Original Article
Reduction in Pulmonary Vascular Resistance with Long-Term Epoprostenol (Prostacyclin) Therapy in Primary Pulmonary Hypertension
N Engl J Med 1998; 338:273-277January 29, 1998
- Abstract
Background
Primary (idiopathic) pulmonary hypertension is a progressive, fatal disease. Conventional therapy with anticoagulant and vasodilator drugs may improve symptoms and survival among selected patients, but there is no evidence that the disease can be reversed.
Methods
We evaluated the effects of long-term therapy (i.e., for more than one year) with intravenous epoprostenol (prostacyclin) in patients with advanced primary pulmonary hypertension. The base-line evaluation included an assessment of pulmonary vascular dilation in response to intravenous adenosine. The epoprostenol dose was increased monthly to the maximum tolerated. Long-term therapy was evaluated by measuring improvement in symptoms, exercise capacity, and hemodynamic variables.
Results
We evaluated 27 patients with primary pulmonary hypertension over a mean (±SD) period of 16.7±5.2 months. Intravenous adenosine had a variable effect on pulmonary vascular resistance (mean reduction, 27 percent; range, 0 to 56; P<0.001). Epoprostenol therapy was initiated and the rate of infusion was increased by an average of 2.4 ng per kilogram of body weight per minute each month. Twenty-six of the 27 patients had improvement in symptoms and hemodynamic measures, and overall, pulmonary vascular resistance declined by 53 percent to 7.9±3.8 resistance units (P<0.001) at the time of restudy. The long-term effects of epoprostenol exceeded the short-term pulmonary vasodilator response to adenosine in all but one patient. Seven of the eight patients who had minimal pulmonary vasodilation in response to adenosine (mean reduction in resistance units, <20 percent) still had a significant reduction in pulmonary vascular resistance when treated with epoprostenol (mean, 39±14 percent; P = 0.002).
Conclusions
In primary pulmonary hypertension, long-term therapy with epoprostenol lowers pulmonary vascular resistance beyond the level achieved in the short term with intravenous adenosine. Epoprostenol appears to have sustained efficacy in this disorder.
Media in This Article
Figure 1
Pulmonary Vascular Resistance at Base Line, after the Administration of Intravenous Adenosine to Test Pulmonary Vasoreactivity, and after Long-Term Epoprostenol Therapy.Figure 2
Reduction in Pulmonary Vascular Resistance with Epoprostenol Therapy in Relation to the Short-Term Reduction after the Administration of Adenosine.Article Activity
- Article
The treatment of primary (idiopathic) pulmonary hypertension is problematic. Long-term anticoagulation with warfarin has been associated with improved survival without affecting symptoms, suggesting that it slows the progression of the disease.1,2 Calcium-channel blockers may produce immediate vasodilation that, when the drugs are given in relatively high doses, can be sustained and may be associated with improved symptoms and survival in a selected minority of patients.2
Recently, intravenous epoprostenol (Flolan, Glaxo Wellcome, Research Triangle Park, N.C.), also known as prostacyclin, was introduced as a treatment for advanced primary pulmonary hypertension.3 It has antithrombotic properties related to its effects on platelets and is a potent vasodilator of both systemic and pulmonary arteries.4 Previous studies of intravenous epoprostenol in primary pulmonary hypertension have shown that, when given over the short term, it can produce vasodilation more consistently than calcium-channel blockers.5-7 For these reasons, it has become the preferred long-term treatment for patients with primary pulmonary hypertension who continue to have symptoms in spite of conventional therapy. Tolerance of the medication, which always occurs, has made dosing uncertain. We undertook this study to investigate the effectiveness and potential mechanisms of action of epoprostenol given according to an aggressive dosing strategy for longer than one year in patients with primary pulmonary hypertension.
Methods
The study included consecutive patients referred to our center for evaluation of pulmonary hypertension who began to receive epoprostenol between January 1, 1994, and October 31, 1995, and were followed for 12 to 24 months. The diagnosis of primary pulmonary hypertension was established according to the criteria of the National Institutes of Health Registry on Primary Pulmonary Hypertension.8 Patients were in New York Heart Association (NYHA) functional class III or IV despite optimal medical therapy. The base-line evaluation included a history and physical examination, treadmill exercise testing, and cardiac catheterization.
The exercise testing was performed according to a Naughton–Balke protocol with pulse oximetry at rest and during peak exercise. Hemodynamic variables were measured by means of right-sided heart catheterization by a thermodilution balloon-flotation catheter. Resting intracardiac pressure, systemic and pulmonary arterial oxygen saturation, and cardiac output were measured in all patients. After the base-line hemodynamic variables were recorded, the degree of pulmonary vasodilation in response to intravenous adenosine was measured.9 The adenosine infusion was started at a dose of 50 to 100 μg per kilogram of body weight per minute and increased by 50 μg per kilogram per minute every two minutes until the patient had symptom-limiting side effects such as dyspnea or chest discomfort. If no side effects were experienced, the protocol was terminated at a peak dose of 350 μg per kilogram per minute. All hemodynamic measurements were repeated at the peak dose of adenosine.
Epoprostenol therapy was initiated after the insertion of a Hickman catheter into a subclavian vein. Sterile, lyophilized epoprostenol sodium powder was used as long-term therapy and administered continuously with the use of a portable infusion pump (CADD 1, model 5100 HF, Pharmacia Deltec, St. Paul, Minn.). Patients were instructed in sterile techniques for mixing medication, catheter care, preparation of dressings, and drug administration by clinical nurse specialists. Epoprostenol therapy was begun at a dose of 2 ng per kilogram per minute and gradually increased to the maximal tolerated doses within seven days. Patients were then instructed to report to a nurse specialist every 30 days, or more often if they had symptoms of pulmonary hypertension (e.g., increased dyspnea) or if the side effects of the medication (e.g., jaw pain) disappeared. The dose of the medication was increased further if a reduction in side effects permitted or, in patients with minimal side effects, any time the patient had a return of symptoms that could be attributed to pulmonary hypertension. The goal was to have patients receive as high a dose of epoprostenol as possible.
At the time of the follow-up evaluation, another history was obtained and patients again underwent a physical examination, treadmill testing, and a hemodynamic assessment. In addition, a questionnaire was administered to identify any illness associated with treatment, with particular focus on pump malfunction and infections related to the Hickman catheter system.
Statistical Analysis
Base-line demographic and hemodynamic variables were recorded and are presented as means ±SD. Comparisons of variables measured at base line and during treatment in the same patients were made with use of Student's t-test for paired data. Comparisons between subgroups of patients were made with Student's t-test for unpaired data. The Pearson correlation coefficient was computed to test the association between base-line variables and measures of the drug's effectiveness. A chi-square analysis was used to determine the effect of treatment on the NYHA functional class. All tests were two-sided; P values below 0.05 were considered to indicate statistical significance.
Results
Of the 38 patients treated, 27 underwent a second evaluation at our institution during the study period. There were 19 women and 8 men, with a mean age of 39.8±12.1 years. The patients had severe symptoms; 63 percent were in NYHA functional class III, and 37 percent in NYHA functional class IV. Eleven of the original 38 patients were excluded, for the following reasons: 5 had follow-up performed by a local doctor, 3 had follow-up catheterization performed more than 24 months after the initiation of epoprostenol therapy, and 3 declined to return for the second evaluation. Eight of these 11 patients underwent cardiac catheterization at various times after enrollment (3 to 36 months). In all eight, the pulmonary vascular resistance at base line (18.5±8.6 resistance units) was lower on restudy (8.2±3.2 resistance units, P = 0.01). None of the 11 patients died during the study period. One patient, who declined catheterization, died subsequently.
At base line, the mean duration of exercise was 261±175 seconds (range, 0 to 695). The mean pulmonary-artery pressure was 67±10 mm Hg, and the pulmonary vascular resistance was 16.7±5.4 units (Table 1Table 1
Hemodynamic Variables at Base Line, in Response to the Administration of Adenosine, and after Long-Term Epoprostenol Therapy.). Adenosine caused a variable but significant decrease of 27±18 percent in pulmonary vascular resistance (range, 0 to 56 percent; P<0.001) (Table 1). The mean dose of adenosine used was 211±70 μg per kilogram per minute.After the base-line evaluation, epoprostenol therapy was initiated, and the dose was increased to the maximal tolerated dose over a period of seven days. Doses were subsequently increased by 2 ng per kilogram per minute every month if side effects permitted, or whenever the patient reported an increase in dyspnea or fatigue that was attributed to primary pulmonary hypertension. The mean duration of treatment at follow-up was 16.7±5.2 months (range, 12 to 24). The mean dose of epoprostenol at the time of the follow-up study was 40±15 ng per kilogram per minute, which corresponds to a mean increase of 2.4 ng per kilogram per minute each month. Concurrent medications also included digoxin (used by 93 percent of patients), diuretics (85 percent), warfarin (100 percent), and calcium-channel blockers (41 percent). Patients whose condition had deteriorated while they were receiving calcium-channel blockers had this medication withdrawn before the initiation of epoprostenol therapy. Patients whose condition was stable but who had symptoms while receiving calcium-channel blockers continued to receive these drugs throughout the study period. In no instance were calcium-channel blockers added to the patient's treatment regimen while he or she was receiving epoprostenol.
