| Hemodynamic and gas exchange effects of sildenafil in patients with chronic obstructive pulmonary disease and pulmonary hypertension. | |
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MedLine Citation:
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PMID: 19875684 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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RATIONALE: Sildenafil, a phosphodiesterase-5 inhibitor, could be useful for treating pulmonary hypertension (PH) in chronic obstructive pulmonary disease (COPD). However, vasodilators may inhibit hypoxic pulmonary vasoconstriction and impair gas exchange in this condition. OBJECTIVES: To assess the acute hemodynamic and gas exchange effects of sildenafil in patients with COPD-associated PH. METHODS: We conducted a randomized, dose comparison trial in 20 patients with COPD-associated PH. Eleven patients were assigned to 20 mg, and 9 patients to 40 mg, of sildenafil. Pulmonary hemodynamics and gas exchange, including ventilation-perfusion (V(A)/Q) relationships, were assessed at rest and during constant-work rate exercise, before and 1 hour after sildenafil administration. MEASUREMENTS AND MAIN RESULTS: Both sildenafil doses reduced the mean pulmonary arterial pressure (PAP) at rest and during exercise, without differences between them. Overall, PAP decreased -6 mm Hg (95% confidence interval [95% CI], -7 to -4) at rest and -11 mm Hg (95% CI, -14 to -8) during exercise. After sildenafil, Pa(O(2)) decreased -6 mm Hg (95% CI, -8 to -4) at rest because of increased perfusion in units with low V(A)/Q ratio, without differences between doses. No change in Pa(O(2)) (95% CI, -3 to 0.2 mm Hg) or V(A)/Q relationships occurred during exercise after sildenafil. Changes induced by sildenafil in Pa(O(2)) and V(A)/Q distributions at rest correlated with their respective values at baseline. CONCLUSIONS: In patients with COPD-associated PH, sildenafil improves pulmonary hemodynamics at rest and during exercise. This effect is accompanied by the inhibition of hypoxic vasoconstriction, which impairs arterial oxygenation at rest. The use of sildenafil in COPD should be done cautiously and under close monitoring of blood gases. Clinical trial registered with www.clinicaltrials.gov (NCT00491803). |
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Authors:
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Isabel Blanco; Elena Gimeno; Phillip A Munoz; Sandra Pizarro; Concepción Gistau; Robert Rodriguez-Roisin; Josep Roca; Joan Albert Barberà |
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Publication Detail:
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Type: Comparative Study; Journal Article; Randomized Controlled Trial; Research Support, Non-U.S. Gov't Date: 2009-10-29 |
Journal Detail:
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Title: American journal of respiratory and critical care medicine Volume: 181 ISSN: 1535-4970 ISO Abbreviation: Am. J. Respir. Crit. Care Med. Publication Date: 2010 Feb |
Date Detail:
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Created Date: 2010-01-22 Completed Date: 2010-02-18 Revised Date: 2010-11-10 |
Medline Journal Info:
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Nlm Unique ID: 9421642 Medline TA: Am J Respir Crit Care Med Country: United States |
Other Details:
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Languages: eng Pagination: 270-8 Citation Subset: AIM; IM |
Affiliation:
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Department of Pulmonary Medicine, Hospital Clínic-Institut d'Investigacions Biomèdiques August Pi i Sunyer, University of Barcelona, Barcelona. |
| Data Bank Information | |
Bank Name/Acc. No.:
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ClinicalTrials.gov/NCT00491803 |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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3',5'-Cyclic-GMP Phosphodiesterases
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antagonists & inhibitors Aged Dose-Response Relationship, Drug Exercise / physiology Exercise Test Female Follow-Up Studies Hemodynamics / drug effects*, physiology Humans Hypertension, Pulmonary / drug therapy, etiology, physiopathology* Male Middle Aged Piperazines / administration & dosage, therapeutic use* Pulmonary Disease, Chronic Obstructive / complications, drug therapy, physiopathology* Pulmonary Gas Exchange / drug effects*, physiology Pulmonary Wedge Pressure / drug effects, physiology Purines / administration & dosage, therapeutic use Rest / physiology Severity of Illness Index Sulfones / administration & dosage, therapeutic use* Treatment Outcome Vasodilator Agents / administration & dosage, therapeutic use* |
| Chemical | |
Reg. No./Substance:
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0/Piperazines; 0/Purines; 0/Sulfones; 0/Vasodilator Agents; 139755-83-2/sildenafil; EC 3.1.4.35/3',5'-Cyclic-GMP Phosphodiesterases |
| Comments/Corrections | |
Comment In:
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Am J Respir Crit Care Med. 2010 Nov 1;182(9):1206; author reply 1206-7
[PMID:
21041564
]
Am J Respir Crit Care Med. 2010 Feb 1;181(3):202-3 [PMID: 20093654 ] |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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