Acute Vasoreactivity Research Articles

Evaluation of acute hemodymamic effect of inhaled iloprost in pulmonary artery hypertension with right heart catheterization

Pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH) are the major classes of pulmonary hypertensive disorders according to the World Health Organization; both lead to right heart failure and death. A better understanding of disease mechanisms has led to the suggestion that the thromboembolic and nonthromboembolic types of pulmonary hypertension may share pathophysiologic features. We therefore compared acute vasoreactivity and proximal pulmonary artery compliance in patients with PAH and CTEPH during the initial diagnostic heart catheterization.Right heart catheterization using a flow-directed Swan-Ganz catheter was performed in patients with CTEPH (n = 22) and PAH (n = 35). Pulmonary hemodynamics were assessed at baseline, during the inhalation of 40 ppm of nitric oxide, and 30 min after the inhalation of 10 μg of iloprost. To assess the proximal pulmonary artery compliance, the pulse pressure (PP) [systolic − diastolic pressure] and the fractional PP (PPf) [divided by the mean pressure] were calculated.Both vasodilators produced similar hemodynamic improvement, and the difference between CTEPH and PAH was not significant. The baseline PP and PPf did not vary between the two groups.Patients with PAH and CTEPH show similar acute vasoreactivity to inhaled nitric oxide and iloprost, and have similar pulmonary artery compliance. These findings support the presence of some shared pathophysiologic pathways in both disorders and may lead to therapeutic implications in patients with inoperable CTEPH.

Acute vasodilator testing in idiopathic pulmonary arterial hypertension: must we take NO for the answer?

The earliest clinical descriptions of primary pulmonary hypertension, now known as idiopathic pulmonary arterial hypertension (IPAH), were accompanied by the hypothesis that pulmonary vasoconstriction was one of its key pathophysiological elements 1 and that vasodilators could, therefore, be therapeutically useful. In support of this concept, Dresdale et al. 2 first reported attenuation of pulmonary hypertension with the systemic vasodilator tolazoline, while Harris 3 and Wood et al. 4 achieved more preferential pulmonary vasodilation with acetylcholine infused directly in the pulmonary artery. Only years later, when Furchgott and Zawadzki 5 demonstrated that acetylcholine-induced vasodilation was mediated by nitric oxide (NO), an observation for which R.F. Furchgott shared the Nobel Prize in Medicine in 1998, was the importance of endothelial dysfunction in the pathogenesis of IPAH appreciated, and the rationale for testing acute vasoreactivity in IPAH using inhaled NO (iNO) or other endothelial-derived vasodilator substances established. When Rich and Brundage 6 treated patients with high-dose calcium channel blockers (CCBs) in an attempt to reverse pulmonary vasoconstriction it became clear, however, that only a subgroup of IPAH patients responded with haemodynamic and clinical improvement. Furthermore, since it was impossible to identify a priori any clinical or haemodynamic predictors for a positive responder status, nonresponders were subjected both acutely and chronically to the risks of potent systemic vasodilator agents without any chance of benefit. Additionally, the criteria for “acute response” that was predictive of at least a reasonable chance of achieving a favourable long-term response to treatment with CCB was not clear …

Pulmonary Vascular Reactivity and Prognosis in Patients With Chronic Thromboembolic Pulmonary Hypertension

Surgical pulmonary endarterectomy is the preferred treatment for chronic thromboembolic pulmonary hypertension. Persistent pulmonary hypertension after pulmonary endarterectomy has been recognized as a major determinant of poor outcome. We tested whether acute vasoreactivity identifies chronic thromboembolic pulmonary hypertension patients prone to develop persistent/recurrent pulmonary hypertension after pulmonary endarterectomy and whether the degree of acute vasoreactivity affects survival or freedom from lung transplantation. Right-sided heart catheterization at baseline and after inhalation of 40 ppm nitric oxide for 20 minutes was performed in 103 patients (56.3+/-15.3 years old, 53 women). Reductions in mean pulmonary arterial pressure (DeltamPAP; -8.8+/-12.6%; P<0.0001) and pulmonary vascular resistance (-16.1+/-18.1%; P<0.0001) and an increase in mixed venous saturation during inhaled nitric oxide (9.1+/-11.6%; P<0.0001) were observed. Sixty-two patients underwent pulmonary endarterectomy after a median of 49 days (25th and 75th percentiles: 24 and 123 days). Operated patients were followed up for a median of 70.9 months (25th and 75th percentiles: 14 and 97 months). Change in mPAP during inhaled NO was identified as a predictor of persistent/recurrent pulmonary hypertension after pulmonary endarterectomy. Patients experiencing a reduction in mPAP >10.4% with nitric oxide inhalation had a better postoperative outcome. A significant correlation was found between DeltamPAP and immediate postoperative pulmonary vascular resistance (r=0.5, P<0.0001). A total of 80 (77.7%) of 103 patients demonstrated acute pulmonary vascular reactivity of some degree. A decrease in mPAP >10.4% under inhaled nitric oxide is a predictor of long-term survival and freedom from lung transplantation in adult patients with chronic thromboembolic pulmonary hypertension who are undergoing pulmonary endarterectomy.