At the time of the follow-up evaluation, all patients had improvement in their symptoms; 22 percent were in NYHA functional class I, 74 percent in class II, and 4 percent in class III (P<0.001). The duration of exercise on the treadmill increased by 142 percent to 631±283 seconds (P<0.001). The improvement in treadmill time did not correlate with the decrease in pulmonary vascular resistance (r = 0.33, P = 0.16). Systemic arterial oxygen saturation during exercise at base line (93±6 percent) was not significantly changed at follow-up (91±4 percent, P = 0.11).
At the time of repeated cardiac catheterization, the mean pulmonary arterial pressure was 22 percent lower than at base line (range, 0 to 51 percent lower; P<0.001), and the cardiac output had increased by 67 percent (range, -15 to 155 percent; P<0.001) (Table 1). Pulmonary vascular resistance fell to 7.9±3.8 units (P<0.001), a mean reduction of 53 percent (range, 3 to 78 percent). Twenty-six of the 27 patients had a long-term reduction of at least 20 percent in pulmonary vascular resistance.
We compared the short-term vasodilator response to adenosine with the long-term effects of epoprostenol. In all but one instance, the decrease in pulmonary vascular resistance with long-term epoprostenol therapy exceeded the short-term decrease in resistance in response to adenosine challenge at base line (Figure 1Figure 1
Pulmonary Vascular Resistance at Base Line, after the Administration of Intravenous Adenosine to Test Pulmonary Vasoreactivity, and after Long-Term Epoprostenol Therapy.). In addition, the greater the short-term decrease in pulmonary vascular resistance with adenosine, the lower the pulmonary vascular resistance became with long-term epoprostenol therapy (r = 0.65, P = 0.01). However, seven of eight patients with a minimal response to adenosine (decrease in resistance, <20 percent; mean, 6±13) still had a significant long-term reduction in pulmonary vascular resistance with epoprostenol (mean, 39±14 percent; range, 20 to 66; P = 0.002) (Figure 2Figure 2Reduction in Pulmonary Vascular Resistance with Epoprostenol Therapy in Relation to the Short-Term Reduction after the Administration of Adenosine.). One patient who had a minimal decrease in pulmonary vascular resistance in response to adenosine had little further reduction after 15 months of epoprostenol.The change in pulmonary vascular resistance after long-term epoprostenol therapy was not related to pulmonary vascular resistance at base line (r = 0.117, P = 0.56). Thus, even patients with extremely advanced disease and markedly elevated pulmonary vascular resistance had a significant improvement with epoprostenol.
Eleven patients received epoprostenol and calcium-channel blockers concurrently. To test whether the combination treatment influenced the long-term response to epoprostenol, we compared these 11 patients with the 16 who received epoprostenol but not calcium-channel blockers. The patients who received both epoprostenol and calcium-channel blockers were similar to those who received epoprostenol but not calcium-channel blockers with respect to the severity of their pulmonary hypertension (pulmonary vascular resistance, 14.3 vs. 18.2 units; P = 0.07), the short-term vasodilator response to adenosine (decrease in pulmonary vascular resistance, 29 percent vs. 26 percent; P = 0.67), and the long-term reduction in pulmonary vascular resistance achieved (56 percent vs. 50 percent, P = 0.40).
Morbidity
Side effects related to the use of epoprostenol were common and included diarrhea, jaw pain, headaches, and flushing in all patients. All the serious complications were related to the delivery system. No patient had failure of the ambulatory infusion pump or thrombosis of the Hickman catheter. Ten patients had a total of 17 local infections at the exit site of the Hickman catheter; these were successfully treated with oral antibiotic agents. Three of these 10 patients also had an episode of sepsis, documented by positive blood cultures, that required treatment with intravenous antibiotic agents. The rate of local infection was 0.49 per patient-year, and that of blood-borne infections was 0.09 per patient-year.
Discussion
Primary pulmonary hypertension is caused by a pulmonary vascular arteriopathy that affects predominantly the arteriolar vessels, the mechanism of which is unclear. Pathological studies reveal medial hypertrophy, intimal proliferation and fibrosis, and thrombotic lesions, which are unevenly distributed throughout the pulmonary vasculature.10,11 Although some of these lesions appear histologically very complex, it remains unknown which lesions reflect irreversible vascular changes.12
The established conventional therapy for this disease has been anticoagulant and vasodilator agents. Anticoagulant agents are believed to reduce or halt in situ thrombosis, thus slowing the progression of the disease. In this respect, one prospective and one retrospective study suggest that they are effective.1,2 There are no data, however, demonstrating that warfarin directly influences the extent of medial hypertrophy, vasoconstriction, or intimal proliferation.
Calcium-channel blockers have been used to reduce the level of vasoconstriction, and they appear to be effective in selected patients.2,13 They are not expected to be effective in patients whose vascular changes are not related to vasoconstriction (such as those with changes caused by thrombotic lesions) and who are thus unresponsive to vasodilator challenge. Calcium-channel blockers are also unlikely to be effective in patients with vasoconstriction that is associated with extensive intimal proliferation and fibrosis that is too severe to be reversed. Studies of the long-term effectiveness of calcium-channel blockers in patients who respond to these agents in the short term demonstrate that the level of vasodilation achieved in the short term remains relatively constant when therapy continues.2,13,14
Epoprostenol is an appealing therapy because of its antithrombotic and vasodilator properties.4 The use of intravenous epoprostenol in this illness represents a novel treatment strategy. It is the first instance in which a substance produced by normal vascular endothelium has been used as a treatment for a vasculopathy. Clearly, some of the therapeutic properties of epoprostenol are not yet understood.
When epoprostenol was introduced as a treatment for primary pulmonary hypertension, it was characterized as a bridge to lung transplantation, and it was hoped that it could cause immediate vasodilation that might be sustained until the patient could receive a graft.15 Subsequently, prospective studies have shown sustained clinical benefits of epoprostenol and improved long-term survival in patients who received this agent, as compared with historical controls.3,7,16 Its mechanism of action has been attributed to long-term pulmonary vasodilation and possibly to its antiplatelet effects.
Our results, however, show that long-term treatment is associated not only with vasodilation, but also with significant reductions in pulmonary vascular resistance that go beyond immediate vasodilation. Although there was no control group in this study, spontaneous reductions in pulmonary vascular resistance would be unlikely to occur.8 The fact that epoprostenol caused a long-term reduction in pulmonary vascular resistance that exceeded that which could be achieved through vasodilator challenge is consistent with the drug's having a different effect on the pulmonary vasculature when given over the long term. The existence of such a different mechanism is supported by the fact that long-term epoprostenol therapy was effective in lowering pulmonary vascular resistance in patients who had no short-term response to adenosine at all. The process by which epoprostenol affects the pulmonary vasculature in such patients remains speculative, since only serial open-lung biopsies could reveal the precise nature of the vascular changes. However, experimental data from studies of epoprostenol in animals with vascular disease have demonstrated its potential to reverse vascular lesions.4,17
Tolerance of epoprostenol with long-term treatment, manifested by a return of symptoms, is poorly understood, but it can be overcome by continuing to increase the dosage over time. The optimal strategy is unclear. In previous studies, the dose was increased if the patient had worsening symptoms or if his or her condition was deteriorating.7,16 Our strategy was more aggressive and was designed to maintain therapy at the highest dose tolerated. Patients often received a dose increase even if they had clinical improvement, if side effects permitted. Whether this aggressive strategy is essential to achieve this level of long-term reduction in pulmonary vascular resistance was not tested.
The fact that all but one of our patients had a significant improvement in hemodynamic variables with long-term epoprostenol treatment indicates the remarkable success rate of this therapy. Indeed, were it not for the complexity and expense of the delivery system, epoprostenol might be considered first-line therapy for all patients with primary pulmonary hypertension. The chief adverse effects of treatment were serious infections related to the delivery system. The incidence of sepsis, however, was lower than previously reported in a multicenter trial.3 We attribute this lower rate to the careful measures taken to educate the patients and referring physicians about the use of a sterile technique in mixing the medications and the early detection of any serious infection.
In summary, in this study epoprostenol caused substantial long-term reductions in pulmonary vascular resistance in patients with severe primary pulmonary hypertension; these reductions exceeded the short-term reductions in pulmonary vascular resistance achieved with adenosine. Our results should encourage physicians to consider long-term epoprostenol treatment for patients with less advanced disease, with the possibility of achieving even better results. As pulmonary vascular resistance returns toward normal with long-term use, patients waiting for lung grafts may no longer need transplantation. This study also raises the question of whether epoprostenol could eventually be withdrawn or substituted for calcium-channel blockers, other oral agents, or both. The answers to these questions may hold promise for the long-term treatment of this once fatal illness.
Source Information
From the Section of Cardiology, Rush Medical College, Rush–Presbyterian–St. Luke's Medical Center, Chicago.
Address reprint requests to Dr. Rich at the Rush Heart Institute, Center for Pulmonary Heart Disease, Rush–Presbyterian–St. Luke's Medical Center, 1725 W. Harrison St., Suite 020, Chicago, IL 60612-3824.
