Intravenous Prostacyclin Research Articles

Current treatment strategies for pulmonary arterial hypertension

Pulmonary arterial hypertension (PAH) is a disease characterized by an elevation in pulmonary artery pressure that can lead to right ventricular failure and death. Although there is no cure for PAH, newer medical therapies have been shown to improve a variety of clinically relevant end-points including survival, exercise tolerance, functional class, haemodynamics, echocardiographic parameters and quality of life measures. Since the introduction of continuous intravenous prostacyclin, the treatment armamentarium of approved drugs for PAH has expanded to include prostacyclin analogues with differing routes of administration, a dual endothelin receptor antagonist, and a phosphodiesterase-5 inhibitor. Selective endothelin-A receptor antagonists have shown promise in clinical trials and are likely to be added to the list of options. As the number of medications available for PAH continues to increase, treatment decisions regarding first-line therapy, combination treatments, and add-on strategies are becoming more complex. This article reviews the current treatments strategies for PAH and provides guidelines for its management.

Atrial septal defect closure in a patient with “irreversible” pulmonary hypertensive arteriopathy

The presence of irreversible pulmonary hypertension in patients with atrial septal defect (ASD) is thought to preclude shunt closure. We report the case of a woman with plexiform pulmonary arteriopathy secondary to an ostium secundum ASD who was able to successfully undergo percutaneous shunt closure following therapy with chronic intravenous prostacyclin (Flolan). One year after closure, the patient was weaned off Flolan over a period of 7 months following the institution of oral Bosentan therapy. Our case illustrates how aggressive vasodilator therapy with prostaglandins may be capable of reducing pulmonary artery pressure and permitting shunt closure in a patient once considered to have “inoperable” pulmonary arteriopathy.

Inhaled Nitric Oxide Therapy in the Preterm Infant Who Has Respiratory Distress Syndrome

After completing this article, readers should be able to: 1. Delineate the rationale for inhaled nitric oxide (iNO) use in respiratory distress syndrome. 2. List the toxicities of iNO. 3. Describe the primary findings of iNO therapy in major clinical trials. Respiratory distress syndrome (RDS) has been a major factor determining the limits of viability in the preterm infant. RDS is, in large part, the result of surfactant deficiency. Surfactant replacement and antenatal steroid use are the two major advances in the treatment of RDS to date and have resulted in significant decreases in mortality and chronic lung disease (CLD). Surfactant replacement became widely available in 1991, and antenatal steroids achieved widespread use following the National Institutes of Health Consensus Conference in 1994. (1) However, substantial mortality and CLD still are seen in the very low-birthweight infant (Fig. 1). Figure 1 National Institute of Child and Human Development (NICHD) Neonatal Research Network mortality and CLD rates for 2003 in preterm infants born at 23 to 30 weeks’ gestation. Following the identification of nitric oxide (NO) as the vascular endothelial relaxing factor, use of the agent has moved rapidly from bench to bedside. Inhaled nitric oxide (iNO) was found to improve oxygenation in adult and pediatric patients who had hypoxic respiratory failure. (2)(3)(4) Subsequent randomized, controlled trials in term and near-term infants who had hypoxic respiratory failure demonstrated an improvement in oxygenation as well as a significant decrease in death or the need for extracorporeal membrane oxygenation. (5)(6)(7) Following United States Food and Drug Administration review of these trials, iNO was approved for use in term and near-term infants who had hypoxic respiratory failure. The role of iNO in the preterm infant who has RDS has been an active area of investigation over the last decade. This …

