Search

Selexipag (Uptravi ® tablets) is a novel prostacyclin receptor (IP receptor) agonist designed and synthesized at Nippon Shinyaku Co., Ltd., and approved for the treatment of pulmonary arterial hypertension (PAH). Selexipag is converted to MRE-269 in vivo, and the plasma concentration of MRE-269 is maintained at a therapeutic level for a long time. MRE-269 has selective IP receptor agonist activity and exerts vasodilatory and anti-proliferative effects on pulmonary arterial smooth muscle cells. In a study to investigate its vasodilatory effect in isolated rat pulmonary arteries, MRE-269 showed potent vasodilatory effects not only in extralobar but also in small intralobar pulmonary arteries. In a Sugen 5416/hypoxia rat model of PAH, selexipag significantly improved pulmonary artery obstruction, decreased right ventricular systolic pressure, decreased right ventricular hypertrophy and improved survival rate. In a phase II clinical trial for treatment with PAH conducted in Europe, selexipag showed good tolerability with promising efficacy. In an open-label phase II study in 37 patients with PAH in Japan, selexipag significantly decreased pulmonary vascular resistance compared with baseline. In the GRIPHON (Prostacyclin (PGI 2 ) Receptor agonist In Pulmonary arterial HypertensiON) study in 1156 patients with PAH, the largest outcome study ever conducted in PAH, the selexipag treatment group showed a significant reduction in the risk of the primary composite endpoint of death or a complication related to PAH compared with placebo. Selexipag has been shown in clinical trials to prevent the progression of PAH, and is expected to contribute to the treatment of patients with PAH.

POEMS syndrome is often complicated by pulmonary hypertension. The standard therapy for patients with POEMS syndrome is high-dose chemotherapy followed by autologous stem cell transplantation. However, the safety of high-dose chemotherapy for patients complicated with pulmonary hypertension remains unclear, and the optimal therapy for these patients is yet to be establishment. Herein, we report the case of a 54-year-old woman with POEMS syndrome accompanied by pulmonary hypertension. We successfully and safely performed lenalidomide and dexamethasone (Ld) therapy followed by high-dose chemotherapy and autologous stem cell transplantation, which improved her pulmonary hypertension. Thus, Ld can be considered as safe and effective for pulmonary hypertension with POEMS syndrome.

Pulmonary arterial hypertension (PAH) is a known risk factor of perioperative complications, but the risks for non-cardiac operations have not yet been examined sufficiently. We report a case of a right lower lobectomy in a patient with PAH. A 73-year-old woman with Sjögren's syndrome was scheduled for right lowr lobectomy for primary lung cancer under general anesthesia. She was diagnosed with symptomatic PAH (estimated mean pulmonary arterial pressure, 40 mmHg) and medicated with ambrisentan. After induction of general anesthesia with propofol and fentanyl, a pulmonary artery catheter was placed to measure pulmonary artery pressure. The Pp/Ps was roughly 0.4 and the pulmonary artery clamp elevated it to 0.5. Milrinone administration gradually improved the Pp/Ps to 0.3. To avoid pulmonary artery pressure elevation during emergence of anesthesia, continuous dexmedetomidine was administered. The double-lumen tracheal tube was extubated uneventfully with minimal elevation in pulmonary arterial pressure.

Idiopathic pulmonary arterial hypertension (IPAH) is a progressive and fatal disease of unidentified pathogenesis. IPAH is pathologically characterized as sustained vasoconstriction and vascular remodeling of the pulmonary artery. In pulmonary arterial smooth muscle cells (PASMCs), an increase in cytosolic Ca 2+ concentration ([Ca 2+ ] cyt ) triggers vasoconstriction and stimulates cell proliferation leading to vascular remodeling. However, dihydropyridine-type voltage-dependent Ca 2+ channel blockers are only effective in very few patients with IPAH (<10%). It is unclear why dihydropyridine Ca 2+ channel blockers are not therapeutically effective in a majority of IPAH patients. We have previously shown that extracellular Ca 2+ -sensing receptor (CaSR) is upregulated in PASMCs from IPAH patients, and it contributes to enhanced [Ca 2+ ] cyt responses and augmented cell proliferation. In this study, the effects of dihydropyridine Ca 2+ channel blockers on [Ca 2+ ] cyt responses mediated by CaSR were examined in IPAH-PASMCs. Nifedipine (dihydropyridines) enhanced the CaSR-mediated increase in [Ca 2+ ] cyt in IPAH-PASMCs, but not in PASMCs from normal subjects. Nicardipine (dihydropyridines) and Bay K 8644 (a dihydropyridine Ca 2+ channel activator) also augmented the CaSR-mediated [Ca 2+ ] cyt increase in IPAH-PASMCs. In contrast, non-dihydropyridine Ca 2+ channel blockers such as diltiazem (benzothiazepines) and verapamil (phenylalkylamines) had no effect on the [Ca 2+ ] cyt response in IPAH-PASMCs. Finally, in monocrotaline-induced pulmonary hypertensive rats, nifedipine caused further increase in right ventricular systolic pressure and thus right ventricular hypertrophy. In conclusion, dihydropyridine Ca 2+ channel blockers could exacerbate symptoms of pulmonary hypertension in IPAH patients with upregulated CaSR in PASMCs.

