Prostacyclin Infusion Research Articles

Intermittent Epoprostenol Infusions in Systemic Lupus Erythematosus Associated Pulmonary Hypertension—A Series of Three Cases

Introduction: Pulmonary hypertension (PHT) associated with systemic lupus erythematosus (SLE) has a grave prognosis. Continuous prostacyclin infusion significantly reduces pulmonary arterial pressure (PAP) and may improve survival in patients with primary and secondary PHT. We report our experience with intermittent epoprostenol (EPO) infusion in SLE patients with PHT. Clinical Characteristics: We reviewed patients with SLE associated PHT who were treated with intermittent EPO infusions in 1998. All 3 patients had severe PHT, with maximum systolic PAP (PASP) of 58, 96 and 67 mm Hg, respectively, when measured using Doppler echocardiography, and were in New York Heart Association functional class III. Treatment: All patients were given 6 infusions of EPO monthly via peripheral venous access without significant side effects. Outcome: The PASP of all patients remained stable during the therapy. The therapeutic response as measured by patient symptoms and PASP was variable. No patient had significant reduction of PASP during the 6-month treatment period. Two patients developed rebound elevation of PASP after cessation of treatment, while the PASP of the other patient remained stable for 10 months. Conclusion: Although intermittent EPO infusion did not substantially reduce PASP, it prevented further rise in PAP during the treatment period, suggesting that this regimen may benefit a subset of SLE patients with PHT.

Paraneoplastic acral vascular syndrome: Epidemiologic features, clinical manifestations, and disease sequelae

Background: Acral vascular syndromes associated with malignancy have rarely been reported. Objective: Our purpose was to assess the clinical and evolving features of paraneoplastic acral vascular syndromes. Patients and Methods: Two cases of paraneoplastic gangrene are described and analyzed together with previously reported cases identified by a MEDLINE search. Results: Among the 68 patients identified, 40 had gangrene, 16 had acrocyanosis, and 12 had Raynaud's phenomenon. The male to female ratio was 0.89; median age was 59 years. Fingers were affected in 94%. Adenocarcinomas were the predominant associated malignancies (41%), and metastases were observed in 41%. The acral vascular syndromes in 48% of the patients definitively regressed after tumor treatment. Forty-four percent of the patients died within 2 years. A favorable cutaneous outcome was obtained with prostacyclin infusions in 6 patients. Conclusion: A neoplastic origin of acral vascular syndrome should be considered in elderly patients, especially men, in the absence of usual causative conditions. (J Am Acad Dermatol 2002;47:47-52.)

Effect of a Prostacyclin Analogue, Iloprost, on Urinary Aquaporin-2 Excretion in Humans

The regulation of aquaporin-2 (AQP2) water channel excretion in the collecting duct depends mainly on the action of vasopressin (AVP). Recently, however, other regulatory factors have been identified: atrial natriuretic factor, oxytocin and prostaglandins. In healthy volunteers (5 males, 5 females; mean age 23 ± 3 years) we therefore evaluated the effect of a stable analogue of prostacyclin-2 (PGI₂), iloprost, on renal function and on the urinary excretion of AQP2 (U-AQP2). After 6 h of iloprost infusion, U-AQP2 increased from 0.8 ± 0.15 to 1.8 ± 0.2 pmol/mg creatinine (p < 0.001), while the urinary flow rate increased from 1.4 ± 0.2 to 1.8 ± 4 (p < 0.01). No significant change was found in the AVP serum concentration, with a basal value of 3.17 ± 0.12 vs. 3.15 ± 0.12 pg/ml after 6 h of prostacyclin infusion. All the values returned to pre-study levels after a recovery period of 6 h. In conclusion, the PGI₂ analogue, iloprost, can induce U-AQP2 excretion independent of AVP.

Effects of beraprost sodium, an oral prostacyclin analogue, in patients with pulmonary arterial hypertension: a randomized, double-blind, placebo-controlled trial