Prostacyclin for pulmonary hypertension in adults

Primary pulmonary hypertension (PPH) is progressive, resulting in right ventricular failure. Pulmonary hypertension can be idiopathic or associated with other conditions. Prostacyclin is a potent vasodilator and inhibitor of platelet aggregation, and can be given orally, subcutaneously, intravenously or inhaled via a nebuliser. To determine the efficacy of prostacyclin or one of its analogues in idiopathic primary pulmonary hypertension. Electronic searches were carried out with pre-specified terms. Searches were current as of July 2004. Two reviewers selected randomised controlled trials (RCTs) involving adults with pulmonary hypertension for inclusion. Study quality was assessed and data extracted independently by two reviewers. Outcomes were analysed as continuous and dichotomous outcomes. We sub-grouped data where possible by aetiology of PH (PPH, PH secondary to connective tissue disorder or mixed populations). Nine RCTs of mixed duration (3 days-52 weeks), recruiting 1175 participants were included (NYHA functional classes II-IV). Intravenous prostacyclin versus usual care (four studies): There were significant improvements in exercise capacity of around 90 metres, cardiopulmonary haemodynamics and NYHA functional class over 3 days-12 weeks. Effects were consistent in primary and secondary pulmonary hypertension. Oral prostacyclin versus placebo (two studies): Short-term data (3-6 months) indicated that there was a significant improvement in exercise capacity, but data from one study of 52 weeks reported no significant difference at 12 months. No significant differences were observed for any other outcome. Subcutaneous treprostinil versus placebo (two studies, 8-12 weeks):One large study reported a significant median improvement in exercise capacity of around 16 metres. Cardiopulmonary haemodynamics and symptom scores favoured treprostinil. Infusion site pain and withdrawals due to adverse events were more frequent with treprostinil. Inhaled prostacyclin versus placebo (one study, 12 weeks):There was a significant increase in exercise capacity of approximately 36 metres. Treatment led to better symptom scores and functional class status than with placebo. Subgroup analyses reported by individual studies showed a better exercise capacity in participants with PPH, than those participants with PH secondary to other diseases. Side effects and adverse events were common in the studies. There is evidence that intravenous prostacyclin in addition to conventional therapy at tolerable doses optimised by titration, can confer some short-term benefits (up to 12 weeks of treatment) in exercise capacity, NYHA functional class and cardiopulmonary haemodynamics. There is also some evidence that patients with more severe disease based upon NYHA functional class showed a greater response to treatment.

Pulmonary and systemic hemodynamic responses to intravenous prostacyclin in broilers

The eicosanoid vasodilator prostacyclin (PGI2) reduces resistance to pulmonary blood flow and attenuates pulmonary hypertension in mammals. However, sparse information is available regarding the responsiveness of the avian pulmonary vasculature to PGI2. Accordingly, in 3 experiments we evaluated the pulmonary vascular responses to PGI2 in male broilers. In experiment 1, infusing PGI2 (10 microg/min) into clinically healthy broilers did not reduce their pulmonary vascular resistance (PVR) but did reduce their pulmonary arterial pressure (PAP) by lowering their cardiac output. Within 4 min after stopping the PGI2 infusion, the cardiac output and PAP returned to preinfusion levels. In experiment 2, the responses to PGI2 were evaluated after arachidonic acid (AA) had been infused to preconstrict the pulmonary vasculature. The AA infusion (400 microg/min) consistently triggered dramatic, sustained pulmonary vasoconstriction (increased PVR) and pulmonary hypertension (increased PAP). Concurrent PGI2 infusions did not reduce PVR but did reduce PAP by lowering cardiac output. Within 4 min after stopping the PGI2 infusion, PAP and cardiac output returned to their previous (hypertensive) levels attributable to the ongoing AA infusion. In experiment 3, PGI2 was infused (10 microg/min) into clinically healthy (PAP < or = 24 mmHg) or subclinically hypertensive (PAP > or = 27 mmHg) broilers. Throughout this experiment broilers in the hypertensive group had higher PAP values than broilers in the healthy group. The PGI2 infusion reduced PAP in both groups but did not reduce PVR. Instead, the pulmonary hypotensive response to PGI2 infusion was associated with a reduction in cardiac output in both groups. In all 3 experiments PGI2 reduced PAP by reducing cardiac output rather than by reducing PVR. There was no evidence that PGI2 acts as an effective pulmonary vasodilator in broilers regardless of whether their pulmonary vasculature was apparently normal (clinically healthy), had been pharmacologically preconstricted (AA infusion), or initially exhibited the vasoconstriction that is typical of the pathogenesis of pulmonary hypertension syndrome in broilers (PAP > or = 27 mmHg). The consistent failure of PGI2 to elicit pulmonary vasodilation in this study suggests fundamental differences in AA metabolism or the etiology of pulmonary hypertension may exist when broilers are compared with mammals.