Prognosis After Heart Transplant in Patients With Pulmonary Hypertension Secondary to Cardiopathy

Introduction Pulmonary hypertension (PHT) is associated with greater posttransplant mortality. In the last few years, many vasodilator drugs have been developed and some patients have therefore been transplanted. However, conflicting data exist regarding the impact of reversible PHT on posttransplant outcomes. The aim of this study was to determine the evolution of our transplanted patients with reactive PHT and the causes of right cardiac insufficiency and perioperative mortality. Material and Methods We performed a retrospective analysis of 39 consecutive heart transplant recipients from January 2005 to December 2006. We analyzed significant pretransplant PHT, the percentage of emergency transplants, surgical technique, as well as ischemia and extracorporeal circulation times. Results Before transplantation, significant PHT was present in 12 patients (30.8%), all of whom had a positive acute vasoreactivity test or response to oral treatment with pulmonary vasodilators. A nonsignificant tendency to increased posttransplant mortality was observed among patients with pretransplant PHT. We observed a significant increase in mortality in patients with prolonged operative times, over the third percentile, odds ratio (OR) for ECC of 21% ( P = .001) and OR for prolonged ischemia time of 9.5% ( P = .022). However, mortality did not increase significantly in cases of emergent transplantation ( P = .08) or in the use of the Shumway bicaval surgical technique ( P = .9). Conclusions There seemed to be a slight tendency to increased mortality among patients with reversible HTP, suggesting that high-risk patients need closer monitoring but are not absolutely contraindicated for transplantation.

Clinical Implications of Determining BMPR2 Mutation Status in a Large Cohort of Children and Adults With Pulmonary Arterial Hypertension

Bone morphogenetic protein receptor type 2 (BMPR2) mutations occur in idiopathic and familial pulmonary arterial hypertension (IPAH, FPAH); however, the impact of these mutations on clinical assessment and disease severity remains unclear. We investigated the role of BMPR2 mutations on acute vasoreactivity and disease severity in IPAH/FPAH children and adults. BMPR2 mutation types were determined in 147 IPAH/FPAH patients. Hemodynamics were obtained at baseline and with acute vasodilator testing. Of 147 patients (69 adults, 78 children; 114 with IPAH, 33 with FPAH), 124 (84%) were BMPR2 mutation-negative, and 23 (16%) were mutation-positive. BMPR2 mutation-positive patients were less likely to respond to acute vasodilator testing than mutation-negative patients (4% vs 33%; p < 0.003; n = 147). BMPR2 mutation-positive children also appeared less likely to respond to acute vasodilator testing than mutation-negative children. BMPR2-positive patients had lower mixed venous saturation (57 +/- 9% vs 62 +/- 10%; p < 0.05) and cardiac index (CI; 2.0 +/- 1.1 vs 2.4 +/- 1.5 liters/min; p < 0.05) than BMPR2-negative patients. Patients with BMPR2 mutations are less likely to respond to acute vasodilator testing than mutation-negative patients and appear to have more severe disease at diagnosis. Determination of BMPR2 mutations appears to help identify IPAH/FPAH children and adults who are unlikely to respond to acute vasodilator testing and, thus, unlikely to benefit from calcium channel blockade (CCB) treatment.