ObjectivesThe purpose of this study was to assess the efficacy and safety of beraprost sodium, an orally active prostacyclin analogue, in New York Heart Association (NYHA) functional class II and III patients with pulmonary arterial hypertension (PAH). BackgroundPulmonary arterial hypertension is a life-threatening disease for which continuous intravenous infusion of prostacyclin has been proven effective. However, this treatment is associated with serious complications arising from the complex delivery system. MethodsIn this double-blind, placebo-controlled study, 130 patients with PAH were randomized to the maximal tolerated dose of beraprost (median dose 80 μg four times a day) or to placebo for 12 weeks. The primary end point was the change in exercise capacity assessed by the 6-min walk test. Secondary end points included changes in Borg dyspnea index, cardiopulmonary hemodynamics and NYHA functional class. ResultsPatients treated with beraprost improved exercise capacity and symptoms. The difference between treatment groups in the mean change of 6-min walking distance at week 12 was 25.1 m (95% confidence interval [CI]: 1.8 to 48.3, p = 0.036). The difference in the mean change of Borg dyspnea index was −0.94 (95% CI: −1.63 to −0.24, p = 0.009). In the sub-group of patients with primary pulmonary hypertension, the difference in the mean change of 6-min walking distance was 46.1 m (95% CI: 3.0 to 89.3, p = 0.035). Cardiopulmonary hemodynamics and NYHA functional class had no statistically significant changes. Drug-related adverse events were common in the titration phase and decreased in the maintenance period. ConclusionsBeraprost improves exercise capacity and symptoms in NYHA functional class II and III patients with PAH and, in particular, in those with primary pulmonary hypertension.

A New Classification of Pulmonary Hypertension

A New Classification of Pulmonary Hypertension

Cellular pathophysiology and therapy of pulmonary hypertension

The identification of several mutations of the bone morphogenetic protein receptor 2 (BMPR2) gene, a member of the transforming growth factor β receptor family, gives hope for new insights into the pathophysiology of pulmonary hypertension. Genetic predisposition might dictate the responses of pulmonary artery fibroblasts, smooth muscle cells, and endothelial cells, as well as platelets and leukocytes, or their specific interactions with different extrinsic factors. These cells possess distinct subtypes and interact with each other. Pulmonary hypertension is associated with vasoconstriction, remodeling, and in situ thrombosis of the pulmonary arteries, but the initial events and their relationship to the genetic background are presently unknown. Current therapeutic approaches are based on our knowledge of the physiologic regulation of pulmonary artery tone, pathophysiologic changes, and our clinical experience with different treatment strategies. Beyond diuretics and anticoagulants, prostaglandins are generally accepted therapeutic agents for primary pulmonary hypertension and related diseases, whereas high-dose calcium-channel blockers are reserved for a small subset of patients, those who respond favorably to vasodilators in an acute test. Long-term intravenous prostacyclin infusion has become the most important specific therapy for primary pulmonary hypertension and associated diseases. However, this therapy is hampered by catheter complications and systemic side effects. Alternative application routes of prostacyclin or its stable analogs may avoid these problems. Inhaled application of the prostacyclin analog iloprost results in predominant pulmonary vasodilation with few systemic side effects and may possess clinical efficacy similar to that of intravenous prostacyclin. Inhaled nitric oxide is widely accepted as a screening agent for active responders to vasodilators and has a similar hemodynamic profile as inhaled iloprost, although the percentage of responders is considerably lower. However, there are unsolved toxicologic questions and practical difficulties concerning the safe long-term application of nitric oxide. Combining inhaled vasodilators with phosphodiesterase inhibitors may prolong the duration of the effects and improve the convenience of inhaled therapy for pulmonary hypertension. Therapeutic approaches in the future may aim at the transforming growth factor β pathway and at the identification of early stages of the disease to prevent further disease progression. (J Lab Clin Med 2001;138:367-77)

Catastrophic Antiphospholipid Syndrome

Catastrophic Antiphospholipid Syndrome

Primary pulmonary hypertension in pregnancy; a role for novel vasodilators

We describe the case of a 28-week pregnant woman presenting with severe primary pulmonary hypertension (PPH). She had an elective Caesarean section under general anaesthesia at 32 weeks gestation. Pulmonary artery pressures (PAP) measured from a pulmonary artery catheter before anaesthesia were in excess of 100 mm Hg. Intraoperative nitric oxide was used to reduce PAP. After the delivery of a healthy infant PAP was controlled with nebulized iloprost and a prostacyclin infusion. Seven days later she was discharged from intensive care taking an oral calcium antagonist and warfarin. She developed intractable right heart failure and died 14 days after delivery. Despite increasing experience in the use of drugs to reduce PAP, the clinical course of pregnancy complicated by severe PPH is usually fatal.

Prostacyclin is neither sufficient alone nor necessary to cause pulmonary dysfunction: results from infusions of prostacyclin and antiprostacyclin antibody in porcine septic shock.