Peripheral gangrene in adult‐onset Kawasaki disease

Kawasaki disease (KD) is an acute vasculitis characterized by marked tropism of the coronary vessels. Usually a childhood disease, KD can occasionally be observed in adults. We report a case of adult‐onset KD that presented as a prolonged fever of unknown origin with subsequent development of severe vasculitis, manifested by coronary aneurysms and peripheral gangrene of the lower limbs. Therapy with intravenous immunoglobulins, corticosteroids, aspirin, anticoagulants, and prostacyclin analogue resulted in rapid improvement in the patient's condition but he required partial distal amputation for irreversible gangrene. Peripheral ischaemia leading to gangrene is a very rare feature of KD vasculitis with only 19 cases previously published in the Medline‐indexed literature. The outcomes of those patients were poor, being either fatal or requiring distal amputation. All prior cases affected young children less than 1 year old and, to the best of our knowledge, the present case is the first description of peripheral gangrene in adult‐onset KD.

A novel association of alveolar capillary dysplasia and duodenal atresia with paradoxical dilatation of the duodenum

Background/purpose The authors experienced 3 cases of persistent pulmonary hypertension of the neonate (PPHN) associated with duodenal atresia with paradoxical dilatation of the distal blind end of the duodenum. The aim of this study was to clarify the characteristics of this novel association. Methods The medical charts of the patients were reviewed retrospectively. Results Case 1 was a 2,862-g male infant with a prenatal diagnosis of duodenal atresia. The dilated intestine was identified as the distal blind end of the duodenum during duodeno- duodenostomy. PPHN developed after surgery, and the patient died despite treatment with inhaled nitric oxide (iNO) and extracorporeal membrane oxygenation (ECMO). Lung biopsy results showed alveolar capillary dysplasia (ACD) with misalignment of pulmonary vessels. Case 2 was a 2,244-g female infant with duodenal atresia. Surgery could not be performed because of refractory PPHN, which resulted in death. Autopsy results showed ACD with misalignment of pulmonary vessels and duodenal atresia associated with dilatation of the distal blind end. Case 3 was a 2,462-g female infant with a prenatal diagnosis of duodenal atresia associated with dilatation of the distal blind end. Enlarged echogenic fetal lungs were noted antenatally. PPHN developed after surgery, and she was extubated successfully under combined therapy with iNO and intravenous prostacyclin. Unfortunately, she finally died of refractory PPHN. A retrospective review of the prenatal ultrasonographic findings showed enlarged echogenic fetal lungs as in the first 2 cases. Conclusions The characteristics of this novel association are enlarged echogenic fetal lungs, duodenal atresia associated with paradoxical dilatation of the distal blind end, and refractory PPHN resistant to iNO.

Descriptive patterns of severe chronic pulmonary hypertension by chest radiography

To find chest roentgenographic (CXR) features to help differentiate two representative diseases with severe chronic pulmonary hypertension (PH). Thirty-six consecutive patients with chronic thromboembolic PH (CTEPH), 38 with primary PH (PPH), and 37 with left heart disease and PH. CXRs were reviewed about 6 features (left 2nd arc protrusion, right descending pulmonary artery diameter (rPAD), cardiothoracic ratio (CTR), right 2nd arc width, avascular area and pleural abnormality). Hemodynamic data and the degree of tricuspid regurgitation (TR) on echocardiography were compared with CXR findings. The diagnostic pattern of CTEPH was the presence of one of two findings, an avascular area or marked rPAD (>20mm) together with pleuritic change. The diagnostic pattern of PPH was one of the two features; without pleuritic abnormality, marked left 2nd arc protrusion (>10mm) or moderate left 2nd arc protrusion (5-10mm) with marked rPAD (<20mm). The sensitivity for the diagnosis of CTEPH among the three diseases was 78% and specificity was 92%. The sensitivity for the diagnosis of PPH was 45% and specificity was 88%. CTR and right 2nd arc width were related to the degree of TR in CTEPH and PPH. Characteristic roentgenographic findings can help differentiate two frequent diseases associated with chronic pulmonary hypertension and reflect the severity of disease.