- References
References
1
Fuster V ,Steele PM ,Edwards WD ,Gersh BJ ,McGoon MD ,Frye RL . Primary pulmonary hypertension: natural history and the importance of thrombosis. Circulation 1984;70:580-587
CrossRef | Web of Science | Medline2
Rich S ,Kaufmann E ,Levy PS . The effect of high doses of calcium-channel blockers on survival in primary pulmonary hypertension. N Engl J Med 1992;327:76-81
Full Text | Web of Science | Medline3
Barst RJ ,Rubin LJ ,Long WA , et al. A comparison of continuous intravenous epoprostenol (prostacyclin) with conventional therapy for primary pulmonary hypertension. N Engl J Med 1996;334:296-301
Full Text | Web of Science | Medline4
Vane JR ,Botting RM . Pharmacodynamic profile of prostacyclin. Am J Cardiol 1995;75:3A-10A
CrossRef | Web of Science | Medline5
Barst RJ . Pharmacologically induced pulmonary vasodilatation in children and young adults with primary pulmonary hypertension. Chest 1986;89:497-503
CrossRef | Web of Science | Medline6
Weir EK ,Rubin LJ ,Ayres SM , et al. The acute administration of vasodilators in primary pulmonary hypertension: experience from the National Institutes of Health Registry on Primary Pulmonary Hypertension. Am Rev Respir Dis 1989;140:1623-1630
CrossRef | Web of Science | Medline7
Barst RJ ,Rubin LJ ,McGoon MD ,Caldwell EJ ,Long WA ,Levy PS . Survival in primary pulmonary hypertension with long-term continuous intravenous prostacyclin. Ann Intern Med 1994;121:409-415
Web of Science | Medline8
Rich S ,Dantzker DR ,Ayres SM , et al. Primary pulmonary hypertension: a national prospective study. Ann Intern Med 1987;107:216-223
Web of Science | Medline9
Nootens M ,Schrader B ,Kaufmann E ,Vestal R ,Long W ,Rich S . Comparative acute effects of adenosine and prostacyclin in primary pulmonary hypertension. Chest 1995;107:54-57
CrossRef | Web of Science | Medline10
Wagenvoort CA ,Wagenvoort N . Primary pulmonary hypertension: a pathologic study of the lung vessels in 156 clinically diagnosed cases. Circulation 1970;42:1163-1184
Web of Science11
Pietra GG ,Edwards WD ,Kay JM , et al. Histopathology of primary pulmonary hypertension: a qualitative and quantitative study of pulmonary blood vessels from 58 patients in the National Heart, Lung, and Blood Institute, Primary Pulmonary Hypertension Registry. Circulation 1989;80:1198-1206
CrossRef | Web of Science | Medline12
Wagenvoort CA . Hypertensive pulmonary vascular disease: the point of no return. Minn Med 1985;68:45-48
Medline13
Rich S ,Brundage BH . High-dose calcium channel-blocking therapy for primary pulmonary hypertension: evidence for long-term reduction in pulmonary arterial pressure and regression of right ventricular hypertrophy. Circulation 1987;76:135-141
CrossRef | Web of Science | Medline14
Rubin LJ ,Nicod P ,Hillis LD ,Firth BG . Treatment of primary pulmonary hypertension with nifedipine: a hemodynamic and scintigraphic evaluation. Ann Intern Med 1983;99:433-438
Web of Science | Medline15
Higenbottam TW ,Wheeldon D ,Wells F ,Wallwork J . Long-term treatment of primary pulmonary hypertension with continuous intravenous epoprostenol (prostacyclin). Lancet 1984;1:1046-1047
CrossRef | Web of Science | Medline16
Shapiro SM ,Oudiz RJ ,Cao T , et al. Primary pulmonary hypertension: improved long-term effects and survival with continuous intravenous epoprostenol infusion. J Am Coll Cardiol 1997;30:343-349
CrossRef | Web of Science | Medline17
Jones DA ,Benjamin CW ,Linseman DA . Activation of thromboxane and prostacyclin receptors elicits opposing effects on vascular smooth muscle cell growth and mitogen-activated protein kinase signaling cascades. Mol Pharmacol 1995;48:890-896
Web of Science | Medline
- Citing Articles (182)
Citing Articles
1
Christian F. Opitz, Rüdiger Blindt, Friedrich Blumberg, Mathias M. Borst, Leonhard Bruch, Hanno H. Leuchte, Mona Lichtblau, Christian Nagel, Klaus Peters, Stephan Rosenkranz, Dietmar Schranz, Dirk Skowasch, Henning Tiede, Joachim Weil, Ralf Ewert. (2011) Pulmonary hypertension: Hemodynamic evaluation. Updated Recommendations of the Cologne Consensus Conference 2011. International Journal of Cardiology 154, S13-S19
CrossRef2
Satoshi Akagi, Kazufumi Nakamura, Hiromi Matsubara, Kengo Fukushima Kusano, Noriyuki Kataoka, Takahiro Oto, Katsumasa Miyaji, Aya Miura, Aiko Ogawa, Masashi Yoshida, Hatsue Ueda-Ishibashi, Chikao Yutani, Hiroshi Ito. (2011) Prostaglandin I2 induces apoptosis via upregulation of Fas ligand in pulmonary artery smooth muscle cells from patients with idiopathic pulmonary arterial hypertension. International Journal of Cardiology
CrossRef3
Kengo F. Kusano. (2011) Treatment for pulmonary hypertension including lung transplantation. General Thoracic and Cardiovascular Surgery 59:8, 538-546
CrossRef4
Peter Oishi, Sanjeev A Datar, Jeffrey R Fineman. (2011) Pediatric pulmonary arterial hypertension: current and emerging therapeutic options. Expert Opinion on Pharmacotherapy 12:12, 1845-1864
CrossRef5
Gan Hui-li. (2011) The Management of Acute Pulmonary Arterial Hypertension. Cardiovascular Therapeutics 29:3, 153-175
CrossRef6
Richard A. Krasuski, Ganesh P. Devendra, Stephen A. Hart, Andrew Wang, J. Kevin Harrison, Thomas M. Bashore. (2011) Response to Inhaled Nitric Oxide Predicts Survival in Patients With Pulmonary Hypertension. Journal of Cardiac Failure 17:4, 265-271
CrossRef7
Jérôme Pavec, David Launay, Stephen C. Mathai, Paul M. Hassoun, Marc Humbert. (2011) Scleroderma Lung Disease. Clinical Reviews in Allergy & Immunology 40:2, 104-116
CrossRef8
H. Yamasaki, Y. Maeshima, T. Nasu, D. Saito, K. Tanabe, K. Hirokoshi-Kawahara, H. Sugiyama, Y. Sakai, H. Makino. (2011) Intermittent administration of a sustained-release prostacyclin analog ONO-1301 ameliorates renal alterations in a rat type 1 diabetes model. Prostaglandins, Leukotrienes and Essential Fatty Acids 84:3-4, 99-107
CrossRef9
Tomoko Morikawa, Mitsushige Murata, Shigeo Okuda, Hikaru Tsuruta, Shiro Iwanaga, Mitsuru Murata, Toru Satoh, Satoshi Ogawa, Keiichi Fukuda. (2011) Quantitative Analysis of Right Ventricular Function in Patients With Pulmonary Hypertension Using Three-Dimensional Echocardiography and a Two-Dimensional Summation Method Compared to Magnetic Resonance Imaging. The American Journal of Cardiology 107:3, 484-489
CrossRef10
K. Stenson, J.R.W. Brownrigg, M. Mohamed. (2011) Occurrence and Multiple Recurrence of Severe Vasospasm of the Upper Extremity Following Thorascopic Sympathectomy for Hyperhidrosis. European Journal of Vascular and Endovascular Surgery 41:2, 264-266
CrossRef11
L. Savale, D. S. O’Callaghan, R. Magnier, J. Le Pavec, P. Hervé, X. Jaïs, A. Seferian, M. Humbert, G. Simonneau, O. Sitbon. (2011) Current management approaches to portopulmonary hypertension. International Journal of Clinical Practice 65, 11-18
CrossRef12
Walid Habre, Gergely Albu, Tibor Z Janosi, Fabienne Fontao, Britta S von Ungern-Sternberg, Maurice Beghetti, Ferenc Petak. (2011) Prevention of bronchial hyperreactivity in a rat model of precapillary pulmonary hypertension. Respiratory Research 12:1, 58
CrossRef13
Satyan Lakshminrusimha, Vasanth H. Kumar. 2011. Diseases of Pulmonary Circulation. , 632-656.