The prognosis of connective tissue disease (CTD)-associated pulmonary arterial hypertension (PAH) is so poor that early therapeutic intervention is advisable. Borderline PAH (21-24 mmHg mean pulmonary arterial pressure) is a concept created to distinguish cases that would become definite PAH. It is controversial whether borderline PAH cases with no symptoms should be treated, but therapeutic intervention in the case of borderline PAH is justified when systemic sclerosis (SSc) is in the background, because SSc-associated PAH shows an especially poor prognosis compared to PAH associated with other CTDs, while 42-55% of SSc-associated borderline PAH cases become definite PAH within several years. However, cautious attention should be paid when pulmonary vasodilators are administered to SSc-associated PAH cases, because complications caused by SSc such as lung lesions, left heart diseases and pulmonary venous lesions can be obstacles to the success of the therapy. There is very little evidence of the efficacy of therapeutic intervention in borderline PAH. Clinical trials should be planned.

Background: Clinical characteristics of phosphodiesterase (PDE) III inhibitors, milrinone and olprinone, is not fully understood in infants. We therefore retrospectively examined the hemodynamics, metabolism, and oxygenation of two different PDE III inhibitors in infants undergoing radical correction of ventricular septal defect with pulmonary hypertension., Methods: Twenty-six infants with pulmonary hypertension undergoing ventricular septum defect repair were retrospectively allocated to milrinone group (n= 13)and olprinone group(n=13). Hemodynamic parameters, acid-base balance, oxygenation and postoperative mechanical ventilation period were compared between the two groups at induction of anesthesia, weaning from cardiopulmonary bypass and the end of the surgery., Results: The patients' mean age was 4.4 +/- 2.5 months. Demographic data were almost similar between the two groups. Milrinone and olprinone were administered at the rates of 0.5 and 0.3 microg x kg-1 x min-1 at the end of surgery, respectively. Hemodynamic variables, acid-base balance, Pao2 /FIo2 ratio and mechanical ventilation period were not significantly different between the two groups. No adverse side effects were observed during the study period., Conclusions: The effects of the PDE III inhibitors, milrinone and olprinone, on hemodynamic parameters, acid-base balance and oxygenation were similar in these infants. Both milrinone and olprinone could be used safely in infant cardiac surgery.

A 68-year-old female who had Raynaud phenomenon for a decade was admitted to our hospital in January 2012. She complained of sclerodactyly and scleroderma that did not extend past the elbows. She also had fingertip ulcers that repeatedly disappeared and recurred for several years. Blood tests showed that she was anti-centromere antibody positive. Therefore, she was diagnosed with limited cutaneous systemic sclerosis. Two months after diagnosis, she returned to our hospital because she experienced dyspnea on exertion and exacerbation of her fingertip ulcers. Chest X-rays revealed cardiac enlargement, an echocardiography showed tricuspid regurgitation with an increased tricuspid pressure gradient (91 mmHg) and right heart catheterization showed a mean pulmonary arterial pressure of 59 mmHg. Chest computed tomography and lung perfusion scintigraphy showed no abnormalities. She was then diagnosed with pulmonary arterial hypertension associated with systemic sclerosis. She improved rapidly with daily treatments of prednisolone in addition to warfarin, bosentan and beraprost sodium. This is a rare case of rapidly progressive pulmonary arterial hypertension associated with systemic sclerosis that can be markedly improved with early diagnosis and treatment.

