BACKGROUNDIloprost has been used to test acute pulmonary vasoreactivity in idiopathic pulmonary arterial hypertension (PAH). We aimed to investigate the acute hemodynamic and oxygenation responses and tolerability to 20 µg aerosolized Iloprost in Chinese patients with pulmonary hypertension.

METHODSBetween March 2005 and May 2010, 212 pulmonary hypertension patients inhaled a single dose of 20 µg Iloprost over 10 - 15 minutes for vasoreactivity testing. The acute hemodynamic and oxygenation responses and adverse events were recorded.

RESULTSIloprost decreased total pulmonary resistance ((1747 ± 918) dyn×s×cm(-5) vs. (1581 ± 937) dyn×s×cm(-5), P < 0.001), increased stroke volume ((45.0 ± 22.1) ml vs. (47.0 ± 24.2) ml, P = 0.002), and cardiac output ((3.7 ± 1.7) L/ml vs. (3.9 ± 1.9) L/min, P = 0.009). Heart rate and systemic vascular resistance remained stable during inhalation. However, systemic arterial blood oxygen saturation fell slightly ((91.0 ± 6.8)% vs. (90.3 ± 6.7)%, P = 0.002). Pulmonary and systemic arterial blood pressures declined within 1 - 3 minutes after inhalation initiation and reached their lowest levels within 10 - 15 minutes. Idiopathic PAH responded more favorably than pulmonary hypertension due to other causes (P £0.001) and patients with less severe pulmonary hypertension have better responses to Iloprost. No adverse events requiring medical care or leading to termination of inhalation occurred.

CONCLUSIONSInhalation of 20 µg Iloprost showed potent and selective pulmonary hemodynamic effects and was well tolerated in the Chinese pulmonary hypertension patients. Patients with idiopathic PAH and less severe pulmonary hypertension responded more favorably to inhalation of Iloprost.

Administration, Inhalation ; China ; Hemodynamics ; drug effects ; Humans ; Hypertension, Pulmonary ; drug therapy ; Iloprost ; administration & dosage ; adverse effects ; therapeutic use

This paper provides an overview of the current state of pharmacotherapy in children with pulmonary arterial hypertension (PAH) and a brief introduction to the potentially novel pharmacologic targets for PAH. Currently, 3 classes of drugs including prostacyclin analogues, endothelin receptor antagonists and phosphodiesterase-5 inhibitors are approved for the treatment of PAH in children, which has led to improved hemodynamics, increased exercise capacity and prolonged survival. Despite these improvements, there is still a need to carry out well-designed, randomized, controlled studies with larger samples. In addition, novel drugs targeting other molecular pathways should be developed.
1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine ; analogs & derivatives ; therapeutic use ; Calcium Channel Blockers ; therapeutic use ; Child ; Epoprostenol ; analogs & derivatives ; therapeutic use ; Familial Primary Pulmonary Hypertension ; Humans ; Hypertension, Pulmonary ; diagnosis ; drug therapy ; Iloprost ; therapeutic use ; Sulfonamides ; therapeutic use

Administration, Inhalation ; Adult ; Carbolines ; administration & dosage ; therapeutic use ; Female ; Heart Defects, Congenital ; drug therapy ; Humans ; Hypertension, Pulmonary ; drug therapy ; Iloprost ; administration & dosage ; therapeutic use ; Male ; Tadalafil ; Young Adult

OBJECTIVETo summary the efficacy and safety of aerosolized iloprost in patients with pulmonary hypertensive crisis.

METHODSOn the basis of conventional therapy, aerosolized iloprost (10 µg per time for 10 - 15 min in 2 hours interval, 8 times per day) was administered to four patients with idiopathic pulmonary arterial hypertension and pulmonary hypertensive crisis. Blood pressure, heart rate, systemic artery oxygen saturation, systolic pulmonary arterial pressure (sPAP) measured by echocardiography and the adverse events were analyzed.

RESULTSAfter aerosolized iloprost therapy, sPAP was significantly decreased and systemic artery oxygen saturation was improved. Adverse events (nausea, vomiting, diarrhea, dry cough) were observed in two patients, and the iloprost use was stopped in one patient due to severe vomiting and diarrhea.

CONCLUSIONAerosolized iloprost could significantly reduce the sPAP and improve the systemic artery oxygen saturation in patients with pulmonary hypertension crisis.

Administration, Inhalation ; Adult ; Blood Pressure ; Child ; Familial Primary Pulmonary Hypertension ; Female ; Humans ; Hypertension, Pulmonary ; drug therapy ; physiopathology ; Iloprost ; administration & dosage ; therapeutic use ; Male ; Middle Aged ; Young Adult

OBJECTIVETo investigate the immediately effects of inhaled aerosolized iloprost in adult patients with severe pulmonary arterial hypertension (PAH) secondary to congenital heart diseases (CHD).