CrossRef14
Sherif Afifi, Shahriar Shayan, Abbas Al-Qamari. (2010) Pulmonary Hypertension and Right Ventricular Function. International Anesthesiology Clinics 47:1, 97-120
CrossRef15
R. Barst. (2010) How has epoprostenol changed the outcome for patients with pulmonary arterial hypertension?. International Journal of Clinical Practice 64, 23-32
CrossRef16
Eun A. Ko, Michael Y. Song, Reshma Donthamsetty, Ayako Makino, Jason X-J. Yuan. (2010) Tension measurement in isolated rat and mouse pulmonary artery. Drug Discovery Today: Disease Models 7:3-4, 123-130
CrossRef17
Nazzareno Galiè, Massimiliano Palazzini, Enri Leci, Alessandra Manes. (2010) Estrategias terapéuticas actuales en la hipertensión arterial pulmonar. Revista Española de Cardiología 63:6, 708-724
CrossRef18
Joe R. Anderson, James J. Nawarskas. (2010) Pharmacotherapeutic Management of Pulmonary Arterial Hypertension. Cardiology in Review 18:3, 148-162
CrossRef19
Adriano R. Tonelli, Hassan Alnuaimat, Kamal Mubarak. (2010) Pulmonary vasodilator testing and use of calcium channel blockers in pulmonary arterial hypertension. Respiratory Medicine 104:4, 481-496
CrossRef20
Monnipa Suesaowalak, John P. Cleary, Anthony C. Chang. (2010) Advances in diagnosis and treatment of pulmonary arterial hypertension in neonates and children with congenital heart disease. World Journal of Pediatrics 6:1, 13-31
CrossRef21
Jagdish Hiremath, Sadagopa Thanikachalam, Keyur Parikh, Somasundaram Shanmugasundaram, Sudhakar Bangera, Leland Shapiro, Gregory B. Pott, Cindy L. Vnencak-Jones, Carl Arneson, Michael Wade, R. James White. (2010) Exercise improvement and plasma biomarker changes with intravenous treprostinil therapy for pulmonary arterial hypertension: A placebo-controlled trial. The Journal of Heart and Lung Transplantation 29:2, 137-149
CrossRef22
Kamal K. Mubarak. (2010) A review of prostaglandin analogs in the management of patients with pulmonary arterial hypertension. Respiratory Medicine 104:1, 9-21
CrossRef23
Cha Gon Lee, Su In Jeong, June Huh, I-Seok Kang, Heung Jae Lee, Ji-Hyuk Yang, Tae Gook Jun. (2010) Surgical outcome of severe pulmonary arterial hypertension secondary to left-to-right shunt lesions. Korean Journal of Pediatrics 53:2, 195
CrossRef24
Nazzareno Galiè, Marius M. Hoeper, Marc Humbert, Adam Torbicki, Jean-Luc Vachiery, Joan Albert Barberá, Maurice Beghetti, Paul Corris, Sean Gaine, J. Simon Gibbs, Miguel Ángel Gómez-Sánchez, Guillaume Jondeau, Walter Klepetko, Christian Opitz, Andrew Peacock, Lewis Rubin, Michael Zellweger, Gerald Simonneau. (2009) Guía de práctica clínica para el diagnóstico y tratamiento de la hipertensión pulmonar. Revista Española de Cardiología 62:12, 1464.e1-1464.e58
CrossRef25
, N. Galie, M. M. Hoeper, M. Humbert, A. Torbicki, J.-L. Vachiery, J. A. Barbera, M. Beghetti, P. Corris, S. Gaine, J. S. Gibbs, M. A. Gomez-Sanchez, G. Jondeau, W. Klepetko, C. Opitz, A. Peacock, L. Rubin, M. Zellweger, G. Simonneau, , A. Vahanian, A. Auricchio, J. Bax, C. Ceconi, V. Dean, G. Filippatos, C. Funck-Brentano, R. Hobbs, P. Kearney, T. McDonagh, K. McGregor, B. A. Popescu, Z. Reiner, U. Sechtem, P. A. Sirnes, M. Tendera, P. Vardas, P. Widimsky, , U. Sechtem, N. Al Attar, F. Andreotti, M. Aschermann, R. Asteggiano, R. Benza, R. Berger, D. Bonnet, M. Delcroix, L. Howard, A. N. Kitsiou, I. Lang, A. Maggioni, J. E. Nielsen-Kudsk, M. Park, P. Perrone-Filardi, S. Price, M. T. S. Domenech, A. Vonk-Noordegraaf, J. L. Zamorano. (2009) Guidelines for the diagnosis and treatment of pulmonary hypertension: The Task Force for the Diagnosis and Treatment of Pulmonary Hypertension of the European Society of Cardiology (ESC) and the European Respiratory Society (ERS), endorsed by the International Society of Heart and Lung Transplantation (ISHLT). European Heart Journal 30:20, 2493-2537
CrossRef26
Nedim Selimovic, Bert Andersson, Claes-Håkan Bergh, Egidija Sakiniene, Hans Carlsten, Bengt Rundqvist. (2009) Endothelin-1 Across the Lung Circulation in Patients With Pulmonary Arterial Hypertension and Influence of Epoprostenol Infusion. The Journal of Heart and Lung Transplantation 28:8, 808-814
CrossRef27
Maria J. Ruiz-Cano, Pilar Escribano, Rafael Alonso, Juan Delgado, Patricia Carreira, Teresa Velazquez, Miguel A. Gomez Sanchez, Carlos Sáenz de la Calzada. (2009) Comparison of Baseline Characteristics and Survival Between Patients With Idiopathic and Connective Tissue Disease–related Pulmonary Arterial Hypertension. The Journal of Heart and Lung Transplantation 28:6, 621-627
CrossRef28
Robyn J. Barst, Duncan Stewart. (2009) Conventional and targeted medical therapies. Cardiology in the Young 19:S1, 28
CrossRef29
Ronald J. Oudiz, Harrison W. Farber. (2009) Dosing considerations in the use of intravenous prostanoids in pulmonary arterial hypertension: An experience-based review. American Heart Journal 157:4, 625-635
CrossRef30
Paul M Hassoun. (2009) Therapies for scleroderma-related pulmonary arterial hypertension. Expert Review of Respiratory Medicine 3:2, 187-196
CrossRef31
Michael G. Dickinson, Elisabeth H. Schölvinck, Anco Boonstra, Anton Vonk-Noordegraaf, Repke J. Snijder, Rolf M.F. Berger. (2009) Low Complication Rates With Totally Implantable Access Port Use in Epoprostenol Treatment of Pulmonary Hypertension. The Journal of Heart and Lung Transplantation 28:3, 273-279
CrossRef32
Christopher J. Rhodes, Alexandra Davidson, J. Simon R. Gibbs, John Wharton, Martin R. Wilkins. (2009) Therapeutic targets in pulmonary arterial hypertension. Pharmacology & Therapeutics 121:1, 69-88
CrossRef33
Konstantinos Dimopoulos, Ana Peset, Michael A. Gatzoulis. (2008) Evaluating operability in adults with congenital heart disease and the role of pretreatment with targeted pulmonary arterial hypertension therapy. International Journal of Cardiology 129:2, 163-171
CrossRef34
Antonios P. Vlahos, Jeffrey A. Feinstein, Nelson B. Schiller, Norman H. Silverman. (2008) Extension of Doppler-Derived Echocardiographic Measures of Pulmonary Vascular Resistance to Patients with Moderate or Severe Pulmonary Vascular Disease. Journal of the American Society of Echocardiography 21:6, 711-714
CrossRef35
Tobias Gessler, Werner Seeger, Thomas Schmehl. (2008) Inhaled Prostanoids in the Therapy of Pulmonary Hypertension. Journal of Aerosol Medicine and Pulmonary Drug Delivery 21:1, 1-12
CrossRef36
Tobias Gessler, Werner Seeger, Thomas Schmehl. (2008) Inhaled Prostanoids in the Therapy of Pulmonary Hypertension. Journal of Aerosol Medicine 0:0, 080116123756336-12
CrossRef37
Steffen Rex, Carlo Missant, Patrick Segers, Rolf Rossaint, Patrick F. Wouters. (2008) Epoprostenol treatment of acute pulmonary hypertension is associated with a paradoxical decrease in right ventricular contractility. Intensive Care Medicine 34:1, 179-189
CrossRef38
Satoshi Akagi, Hiromi Matsubara, Katsumasa Miyaji, Etsuko Ikeda, Kazuhiro Dan, Naoto Tokunaga, Kenichi Hisamatsu, Mitsuru Munemasa, Yoshihisa Fujimoto, Tohru Ohe. (2008) Additional Effects of Bosentan in Patients With Idiopathic Pulmonary Arterial Hypertension Already Treated With High-Dose Epoprostenol. Circulation Journal 72:7, 1142-1146
CrossRef39
David Launay, Eric Hachulla, Pierre-Yves Hatron, Xavier Jais, Gérald Simonneau, Marc Humbert. (2007) Pulmonary Arterial Hypertension: A Rare Complication of Primary Sjögren Syndrome. Medicine 86:5, 299-315
CrossRef40
Kesavarao K Ebenezar, Francine G Smith. (2007) Prostaglandins in the patent literature. Expert Opinion on Therapeutic Patents 17:9, 1131-1145
CrossRef41
Roham T. Zamanian, Francois Haddad, Ramona L. Doyle, Ann B. Weinacker. (2007) Management strategies for patients with pulmonary hypertension in the intensive care unit*. Critical Care Medicine 35:9, 2037-2050
CrossRef42
Michael Dandel, Hans B. Lehmkuhl, Sead Mulahasanovic, Yuguo Weng, Dagmar Kemper, Onnen Grauhan, Christoph Knosalla, Roland Hetzer. (2007) Survival of Patients With Idiopathic Pulmonary Arterial Hypertension After Listing for Transplantation: Impact of Iloprost and Bosentan Treatment. The Journal of Heart and Lung Transplantation 26:9, 898-906
