Effects of sildenafil on gas exchange, ventilatory, and sensory responses to exercise in subjects with mild-to-moderate COPD: A randomized cross-over trial.

Autor: Gass R; Programa de Pós-Graduação em Ciências Pneumológicas, Universidade Federal do Rio Grande do Sul (UFRGS) & Unidade de Fisiologia Pulmonar, Hospital de Clínicas de Porto Alegre (HCPA), Brazil., Plachi F; Programa de Pós-Graduação em Ciências Pneumológicas, Universidade Federal do Rio Grande do Sul (UFRGS) & Unidade de Fisiologia Pulmonar, Hospital de Clínicas de Porto Alegre (HCPA), Brazil., Silva FOB; Programa de Pós-Graduação em Ciências Pneumológicas, Universidade Federal do Rio Grande do Sul (UFRGS) & Unidade de Fisiologia Pulmonar, Hospital de Clínicas de Porto Alegre (HCPA), Brazil., Nolasco T; Programa de Pós-Graduação em Ciências Pneumológicas, Universidade Federal do Rio Grande do Sul (UFRGS) & Unidade de Fisiologia Pulmonar, Hospital de Clínicas de Porto Alegre (HCPA), Brazil., Tonetto MS; Programa de Pós-Graduação em Ciências Pneumológicas, Universidade Federal do Rio Grande do Sul (UFRGS) & Unidade de Fisiologia Pulmonar, Hospital de Clínicas de Porto Alegre (HCPA), Brazil., Goelzer LS; Laboratório de Fisiopatologia Respiratória (LAFIR), Hospital Universitário Maria Aparecida Pedrossian (HUMAP) & Universidade Federal do Mato Grosso do Sul (UFMS), Campo Grande, Brazil., Muller PT; Laboratório de Fisiopatologia Respiratória (LAFIR), Hospital Universitário Maria Aparecida Pedrossian (HUMAP) & Universidade Federal do Mato Grosso do Sul (UFMS), Campo Grande, Brazil., Knorst MM; Programa de Pós-Graduação em Ciências Pneumológicas, Universidade Federal do Rio Grande do Sul (UFRGS) & Unidade de Fisiologia Pulmonar, Hospital de Clínicas de Porto Alegre (HCPA), Brazil., Neder JA; Pulmonary Function Laboratory and Respiratory Investigation Unit, Division of Respirology, Kingston Health Science Center & Queen's University, Kingston, ON, Canada., Berton DC; Programa de Pós-Graduação em Ciências Pneumológicas, Universidade Federal do Rio Grande do Sul (UFRGS) & Unidade de Fisiologia Pulmonar, Hospital de Clínicas de Porto Alegre (HCPA), Brazil. Electronic address: dberton@hcpa.edu.br.
Jazyk: angličtina
Zdroj: Respiratory physiology & neurobiology [Respir Physiol Neurobiol] 2025 Jan; Vol. 331, pp. 104359. Date of Electronic Publication: 2024 Oct 09.
DOI: 10.1016/j.resp.2024.104359
Abstrakt: Excess exercise ventilation (high ventilation (V̇ E )/carbon dioxide output (V̇CO 2 )) contributes significantly to dyspnea and exercise intolerance since the earlier stages of chronic obstructive pulmonary disease (COPD). A selective pulmonary vasodilator (inhaled nitric oxide) has shown to increase exercise tolerance secondary to lower V̇ E /V̇CO 2 and dyspnea in this patient population. We aimed to assess whether a clinically more practical option - oral sildenafil - would be associated with similar beneficial effects. In a randomized, placebo-controlled study, twenty-four patients with mild-to-moderate COPD completed, on different days, two incremental cardiopulmonary exercise tests (CPET) one hour after sildenafil or placebo. Eleven healthy participants performed a CPET in a non-interventional visit for comparative purposes with patients when receiving placebo. Patients (FEV 1 = 69.4 ± 13.5 % predicted) showed higher ventilatory demands (V̇ E /V̇CO 2 ), worse pulmonary gas exchange, and higher dyspnea during exercise compared to controls (FEV 1 = 98.3 ±11.6 % predicted). Contrary to our expectations, however, sildenafil (50 mg; N= 15) did not change exertional V̇ E /V̇CO 2 , dead space/tidal volume ratio, operating lung volumes, dyspnea, or exercise tolerance compared to placebo (P>0.05). Due to the lack of significant beneficial effects, nine additional patients were trialed with a higher dose (100 mg). Similarly, active intervention was not associated with positive physiological or sensory effects. In conclusion, acute oral sildenafil (50 or 100 mg) failed to improve gas exchange efficiency or excess exercise ventilation in patients with predominantly moderate COPD. The current study does not endorse a therapeutic role for sildenafil to mitigate exertional dyspnea in this specific patient subpopulation. Clinical trial registry: https://ensaiosclinicos.gov.br/rg/RBR-4qhkf4 Web of Science Researcher ID: O-7665-2019.
Competing Interests: Declaration of Competing Interest No authors declare conflicts of interest related to this work.
(Copyright © 2024 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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