Impaired peripheral endothelial function in severe idiopathic pulmonary hypertension correlates with the pulmonary vascular response to inhaled iloprost

Pulmonary endothelial function is known to be impaired in subjects with idiopathic pulmonary arterial hypertension (IPAH), but peripheral endothelial dysfunction and its predictive value for pulmonary vasoreactivity have not been previously investigated. Measurements of peripheral endothelium-dependent and endothelium-independent vasoreactivity using flow-mediated dilation (FMD) and nitroglycerin-mediated dilation of the brachial artery were performed in 18 patients with severe IPAH (15 women; mean age 50 years [95% confidence interval 46-55 years], mean pulmonary artery pressure [PAP] 51 mm Hg [43-59 mm Hg], pulmonary vascular resistance [PVR] 1239 dyn s cm(-5) [861-1618 dyn s cm(-5)] at baseline) and in 36 age- and sex-matched controls. In patients with IPAH, acute pulmonary vasoreactivity was measured as pulmonary vascular response to inhaled iloprost (PVRII) during pulmonary catheterization. Compared to controls, patients with IPAH demonstrated impaired peripheral endothelial function (FMD, 0.19 [0.07-0.31] vs 0.38 [0.30-0.44] mm among controls; P =.002). No such impairment was observed for nitroglycerin-mediated dilation (0.34 [0.23-0.46] vs 0.36 [0.20-0.51] mm among controls; P = .679). Among patients with IPAH, iloprost lowered mean PAP by 8.2 mm Hg (2.0-14.5 mm Hg) (P = .001) and PVR by 395 dyn s cm(-5) (109-680 dyn s cm(-5)) (P < .001). Subsequent analysis of the association between peripheral endothelial function and PVRII disclosed a correlation of FMD with the percent decrease in mean PAP (r = .65, P = .003) and PVR (r = 0.67, P = .002), in which patients with IPAH with the greatest PVRII also exhibited the highest FMD values. Idiopathic pulmonary arterial hypertension is associated with peripheral endothelial dysfunction. Peripheral endothelium-dependent vasoreactivity correlates with the PVRII. It remains to be established if FMD has the potential as a clinical tool for noninvasive estimation of pulmonary vasoreactivity in IPAH.

Chronic Thromboembolic and Pulmonary Arterial Hypertension Share Acute Vasoreactivity Properties

Pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH) are the major classes of pulmonary hypertensive disorders according to the World Health Organization; both lead to right heart failure and death. A better understanding of disease mechanisms has led to the suggestion that the thromboembolic and nonthromboembolic types of pulmonary hypertension may share pathophysiologic features. We therefore compared acute vasoreactivity and proximal pulmonary artery compliance in patients with PAH and CTEPH during the initial diagnostic heart catheterization. Right heart catheterization using a flow-directed Swan-Ganz catheter was performed in patients with CTEPH (n = 22) and PAH (n = 35). Pulmonary hemodynamics were assessed at baseline, during the inhalation of 40 ppm of nitric oxide, and 30 min after the inhalation of 10 mug of iloprost. To assess the proximal pulmonary artery compliance, the pulse pressure (PP) [systolic-diastolic pressure] and the fractional PP (PPf) [divided by the mean pressure] were calculated. Both vasodilators produced similar hemodynamic improvement, and the difference between CTEPH and PAH was not significant. The baseline PP and PPf did not vary between the two groups. Patients with PAH and CTEPH show similar acute vasoreactivity to inhaled nitric oxide and iloprost, and have similar pulmonary artery compliance. These findings support the presence of some shared pathophysiologic pathways in both disorders and may lead to therapeutic implications in patients with inoperable CTEPH.

N-Terminal Pro-B-Type Natriuretic Peptide as an Indicator of Disease Severity in a Heterogeneous Group of Patients With Chronic Precapillary Pulmonary Hypertension

