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

IF 16.4 1区化学 Q1 CHEMISTRY, MULTIDISCIPLINARY

Accounts of Chemical Research Pub Date : 2024-10-09 DOI:10.1016/j.resp.2024.104359

Ricardo Gass , Franciele Plachi , Fernanda O.B. Silva , Talmir Nolasco , Mateus Samuel Tonetto , Leandro S. Goelzer , Paulo T. Muller , Marli M. Knorst , J. Alberto Neder , Danilo C. Berton

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引用次数: 0

Abstract

Excess exercise ventilation (high ventilation (V̇_E)/carbon dioxide output (V̇CO₂)) 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/V̇CO₂ 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 (FEV₁= 69.4 ± 13.5 % predicted) showed higher ventilatory demands (V̇_E/V̇CO₂), worse pulmonary gas exchange, and higher dyspnea during exercise compared to controls (FEV₁= 98.3 ±11.6 % predicted). Contrary to our expectations, however, sildenafil (50 mg; N= 15) did not change exertional V̇_E/V̇CO₂, 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

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西地那非对轻度至中度慢性阻塞性肺病患者运动时气体交换、通气和感觉反应的影响：随机交叉试验。

自慢性阻塞性肺病（COPD）早期阶段以来，运动通气量过大（通气量（V鄄E）/二氧化碳排出量（VCO2）过高）在很大程度上导致了呼吸困难和运动耐受不良。有研究表明，选择性肺血管扩张剂（吸入一氧化氮）可增加早期慢性阻塞性肺疾病患者的运动耐受性，继而降低 V̇E/VÒCO2 和呼吸困难。我们旨在评估一种临床上更实用的选择--口服西地那非--是否会带来类似的有益效果。在一项随机、安慰剂对照研究中，24 名轻度至中度慢性阻塞性肺病患者在不同的日子里，在服用西地那非或安慰剂一小时后完成了两次增量心肺运动测试（CPET）。11 名健康参与者在一次非干预性访问中进行了 CPET，以便与接受安慰剂治疗的患者进行比较。与对照组（FEV1= 98.3 ±11.6% 预估值）相比，患者（FEV1= 69.4 ±13.5% 预估值）的通气需求（V.M.E./V.M.CO2）更高，肺气体交换更差，运动时呼吸困难更严重。然而，与我们的预期相反，与安慰剂相比，西地那非（50 毫克；N= 15）并未改变用力时的 V̇E/V̇CO2、死腔/潮气量比率、肺活量、呼吸困难或运动耐受性（P>0.05）。由于疗效不明显，又有九名患者接受了更高剂量（100 毫克）的试验。同样，积极干预也没有产生积极的生理或感官效应。总之，急性口服西地那非（50 毫克或 100 毫克）未能改善以中度慢性阻塞性肺病为主的患者的气体交换效率或运动过量通气。目前的研究并不认可西地那非在缓解这一特定患者亚群的运动性呼吸困难方面的治疗作用。临床试验登记：https://ensaiosclinicos.gov.br/rg/RBR-4qhkf4 Web of Science Researcher ID：O-7665-2019.

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来源期刊

Accounts of Chemical Research 化学-化学综合

CiteScore

31.40

自引率

1.10%

发文量

312

审稿时长

2 months

期刊介绍： Accounts of Chemical Research presents short, concise and critical articles offering easy-to-read overviews of basic research and applications in all areas of chemistry and biochemistry. These short reviews focus on research from the author’s own laboratory and are designed to teach the reader about a research project. In addition, Accounts of Chemical Research publishes commentaries that give an informed opinion on a current research problem. Special Issues online are devoted to a single topic of unusual activity and significance. Accounts of Chemical Research replaces the traditional article abstract with an article "Conspectus." These entries synopsize the research affording the reader a closer look at the content and significance of an article. Through this provision of a more detailed description of the article contents, the Conspectus enhances the article's discoverability by search engines and the exposure for the research.