PURPOSE: Persistent pulmonary hypertension of the newborn (PPHN) is a potentially fatal disease. Inhaled iloprost, a stable analogue of prostacyclin, has recently been used as a therapeutic option. However, there are no clinical guidelines on the use of iloprost, specifically for neonates. This study aimed to suggest the use of inhaled iloprost as a rescue therapy for PPHN based on our experience.METHODS: The efficacy and adverse events of inhaled iloprost were evaluated prospectively in nine full-term neonates with PPHN. We monitored the following parameters: fraction of inspired oxygen (FiO₂), respiratory severity score (RSS), heart rate, and mean blood pressure.RESULTS: The inhalation dose was 1 to 2 µg/kg initially, and 4 to 8 inhalations per day were applied over 2 to 8 days, except in the case of one neonate who died 2 days after birth. Echocardiographic findings, changes in FiO₂, and RSS improved within the next 7 days in eight of the nine patients. Severe side effects on heart rate and blood pressure were not observed.CONCLUSION: Our experience suggests that inhaled iloprost can be used as a first-line treatment in newborn infants with PPHN when inhaled nitric oxide is not available. To the best of our knowledge, this report is the first prospective case series on the use of inhaled iloprost in PPHN.
Blood Pressure ; Echocardiography ; Epoprostenol ; Female ; Heart Rate ; Humans ; Hypertension, Pulmonary ; Iloprost ; Infant, Newborn ; Inhalation ; Nitric Oxide ; Oxygen ; Parturition ; Persistent Fetal Circulation Syndrome ; Prospective Studies

BACKGROUND: Various pharmacological treatments have been suggested to treat osteonecrosis of the femoral head. However, their practicability remains a controversial issue. METHODS: We systemically reviewed articles published during last 20 years to assess the efficacy and safety of the pharmacological treatments. RESULTS: To date, enoxaparin, statins, bisphosphonates, iloprost and acetylsalicylic acid have been practiced for the treatment of osteonecrosis. However, none of them were proven to be effective by high level studies, and most of them have adverse reactions. CONCLUSIONS: No pharmacological prevention or treatment of osteonecrosis is recommendable at this moment.
Aspirin ; Bone Remodeling ; Diphosphonates ; Drug Therapy ; Enoxaparin ; Head ; Hydroxymethylglutaryl-CoA Reductase Inhibitors ; Iloprost ; Osteonecrosis

PURPOSE: To research the effects of iloprost (IL) and hyperbaric oxygen (HBO) combination treatment on lung injury and on tumor necrosis factor alpha (TNF-α), myeloperoxidase (MPO), malondialdehyde (MDA), and soluble intercellular adhesion molecule-1 (sICAM-1) levels after tissue or organ ischemia-reperfusion, and on ischemia-reperfusion induced lung neutrophil sequestration. METHODS: Forty white New Zealand rabbits were assigned randomly into 5 groups: HBO, IL, HBO+IL, control, and sham groups. TNF-α values were checked before ischemia, in the 1st hour of ischemia and in the 1st and 4th hours of reperfusion, also at the end of reperfusion period, plasma and tissue MPO values, MDA values, and sICAM-1 levels were detected. After sacrifice, the degree of lung injury was determined by histopathological examination. RESULTS: Compared to the control group all therapy groups showed a drastically meaningful reduction in TNF-α increase in 1, 2, and 4 hours. Plasma and lung MDA, MPO, and sICAM-1 levels were significantly lower in IL, HBO, HBO+IL, and sham groups compared with the control group. IL and/or HBO suppressed MDA and MPO increase in the lung tissue and in plasma. Additionally, histopathological score was significantly lower in HBO, IL, HBO+IL, and sham groups than that of the control group. CONCLUSION: Both HBO and IL therapy have a beneficial effect by causing a meaningful reduction in TNF-α production, MPO, MDA, sICAM-1 levels and pulmonary neutrophil sequestration; which play a role, especially, in ischemia reperfusion induced lung damage.
Acute Lung Injury* ; Hyperbaric Oxygenation ; Iloprost* ; Intercellular Adhesion Molecule-1 ; Ischemia ; Lung ; Lung Injury ; Malondialdehyde ; Neutrophils ; Oxygen* ; Peroxidase ; Plasma ; Rabbits ; Reperfusion ; Reperfusion Injury ; Tumor Necrosis Factor-alpha

