Adenosine plasma concentration in pulmonary hypertension.

OBJECTIVE: In this study, we sought to appreciate the role of adenosine in the regulation of pulmonary vascular tone, especially in the case of clinical pulmonary hypertension, by investigating the relationship between endogenous plasma adenosine levels and pulmonary artery vasoconstriction. METHODS: Adenosine plasma concentrations, were measured simultaneously in the distal right pulmonary artery and in the femoral artery, both at steady state (room air) and during pure oxygen inhalation. Three clinical situations were considered: (1) normal hemodynamics [7 control subjects, mean pulmonary artery pressure (MPAP) = 18.5 +/- 1 mm Hg], (2) moderate pulmonary hypertension secondary to chronic obstructive pulmonary disease (COPD), (8 patients, MPAP = 31 +/- 3 mm Hg), (3) severe primary pulmonary hypertension (PPH), (8 patients, MPAP = 70 +/- 5 mm Hg). RESULTS: In every instance, adenosine evaluated by HPLC was higher in the pulmonary than in the systemic circulation. For room air, adenosine plasma concentrations were significantly lower in COPD (0.49 +/- 0.16 mumol l-1) and PPH patients (0.45 +/- 0.14 mumol l-1) than in controls (1.26 +/- 0.12 mumol l-1). During O2 administration, adenosine plasma concentrations all decreased but more so in COPD and PPH patients. The significant correlations between adenosine plasma concentrations and both pulmonary vascular resistance and PvO2, in controls, were not found in COPD or PPH patients. CONCLUSION: The adenosine plasma concentrations in the pulmonary circulation of PPH and COPD patients are low, and may contribute to pulmonary artery hypertension.     

Thrombotic risk factors in pulmonary hypertension.

Thrombotic lesions are consistently observed in chronic thromboembolic pulmonary hypertension (CTEPH) and frequently found in primary pulmonary hypertension (PPH). It remains unknown, however, whether thrombosis is related to defects of the antithrombotic pathway or to previous vascular injury. This study therefore analysed the frequency of both hereditary and acquired thrombotic risk factors in CTEPH and PPH. One hundred and forty-seven consecutive patients with CTEPH investigated in the author's institution were compared to 99 consecutive patients with PPH. In 116 CTEPH patients and 83 PPH patients, phospholipid-dependent antibodies (antiphospholipid antibodies and lupus anticoagulant) were analysed by both immunological and clotting assays. In patients enrolled since 1994 (46 CTEPH and 64 PPH), hereditary thrombotic risk factors were also determined. Antithrombin, protein C and protein S activities were measured by functional assays. Mutations of factor V and factor II were identified by polymerase chain reaction. The prevalence of hereditary thrombotic risk factors was not increased in patients with either PPH or CTEPH. In contrast, a high frequency of phospholipid-dependent antibodies was observed in PPH (10%) and more notably in CTEPH (20%). Moreover, in PPH, antibodies were present only in low titre whereas in CTEPH, half of the patients with antiphospholipid antibodies had high titres. In addition, in CTEPH all but one of the patients with lupus anticoagulant also had antiphospholipid antibodies. The most striking finding of this study was the high prevalence of phospholipid-dependent antibodies but their clinical relevance appears to be different in primary pulmonary hypertension and chronic thromboembolic pulmonary hypertension. In primary pulmonary hypertension, these antibodies in low titre probably reflect endothelial dysfunction. In contrast, in chronic thromboembolic pulmonary hypertension the presence of antibodies in high titre associated with lupus anticoagulant, underlines the role of thrombosis in the pathogenesis of this condition.     