This study evaluated whether prostacyclin is a necessary mediator of inflammation in graded bacteremia or is sufficient alone in pathophysiologic concentrations to cause the pulmonary derangement of bacteremic shock. Experimental. Laboratory. Twenty-three anesthetized adult swine. INTERVENSIONS: Swine were studied in four groups for 4 hrs: a) an anesthesia control group (n = 6); b) a septic control group (n = 6), in which 1010/mL Aeromonas hydrophila was infused intravenously at 0.2 mL.kg-1.hr-1 and increased to 4.0 mL.kg-1.hr-1 over 3 hrs; c) a prostacyclin infusion group (n = 6), which received prostacyclin infusion to match septic control plasma concentrationsclm without bacteremia; and d) an antiprostacyclin antibody group (n = 5), which received continuous Aeromonas hydrophila infusion plus antiprostacyclin antibody infusion. Pulmonary hemodynamics, arterial blood gases, and plasma concentrations of arachidonate metabolites were measured hourly over a 4-hr period. In the septic control group and antiprostacyclin antibody group, elevated pulmonary vascular resistance index and pulmonary artery pressure with decreased Pao2, as well as lower pH, were documented after 1 and 3 hrs of graded bacteremia compared with the anesthesia control group and prostacyclin infusion group (p <.05). Thromboxane B2 concentration increased significantly in all groups during septic shock. In the antiprostacyclin antibody group, leukotriene B4 increased immediately after starting antiprostacyclin antibody infusion and reached significance at 3 hrs compared with the septic control group (p <.05). The prostacyclin infusion group had consistently lower concentrations of leukotrienes C4, D4, and E4 than all other groups. Prostacyclin does not mediate blood gas changes, alterations of pulmonary hemodynamics, or platelet abnormalities in porcine septic shock, because antiprostacyclin antibody infusion did not change the pulmonary hypertension and hypoxemia, and infusion of prostacyclin to pathophysiologic blood concentrations did not reproduce such changes. Antiprostacyclin blockade during bacteremia significantly increased concentrations of leukotrienes C4, D4, and E4 and leukotriene B4, whereas prostacyclin infusion suppressed concentrations of leukotrienes C4, D4, and E4, suggesting that endogenous prostacyclin may blunt leukotriene release.

Long-term prostacyclin infusion to reduce pulmonary hypertension in a pediatric cardiac transplant candidate prior to transplantation

Pulmonary hypertension represents a significant risk factor for peri-operative death in patients undergoing cardiac transplantation. Heart–lung transplantation is generally the only procedure available for patients whose pulmonary hypertension can not be reversed by conventional pharmacologic means. We present a pediatric patient with end-stage cardiac disease and refractory pulmonary hypertension who was treated with long-term intravenous prostacyclin. This resulted in a significant enough improvement in her hemodynamics to allow for successful cardiac transplantation alone.

Current and future strategies in the treatment of childhood pulmonary hypertension

Strategies for treating pulmonary hypertension in children vary with the severity and acuity of the disorder. Treatment of acute life threatening pulmonary hypertension is focused on principles of perioperative and critical care. These entail exclusion of anatomic and correctable causes of pulmonary hypertension, selective use of intracardiac right to left shunting, sedation, moderate hyperventilation and alkalosis, supplemental oxygen, normalization of lung volumes, judicious use of inotropic support and use of vasodilators. Newer vasodilators target excess or deficient endothelial cell production; prostacyclin and endothelin receptor blockers may be particularly useful after interventions such as cardiopulmonary bypass that render the pulmonary vascular endothelium transiently dysfunctional. Inhaled vasodilators, including aerosolized prostacyclin and inhaled nitric oxide, offer more selectivity and may improve intrapulmonary shunting in patients with pulmonary hypertension and concomitant lung disease. The underpinning for new treatments of chronic (including primary) pulmonary hypertension emphasizes discoveries in genetics and vascular biology which may permit new vessel growth, repair or remodeling, and even normalization of pathologic vessels in the lung. Traditional therapy for primary pulmonary hypertension involves supplemental oxygen, digoxin, diuretics, warfarin for older patients and calcium channel blockers for responders to acute testing. Recent trials have shown reduction in mortality and improvement in symptoms as well as the hemodynamic profile of patients treated with continuous prostacyclin infusions. Indeed, reversal of presumed progressive, fatal disease has been reported with prostacyclin, as well as with chronic inhaled nitric oxide. This is further inspired by exciting animal studies using elastase inhibitors, endothelin receptor blockers, type V phosphodiesterase inhibitors and gene transfer therapy to induce over expression of vasodilator genes, notably endothelial nitric oxide synthase and prostaglandin I synthase. These therapies alone or in combination offer promise for the future and hope of reversibility of even advanced forms of pulmonary hypertension.