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

Pulmonary arterial hypertension is a critical manifestation of systemic sclerosis (SSc) and is a main cause of death. Several treatment modalities for SSc have been identified, with effects that improve quality of life and mortality rates. However, whether these drugs can also normalize pulmonary arterial pressure, remains unclear. Here, we report the case of a woman with diffuse SSc with pulmonary arterial hypertension, who had a functional status equivalent to the New York Heart Association class III. The patient was treated with inhaled iloprost. After six years of inhaled iloprost therapy, echocardiography showed that pulmonary arterial pressure normalized, accompanied by improvement in functional capacity. Inhaled iloprost might not only normalize pulmonary arterial pressure, but also improve the functional status of patients with SSc with pulmonary arterial hypertension.
Arterial Pressure ; Cause of Death ; Echocardiography ; Female ; Heart ; Humans ; Hypertension* ; Hypertension, Pulmonary ; Iloprost* ; Mortality ; Quality of Life ; Scleroderma, Systemic*

Severe portopulmonary hypertension (PPHT) is considered a contraindication for liver transplantation (LT) because of the associated high mortality and poor prognosis. We report the case of a 57-year-old cirrhotic woman with severe PPHT (mean pulmonary artery pressure [mPAP] > 65 mmHg), who underwent a successful living donor LT. Intra-operative use of inhaled iloprost, milrinone, dobutamine, and postoperative use of inhaled nitric oxide and oral sildenafil failed to lower the pulmonary artery pressure (PAP). The patient responded only to nitroglycerin and drainage of massive ascites. Meticulous intra-operative volume control, which included minimizing blood loss and subsequent transfusion, was carried out. The use of vasopressors, which may have elevated the PAP, was strictly restricted. Intra-operative PAP did not show an increase, and the hemodynamics was maintained within relatively normal range, compared to the preoperative state. The patient was discharged without any complications or related symptoms.
Ascites ; Dobutamine ; Drainage ; Female ; Hemodynamics ; Humans ; Hypertension* ; Iloprost ; Liver Transplantation* ; Living Donors ; Middle Aged ; Milrinone ; Mortality ; Nitric Oxide ; Nitroglycerin ; Prognosis ; Pulmonary Artery ; Reference Values ; Sildenafil Citrate

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

BACKGROUNDPrevious studies have shown that prostaglandins (PGs) dramatically stimulate healing processes in bone. However, the effect of prostaglandin I2 (PGI2) on fracture healing remains unclear. To investigate the effect of PGI2, a study on fracture healing process in closed tibia fractures was designed.

METHODSThirty-six Sprague-Dawley male rats were randomized into two groups. On the first day, their right tibias were fractured by three-point bending technique. The study group (n = 18) received a single injection of 10 µg/kg iloprost for 5 days, while the control group (n = 18) received saline solution in the same way. On the 7th, 14th and 28th days following the fracture, six rats were sacrificed and their right legs were harvested in each group. The progression of fracture healing was assessed for each specimen by the scores of radiography (by Lane-Sandhu) and histology (by Huo et al).

RESULTSOn the 7th day, the radiographic and histologic scores were equal. On the 14th day radiographic total score was 6 and histologic total score was 23 in the iloprost group, whereas radiographic total score was 11 and histologic total score was 33 in the control group. On the 14th day radiographic and histologic scores were significantly decreased in the iloprost group compared to the control group (P < 0.05). On the 28th day radiographic total score was 12 and histologic total score was 37 in the iloprost group, whereas radiographic total score was 15 and histologic total score was 40 in the control group. On the 28th day although there was a decrease in radiographic and histologic scores of the iloprost group acording to control group, it was not statistically significant (P > 0.05).

CONCLUSIONIloprost delays fracture healing in early stage in rats.

Animals ; Epoprostenol ; pharmacology ; Fracture Healing ; drug effects ; Fractures, Bone ; pathology ; Iloprost ; pharmacology ; Male ; Rats ; Rats, Sprague-Dawley ; Tibial Fractures ; pathology ; Wound Healing ; drug effects

Decreased exercise capacity after Fontan surgery is relatively common and the failure of the Fontan state gradually increases with age. However, there is no further treatment for patients with Fontan circulation. Pulmonary vasodilation therapy is an effective method to solve this problem because pulmonary vascular resistance is a major factor of the Fontan problem. Inhaled iloprost is a chemically stable prostacyclin analogue and a potent pulmonary vasodilator. We experienced two cases of Fontan patients treated with inhaled iloprost for 12 weeks. The first patient was an 18-year-old female with pulmonary atresia with an intact ventricular septum, and the second patient was a 22-year-old male with a double outlet right ventricle. Fifteen years have passed since both patients received Fontan surgery. While the pulmonary pressure was not decreased significantly, improved exercise capacity and cardiac output were observed without any major side effects in both patients. The iloprost inhalation therapy was well tolerated and effective for the symptomatic treatment of Fontan patients.
Adolescent ; Cardiac Output ; Double Outlet Right Ventricle ; Epoprostenol ; Female ; Fontan Procedure ; Humans ; Iloprost* ; Male ; Pulmonary Atresia ; Respiratory Therapy ; Vascular Resistance ; Vasodilation ; Ventricular Septum ; Young Adult

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