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Intravenous sildenafil acutely improves hemodynamic response to exercise in patients with connective tissue disease

BACKGROUND: Hemodynamic assessment during exercise may unmask an impaired functional reserve of the right ventricle and the pulmonary vasculature in patients with connective tissue disease. We assessed the effect of intravenous sildenafil on the hemodynamic response to exercise in patients with conn...

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Autores principales: Rieth, Andreas J., Richter, Manuel J., Berkowitsch, Alexander, Frerix, Marc, Tarner, Ingo H., Mitrovic, Veselin, Hamm, Christian W.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6147445/
https://www.ncbi.nlm.nih.gov/pubmed/30235235
http://dx.doi.org/10.1371/journal.pone.0203947
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author Rieth, Andreas J.
Richter, Manuel J.
Berkowitsch, Alexander
Frerix, Marc
Tarner, Ingo H.
Mitrovic, Veselin
Hamm, Christian W.
author_facet Rieth, Andreas J.
Richter, Manuel J.
Berkowitsch, Alexander
Frerix, Marc
Tarner, Ingo H.
Mitrovic, Veselin
Hamm, Christian W.
author_sort Rieth, Andreas J.
collection PubMed
description BACKGROUND: Hemodynamic assessment during exercise may unmask an impaired functional reserve of the right ventricle and the pulmonary vasculature in patients with connective tissue disease. We assessed the effect of intravenous sildenafil on the hemodynamic response to exercise in patients with connective tissue disease. METHODS: In this proof-of-concept study, patients with connective tissue disease and mean pulmonary arterial pressure (mPAP) >20 mm Hg were subjected to a supine exercise hemodynamic evaluation before and after administration of intravenous sildenafil 10 mg. RESULTS: Ten patients (four with moderately elevated mPAP 21–24 mm Hg; six with mPAP >25 mm Hg) underwent hemodynamic assessment. All of them showed markedly abnormal exercise hemodynamics. Intravenous sildenafil was well tolerated and had significant hemodynamic effects at rest and during exercise, although without pulmonary selectivity. Sildenafil reduced median total pulmonary resistance during exercise from 6.22 (IQR 4.61–8.54) to 5.24 (3.95–6.96) mm Hg·min·L(-1) (p = 0.005) and increased median pulmonary arterial capacitance during exercise from 1.59 (0.93–2.28) to 1.74 (1.12–2.69) mL/mm Hg (p = 0.005). CONCLUSIONS: In patients with connective tissue disease who have an abnormal hemodynamic response to exercise, intravenous sildenafil improved adaption of the right ventricular-pulmonary vascular unit to exercise independent of resting mPAP. The impact of acute pharmacological interventions on exercise hemodynamics in patients with pulmonary vascular disease warrants further investigation. TRIAL REGISTRATION: Clinicaltrials.gov NCT01889966.
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spelling pubmed-61474452018-10-08 Intravenous sildenafil acutely improves hemodynamic response to exercise in patients with connective tissue disease Rieth, Andreas J. Richter, Manuel J. Berkowitsch, Alexander Frerix, Marc Tarner, Ingo H. Mitrovic, Veselin Hamm, Christian W. PLoS One Research Article BACKGROUND: Hemodynamic assessment during exercise may unmask an impaired functional reserve of the right ventricle and the pulmonary vasculature in patients with connective tissue disease. We assessed the effect of intravenous sildenafil on the hemodynamic response to exercise in patients with connective tissue disease. METHODS: In this proof-of-concept study, patients with connective tissue disease and mean pulmonary arterial pressure (mPAP) >20 mm Hg were subjected to a supine exercise hemodynamic evaluation before and after administration of intravenous sildenafil 10 mg. RESULTS: Ten patients (four with moderately elevated mPAP 21–24 mm Hg; six with mPAP >25 mm Hg) underwent hemodynamic assessment. All of them showed markedly abnormal exercise hemodynamics. Intravenous sildenafil was well tolerated and had significant hemodynamic effects at rest and during exercise, although without pulmonary selectivity. Sildenafil reduced median total pulmonary resistance during exercise from 6.22 (IQR 4.61–8.54) to 5.24 (3.95–6.96) mm Hg·min·L(-1) (p = 0.005) and increased median pulmonary arterial capacitance during exercise from 1.59 (0.93–2.28) to 1.74 (1.12–2.69) mL/mm Hg (p = 0.005). CONCLUSIONS: In patients with connective tissue disease who have an abnormal hemodynamic response to exercise, intravenous sildenafil improved adaption of the right ventricular-pulmonary vascular unit to exercise independent of resting mPAP. The impact of acute pharmacological interventions on exercise hemodynamics in patients with pulmonary vascular disease warrants further investigation. TRIAL REGISTRATION: Clinicaltrials.gov NCT01889966. Public Library of Science 2018-09-20 /pmc/articles/PMC6147445/ /pubmed/30235235 http://dx.doi.org/10.1371/journal.pone.0203947 Text en © 2018 Rieth et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Rieth, Andreas J.
Richter, Manuel J.
Berkowitsch, Alexander
Frerix, Marc
Tarner, Ingo H.
Mitrovic, Veselin
Hamm, Christian W.
Intravenous sildenafil acutely improves hemodynamic response to exercise in patients with connective tissue disease
title Intravenous sildenafil acutely improves hemodynamic response to exercise in patients with connective tissue disease
title_full Intravenous sildenafil acutely improves hemodynamic response to exercise in patients with connective tissue disease
title_fullStr Intravenous sildenafil acutely improves hemodynamic response to exercise in patients with connective tissue disease
title_full_unstemmed Intravenous sildenafil acutely improves hemodynamic response to exercise in patients with connective tissue disease
title_short Intravenous sildenafil acutely improves hemodynamic response to exercise in patients with connective tissue disease
title_sort intravenous sildenafil acutely improves hemodynamic response to exercise in patients with connective tissue disease
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6147445/
https://www.ncbi.nlm.nih.gov/pubmed/30235235
http://dx.doi.org/10.1371/journal.pone.0203947
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