Dataset Information

Acute effects of aerosolized iloprost in COPD related pulmonary hypertension - a randomized controlled crossover trial.

ABSTRACT:

Background

Inhaled iloprost potentially improves hemodynamics and gas exchange in patients with chronic obstructive pulmonary disease (COPD) and secondary pulmonary hypertension (PH).

Objectives

To evaluate acute effects of aerosolized iloprost in patients with COPD-associated PH.

Methods

A randomized, double blind, crossover study was conducted in 16 COPD patients with invasively confirmed PH in a single tertiary care center. Each patient received a single dose of 10 µg iloprost (low dose), 20 µg iloprost (high dose) and placebo during distinct study-visits. The primary end-point of the study was exercise capacity as assessed by the six minute walking distance.

Results

Both iloprost doses failed to improve six-minute walking distance (p?=?0.36). Low dose iloprost (estimated difference of the means -1.0%, p?=?0.035) as well as high dose iloprost (-2.2%, p<0.001) significantly impaired oxygenation at rest. Peak oxygen consumption and carbon dioxide production differed significantly over the three study days (p?=?0.002 and p?=?0.003, accordingly). As compared to placebo, low dose iloprost was associated with reduced peak oxygen consumption (-76 ml/min, p?=?0.002), elevated partial pressure of carbon dioxide (0.27 kPa, p?=?0.040) and impaired ventilation during exercise (-3.0l/min, p<0.001).

Conclusions

Improvement of the exercise capacity after iloprost inhalation in patients with COPD-associated mild to moderate PH is very unlikely.

Trial registration

Controlled-Trials.com ISRCTN61661881.

SUBMITTER: Boeck L

PROVIDER: S-EPMC3531427 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

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Publications

Acute effects of aerosolized iloprost in COPD related pulmonary hypertension - a randomized controlled crossover trial.

Boeck Lucas L Tamm Michael M Grendelmeier Peter P Stolz Daiana D

PloS one 20121227 12

<h4>Background</h4>Inhaled iloprost potentially improves hemodynamics and gas exchange in patients with chronic obstructive pulmonary disease (COPD) and secondary pulmonary hypertension (PH).<h4>Objectives</h4>To evaluate acute effects of aerosolized iloprost in patients with COPD-associated PH.<h4>Methods</h4>A randomized, double blind, crossover study was conducted in 16 COPD patients with invasively confirmed PH in a single tertiary care center. Each patient received a single dose of 10 µg il ...[more]

PMID: 23300624

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Project description:IntroductionProstacyclin inhalation is increasingly used to treat acute pulmonary hypertension and right ventricular failure, although its pharmacodynamic properties remain controversial. Prostacyclins not only affect vasomotor tone but may also have cAMP-mediated positive inotropic effects and modulate autonomic nervous system tone. We studied the role of these different mechanisms in the overall haemodynamic effects produced by iloprost inhalation in an experimental model of acute pulmonary hypertension.MethodsIn this prospective, randomized, placebo-controlled animal study, twenty-six pigs (mean weight 35 +/- 2 kg) were instrumented with biventricular conductance catheters, a pulmonary artery flow probe and a high-fidelity pulmonary artery pressure catheter. The effects of inhaled iloprost (50 microg) were studied in the following groups: animals with acute hypoxia-induced pulmonary hypertension, and healthy animals with and without blockade of the autonomic nervous system.ResultsDuring pulmonary hypertension, inhalation of iloprost resulted in a 51% increase in cardiac output compared with placebo (5.6 +/- 0.7 versus 3.7 +/- 0.8 l/minute; P = 0.0013), a selective reduction in right ventricular afterload (effective pulmonary arterial elastance: 0.6 +/- 0.3 versus 1.2 +/- 0.5 mmHg/ml; P = 0.0005) and a significant increase in left ventricular end-diastolic volume (91 +/- 12 versus 70 +/- 20 ml; P = 0.006). Interestingly, right ventricular contractility was reduced after iloprost-treatment (slope of preload recruitable stroke work: 2.2 +/- 0.5 versus 3.4 +/- 0.8 mWatt.s/ml; P = 0.0002), whereas ventriculo-vascular coupling remained essentially preserved (ratio of right ventricular end-systolic elastance to effective pulmonary arterial elastance: 0.97 +/- 0.33 versus 1.03 +/- 0.15). In healthy animals, inhaled iloprost had only minimal haemodynamic effects and produced no direct effects on myocardial contractility, even after pharmacological blockade of the autonomic nervous system.ConclusionsIn animals with acute pulmonary hypertension, inhaled iloprost improved global haemodynamics primarily via selective pulmonary vasodilatation and restoration of left ventricular preload. The reduction in right ventricular afterload is associated with a paradoxical decrease in right ventricular contractility. Our data suggest that this reflects an indirect mechanism by which ventriculo-vascular coupling is maintained at the lowest possible energetic cost. We found no evidence for a direct negative inotropic effect of iloprost.

Project description:Pulmonary vascular arterial remodeling is an integral and well-understood component of pulmonary hypertension (PH). In contrast, morphological alterations of pulmonary veins in PH are scarcely described. Explanted lungs (n = 101) from transplant recipients with advanced chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary arterial hypertension (IPAH) were analyzed for venous vascular involvement according to a pre-specified, semi-quantitative grading scheme, which categorizes the intensity of venous remodeling in three groups of incremental severity: venous hypertensive (VH) grade 0 = characterized by an absence of venous vascular remodeling; VH grade 1 = defined by a dominance of either arterialization or intimal fibrosis; and VH grade 2 = a substantial composite of arterialization and intimal fibrosis. Patients were grouped according to clinical and hemodynamic characteristics in three groups: COPD non-PH, COPD-PH, and IPAH, respectively. Histological specimens were examined by a cardiovascular pathologist blinded to clinical and hemodynamic data. Pathological alterations of pulmonary veins were present in all hemodynamic groups, with the following incidences of VH grade 0/1/2: 34/66/0% in COPD non-PH; 19/71/10% in COPD-PH; and 11/61/28% in IPAH. In COPD, explorative correlation analysis of venous remodeling suggested a modest positive correlation with systolic and mean pulmonary artery pressure ( P = 0.032, respectively) and an inverse modest correlation with diffusion capacity for carbon monoxide ( P = 0.027). In addition, venous remodeling correlated positively with the degree of arterial remodeling ( P = 0.014). In COPD-PH and IPAH, advanced forms of pulmonary venous remodeling are present, emphasizing that the disease is not exclusively restricted to arterial lesions. In addition, venous remodeling may be related to the hemodynamic severity, but more rigorous analysis is required to clearly define potential relationships.

Dataset Information

Acute effects of aerosolized iloprost in COPD related pulmonary hypertension - a randomized controlled crossover trial.

Background

Objectives

Methods

Results

Conclusions

Trial registration

Publications

Acute effects of aerosolized iloprost in COPD related pulmonary hypertension - a randomized controlled crossover trial.

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