Dysplasie alvéolo-capillaire avec défaut d’alignement des vaisseaux pulmonaires: Revue de la littérature à propos d’un nouveau cas

Alveolar capillary dysplasia (ACD), with or without pulmonary vein misalignment is a uniformly fatal cause of persistent pulmonary hypertension and respiratory failure, first described in 1981. We report the case of ACD in a full term newborn with post mortem pathologic confirmation. Sixty five cases have been reported in the literature, most are sporadic, but a few cases of familial ACD suggest an autosomal recessive inheritance. In 55% of the reported cases of ACD other cardiovascular, digestive or urogenital anomalies were associated. ACD is presumed to be a primary capillary disorder. It affects full-term neonates who exhibit respiratory distress during the early post natal period due to pulmonary hypertension and die within 3 weeks of birth. Histologic findings include a decrease in the number of alveolar capillaries, which are placed centrally within the intralobular septa, ectatic veins accompany the bronchovascular bundles instead of being in their normal position in the interlobular septum, and muscularized pulmonary arteries extend to the distal level. Prognosis is very poor, intravenous prostacyclin with inhaled nitric oxide have been reported in the cases with the best survival.

Traitement de l'hypertension artérielle pulmonaire

Purpose. – Pulmonary arterial hypertension (PAH) is characterized by vasoconstriction, in situ thrombosis and vascular remodeling of small pulmonary arteries inducing a fixed pulmonary arterial obstruction and persistent elevation of pulmonary arterial resistance. Conventional treatment is based on simple measures (exercise limitation) and non-specific drugs (warfarine, diuretics, oxygen). Current knowledge and key points. – Pure vasodilators like calcium channel antagonists have little or no effect on the vast majority of patients, presumably because fixed pulmonary arteriopathy predominate over vasoconstriction. Intravenous prostacyclin (epoprostenol) and endothelin receptor antagonists have vasodilator and antiproliferative properties. Epoprostenol therapy has resulted in significant improvements in prognosis of this disease and this drug remains the first-line treatment of the most severe patients. Bosentan is an interesting first-line treatment for NYHA functional class III patients. Availability of novel specific drugs (endothelin receptor type A antagonists, prostacyclin analogues, type 5 phosphodiesterase inhibitors) open new perspectives in treatment of PAH. The long-term benefit of these drugs remains to be evaluated and their respective place in treatment of these patients is still uncertain. We here present the different therapeutic alternatives available in the PAH and propose an algorithm for treatment of these patients. Future prospects and projects. – The evolution of therapy from vasodilators to antiproliferative agents reflects the advancement in our understanding of the mechanisms mediating pulmonary arterial hypertension.

Congenital diaphragmatic hernia: prenatal diagnosis permits immediate intensive care with high survival rate in isolated cases. A population-based study.