Pulmonary arterial hypertension (PAH) is a rare, progressive, and fetal disease. The five-year survival rate after diagnosis is ～50%. In Japan, PAH is listed in the Specified Rare and Intractable Diseases. Pulmonary vascular remodeling and sustained pulmonary vasoconstriction are the major causes for the elevated pulmonary vascular resistance (PVR) in PAH. The pathogenic mechanisms involved in the pulmonary vascular abnormalities in PAH remain unclear. Sustained vasoconstriction and vascular remodeling owing to proliferation of pulmonary arterial smooth muscle cells (PASMCs) are key pathogenic events that lead to early morbidity and mortality. These events have been closely linked to Ca(2+) mobilization and signaling in PASMCs. An increase in cytosolic Ca(2+) concentration ([Ca(2+)]cyt) in PASMCs is an important stimulus for pulmonary vasoconstriction and cell proliferation which subsequently cause pulmonary vascular wall thickening followed by the increase in PVR. Increased resting [Ca(2+)]cyt and enhanced Ca(2+) influx have been implicated in PASMCs from PAH patients, but precise therapeutic targets to interrupt these signal pathways have not been identified. We recently found that the extracellular Ca(2+)-sensing receptor (CaSR), a G protein-coupled receptor (GPCR), is upregulated in PASMCs from patients with idiopathic pulmonary arterial hypertension (IPAH). In addition, blockage of the CaSR with an antagonist (NPS2143) prevents the development of pulmonary hypertension and right ventricular hypertrophy in animal models of pulmonary hypertension. The functionally upregulated CaSR in PASMCs is a novel pathogenic mechanism contributing to the augmented Ca(2+) signaling and excessive cell proliferation in IPAH. Targeting CaSR in PASMCs may help develop novel therapeutic approach for PAH.

We experienced two pediatric cases of severe pulmonary hypertension after congenital heart surgery. It was difficult to wean two cases from cardiopulmonary bypass for systemic hypotension concomitant with pulmonary hypertension reflactory to conventional therapy, including administration of adrenaline, nitroglycerin, milrinone, and/or inhalation of nitric oxide. In order to increase systemic arterial blood pressure and improve severe right heart failure, we administered arginine vasopressin (AVP) intravenously, which is a potent vasoconstrictor via V1 receptor. The dose of AVP was 0.0002 unit x kg(-1) x min(-1). After administration of AVP, systemic arterial pressure increased markedly and pulmonary arterial pressure decreased slightly, and we succeeded in weaning the patients from cardiopulmonary bypass. No adverse effect with AVP was found. In conclusion, administration of AVP is a therapeutic option for treating systemic hypotension concomitant with severe pulmonary hypertension in pediatric congenital heart surgery.

We report a 43-year-old female who developed pulmonary arterial hypertension (PAH) during intensive immunosuppressive therapy for systematic lupus erythematosus (SLE). She was diagnosed as SLE at the age of 32 years based on serological and hematological abnormalities, oral ulcers, and facial erythema. She experienced frequent flare-ups of disseminated discoid lupus between the ages of 33 and 36 years and developed immune thrombocytopenia at the age of 39 years. In 2007 when she was 43 years old, she developed lupus nephritis (LN) with elevated serum anti-double stranded DNA antibodies and urine protein of less than 1 g/day. Combination therapy for the LN with 35 mg/day prednisolone and intravenous cyclophosphamide (IVCY) led to renal remission. After the seventh monthly session of IVCY, she developed dyspnea on exertion. PAH was diagnosed based on enlarged main pulmonary arteries on the chest x-ray, right ventricular outflow and a peak tricuspid regurgitant pressure gradient exceeding 45 mmHg on echocardiography, an elevated plasma brain natriuretic peptide (BNP) level of 260 pg/ml, the exclusion of pulmonary thromboembolism, and no lung fibrosis. The PAH was treated successfully with bosentan. At present the tricuspid regurgitation has disappeared, and the plasma BNP level has normalized.

A 54-year-old woman with a 20-year history of Raynaud phenomenon was admitted to our hospital complaining of progressive dyspnea on exertion since 5 years previously. Interstitial lung disease was diagnosed, accompanied by pulmonary arterial hypertension (PAH) associated with systemic sclerosis. After oxygen therapy and treatment with sildenafil, her clinical condition and PAH gradually improved. However, she was readmitted due to deterioration of Raynaud phenomenon and progressive dyspnea in March 2009. Right heart catheterization findings demonstrated that her mean pulmonary arterial pressure (PAP) was elevated, at 48 mmHg. Bosentan was therefore added to an increased dose of sildenafil. Consequently, her dyspnea, 6-min walking distance, serum brain natriuretic peptide level, and PAP improved. Combination therapy with bosentan and sildenafil was effective for this case of refractory PAH associated with fibrotic lung in systemic sclerosis.