METHODSAdult patients with severe PAH secondary to CHD (n = 165) were included in this study. Right heart catheterization was performed, Pulmonary and systemic blood flow, the oxygen consumption VO(2) (ml/min) were calculated using Fick's principle. Pulmonary vascular resistances (PVR) were calculated with standard formulas and indexed to body surface area. Hemodynamic parameters were measured before and after iloprost inhalation (20 µg).

RESULTSPost iloprost inhalation, heart rate, mean aortic pressure, pulmonary systolic pressure to aortic systolic pressure ratio all remained un changed (P > 0.05), while pulmonary artery pressure (PAP) were significantly reduced and Qp significantly increased from (7.2 ± 4.8) L/min to (9.9 ± 7.2) L/min (P < 0.01), PVR was also significantly reduced from (13.4 ± 8.7) Wood units to (9.5 ± 6.6) Wood units (P < 0.01), and left-to-right shunt volume increased from (3.2 ± 4.4) L/min to (5.5 ± 7.0) L/min (P < 0.01) and right-to-left shunt volume decreased from (1.0 ± 1.0) L/min to (0.7 ± 0.7) L/min (P < 0.01). Subgroup analysis showed that adult patients with patent ductus arteriosus and/or ventricular septal defects are more likely to develop severe pulmonary arterial hypertension or Eisenmenger syndrome than patients with atrial septal defects.

CONCLUSIONSInhaled Aerosolised iloprost use is effective and safe for adult patients with severe pulmonary arterial hypertension secondary to congenital heart diseases.

Administration, Inhalation ; Adolescent ; Adult ; Female ; Heart Defects, Congenital ; complications ; drug therapy ; Humans ; Hypertension, Pulmonary ; complications ; drug therapy ; Iloprost ; pharmacology ; therapeutic use ; Male ; Vascular Resistance ; Young Adult

OBJECTIVETo evaluate the therapy efficacy of iloprost combined with low dose tadalafil in adult congenital heart disease (CHD) patients with severe pulmonary arterial hypertension (PAH).

METHODSAdult CHD patients with severe PAH were included and divided into the sequential combination therapy group [iloprost: 10 µg/inhalation, 6 times per day for 6 months, and then add oral tadalafil (5 mg/d) till 12 months, n = 32] and upfront combination therapy group [iloprost: 10 µg/inhalation, 6 times per day combined with oral tadalafil (5 mg) for 12 months, n = 36]. Data on 6 min walking test (6MWT), Borg dyspnea score, oxygen saturation measurement, WHO classification, and cardiac catheterization were obtained at baseline, 6 and 12 months.

RESULTSSeventy-two patients were enrolled in the study and 68 patients completed the study. Pulmonary vascular resistance (PVR) was significantly reduced in the sequential combination therapy group[ (12.96 ± 6.48 ) Wood U vs. (16.94 ± 8.11) Wood U, P < 0.05] and in the upfront combination therapy group [(12.45 ± 7.32) Wood U vs. (16.73 ± 9.28) Wood U, P < 0.05] while pulmonary blood flow [(6.77 ± 3.17) L/min vs. (5.08 ± 2.36) L/min, P < 0.05; (6.95 ± 3.32) L/min vs. (5.03 ± 2.32) L/min, P < 0.05], the 6 MWD were significantly increased [(458 ± 59) m vs. (427 ± 65) m, P < 0.05; (494 ± 59) m vs. (436 ± 62) m, P < 0.01], the Borg dyspnea score (2.04 ± 0.72 vs. 2.52 ± 0.79, P < 0.05; 1.72 ± 0.73 vs. 2.51 ± 0.77, P < 0.01) was significantly improved in both groups at 6 months compared to baseline levels. In the upfront combination therapy group, venous oxygen saturation [(68.4 ± 9.3)% vs. (62.9 ± 9.5)%, P < 0.05] and systemic oxygen saturation during exercise[ (87.2 ± 9.7)% vs. (83.1 ± 15.6)%, P < 0.05]at 6 months were also significantly improved compared to baseline. At month 12, significantly lowered pulmonary artery pressure, PVR, Rp/Rs and increased pulmonary blood flow and cardiac index were evidenced in both groups compared to baseline.

CONCLUSIONIloprost combined with low dose tadalafil regimen can effectively reduce PVR, increase 6MWD, and improve cardiopulmonary function in adults CHD patients with severe PAH. Compared with the sequential therapy regimen, the upfront combination therapy regimen can more rapidly improve the clinical symptoms of patients.