CrossRef43
Roger F. Johnson, James E. Loyd, Amy L. Mullican, Cynthia A. Fink, Ivan M. Robbins. (2007) Long-term Follow-up After Conversion from Intravenous Epoprostenol to Oral Therapy With Bosentan or Sildenafil in 13 Patients With Pulmonary Arterial Hypertension. The Journal of Heart and Lung Transplantation 26:4, 363-369
CrossRef44
Wayne L. Strauss, Jeffrey D. Edelman. (2007) Prostanoid Therapy for Pulmonary Arterial Hypertension. Clinics in Chest Medicine 28:1, 127-142
CrossRef45
D. Dunbar Ivy, Lori Claussen, Aimee Doran. (2007) Transition of Stable Pediatric Patients With Pulmonary Arterial Hypertension from Intravenous Epoprostenol to Intravenous Treprostinil. The American Journal of Cardiology 99:5, 696-698
CrossRef46
Jonas Claesson, Stefan Lehtipalo, Ulf Bergstrand, Conny Arnerl??v, Ola Wins??. (2007) Negative mesenteric effects of lung recruitment maneuvers in oleic acid lung injury are transient and short lasting. Critical Care Medicine 35:1, 230-238
CrossRef47
Tomotaka Nakayama, Hiromitsu Shimada, Shinichi Takatsuki, Hiroshi Hoshida, Takashi Ishikita, Hiroyuki Matsuura, Tsutomu Saji. (2007) Efficacy and Limitations of Continuous Intravenous Epoprostenol Therapy for Idiopathic Pulmonary Arterial Hypertension in Japanese Children. Circulation Journal 71:11, 1785-1790
CrossRef48
Hiroaki Kawano, Hideyori Sengyoku, Osami Satoh, Shigetoshi Urabe, Yuji Koide, Katsusuke Yano. (2007) Marked Improvement with Sildenafil in a Patient with Idiopathic Pulmonary Arterial Hypertension Unresponsive to Beraprost and Sarpogrelate. Internal Medicine 46:12, 893-898
CrossRef49
Mirjam E. van Albada, Rolf M.F. Berger, Marnix Niggebrugge, Richard van Veghel, Adri H. Cromme-Dijkhuis, Regien G. Schoemaker. (2006) Prostacyclin therapy increases right ventricular capillarisation in a model for flow-associated pulmonary hypertension. European Journal of Pharmacology 549:1-3, 107-116
CrossRef50
Mirjam E van Albada, Richard van Veghel, Adri H Cromme-Dijkhuis, Regien G Schoemaker, Rolf M F Berger. (2006) Treprostinil in Advanced Experimental Pulmonary Hypertension: Beneficial Outcome Without Reversed Pulmonary Vascular Remodeling. Journal of Cardiovascular Pharmacology 48:5, 249-254
CrossRef51
Stephen L Archer, Evangelos D Michelakis. (2006) An evidence-based approach to the management of pulmonary arterial hypertension. Current Opinion in Internal Medicine 5:5, 453-460
CrossRef52
Son-Mi Chung, Chang-Keun Lee, Eun Young Lee, Bin Yoo, Sang-Do Lee, Hee-Bom Moon. (2006) Clinical aspects of pulmonary hypertension in patients with systemic lupus erythematosus and in patients with idiopathic pulmonary arterial hypertension. Clinical Rheumatology 25:6, 866-872
CrossRef53
Sabina A Antoniu. (2006) Sildenafil for pulmonary arterial hypertension: when blue turns into white. Expert Opinion on Pharmacotherapy 7:13, 1801-1810
CrossRef54
Maria E. Campian, Maxim Hardziyenka, Martin C. Michel, Hanno L. Tan. (2006) How valid are animal models to evaluate treatments for pulmonary hypertension?. Naunyn-Schmiedeberg's Archives of Pharmacology 373:6, 391-400
CrossRef55
M. Beghetti. (2006) Current treatment options in children with pulmonary arterial hypertension and experiences with oral bosentan. European Journal of Clinical Investigation 36:s3, 16-24
CrossRef56
S. Kourouklis, A. Christopoulos, K. Liagkas, G. Paradellis, Z. S. Kyriakides. (2006) Bosentan in Eisenmenger syndrome and chronic thromboembolic pulmonary hypertension. European Journal of Clinical Investigation 36:s3, 39-43
CrossRef57
Stephen B. Miller. (2006) Prostaglandins in Health and Disease: An Overview. Seminars in Arthritis and Rheumatism 36:1, 37-49
CrossRef58
ANDY J. PETROS, CHRISTINE M. PIERCE. (2006) The management of pulmonary hypertension. Pediatric Anesthesia 0:0, 060706013023002-???
CrossRef59
Yannick Allanore, André Kahan. (2006) Treatment of systemic sclerosis. Joint Bone Spine 73:4, 363-368
CrossRef60
Denise H. Tam, Harrison W. Farber. (2006) Pulmonary hypertension and β-thalassemia major: Report of a case, its treatment, and a review of the literature. American Journal of Hematology 81:6, 443-447
CrossRef61
Anna M. Hackman, Thomas E. Lackner. (2006) Pharmacotherapy for Idiopathic Pulmonary Arterial Hypertension During the Past 25 Years. Pharmacotherapy 26:1, 68-94
CrossRef62
2006. Epoprostenol. , 1228-1229.
CrossRef63
Erika Berman Rosenzweig, Robyn J Barst. (2006) Pulmonary Arterial Hypertension. Treatments in Respiratory Medicine 5:2, 117-127
CrossRef64
Amira A Shahin. (2006) Pulmonary Involvement in Systemic Sclerosis. Treatments in Respiratory Medicine 5:6, 429-436
CrossRef65
Emilio Mazza, Darren B. Taichman. 2006. Functions and Control of the Pulmonary Circulation. , 1-19.
CrossRef66
Jess Mandel. 2006. Treatment for Pulmonary Arterial Hypertension. , 99-118.
CrossRef67
Vivek N. Ahya, Jeffrey S. Sager, Robert M. Kotloff. 2006. Lung Transplantation for Pulmonary Arterial Hypertension. , 119-131.
CrossRef68
TAKAYUKI KURIYAMA. (2006) Forefront of molecular disease state elucidation and treatment of pulmonary hypertension.. Nihon Naika Gakkai Zasshi 95:9, 1676-1690
CrossRef69
Kevin B. MARTIN, James R. KLINGER, Sharon I. S. ROUNDS. (2006) Pulmonary arterial hypertension: New insights and new hope. Respirology 11:1, 6-17
CrossRef70
Jennifer L. Snow, Peter Lloyd Jones, Darren B. Taichman. 2006. Pathobiologic Mechanisms of Pulmonary Arterial Hypertension. , 33-49.
CrossRef71
Biljana Dobric, Jasna Petrovic, Ninoslav Radovanovic. (2006) The importance of hemodynamic monitoring in mitrocuspid surgery. Medicinski pregled 59:1-2, 63-66
CrossRef72
A. Limsuwan, P. Pienvichit, P. Khowsathit. (2005) Beraprost Therapy in Children with Pulmonary Hypertension Secondary to Congenital Heart Disease. Pediatric Cardiology 26:6, 787-791
CrossRef73
Ioana R. Preston, James R. Klinger, Jeanne Houtches, David Nelson, Harrison W. Farber, Nicholas S. Hill. (2005) Acute and chronic effects of sildenafil in patients with pulmonary arterial hypertension. Respiratory Medicine 99:12, 1501-1510
CrossRef74
Sabina A Antoniu. (2005) Bosentan for treatment of pulmonary arterial hypertension (I). Therapy 2:6, 843-847
CrossRef75
Minoru Hongo, Eiichiro Mawatari, Akio Sakai, Zonghai Ruan, Tomonobu Koizumi, Fumiko Terasawa, Yoshikazu Yazaki, Osamu Kinoshita, Uichi Ikeda, Toshishige Shibamoto. (2005) Effects of Nicorandil on Monocrotaline-Induced Pulmonary Arterial Hypertension in Rats. Journal of Cardiovascular Pharmacology 46:4, 452-458
CrossRef76
Werner Budts. (2005) Eisenmenger syndrome: medical prevention and management strategies. Expert Opinion on Pharmacotherapy 6:12, 2047-2060
CrossRef77
S. H. LEE, L. J. RUBIN. (2005) Current treatment strategies for pulmonary arterial hypertension. Journal of Internal Medicine 258:3, 199-215
CrossRef78
Erika Berman Rosenzweig, Robyn J Barst. (2005) Idiopathic pulmonary arterial hypertension in children. Current Opinion in Pediatrics 17:3, 372-380
CrossRef79
Roxana Sulica, Howard V. Dinh, Kevin Dunsky, Valentin Fuster, Michael Poon. (2005) The Acute Hemodynamic Effect of IV Nitroglycerin and Dipyridamole in Patients With Pulmonary Arterial Hypertension: Comparison With IV Epoprostenol. Congestive Heart Failure 11:3, 139-146
CrossRef80
Jayant Nath, Teresa DeMarco, Lisa Hourigan, Paul A. Heidenreich, Elyse Foster. (2005) Correlation between Right Ventricular Indices and Clinical Improvement in Epoprostenol Treated Pulmonary Hypertension Patients. Echocardiography 22:5, 374-379
CrossRef81
(2005) Guías de Práctica Clínica sobre el diagnóstico y tratamiento de la hipertensión arterial pulmonar. Revista Española de Cardiología 58:5, 523-566
CrossRef82
N Shanthi Paramothayan, Toby J Lasserson, Athol Wells, E. Haydn Walters, N Shanthi Paramothayan. 2005. Prostacyclin for pulmonary hypertension in adults. .