A 77-year-old woman was admitted to our hospital because of an abnormal chest shadow. She complained of shortness of breath on effort. Chest CT showed patchy areas of ground-glass opacity in right S2 and S6. A high titer of antinuclear antibody with a discrete speckled pattern on immunofluorescent staining was disclosed, and she was positive for anticentromere antibodies. Pulmonary arterial hypertension was found by right heart catheterization. Biopsy by video-assisted thoracoscopic surgery was performed. About one month after surgery, she started to need to inhale oxygen due to gradually progressing dyspnea. Continuous PGI2 administration was not very effective, but administration of methylprednisolone and prednisolone induced improvement of her symptoms. Histopathologic examination of biopsy revealed extensive and diffuse occlusion of pulmonary veins. The pathological diagnosis suggested a pulmonary veno-occlusive disease. Clinical data suggested the association between systemic sclerosis sine scleroderma and probable pulmonary veno-occclusive disease.

Among the cardio-pulmonary disorders associated with collagen vascular disease (CVD), pulmonary arterial hypertension (PAH) is recognized as most serious problem. Because PAH is difficult to manage and its prognosis is terribly poor. Thus, early diagnosis of PAH in CVD is important. Since PAH patients associated with CVD are often asymptomatic in their early stage, screening with echocardiography is needed. The degree of inflammation causing PAH through endothelial injury is closely associated with CVD, and thus, the improvement of PAH may be achieved by immunosuppressant, especially in its early stage. Once the diagnosis of PAH is confirmed, treatment with oral vasodilators should be started as soon as possible. If oral vasodilators prove inadequate, intravenous epoprostenol should be administered without hesitating.

A 52-year-old woman with end-stage renal disease and long-term hemodialysis complained of worsening exertional dyspnea. A chest X-ray showed cardiomegaly. She was admitted to our hospital because an echocardiogram suggested pulmonary hypertension. Right heart catheterization revealed pulmonary hypertension, but pulmonary perfusion scintigraphy with Tc-99m-MAA showed no evidence of pulmonary thromboembolism. We gave her a diagnosis of pulmonary arterial hypertension associated with Sjögren syndrome on the basis of a positive serological test (SS-A. SS-B) and the findings of lip biopsy. After four months of therapy with bosentan, her 6-minute walk distance, estimated pulmonary arterial pressure and brain natriuretic peptide (BNP) improved. Bosentan is mainly cleared by hepatic elimination and its dialysis clearance is low. Bosentan for the treatment of pulmonary hypertension was safe as well as effective in this patient with end-stage renal disease and hemodialysis. In consideration of the relationship between pulmonary hypertension and end-stage renal disease, and hemodialysis, bosentan was considered to be a reasonable and effective treatment.

Pulmonary hypertension is the most ominous complication of connective tissue diseases and its treatment has been a big challenge to clinicians. Vasodilators including epoprostenol (prostacyclin), bosentan (endothelin-receptor antagonist), and a sildenafil (phosphodiesterase type 5 inhibitor) have recently become available in Japan. These vasodilators may improve exercise tolerance, hemodynamics, activities of daily life, and the life span. In this article, we review an endothelin-receptor antagonist and phosphodiesterase type 5 inhibitor recently approved as treatment modalities for pulmonary hypertension in Japan.

Pulmonary arterial hypertension(PAH) is an uncommon disease characterised by a progressive increase in pulmonary vascular resistance. An imbalance between vasoconstrictor/vasodilator activities could be responsible for altered pulmonary vascular tone and structure. In PAH patients, endothelin are increased. Restoration of this imbalance by targeted therapies such as endothelin receptor antagonists should further improve treatment options for the management of PAH. Current treatment algorithms for PAH recommend bosentan as first-line treatment for PAH in functional class III. Recent many trials suggested that endothelin receptor antagonist, bosentan, caused good results in idiopathic PAH and PAH associated with chronic thromboembolism, collagen diseases, and congenital heart diseases.