To estimate the prognosis of prenatally diagnosed isolated congenital diaphragmatic hernia (PDICDH) treated with 'immediate planned care' (IPC) between 1999 and 2003 in Eastern Brittany. The prognosis of PDICDH was compared with the prognosis of the other live-born CDH, either prenatally undiagnosed or not having had IPC. IPC consisted in prenatal lung maturation with corticosteroids, elective caesarean section at 37 weeks, immediate intubation, surfactant, high- frequency ventilation or oscillation, nitric oxide, intravenous prostacyclin, anaesthesia and haemodynamic support. Surgical repair was performed in the NICU 34 h after birth. The incidence of CDH was 0.8 per thousand with a prenatal diagnosis rate of 27/30 (90%), leading to a termination of pregnancy in nine cases. Ten CDH were associated with other malformations. IPC in PDICDH was performed in 12 cases. The survival rate of PDICDH with IPC was 11/12 versus 1/9 in CDH with no IPC or no prenatal diagnosis (p < 0.01). Logistic regression analysis showed that IPC was determinant for survival (p < 0.01). Prenatal diagnosis of isolated CDH treated with immediate planned care is associated with a high survival rate. This suggests that prenatal diagnosis associated with specifically adapted postnatal procedure may improve the prognosis of isolated CDH.

Tratamiento combinado con prostaciclina intravenosa y sildenafilo en pacientes con hipertensión arterial pulmonar: descripción de 4 casos

Here we report the experience obtained from a combined treatment with intravenous (i.v) prostacyclin and oral sildenafil in patients with severe pulmonary hypertension (PHT) who had a poor response to prior treatment with prostacyclin alone. Sildenafil was added to the treatment in four patients with PHT (primary in two patients and secondary to collagenosis in the other two) with no adequate response to i.v. prostacyclin treatment. The clinical course, 6minutes walking test and echocardiogram were evaluated. Initial sildenafil dose was 12.5 mg three times daily, which was increased up to 50 mg three times daily in one patient and up to 50 mg four times daily in the other three. The symptoms of right heart failure were controlled in all cases. Before the start of sildenafil administration, two patients had class III dyspnea and two patients had class IV dyspnea. Two patients converted to class I (previously class III and IV), and the other two converted to class II. The distance walked within 6 minutes increased (average increase 55%) and systolic pulmonary artery pressure decreased in all patients (average reduction 27%). Effects of sildenafil were substained. The only side effect seen was mild headache. Our experience supports the value of sildenafil in the treatment of PHT and suggests that combined treatment is useful for rescuing patients who fail to respond to initial treatment with i.v. prostacyclin.

Drug therapy of primary pulmonary hypertension.

Primary pulmonary hypertension (PPH) is a rare but life-threatening disease. Median survival, from the time of diagnosis, is considered to be 2.8 years. However, therapeutic medical advances over the past 2 decades have resulted in significant improvements in quality of life and survival in patients with PPH. Because pulmonary vasoconstriction, endothelial cell proliferation, smooth muscle cell proliferation, and in situ thrombosis contribute to the development of this disease, treatment with vasodilators, anti-proliferative agents, and anticoagulants is recommended.Currently, oral administration of calcium channel antagonists and intravenous infusion of epoprostenol (prostacyclin) are established as treatment of PPH. Epoprostenol has vasoprotective effects including vasodilation, anti-platelet aggregation, and inhibition of smooth muscle cell proliferation. Interestingly, prostacyclin synthase deficiency in the lungs, and impaired prostacyclin production, have been linked to the development of pulmonary hypertension in this disease. As a result, continuous intravenous infusion of epoprostenol has become recognized as a therapeutic breakthrough that can improve hemodynamics and survival in patients with PPH. The dramatic success of long-term intravenous prostacyclin is now leading to the development of epoprostenol analogs using newer drug delivery systems (oral beraprost, aerosolized iloprost, and subcutaneous treprostinil). In addition, promising drugs including endothelin antagonists and type V phosphodiesterase inhibitors have recently been developed. Furthermore, gene therapy with endothelial nitric oxide synthase gene or prostacyclin synthase gene may hold great promise in the treatment of PPH. Finally, accurate evaluation of disease severity and the efficacy of vasodilator therapy are important in the management of patients with PPH. In addition to invasive assessment by cardiac catheterization, we recommend repeated measurements of plasma brain natriuretic peptide, serum uric acid, and the distance walked in 6 minutes. These noninvasive parameters may be helpful as part of the evaluation of treatment in patients with PPH and, in particular, as a guide to the selection and timing for alternative therapies.

