Aerosolized Prostacyclin and Iloprost in Severe Pulmonary Hypertension

Olschewski, Horst; Walmrath, D.; Schermuly, Ralph Theo; Ghofrani, Hossein Ardeschir; Grimminger, Friedrich; Seeger, Werner

doi:10.7326/0003-4819-124-9-199605010-00006

Cited by 355 publications

(234 citation statements)

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“…12 When administered during a short aerosolization ma-neuver to patients with pulmonary hypertension, its pulmonary vasodilative potency was similar to that of prostacyclin, but its effects lasted for 30 to 90 minutes, as compared with 15 minutes. 4,11,[13][14][15] Several open-label, uncontrolled studies of patients with severe pulmonary hypertension suggested that longterm use of aerosolized iloprost results in substantial clinical improvement. 11,13,[16][17][18][19][20] Our objective in this trial was to evaluate the effects of inhaled iloprost using a rigorous end point of clinical efficacy.…”

Section: Resultsmentioning

confidence: 99%

“…Postinhalation assessments of hemodynamic variables demonstrated a significant improvement in the iloprost group, as was anticipated on the basis of previous reports. 4,11,13,16 Since the acute hemodynamic response did not differ between the groups, it appears unlikely that tolerance developed over the 12-week course of iloprost treatment. During long-term treatment, the patients' hemodynamic status is somewhere between preinhalation and postinhalation values.…”

Section: Discussionmentioning

confidence: 99%

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Inhaled Iloprost for Severe Pulmonary Hypertension

Olschewski¹,

et al. 2002

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Inhaled Iloprost for Severe Pulmonary Hypertension

Olschewski¹,

et al. 2002

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“…Treprostinil is a potent IP receptor agonist (7), although its specificity for this receptor is unknown. Iloprost (8) is an inhaled prostacyclin analog with a half-life between those of epoprostenol and treprostinil that was also approved by the FDA for use in PAH. Though iloprost is a potent IP receptor agonist that is commonly used in vitro, it also demonstrates significant binding to two of the four E prostanoid (EP) receptors, namely the G ␣q -coupled EP1 and the G ␣i -coupled EP3 subtypes (9).…”

Section: Synthetic Prostacyclin Analogs Differentially Regulate Macromentioning

confidence: 99%

Synthetic Prostacyclin Analogs Differentially Regulate Macrophage Function via Distinct Analog-Receptor Binding Specificities

Aronoff

Peres

Serezani

et al. 2007

The Journal of Immunology

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PGI2 (prostacyclin) is a lipid mediator with vasodilatory and antithrombotic effects used in the treatment of vasoconstrictive/ischemic diseases including pulmonary artery hypertension. However, emerging research supports a role for PGs, including PGI2, in the regulation of both innate and acquired immunity. As PGI2 is unstable, we sought to define the effects of various PGI2 analogs on resident alveolar macrophage (AM) and peritoneal macrophage (PM) innate immune functions. The effects of iloprost, carbaprostacyclin, and treprostinil on the regulation of phagocytosis, bacterial killing, and inflammatory mediator production were determined in both macrophage populations from rats. Iloprost failed to suppress AM functions to the same degree that it did in PMs, a characteristic shared by carbaprostacyclin. This difference reflected greater expression of the Gαs protein-coupled I prostanoid receptor and greater cAMP generation in PMs than AMs. Treprostinil inhibited phagocytosis, bacterial killing, and cytokine generation in AMs to a much greater degree than the other PGI2 analogs and more closely resembled the effects of PGE2. Studies with the E prostanoid (EP) 2 receptor antagonist AH-6809 and EP2-null macrophages indicated that this was due in part to the previously unknown ability of treprostinil to stimulate the EP2 receptor. The present investigation for the first time identifies differences in immunoregulatory properties of clinically administered PGI2 analogs. These studies are the first to explore the capacity of PGI2 to regulate bacterial killing and phagocytosis in macrophages, and our findings may hold important consequences regarding the risk of infection for patients receiving such agents.

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“…10 The advantages of inhaled PGI 2 and iloprost include a lack of toxic reactions and ease of administration. 7,11 On the other hand, Haraldsson et al found no improved effects on hemodynamic variables, comparing inhaled PGI 2 with inhaled NO in the evaluation of heart transplant candidates. 6 Currently, there exists little information regarding the use of milrinone by inhalation.…”

Section: Objectifmentioning

confidence: 99%

Selective pulmonary vasodilation with inhaled aerosolized milrinone in heart transplant candidates

Sablotzki¹,

Starzmann²,

Scheubel

et al. 2005

Can J Anesth/J Can Anesth

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Purpose: Selective pulmonary vasodilation is an advantageous method for testing the responsiveness of the pulmonary vasculature of heart transplant candidates. A pilot study was undertaken to test the hypothesis that inhaled aerosolized milrinone may cause selective pulmonary vasodilation.Methods: 18 consecutive male heart transplant candidates with either dilated or ischemic cardiomyopathy were included in this open clinical study. Nine of the patients had significant pulmonary hypertension with a mean pulmonary arterial pressure > 30 mmHg. After baseline measurements, 2 mg of milrinone was administered by ultrasonic nebulization. Pulmonary and systemic hemodynamics were measured ten, 30, and 60 min after inhalation. Results:After inhalation for ten minutes, milrinone induced a significant reduction of mean pulmonary arterial pressure (32.7 ± 9.1 vs 37.7 ± 7.5 mmHg, P = 0.01), pulmonary vascular resistance index (296 ± 150 vs 396 ± 151 dyn·sec -1 ·cm -5 · · m 2 , P = 0.02) and transpulmonary gradient (10.6 ± 5.5 vs 15 ± 4.9, P = 0.01) only in patients with significant pulmonary hypertension. There was no significant effect on mean arterial pressure or systemic vascular resistance at any time after inhalation in either group. Furthermore, there was no influence on extravascular lung water or intrathoracic blood volume. Conclusions:We conclude that inhaled aerosolized milrinone for a short period selectively dilates the pulmonary vasculature in heart transplant candidates with elevated pulmonary arterial pressure, without producing systemic side effects. Further comparative studies are necessary to evaluate possible advantages of milrinone compared to other inhaled vasodilators. Résultats : Après avoir été inhalée pendant 10 min, la milrinone a réduit significativement la tension artérielle pulmonaire moyenne (32,7 ± 9,1 vs 37,7 ± 7,5 mmHg, P = 0,01), l'index de résistance vasculaire pulmonaire (296 ± 15 vs 396 ± 151 dyn·s -1 ·cm -5 ·m 2 , P = 0,02) et le gradient transpulmonaire (10,6 ± 5,5 vs 15 ± 4,9, P = 0,01) Objectif

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Aerosolized Prostacyclin and Iloprost in Severe Pulmonary Hypertension

Abstract: Aerosolization of prostacyclin or its stable analog iloprost causes selective pulmonary vasodilatation, increases cardiac output, and improves venous and arterial oxygenation in patients with severe pulmonary hypertension. Thus, it may offer a new strategy for treatment of this disease.

Cited by 355 publications

References 0 publications

Inhaled Iloprost for Severe Pulmonary Hypertension

Inhaled Iloprost for Severe Pulmonary Hypertension

Synthetic Prostacyclin Analogs Differentially Regulate Macrophage Function via Distinct Analog-Receptor Binding Specificities

Selective pulmonary vasodilation with inhaled aerosolized milrinone in heart transplant candidates

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