CrossRef83
Toru Satoh, Shingo Kyotani, Yoshiaki Okano, Norifumi Nakanishi, Takeyoshi Kunieda. (2005) Descriptive patterns of severe chronic pulmonary hypertension by chest radiography. Respiratory Medicine 99:3, 329-336
CrossRef84
Roxana Sulica, Michael Poon. (2005) Medical therapeutics for pulmonary arterial hypertension: from basic science and clinical trial design to evidence-based medicine. Expert Review of Cardiovascular Therapy 3:2, 347-360
CrossRef85
Brian Widmar. (2005) When cure is care: Diagnosis and management of pulmonary arterial hypertension. Journal of the American Academy of Nurse Practitioners 17:3, 104-112
CrossRef86
Masaharu Kataoka, Toru Satoh, Tomohiro Manabe, Toshihisa Anzai, Tsutomu Yoshikawa, Hideo Mitamura, Satoshi Ogawa. (2005) Oral Sildenafil Improves Primary Pulmonary Hypertension Refractory to Epoprostenol. Circulation Journal 69:4, 461-465
CrossRef87
Michael Dandel, Hans B. Lehmkuhl, Roland Hetzer. (2005) Advances in the Medical Treatment of Pulmonary Hypertension. Kidney and Blood Pressure Research 28:5-6, 311-324
CrossRef88
Martin L. Mai, Daniel S. Yip, Cesar A. Keller, Thomas A. Gonwa. 2005. Pretransplantation Evaluation: Pulmonary, Cardiac, and Renal. , 405-427.
CrossRef89
Abhijat Sheth, John E.S. Park, Yee Ean Ong, Timothy B. Ho, Brendan P. Madden. (2005) Early haemodynamic benefit of sildenafil in patients with coexisting chronic thromboembolic pulmonary hypertension and left ventricular dysfunction. Vascular Pharmacology 42:2, 41-45
CrossRef90
Nobuhiro Tahara, Hisashi Kai, Hiroshi Niiyama, Takahiro Mori, Yusuke Sugi, Narimasa Takayama, Hideo Yasukawa, Yasushi Numaguchi, Hideo Matsui, Kenji Okumura, Tsutomu Imaizumi. (2004) Repeated Gene Transfer of Naked Prostacyclin Synthase Plasmid into Skeletal Muscles Attenuates Monocrotaline-Induced Pulmonary Hypertension and Prolongs Survival in Rats. Human Gene Therapy 15:12, 1270-1278
CrossRef91
Noritoshi Nagaya, Kenji Kangawa. (2004) Adrenomedullin in the treatment of pulmonary hypertension. Peptides 25:11, 2013-2018
CrossRef92
Nobuhiro Tahara, Hisashi Kai, Hiroshi Niiyama, Takahiro Mori, Yusuke Sugi, Narimasa Takayama, Hideo Yasukawa, Yasushi Numaguchi, Hideo Matsui, Kenji Okumura, Tsutomu Imaizumi. (2004) Repeated Gene Transfer of Naked Prostacyclin Synthase Plasmid into Skeletal Muscles Attenuates Monocrotaline-Induced Pulmonary Hypertension and Prolongs Survival in Rats. Human Gene Therapy 0:0, 041208051131001
CrossRef93
Nazzareno Galiè, Alessandra Manes, Angelo Branzi. (2004) Evaluation of pulmonary arterial hypertension. Current Opinion in Cardiology 19:6, 575-581
CrossRef94
Hiroshi Morimatsu, Keiji Goto, Takashi Matsusaki, Hiroshi Katayama, Hiromi Matsubara, Tohru Ohe, Kiyoshi Morita. (2004) Rapid Development of Severe Interstitial Pneumonia Caused by Epoprostenol in a Patient with Primary Pulmonary Hypertension. Anesthesia & Analgesia 99:4, 1205-1207
CrossRef95
Pierre Tissières, Laurent Nicod, Constance Barazzone-Argiroffo, Peter C. Rimensberger, Maurice Beghetti. (2004) Aerosolized iloprost as a bridge to lung transplantation in a patient with cystic fibrosis and pulmonary hypertension. The Annals of Thoracic Surgery 78:3, e48-e50
CrossRef96
Aaron N. Hata, Richard M. Breyer. (2004) Pharmacology and signaling of prostaglandin receptors: Multiple roles in inflammation and immune modulation. Pharmacology & Therapeutics 103:2, 147-166
CrossRef97
Erika Berman Rosenzweig, Allison C. Widlitz, Robyn J. Barst. (2004) Pulmonary arterial hypertension in children. Pediatric Pulmonology 38:1, 2-22
CrossRef98
Edward B. Braun, Christopher A. Palin, Charles W. Hogue. (2004) Vasopressin During Spinal Anesthesia in a Patient with Primary Pulmonary Hypertension Treated with Intravenous Epoprostenol. Anesthesia & Analgesia 99:1, 36-37
CrossRef99
Aymarah M Robles, Deborah Shure. (2004) Gender issues in pulmonary vascular disease. Clinics in Chest Medicine 25:2, 373-377
CrossRef100
David B Badesch, Vallerie V McLaughlin, Marion Delcroix, CarmineDario Vizza, Horst Olschewski, Olivier Sitbon, Robyn J Barst. (2004) Prostanoid therapy for pulmonary arterial hypertension. Journal of the American College of Cardiology 43:12, S56-S61
CrossRef101
Horst Olschewski, Frank Rose, Ralph Schermuly, H.Ardeschir Ghofrani, Beate Enke, Andrea Olschewski, Werner Seeger. (2004) Prostacyclin and its analogues in the treatment of pulmonary hypertension. Pharmacology & Therapeutics 102:2, 139-153
CrossRef102
H. Erhan Dincer, Kenneth W. Presberg. (2004) Current Management of Pulmonary Hypertension. Clinical Pulmonary Medicine 11:1, 40-53
CrossRef103
Mark Avdalovic, Christian Sandrock, Andrea Hoso, Roblee Allen, Timothy E Albertson. (2004) Epoprostenol in Pregnant Patients with Secondary Pulmonary Hypertension. Treatments in Respiratory Medicine 3:1, 29-34
CrossRef104
Hirahito ENDO, Sumiaki TANAKA, Miho SAKAI. (2004) Japanese Journal of Clinical Immunology 27:3, 127-136
CrossRef105
Masaharu KATAOKA, Toru SATOH, Tomohiro MANABE, Toshihisa ANZAI, Tsutomu YOSHIKAWA, Hideo MITAMURA, Satoshi OGAWA. (2004) Marked Improvement with Sildenafil in a Patient with Primary Pulmonary Hypertension Unresponsive to Epoprostenol. Internal Medicine 43:10, 945-950
CrossRef106
Hashimoto Katsushi, Nakamura Kazufumi, Fujio Hideki, Miyaji Katsumasa, Morita Hiroshi, Kusano Kengo, Date Hiroshi, Shimizu Nobuyoshi, Emori Tetsuro, Matsubara Hiromi, Ohe Tohru. (2004) Epoprostenol Therapy Decreases Elevated Circulating Levels of Monocyte Chemoattractant Protein-1 in Patients With Primary Pulmonary Hypertension. Circulation Journal 68:3, 227-231
CrossRef107
Kazuhiro Takahashi, Yoshiki Mori, Hideshi Yamamura, Toshio Nakanishi, Makoto Nakazawa. (2003) Effect of beraprost sodium on pulmonary vascular resistance in candidates for a Fontan procedure: A preliminary study. Pediatrics International 45:6, 671-675
CrossRef108
Kazuhiro Takahashi, Yoshiki Mori, Hideshi Yamamura, Toshio Nakanishi, Makoto Nakazawa. (2003) Effect of beraprost sodium on pulmonaryvascular resistance in candidates for a Fontan procedure: A preliminarystudy. Pediatrics International 45:6, 671-675
CrossRef109
Kathleen Srock, Leslie Dubin Kerr, Michael Poon, John T. Fallon. (2003) Refractory Pulmonary Hypertension in a Lupus Patient with Occult Pulmonary Vasculitis. JCR: Journal of Clinical Rheumatology 9:4, 263-266
CrossRef110
Khalid F. Almoosa, Saeb F. Khoury, Francis X. McCormack. (2003) Acute Myocardial Infarction Complicating Sudden Interruption of Chronic Prostacyclin Therapy for Pulmonary Hypertension. Clinical Pulmonary Medicine 10:4, 231-234
CrossRef111
Michael Wade, Thomas L. Hunt, Allen A. Lai. (2003) Effect of Continuous Subcutaneous Treprostinil Therapy on the Pharmacodynamics and Pharmacokinetics of Warfarin. Journal of Cardiovascular Pharmacology 41:6, 908-915
CrossRef112
Robyn J Barst, Michael McGoon, Vallerie McLaughlin, Victor Tapson, Ronald Oudiz, Shelley Shapiro, Ivan M Robbins, Richard Channick, David Badesch, Barry K Rayburn, Robin Flinchbaugh, Jeff Sigman, Carl Arneson, Roger Jeffs. (2003) Beraprost therapy for pulmonary arterial hypertension. Journal of the American College of Cardiology 41:12, 2119-2125
CrossRef113
Rolf Ziesche. (2003) Konsensus-Empfehlungen der Arbeitsgruppe Pulmonalarterielle Hypertension der Österreichischen Gesellschaft für Lungenerkrankungen und Tuberkulose. Wiener Klinische Wochenschrift 115:10, 351-365
CrossRef114
James R Runo, James E Loyd. (2003) Primary pulmonary hypertension. The Lancet 361:9368, 1533-1544
CrossRef115
Judy W. M. Cheng. (2003) Bosentan. Heart Disease 5:2, 161-169
CrossRef116