Plasma beta-endorphin and adenosine concentration in pulmonary hypertension

To determine whether beta-endorphin plays a role in the regulation of pulmonary vascular tone in patients with pulmonary hypertension, we investigated the relations between hemodynamics and beta-endorphin and adenosine concentrations in 3 clinical situations: (1) normal hemodynamics (7 subjects, mean pulmonary artery [PA] pressure 18.5 +/- 1 mm Hg); (2) moderate pulmonary hypertension secondary to chronic obstructive pulmonary disease (COPD) (8 patients, mean PA pressure 31 +/- 3 mm Hg); and (3) severe primary pulmonary hypertension (PPH) (8 patients, mean PA pressure 70 +/-5 mm Hg). Plasma beta-endorphin and adenosine were measured in a distal PA and in the femoral artery in room air and during oxygen inhalation. Beta-endorphin levels were similar in the pulmonary and systemic circulations. No difference was observed between patients with COPD and PPH, but relative to controls, both had significantly higher beta-endorphin levels. Pulmonary adenosine was significantly lower in patients with pulmonary hypertension than in controls (-60% in COPD [p <0.005] and -70% in PPH [p <0.001]). Pure oxygen administration significantly decreased adenosine and beta-endorphin levels, much more so in patients with COPD and PPH. We found a negative correlation between beta-endorphin and adenosine concentrations (r = -0.751, p <0.001): the higher the adenosine, the lower the beta-endorphin level. These observations suggest that because adenosine release by pulmonary vascular endothelium is reduced in pulmonary hypertension, the resulting worsened hypoperfusion and tissue oxygenation may cause increased beta-endorphin release.     

Atrial natriuretic peptide in severe primary and nonprimary pulmonary hypertension: response to iloprost inhalation

OBJECTIVES: The goal of this study was to assess atrial natriuretic peptide (ANP) levels during inhalation of iloprost in severe primary (PPH) and nonprimary pulmonary hypertension (NPPH). BACKGROUND: The ANP system is activated in pulmonary hypertension and may help protect from right ventricular (RV) decompensation. It is unknown if ANP regulation is the same in severe PPH and NPPH and if the dynamic regulation is intact in a highly activated ANP system. METHODS: In 11 patients with PPH and seven patients with NPPH, right heart catheter investigations were performed. Pulmonary and systemic artery ANP and cyclic guanosine monophosphate (cGMP) levels as well as hemodynamics were measured before and after iloprost inhalation. RESULTS: The baseline hemodynamics of patients with PPH and patients with NPPH were comparable (mean pulmonary artery pressure [mPAP]: 61 +/- 5 mm Hg vs. 52 +/- 5 mm Hg, pulmonary vascular resistance [PVR]: 1,504 +/- 153 dyne.s.cm(-5) vs. 1,219 +/- 270 dyne.s.cm(-5). Atrial natriuretic peptide and cGMP levels were increased about tenfold and fivefold compared with controls in both PPH and NPPH. Iloprost inhalation significantly decreased mPAP (-9.1 +/- 2.5 mm Hg vs. -7.9 +/- 1.5 mm Hg), PVR (-453 +/- 103 dyne.s.cm(-5) vs. -381 +/- 114 dyne.s.cm(-5)), ANP (-99 +/- 63 pg/ml vs. -108 +/- 47 pg/ml) and cGMP (-4.6 +/- 0.9 nM vs. -4.2 +/- 1.6 nM). Baseline ANP including all patients significantly correlated with PVR, right atrial pressure, cardiac index, RV ejection fraction, mixed venous oxygen saturation and cGMP. CONCLUSIONS: The ANP system is highly activated in patients with severe PPH and NPPH. Atrial natriuretic peptide levels are significantly correlated with parameters of RV function and pre- and afterload. Iloprost inhalation causes a rapid decrease in ANP and cGMP in parallel with pulmonary vasodilation and hemodynamic improvement.     

Diffusion capacity and haemodynamics in primary and chronic thromboembolic pulmonary hypertension.