An outcome study of severe traumatic head injury using the "Lund therapy" with low-dose prostacyclin.

There are two independent head injury outcome studies using the "Lund concept", and both showed a mortality rate of about 10%, and a favourable outcome (Glasgow outcome scale, GOS 4 and 5) of about 70%. The Lund concept aims at controlling intracranial pressure, and improving microcirculation around contusions. Intracranial pressure is controlled by maintaining a normal colloid osmotic pressure and reducing the hydrostatic capillary pressure. Microcirculation is improved by ensuring strict normovolaemia and reducing sympathetic discharge. The endogenous substance prostacyclin with its antiaggregatory/antiadhesive effects may further improve microcirculation, which finds support from a microdialysis-based clinical study and an experimental brain trauma study. The present clinical outcome study aims at evaluating whether the previously obtained good outcome with the Lund therapy can be reproduced, and whether the addition of prostacyclin has any adverse side-effects. All 31 consecutive patients with severe head injury, Glasgow coma scale (GCS) < or = 8, admitted to the University Hospital of Umeå during 1998 were included. The Lund therapy including prostacyclin infusion for the first three days at a dose of 0.5 ng kg(-1) min(-1). Outcome was evaluated according to the GOS >10 months after the injury. One patient died, another suffered vegetative state and 7 severe disability. Of the 22 patients with favourable outcome, 19 showed good recovery and 3 moderate disability. No adverse side-effects of prostacyclin were observed. The outcome results from previous studies using the Lund therapy were reproduced, and no adverse side-effects of low-dose prostacyclin were observed.

Infusion of prostacyclin following experimental brain injury in the rat reduces cortical lesion volume.

Endothelial-derived prostacyclin is an important regulator of microvascular function, and its main actions are inhibition of platelet/leukocyte aggregation and adhesion, and vasodilation. Disturbances in endothelial integrity following traumatic brain injury (TBI) may result in insufficient prostacyclin production and participate in the pathophysiological sequelae of brain injury. The objective of this study was to evaluate the potential therapeutic effects of a low-dose prostacyclin infusion on cortical lesion volume, CA3 neuron survival and functional outcome following TBI in the rat. Anesthetized animals (sodium pentobarbital, 60 mg/kg, i.p.) were subjected to a lateral fluid percussion brain injury (2.5 atm) or sham injury. Following TBI, animals were randomized to receive a constant infusion of either prostacyclin (1 ng/kg x min(-1) i.v.) or vehicle over 48 h. All sham animals received vehicle (n = 6). Evaluation of neuromotor function, lesion volume, and CA3 neuronal loss was performed blindly. By 7 days postinjury, cortical lesion volume was significantly reduced by 43% in the prostacyclin-treated group as compared to the vehicle treated group (p < 0.01; n = 12 prostacyclin, n = 12 vehicle). No differences were observed in neuromotor function (48 h and 7 days following TBI), or in hippocampal cell loss (7 days following TBI) between the prostacyclin- and vehicle-treated groups. We conclude that prostacyclin in a low dose reduces loss of neocortical neurons following TBI and may be a potential clinical therapeutic agent to reduce neuronal cell death associated with brain trauma.

A Noninvasive Assessment of Pulmonary Perfusion Abnormality in Patients With Primary Pulmonary Hypertension

