Document Detail


Hemodynamic and gas exchange effects of sildenafil in patients with chronic obstructive pulmonary disease and pulmonary hypertension.
MedLine Citation:
PMID:  19875684     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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).
Authors:
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:
Type:  Comparative Study; Journal Article; Randomized Controlled Trial; Research Support, Non-U.S. Gov't     Date:  2009-10-29
Journal Detail:
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:
Created Date:  2010-01-22     Completed Date:  2010-02-18     Revised Date:  2010-11-10    
Medline Journal Info:
Nlm Unique ID:  9421642     Medline TA:  Am J Respir Crit Care Med     Country:  United States    
Other Details:
Languages:  eng     Pagination:  270-8     Citation Subset:  AIM; IM    
Affiliation:
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.:
ClinicalTrials.gov/NCT00491803
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MeSH Terms
Descriptor/Qualifier:
3',5'-Cyclic-GMP Phosphodiesterases / 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:
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:
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 ]

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