The transfer factor of the lung for carbon monoxide (TL,CO) is decreased in patients with pulmonary hypertension. The pulmonary membrane diffusion capacity (Dm) and pulmonary capillary blood volume (Vc), were studied to establish: 1) the relative contribution of the components of the transfer factor to the decrease in TL,CO; 2) whether differences exist between primary pulmonary hypertension (PPH) and chronic thromboembolic pulmonary hypertension (CTEPH); and 3) the relationship between these parameters and haemodynamic parameters. Dm and Vc were determined in 19 patients with PPH and in eight patients with CTEPH. The patients had been referred for consideration for lung transplantation. Haemodynamic parameters were assessed by heart catheterization. In the PPH group, Vc was reduced in 12 of 19 patients (mean+/-SD Vc 72+/-14% of the predicted value) and Dm in 17 of 19 patients (60+/-22% pred). In the CTEPH group, Vc was reduced in six of eight patients and Dm in seven of eight patients. The mean TL,CO Dm and Vc values were similar to those in the PPH group. The reduction in pulmonary membrane diffusion capacity was significantly greater than that in pulmonary capillary blood volume. No differences in pulmonary and cardiovascular functional values were found between the groups. Right atrial pressure showed a significant negative correlation with pulmonary capillary blood volume and an increased pulmonary vascular resistance was associated with a decrease in pulmonary membrane diffusion capacity. These results suggest pronounced functional impairment of the alveolocapillary membrane in these patients.     

The influence of fractional pulse pressure on the outcome of pulmonary thromboendarterectomy.

Although pulmonary thromboendarterectomy is an effective modality for the treatment of chronic thromboembolic pulmonary hypertension (CTEPH), the mortality in patients with severe haemodynamic disease is still high. Recently it was reported that fractional pulse pressure (pulmonary arterial pulse pressure/mean pulmonary arterial pressure) was higher in CTEPH than in primary pulmonary hypertension (PPH). It was hypothesized that fractional pulse pressure might be low in CTEPH with inaccessible distal thrombi and/or secondary pulmonary hypertensive change, resulting to the high operative mortality. To determine the influence of fractional pulse pressure to the outcome of surgery, 32 patients with CTEPH who had thromboendarterectomy between 1985 and 1998 were studied. Pulmonary haemodynamics and fractional pulse pressure were compared between survivors (n=26) and nonsurvivors (n=6) postoperatively. Those parameters in PPH (n=18) and large vessel pulmonary arteritis (n=6) were also analysed. Fractional pulse pressure in CTEPH (1.23+/-0.21) was significantly higher than in PPH (0.93+/-0.22; p=0.0017) and lower than in pulmonary arteritis (1.69+/-0.32; p=0.03). Fractional pulse pressure in survivors (1.26+/-0.21) was significantly higher than in nonsurvivors (1.06+/-0.16; p=0.03). Fractional pulse pressure is a significant predictor for mortality in patients with high pulmonary vascular resistance >1100 dynes.sec.cm(-5). To conclude fractional pulse pressure in addition to pulmonary vascular resistance might be useful in predicting for the outcome of surgery, especially in patients with severe haemodynamic impairment.     

Increase in thrombomodulin concentrations after pulmonary thromboendarterectomy in chronic thromboembolic pulmonary hypertension

STUDY OBJECTIVES: The objectives of the study were as follows: (1) to identify differences in endothelial dysfunction and altered hemostasis in patients with chronic thromboembolic pulmonary hypertension (CTEPH) compared with patients with acute pulmonary thromboembolism (APTE) uncomplicated by pulmonary arterial hypertension, by measuring the concentrations of thrombomodulin (TM), a receptor for thrombin and a major anticoagulant proteoglycan on the endothelial membrane, and other plasma factors of coagulation and fibrinolysis; and (2) to examine the effects of thromboendarterectomy on TM levels as a parameter of endothelial cell injury leading to abnormal hemostasis as well as to examine the clinical significance of TM as a marker of endothelial injury. DESIGN: Prospective comparison of concentrations of TM and other plasma parameters among patients with CTEPH or APTE and control subjects. PARTICIPANTS: We studied 22 healthy subjects (ie, control subjects), 22 patients who had been clinically stabilized after APTE, and 44 patients with CTEPH. In 21 of the patients with CTEPH, measurements were repeated after they had undergone pulmonary thromboendarterectomy. MEASUREMENTS AND RESULTS: Plasma concentrations of soluble TM in patients with CTEPH were measured and compared with those in patients with APTE. The mean (+/- SD) TM concentration in the CTEPH group (2.5 +/- 0.7 ng/mL) was significantly lower than that in the control group (4.0 +/- 0.6 ng/mL; p < 0.05). In contrast, the mean plasma TM concentration in the APTE group (4.6 +/- 1.9 ng/mL) was similar to that in the control group. After patients underwent pulmonary thromboendarterectomy, the mean TM concentration increased from 2.0 +/- 0.4 to 2.9 +/- 0.7 ng/mL (p < 0.05). In the CTEPH group, the plasma TM concentration was negatively correlated with mean pulmonary arterial pressure and total pulmonary resistance (p < 0.05). CONCLUSIONS: A decreased plasma TM concentration may reflect pulmonary vascular endothelial dysfunction leading to altered anticoagulant and fibrinolytic function in CTEPH, which rarely develops after APTE. Plasma TM measurements may be useful in distinguishing CTEPH with severe pulmonary hypertension from recurrent APTE.     

