia and normoxia, contributes to OSAS pathogenesis. Here, we studied the role of arginase and aging in the pathogenesis of PAH in adult (9-mo-old) and young (2-mo-old) male Sprague-Dawley rats subjected to IH or normoxia for 4 weeks and analyzed them with a pressure-volume catheter inserted into the right ventricle (RV) and by pulsed Doppler echocardiography. Western blot analysis was conducted on arginase, NO synthase isoforms, and nitrotyrosine. IH induced PAH, as shown by increased RV systolic pressure and RV hypertrophy, in adult rats but not in young rats. IH increased expression levels of arginase I and II proteins in the adult rats. IH also increased arginase I expression in the pulmonary artery endothelium and arginase II in the pulmonary artery adventitia. Furthermore, IH reduced pulmonary levels of nitrate and nitrite but increased nitrotyrosine levels in adult rats. An arginase inhibitor (N(ω)-hydroxy-nor-1-arginine) prevented IH-induced PAH and normalized nitrite and nitrate levels in adult rats. IH induced arginase up-regulation and PAH in adult rats, but not in young rats, through reduced NO production. Our findings suggest that arginase inhibition prevents or reverses PAH.
Hadley, A. T., III; Conkin, J.; Waligora, J. M.; Horrigan, D. J., Jr.
Doppler, or ultrasonic, monitoring for pain manifestations of decompression sickness (the bends) is accomplished by placing a sensor on the chest over the pulmonary artery and listening for bubbles. Difficulties have arisen because the technician notes that the pulmonary artery seems to move with subject movement in a one-g field and because the sensor output is influenced by only slight degrees of sensor movement. This study used two subjects and mapped the position of the pulmonary artery in one-g, microgravity, and two-g environments using ultrasound. The results showed that the pulmonary artery is fixed in location in microgravity and not affected by subject position change. The optimal position corresponded to where the Doppler signal is best heard with the subject in a supine position in a one-g environment. The impact of this result is that a proposed multiple sensor array on the chest proposed for microgravity use may not be necessary to monitor an astronaut during extravehicular activities. Instead, a single sensor of approximately 1 inch diameter and mounted in the position described above may suffice.
Junqueira, F P; Lima, C M A O; Coutinho, A C; Parente, D B; Bittencourt, L K; Bessa, L G P; Domingues, R C; Marchiori, E
Pulmonary hypertension (PH) is a progressive disease that leads to substantial morbidity and eventual death. Pulmonary multidetector CT angiography (MDCTA), pulmonary MR angiography (MRA) and MR-derived pulmonary perfusion (MRPP) imaging are non-invasive imaging techniques for the differential diagnosis of PH. MDCTA is considered the gold standard for the diagnosis of pulmonary embolism, one of the most common causes of PH. MRA and MRPP are promising techniques that do not require the use of ionising radiation or iodinated contrast material, and can be useful for patients for whom such material cannot be used. This review compares the imaging aspects of pulmonary MRA and 64-row MDCTA in patients with chronic thromboembolic or idiopathic PH.
Junqueira, F P; Lima, C M A O; Coutinho, A C; Parente, D B; Bittencourt, L K; Bessa, L G P; Domingues, R C; Marchiori, E
Pulmonary hypertension (PH) is a progressive disease that leads to substantial morbidity and eventual death. Pulmonary multidetector CT angiography (MDCTA), pulmonary MR angiography (MRA) and MR-derived pulmonary perfusion (MRPP) imaging are non-invasive imaging techniques for the differential diagnosis of PH. MDCTA is considered the gold standard for the diagnosis of pulmonary embolism, one of the most common causes of PH. MRA and MRPP are promising techniques that do not require the use of ionising radiation or iodinated contrast material, and can be useful for patients for whom such material cannot be used. This review compares the imaging aspects of pulmonary MRA and 64-row MDCTA in patients with chronic thromboembolic or idiopathic PH. PMID:22932061