N-terminal-pro-B-type natriuretic peptide (NT-pro-BNP) is well established as a predictor of prognosis in patients with left ventricular dysfunction. Although a similar prognostic significance has been suggested in 1 study of right ventricular failure and idiopathic pulmonary arterial hypertension, NT-pro-BNP has not been assessed as a marker of disease severity in a more heterogenous group of patients with chronic precapillary pulmonary hypertension (PH). Hence, this study assessed plasma NT-pro-BNP and other clinical variables in 61 consecutively recruited patients with various forms of chronic precapillary PH. Right-sided cardiac catheterization and cardiopulmonary exercise testing were performed at baseline, and the prognostic significance of NT-pro-BNP was investigated with a mean follow-up of 25 months. Compared with age-matched controls (n = 10), plasma NT-pro-BNP was significantly greater in those with idiopathic pulmonary arterial hypertension (n = 16), chronic precapillary PH associated with other diseases (n = 26), and chronic thromboembolic disease (n = 19) and was correlated with hemodynamic variables and functional capacity. In 17 medically treated patients, the significant decrease in NT-pro-BNP levels correlated with improved hemodynamics. During follow-up, 15 patients died from cardiopulmonary causes. Baseline NT-pro-BNP was an independent predictor of mortality. Kaplan-Meier survival analysis according to the median value of NT-pro-BNP (168 pmol/L) demonstrated a significantly higher mortality rate in those with supramedian values than in those with low plasma levels (p = 0.010). In conclusion, these findings suggest that in a heterogenous group of patients with chronic precapillary PH, plasma NT-pro-BNP can be used to determine the clinical severity of disease and is independently associated with long-term mortality.

Selective serotonin reuptake inhibitor use and outcomes in pulmonary arterial hypertension

Background Pulmonary arterial hypertension (PAH) is characterized by elevated pulmonary vascular resistance which leads to right ventricular failure. Serotonin and the serotonin transporter play an important role in animal and human studies of PAH. We therefore hypothesized that PAH patients treated with high-affinity selective serotonin reuptake inhibitors (SSRIs) would have a reduced risk of death compared to PAH patients not treated with SSRIs. Methods We performed a retrospective cohort study of 84 consecutive adult PAH patients who underwent initial evaluation from January 1994 to June 2002 at the Pulmonary Hypertension Center of the New York Presbyterian Hospital. Patient–time while receiving high-affinity SSRIs ( K d<1 nmol) (paroxetine, sertraline, or fluoxetine) was considered “exposed”. Patient–time while receiving tricyclic, atypical, or no antidepressants was considered “unexposed”. Results Thirteen of the 84 patients (15%) used high-affinity SSRIs during the study period. Five patients were taking high-affinity SSRIs at baseline and 8 initiated high-affinity SSRIs during the follow-up period. The median time from baseline evaluation until initiation of high-affinity SSRIs was 125 (0–1227) days. The median duration of high-affinity SSRI use was 482 (110–1624) days and the total at-risk time on high-affinity SSRIs was 18.1 person-years. Seventy-nine (94%) patients were treated with warfarin; 38 (45%) received continuous intravenous epoprostenol; 12 (14%) received continuous subcutaneous treprostinil, and 23 (27%) were treated with oral bosentan. The median follow-up was 764 days. Twenty-four patients died and one underwent lung transplantation during the study period. There were no differences in age, gender, diagnosis, hemodynamics, or incidence of acute vasoreactivity between SSRI users and non-users. The risk of death for high-affinity SSRI users was lower but not statistically significantly different from that of non-users (hazard ratio=0.53, 95% CI 0.07 to 3.9, p = 0.53 ). Adjustment for demographics, diagnosis, hemodynamics, or other therapies did not significantly change this result. Conclusions SSRI use was associated with a 50% reduction in the risk of death in a cohort of PAH patients which was not statistically significant. Larger cohort studies may better define this relationship; an adequately powered trial of high-affinity SSRIs in PAH patients may be warranted.

Chronic Thromboembolic and Pulmonary Arterial Hypertension Share Acute Vasoreactivity Properties

Structural and functional changes in the vascular wall and thrombus formation are the main factors responsible for increased pulmonary vascular resistance in patients with pulmonary hypertension (PH).1,2 The contribution of each of these factors is thought to be different among the variable underlying causes of PH, thereby accounting for varying response to vasodilatative and antiproliferative agents in PH of different aetiology.3 Accordingly, pulmonary vasodilators have been used primarily for patients with pulmonary arterial hypertension (PAH) an