The ventilatory equivalent for CO(2) (ie, the ratio of minute ventilation [VE] to carbon dioxide output [VCO(2)]) is increased in patients with primary pulmonary hypertension (PPH) consequent to an increase in physiologic dead space and alveolar ventilation. We wished to see whether the VE/V(2) ratio correlated with the abnormality in pulmonary hemodynamics in PPH patients and whether it changed in response to prostacyclin infusion. Following right-sided heart catheterization, 10 patients with severe PPH were studied in the coronary-care unit while hemodynamic and gas exchange measurements were measured simultaneously before and after infusion with epoprostenol (Epo), a prostacyclin analog. Studies were performed at baseline and during IV infusion of two to three increasing dosages of Epo in 10 PPH patients (NYHA class III-IV). Four patients had radial artery catheters for simultaneous blood gas measurements. Nine healthy subjects who were matched by sex, height, and weight underwent gas exchange analyses only. The mean (+/- SD) VE/VCO(2) ratio was higher in PPH patients than in control subjects (50.7 +/- 9.7 vs 30.6 +/- 3.8; p < 0.001). Thirteen measurements made in four patients showed that the VE/VCO(2) ratio correlated with the physiologic dead space/tidal volume ratio (r = 0.78; p = 0.002). The VE/VCO(2) ratio measurement at baseline correlated significantly with total pulmonary vascular resistance (TPVR) (r = 0.70; p = 0.02) but not with mean pulmonary artery pressure (mPAP) or cardiac index. During Epo infusion, the VE/VCO(2) ratio decreased with increasing dosage in 6 of 10 patients, with no change or slight increases in the 4 remaining patients. Considering all doses, the VE/VCO(2) ratio decreased significantly in response to the short-term administration of Epo. The decrease tended to parallel the pattern of decrease in TPVR, but the changes in both variables were too small to provide a statistically significant correlation. The mPAP did not change significantly in response to Epo infusion, although TPVR did change at the highest dosage. In patients with severe PPH, the VE/VCO(2) ratio correlated significantly with TPVR but not with mPAP or cardiac index. The VE/VCO(2) ratio decreased systematically from baseline with the dose of Epo in some but not all patients. The VE/VCO(2) ratio and TPVR decreased significantly in response to Epo when all doses were considered. Further studies are needed to elucidate whether noninvasive gas exchange measurements may be clinically useful in the evaluation of the severity of pulmonary vascular disease and the effectiveness of pulmonary vasodilator therapy.

Beneficial effects of low-dose prostacyclin on cat intestinal perfusion during endotoxemia as evaluated with microdialysis and oxygen transport variables.

To evaluate the effects of low-dose prostacyclin on intestinal perfusion during endotoxemia. A randomized, blinded experimental study. A university laboratory. Sixteen anesthetized cats. The animals received endotoxin by continuous intravenous infusion (0.5 mg/kg plus 0.5 mg x kg(-1) x hr(-1)) and a continuous volume replacement throughout the experiment. Four hours after the start of endotoxin, the animals were randomized to receive an infusion of either prostacyclin at a dose of 1 ng x kg(-1) x min(-1) (prostacyclin group) or vehicle (control group) during the next 4 hrs. Intestinal vascular resistance was calculated from systemic arterial pressure, central venous pressure, and superior mesenteric artery blood flow, and intestinal oxygen delivery and uptake were calculated from superior mesenteric artery and vein blood samples and blood flow. Interstitial lactate, pyruvate, glucose, and glycerol in the ileal wall were measured by using microdialysis. There were no differences in baseline values between the groups. Systemic blood pressure decreased initially but recovered and remained stable in both groups. In the control group, intestinal vascular resistance increased from 10.9 +/- 1.0 to 24.7 +/- 5.3 mm Hg x mL x min(-1) x kg(-1) (p <.05) at 8 hrs, and oxygen delivery decreased from 2.6 +/- 0.2 to 1.3 +/- 0.3 mL x min(-1) x kg(-1) (p <.05). Simultaneously, microdialysis lactate increased from 1.6 +/- 0.1 to 3.6 +/- 0.5 mmol/L (p <.05) with concomitant pyruvate increase and unchanged lactate/pyruvate ratio. Blood lactate increased and pH decreased. In the prostacyclin group at 8 hrs, intestinal vascular resistance of 6.9 +/- 0.8 mm Hg x mL x min(-1) x kg(-1) was lower and intestinal oxygen delivery of 3.2 +/- 0.3 was higher (p <.05) than in the control group at 8 hrs. Intestinal oxygen uptake of 0.54 +/- 0.10 mL x min(-1) x kg(-1) was higher than in the control group, in which oxygen uptake was 0.26 +/- 0.04 mL x min(-1) x kg(-1). Lactate, pyruvate, and pH were normalized at 8 hrs in the prostacyclin group. Low-dose prostacyclin has beneficial effects on small intestinal perfusion during endotoxemia in this experimental cat model.

訂正のお知らせ

訂正のお知らせ

Imbalance between platelet vascular endothelial growth factor and platelet-derived growth factor in pulmonary hypertension. Effect of prostacyclin therapy.