Descriptive patterns of severe chronic pulmonary hypertension by chest radiography

BACKGROUND: To find chest roentgenographic (CXR) features to help differentiate two representative diseases with severe chronic pulmonary hypertension (PH). STUDY SUBJECTS: Thirty-six consecutive patients with chronic thromboembolic PH (CTEPH), 38 with primary PH (PPH), and 37 with left heart disease and PH. METHODS: 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. RESULTS: 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. CONCLUSIONS: Characteristic roentgenographic findings can help differentiate two frequent diseases associated with chronic pulmonary hypertension and reflect the severity of disease.     

Effects of inhaled salbutamol in primary pulmonary hypertension.

Although lung function is grossly normal in patients with primary pulmonary hypertension (PPH), mild-to-moderate peripheral airflow obstruction can be found in the majority of patients with this disease. Therefore, beta2-agonists may affect pulmonary function, blood gases and haemodynamics in patients with PPH. Pulmonary function testing, blood gas measurements and right heart catheterisation was performed in 22 patients with PPH and the acute effects of inhaled salbutamol (0.2 mg) were measured. Salbutamol caused an increase in the forced expiratory volume in one second (FEV1) from 2446+/-704 to 2550+/-776 mL. The mean expiratory flow at 50% of the vital capacity (MEF50) rose from 58+/-17 to 66+/-21% pred. The pulmonary artery pressures remained unchanged after inhalation of salbutamol, but the cardiac output increased significantly from 3.9+/-1.4 to 4.2+/-1.4 L x min(-1) accompanied by significant increases in stroke volume and mixed venous oxygen saturation as well as a significant decrease in pulmonary vascular resistance. The arterial oxygen tension rose from 9+/-2.4 kPa (68+/-18 mmHg) at baseline to 9.7+/-2.8 kPa (73+/-21 mmHg) after inhalation of salbutamol, the alveolo-arterial oxygen gradient values improved from 6+/-2.5 kPa (45+/-19 mmHg) to 5.1+/-2.9 kPa (38+/-22 mmHg), respectively. Inhaled salbutamol has beneficial acute effects on pulmonary function, blood gases and haemodynamics in patients with primary pulmonary hypertension.     

Prostacyclin therapy before pulmonary thromboendarterectomy in patients with chronic thromboembolic pulmonary hypertension