Issue Highlights

HomeCirculationVol. 111, No. 23Issue Highlights Free AccessIn BriefPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessIn BriefPDF/EPUBIssue Highlights Originally published14 Jun 2005https://doi.org/10.1161/circ.111.23.3015Circulation. 2005;111:3015ALDOSTERONE SYNTHASE INHIBITOR AMELIORATES ANGIOTENSIN II–INDUCED ORGAN DAMAGE, by Fiebeler et al.Aldosterone has been shown to contribute to angiotensin II–induced end-organ damage, and clinical studies have confirmed the benefit of adding aldosterone antagonists to angiotensin-converting enzyme inhibitor agents to prevent adverse remodeling. Angiotensin II increases circulating levels of aldosterone levels as well as de novo tissue synthesis of aldosterone by stimulating aldosterone synthase (CYP11B2); however, it is unknown which source of aldosterone plays a greater role in tissue remodeling and damage. In these studies, Fiebeler et al examine this question by utilizing both FAD286, a novel CYP11B2 inhibitor, and adrenalectomy in transgenic rats overexpressing human renin and angiotensinogen genes. Using these models, they are able to isolate the source of aldosterone that modulates some of the adverse cardiac and renal effects associated with hyperaldosteronism. See p 3087.LONG-TERM RESPONSE TO CALCIUM CHANNEL BLOCKERS IN IDIOPATHIC PULMONARY ARTERIAL HYPERTENSION, by Sitbon et al.Characteristics of patients with idiopathic pulmonary arterial hypertension (IPAH) who benefit from long-term calcium channel blockers (CCBs) are unknown. Sitbon and colleagues performed acute pulmonary vasodilator testing with epoprostenol or nitric oxide during initial right heart catheterization in 557 IPAH patients. Acute responders were treated initially with oral CCB. Long-term CCB responders were defined as those being in functional class I or II after at least 1 year on CCB monotherapy. Among the 70 patients (12.6%) who displayed acute pulmonary vasoreactivity and received CCB therapy, 38 (6.7%) improved long term. Long-term CCB responders had less severe disease at baseline and displayed a more pronounced fall in mean pulmonary artery pressure during acute vasodilator testing. Of note, long-term CCB responders represented less than 10% of IPAH patients evaluated in a pulmonary vascular referral center. These data suggest that routine administration of CCB as first-line therapy in IPAH patients may be ill advised. See p 3105.APOLIPOPROTEIN E MIMETIC PEPTIDE DRAMATICALLY LOWERS PLASMA CHOLESTEROL AND RESTORES ENDOTHELIAL FUNCTION IN WATANABE HERITABLE HYPERLIPIDEMIC RABBITS, by Gupta et al.Elevated high-density lipoprotein (HDL) levels are associated with a reduction in the frequency of cardiovascular events. To develop new drugs for the treatment of atherosclerosis, investigators have been evaluating the therapeutic properties of HDL components in both animal models of vascular disease and patients with coronary atherosclerosis. However, some of these agents are structurally complex and difficult to produce. In this issue of Circulation, Gupta et al analyze the atheroprotective properties of a synthetic peptide containing the arginine-rich receptor-binding domain of ApoE fused to an amphipathic helical peptide that possesses ApoA-I–like properties. A single administration of the dual-domain peptide dramatically reduces plasma cholesterol levels and improves vascular reactivity in a dyslipidemic rabbit model. These improvements coincide with a reduction in markers of oxidative stress that are associated with vascular inflammation. These data suggest that this HDL-mimetic peptide could make ‘good‘ cholesterol better and have utility for the treatment of atherosclerosis. See p 3112.Visit http://www.circ.ahajournals.org:Cardiology Patient PageHow to Respond to an Implantable Cardioverter-Defibrillator Shock. See p e380.Images in Cardiovascular MedicineReversible Right Ventricular Hypertrophy Due to Cardiac Sarcoidosis. See p e383. Download figureDownload PowerPointThree-Dimensional Imaging in Rupture of Papillary Muscle After Acute Myocardial Infarction. See p e385.Angiosarcoma of the Pericardium: A Fatal Disease. See p e388.CorrespondenceSee p e390. Previous Back to top Next FiguresReferencesRelatedDetails June 14, 2005Vol 111, Issue 23 Advertisement Article InformationMetrics https://doi.org/10.1161/circ.111.23.3015 Originally publishedJune 14, 2005 PDF download Advertisement

