Background: Chronic thromboembolic pulmonary hypertension (CTEPH) is a potential consequence to pulmonary embolism. The histologic picture is similar to idiopathic pulmonary hypertension (IPAH) suggesting that vascular remodeling also contributes to CTEPH. The treatment of choice is pulmonary endarterectomy. However, this treatment option is not adequate for all patients with CTEPH. Currently, no data exist on standard vasodilative therapy for CTEPH. Intravenous and oral prostanoids, both well-known vasodilators in IPAH, have been used with promising results, whereas the same has not been consistently observed for inhaled iloprost. Objective: In this study, we examined acute hemodynamic effects of inhaled iloprost in patients with CTEPH. Methods: In a prospective study, right heart catheterization was performed in 20 patients (mean age 56 years, New York Heart Association class II–IV) at the time of diagnosis of CTEPH. Pulmonary vascular resistance (PVR), mean pulmonary arterial pressure (mPAP), cardiac output (CO), mean systemic arterial pressure (MAP) and oxygen partial pressure (PaO₂) were obtained before and 20 min after inhaling 5 µg iloprost. Subsequently, all patients were evaluated for pulmonary endarterectomy. Six patients were eligible for surgery. Results: Significant changes in pulmonary and systemic hemodynamics were observed following the inhalation of iloprost (before to after inhalation): PVR: 1,057 ± 404.3 to 821.3 ± 294.3 dyn·s·cm^–5, p < 0.0001; mPAP: 50.55 ± 8.43 to 45.75 ± 8.09 mm Hg, p = 0.0002; CO: 3.66 ± 1.05 to 4.05 ± 0.91 l/min, p < 0.0106. MAP and PaO₂ decreased significantly (MAP: 94.15 ± 11.58 to 89.45 ± 14.29 mm Hg, p = 0.0111; PaO₂: 7.33 ± 1.17 to 6.64 ± 1.25 kPa, p = 0.0260). Conclusions: Hemodynamic changes directly following inhalation of iloprost suggest a significant contribution of a reversible component of vasoconstriction to pulmonary arterial hypertension in patients with CTEPH.

Pulmonary arterial hypertension (PAH) is a life-threatening disease characterized by an elevated pulmonary arterial pressure and vascular resistance with a poor prognosis. Various pulmonary and extrapulmonary causes are now recognized to exist separately from the idiopathic form of pulmonary hypertension. An imbalance in the presence of vasoconstrictors and vasodilators plays an important role in the pathophysiology of the disease, one example being the lack of prostacyclin. Prostacyclin and its analogues are potent vasodilators with antithrombotic, antiproliferative and anti-inflammatory qualities, all of which are important factors in the pathogenesis of precapillary pulmonary hypertension. Iloprost is a stable prostacyclin analogue available for intravenous and aerosolized application. Due to the severe side effects of intravenous administration, the use of inhaled iloprost has become a mainstay in PAH therapy. However, owing to the necessity for 6 to 9 inhalations a day, oral treatment is often preferred as a first-line therapy. Numerous studies proving the efficacy and safety of inhaled iloprost have been performed. It is therefore available for a first-line therapy for PAH. The combination with endothelin-receptor antagonists or sildenafil has shown encouraging effects. Further studies with larger patient populations will have to demonstrate the use of combination therapy for long-term treatment of pulmonary hypertension.

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by the intracellular accumulation of highly phosphorylated tau protein, the extracellular formation of amyloid plaques and a significant loss of neurons. Recent evidence suggests that neuronal death in AD involves an aborted attempt of cells to re-enter the cell cycle. To study the effect of amyloid deposits on cell cycle related events in vivo, the expression of cell cycle markers was examined by immunohistochemistry in amyloid precursor protein (APP) transgenic mice (APP23 mice, Swedish double mutation). Abeta deposition in APP23 mice is associated with prominent gliosis that is characterized by an astrocytic expression of cyclins D1, E and B1 as well as the nuclear translocation of cyclin-dependent protein kinase 4. However, amyloid plaque formation is not accompanied by significant changes in the neuronal expression of cyclins or cyclin-dependent kinase inhibitors. It is concluded, therefore, that in contrast to AD, amyloid pathology in APP23 mice is not associated with changes in the expression of cell cycle markers in neurons. The results support the assumption that the neuronal re-expression of cell cycle components in AD is not a consequence of Abeta formation and deposition.

Hepatopulmonary syndrome is characterized by advanced liver disease, hypoxemia, and intrapulmonary shunting. The only reported curative option is orthotopic liver transplantation. We describe here a beneficial effect of inhaled prostacyclin including a decrease in respiratory symptoms and improved oxygenation in this clinical situation, with no approved pharmacological long-term therapy. The prostanoid iloprost, approved for pulmonary and portopulmonary hypertension, caused an increase in oxygenation, relief of dyspnea, and increased exercise tolerance in a patient suffering from liver-cirrhosis-associated hepatopulmonary syndrome. After liver transplantation, restitution of hepatopulmonary syndrome did not occur immediately. Inhaling iloprost resulted in improved physical condition and better clinical rehabilitation potential until hypoxemia finally resolved 3 months after transplantation. Therefore, iloprost could improve quality of life in patients with hepatopulmonary syndrome waiting for liver transplantation and post surgery until the resolution of the hypoxemia.

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