OBJECTIVES: The continuous IV administration of prostacyclin improves pulmonary hemodynamics and prognosis in patients with primary pulmonary hypertension. We investigated whether the administration of prostacyclin therapy to patients before they undergo pulmonary thromboendarterectomy ameliorates pulmonary hypertension in patients with the most severe form of chronic thromboembolic pulmonary hypertension (CTEPH). METHODS: Of the 33 patients with CTEPH who were candidates for pulmonary thromboendarterectomy, 12 patients with severe pulmonary hypertension (pulmonary vascular resistance, > 1,200 dyne. s. cm(-5)) received IV prostacyclin prior to undergoing pulmonary thromboendarterectomy. Right heart catheterization and plasma brain natriuretic peptide (BNP) measurements were repeated at baseline, immediately before surgery, and 1 month after surgery. RESULTS: During a mean (+/- SEM) follow-up period of 46 +/- 12 days, the IV administration of prostacyclin resulted in a 28% decrease in pulmonary vascular resistance (1,510 +/- 53 to 1,088 +/- 58 dyne. s. cm(-5); p < 0.001) before surgery. Prostacyclin therapy markedly decreased plasma BNP level (547 +/- 112 to 188 +/- 30 pg/mL; p < 0.01), suggesting improvement in right heart failure. Pulmonary thromboendarterectomy caused a further reduction of pulmonary vascular resistance (302 +/- 47 dyne. s. cm(-5)) and plasma BNP levels (60 +/- 11 pg/mL) compared to each preoperative value (p < 0.05). Operative mortality rates were relatively low (8.3%) in patients with the most severe form of CTEPH. CONCLUSION: The IV administration of prostacyclin caused beneficial hemodynamic effects in patients with severe CTEPH and may serve as pretreatment for patients undergoing pulmonary thromboendarterectomy.     

The effects of oxygen and vasodilators on pulmonary hemodynamics and blood gases in chronic lung disease]

The effects of oxygen inhalation, nitroglycerin (NTG) and prostaglandin E1 (PGE1) on pulmonary hemodynamics and blood gases were studied in 15 patients with chronic lung disease (CLD). Cardiac catheterization was performed with Swan-Ganz catheter, and pulmonary hemodynamics and cardiac output were measured. After baseline hemodynamics and blood gas measurements were made, 15 patients inhaled oxygen for 15 minutes and the same measurements were repeated. Twenty minutes later, oxygen inhalation was stopped. Then the 15 patients were divided into two groups; one group was administered sublingual NTG (7 patients) and the other was administered PGE1 by continuous intravenous infusion (8 patients). Pulmonary hemodynamics and blood gas measurements were then performed. Oxygen inhalation significantly reduced mean pulmonary artery pressure (from 22.2 +/- 8.8 to 20.0 +/- 6.4 mmHg; p < 0.01) and heart rate (from 78.1 +/- 12.0 to 75.5 +/- 12.5 beats/min; p < 0.05). With respect to oxygenation, oxygen inhalation significantly increased PaO2 (from 68.6 +/- 10.7 to 113.4 +/- 31.4 mmHg; p < 0.01), PvO2 (from 35.1 +/- 3.7 to 38.0 +/- 3.3 mmHg; p < 0.01). Therefore, oxygen inhalation was thought to be useful in patients with chronic lung disease with pulmonary hypertension. Sublingual administration of NTG significantly reduced mean pulmonary artery pressure (from 24.1 +/- 0.2 to 17.6 +/- 6.8 mmHg; p < 0.01), C.I. (from 2.9 +/- 0.2 to 2.3 +/- 0.2 ml/min/m; p < 0.01), O2-transport (from 589.1 +/- 168.4 to 457.0 +/- 105.8 ml/min; p < 0.01), and had a tendency to decrease PvO2 (from 34.3 +/- 3.0 to 32.1 +/- 1.8 mmHg; p < 0.1).(ABSTRACT TRUNCATED AT 250 WORDS)     