Long-Term Response to Calcium Channel Blockers in Idiopathic Pulmonary Arterial Hypertension

Characteristics of patients with idiopathic pulmonary arterial hypertension (IPAH) who benefit from long-term calcium channel blockers (CCB) are unknown. Acute pulmonary vasodilator testing with epoprostenol or nitric oxide was performed in 557 IPAH patients. Acute responders, defined by a fall in both mean pulmonary artery pressure (PAP) and pulmonary vascular resistance (PVR) >20%, received long-term oral CCB. Patients who benefit from long-term CCB were defined as those being in New York Heart Association (NYHA) functional class I or II after at least 1 year on CCB monotherapy. Among the 70 patients who displayed acute pulmonary vasoreactivity (12.6%; 95% CI, 9.8% to 15.3%) and received CCB therapy, only 38 showed long-term improvement (6.8%; 95% CI, 4.7% to 8.9%). Long-term CCB responders had less severe disease at baseline than patients who failed. During acute vasodilator testing, long-term CCB responders displayed a more pronounced fall in mean PAP (-39+/-11% versus -26+/-7%; P<0.0001), reaching an absolute value of mean PAP lower than that measured in patients who failed (33+/-8 versus 46+/-10 mm Hg; P<0.0001). After 7.0+/-4.1 years, all but 1 long-term CCB responders were alive in NYHA class I or II, with a sustained hemodynamic improvement. In the group of patients who failed on CCB, the 5-year survival rate was 48%. Long-term CCB responders represent <10% of IPAH patients evaluated in a pulmonary vascular referral center. During acute vasodilator testing, these patients showed significantly lower levels of both mean PAP and PVR, which reached near-normal values.

New predictors of outcome in idiopathic pulmonary arterial hypertension

Idiopathic pulmonary arterial hypertension (PAH) is a rare disease with a poor prognosis. New therapies have improved the outcome of this condition; accordingly, the factors that determine outcome may have changed. We aimed to identify determinants of survival in a cohort of consecutive patients with PAH: which was idiopathic, familial, or associated with anorexigen use. We performed a retrospective cohort study of 84 consecutive patients with PAH who underwent initial evaluation at our center from January 1994 to June 2002. The primary outcome was death or lung transplantation. Survival at 1, 3, and 5 [corrected] years was 87%, 75%, and 61%, respectively. Multivariate analysis showed that being of African-American or Asian descent was associated with an increased risk of death. Warfarin use was associated with a reduced risk of death. Higher serum albumin and cardiac index and acute vasoreactivity were independently associated with improved survival. These data suggest that the determinants of outcome have changed. Race is identified as a new risk factor, which may be attributable to biologic or socioeconomic differences. Cardiac function and acute reactivity of the pulmonary vascular bed remain strong independent predictors of outcome.

Advances in Prostacyclin Therapy for Pulmonary Arterial Hypertension

Advances in Prostacyclin Therapy for Pulmonary Arterial Hypertension

Pulmonary Edema Caused by Inhaled Nitric Oxide Therapy in Two Patients With Pulmonary Hypertension Associated With the CREST Syndrome

Pulmonary arterial hypertension (PAH) is commonly associated with the CREST (calcinosis, Raynaud phenomenon, esophageal dysmotility, sclerodactyly, telangiectasia) syndrome. Inhaled nitric oxide (iNO) is often used to assess acute vasoresponsiveness in patients with PAH, and reports of adverse reactions have been infrequent. We describe two of nine patients with PAH and CREST syndrome who had pulmonary edema develop during acute iNO testing. This complication was not encountered in the 46 patients with other forms of PAH tested with iNO. We suggest that iNO should be used with caution, if at all, to test acute vasoreactivity in patients with CREST syndrome.