Inhaled nitric oxide versus prostacyclin in chronic shunt-induced pulmonary hypertension

Objective Cardiac surgery for congenital heart defects is commonly complicated by shunt-induced chronic pulmonary hypertension and associated acute hypertensive crises. To investigate the effects of vasodilators in chronic and acute pulmonary hypertension, we used the innominate artery to create a growing aortopulmonary shunt in young piglets. Methods Pulmonary hemodynamics and right ventricular function and their responses to hypoxia, intravenous prostacyclin, and inhaled nitric oxide were investigated after closure of the shunt by using pulmonary flow-pressure relationships, pulmonary vascular resistance partitioning, pulmonary vascular impedance, and ventriculoarterial coupling expressed as the ratio of right ventricular end-systolic elastance to effective pulmonary arterial elastance. Results Shunt-induced pulmonary hypertension was associated with medial hypertrophy of pulmonary arteries, increased resistance, increased elastance, increased wave reflection, and preserved ventriculoarterial coupling. Hypoxic pulmonary vasoconstriction was blunted in the shunt group. Compared with prostacyclin, inhaled nitric oxide was a more effective vasodilator in the shunt group and in hypoxia. Effective pulmonary arterial elastance and right ventricular end-systolic elastance increased in chronic (shunt) and acute (hypoxic) hypertension and decreased with vasodilators, preserving a normal coupling. Conclusions A growing aortopulmonary shunt in the young pig is a reliable model of chronic pulmonary hypertension, with medial hypertrophy, increased resistance, and increased elastance. In this model inhaled nitric oxide is a better pulmonary vasodilator than intravenous prostacyclin, with neither drug having a specific inotropic effect, and normal coupling is preserved in chronic and acute pulmonary hypertension.

Prostanoids for intermittent claudication.

Peripheral arterial occlusive disease (PAOD) is a common cause of morbidity in the general population. While numerous studies have established the efficacy of prostanoids in PAOD stages III and IV the question of the role of prostanoids as an alternative or additive treatment in patients suffering from claudicatio intermittens (PAOD II) has not yet been clearly answered. The aim of this review was to evaluate effects of prostanoids in patients with intermittent claudication. Computerised searches of the Cochrane Peripheral Vascular Diseases Specialised Register (last searched April 2003), The Cochrane Central Register of Controlled Trials (CENTRAL) (last searched Issue 1, 2003), MEDLINE and EMBASE were undertaken. In addition relevant journals were hand-searched. Randomized clinical trials describing the effects of prostanoids in the treatment of patients suffering from intermittent claudication have been considered for inclusion. All reviewers assessed the quality of studies and extracted data unblinded. Statistical analysis including tests for heterogeneity and overall effect were performed by using MetaView of Review Manager 4.2. All numeric values are expressed as mean +/- Standard deviation (SD). Eighteen studies were included for analysis. A significant heterogeneity between the included studies was detected in most of the subgroup analysis. Five studies compared the effects of prostaglandin E1 (PGE1) versus placebo, and reported in their individual results significant increases in walking distances after the administration of PGE1. The attained increase in walking distances appears to be not merely a short-term effect because several studies reported that walking capacity remained increased even after termination of treatment. On the other hand, oral or intravenous prostacyclin did not increase the walking distances significantly. At least one adverse reaction was reported from 23.6% of the patients treated with prostacyclin (PGI2), and its analogues and from 13.7% of the patients treated with PGE1. Because of the heterogeneity between most of the included studies, we did not pool relevant parts of the data by meta-analysis. Based on the individual results of the published literature, patients with intermittent claudication seem to benefit from administration (intravenous or intra-arterial) of PGE1 by a significant improvement of their walking capacity. Further well-conducted randomized, double blinded trials, with a sufficient number of patients to provide statistical powerful information, should be performed to confirm the results of this review.

Clinical value of prostacyclin and its analogs in the management of pulmonary arterial hypertension.