Anticoagulant agents, vasodilators, and lung transplantation are currently used for the treatment of pulmonary arterial hypertension (PAH); however, more effective treatment needs to be developed. Rho-kinase-mediated pathway plays an important role in various cellular functions, such as vascular smooth muscle hyperconstriction or cell adhesion and motility. We have demonstrated that Rho-kinase is activated in animal models of PAH associated with enhanced pulmonary vasoconstricting and proliferating responses, impaired endothelial vasodilator functions, and pulmonary remodeling and that intravenous fasudil, a selective Rho-kinase inhibitor, exerts acute pulmonary vasodilator effects in patients with severe PAH. Our findings indicate that Rho-kinase is a novel and important therapeutic target of PAH and that Rho-kinase inhibitors are a promising new class of drugs for the disorder.

Pulmonary arterial hypertension (PAH), previously known as primary pulmonary hypertension, is characterized by a progressive increase in pulmonary vascular resistance leading to right ventricular failure and death. Recently dramatic advance in medical therapy including prostanoids, endothelin-receptor antagonists, phosphodiesterase 5 inhibitors, has occurred, and American College of Chest Physicians(ACCP) Evidence-Based Clinical Practice Guidelines have been proposed, followed by several guidelines for treatment of pulmonary hypertension in our country. Additionally several reports have provided utility of combination therapy. This article summarizes recent medical therapy for PAH including updated ACCP guidelines in 2007, further advance, and recommended therapeutic approach for PAH, available in our country.

Vascular thrombosis implicates in the pathogenesis of pulmonary arterial hypertension (PAH). Anticoagulation therapy (warfarin) has been recommended by many experts in the treatment of PAH. However, the long-term effectiveness of anticoagulation therapy remains controversial. Because of the various drugs, such as epoprostenol, bosentan, and sildenafil, for the treatment of PAH recently, warfarin alone is not a realistic therapy for PAH. Accordingly we reviewed the previous manuscript regarding anticoagulation therapy for PAH, and looked at the current role of anticoagulation therapy in Japan.

The goal of combination therapy in patients with pulmonary arterial hypertension (PAH) is aimed at maximizing therapeutic efficacy while limiting toxicity and drug interactions. Because PAH is a rare disease, it is difficult to adequately power therapeutic trials to evaluate significant morbidity or mortality differences between various drug therapies. At this point, it is premature to either dismiss or strongly favor any one combination of therapies over another. There is debate among PAH specialists as to whether combination therapy should be reserved for patients whose condition deteriorates (add on therapy) or should be started up front and followed by maintenance therapy with one or more agents once patients have improved. Careful design of future trials testing these comparisons is very important.

Inhaled nitric oxide (NO) therapy is a measure to improve pulmonary hypertension and ventilation-perfusion inequality by administering NO gas. Basic studies suggest that low concentrations of inhaled NO decreases the increased pulmonary capillary pressure, depresses the increased permeability of pulmonary vasculature, inhibits the increased agglutination and adhesion of leucocytes to the lungs, depresses the increased agglutination and adhesion of platelets, and decreases the hypertensive remodeling of pulmonary vasculature. In the emergency and critical care settings, quite a lot of life-threatening patients with the exacerbation of pulmonary hypertension and/or hypoxemia by trauma, surgery and infections are admitted for treatment. In this paper, we discuss the present status of inhaled NO therapy from the point of view of an emergency and critical care physician.

Epoprostenol (prostacyclin) has been shown to improve survival in pulmonary arterial hypertension. However, this therapy needs continuous intravenous administration devises because of its short half-life. Recently, an orally active prostacyclin analogue, beraprost sodium, and its drug delivery system have been developed in Japan. Beraprost sodium improves pulmonary hemodynamics in patients with pulmonary arterial hypertension. In addition, we have developed ONO-1301, a novel long-acting prostacyclin agonist with thromboxane synthase inhibitory activity. Subcutaneous administration of ONO-1301 markedly attenuated monocrotaline-induced pulmonary hypertension and improved survival in rats. These prostacycline derivates may be promising for the treatment of pulmonary arterial hypertension.