Vallerie V. McLaughlin, Sean P. Gaine, Robyn J. Barst, Ronald J. Oudiz, Robert C. Bourge, Adaani Frost, Ivan M. Robbins, Victor F. Tapson, Michael D. McGoon, David B. Badesch, Jeff Sigman, Robert Roscigno, Shelmer D. Blackburn, Carl Arneson, Lewis J. Rubin, Stuart Rich. (2003) Efficacy and Safety of Treprostinil: An Epoprostenol Analog for Primary Pulmonary Hypertension. Journal of Cardiovascular Pharmacology 41:2, 293-299
CrossRef117
D BENDAYAN, D SHITRIT, M YGLA, M HUERTA, G FINK, M.R KRAMER. (2003) Hyperuricemia as a prognostic factor in pulmonary arterial hypertension. Respiratory Medicine 97:2, 130-133
CrossRef118
Fumiaki Ono, Noritoshi Nagaya, Shingo Kyotani, Hideo Oya, Norifumi Nakanishi, Kunio Miyatake. (2003) Hemodynamic and Hormonal Effects of Beraprost Sodium, an Orally Active Prostacyclin Analogue, in Patients With Secondary Precapillary Pulmonary Hypertension. Circulation Journal 67:5, 375-378
CrossRef119
Noritoshi NAGAYA, Kunio MIYATAKE, Shingo KYOTANI, Toshio NISHIKIMI, Norifumi NAKANISHI, Kenji KANGAWA. (2003) Pulmonary Vasodilator Response to Adrenomedullin in Patients with Pulmonary Hypertension. Hypertension Research 26:Suppl, S141-S146
CrossRef120
Hitoaki Satoh, Yuichiro Masuda, Shinichiro Izuta, Hideaki Yaku, Hidefumi Obara. (2002) Pregnant Patient with Primary Pulmonary Hypertension: General Anesthesia and Extracorporeal Membrane Oxygenation Support for Termination of Pregnancy. Anesthesiology 97:6, 1638-1640
CrossRef121
Myung H. Park, Robert L. Scott, Patricia A. Uber, Mandeep R. Mehra. (2002) Treatment of pulmonary hypertension: A promising new age. Catheterization and Cardiovascular Interventions 57:3, 395-403
CrossRef122
Lionel Schachna, Fredrick M. Wigley. (2002) Targeting mediators of vascular injury in scleroderma. Current Opinion in Rheumatology 14:6, 686-693
CrossRef123
NS Paramothayan, TJ Lasserson, AU Wells, EH Walters. 2002. Prostacyclin for pulmonary hypertension in adults. .
CrossRef124
Hiroshi Suzuki, Satoshi Sato, Saori Tanabe, Kiyoshi Hayasaka. (2002) Beraprost sodium for pulmonary hypertension with congenital heart disease. Pediatrics International 44:5, 528-529
CrossRef125
P. P. Roeleveld, M. Jongejan, R. M. F. Berger. (2002) Primaire pulmonale hypertensie op de kinderleeftijd. Tijdschrift voor kindergeneeskunde 70:2, 226-231
CrossRef126
M COSSIO, Y MENON, W WILSON, B DEBOISBLANC. (2002) Life-threatening complications of systemic sclerosis. Critical Care Clinics 18:4, 819-839
CrossRef127
STUART LEHRMAN, PATRICIA ROMANO, WILLIAM FRISHMAN, AMBER RASHID, JAY DOBKIN, JOSEPH REICHEL. (2002) Primary Pulmonary Hypertension and Cor Pulmonale. Cardiology in Review 10:5, 265-278
CrossRef128
Olschewski, Horst, Simonneau, Gerald, Galiè, Nazzareno, Higenbottam, Timothy, Naeije, Robert, Rubin, Lewis J., Nikkho, Sylvia, Speich, Rudolf, Hoeper, Marius M., Behr, Jürgen, Winkler, Jörg, Sitbon, Olivier, Popov, Wladimir, Ghofrani, H. Ardeschir, Manes, Alessandra, Kiely, David G., Ewert, Ralph, Meyer, Andreas, Corris, Paul A., Delcroix, Marion, Gomez-Sanchez, Miguel, Siedentop, Harald, Seeger, Werner, . (2002) Inhaled Iloprost for Severe Pulmonary Hypertension. New England Journal of Medicine 347:5, 322-329
Full Text129
M. Magliano, D. A. Isenberg, J. Hillson. (2002) Pulmonary hypertension in autoimmune rheumatic diseases: Where are we now?. Arthritis & Rheumatism 46:8, 1997-2009
CrossRef130
Baisakhi Raychaudhuri, Tracey L. Bonfield, Anagha Malur, Kathleen Hague, Mani S. Kavuru, Alejandro C. Arroliga, Mary Jane Thomassen. (2002) Circulating Monocytes from Patients with Primary Pulmonary Hypertension Are Hyporesponsive. Clinical Immunology 104:2, 191-198
CrossRef131
Olivier Sitbon, Marc Humbert, Hilario Nunes, Florence Parent, Gilles Garcia, Philippe Hervé, Maurizio Rainisio, G.érald Simonneau. (2002) Long-term intravenous epoprostenol infusion in primary pulmonary hypertension. Journal of the American College of Cardiology 40:4, 780-788
CrossRef132
Michihiko Ueno, Takashi Miyauchi, Satoshi Sakai, Rikako Yamauchi-Kohno, Katsutoshi Goto, Iwao Yamaguchi. (2002) A combination of oral endothelin-areceptor antagonist and oral prostacyclinanalogue is superior to each drug alone inameliorating pulmonary hypertension in rats. Journal of the American College of Cardiology 40:1, 175-181
CrossRef133
Stuart M. Lowson. (2002) Inhaled Alternatives to Nitric Oxide. Anesthesiology 96:6, 1504-1513
CrossRef134
Ian Adatia. (2002) Recent advances in pulmonary vascular disease. Current Opinion in Pediatrics 14:3, 292-297
CrossRef135
Dermot O'Callaghan, Seán P. Gaine. (2002) Hepatopulmonary syndromes: treatment of liver transplantation candidates. Current Opinion in Organ Transplantation 7:2, 107-113
CrossRef136
WATARU HIDA, YE TUN, YOSHIHIRO KIKUCHI, SHINICHI OKABE, KUNIO SHIRATO. (2002) Pulmonary hypertension in patients with chronic obstructive pulmonary disease: Recent advances in pathophysiology and management. Respirology 7:1, 3-13
CrossRef137
Vallerie V McLaughlin. (2002) Medical management of primary pulmonary hypertension. Expert Opinion on Pharmacotherapy 3:2, 159-165
CrossRef138
H J Smit, A Vonk Noordegraaf, R J Roeleveld, J G F Bronzwaer, P E Postmus, P M J M de Vries, A Boonstra. (2002) Epoprostenol-induced pulmonary vasodilatation in patients with pulmonary hypertension measured by electrical impedance tomography. Physiological Measurement 23:1, 237-243
CrossRef139
Eric N Mendeloff, Bryan F Meyers, Thoralf M Sundt, Tracey J Guthrie, Stuart C Sweet, Maite de la Morena, Steve Shapiro, David T Balzer, Elbert P Trulock, John P Lynch, Michael K Pasque, Joel D Cooper, Charles B Huddleston, G.Alexander Patterson. (2002) Lung transplantation for pulmonary vascular disease. The Annals of Thoracic Surgery 73:1, 209-219
CrossRef140
O Sanchez, M Humbert, O Sitbon, H Nunes, G Garcia, G Simonneau. (2002) Hypertension artérielle pulmonaire associée aux connectivites. La Revue de Médecine Interne 23:1, 41-54
CrossRef141
Mark W Weston, Barton F Isaac, Christine Crain. (2001) The use of inhaled prostacyclin in nitroprusside-resistant pulmonary artery hypertension. The Journal of Heart and Lung Transplantation 20:12, 1340-1344
CrossRef142
Trina K Jeffery, Janet C Wanstall. (2001) Pulmonary vascular remodeling: a target for therapeutic intervention in pulmonary hypertension. Pharmacology & Therapeutics 92:1, 1-20
CrossRef143
Alfred P. Fishman. (2001) CLINICAL CLASSIFICATION OF PULMONARY HYPERTERNSION. Clinics in Chest Medicine 22:3, 385-391
CrossRef144
Robyn J. Barst. (2001) MEDICAL THERPAY OF PULMONARY HYPERTENSION. Clinics in Chest Medicine 22:3, 509-515
CrossRef145
Elbert P. Trulock. (2001) LUNG TRANSPLANTATION FOR PRIMARY PULMONARY HYPERTENSION. Clinics in Chest Medicine 22:3, 583-593
CrossRef146
Nazzareno Galié, Alessandra Manes, Angelo Branzi. (2001) MEDICAL THERAPY OF PULMONARY HYPERTENSION. Clinics in Chest Medicine 22:3, 529-537
CrossRef147
D NAIDOO, J MOODLEY. (2001) Management of the critically ill cardiac patient. Best Practice & Research Clinical Obstetrics & Gynaecology 15:4, 523-544
CrossRef148
Bernard Kao, David T Balzer, Charles B Huddleston, Charles E Canter. (2001) Long-term prostacyclin infusion to reduce pulmonary hypertension in a pediatric cardiac transplant candidate prior to transplantation. The Journal of Heart and Lung Transplantation 20:7, 785-788
CrossRef149
Ariane L Herrick. (2001) Development of agents for the treatment of systemic sclerosis. Expert Opinion on Investigational Drugs 10:7, 1255-1264
CrossRef150
Ronald G Tilton, Tommy A Brock, Richard AF Dixon. (2001) Therapeutic potential of endothelin receptor antagonists and nitric oxide donors in pulmonary hypertension. Expert Opinion on Investigational Drugs 10:7, 1291-1308
CrossRef151
Erika Berman Rosenzweig, Robyn J Barst. (2001) Novel therapeutics for the treatment of paediatric pulmonary arterial hypertension. Expert Opinion on Investigational Drugs 10:5, 811-823
CrossRef152
David B Badesch. 2001. Pulmonary Hypertension. .