Adolescent ; Adult ; Carbolines ; therapeutic use ; Female ; Follow-Up Studies ; Heart Defects, Congenital ; complications ; drug therapy ; Humans ; Hypertension, Pulmonary ; complications ; drug therapy ; Iloprost ; therapeutic use ; Male ; Middle Aged ; Tadalafil ; Treatment Outcome ; Young Adult

Congenital extrahepatic portocaval shunt (CEPS) is a rare anomaly of the mesenteric vasculature in which the intestinal and splenic venous drainage bypasses the liver and drains directly into the inferior vena cava, the left hepatic vein or the left renal vein. This uncommon disease is frequently associated with other malformations and mainly affects females. Here we report a case of pulmonary arterial hypertension associated with CEPS (Abernethy type 1b shunt) in a 20-yr-old man who was incidentally diagnosed during evaluation of multiple nodules of the liver. The patient was treated by inhalation of iloprost (40 microg/day) with improved condition and walking test. Physicians should note that congenital portocaval shunt may cause pulmonary hypertension.
Echocardiography, Doppler ; Humans ; Hypertension, Pulmonary/*diagnosis/drug therapy ; Iloprost/therapeutic use ; Liver/blood supply/radiography ; Magnetic Resonance Imaging ; Male ; Thoracic Arteries/ultrasonography ; Tomography, X-Ray Computed ; Vasodilator Agents/therapeutic use ; Vena Cava, Inferior/*abnormalities/ultrasonography ; Young Adult

BACKGROUNDThe clinical significance of acute vasoreactivity testing (AVT) in patients with chronic thromboembolic pulmonary hypertension (CTEPH) remains unclear. We analyzed changes in hemodynamics and oxygenation dynamics indices after AVT in patients with CTEPH using patients with pulmonary arterial hypertension (PAH) as controls.

METHODSWe analyzed retrospectively the results of AVT in 80 patients with PAH and 175 patients with CTEPH registered in the research database of Beijing Chao-Yang Hospital between October 2005 and August 2014. Demographic variables, cardiopulmonary indicators, and laboratory findings were compared in these two subgroups. A long-term follow-up was conducted in patients with CTEPH. Between-group comparisons were performed using the independent-sample t-test or the rank sum test, within-group comparisons were conducted using the paired t-test or the Wilcoxon signed-rank test, and count data were analyzed using the Chi-squared test. Survival was estimated using the Kaplan-Meier method and log-rank test.

RESULTSThe rates of positive response to AVT were similar in the CTEPH (25/175, 14.3%) and PAH (9/80, 11.3%) groups (P > 0.05). Factors significantly associated a positive response to AVT in the CTEPH group were level of N-terminal pro-brain natriuretic peptide (≤1131.000 ng/L), mean pulmonary arterial pressure (mPAP, ≤44.500 mmHg), pulmonary vascular resistance (PVR, ≤846.500 dyn·s-1·m-5), cardiac output (CO, ≥3.475 L/min), and mixed venous oxygen partial pressure (PvO2, ≥35.150 mmHg). Inhalation of iloprost resulted in similar changes in mean blood pressure, mPAP, PVR, systemic vascular resistance, CO, arterial oxygen saturation (SaO2), mixed venous oxygen saturation, partial pressure of oxygen in arterial blood (PaO2), PvO2, and intrapulmonary shunt (Qs/Qt) in the PAH and CTEPH groups (all P > 0.05). The survival time in patients with CTEPH with a negative response to AVT was somewhat shorter than that in AVT-responders although the difference was not statistically significant (χ2 =3.613, P = 0.057). The survival time of patients with CTEPH who received calcium channel blockers (CCBs) was longer than that in the group with only basic treatment and not shorter than that of patients who receiving targeted drugs or underwent pulmonary endarterectomy (PEA) although there was no significant difference between the four different treatment regimens (χ2 =3.069, P = 0.381).

CONCLUSIONSThe rates of positive response to AVT were similar in the CTEPH and PAH groups, and iloprost inhalation induced similar changes in hemodynamics and oxygenation dynamics indices. A positive response to AVT in the CTEPH group was significantly correlated with milder disease and better survival. Patients with CTEPH who cannot undergo PEA or receive targeted therapy but have a positive response to AVT might benefit from CCB treatment.

Administration, Inhalation ; Adult ; Aged ; Arterial Pressure ; drug effects ; Atrial Natriuretic Factor ; metabolism ; Calcium Channel Blockers ; administration & dosage ; therapeutic use ; Endarterectomy ; Familial Primary Pulmonary Hypertension ; drug therapy ; physiopathology ; Female ; Hemodynamics ; drug effects ; Humans ; Hypertension, Pulmonary ; drug therapy ; physiopathology ; Iloprost ; administration & dosage ; therapeutic use ; Male ; Middle Aged ; Protein Precursors ; metabolism ; Retrospective Studies ; Software ; Vasodilator Agents ; administration & dosage ; therapeutic use