Pulmonary arterial hypertension (PAH) is associated with changes in vascular tone as well as vascular structure, with the relative contribution of each dependent upon the etiology of the increased vascular resistance. Prostacyclin treatment has markedly improved both the therapeutic options and the prognosis of PAH. The beneficial effect of prostacyclin in PAH is linked to the powerful vasodilating capacity and, even more importantly, to the inhibition of platelet aggregation, smooth muscle proliferation and antiinflammatory actions. Since prostacyclin has a very short plasma half-life, continuous intravenous administration via a portable infusion pump must be carried out. Because of the complexity of the delivery and the associated complications, intravenous prostacyclin (epoprostenol) therapy is restricted to patients with late NYHA Class III and Class IV and thus alternative modes of delivery in less advanced PAH are desirable. Recent clinical studies with more stable prostacyclin analogs such as subcutaneously delivered treprostinil, orally active beraprost and aerosolized iloprost have demonstrated beneficial effects of each of these prostanoids, especially in NYHA Class II and III patients and, therefore, these agents should be considered first for prostanoid therapy in the early stages of PAH. Prostaglandins may be more effective in conjunction with endothelin receptor antagonists or phosphodiesterase inhibitors and an increasing number of studies are now addressing the combined efficiency and safety of these combinations. This update will focus on the current development status of PAH therapy with prostacyclin and its analogs. Special attention will be accorded to the selection of patients for prostanoid therapy, therapy monitoring and improvement of therapeutic efficacy by addition of other new therapeutic agents to prostaglandins. Survival benefits and special aspects of bridging-to-transplant therapy are also important aspects of the review.

Transición de prostaciclina intravenosa a subcutánea en la hipertensión pulmonar

Treatment of arterial pulmonary hypertension with epoprostenol (intravenous prostacyclin) improves survival and quality of life, but the need for an implanted central venous catheter is associated with frequent complications, that often (as in the case of infection or dislodgment) are serious and require catheter replacement. Treprostinil is a prostacyclin analogue suitable for continuous subcutaneous administration. We report the successful transition from intravenous epoprostenol to subcutaneuos treprostinil in four patients with severe pulmonary hypertension who suffered from serious complications associated with the epoprostenol infusion system.

Intravenous prostacyclin combined with inhaled nitric oxide therapy for an infant with alveolar capillary dysplasia

Intravenous prostacyclin combined with inhaled nitric oxide therapy for an infant with alveolar capillary dysplasia

Intravenous prostacyclin combined with inhaled nitric oxide therapy for an infant with alveolar capillary dysplasia

Intravenous prostacyclin combined with inhaled nitric oxide therapy for an infant with alveolar capillary dysplasia

Elevation of ELISA D-Dimer Levels in Patients with Primary Pulmonary Hypertension

Background: Vasoconstriction, vascular wall remodeling and thrombosis are considered as possible etiologies of primary pulmonary hypertension (PPH). D-dimer, a degradation product of fibrin, has been increasingly used as a marker and prognostic factor in various diseases. Objective: To assess elevated ELISA D-dimer levels as a marker of endogenous fibrinolysis in patients with PPH. Patients and Methods: Comparison of ELISA D-dimer levels of 12 PPH patients (11 female, 1 male) aged 27–73 years (median 51 years) with those of sex- and age-matched healthy controls. Results: Eleven patients had New York Heart Association (NYHA) class III or IV symptoms, and one patient had NYHA class II symptoms. All patients with PPH were treated with anticoagulants and vasodilators: 5 patients were treated with continuous intravenous prostacyclin, 4 patients with continuous UT-15 and 2 patients with intermittent intravenous iloprost. Mean ELISA D-dimer levels ± SD were significantly higher in the PPH group than in the matched control group (473 ± 109 vs. 182 ± 103 ng/ml; mean difference: 291 ± 79, 95% CI: 240–341, p < 0.0001). Conclusion: These results suggest the possible involvement of endogenous fibrinolysis in the pathophysiology of PPH.