Focal vascular injury and impaired endothelial function are features of pulmonary hypertension (PH) that lead to enhanced platelet endothelial cell interactions. Vascular endothelial growth factor (VEGF) is contained in platelets and released at sites of vascular injury to promote endothelial repair and wound healing in combination with platelet-derived nonspecific mitogens such as platelet-derived growth factor (PDGF). The overall balance between platelet VEGF and PDGF was investigated in 21 patients with primary PH, 8 with secondary PH, and 27 with chronic hypoxemic lung disease (CHLD), as well as in 29 control subjects. Platelet VEGF content was increased in patients with primary and secondary PH as compared with control subjects (518 +/- 89, 675 +/- 156, and 166 +/- 29 fg/10(5) platelets, respectively; p < 0.01), whereas platelet PDGF content was similar in the three groups (31 +/- 2, 36 +/- 4, and 33 +/- 3 pg/10(5) platelets, respectively; NS). Patients treated with a continuous prostacyclin infusion had a higher platelet VEGF but a similar platelet PDGF content as compared with untreated patients. Moderate increases in platelet VEGF and PDGF contents were observed in the CHLD patients. We conclude that patients with primary or secondary PH have an increase in platelet VEGF content, but not in platelet PDGF content, and that their platelet VEGF content increases further in response to prostacyclin infusion. We suggest that imbalance between platelet VEGF and PDGF is beneficial to patients with PH.

Diagnosis and management of primary pulmonary hypertension.

Pulmonary arterial hypertension in children can occur secondary to shunt lesion like ventricular septal defect, patent ductus arteriosus or it may be idiopathic, the so-called primary pulmonary hypertension (PPH). The progression of PPH is usually rapid in children as compared to adults and the mean survival is 2-3 years after the diagnosis is made. Histological changes in the form of medical muscular hypertrophy, intinal hyperplasia and later angiornatous, plexiform lesions occur in pulmonary vasculature. The pulmonary vasculature normally is a high flow, low resistance circuit and allows large blood flow without marked increase in pulmonary arterial pressure. However, with prolonged increased flow or any other vasoconstrictor stimulus, histological changes start occurring in the pulmonary bed resulting in increasing pressure in pulmonary artery. Right ventricular hypertension follows resulting in right ventricular hypertrophy and later dysfunction. Life threatening arrhythmias may result in sudden death in some of these patients. Clinical presentation is in the form of exertional dyspnoea with syncope at times. Over 50% of children with PPH are helped by vasodilators. They may be treated with calcium channel blockers (e.g. nifedipine, dose titrated to blood pressure) orally. Those not responding to oral vasodilators can be put on chronic inhaled nitric oxide or continuous intravenous prostacyclin infusion. Chronic anticoagulation therapy may also increase survival. In symptomatic cases, blade/balloon atrial septostomy may increase survival in patients of PPH with intact atrial sptum. For children not responding to medical therapy, lung transplantation may be the answer in near future.

Cellular activation during haemofiltration and prostacyclin infusion

Cellular activation during haemofiltration and prostacyclin infusion

Hyperuricemia in Severe Pulmonary Hypertension

Hyperuricemia occurs frequently in patients with myeloproliferative and lymphoproliferative disorders and in patients with congenital heart disease associated with polycythemia. Whether hyperuricemia is common in patients with severe pulmonary hypertension is not known. In the Pulmonary Hypertension Center at the University of Colorado Health Sciences Center between September 1991 and August 1997, 442 consecutive patients were evaluated with right heart catheterization; 191 patients also had a measurement of the serum uric acid (UA) in close temporal proximity to the hemodynamic evaluation. Of the 191 patients with a complete data set, 99 patients had primary pulmonary hypertension (PPH) and 92 had secondary pulmonary hypertension. For the entire cohort with severe pulmonary hypertension (n = 191), there was a positive correlation between the natural logarithm of the serum UA (lnUA) and the mean right atrial pressure (RAP; r = 0.47; p < 0.001). When analyzed separately, the correlation between lnUA and RAP was stronger in the patients with PPH (r = 0.642; p < 0.001). This correlation cannot be explained by diuretic use or impaired hepatocellular function. Neither mean pulmonary artery pressure nor cardiac output was as well correlated with the RAP when compared with the lnUA. Some patients with PPH had serum UA measurements repeated during treatment with chronic IV prostacyclin infusion. Eleven of these 18 patients (61%) demonstrated a decrease in serum UA during prostacyclin treatment. There is a positive correlation between the RAP elevation and the serum UA levels in patients with PPH. Serum UA levels drop in some, but not all PPH patients during chronic prostacyclin infusion therapy.