CrossRef153
V MCLAUGHLIN, S RICH. (2001) SEVERE PULMONARY HYPERTENSION: CRITICAL CARE CLINICS. Critical Care Clinics 17:2, 453-467
CrossRef154
Yuzo Abe, Koichiro Tatsumi, Kazutoshi Sugito, Yuji Ikeda, Hiroshi Kimura, Takayuki Kuriyama. (2001) Effects of Inhaled Prostacyclin Analogue on Chronic Hypoxic Pulmonary Hypertension. Journal of Cardiovascular Pharmacology 37:3, 239-251
CrossRef155
Elizabeth S. Klings, Harrison W. Farber. (2001) Current Management of Primary Pulmonary Hypertension. Drugs 61:13, 1945-1956
CrossRef156
Tine L.M. De Backer, Jan-Peter Smedema, St??phane G. Carlier. (2001) Current Management of Primary Pulmonary Hypertension. BioDrugs 15:12, 801-817
CrossRef157
Rajiv D Machado, Michael W. Pauciulo, Jennifer R. Thomson, Kirk B. Lane, Neil V. Morgan, Lisa Wheeler, John A. Phillips III, John Newman, Denise Williams, Nazzareno Galiè, Alessandra Manes, Keith McNeil, Magdi Yacoub, Ghada Mikhail, Paula Rogers, Paul Corris, Marc Humbert, Dian Donnai, Gunnar Martensson, Lisbeth Tranebjaerg, James E. Loyd, Richard C. Trembath, William C. Nichols. (2001) BMPR2 Haploinsufficiency as the Inherited Molecular Mechanism for Primary Pulmonary Hypertension. The American Journal of Human Genetics 68:1, 92-102
CrossRef158
SD Lee, DS Lee, YG Chun, SH Paik, WS Kim, DS Kim, WD Kim, RM Tuder, NF Voelkel. (2000) Transforming Growth Factor-β1 Induces Endothelin-1 in a Bovine Pulmonary Artery Endothelial Cell Line and Rat Lungs via cAMP. Pulmonary Pharmacology & Therapeutics 13:6, 257-265
CrossRef159
Aidan O'Brien, Sharon Rounds. (2000) Pulmonary hypertension update. Comprehensive Therapy 26:3, 190-196
CrossRef160
Tim Higenbottam, Tom Siddons, Eric Demoncheaux. (2000) A therapeutic role for chronic inhaled nitric oxide?. The Lancet 356:9228, 446-447
CrossRef161
Hoeper, Marius M., Schwarze, MichaelEhlerding, StefanAdler-Schuermeyer, Angelika, Spiekerkoetter, Edda, Niedermeyer, Jost, Hamm, Michael, Fabel, Helmut, . (2000) Long-Term Treatment of Primary Pulmonary Hypertension with Aerosolized Iloprost, a Prostacyclin Analogue. New England Journal of Medicine 342:25, 1866-1870
Full Text162
M J Krowka. (2000) Pulmonary hypertension: diagnostics and therapeutics.. Mayo Clinic Proceedings 75:6, 625-630
CrossRef163
Shelley R. Hankins, Evelyn M. Horn. (2000) Current management of patients with pulmonary hypertension and right ventricular insufficiency. Current Cardiology Reports 2:3, 244-251
CrossRef164
Branko M. Weiss, Marco Maggiorini, Rolf Jenni, Urs Lauper, Vladimir Popov, Thomas Bombeli, Donat R. Spahn. (2000) Pregnant Patient with Primary Pulmonary Hypertension: Inhaled Pulmonary Vasodilators and Epidural Anesthesia for Cesarean Delivery. Anesthesiology 92:4, 1191
CrossRef165
Stuart Rich. (2000) Primary pulmonary hypertension. Current Treatment Options in Cardiovascular Medicine 2:2, 135-139
CrossRef166
Marius M. Hoeper, Horst Olschewski, Hossein A. Ghofrani, Heinrike Wilkens, Joerg Winkler, Mathias M. Borst, Jost Niedermeyer, Helmut Fabel, Werner Seeger. (2000) A comparison of the acute hemodynamic effects of inhaled nitric oxide and aerosolized iloprost in primary pulmonary hypertension. Journal of the American College of Cardiology 35:1, 176-182
CrossRef167
Elizabeth S. Klings, Nicholas S. Hill, Michael H. Ieong, Robert W. Simms, Joseph H. Korn, Harrison W. Farber. (1999) Systemic sclerosis-associated pulmonary hypertension: Short- and long-term effects of epoprostenol (prostacyclin). Arthritis & Rheumatism 42:12, 2638-2645
CrossRef168
William E. Hopkins. (1999) Atrial septal defect. Current Treatment Options in Cardiovascular Medicine 1:4, 301-310
CrossRef169
I MARIE, H LEVESQUE, P HATRON, S DOMINIQUE, H COURTOIS. (1999) Atteinte pulmonaire au cours de la sclérodermie systémique. Partie II. Hypertension artérielle pulmonaire isolée, cancer bronchopulmonaire, hémorragie alvéolaire. La Revue de Médecine Interne 20:11, 1017-1027
CrossRef170
Catherine L. Dent, J. Julio Pérez Fontán. (1999) Long-term therapy for pulmonary hypertension in children. Current Opinion in Pulmonary Medicine 5:6, 390
CrossRef171
Noritoshi Nagaya, Masaaki Uematsu, Yoshiaki Okano, Toru Satoh, Shingo Kyotani, Fumio Sakamaki, Norifumi Nakanishi, Kunio Miyatake, Takeyoshi Kunieda. (1999) Effect of orally active prostacyclin analogue on survival of outpatients with primary pulmonary hypertension. Journal of the American College of Cardiology 34:4, 1188-1192
CrossRef172
Stuart Rich, Vallerie V McLaughlin. (1999) The effects of chronic prostacyclin therapy on cardiac output and symptoms in primary pulmonary hypertension. Journal of the American College of Cardiology 34:4, 1184-1187
CrossRef173
Omar A Minai, Janet R Maurer, Steven Kesten. (1999) Comorbidities in end-stage lung disease. The Journal of Heart and Lung Transplantation 18:9, 891-903
CrossRef174
Michael J. Krowka, Robert P. Frantz, Michael D. McGoon, Cathy Severson, David J. Plevak, Russell H. Wiesner. (1999) Improvement in pulmonary hemodynamics during intravenous epoprostenol (prostacyclin): A study of 15 patients with moderate to severe portopulmonary hypertension. Hepatology 30:3, 641-648
CrossRef175
Margaret Aranda, Katherine Kilroy Bradford, Ronald G. Pearl. (1999) Combined Therapy with Inhaled Nitric Oxide and Intravenous Vasodilators During Acute and Chronic Experimental Pulmonary Hypertension. Anesthesia & Analgesia 89:1, 152-158
CrossRef176
Catherine L Dent, J. Julio Perez Fontan. (1999) Long-term therapy for pulmonary hypertension in children. Current Opinion in Pediatrics 11:3, 218-222
CrossRef177
Philip W. Shaul. (1999) Regulation of vasodilator synthesis during lung development. Early Human Development 54:3, 271-294
CrossRef178
Paul C. Kuo, Jeffrey S. Plotkin, Sean Gaine, Rebecca A. Schroeder, Vinod K. Rustgi, Lewis J. Rubin, Lynt B. Johnson. (1999) PORTOPULMONARY HYPERTENSION AND THE LIVER TRANSPLANT CANDIDATE. Transplantation 67:8, 1087-1093
CrossRef179
Guillermo Garc
a-Manero, Stephen J. Schuster, Herbert Patrick, Jos
CrossRef180
Alberto Tedeschi, Pier Luigi Meroni, Nicoletta Del Papa, Carla Boschetti, Antonio Miadonna. (1999) Reply. Arthritis & Rheumatism 42:1, 197-198
CrossRef181
(1998) Epoprostenol (Prostacyclin) Therapy in Primary Pulmonary Hypertension. New England Journal of Medicine 338:24, 1773-1774
Full Text182
Fishman, Alfred P., . (1998) Pulmonary Hypertension — Beyond Vasodilator Therapy. New England Journal of Medicine 338:5, 321-322
Full Text
- Letters
