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 1.9 4区医学 Q3 PHYSIOLOGY

Respiratory Physiology & Neurobiology 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

Respiratory Physiology & Neurobiology 医学-呼吸系统

CiteScore

4.80

自引率

8.70%

发文量

104

审稿时长

54 days

期刊介绍： Respiratory Physiology & Neurobiology (RESPNB) publishes original articles and invited reviews concerning physiology and pathophysiology of respiration in its broadest sense. Although a special focus is on topics in neurobiology, high quality papers in respiratory molecular and cellular biology are also welcome, as are high-quality papers in traditional areas, such as: -Mechanics of breathing- Gas exchange and acid-base balance- Respiration at rest and exercise- Respiration in unusual conditions, like high or low pressure or changes of temperature, low ambient oxygen- Embryonic and adult respiration- Comparative respiratory physiology. Papers on clinical aspects, original methods, as well as theoretical papers are also considered as long as they foster the understanding of respiratory physiology and pathophysiology.