Primary pulmonary hypertension: Current therapy

Because the causes of primary pulmonary hypertension (PPH) remains unknown, the therapeutic approach of the disease can be only empirical, based on the pathology and pathobiology of pulmonary circulation. Despite the inability to cure the disease, therapeutic advances over the past 20 years have contributed to an improvement of quality of life and prolonged survival in PPH patients. Current therapeutic approach of PPH mostly includes limitation of physical activity, long-term anticoagulation, and vasodilator therapy. Among all tested oral vasodilators, calcium-channel blockers are the most efficient long-term therapies by improving symptoms and hemodynamics in a subset of PPH patients (10% to 15%) who acutely respond to such drugs. Acute pulmonary vasodilator response to inhalation of nitric oxide can predict acute and chronic responses to oral calcium-channel blockers. A better understanding of the pathogenesis of PPH has changed the focus of medical treatments from purely chronic vasodilator therapy to the evaluation of agents, such as prostaglandins, that may reverse the proliferation of pulmonary vascular cells and result in regression of the pulmonary vascular hypertrophy and remodeling. Long-term treatment with intravenous epoprostenol (prostaglandin I(2) or prostacyclin) improves exercise capacity, hemodynamics and survival in most patients with PPH in functional class NYHA III or IV, and may be currently considered as the "gold standard" therapy for severe patients. However, response to long-term epoprostenol therapy may be incomplete, adverse effects are common, and survival remains unsatisfactory (55% at 5 years). In such patients with severe pulmonary hypertension refractory to medical therapy, atrioseptostomy and lung transplantation can be indicated.     

Chronic thromboembolic and pulmonary arterial hypertension share acute vasoreactivity properties

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.     

Inhaled nitric oxide selectively dilates pulmonary vasculature in adult patients with pulmonary hypertension, irrespective of etiology

OBJECTIVES

We sought to compare the responses of patients with pulmonary hypertension from primary and secondary causes (PPH and SPH, respectively) to inhaled nitric oxide (iNO) in the cardiac catheterization laboratory.

BACKGROUND

Pulmonary hypertension can lead to right ventricular pressure overload and failure. Although vasodilators are effective as therapy in patients with PPH, less is known about their role in adults with SPH. Inhaled nitric oxide can accurately predict the response to other vasodilators in PPH and could be similarly utilized in SPH.

METHODS

Forty-two patients (26 to 77 years old) with pulmonary hypertension during cardiac catheterization received iNO. Demographic and hemodynamic data were collected. Their response to iNO was defined by a decrease of ≥20% in mean pulmonary artery (PA) pressure or pulmonary vascular resistance (PVR).

RESULTS

Mean PA pressures and PVR were lower during nitric oxide (NO) inhalation in all patients with pulmonary hypertension. Seventy-eight percent of patients with PPH and 83% of patients with SPH were responders to iNO. A trend was seen toward a greater response with larger doses of NO in patients with SPH. Nitric oxide was a more sensitive predictor of response (79%), compared with inhaled oxygen (64%), and was well tolerated, with no evidence of systemic effects. Elevation in right ventricular end-diastolic pressure appeared to predict poor vasodilatory response to iNO.

CONCLUSIONS

Nitric oxide is a safe and effective screening agent for pulmonary vasoreactivity. Regardless of etiology of pulmonary hypertension, pulmonary vasoreactivity is frequently demonstrated with the use of NO. Right ventricular diastolic dysfunction may predict a poor vasodilator response.     

Nocturnal periodic breathing in primary pulmonary hypertension.

Cheyne-Stokes respiration is frequently observed in congestive heart failure. Among other factors, prolongation of circulation time, hypocapnia and hypoxia are thought to underlie this sleep-related breathing disorder. Primary pulmonary hypertension (PPH) is also characterized by reduced cardiac output and blood gas alterations. Therefore, the aim of the present study was to determine whether a nocturnal periodic breathing (PB) occurs in PPH. A total of 20 consecutive patients with PPH who had been admitted for pharmacological investigation of pulmonary vasoreactivity were investigated by lung function testing, right heart catheterization and full-night attended polysomnography. PB was detected in six patients (30%) (mean +/- SEM: apnoea/hypopnoea index 37 +/- 5 h(-1); arterial oxygen saturation was <90% during 56 +/- 6.5% of total sleep time). The patients with PB had more severe haemodynamic impairment than those without. They also had a more marked reduction in the pulmonary diffusion capacity and greater arterial hypoxia. PB was markedly improved or even eradicated by nasal oxygen during the night. Periodic breathing occurs in patients with advanced primary pulmonary hypertension and can be reversed by nocturnal nasal oxygen. The clinical and prognostic significance of periodic breathing in primary pulmonary hypertension needs to be determined by further studies.     