Circulating Immunoreactive Endothelin-1 in Children with Pulmonary Hypertension: Association with Acute Hypoxic Pulmonary Vasoreactivity

To determine whether circulating levels of endothelin-1 (ET-1), a potent vasoconstrictor peptide, are elevated in children with pulmonary hypertension and related to the degree of hypoxic pulmonary vasoconstriction, we measured arterial and mixed venous plasma concentrations of immunoreactive ET-1 (irET-1) in 13 children during cardiac catheterization. Clinical diagnoses in seven children with pulmonary hypertension (PH) included chronic lung disease (four children), congenital heart disease after surgical repair (two children), and primary ("reactive") pulmonary hypertension (one child). Blood samples were simultaneously obtained from pulmonary artery (venous) and systemic arterial sites during baseline conditions. Plasma irET-1 was elevated in children with PH (12.3 +/- 3.4 versus 3.6 +/- 0.7 pg/ml, PH versus non-PH; p < 0.01). Arterial/venous irET-1 ratios in the PH group (1.1 +/- 0.2) were not different from those in the non-PH group. During acute hypoxia, mean Ppa increased from 27 +/- 3 to 40 +/- 5 mm Hg. Basal irET-1 correlated strongly with the degree of elevation of mean Ppa during acute hypoxia (r = 0.69; p < 0.02). We conclude that irET-1 levels are often elevated in children with PH, and they are strongly correlated with pulmonary vasoreactivity during acute hypoxia. Whether elevated irET-1 levels contribute directly to or are markers of altered pulmonary vascular tone and reactivity in children with PH remains speculative.

Current Approach to Treatment of Primary Pulmonary Hypertension

Based upon our experience with a cohort of 46 patients referred to the UCHSC from April, 1980 to April, 1987 for evaluation and treatment of PPH, we currently assess acute pulmonary vasoreactivity as defined by the patient's response to intravenous PGI2 during the initial diagnostic catheterization. A 3 to 5 day trial of high dose oral diltiazem treatment (720 mg/day maximum) is given while monitoring the patient in the clinical research center to detect significant side effects including arrhythmias, orthostatic systemic hypotension, arterial desaturation, and worsened right ventricular dysfunction. We believe it is necessary to recatheterize each patient to establish the efficacy of calcium antagonist treatment prior to discharge. Those patients who are responsive to diltiazem are discharged and followed in our pulmonary hypertension clinic. Since an occasional patient will deteriorate after several weeks of therapy, repeat right heart catheterization after 8 weeks of treatment is used to determine which patients should be continued on diltiazem for chronic therapy. Approximately 30 percent of our patients with PPH have been improved on diltiazem treatment. Most patients who have a good response to treatment after eight weeks continue to benefit from long-term treatment. It appears that the response to an acute infusion of PGI2 is useful in safely identifying those PPH patients who are likely to benefit from vasodilator therapy. Debilitated patients who are unresponsive to PGI2 and vasodilator therapy are considered potential candidates for cardiopulmonary transplantation.

Sympathetic ophthalmia following an operation for retinal detachment.

Introduction: Vasoreactivity testing with inhaled nitric oxide (iNO) is recommended in patients with pulmonary arterial hypertension (PAH) because of therapeutical and prognostic implications. Sildenafil is a promising agent for acute vasoreactivity testing since it is more stable and easier to handle than iNO. But it is not known if the acute responses to sildenafil and NO are equal. Objectives: The aim of this study is to compare acute vasoreactivity in response to sildenafil vs iNO in patients with PAH. Methods: In this retrospective, open-label, and single-centre study we included all patients who were admitted to our adult pulmonary hypertension unit from 2002 to 2011, met the criteria for PAH, and underwent vasoreactivity testing with iNO and sildenafil. Results: 198 patients were included. 9.6% of the patients met the responder criteria (as defined by the current guidelines) for iNO and 11.6% for sildenafil. Intra-individually, the responses in mPAP and cardiac index (CI) after sildenafil and NO administration correlated (r_mPAP= 0.516, p&lt;0.001, r_CI=0.521, p&lt;0.001). At mean there was a significantly higher CI after sildenafil than after iNO application (CI_NO=2.40±0.69l/min/m²; CI_sildenafil=2.56±0.76l/min/m²). Applying the current response criteria, the sensitivity to detect NO-responders by sildenafil vasoreactivity was 81.3%, the specificity was 94%, the positive predicitive value was 56%. Conclusions: In PAH patients the vasoreactive response to sildenafil is stronger than to iNO. The intra-individual vasoreactive responses to both drugs correlate. The sensitivity to detect NO-responders by using sildenafil for vasoreactivity testing was moderate, but the positive predictive value was low.