The therapeutic effects of phosphodiesterase type 5 inhibitors in patients with pulmonary arterial hypertension (PAH) were reviewed. A double-blind, placebo-controlled study named SUPER-1 showed that sildenafil improved exercise capacity, WHO functional class, hemodynamics, and quality of life. Two randomized, double-blind, crossover studies, showed that sildenafil improved exercise tolerance and quality of life, and reduced estimated pulmonary artery systolic pressure. The dose independent effects of sildenafil on PAH are controversial. There are few case-reports that show vardenafil and tadalafil have benefits in PAH patients. A double-blind study of tadalafil in PAH patients is ongoing.

Microarray analysis demonstrated lung gene encoding osteopontin (OPN), a soluble secreted phosphoprotein, was significantly elevated in rats with hypoxic pulmonary arterial hypertension (PAH). Since OPN enhances vascular smooth muscle cell proliferation, we hypothesized that OPN played a role in the pathogenesis of PAH. Some patients with idiopathic PAH showed increased expression of plasma OPN and lung OPN gene. OPN overexpression in mice caused pronounced pulmonary hypertension and vascular remodeling under hypoxic conditions. A PPARgamma ligand, pioglitazone, which was reported to inhibit OPN gene expression in vitro, attenuated hypoxia-induced increase in lung OPN gene and pulmonary vascular remodeling in rats. These findings indicate that OPN may be responsible for pulmonary vascular remodeling and could be a therapeutic target for PAH.

Intravenous prostacyclin therapy has been established as the standard therapy for patients with pulmonary arterial hypertension. Thus, it is strongly recommended by the guidelines in United States, Europe, and Japan on treatment of severely ill patients with pulmonary arterial hypertension based on the several controlled trials. The half-life of epoprostenol is so short that it needs to be administered by continuous infusion pump and indwelled central venous catheter, which could induce life-threatening adverse events such as pump malfunction, catheter obstruction and infection. Despite such complexities, it should not be hesitated to introduce the most effective treatment--continuous intravenous prostacyclin therapy--for patients with severe pulmonary arterial hypertension.

Pulmonary arterial hypertension (PAH) is serious and a progressive disease with relatively poor prognosis if not identified and treated early in children. In pediatric age group, the transition of the pulmonary circulation from fetal life to neonatal period plays a pivotal role to maintain the pulmonary vascular resistance to be low. In children with iPAH, acute drug response to vasodilator is more prominent than that in adult. But, prognosis is relatively poor. Recently, phosphodiesterase (PDE) 5 inhibitor (sildenafil, Viagra) and endothelin receptor antagonist (bosentan, Tracleer) in addition to prostacyclin used as a combination therapy can be used for this age population. The 5-year survival has been improved to > 80%. In this chapter, we focus on pathophysiological aspects and treatment strategy of idiopathic PAH, familial PAH, and PAH in the neonate (ex. PPHN).

A rare case of chronic obstructive pulmonary disease (COPD) with severe pulmonary hypertension (PH) was found in a 68-year-old man. COPD was diagnosed in his 50s, from which time he received home oxygen therapy. In January 2007, he was admitted due to progression of dyspnea. On admission to our hospital, arterial blood gas analysis showed severe hypoxemia. Moreover, echocardiographic findings demonstrated severe deviation of the interventricular septum toward the left ventricle, with right ventricular dilatation. Cardiac catheterization data demonstrated pulmonary arterial hypertension with a low cardiac output. Because severe PH is uncommon in patients with COPD and there was no apparent etiology of PH other than COPD, we thought this case was predominantly a pulmonary vascular disease such as idiopathic pulmonary arterial hypertension. Though we first treated this patient with bosentan, it was not effective. Therefore, he was treated with continuous infusion of epoprostenol. Epoprostenol administration along with bosentan resulted in decrease of BNP and right ventricular function improvement. We report a case of severe PH due to severe COPD treated with continuous administration of epoprostenol.

We report an initial experience of successful application of bosentan (BOS), a endotheline-1 dual-receptor blocker, in the treatment of sustained pulmonary hypertension (PH) early after surgical correction of congenital heart disease. Two infants (5 and 9-months-old girls undergone repair of complete atrioventricular septal defect and closure of ventricular septal defect, respectively) suffered from PH-relating symptoms after extubation despite oral sildenafil (SIL) treatment. After administration of BOS (1.5 mg/kg/day), the symptoms were dramatically relieved and SIL was uneventfully discontinued. Although BOS caused a transient increment of liver transaminase in the 5-month-old girl, BOS is a possible alternate in the treatment of the postoperative sustained PH as reported in a various type of chronic PH.