Gadolinium contrast balloon pulmonary angioplasty for a patient with chronic thromboembolic pulmonary hypertension and severe iodine allergy

Chronic thromboembolic pulmonary hypertension (CTEPH) is group 4 pulmonary hypertension caused by organized thrombi in the pulmonary arteries. Balloon pulmonary angioplasty (BPA) is an emerging treatment option for patients with inoperable CTEPH but needs contrast media. Therefore, management can be very difficult in patients who have severe iodine allergies. We present a case of a 61-year-old female with CTEPH. Right heart catheterization showed that the mean pulmonary arterial pressure (mPAP) was 47 mmHg. Her organized thrombi were not surgically accessible, so we performed BPA to improve her hemodynamic status. One session of BPA was performed, but the second session was halted because of iodine-induced anaphylactic shock. Despite the administration of pulmonary arterial hypertension-specific drugs for 3 months, the patient's mPAP was still 33 mmHg. CTEPH patients with mPAP ≥30 mmHg have a poor prognosis, so we decided to perform BPA using gadolinium contrast media. A total of six sessions of gadolinium contrast BPA (Gd-BPA) improved the patient's mPAP to the normal range. Gadolinium contrast media could also be used for visualizing pulmonary arteries during BPA. Our report is the first successful case of Gd-BPA, which improved the patient's hemodynamic status to the almost normal range. Gd-BPA may be an attractive treatment option for patients with inoperable CTEPH and severe iodine allergy.     

Comparative actions of hydralazine, nifedipine and amrinone in primary pulmonary hypertension

The effects of 3 types of vasoactive agents, hydralazine, nifedipine and amrinone, were evaluated in 7 patients with primary pulmonary hypertension (PPH). Hemodynamic values were measured before and after drug administration in every patient. All drugs increased cardiac output and reduced both systemic and pulmonary resistance in the patients studied. Only nifedipine significantly reduced pulmonary artery (PA) pressure (6 +/- 5 mm Hg). In addition, it decreased pulmonary resistance to a greater degree than systemic resistance in 2 of the 7 patients, suggesting that nifedipine can cause selective pulmonary vasodilation in some patients. Hydralazine appeared to increase cardiac output and stroke volume by reducing systemic resistance. There was no evidence of direct pulmonary vasodilating effects; it decreased systemic resistance more than pulmonary resistance in every case. The increase in cardiac output from amrinone was secondary to a decrease in systemic arterial pressure with reflex tachycardia; stroke volume was unchanged. Amrinone had little pulmonary effect in all but 1 patient, in whom it substantially reduced PA pressure and pulmonary resistance. The mechanism of action of these 3 drugs in PPH differs. Nifedipine holds the most promise as an effective pulmonary vasodilator. A study of the effects of long-term administration of nifedipine in PPH is warranted.     

Oxygen-mediated pulmonary vasodilation and plasma levels of endothelin-1, atrial natriuretic peptide and cyclic GMP in patients with left-to-right shunt and pulmonary hypertension

This study was performed to evaluate the role of endogenous endothelin-1 (ET-1), atrial natriuretic peptide (ANP) and cyclic guanosine monophosphate (cGMP) in patients with left-to-right shunt and pulmonary hypertension. Further objectives were to study a possible feedback mechanism between ANP and ET-1 and to examine the influence of ANP on cGMP plasma levels. Finally, the role of these hormones in oxygen-mediated pulmonary vasodilation was examined. Plasma concentrations of ET-1, ANP and cGMP were studied in 39 patients with congenital heart disease and left-to-right shunt. Blood samples were taken from the pulmonary artery and pulmonary vein at cardiac catheterization at baseline and after breathing oxygen for 20 min. Patients were grouped according to the presence or absence of pulmonary hypertension (defined as mean Pp/Ps > or = 0.5). Patients with pulmonary hypertension (n = 18) were found to have significantly higher plasma ANP (665 [59-1358] versus 267 [47-832] pg/ml) and cGMP (21.5 [3.6-82.2] versus 7.8 [0-14.6] nM/L) levels than patients without pulmonary hypertension (n = 21). Pulmonary venous ET-1 plasma concentrations were above normal limits in one patient only. ANP plasma levels were not related to ET-1 and cGMP concentrations. There was no transpulmonary gradient for any of the factors. Pulmonary vasodilation in response to oxygen was found in 7 of 18 patients with PH, but was not associated with significant changes in ET-1, ANP or cGMP plasma concentrations. Patients with congenital heart disease and PH show an increase both in vasoconstrictive and vasodilating factors. The mechanism of oxygen-mediated vasodilation in these patients remains to be elucidated.     

吸入伊洛前列素对不同类型肺动脉高压患者氧动力学的影响

目的 分析雾化吸入伊洛前列素对动脉型肺动脉高压(PAH)及慢性血栓栓寒性肺动脉高压(CTEPH)患者的氧动力学的急性影响.方法 顺序收集北京朝阳医院2006年6月至2009年1月连续收治的明确诊断为PAH的患者22例及CTEPH患者24例,均行右心导管检查,监测基线状态及吸人伊洛前列素20μg后的即刻血流动力学特征,同步抽取肺动脉及股动脉血行血气分析,计算氧动力学参数.结果 基线状态PAH及CTEPH患者的PaO2分别为(63±10)mm Hg(1 mm Hg=0.133 kPa)及(59 ±10)mm Hg,氧输送指数(DO2I)分别为(458±136)ml·min-1·m-2及(386 ±92)ml·min-1·m-2,氧消耗指数分别为(135±53)ml·min-1·m-2及(131±43)ml·min-1·m-2.吸入伊洛前列素后即刻,2组患者肺内分流率均显著升高(均P<0.01),P4O2显著升高(均P<0.01);动脉血氧含量均显著降低(均P<0.05);混合静脉血氧合指标及氧摄取率无明显变化;DO2I无明显增加,氧消耗指数出现不同程度降低;2组患者各项氧动力学参数变化幅度无差异.基线状态CTEPH患者混合静脉血氧饱和度(SvO2)、静脉血氧含量(CvO2)及DO2I均显著低于PAH患者(均P<0.05).吸药后,CTEPH患者PaO2、SvO2及CvO2均显著低于PAH患者(均P<0.05).结论 PAH及CTEPH患者存在低氧血症及氧动力学异常;雾化吸入伊洛前列素后患者肺内分流增加,氧动力学状态无改善.CTEPH患者的氧动力学状态较PAH患者更差,应用伊洛前列素时需加强氧合功能监测,必要时给予氧疗支持.     

Comparison of progressive exercise performance of normal subjects and patients with primary pulmonary hypertension

The extent of exercise limitation and the mechanisms for that limitation in 11 patients with primary pulmonary hypertension (PPH) were studied by progressive, upright cycle ergometry. All patients had a mean pulmonary artery pressure of 30 mm Hg or higher (mean, 56 +/- 15), normal pulmonary function testing, normal pulmonary capillary wedge pressure, and pulmonary angiography consistent with the diagnosis. Rest and exercise data obtained from the patients with PPh were compared with data obtained from 11 matched, sedentary control subjects. Mean maximal oxygen consumption (VO2) was 13 +/- 4 ml/kg/min in the PPH group compared with 28 +/- 7 ml/kg/min in the controls. At maximal VO2 the minute ventilation (VE) was similar; however, the VE at any level of carbon dioxide production (VCO2) during rest and exercise was significantly higher in the PPH group. Maximal heart rate and oxygen pulse (VO2/heart rate) was significantly higher in the control group (148 +/- 18 vs 180 +/- 24, and 6.3 +/- 2.2 vs 9.9 +/- 3.9, respectively). Anaerobic threshold occurred earlier during progressive exercise in the PPH group and correlated positively with the maximal oxygen pulse achieved in patients with PPH. In conclusion, patients with PPH have severe exertional limitation due to cardiovascular factors with an inability to maintain appropriate oxygen delivery to the body during exercise. No respiratory impairment was recognized; however, an exaggerated ventilatory response to exercise at any level of VCO2 was found.